Category Archives: Kentucky Stem Cells

Here's one way to mend a broken heart: Researchers from the University of Louisville, Kentucky, used cardiac stem cells to repair the damaged heart muscles of patients who had experienced severe heart attacks. Some call the findings, which were published in the journal Lancet, the field's "biggest breakthrough in a generation." Here's what you should know:

Wait, this treatment helps after a heart attack?

It does. Usually, the recovery phase after a heart attack is dangerous because of the possibility of heart failure, says Britain's Telegraph. Heart failure which is often linked with heart attack victims, but can strike other people, too "occurs when a damaged heart is weakened and unable to pump enough blood around the body." This treatment helps reduce that risk.

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How does the treatment work?

It uses cardiac stem cells taken directly from the heart to repair the organ. "Cardiac stem cells can renew themselves and can form one of three types of cell that make up heart tissue," says Jessica Hamzelou at New Scientist. Researchers hypothesized that injecting stem cells directly into damaged areas might help improve the heart's recovery after an attack. In this new study, researchers extracted stem cells from the hearts of 16 patients during bypass surgery, then "multiplied them in culture and injected them back into each original patient's heart" four months later.

And this helped them recover?

It did. When controlled against patients who received standard care, the 16 patients demonstrated "striking" improvements. Their "pumping efficiency" was noticeably better, says the Telegraph, and surgical scars even shrank. After a year, eight of the patients saw a 12 percent improvement in pumping efficiency triple what researchers initially expected.

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Why is this such a big deal?

"It's long been an article of faith that human heart muscle, once damaged, cannot regenerate," says Eryn Brown at the Los Angeles Times. This study proves that not only can the heart be repaired, but that with a little assistance, it can repair itself using its own cells. That's very good news, as an estimated 6 million people in the U.S. experience heart failure every year.

Sources: LA Times, New Scientist, Telegraph

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Treating heart attacks with stem cells: The 'biggest breakthrough' yet? - The Week

LEXINGTON Because many blood cancers can be highly treatable if caught early, there is an urgent need to raise public awareness of the signs and symptoms of the disease.

Blood cancers, which include leukemia, lymphoma and myeloma, form in the bone marrow where blood is made or in the lymphatic system, which fights infections. Affecting both children and adults, blood cancers account for almost 10% of new cancer cases in the U.S. each year.

While prognosis, or chance of recovery, depends on many factors including the type of blood cancer, survival rates have significantly improved. With modern treatment, patients with chronic myeloid leukemia can have close to normal life expectance. Elderly patients with acute leukemia, which was previously rapidly fatal, are now living one to three years from their diagnosis, and cellular therapy (involving a patients own cells or donor cells) is capable of offering a cure for some types of lymphomas and acute leukemias.

Because there is not yet a screening test for the early detection of blood cancers, people dont typically know something is wrong until they develop symptoms. Thats why its especially important to learn to recognize the symptoms and be aware of any changes in your body.

People who have had prior chemotherapy or radiation or a prior toxic chemical exposure are at increased risk of developing blood cancers.

Common blood cancer symptoms include: fever, drenching night sweats, persistent fatigue and weakness, bone or joint pain, unexplained weight loss, swollen lymph nodes, liver and spleen, ands easy bruising or bleeding.

If you are experiencing any of these symptoms, bring it to the attention of a health care professional right away. It could potentially save your life.

Blood cancer treatment options vary by diagnosis as well as stage of the disease and include chemotherapy, targeted therapies, radiation therapy, immunotherapy, stem cell transplant and blood transfusion.

Part of the University of Kentucky Markey Cancer Center, the Hematology and Blood & Marrow Transplant and Cellular Therapy Program at UK HealthCare treats all blood related diseases, including blood cancers. There are also a variety of clinical trials and research studies underway at UK Markey Cancer Center that can give blood cancer patients additional treatment options and the best chance for survival.

We are making critical coverage of the coronavirus available for free. Please consider subscribing so we can continue to bring you the latest news and information on this developing story.

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Blood cancer awareness month: learn to recognize the signs and symptoms - Commonwealth Journal's History

Esteemed award is an international forum celebrating noteworthy achievements in equine research and individuals who have significantly impacted equine health

The University of Kentucky (UK) Gluck Equine Research Center unveiled the 2022 inductees to the Equine Research Hall of Fame. The winners include Lisa Fortier, DVM, PhD, DACVS; Katrin Hinrichs, DVM, PhD; Jennifer Anne Mumford, DVM; and Stephen M. Reed, DVM.

The scientists were nominated by their fellow peers and past awardees. Nominees may be living or deceased, active in or retired from the field of equine research.

In research, we always stand on the shoulders of those who go before us with great discoveries. This years recipients have made substantial contributions that will ensure an excellent future for equine research, expressed Nancy Cox, UK vice president for land-grant engagement and College of Agriculture, Food and Environment dean, in a university release.1

The success of Kentuckys horse industry is inseparable from the decades of hard work by outstanding equine researchers, added Stuart Brown, chair of the Gluck Equine Research Foundation. Though impossible to measure, it is a unique privilege to recognize the impact made by these four scientists in advancing the health and wellbeing of the horse and, on behalf of the entire equine community, show our appreciation.

Below are the details of each awardee1:

Throughout the past 30 years, Fortier has been renowned for her substantial contributions in equine joint disease, cartilage biology, and regenerative medicine. Her research focuses on early diagnosis and treatment of equine orthopedic injuries to prevent permanent damage to joints and tendons. She is most well-known for her work in regenerative medicine, spearheading the use of biologics such as platelet rich plasma, bone marrow concentrate, and stem cells for use in horses and humans. Additionally, Fortiers lab has been key in strides associated with cartilage damage diagnosis and clinical orthopedic work.

Fortier achieved her bachelors degree and doctor of veterinary medicine degree from Colorado State University. She finished her residency at Cornell, where she also earned a PhD and was a postdoctoral fellow in pharmacology. Currently, she serves as the James Law Professor of Surgery at Cornells College of Veterinary Medicine. She is the editor-in-chief of the Journal of the American Veterinary Medical Association and serves on the Horseracing Integrity and Safety Authority Racetrack Safety Standing Committee.

Hinrichs dedicates her career to research mainly in equine reproductive physiology and assisted reproduction techniques. Her focus has consisted of equine endocrinology, oocyte maturation, fertilization, sperm capacitation, and their application to assisted reproduction techniques.

Her 40 years of research have resulted in various notable basic and applied research accomplishments. The applied achievements include generating the first cloned horse in North America and creating the medical standard for effective intracytoplasmic sperm injection and in vitro culture for equine embryo production. She has mentored over 85 veterinary students, residents, graduate students, and postdoctoral fellows in basic and applied veterinary research. Her laboratories have hosted about 50 visiting scholars worldwide.

Hinrichs achieved her bachelors degree and doctor of veterinary medicine degree from the University of California, Davis. She finished residency training in large animal reproduction at the University of Pennsylvanias New Bolton Center and received a PhD at the University of Pennsylvania.

Mumford is a posthumous inductee who received international respect as among the most prominent researchers of equine infectious diseases, specifically equine viral diseases. Her career at the Animal Health Trust, Newmarket, United Kingdom, began when she was deemed the first head of the newly established equine virology unit. Her work focused on the leading causes of acute infectious respiratory disease in the horse, mainly equine herpesvirus and equine influenza virus, and to a lesser extent,Streptococcus equi.

Mumford impacted several of these realms, including developing enhanced vaccines, diagnostics, and international surveillance. Additionally, she helped create research groups in the related fields of equine genetics and immunology.

Throughout Mumfords over 30 year-career, she helped the Animal Health Trust be recognized as one of the worlds leading centers for the study of the biology, epidemiology, immunology and pathology of diseases.

Reeds nominators deemed his as the last word in equine neurology. He is known as among the most prominent equine neurologists worldwide. His list of 180 peer-reviewed publications feature important contributions to equine medicine, neurology, physiology and pathophysiology. He has shared in his accomplishments as a mentor and role-model for hundreds of aspiring equine practitioners.

Reed received his bachelors degree and doctor of veterinary medicine degree from The Ohio State University. He finished his internship and residency training in large animal medicine at Michigan State University.

The UK Gluck Equine Research Foundation will induct the 4 winners into the UK Equine Research Hall of Fame October 26, 2022 at Kroger Field in Lexington, Kentucky.

Reference

Wiemers H. UK Equine Research Hall of Fame inductees announced. UK College of Agriculture, Food and Environment. News release. September 13, 2022. Accessed September 20, 2022. https://news.ca.uky.edu/article/uk-equine-research-hall-fame-inductees-announced-1

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University of Kentucky Equine Research Hall of Fame announces awardees - DVM 360

Early detection is the first step in successful cancer treatment.

Cancer has a major adverse impact on lives and societies across the globe. This fact is particularly true in the United States which has one of the highest rates of cancer in the world. Not only is cancer tragic for the patients and their families, but it is also detrimental to the healthcare system. In 2010, national expenditures for cancer reached $125 billion, and this figure is expected to increase to $156 billion by 2020. The cancer rate in the US is approximately 318 cases per 100,000 people. This article provides an outline of the states with the highest cancer rates.

Why is cancer so common in the US? Health professionals believe that some cancers cases are caused by unhealthy lifestyle choices. Residents in this country are more likely to be obese, consume large amounts of alcohol, and have sedentary lifestyles than in other parts of the world. This, however, does not mean that the country is doomed to suffer from high cancer rates. Lifestyle is a choice, and the risk of developing cancer can be decreased by becoming physically active, losing weight, and eating healthy.

Cancer rates in the US are highest in the eastern side of the country. Kentucky has the highest incidence with 512 people out of 100,000 developing the disease every year. One of the poorest states in the nation, it has not sufficiently invested in cancer prevention and detection; therefore, the state also has the highest rate of deaths from cancer. Kentucky was founded on the tobacco industry, a legacy that remains today as nearly a quarter of the population smokes cigarettes. This smoking habit explains why lung cancer is higher here than any other state in the nation.

The second highest cancer rate is found in Delaware where 490.6 out of every 100,000 residents will develop the disease annually. After being named as one of the states with the highest rates of cancer, Delaware increased its screening and prevention programs which has helped to improve survival and diagnoses rates. Common cancers here are colorectal and prostate. Both can be prevented through early detection.

Number 3 on the list is Pennsylvania. In this state, the incidence of cancer is 483.1. Cancer is one of the most common chronic diseases here and the second leading cause of death (after heart disease). The most commonly diagnosed type of cancer is prostate followed by lung, breast, and colorectal. Lifestyle behaviors are again to blame, residents here report high tobacco use and unhealthy diets.

The other states with the highest cancer rates include New York (482), New Jersey (479.5), Louisiana (477.5), Minnesota (475), and Iowa (470.2).

The most common types of cancer throughout the country include breast, lung, prostate, colon, bladder, and skin. Additionally, rates of non-Hodgkin lymphoma, thyroid, kidney, leukemia, endometrial, and pancreatic cancers are expected to rise in 2016. Many of these are treatable with early detection.

Cancer treatment options in the US include surgery, radiation therapy, chemotherapy, targeted therapy, hormone therapy, stem cell transplant, and precision medicine. The treatment module chosen depends on the kind of cancer and its level of advance. Scientists are currently working on immunotherapy, a treatment that will retrain immune systems to fight cancer cells. It involves removing white blood cells and genetically modifying them with a new targeting method. So far this has only been used with leukemia patients and has yet to be fully developed.

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U.S. States With The Highest Cancer Rates - WorldAtlas

Robin F.B. Turner and James M. Piret are the winners of the 2022 William F. Meggers Award, to be presented this fall at the SciX conference, which will be held October 27 at the Northern Kentucky Convention Center in Greater Cincinnati. The Meggers Award, from the Society for Applied Spectroscopy, is given to the authors of the outstanding paper appearing in the journal Applied Spectroscopy. It is presented at the SciX conference in the year following the calendar year of publication.

Turner and Piret are receiving the award for their paper, Augmented Two-Dimensional Correlation Spectroscopy for the Joint Analysis of Correlated Changes in Spectroscopic and Disparate Sources, published in the May 2021 issue of the journal (Appl. Spectrosc. 75(5), 520-530, 2021), along with their co-authors, H. Georg Schultze, Shreyas Rangan, Martha Vardaki, Timothy Kieffer, Michael Blades, and Diepiriye Iworima. The paper presents an augmented form of two-dimensional correlation spectroscopy that integrates in a single format data from spectroscopic and multiple non-spectroscopic sources for analysis. It demonstrates the approach with data using Raman spectra from human embryonic stem cell aggregates undergoing directed differentiation toward pancreatic endocrine cells.

Turner is a professor at The University of British Columbia with joint appointments in the Michael Smith Laboratories and Department of Electrical & Computer Engineering, and an Associate Member of the Department of Chemistry. He earned his PhD in electrical engineering from the University of Alberta in 1990. His current research activities focus on applications of Raman spectroscopy to analytical problems in biochemistry, biotechnology, and biomedical engineering.

Piret is a professor at the University of British Columbia in the Department of Chemical & Biological Engineering and the Michael Smith Laboratories. He received a bachelors degree from Harvard University in Applied Mathematics to Biochemistry, and a chemical engineering doctoral degree from MIT in 1989. His research focus is on innovative process and device technology development for mammalian cell culture therapeutic protein or cell manufacturing.

Turner and Piret discussed this work, and other work being done with their team, in a recent interview in Spectroscopy.

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Robin Turner and James Piret Receive 2022 William F. Meggers Award - Spectroscopy Online

- AUTO4 shows high level of clinical activity with a novel targeting approach for patients with T Cell Lymphoma

- AUTO1/22 demonstrates encouraging and durable responses in children ineligible for commercial CAR T product

- Obe-cel shows high level of sustained clinical activity in B-NHL patients and first activity in Primary CNS Lymphoma

Conference call to be held on Monday June 13, 2022 at 7:30 am EST/12:30 pm BST

LONDON, June 10, 2022 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc(Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announces the publication of clinical data across multiple programs at the European Hematology Association (EHA) Congress, being held June 9-12, 2022.

Autolus will hold a conference call on Monday June 13 2022 at 7:30 am EST / 12:30 pm BST, which will include participation from; Dr. Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center; Dr. Kate Cwynarski, Chair UK T cell Lymphoma Group, Consultant Hematologist, University College London Hospital; and Autolus management team.

We are excited to be presenting this first clinical data for two new product candidates, AUTO4 with its unique targeting approach for T cell lymphoma and AUTO1/22 a dual targeting CAR T product for the treatment of children with ALL, said Dr. Christian Itin, CEO of Autolus. With obe-cel progressing towards pivotal data in the FELIX trial in adult patients with ALL, we are pleased to show obe-cels broader utility in B-NHL patients, mirroring the high level of activity and well manageable safety profile we have seen in previous trials.

This year's EHA is an important meeting for Autolus with four presentations providing updates from ongoing clinical studies, said Dr. Martin Pule, Chief Scientific Officer of Autolus. In an oral presentation we will present AUTO4 clinical data for the first time. These data suggest that AUTO4 has the potential to become an important therapeutic option for patients with T cell lymphoma. In a second presentation, we will present our finding from clinical testing of AUTO1/22. These data show that AUTO1/22 can induce remission in children with B-ALL, including in those whose disease was not successfully treated with commercial CAR T product. Further, data suggest that AUTO1/22 can prevent antigen escape. In two additional presentations, we demonstrate incremental obe-cel data in B-NHL and B-CLL, as well as some early data in PCNSL. Obe-cel continues to have consistent safety and efficacy data across these indications.

As clinicians, we are always searching for new strategies to address unmet needs in aggressive blood cancers, saidDr. Steven Horwitz, M.D.,Department of Medicine, Lymphoma Service,Memorial Sloan Kettering Cancer Center,New York. T Cell Lymphomas are particularly challenging, and Ive been following Dr. Pules strategy of CAR T targeting based on the mutually exclusive expressions of TRBC1 or TRBC2 with great interest. Any advance in bringing new effective therapies to patients with T cell lymphomas is of great importance.

Data presentations:

1.Title: Safety and preliminary efficacy findings of AUTO4, a TRBC1-targetting CAR, in relapsed/refractory TRBC1 positive selected T Cell Non-Hodgkin Lymphoma

Session Title: Gene therapy and cellular immunotherapy - Clinical 2

Session date and time: Saturday, June 11, 2022 16:30 - 17:45 CEST

Session room: Hall Strauss 1-2

Final Abstract Code: S261

Presenting Author: Kate Cwynarski

Conclusions: As of April 26 2022, 10 patients with TRBC1-positive r/r T-cell lymphoma (Peripheral T-cell lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell lymphoma (AITL), Anaplastic Large cell lymphoma (ALCL)) have been treated with AUTO4 in a Phase I dose escalation trial. Three patients had prior stem cell transplantation. After lymphodepletion with Flu/Cy, patients received either 25, 75, 225 or 450 x 106 CAR T cells. AUTO4 demonstrated a tolerable safety profile, with no patient experiencing any dose limiting toxicities, and no neurotoxicity/immune effector cell-associated neurotoxicity (ICANS) and no Grade 3 or higher infections. CRS was only seen at the highest dose level of 450 x 106 CAR T cells (Grade 3 in 1 patient; Grade 1-2 in 3 patients). As of 26 April 2022, 9 patients were evaluable for efficacy. At the highest dose level 3 of the 3 patients dosed achieved a complete metabolic remission (CMR) at 1 month. 2 of these patients remain in ongoing CMR by PET-CT at Month 3 and 6 respectively, whilst the 3rd relapsed at 3 months.

2.Title: Dual antigen targeting with co-transduced CD19/22 CAR T cells for relapsed/refractory ALL (AUTO1/22)

Session Title: Gene therapy and cellular immunotherapy - Clinical 1

Session date and time: Saturday, June 11, 2022 11:30 - 12:45 CEST

Session room: Hall Strauss 1-2

Final Abstract Code: S259

Presenting Author: Sara Ghorashian

Conclusions: As of May 27 2022, in 11 treated patients, we have reproducibly generated a product that is balanced in CD19 and CD22 CAR expression, with predominance of dual CAR T cells and having a mostly central memory phenotype. To date and in Kymriah-ineligible patients, AUTO1/22 has demonstrated a favorable safety profile. There have been no incidences of severe CRS, and one Grade 4 ICANS which was indistinguishable from chemotherapy-related leukoencephalopathy. We have seen excellent CAR T expansion, with only 4 patients losing CAR T persistence at the last follow up. Overall, 9 out of 11 patients achieved complete response, and there were 2 non-responders. Notably, 2 out of 3 patients with CD19-ve disease achieved complete response demonstrating the efficacy of the CD22 CAR. Two patients relapsed with CD19+CD22+ disease, a further patient had emergence of molecular MRD and all these events were associated with lack of CAR T Cell persistence. No antigen negative relapses were seen in responding patients. At a median follow up of 8.7 months, 6 of 9 responding patients were in MRD-negative complete remission (1-12 months) and the median duration of b-cell aplasia has not been reached.

3.Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory Primary CNS Lymphoma

Session Title: Poster session

Session date and time: Friday, June 10, 2022 - 16:30 - 17:45 CEST

Final Abstract Code: P1460

Presenting Author: Claire Roddie

Conclusions: Excellent AUTO1 expansion was observed in the peripheral blood by qPCR, with persistence in all treated patients at last follow-up. No grade >/=3 CRS was observed using IV or I-VEN AUTO1 administration. Two cases of grade 3 ICANS were reported following IV infusion. In the first case the patient had several neurological deficits that evolved despite ICANS treatment and were compatible with progressive PCNSL, as confirmed with the month 1 MRI scan. The second case was a patient whose neurological deficits improved with steroids/anakinra. Encouraging response rates were observed: of 6 patients evaluable for efficacy following IV AUTO1, the ORR was 4/6 (67%), with 2 CRs and 2 PRs. These four responding patients are without disease progression at last follow up. Two patients died from progressive PCNSL on study. Longer follow-up is needed and enrolment of additional patients is ongoing.

4.Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory B-Cell Non-Hodgkins Lymphoma (B-NHL), and chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

Session Title: Poster session

Session date and time: Friday, June 10, 2022 - 16:30 - 17:45 CEST

Final Abstract Code: P1459

Presenting Author: Claire Roddie

Conclusions: AUTO1 continues to display a favorable safety profile with no ICANS or Grade 3 CRS. Long term persistence of AUTO1 in the peripheral blood was demonstrated by qPCR. Of the 20 patients evaluable for efficacy, the overall response rate was 18/20 (90%). In the B-NHL cohorts the CRR was 16/17 (94%) (FL: 7/7, MCL: 3/3, DBCL: 6/7). In the CLL cohort a best response of a PR was achieved in 2/3 patients, notably both achieved MRD-negativity in their marrow and both remain in PR at 10 and 6 months respectively. Of the responding MCL, DLBCL, FL and CLL patients, 17/18 (94%) are without disease progression at last follow-up. One MCL patient relapsed six months following treatment and 1 FL patient died in CR from COVID-19. Longer follow-up and enrolment of additional MCL, FL, DLBCL and CLL patients is ongoing.

Conference Call

Management will host a conference call and webcast on June 13, 2022 at7:30 am ET/12:30 pm BST to discuss the EHA data. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus website.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID: 6594553. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID: 6594553.

About Autolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the Company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information, please visit http://www.autolus.com.

About obe-cel(AUTO1)

Obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies.Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, obe-cel may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. In collaboration with Autolus academic partner, UCL, obe-cel is currently being evaluated in a Phase 1 clinical trials for B-NHL. Autolus has progressed obe-cel to the FELIX trial, a potential pivotal trial for adult ALL.

About obe-cel FELIX clinical trial

Autolus Phase 1b/2 clinical trial of obe-cel is enrolling adult patients with relapsed / refractory B-precursor ALL. The trial had a Phase 1b component prior to proceeding to the single arm, Phase 2 clinical trial. The primary endpoint is overall response rate, and the secondary endpoints include duration of response, MRD negative CR rate and safety. The trial is designed to enroll approximately 100 patients across 30 of the leading academic and non-academic centers in the United States,United KingdomandEurope. [NCT04404660]

About AUTO1/22

AUTO1/22 is a novel dual targeting CAR T cell based therapy candidate based on obe-cel. It is designed to combine the enhanced safety, robust expansion & persistence seen with the fast off rate CD19 CAR from obe-cel with a high sensitivity CD22 CAR to reduce antigen negative relapses. This product candidate is currently in a Phase 1 clinical trial called CARPALL for patients with r/r pediatric ALL. [ NCT02443831 ]

About AUTO4

AUTO4 is a programmed T cell product candidate in clinical development for T cell lymphoma, a setting where there are currently no approved programmed T cell therapies. AUTO4 is specifically designed to target TRBC1 derived cancers, which account for approximately 40% of T cell lymphomas, and is a complement to the AUTO5 T cell product candidate, which is in pre-clinical development. AUTO4 has been tested in a Phase 1 clinical trial, LibRA1 for patients with peripheral T cell Lymphoma.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus development of the obe-cel program; the future clinical development, efficacy, safety and therapeutic potential of its product candidates, including progress, expectations as to the reporting of data, conduct and timing and potential future clinical activity and milestones; expectations regarding the initiation, design and reporting of data from clinical trials; expectations regarding regulatory approval process for any product candidates; the collaboration between Autolus and Blackstone; the discovery, development and potential commercialization of potential product candidates including obe-cel using Autolus technology and under the collaboration agreement; the therapeutic potential for Autolus in next generation product developments of obe-cel in B-cell malignancies; the potential and timing to receive milestone payments and pay royalties under the strategic collaboration; and the Companys anticipated cash runway. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. These risks and uncertainties include, but are not limited to, the risks that Autolus preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; the results of early clinical trials are not always being predictive of future results; the cost, timing and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all; the ability to enroll patients in clinical trials; possible safety and efficacy concerns; and the impact of the ongoing COVID-19 pandemic on Autolus business. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 10, 2022, as well as discussions of potential risks, uncertainties, and other important factors in Autolus' subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Contact:

Olivia Manser

+44 (0) 7780 471568

o.manser@autolus.com

Julia Wilson

+44 (0) 7818 430877

j.wilson@autolus.com

Susan A. Noonan

S.A. Noonan Communications

+1-917-513-5303

susan@sanoonan.com

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Autolus Therapeutics Presents Clinical Data Updates at the European Hematology Association Congress - Kentucky Today

More than two years into the pandemic, some of todays students may not remember school prior to COVID-19. Many have been part of quarantined sports teams, wearing masks to class and moves to online remote learning.

The students are not just watching COVID-19 play out on the news. The students are living it, Alameh said.

Alamehs project is designed to evoke interest in the science behind pandemic-related issues debated in schools and communities across the U.S. and around the globe. The curriculum sets middle and high school students up to act as disease detectives, and their investigation will focus on a novel source wastewater.

Wastewater testing is a non-invasive way to track disease prevalence in places such as college residence halls, nursing homes and school buildings. People infected with the coronavirus shed it in their feces, even if they are not symptomatic. If levels of SARS-CoV-2 rise in wastewater testing, decisions can be made about how to best mitigate additional spread in the population.

Since the early days of the pandemic, a group of UK faculty members have been acting as real-life disease detectives, collecting wastewater and breaking samples down to test for COVID-19. They are now ready to take their work on the road in a white Ford van outfitted as a mobile wastewater testing facility. While providing wastewater testing and training in rural parts of Kentucky, they will visit schools to get students excited about science, technology, engineering and mathematics

(STEM).

"Wastewater testing has seen limited use in the past as a public health surveillance tool, but the COVID-19 pandemic has brought newfound interest in the approach due to its ability to monitor infection trends without extensive clinical testing," said UK College of Medicine Assistant Professor of Family and Community Medicine James Keck, M.D.Keck, along with Scott Berry, Ph.D., an associate professor in the UK College of Engineering, are leading two grant-funded research projects involving the detection of SARS-CoV-2 in wastewater.

Alameh, an assistant professor of STEM Education, is a co-investigator leading an offshoot project from the grants developing curriculum for middle and high school students.

Students will begin to see that science is not something that is removed from society at all. Science is ingrained in nearly all things and this project creates a perfect opportunity for us to talk about the nature of science and how socio-scientific issues affect our day to day lives.

High-quality curriculum should not just be interesting. It should come from a felt need. This is what we call problem-based learning and what more of a problem is this, Alameh said.

Ensuring the lessons are a good fit within teachers existing curriculum is a key target of the project. Alameh and UK STEM Education Ph.D candidate, Sagan Goodpaster, are also working with five middle and high school science teachers to review the lessons for their applicability. Together, they are examining the Kentucky standards for teaching science, biology and chemistry and integrating the knowledge students are required to learn, outlined in those standards, into the new lessons being developed around wastewater testing.

The five teachers are helping evaluate whether the lessons are something they think other teachers would want to implement. We need to ensure there would be a time and place for them in the existingcurriculum, Alameh said. They are offering suggestions on all components of the lessons. For example, they might say the way we explain virus modeling is too advanced for middle school, so maybe we can teach it another way instead.

Alameh, who taught high school for seven years prior to working in higher education, worked with the Markey Cancer Center on a similar project, reviewing a science curriculum developed about cancer to ensure it aligned with Kentucky standards.

By showing students content based on real life topics facing their families like cancer and COVID-19, students begin to see that science is what brings us the information that impacts decision-making. With the coronavirus, if they test wastewater at a school and start to detect very high results, what happens next? Do we close schools or not? Put mask mandates in place? Reinforce washing hands? Those little things we usually see in social media and news, they are always so controversial.

But we forget the back story happens because of science, Alameh said. Students will learn how sewer lines are accessed by scientists to collect wastewater and how samples are prepared, as well as have achance to analyze slides themselves in the van. All samples used with schools will be contrived and therefore safe to handle.

Divided into six lessons, the program starts by asking students to consider what viruses are, whether they are alive, the difference between living and non-living things and what defines life. They willalso learn about the structure of viruses and develop a more in-depth understanding of COVID 19, focusing on what sets it apart from other viruses. Lessons also cover how soap and water kill viruses, and how viruses hijack host cells. Students will also explore how viruses spread and the idea of using wastewater to test the prevalence of COVID-19 in a community.

The culminating project has students write a report connecting public health decision-making with wastewater surveillance. Alameh is also working with Anna Hoover, Ph.D., assistant professor in the UK College of Public Health Department of Preventive Medicine and Environmental Health, to tailor lessons to the public health decision-making process.

Students will have a chance to say now that I get the science, now that I understand what viruses are and how they spread and now that I have learned about wastewater testing, this is how I think this information can inform the decision-making process, Alameh said.

This summer, the participating teachers will meet for professional development sessions where they will talk pedagogy, content, go over materials and have a chance to discuss what works and doesnt work forthem.

Its a learning process for all of us, Alameh said. I know from my time as a high school teacher that if a researcher comes to you in isolation, you wont always be able to implement the curriculum in classunless it fits within existing needs. You dont want to add to the teachers loads. They are already doing a lot. But on the other side, you cannot in these times talk about viruses in biology class and not mention the coronavirus. It is exciting to build a curriculum around a topic that is already at the forefront of teachers and students minds.

Science impacts politics, day to day life, society and it even goes into the personal level and influences how families interact. These are conversations we need to embrace. We cannot shy away and say it ispolitics. Thats why we call them socio-scientific issues. There are a lot of driving forces around them.

As a faculty member in the College of Education, Alamehs research stems from the question What is science? and this project will help inform her work. Students, as well as their teachers, will take a testand fill out a survey before they begin the lessons on wastewater testing. After completing the wastewater curriculum and turning in their final paper, they will take the surveys again.

We are testing whether students views related to COVID-19 will change after having a front-row seat for hands-on exploration of the disease. We also want to see if their performance on the scientificconcepts test shows a correlation with their opinions about science and coronavirus. And, we are curious to see if their understanding of the nature of science will be influenced after participating in this project, Alameh said.

Understanding the nature of science is an integral part of students gaining scientific literacy, Alameh said. She will be testing to see if participants understand how cultural and social values can influence interpretation of data. It is also important for students to understand that knowledge they come to know now, such as that the earth is round,was developed through scientific methods, Alameh said.

Often, we have years of evidence that support testable explanations. Before we learned what oxygen is, we didnt know oxygen is needed tomake something burn, but now we have years of evidence to prove it.

However, science is tentative and can change when new evidence comes in.

Particularly when we are dealing with something new, we must adjust and be ready to make new decisions, she said.

Alameh said the pandemic has given everyone the opportunity to watch science evolve in real time as new information is gathered. The process likely has contributed to a distrust of information, since it seems to be changing and updating continuously, Alameh said.

I hope this project will help us gauge how an understanding of the nature of science that scientific explanations is tentative until new evidence arrives influences opinions about COVID-19, Alameh said.

Alameh hopes her research will, ultimately, contribute to helping students improve their ability to understand scientific phenomena, as well as explain their reasoning to others.

To learn more about become a STEM Education teacher, visit education.uky.edu/STEM.

Here is the original post:
College of Education professor takes Covid-19 research to Kentucky schools - WUKY

Int J Mol Sci. 2013 Jun; 14(6): 1222212248.

1Graduate Center for Toxicology and the Departments of Pediatrics, Biomedical and Molecular Pharmacology and Physiology, Markey Cancer Center, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA

2Markey Cancer Center, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA; E-Mail: ude.yku@tterraj.trauts

3Graduate Center for Toxicology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA; E-Mail: ude.yku@2amlaa (A.A.-O.); ude.yku@ttocs.mit (T.S.)

3Graduate Center for Toxicology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA; E-Mail: ude.yku@2amlaa (A.A.-O.); ude.yku@ttocs.mit (T.S.)

1Graduate Center for Toxicology and the Departments of Pediatrics, Biomedical and Molecular Pharmacology and Physiology, Markey Cancer Center, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA

Received 2013 Apr 25; Revised 2013 May 18; Accepted 2013 May 24.

UV radiation (UV) is classified as a complete carcinogen because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R) gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance.

Keywords: Ultraviolet radiation, skin, carcinogenesis, mutagenesis, pigmentation, cancer, melanin, melanocortin 1 receptor

Comprising roughly 16% of body mass, the skin is the largest organ of the body. Skin is organized into two primary layers, epidermis and dermis, which together are made up of epithelial, mesenchymal, glandular and neurovascular components. The epidermis, of ectodermal origin, is the outermost layer and serves as the bodys point of contact with the environment. As such, epidermal biological and physical characteristics play an enormous role in resistance to environmental stressors such as infectious pathogens, chemical agents and UV [16]. Keratinocytes are the most abundant cells in the epidermis and are characterized by their expression of cytokeratins and formation of desmosomes and tight junctions with each other to form an effective physicochemical barrier. The dermis, derived from mesoderm, underlies the epidermis and harbors cutaneous structures including hair follicles, nerves, sebaceous glands and sweat glands. The dermis also contains abundant immune cells and fibroblasts, which actively participate in many physiologic responses in the skin. The epidermis, demarcated from the dermis by a basement membrane, is organized into functional layers defined largely by keratinocyte characteristics such as size, shape, nucleation and keratin expression [7] (). Nascent epidermal keratinocytes formed as a result of cell division by keratinocyte stem cells in the stratum basale undergo a programmed differentiation as they migrate outward toward the surface of the skin to eventually form corneocytes, which are tightly-linked dead but intact cells that form the principle barrier of the outermost epidermal layer [8,9].

Epidermal structure and keratinocyte differentiation. The epidermis is a self-renewing tissue composed mainly of keratinocytes in various stages of terminal differentiation. Keratinocytes are produced in the stratum basale (basal layer), and move outward through the epidermis, undergoing a programmed series of differentiation involving enucleation and accumulation of cytokeratins and tight junctions with each other. Keratinocytes also receive melanin from melanocytes in the form of pre-packaged organelles termed melanosomes. The basic layers from the basement membrane outward are the stratum basale, stratum spinosum, stratum granulosum, and the stratum corneum, each identified by the morphology and differentiation state of the keratinocyte as indicated by expression of cytokeratins and other proteins.

Besides the creation of a highly effective physical barrier, keratinocytes also accumulate melanin pigments as they mature, and epidermal melanin functions to potently block UV penetration into the skin. Although melanin may be found in abundance in epidermal keratinocytes, it is not manufactured in these cells. Rather, melanin synthesis is restricted to melanocytes, which are derived from neural crest and are the second most abundant cell in the epidermis [10,11]. In fact, melanocytes can be found both in the dermis and epidermis. Epidermal melanocytes are generally positioned in the basal layer above the basement membrane. Melanocytes are also found in hair follicles to impart pigment to nascent hair [12]. Dermal melanocytes can be found in nevi (moles). Because melanocytes are the only source of pigment in the skin, inherited pigmentary defects such as albinism tend to be caused by melanocytic genetic defects [10,13]. Through dendritic extensions, melanocytes may be in intimate contact with as many as fifty neighboring keratinocytes in what is known as an epidermal melanin unit [11,14]. There are many contact-dependent and paracrine interactions that occur between keratinocytes and melanocytes in the epidermal melanin unit. Pigment made by melanocytes is transferred to adjacent keratinocytes in cellular organelles termed melanosomes by way of melanocytic dendrites [1517]. In fact, most of the melanin in the skin is found in keratinocytes where it accumulates to function as a natural sunscreen to protect the skin against incoming UV photons. Besides blocking UV penetration into the skin, melanin may have many other important physiologic effects including regulatory influences over epidermal homeostasis, free radical scavenging to protect against oxidative injury, and possibly even antimicrobial activity [10,1824].

The amount and type of epidermal melanin is the main factor that determines skin complexion and UV sensitivity. Melanin is a large bio-aggregate composed of subunits of different pigment species formed by oxidation and cyclization of the amino acid tyrosine [10,25,26] (). Intriguingly, the intermediates of melanogenesis may have important regulatory roles in the skin [2729]. Melanin exists in two main chemical forms: (1) eumelanin, a dark pigment expressed abundantly in the skin of heavily pigmented individuals, and (2) pheomelanin, a light-colored sulfated pigment resulting from incorporation of cysteines into melanin precursors [30]. Eumelanin is much more efficient at blocking UV photons than pheomelanin, thus the more eumelanin in the skin, the less UV-permeable is the epidermis [31]. Fair-skinned people who are almost always UV-sensitive and have high risk of skin cancer have little epidermal eumelanin and therefore realize much more UV than darker-skinned individuals. Therefore, the fairer the skin, the more damaging UV exposure will be. In fact, pheomelanin levels are similar between dark-skinned and light-skinned individuals, and it is the amount of epidermal eumelanin that determines skin complexion, UV sensitivity and cancer risk. Data suggest that pheomelanin may promote oxidative DNA injury and melanomagenesis by generating free radicals in melanocytes even in the absence of UV [3237].

Melanin Biosynthesis. Melanin, a large bioaggregate composed of pigmented chemical species, is found in two major forms: the brown/black highly UV-protective eumelanin pigment and the red/blonde UV-permeable pheomelanin. Both eumelanin and pheomelanin are derived from the amino acid tyrosine. Tyrosinase is the enzyme that catalyzes the rate-limiting synthetic reaction for both melanin species and when defective causes albinism. Incorporation of cysteine into pheomelanin results in the retention of sulfur into the pigment, which yields a light color to the final melanin product and may contribute to oxidative injury in the skin. The melanocyte stimulating hormone (MSH)melanocortin 1 receptor (MC1R) signaling axis is a major determinant of the type and amount of melanin produced by melanocytes in the skin.

Skin complexion is among the most important determinants of UV sensitivity and skin cancer risk. The Fitzpatrick Scale is a semi-quantitative scale made up of six phototypes that describe skin color by basal complexion, melanin level, inflammatory response to UV and cancer risk [13] (). Minimal erythematous dose (MED) is a quantitative method to report the amount of UV (particularly UVB) needed to induce sunburn in the skin 2448 h after exposure by determining erythema (redness) and edema (swelling) as endpoints. The fairer the skin, the easier it is for UV to cause inflammation (sunburn). MED, therefore is highest in dark-skinned persons since more UV radiation is needed to burn eumelanin-rich skin [3840]. In contrast, fair-skinned people whose skin expresses predominantly pheomelanin have low MEDs. Low Fitzpatrick phototype correlates with both MED and with melanoma and other skin cancer risk [41].

Skin pigmentation, the Fitzpatrick scale and UV risk.

Abundant in the environment, UV contributes to a variety of skin maladies including inflammation, degenerative aging and cancer [1]. Historically, humans have been exposed to UV radiation mainly through occupational exposure to sunlight. Recreational UV exposure, however, has increased dramatically in recent years because of outdoor leisure activities and to purposely tan for cosmetic purposes [42,43]. Being a component of the electromagnetic spectrum, UV photons fall between the wavelengths of visible light and gamma radiation. UV energy can be subdivided into UV-A, -B and -C components based on electro physical properties, with UV-C photons having the shortest wavelengths (100280 nm) and highest energy, UV-A having the longest (315400 nm) but least energetic photons and UV-B falling in between (). Each component of UV can exert a variety of effects on cells, tissues and molecules.

Electromagnetic spectrum of visible and UV radiation and biologic effects on the skin. Solar UV radiation can be subdivided into UVA, UVB and UVC components, however because of atmospheric ozone that absorbs UVC, ambient sunlight is predominantly UVA (90%95%) and UVB (5%10%). UV penetrates the skin in a wavelengthdependent manner. Longer wavelength UVA penetrates deeply into the dermis reaching well into the dermis. In contrast, UVB is almost completely absorbed by the epidermis, with comparatively little reaching the dermis. UVA is efficient at generating reactive oxygen species that can damage DNA via indirect photosensitizing reactions. UVB is directly absorbed by DNA which causes molecular rearrangements forming the specific photoproducts such as cyclobutane dimers and 64 photoproducts. Mutations and cancer can result from many of these modifications to DNA.

Ambient UV exposure varies geographically according to intensity of sunlight in a particular location on Earth. Since UV radiation can be reflected, scattered and dampened by atmospheric particles, ambient UV dose varies according to the amount of atmosphere it must pass through, making UV doses higher nearest the Equator (where sunlight strikes the Earth most directly), at higher altitudes and in conditions of minimal cloud or particulate cover. Personal UV dosing depends not only on strength of solar radiation, but also on time spent outdoors occupationally or recreationally and the usage of UV-protective clothing, shade and sun blocks. Since equatorial locations tend to be warm and conducive to recreational or occupational outdoor activities, people living such locales typically wear less clothing and have more contact with ambient sunlight and usually receive much higher ambient UV doses than persons inhabiting temperate climates. Not surprisingly, skin cancer risk generally mirrors this geographic pattern, particularly among fair-skinned sun-sensitive persons [4446].

The number and use of indoor tanning salons has skyrocketed over the last several years. In America alone, only 1% of the population had ever used a tanning bed in the late 1980s. Now it is estimated that over 25% of Americans have engaged in purposeful exposure to artificial UV radiation [47]. Indoor tanning is an important industry with nearly 30 million clients, 100,000 employees and billions of dollars of annual business. Indoor tanning machines are poorly regulated and vary widely with respect to UV composition and strength. UV output from tanning beds can be up to ten times more powerful than sunlight [48,49], making the tanning bed an authentic carcinogenic instrument. Tanning can be addictive, leading to frequent and significant UV exposure over time [5052], and since tanning often appeals to adolescents and young adults, tanning patrons UV history can be significant for many years [53].

Indoor tanning clearly increases incidence of skin cancers [54,55]. With respect to melanoma, the deadliest of skin malignancies, lifetime risk increases by 75% if people engage in artificial tanning before the age of 35 years [5658]. Cancer risk increases with years of use, number of sessions, and total number of UV h exposed [54,56,59,60]. Since the molecular pathways in the skin that activate UV-induced tanning result from cellular and DNA damage which underlie skin damage and carcinogenesis (), it appears as though there is no safe use of tanning salons [57]. The tanning industry has engaged a powerful political lobby to further its commercial interests by downplaying the adverse health risks of UV. Instead, the industry publicizes the health benefits of UV to its clients, emphasizing vitamin D production which is naturally made in the skin by the chemical conversion of 7-dehydrocholesterol into vitamin D3 (cholecalciferol) after UVB exposure [6169]. In fact, UV doses that induce tanning far exceed what is required for adequate vitamin D production and the widespread availability of vitamin D in supplements and fortified foods minimizes the need for UV exposure to avoid symptoms of rickets and vitamin D deficiency [7074]. Multiple studies report overwhelming evidence that the risks of indoor tanning far outweigh potential health benefits, most significantly for malignancy. Decreasing UV radiation exposure, both naturally from sunlight and artificially from tanning bed use, may be the single best way to reduce incidence of melanoma and other skin cancers [75].

Mechanisms of the physiologic tanning response. Hormonal interactions between epidermal keratinocytes and melanocytes mediate much of the cutaneous melanization response. DNA and cellular damage in keratinocytes up-regulates transcription of the pro-opiomelanocortin (POMC) gene which encodes production and secretion of melanocyte stimulating hormone (-MSH). -MSH binding to melanocortin 1 receptor (MC1R) on melanocytes in the basal epidermis generates the second messenger cAMP via interactions between MC1R and adenylyl cyclase, and leads to activation of protein kinase A and the cAMP responsive binding element (CREB) and microphthalmia (Mitf) transcription factors. CREB and Mitf directly enhance melanin production by raising levels of tyrosinase and other melanin biosynthetic enzymes. Thus, MSH-MC1R signaling leads to enhanced pigment synthesis by melanocytes and accumulation of melanin by epidermal keratinocytes. By this mechanism, the skin is better protected against UV insults. Of note, UV-induced pigmentation may also occur through other signaling pathways as well as direct effects of UV on melanocytes, and there is some disagreement in the field over the role of epidermal MSH in the adaptive pigmentary response.

UV has many effects on skin physiology, with some consequences occurring acutely and others in a delayed manner. One of the most obvious acute effects of UV on the skin is the induction of inflammation. UVB induces a cascade of cytokines, vasoactive and neuroactive mediators in the skin that together result in an inflammatory response and causes sunburn [3,4,6,7679]. If the dose of UV exceeds a threshold damage response, keratinocytes activate apoptotic pathways and die. Such apoptotic keratinocytes can be identified by their pyknotic nuclei and are known as sunburn cells [80]. UV also leads to an increase in epidermal thickness, termed hyperkeratosis. By causing cell injury, UV induces damage response pathways in keratinocytes. Damage signals such as p53 activation profoundly alter keratinocyte physiology, mediating cell cycle arrest, activating DNA repair and inducing apoptosis if the damage is sufficiently great. Several h after UV exposure, however, and damage response signals abate, epidermal keratinocytes proliferate robustly [81], mediated by a variety of epidermal growth factors. Increased keratinocyte cell division after UV exposure leads to accumulation of epidermal keratinocytes which increases epidermal thickness. Epidermal hyperplasia protects the skin better against UV penetration [82].

Coupled with epidermal hyperkeratosis is adaptive melanization of the skin, also known as tanning [4,10,8386]. UV up-regulates production and epidermal accumulation of melanin pigment in the skin [8791]. This important physiologic response protects the skin against subsequent UV damage, and defects in this pathway are linked with cancer susceptibility. UV-mediated skin darkening is actually biphasic, with initial skin darkening occurring from redistribution and/or molecular changes to existing epidermal melanin pigments. Delayed increases in skin darkening, mediated by actual up-regulation in melanin synthesis and transfer to keratinocytes, begin several h to days after UV exposure [92,93]. Adaptive melanization is likely a complex physiologic response [4,10,83,85] involving multiple skin cell types interacting in a variety of ways () [86,94102]. UV has many other effects on the skin, including induction of an immune-tolerant or immunosuppressive state [103110] and production of vitamin D by direct conversion of 7-dehydrocholesterol into vitamin D3 (cholecalciferol) [6169]. Ambient sunlight, for the most part, is a mixture of UVA and UVB, yet each UV component may exert different and distinct effects on the skin [111,112]. UVB, for example, is a potent stimulator of inflammation and the formation of DNA photolesions (such as mutagenic thymine dimers) [112,113], whereas UVA is much less active in these measures but instead is a potent driver of oxidative free radical damage to DNA and other macromolecules [114116]. Thus, each may contribute to carcinogenesis through different mechanisms [117119]. The influence of UVA and UVB on skin physiology is an active area of investigation.

Besides promoting formation of photodimers in the genome, UV causes mutations by generating reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide and the hydroxyl radical [21] (). Nucleotides are highly susceptible to free radical injury. Oxidation of nucleotide bases promotes mispairing outside of normal Watson-Crick parameters, causing mutagenesis [120]. The transversion guaninethymine, for example, is a well-characterized mutation caused by ROS by oxidizing guanine at the 8th position to produce 8-hydroxy-2-deoxyguanine (8-OHdG) [121,122]. 8-OHdG tends to pair with an adenine instead of cytosine and therefore this oxidative change mutates a G/C pair into an A/T pair. Such mutations can be found in tumors isolated from the skin, suggesting that oxidative injury can be carcinogenic [123]. Cellular maintenance pathways exist to inactivate oxidative species as well as to repair the DNA damage they cause. The base excision repair pathway (BER) is the main molecular means by which cells reverse free radical damage in DNA to avoid oxidative mutagenesis. This pathway is initiated by damage-specific glycosylases that scan DNA for specific alterations including deaminated, alkylated or oxidized bases. After altered or inappropriate bases are recognized by a lesion-specific glycosylase, the enzyme cleaves the nucleotide base from the sugar and phosphodiesterase backbone by lysis of the N-glycosylic bond between the base and the deoxyribose. This step forms an abasic or apurinic/apyrimidinic (AP) site in the DNA, which is then processed and repaired using the complementary strand as a template to ensure fidelity.

UV generates oxidative free radicals. UV photons interact with atomic oxygen to promote formation of free radical derivatives such as superoxide, hydrogen peroxide and the highly reactive hydroxyl radical. Free radicals avidly attack macromolecules such as protein, lipid, RNA and DNA, altering their structure and interfering with their function. Detoxifying and protective enzymes such as superoxide dismutase, catalase and glutathione peroxidase detoxify and reduce levels of oxidative species in the cell.

Cells also have a complex and robust network of anti-oxidant molecules that detoxify reactive species to prevent free radical changes to DNA and other macromolecules. Glutathione (GSH) is an oligopeptide made up of three amino acids- cysteine, glycine and glutamine and is among the most important cellular antioxidant molecules. By donating electrons to otherwise reactive molecules, GSH functions as a reducing agent to neutralize reactivity of free radicals. In the process, glutathione itself becomes oxidized but can be reduced to its basal state by glutathione reductase using NADPH as an electron donor and be recycled. In any cell, therefore, glutathione can be found in both its reduced and oxidized forms and abnormalities in the ratio of reduced to oxidized glutathione can indicate oxidative stress. Catalase is another major antioxidant enzyme that detoxifies hydrogen peroxide [124126], whereas superoxide dismutases (SODs) inactivate superoxide anions [127]. Regulation of these antioxidant enzymes is a major area of investigation [128,129] since it is critical in determining cutaneous responses to UV radiation.

Besides free radical formation, UV directly affects nucleotide base pairing in DNA [130,131]. Pyrimidine bases are particularly vulnerable to chemical alteration by absorption of UV energy. Shorter-wavelength UV photons, particularly UV-B and UV-C, cleave internal 56 double bonds of pyrimidines. When this occurs between adjacent pyrimidines, abnormal covalent bonds may form and alter the three-dimensional structure of the double helix. Two major photolesions- cyclobutane pyrimidine dimers or (6,4)- photoproducts- predictably form in this way after UV exposure, and both are highly mutagenic [132]. It is estimated that one days worth of sun exposure results in up to 105 UV-induced photolesions in every skin cell [133]. UV-induced photolesions impair transcription, block DNA replication and base pair abnormally. They cause characteristic transition mutations known as UV signature mutations, for example, TTCC. The abundance of UV signature mutations in cancer-regulatory genes among many primary skin cancer isolates strongly supports UV as a cancer-causing agent [134137].

Nucleotide excision repair (NER) is an evolutionarily-conserved mechanism for repairing UV-induced photoproducts and other bulky DNA lesions [138]. The importance of NER in cancer resistance is best illustrated by considering the natural history of patients with Xeroderma Pigmentosum (XP), a rare UV hypersensitivity syndrome caused by homozygous defects in any one of at least eight required effector proteins of a common pathway that executes NER: XPA, ERCC1, ERCC3 (XP-B), XPC, ERCC2 (XP-D), DDB2 (XP-E), ERCC4 (XP-F), ERCC5 (XP-G) and POLH. XP patients demonstrate profound UV sensitivity and develop characteristic skin changes including pigmentary abnormalities, capillary telangiectasias and atrophy on UV-exposed anatomic sites at very early ages. Premalignant lesions and skin cancers develop in high frequency and much sooner than in unaffected persons. Basal cell carcinomas, squamous cell carcinomas and melanomas often develop before the second decade of life, decades before the general population [139]. Moreover, XP-associated skin cancers frequently demonstrate UV signature mutations, clearly indicating the importance of NER in the cancer resistance [140]. The NER pathway represents an orchestrated interaction of enzymes that function together to repair lesions that alter the three-dimensional structure of DNA. After recognition of damage and recruitment of a multiprotein repair complex to the damaged site, the damage strand is nicked several nucleotides away on either side of the damaged bases. The damaged region is excised and the resulting gap is filled in by a DNA polymerase using the non-damaged strand as a template [141143] (). Though only a handful of core factors are necessary and sufficient for the repair of UV-induced DNA lesions, there are numerous accessory factors that regulate this genome maintenance pathway. While the importance of NER in UV and skin cancer resistance is most clearly demonstrated by the natural history of patients with XP, attention is being paid to the role of NER polymorphisms on UV sensitivity and skin cancer incidence in sporadic populations.

UV-induced cyclobutane dimers- structure (A) and repair by the Nucleotide Excision DNA Repair (NER) pathway (B). The NER pathway is mediated by at least eight enzymes that work together to identify bulky DNA lesions that distort the structure of the double helix, excise the damaged portion and replace the excised region by DNA synthesis directed by the complementary strand. Homozygous deficiency in any one of the NER enzymes leads to the clinical condition known as Xeroderma Pigmentosum (XP). Although not shown, NER can also be initiated in actively transcribed regions of the genome by involvement of the Cockayne syndrome proteins A and B.

Skin cancers are by far the most common malignancies of humans, with well over a million cases diagnosed each year [144]. Roughly 1 in 5 Americans will develop skin cancer in their lifetime [145]. They account for nearly 15,000 deaths and more than three billion dollars each year in medical costs in the United States alone [146,147]. Like many other cancers contributed to by environmental etiologies (in this case UV), skin cancer incidence increases markedly with age presumably reflecting the long latency between carcinogen exposure and cancer formation. Skin cancers are commonly grouped into two main categories, melanoma and non-melanoma skin cancers (NMSC), based on cell of origin and clinical behavior. Risk of skin cancer is heavily influenced by UV exposure and by skin pigmentation [148] ().

Influence of pigmentation on skin cancer risk. Fair-skinned individuals with low levels of melanin in the epidermis display a UV sensitive phenotype, tending to burn rather than tan, after UV exposure. Recent data suggest that mutations that contribute to fair complexion and tanning impairment, specifically signaling defects in the melanocortin 1 receptor (MC1R), may also be associated with less efficient DNA repair in melanocytes. MC1R-defective individuals not only suffer higher realized doses of UV radiation because their skin is less able to block UV photons, but they may also accumulate more mutations from UV exposure because of defective DNA repair.

Malignant melanoma of the skin is the deadliest form of skin cancer. Thought to arise from epidermal melanocytes, melanoma is a treatment-refractory and metastasis-prone malignancy whose incidence has increased steadily and significantly over the last several decades [149]. Whereas only one in 1500 Americans was ever diagnosed with melanoma in the 1930s, now roughly one in sixty will be affected by the disease [150]. Melanoma accounts for about three quarters of all deaths from skin cancers, numbering nearly ten thousand per year in the U.S., despite accounting for far fewer than ten percent of all skin malignancies. Melanoma burden is predictably largest in places with large numbers of fair-skinned individuals living in warm, sunny climates [151]. Most melanomas arise out of pre-existing moles, therefore having many nevi is another important risk factor for the disease. If caught early, many melanomas can be managed by surgical excision alone. However, melanomas are quick to invade and metastasize and long-term survival is poor for advanced disease. Even with recent progress made in targeted therapy [152156] and immunotherapy [157,158], melanoma is notoriously difficult to treat once it has spread beyond its original site. It is not clear why melanoma incidence has increased so dramatically over the past several decades, but it is likely multifactorial, with contributions from increased UV exposure, environmental and inherited cancer risk factors and better surveillance and earlier detection [151,159172].

Non-melanomatous skin cancers greatly outnumber melanomas in incidence, but fortunately most are much easier to treat and have much better long-term prognosis. The two major forms, basal cell carcinomas and squamous cell carcinomas, are both derived from epidermal keratinocytes. They are less deadly than melanoma mainly due to their tendency to remain confined to their primary site of disease, which makes their management much more straightforward. The overwhelming majority of keratinocyte malignancies develop in the areas of skin most exposed to UV, such as on the face and arms. Most are effectively treated by local control measures alone such as resection, MOHS microsurgery or cryosurgery.

There are strong epidemiologic and molecular data linking all forms of skin cancer to UV exposure [173], and it is estimated that UV is causative for nearly 65% of melanoma and 90% of non-melanoma skin cancers [174,175]. UV-signature mutations in key cancer-relevant genes such as the p53 tumor suppressor in squamous cell carcinoma for example are well-characterized, and exome analysis of a panel of melanomas revealed strong genetic evidence for a direct mutagenic role of UV radiation in the pathogenesis of melanoma [137,176183]. Since UV-induced DNA mutations represent a major causative factor for melanoma and other skin cancers, it follows that resistance to UV-mediated mutagenesis is a critical determinant of skin cancer risk [184].

The melanocortin 1 receptor (MC1R) is a critical genetic locus involved in pigmentation, the adaptive tanning response and skin cancer susceptibility [185192]. The MC1R is found on the surface of melanocytes where it binds to -melanocyte stimulating hormone (MSH) and transmits differentiation signals into the cell through activation of adenylyl cyclase and generation of cAMP [193195]. cAMP signaling leads to activation of the protein kinase A (PKA) cascade which, in turn, leads to increased levels and/or activity of many melanogenic enzymes to enhance production and export of melanin by melanocytes [90,196,197] (). MC1R signaling also decreases UV-mediated mutagenesis by enhancing genome maintenance pathways in melanocytes [125,126,192,198]. Loss-of-signaling MC1R polymorphisms are commonly found among fair-skinned, sun-sensitive and skin cancer-prone populations (e.g., Northern Europeans). The most prevalent MC1R mutations (D84E, R151C, R160W and D294H) are commonly referred to as RHC (red hair color) alleles because of their association with red hair color, freckling and tendency to burn after UV exposure [199,200]. Loss of signaling MC1R alleles such as the RHC variants are associated with up to a four-fold increased lifetime risk of melanoma and other skin cancers [201203]. Overall, there is much evidence placing MC1R as a critical determinant of skin cancer risk, and regulation of eumelanin by POMC derived peptides depends on genetic context [204].

MC1R signaling protects the skin from UV damage by at least two major mechanisms. First, by inducing pigment synthesis in melanocytes, MC1R enhance production and accumulation of eumelanin in the epidermis. Epidermal melanization blocks penetration of UV into the skin, reducing realized doses of UV and decreasing mutagenesis and cancer risk. MC1R signaling also directly influences UV resistance of melanocytes by enhancing nucleotide excision DNA repair and oxidative resistance. Since MC1R signaling is potentially targetable by agents that influence cAMP levels [82,84,205], pharmacologic manipulation of cutaneous cAMP may be a useful approach to reduce UV sensitivity and cancer risk. Theoretically, raising cAMP levels in the skin can be accomplished either by stimulating its production (e.g., adenylyl cyclase activation) or by impeding its degradation (e.g., phosphodiesterase inhibition). Both of these approaches have been quite successful in enhancing epidermal melanin levels in animal models [84,206] and each would be expected to be effective even in individuals harboring loss-of-signaling functional mutations in MC1R. Alternatively, -MSH or agonistic MC1R peptide ligands would offer more specificity (working only on melanocytes) but might be less effective in individuals with inherited MC1R signaling defects [192,193,207].

One of the greatest risk factors for the development of cutaneous melanoma is having a fair skin complexion, which is characterized by low levels of a UV-blocking dark pigment called eumelanin in the epidermis. Individuals with light skin pigmentation suffer comparatively more skin damage from UV because it is relatively easy for UV rays to penetrate the epidermis to damage both keratinocytes and melanocytes in the deeper layers of the epidermis. Fair-skinned individuals are exposed to higher realized doses of UV radiation in the skin and UV-induced mutations, which directly contribute to melanoma and other forms of skin cancer, accumulate over time. Much UV-induced pathology, including skin cancer, can be avoided by minimizing UV exposure ().

Minimize time outdoors during peak UV h (10 am to 4 pm). Seek shade as much as possible. Be aware that sunlight bounces off reflective surfaces and can reach you even under an umbrella or tree.

Avoid getting a sunburn. More than 5 sunburns doubles risk of skin cancer.

Use sunscreens with a sun protection factor (SPF) >15. Make sure to apply repeatedly (especially with sweating or swimming) and as directed. Use sunblocks that offer protection from both UV-A and UV-B rays, and be sure to cover often-missed spots- lips, ears, around eyes, neck, scalp, hands and feet.

Wear protective clothing such as rash guards and tightly woven fabrics.

Wear a hat. Wide-brimmed hats protect head, face, ears and neck. If a baseball cap is worn, make sure to use sunscreen on ears and neck.

Wear UV-protective sunglasses

Strength of solar UV increases at high altitude and with less cloud cover. Monitor the UV Index (http://www.epa.gov/sunwise/uvindex.html) and plan accordingly.

Get Vitamin D safely by relying on diet and supplements rather than UV exposure.

Do not frequent tanning beds. They can be more dangerous than sunlight. Frequent use of artificial tanning products clearly increases risk of each of the major kinds of skin cancer, including melanoma.

Sunless self-tanning products seem safe but typically offer little sun-blocking UV protection on their own.

Examine your skin frequently, at least once a month, head to toe. Use a full-length mirror and a hand mirror to check your back, or involve a partner. Have a professional skin examination annually.

Seek professional medical attention for:

Sores that do not heal

Changes in moles (growth, irregularity, asymmetry, color changes, elevation, pain, itching)

Skin cancers are much more easily treated when caught early.

We and others are increasingly interested in heritable factors that determine melanoma risk to be able to intervene in the carcinogenic process. One of the most important alleles that influences skin cancer risk is the melanocortin 1 receptor (MC1R), whose function is central to the adaptive pigmentation (tanning) response in the skin. Besides mediating the tanning response, MC1R exerts a powerful influence on the ability of melanocytes to repair UV-induced DNA damage by the nucleotide excision DNA repair pathway. New insights into the ways in which MC1R and other genes function to protect the skin against the harmful consequences of UV may allow the rational development of pharmacologic strategies to reduce UV sensitivity and cancer risk.

The authors wish to thank current and past funding sources: the National Cancer Institute (R01 CA131075, R01 CA131075-02S1), the Wendy Will Case Cancer Research Fund, the Markey Cancer Foundation, the Childrens Miracle Network and the Jennifer and David Dickens Melanoma Research Foundation.

The authors declare no conflicts of interest.

Excerpt from:
UV Radiation and the Skin - PubMed Central (PMC)

By HEATH HARRISON and MARK SHAFFER

1. COVID-19Everyone wishes it wasnt so, but, unfortunately, the COVID-19 pandemic still dominated headlines this year.

The Lawrence County Health Department worked diligently all year to administer vaccines to the population, hosting clinics at a main location at the South Point Board of Education office, as well as at the health department, in schools and at events throughout the region.

The vaccine was first given to older and at-risk groups, then, by spring, was available to all adults. In the fall, booster shots were available, as well as vaccines for children.

While things seemed to be clearing up in the spring, and the Ironton-Lawrence County Memorial Day Parade and the Lawrence County Fair returned as cases numbers dropped, as the year progressed, both the Delta and Omicron variants of the virus kept the county in the red for high transmission.

Schools struggled with the situation, with the pandemic continuing to impact both the classroom and sports.

All but one school district in the county, Ironton, began the academic year with no mask requirements but, within weeks and cases on the rise, districts changed course and all in the county adopted a policy mandating facial coverings for students and staff.

As the Christmas holiday began, the health department reported that Lawrence County has seen 11,269 cases of COVID-19 since the pandemic began, 721 hospitalizations and 182 deaths.

Ohio Gov. Mike DeWine tours parts of Lawrence County that were hardest hit by Februarys three winter storms. (Submitted photo)

2. Winter stormsThe Tri-State area was brought to a standstill in February, with three winter storms hitting the region hard.

The first brought ice, the second, the most severe, had ice and snow, and a third consisted of only snow.

Residents throughout the area listened as the sounds of buckling trees and branches filled the night during the first two storms. Thousands were left without power and many roads were blocked and impassible.

Restoration of power was a long wait for many in rural parts of the county, with remote lines and poles presenting a challenge for crews from AEP and Buckeye Rural.

In the immediate aftermath of the storms, Gov. Mike DeWine visited Lawrence County, hosting a press conference at South Point High School before touring the hardest hit parts of the county. DeWine activated the National Guard to assist the county in its cleanup.

The impact of the storm lingered into late spring, with volunteer groups, such as teens from Maumee United Methodist Church, located in northern Ohio, continuing to help with cleanup on private properties.

3. New Lawrence County JailBuilt in 1974, the Lawrence County Jail was state of the art at the time but as the years passed, the demand for more cells increased and there wasnt a workable solution until October, when Gov. Mike DeWine announced the county will be getting $16.8 million to fund a new jail facility. Details about total costs, location and when construction could possibly start are still being worked out. DeWine was supposed to make an appearance in Lawrence County but canceled after being exposed to someone with COVID-19.

4. Chesapeake upheaval

New Chesapeake Mayor Nate Ittig and the newly appointed members of village council, along with incumbent council member Paul Hart, at Novembers regular meeting. (The Ironton Tribune | Heath Harrison)

2021 was a chaotic year for Chesapeake. It began with the village council removing Randy Thompson as police chief in February, replacing him with Steven Woodyard.

Then, in the summer, a recall petition against Mayor Kim Oldaker was filed, but ruled invalid by the county board of elections.

In October, the village was left with little of a government when Oldaker and four council members abruptly resigned, citing disagreements with council member Paul Hart, as well as those who were running unopposed for three seats in the November election.

With the resignations, council member Nate Ittig became acting mayor, leaving Hart as the sole member of council.

At Novembers council meeting, Ittig, now mayor, moved to fill the vacancies, naming the three candidates, Lisa Blake, Jacob Wells and Drew Griffin who were set to start their terms in January, to immediately fill those seats. They were joined by Katie Bentley and Marvin Henson, who Ittig chose for the other two vacancies, one of which was his former seat.

Following the appointments, at the same meeting, the council then voted not to retain Woodyard as police chief. This was met with the resignation of two officers.

Sgt. Josh Sammons, the highest ranking of the remaining officers, was named as interim chief.

The year also saw the resignation of street commissioner Danny Burd and fiscal officers Theresa Lawless and Lennie Abrams. Abrams returned when he was named as interim fiscal officer in December, in order to continue to help the village prepare for an audit from the state.

5. Grocery store changesIn April came surprising news that the Bartram and Son grocery store was being closed and the staff was being merged with those at a new Food Fair grocery store in the Ironton Hills Plaza, the site of the former Pick n Save, which closed in the spring.

Bartram and Son was bought by Forth Foods Inc., which owns 16 stores in the area. Tim Forth, the owner and president of Forth Foods Inc. and owner of Ironton Food Fair, said the two companies had worked together for many years and they ran with the Food Fair program, although they chose to run it under the Bartram and Son name.

Maddie Cogan and Robbie Brown are owners of the Ironton Shake Shoppe. (Mark Shaffer | The Ironton Tribune)

6. Shake Shoppe lawsuitOne of Irontons most popular businesses found itself sued in federal court. Maddie Cogan and Robbie Brown, owners of the Shake Shoppe in Ironton since 2019, were sued by Shake Shoppe LLC, the company of the Gallipolis Shake Shoppe, which has been owned by three generations of the Snedaker family since the 1950s.

In the 1950s, six Dairy Queens in southern Ohio, located in Ironton, Gallipolis, New Boston, Jackson, Logan and Portsmouth, saw the patent on their soft serve machine with the company expire. As a result, the six businesses decided to rebrand as the Shake Shoppe, forming a business agreement. They used the same signage, but were individually owned. Of the remaining three locations, only the Gallipolis is run by the same family who originally owned it.

In the suit, Shake Shoppe LLC cited slogans and imagery, which they said were drawn by hand by original owner Marge Snedaker and used as early as 1956. Shake Shoppe LLC had those items trademarked with the state and federal government.

The logos and designs were made into digital renderings and have been used by Shake Shoppe LLC since at least 2015 on social media sites and to make clothing items. The use of the logos on social media, on the Ironton shop and on T-shirts is the issue in the suit. The name and imagery have been used by the Ironton location since the 1950s, under its original owners, the Salisbury family, then two successors, before Cogan and Brown bought the location in 2019.

News of the lawsuit saw a surge of support for the Ironton location, with posts on social media, supportive T-shirt sales and an increase in traffic by those who wanted to back the location.

7. Steve Dodgion retires

New Collins Career Technical Center superintendent Adam Pittis, left, took over after Steve Dodgion, right, retired in the summer. (Submitted photo)

One of the most significant figures in education in Lawrence County wound down his career in 2021, when Steve Dodgion, the superintendent of Collins Career Technical Center for 19 years, retired in July.

Dodgion worked in Lawrence County schools for 47 years, with all but five of those being at CCTC, where he also served as assistant superintendent before taking the top job.

He was hailed by faculty for his work expanding CCTCs offerings and overseeing a growth in its student body, with the school serving more students than any other vocational institution in Ohio.

In addition to being hailed for developing CCTCs health programs, Dodgion said he was most proud of launching the Project Lead the Way STEM program 14 years ago, one of the first in the state to do so.

As Dodgion departs, the PLTW program is set to expand with the addition of an aviation program.

He was succeeded by Adam Pittis as superintendent.

8. Live events returnIn 2020, most local live events were downsized or canceled altogether because of state orders about large groups gathering in an effort to curtail the spread of COVID-19.

After the COVID-19 vaccine roll out in the spring, many events returned in full force like the annual Ironton-Lawrence County Memorial Day Parade and its associated events, the Lawrence County Fair, Ironton Wizardfest and the Ohio River Revival.

Brad Bear, one of the organizers of the Wizardfest, said crowds were happy to be back in Ironton and take it to the next level.

Its going really, really good. Its excellent, its fantastic, he said. Everybody came back to town and is having a great time.

Academic events also saw a return in 2021, with the county spelling bee and Quiz Bowl events making a comeback and schools returning to more traditional graduation ceremonies.

9. InfrastructureThere was a lot of infrastructure work in the area in 2021.

The new Russell, Kentucky viaduct bridge was completed in November and Kentucky Gov. Andy Beshear made a surprise appearance to open it up.In South Point, the Solida Road roundabout is being expanded by the Ohio Department of Transportation.

And ODOT announced a proposed roundabout for the intersection of U.S. 52 and State Route 93 in Ironton in an effort to reduce the number of crashes in the area. The plan calls for the construction of two single-lane roundabouts on State Route 93, one on the north and south sides of the U.S. 52 interchange, replacing signalized intersections. These would be designed in 2022, with construction expected to start in May 2023 and wrap up that October.

The Tower House in Ironton. (Mark Shaffer | The Ironton Tribune)

10. Tower House on TVThanks to an Instagram post, one local house gathered a lot of attention on social media and even ended up featured on national television.

Irontons Tower House was featured on HGTVs Cheap Old Houses, which follows Instagram stars Ethan and Elizabeth Finkelstein as the tour the country looking at houses that sell for under $150,000. The show is based on the Finkelsteins Instagram page, also called Cheap Old Houses, which has 1.4 million followers.

The Tower House, a gray four-story house with a tower that leans slightly, was built in 1874 by ironmaster Frederick Norton, the owner of the Norton and Belfont Iron works. Architectural details include a cameo etched into the front door knob, fretwork molding and the floors are made with yellow poplar, the same type of wood used in the iron blast furnaces.

The whole media sensation began with Heather Williams, a realtor with the Proctorville-based Bunch Real Estate Associates. She was in the process of selling The Tower House and had posted it online and then the Finkelsteins saw it.

I guess they saw the Tower House after I posted it on Historical Houses of America, Williams said. They contacted me and they had chosen, I think five houses in Ohio, and this was one of them.

In our upcoming Wednesday edition of The Ironton Tribune, we will look at notable residents of the Tri-State who passed in 2021.

Excerpt from:
Top 10 stories of 2021 - The Tribune | The Tribune - Ironton Tribune

The new year is underway. If one of your resolutions is a bigger commitment to helping those who need it, there's no better way than giving the gift of life with a blood donation. The Southwestern Indiana Red Cross is giving you the opportunity to do just that during their upcoming Evan's Journey Blood Drive onFriday, January 21st from 1:00 until 7:00 PMat St. Paul's Lutheran Church in Evansville.

Due to thecontinuing COVID-19 pandemic, as well as the numerous devastating weather events taking place around the country, including the tornadoes that ripped through western Kentucky in December, the Red Cross was forced to cancel a number of blood drives in 2021 which has led toits worst blood shortage in over a decade. According to the Red Cross, someone requires a blood product somewhere in the countryevery two seconds, which is why making a donation is so important.

The Evan's Journey Blood Drive on January 21st is named in honor of Reitz High School student, Evan Meyer who is currently battling lymphoma and knows all too wellhow important the need for a consistent blood supply is. Evan's brother, Wes, is currently donating stem cells as part of Evan's treatment. The family, along with the Red Cross, have set a goal of 75 units of blood for the drive.

Appointments aren't required for the drive but arehighly encouraged. You can make an appointment now by visitingRedCrossBlood.orgor by calling 1-800-RED-CROSS.

The Red Cross also strongly encourages individuals withO+, O-, A-, and B- are to sign up for a Power Reddonation. This donation takes a little longer to complete than a standard donation (approximately 90 minutes) as it separates your red blood cells from the plasma and platelets and then returns the latter back to you through a saline solution. This type of donation doubles the impact of your donation for the patients who need it.

The entire month of January is National Blood Donor Month. In an effort to encourage donations, not just during the Evans Journey Blood Drive, but throughout the month, the Red Cross has teamed up with the NFL to give one lucky donor a trip to this year's Super Bowl in Los Angeles which includes:

Plus, another donor during the month of January will win a home theater package for the ultimate at-home Super Bowl experience which includes:

All you have to do to enter is make a blood donation anytime between now and January 31st. Visit RedCrossBlood.org to make your appointment now for either the Evan's Journey Blood Drive or any other drive taking place near you this month.

Read on to learn the average life expectancy in each state.

The 100 Best Places to Live in the Midwest

Continue reading here:
Give the Gift of Life During the Evan's Journey Blood Drive with the Red Cross January 21st - wkdq.com