Employing Recombinant Adeno-associated Viral Vectors for Delivery of a Therapeutic TIMP-3 Transgene to the Equine Distal Extremity

Equine laminitis is a condition that results in lameness, extreme pain, and in many cases, concludes in euthanasia. The epidermal and dermal layers of the hoof\u27s lamina are stabilized by connective tissues. Homeostatic metabolic factors allow for healthy remodeling of the lamina. When laminitis occurs, the enzymes that degrade lamellar connective tissue are upregulated while the concentration of degradative inhibitors (TIMP-3) is not changed. The unbalanced state of the metabolic factors compromises the structural integrity of the lamina and allows for movement of the coffin bone within the hoof capsule. Gene therapy has manifested promising results for preventing laminitis. The current study used recombinant adeno-associated viral vectors (rAAVs) to deliver a therapeutic TIMP-3 transgene to healthy lamellar tissues. Venography was used to visualize the vasculature and evaluate tissue uptake. Hoof tissue samples were harvested for analysis post-injection. We have found that the tissues of the foot were transduced with the therapeutic TIMP-3 gene and we expect to find that the TIMP-3 protein has been produced endogenously by transfected cells. The increased endogenous production of TIMP-3 could restore lamellar metabolic homeostasis within a laminitic hoof. Favorable results of this study will allow for future clinical trials which evaluate the effects of gene therapy on equine laminitis

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND. The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS. Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE. Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.NOAA Coral Reef Conservation Progra

The Efficacy of Biliary Diversion for Benign Disease: Long-Term Follow-up

Retrospective analysis of 70 patients who underwent biliary bypass operations for benign disease over an eight-year period was undertaken to evaluate long-term complications. Operative procedures included choledochoduodenostomy in 60 patients, choledochojejunostomy in four, and cholecystoduodenostomy, cholecystojejunostomy and hepaticojejunostomy in two patients each. The most common indication for surgery was choledocholithiasis, with or without hepatic stones, viscid bile, and ampullary stenosis (61 to 70 patients). Other indications included chronic pancreatitis, choledochal cyst, and sclerosing cholangitis. One patient died postoperatively from hemorrhage, and two others died from causes unrelated to surgery. Two patients developed cholangitis without reflux and demonstrated anastomotic stenosis at re-operation. Sixty-four patients in the series had reflux but remained asymptomatic. Our study supports the concept that cholangitis results from relative obstruction of the anastomosis rather than from reflux

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Long-term survival after onset of blast crisis in chronic granulocytic leukemia: Case report and therapeutic considerations

Current analysis indicates a median survival of 3.6 months in 356 cases of chronic granulocytic leukemia after onset of blast transformation. Thirty-five (10.0%) complete remissions (CR), all of short duration, were observed. Closer scrutiny of the reported clinical experience offers clues for improving this poor outlook. A 76% CR rate can be extracted from this total experience by identifying cases treated with cytoslne arabinoside combined with one or more other agents. In isolated reports, weekly vincristine and prednisone have yielded good remission rates. Two general morphologic types of blasts can be distinguished by cytochemical stains and other features: lymphoid and nonlymphoid (myeloid, monocytoid). We suggest that the lymphoid type of blast crisis Is more responsive to vincristine-prednisone, whereas combination chemotherapy, containing cytoslne arabinoside, is more effective in nonlymphoid crises. We report a blast crisis in which two CRs occurred. The patient survived 19 months after onset, possibly because he also received BCC

Chronic Lymphocytic Leukemia: Rapidly Changing Treatment Landscape

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in developed countries. CLL is diagnosed with absolute B lymphocyte count (B-ALC) >5000/micrL sustained for at least 3 months, morphologically mature-appearing small lymphocytes, and flow cytometry showing the typical immunophenotype of CLL cells. Different prognostic parameters are used to differentiate between low-and high-risk patients, which would affect treatment decisions. Rai and Binet staging systems are the two most commonly used in practice. There has been a significant change in how we manage patients in CLL over the last 5 years. We have shifted away from chemoimmunotherapy toward novel agents such as BTK, PIK3, and BCL-2 inhibitors, which are not only more efficacious but are also safer and better tolerated. New prognostic models are being developed, and it appears that minima residual disease (MRD) directed therapy will become the norm in the future. Many clinical trials are looking at various combinations of novel therapies, with a defined period of treatment based on MRD analysis, to enable patients to have a period of treatment-free remission instead of continuous therapy. In this chapter, we summarize the latest updates in CLL management

Intrahepatic-Cutaneous Biliary Fistulas Secondary to Trauma

Biliary fistula is an unusual complication after operations for hepatic trauma, but only scant information is available concerning its management. This report describes biliary fistulas and presents two cases of their successful resolution, by external drainage in one case and internal drainage in the other. These cases illustrate aspects of fistula management and prevention described in the literature and suggest individualized approaches

Service Provider and Beneficiary Perceptions of Collectivist Domestic Violence Social Issues

In this research I have focused on beneficiary and service providers\u27 perceptions toward Arab social obstacles to help-seeking, appropriate intervention methods and obstacles to reintegration into the community after seeking assistance. Through semi-structured interviews and content analysis of local policies, laws and specific service offerings, I sought to contribute to the limited literature that explores how formal institutions that originate from a Western context are adapted to meet the unique needs of Arab victims of domestic violence. I found that the main social obstacles to help-seeking were attributed to a dearth of knowledge about existing services, a lack of confidence in formal institutions such as non-governmental and government agencies, a fear of rejection or punishment from their families and communities, concerns about laws that might increase a woman\u27s vulnerability and limited economic resources

The Effect of the Coronavirus Disease 2019 Pandemic on University Students' Mental Health and Life Quality: A Retrospective Cohort Study

Background: Mental health disorders and low quality of life are considered common psychiatric problems resulting from the COVID-19 pandemic. Despite the significant importance of the knowledge and research about COVID-19 mental consequences, few studies are addressing it locally in Jordan. Therefore, the present study aims to investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on university students' mental health and life quality.   Method: A retrospective cohort study was undertaken for students in Jordanian universities using an online questionnaire. Our survey consisted of the Generalized Anxiety Disorder 2‐item (GAD-2), The Patient Health Questionnaire 2-item (PHQ-2), UCLA Loneliness Scale, and the COVID-19–Impact on Quality of Life (COV19-QoL) scale to examine students' quality of life, loneliness, besides examining the difference between depression and anxiety, independently, before and during COVID-19 pandemic among Jordanian universities students. We analyzed the data using SPSS Software version 26.   Results: The study included 537 participants, 371 (69.1%) of them were female, with a mean age of participants equal to 19.1 ± 0.84, with a range of 17 to 22 years. Most of the participants were second-year students 393 (54.6%) and more than half of the participants never weekly exercised. the prevalence of depression, anxiety, and loneliness after the COVID-19 pandemic were 305 (56.8%), 311 (57.9%), and 371 (69.1%); respectively. Chi-square analysis revealed that females with loneliness, depression, and anxiety were statistically predominant (p=0.014, p=0.023, p=0.000; respectively). In contrast, there was no significant difference among basic academic years students in terms of these mental outcomes. The impact of the Covid-19 pandemic on depression scores of singles was significantly higher than those who were in relationships (p= 0.008). The less depressed students were those who sleep at the night and those who have hobbies (p=0.02, p=0.007; respectively).   Conclusion: Our study results highlighted and supported a significant change in the participants’ scores regarding their mental status before and after the outbreak. Furthermore, several factors preserve the mental health of students against the consequences of the COVID-19 crisis, such as gender, having hobbies, being in a relationship, bedtime, and sleep hours. Additionally, the study found that loneliness, anxiety, and depression can predict life quality. Eventually, the government should provide more attention to the student’s psychological issues. Future research should investigate which group of students have more susceptibility to being mentally affected by similar outbreaks to develop specific and efficient actions that are targeted to these certain groups, thus improving the chance of the psychological benefits.   Key Words: Cohort, COVID-19, Depression, Mental Healt