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Introduction: Direct-acting oral anticoagulants (DOACs) have recently shown potential efficacy for many conditions without the need for regular monitoring. However, their use in kidney transplant recipients (KTRs) is controversial, with no clear consensus on how they compare to vitamin K antagonists (VKAs), which have traditionally been used as preferred anticoagulation therapy in these patients., Methods: PubMed, Cochrane Central, and Embase databases were systematically searched up to December 2023 for studies comparing DOACs versus VKAs in KTRs. The main outcomes of interest included venous thromboembolism (VTE), major bleeding, graft failure, mortality, and changes in estimated glomerular filtration rate (eGFR). Statistical analyses were performed using RStudio 4.1.2 software., Prospero Id: CRD42024498423., Results: Five studies with a total of 959 participants were included. Of these, 433 (45.15 %) participants were treated with DOACs. The mean age of participants was 60.05 years, and 65.9 % were male. The use of DOACs in KTRs was associated with a significant reduction in major bleeding (RR 0.56; 95 % CI 0.35 to 0.90; p = 0.02; I 2  = 0 %) and mortality (RR 0.49; 95 % CI 0.33 to 0.74; p = 0.0006; I 2  = 0 %). No significant differences were found between groups in VTE (RR 0.82; 95 % CI 0.47 to 1.43; p = 0.48; I 2  = 12 %), graft failure (RR 0.43; 95 % CI 0.14 to 1.27; p = 0.13; I 2  = 52 %), and eGFR (MD 3.72 mL/Kg/1.73 m2; 95 % CI -1.58 to 9.03; p = 0.17; I 2  = 0 %). Evidence quality for some outcomes remains low to moderate, limiting the confidence in these conclusions., Conclusion: Our meta-analysis suggests that DOACs represent an effective anticoagulation strategy in KTR, with a significant reduction in major bleeding and mortality relative to VKA., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite increased recruitment of Latina medical students, the percentage of Latina physicians has remained stagnant, suggesting unique retentive barriers affecting this population. Discriminatory experiences involving bias may contribute to difficulties in the retention and advancement of Latinas in medicine. This qualitative analysis aimed to explore thematic barriers prevalent among Latinas throughout their medical training in the United States., Methods: An anonymous online survey was distributed to Latinas in the continental United States from June 22 to August 12, 2022. Eligibility criteria included self-identifying as Hispanic/Latina, female/woman, and being currently enrolled in or graduated from medical school, residency, or fellowship in the United States in the past 10 years. Content and thematic analyses were done on 602 responses across seven open-ended survey questions., Results: Data were categorized into three main themes: (1) barriers stemming from limited social, cultural, and financial capital; (2) experiences of discrimination, bias, and perceptions of being undervalued; and (3) burdens resulting in notable mental health challenges such as depression and anxiety. Many women questioned their place in medicine throughout training and the value of the sacrifice and trauma endured., Conclusion: This is the first qualitative study evaluating the experiences of Latinas throughout medical training, revealing that they experience disproportionate barriers and discriminatory experiences from both colleagues and patients. Despite calls to enhance institutional climates of diversity, there continues to be an acute need for the reform of medical education to promote an inclusive culture and provide adequate mentorship to marginalized trainees., (© 2025 American Cancer Society.)

Background: Alzheimer's Disease and Related dementias (ADRD) are disproportionately underdiagnosed, misdiagnosed, and undertreated in Latino/a/e/x populations living in the U.S. Latino/a/e/x families also experience low access to ADRD caregiver support services and high levels of depression. Primary care providers (PCPs) are the first point of contact for patients and their families, and they are critical in understanding the factors associated with disparities in accessing services. This project aims to reflect on the barriers that Latino/a/e/x families experience in accessing and using healthcare services from the perspective of PCPs., Methods: The data was collected through structured interviews with 23 diverse PCPs across the US via videoconference or phone calls. Participants were recruited via snowball sampling. Two reviewers used an inductive coding approach to conduct qualitative thematic analysis. The Rigorous and Accelerated Data Reduction (RADaR) technique was used to extract relevant data and organize it into relevant categories., Results: Some of the themes identified reflect the experiences of individuals in the diagnostic process and subsequent care: 1) Family members are usually the first ones to notice the symptoms, 2) Delays in seeking care might be partially influenced by denial from individuals and their families, 3) Language congruency promotes the disclosure of symptoms, 4) Care that is linguistically and literacy appropriate requires additional support of patients and families, and 5) Caregiving expectations and preferences by Latino/a/e/x families do not shield caregivers from feeling burnout. Overall, PCPs reflected that the experiences of individuals are highly influenced by socioeconomic factors, which also influence their care plans., Conclusion: Most Latino/a/e/x older adults with ADRD will be cared for by a PCP at some point during their disease, which means that they require additional support and resources at primary care appointments to address the barriers to accessing care services and enhance health equity in Latino/a/e/x communities.

Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to have lower thromboembolism rates compared to placebo in polycythemia vera (PV) patients. This meta-analysis evaluates ruxolitinib's efficacy and safety against best available therapy (BAT) in patients with PV and in hydroxyurea-resistant/intolerant PV patients. A comprehensive literature search was conducted up to November 2023. We compared ruxolitinib and BAT for efficacy and safety endpoints. Six studies involving 1061 patients were analyzed, with 620 on BAT and 441 on ruxolitinib. Ruxolitinib showed higher hematocrit control (p = 0.015) and treatment response (p = 0.04) compared to BAT. It also significantly improved Myeloproliferative Neoplasms-Symptom Assessment Form scores (MPN-SAF) (p < 0.01). Additionally, patients with PV treated with ruxolitinib had higher rates of nonmelanoma skin cancer (p < 0.01). In subgroup analyses focusing on patients resistant or intolerant to hydroxyurea, ruxolitinib maintained its efficacy, significantly improving treatment response (p < 0.01) and significant improvements in MPN-SAF (p = 0.02) score when compared to BAT. The safety profile was consistent with the overall analyses, showing significantly reduced thromboembolism rates (p = 0.04), increased rates of anemia (p = 0.01), and increased herpes zoster infections (p = 0.02). Ruxolitinib outperforms BAT in PV and patients with PV-resistant or intolerant to hydroxyurea, offering better hematocrit control and reducing symptomatic burden and thromboembolism risk. Yet, it is associated with higher rates of anemia, herpes infection, and skin cancer., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Antibiotic therapy for patients with early Lyme disease is necessary to prevent later-stage Lyme disease complications. This systematic review and meta-analysis compares shorter versus longer antibiotic regimens in treating early Lyme disease., Methods: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted up to November 2023. We examined treatment failure, complete response, and photosensitivity. Short vs. long therapy was defined as ≤10 days vs. >10 days. Subgroup analyses included antibiotic type and varying treatment durations. Analysis utilized RStudio 4.1.2. PROSPERO registration: CRD42023423876., Results: Seven studies, encompassing 1,462 patients, were analyzed. No significant differences in treatment failure, 12-month complete response, final visit complete response were found between short and long durations of antibiotic therapy. Subgroup and sensitivity analyses corroborated these findings., Conclusion: Shorter and longer antibiotic regimens for early Lyme disease show similar efficacy, highlighting the potential of ≤10-day courses, as effective treatment options., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Two rapid, precise, and sensitive stability-indicating high performance chromatographic methods for the measurement of Teriflunomide in its degradation products' existence were developed. These were RP-HPLC and HPTLC using UV detector. HPLC separation was accomplished utilizing Thermo BDS hypercil C18 column (250 × 4.6 mm, 5 μm) and acetonitrile: 0.03 M potassium dihydrogen phosphate: triethylamine (50:50:0.1%, by volume) as mobile phase at flow rate of 1mL/min. The separated peaks were detected at 250.0 nm. The densitometric approach was conducted utilizing HPTLC 60 F254 silica gel plates, and a developing system of benzene: ethanol: acetic acid (7.5:1:0.25, by volume) and detection was done at 250.0 nm. The developed approaches were evaluated regarding the International Conference on Harmonization (ICH) instructions. The calibration curves of both techniques were constructed with linearity ranges of (5-100) µg/mL and (2-10) µg /band, for HPLC and densitometric determination, consecutively. Teriflunomide was exposed to base and acid hydrolysis, oxidation using H 2 O 2 and finally, thermal degradation as stated in ICH guidelines. The degradation product structures' elucidation was achieved through LC-MS., (© 2024. The Author(s).)

Obsessive-compulsive disorder (OCD) is a chronic disease with a prevalence in the general population of around 2%-3%, generally accompanied by a severe impairment of functioning and quality of life. A consistent subgroup of patients may not achieve adequate symptom remission with first-line treatments (i.e., cognitive behavioral therapy, selective serotonin reuptake inhibitors [SSRIs]). The most validated option for treatment-resistant cases relies on the augmentative use of antipsychotics to SSRIs, preferably of the 'second generation'. Indeed, dopamine appears to be crucially involved in OCD neuropathology due to its implication in systems relating to goal-directed behaviour and maladaptive habits. Nevertheless, the mechanism of action of antipsychotics in OCD symptom improvement is still unclear. Risperidone, aripiprazole, and haloperidol seem to be the most useful medications, whereas 'first generation' antipsychotics may be indicated in case of comorbidity with tics and/or Tourette Syndrome. Antipsychotic augmentation may be also related to side-effects, particularly in the long term (e.g., alteration in metabolic profile, sedation, extrapyramidal symptoms). The present mini-review sought to provide the most updated evidence on augmentative antipsychotic use in treatment-resistant patients with OCD, providing a road map for clinicians in daily practice and shedding light on avenues for further research., (© 2024 John Wiley & Sons Ltd.)

Background and Purpose: Radiopharmaceuticals are radioactive compounds used for diagnostic or therapeutic purposes which are most often administered intravenously. Adverse events that may induce both adverse reactions and drug-to-drug interactions with changes in expected biodistribution, potentially affecting patient safety and diagnostic accuracy. Adverse reactions are relatively rare due to the small doses and under-reporting is the norm. The aim of this study is to increase awareness of the need to report in order to create protocols for the management of such adverse events among professionals in a Nuclear Medicine Department., Methods: A reporting system was established a decade ago through an electronic form to enhance adverse event registration. The radiopharmacist collects data for further communication with National Health authorities and develops an annual report with recommendations on the management of these adverse events., Results: A total of 128 reports were collected, including 65 cases of extravasations, 18 adverse reactions, and 45 drug interactions. Over the years, reporting has been increasing, adverse reactions occurred at a higher incidence than reported in the literature, and each anomalous biodistribution was analysed for possible drug interaction. The annual reports have been used to develop a local guideline for the management of adverse reactions and recommendations for discontinuation of treatment to avoid interactions with radiopharmaceuticals., Conclusion: The recognition of adverse events associated with radiopharmaceuticals is increasing, underlining the need for vigilant reporting and improved management strategies. An efficient reporting system promotes awareness of possible interactions between radiopharmaceuticals and other medicines and their potential adverse reactions to enhance patient safety., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The percentage of physicians identifying as Latina has not improved despite improvements in recruitment of Latina medical students, suggesting barriers to retention and career advancement. Discriminatory experiences and mental health inflictions throughout training may contribute to difficulties in recruitment, retainment, and advancement of Hispanic/Latinx trainees, a notably understudied population., Methods: An anonymous, online survey was distributed to Latinas in the continental U.S. between June 22 to August 12, 2022. Eligibility criteria included: self-identifying as Hispanic/Latina, female/woman, and completing or have completed medical school, residency, or fellowship in the continental U.S. in the past 10 years. Recruitment was done via the Twitter account @LatinasInMed and outreach to Latino Medical Student Association chapters. Descriptive statistics summarized the self-reported experiences., Results: The survey included 230 Hispanic/Latinx women, mostly medical students (46.9%). A majority (54.5%) reported negative ethnicity-based interactions from patients and/or patients' families; 71.8%, from others in the medical field. High rates of depression (76.2%) and anxiety (92.6%) during training were reported by Latinas, especially medical students. Feelings of imposter syndrome and burnout were high at 90.7% and 87.4%, respectively., Conclusions: This is the first study evaluating the unique experiences of Latinas in medicine, who reported discrimination and mental health struggles, specifically during medical school, at alarmingly high rates. Our findings could aid in creating the needed interventions to support Latinas in medical training to reduce the existing exodus of Latinas from medicine., (© 2023. The Author(s).)

Introduction: While 9.5 million U.S. Hispanic adults have hearing loss, limited research has focused on their hearing care experiences. This study examines the attitudes, beliefs, behaviors, and barriers to hearing care among Hispanic adult patients with hearing loss (HL) and their caregivers. Methods: In a qualitative study, participants were recruited through community organizations, social media, and word of mouth. Participants were interviewed through virtual platforms and audio recorded. The recording was then transcribed verbatim in Spanish, translated to English, and analyzed using a hybrid deductive and inductive content approach. Results: The 12 participants (age 35-92, 83.3% female) comprised seven individuals with HL and three family caregivers. Most participants attributed HL to aging and genetics, and most shared a stigmatized community attitude toward HL that silenced any discussion of it. Barriers to hearing care included high cost, lack of insurance, and language barriers. These resulted in negative experiences with providers and poor access to hearing tests and auditory devices. Conclusions: The study's findings suggest a need to improve access to comprehensive low-cost hearing services and education in the Hispanic community. Additionally, unique challenges of this community should be addressed to promote hearing health and self-management.

Three smart carbon paste electrodes were fabricated to quantify dorzolamide hydrochloride DRZ, including conventional carbon paste I, modified carbon paste embedding Silica II, and modified carbon paste embedding β-cyclodextrin III. This study is based on the insertion of DRZ with phosphomolybdic acid to create an electroactive moiety dorzolamide-phosphomolybdate ion exchanger using a solvent mediator dibutyl phthalate. The three constructed carbon paste electrodes displayed Nernstian responses and linear concentration ranges with lower detection limits. The vital performance of the created electrodes was verified in relation to various parameters. The electrodes enhance the selective determination of DRZ in the presence of inorganic ions, a co-formulated drug in the dosage form timolol maleate, and the excipient benzalkonium chloride. The modified carbon paste electrode including Silica was utilized to detect DRZ in ophthalmic eye drop form utilizing the direct calibration curve and potentiometric titration methods. Satisfactory findings were achieved by comparing them to other reported methods., (© 2023. Springer Nature Switzerland AG.)

Dengue virus (DENV) is the most important human virus transmitted by mosquitos. Dengue pathogenesis is characterized by a large induction of proinflammatory cytokines. This cytokine induction varies among the four DENV serotypes (DENV1 to 4) and poses a challenge for live DENV vaccine design. Here, we identify a viral mechanism to limit NF-κB activation and cytokine secretion by the DENV protein NS5. Using proteomics, we found that NS5 binds and degrades the host protein ERC1 to antagonize NF-κB activation, limit proinflammatory cytokine secretion, and reduce cell migration. We found that ERC1 degradation involves unique properties of the methyltransferase domain of NS5 that are not conserved among the four DENV serotypes. By obtaining chimeric DENV2 and DENV4 viruses, we map the residues in NS5 for ERC1 degradation, and generate recombinant DENVs exchanging serotype properties by single amino acid substitutions. This work uncovers a function of the viral protein NS5 to limit cytokine production, critical to dengue pathogenesis. Importantly, the information provided about the serotype-specific mechanism for counteracting the antiviral response can be applied to improve live attenuated vaccines.

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Heterologous vaccination against coronavirus disease 2019 (COVID-19) provides a rational strategy to rapidly increase vaccination coverage in many regions of the world. Although data regarding messenger RNA (mRNA) and ChAdOx1 vaccine combinations are available, there is limited information about the combination of these platforms with other vaccines widely used in developing countries, such as BBIBP-CorV and Sputnik V. Here, we assess the immunogenicity and reactogenicity of 15 vaccine combinations in 1,314 participants. We evaluate immunoglobulin G (IgG) anti-spike response and virus neutralizing titers and observe that a number of heterologous vaccine combinations are equivalent or superior to homologous schemes. For all cohorts in this study, the highest antibody response is induced by mRNA-1273 as the second dose. No serious adverse events are detected in any of the schedules analyzed. Our observations provide rational support for the use of different vaccine combinations to achieve wide vaccine coverage in the shortest possible time., Competing Interests: Declaration of interests All authors declare no competing interests. This study has received funding from the Russian Direct Investment Fund, which manufactures and markets the vaccine Sputnik V, developed by the Gamaleya Research Center of Epidemiology and Microbiology., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 reverse zoonosis, particularly to domestic animals, and the potential role of infected animals in perpetuating the spread of the virus is an issue of increasing concern. In this case report, we identified the natural infection of two cats by SARS-CoV-2, in Argentina, whose owner had been previously infected by SARS-CoV-2. Viral genetic material was detected in feline oropharyngeal (OP) and rectal (R) swab by RT-qPCR, and sequence analysis revealed that the virus infecting the owner and one cat were genetically similar. The alpha variant (B.1.1.7 lineage) was identified with a unique additional mutation, strongly suggesting human-to-cat route of transmission. This study reinforces the One Health concept and the importance of integrating human, animal, and environmental perspectives to promptly address relevant health issues., Competing Interests: DM is employed by Diagnogen S.A. JM is employed by Diagnogen S.A. and Diagnotest SRL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pecora, Malacari, Mozgovoj, Díaz, Peralta, Cacciabue, Puebla, Carusso, Mundo, Gonzalez Lopez Ledesma, Gamarnik, Rinaldi, Vidal, Mas and Dus Santos.)

We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs., Competing Interests: The authors have declared that no competing interests exist.

The primary aim of this study was to investigate the functional, physiological and subjective responses to NMES exercise in cancer patients. Participants with a cancer diagnosis, currently undergoing treatment, and an had an Eastern Cooperative Oncology Group (ECOG) performance status (ECOG) of 1 and 2 were recommended to participate by their oncologist. Following a 2-week, no-NMES control period, each participant was asked to undertake a concurrent NMES exercise intervention over a 4-week period. Functional muscle strength [30 s sit-to-stand (30STS)], mobility [timed up and go (TUG)], exercise capacity [6-min walk test (6MWT)] and health related quality of life (HR-QoL) were assessed at baseline 1 (BL1), 2-week post control (BL2) and post 4-week NMES exercise intervention (POST). Physiological and subjective responses to LF-NMES were assessed during a 10-stage incremental session, recorded at BL2 and POST. Fourteen participants [mean age: 62 years (10)] completed the intervention. No adverse events were reported. 30STS (+ 2.4 reps, p = .007), and 6MWT (+ 44.3 m, p = .028) significantly improved after the intervention. No changes in TUG or HR-QoL were observed at POST. Concurrent NMES exercise may be an effective exercise intervention for augmenting physical function in participants with cancer and moderate and poor functional status. Implications for cancer survivors: By allowing participants to achieve therapeutic levels of exercise, concurrent NMES may be an effective supportive intervention in cancer rehabilitation.

Background/objectives: The Community-Academic Aging Research Network (CAARN) was created to increase the capacity and effectiveness of Wisconsin's Aging Network and the University of Wisconsin to conduct community-based research related to aging. The purpose of this article is to describe CAARN's infrastructure, outcomes, and lessons learned., Design: Using principles of community-based participatory research, CAARN engages stakeholders to participate in the design, development, and testing of older adult health interventions that address community needs, are sustainable, and improve health equity., Setting: Academic healthcare and community organizations., Participants: Researchers, community members, and community organizations., Intervention: CAARN matches academic and community partners to develop and test evidence-based programs to be distributed by a dissemination partner., Measurements: Number of partnerships and funding received., Results: CAARN has facilitated 33 projects since its inception in 2010 (30 including rural populations), involving 46 academic investigators, 52 Wisconsin counties, and 1 tribe. These projects have garnered 52 grants totaling $20 million in extramural and $3 million in intramural funding. Four proven interventions are being prepared for national dissemination by the Wisconsin Institute for Healthy Aging: one to improve physical activity; one to reduce bowel and bladder incontinence; one to reduce sedentary behavior; and one to reduce falls risk among Latinx older adults. Additionally, one intervention to improve balance using a modified tai chi program is being disseminated by another organization., Conclusion: CAARN's innovative structure creates a pipeline to dissemination by designing for real-world settings through inclusion of stakeholders in the early stages of design and by packaging community-based health interventions for older adults so they can be disseminated after the research has been completed. These interventions provide opportunities for clinicians to engage with community organizations to improve the health of their patients through self-management. J Am Geriatr Soc 68:1325-1333, 2020., (© 2020 The American Geriatrics Society.)

Purpose: Neuromuscular electrical stimulation (NMES) may be a pragmatic short-term alternative to voluntary exercise to augment cancer rehabilitation. However, previous attempts to use NMES as an exercise modality in this cohort have been unsuccessful, largely due to the use of NMES protocols that were developed for other rehabilitation contexts. We assessed the effects of a personalised and progressive NMES exercise intervention, designed with early-stage cancer rehabilitation in mind, on exercise capacity, lower body functional strength and quality of life in (QoL) in patients who are currently undergoing or have recently completed treatment for cancer., Methods: Ten adult patients were recruited. A personalised and progressive NMES exercise intervention was implemented in each case over a 4-8-week period. The 30-s sit-to-stand test (STS), 6-min walk test (6MWT) and EORTC QLQ C-30 were performed pre- and post-intervention. Patients completed semi-structured interviews post-intervention to explore their experiences and views on the intervention and its impact on their daily lives., Results: Six of the 10 recruited patients completed the intervention and completed pre-and post-assessments. Four of 6 patients improved STS, 5 of 6 patients improved 6MWT and 4 of 6 patients improved Global QoL. Perceived benefits included improved muscle strength and more confidence when walking., Conclusion: A personalised and progressive NMES exercise intervention appears safe and may improve functional capacity and QoL in adults who are undergoing or have recently completed treatment for cancer. Replication of these results in a controlled prospective study is warranted prior to clinical implementation.

Squamous cell carcinoma (SCC) is one of the most common malignant neoplasms in horses, but lingual SCC has seldom been reported. On separate occasions, a 12-year-old American Quarter Horse mare and an 18-year-old American Saddlebred stallion were presented to the Auburn University Large Animal Teaching Hospital for evaluation of weight loss, dysphagia, and ptyalism. Evaluation of each horse included physical examination, skull radiographs, oral examination, complete blood count and serum biochemistry profile, endoscopic evaluation of the mouth, and biopsy of tissue from a lesion found on the tongue. Histopathologic assessment of tissue harvested from the lingual lesions led to a diagnosis of SCC in each case. The diagnosis prompted euthanasia for one horse, but radiation therapy appeared to delay the progression of the lesion in the other horse., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) circulates as a collection of genetically related variants that evolve throughout the chronic infection. Those viral variants that have the greatest fitness are fixed. We recently showed different fitness for HBV variants involved in two epidemiological situations. To understand these fitness differences better, we determined the levels of extracellular HBV DNA, the synthesis of HBV DNA intermediates, and the expression of HBeAg and HBsAg in transfection and cotransfection assays. Our results show that for the subgenotype (sgt) D1, which has an 8-nucleotide deletion (sgtD1del) and exhibits lower fitness, the levels of extracellular DNA and intracellular replicative intermediates were much lower than with sgtD1wt or sgtD1mut (G1896A), which had higher fitness. In addition, in the cotransfection assay, sgtD1del inhibited sgtD1mut but not sgtD1wt replication. We also found that sgtF1b, which exhibits higher fitness, produces significantly higher levels of both extracellular DNA and intracellular replicative intermediates than does the lower-fitness sgtF4. These results demonstrate a relationship between fitness and the replicative ability of the HBV genome in the transfection assay. In addition, the data obtained by cotransfecting cells with sgtD1del and sgtD1mut provide new information about the impact of simultaneous replication of two viral variants in the same cell system on HBV replication.

Background: The purpose of this study is to assess the relationship between self-reported uveitis and purported demographic and clinical risk factors, using an American adult population extracted from the National Health and Nutrition Examination Survey (NHANES) for the years 2009 and 2010. This is a cross-sectional, population-based study using a sample of 5106 subjects between 20 and 69 years old. The main outcome for our study was the self-report of a diagnosis of uveitis. The demographic analysis included age, gender, and ethnicity. Potential predictors were having a diagnosis of ankylosing spondylitis (AS), ulcerative colitis (UC), or Crohn's disease (CD); a history of cigarette smoking; vitamin D deficiency; and different mental health measures. Univariate and multivariate analyses were conducted using RStudio., Results: Of the 5106 participants, 27 had reported a diagnosis of uveitis, showing an adjusted prevalence of 5.4 per 1000 subjects (95% CI 3.4-8.5/1000). Increased age was associated with higher uveitis prevalence in the multivariate analysis (odds ratio [OR] = 1.04, 95% CI 1.01-1.07; p = 0.02). Positive smoking history was reported in 59.2% of patients. Multivariate analysis comparing smoking with the presence of uveitis showed an OR of 3.18 (95% CI 1.59-6.37; p = 0.003), adjusting for age and gender. Moreover, 11.1% of the participants from the uveitis group self-reported a diagnosis of AS and 11.7% informed a diagnosis of UC and 7.1% of CD. The ORs were of 16.64 (95% CI 3.64-76.09; p = 0.001), 11.34 (95% CI 2.69-47.88; p = 0.003), and 22.16 (95% CI 2.64-186.17; p = 0.007), respectively when compared with the non-uveitis group in the multivariate analysis., Conclusions: Age, cigarette smoking, AS, UC, and CD are positively associated with self-reported uveitis. There is previous evidence that smoking and female gender are positive risk factors for uveitis, as well as evidence that HLA-B27-positive spondyloarthritides have the highest association with non-infectious uveitis in the adult population in North America and Europe. However, there are no prior studies that have utilized a representative US population-based sample to validate these findings. The present study supports smoking as a risk factor, which has clinical relevance since this is a modifiable habit.

In the context of pathogenesis of HBV infection, HBV genotypes and mutants have been shown to affect the natural course of chronic infection and treatment outcomes. In this work, we studied the induction of apoptosis by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. Both subgenotypes F1b and F4 HBV genome transfections induced cell death by apoptosis in human hepatocytes. The BCPdm (A1762T/G1764A) and preCore (G1896A) mutants induced higher levels of apoptosis than the wt virus. This increase in apoptosis was not associated with the enhanced viral replication of the variants. HBV-mediated apoptosis was independent of viral subgenotypes, and associated with the modulation of members of the regulatory Bcl-2 family proteins expression in the mitochondrial apoptotic pathway. Finally, the apoptosis induction increase observed for the preCore mutants suggests that HBeAg might have an anti-apoptotic effect in human hepatocytes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) has a high mutation rate and exists as a mixture of genetically different but closely related variants. We present a HBV DNA co-transfection fitness assay and use it to evaluate the relative fitness of different HBV variants in two scenarios: seroconversion process and occupation of an ecological niche. In the seroconversion experiment, subgenotype D1 (sgtD1) deletion (1763-1770) had significantly lower fitness comparing with both sgtD1 wild type and sgtD1mut G1896A, while, in the case of occupation of ecological niche experiment, the results showed the same relative fitness between all of the genotype combinations, except F1b-F4. In this case sgtF1b clearly overgrow sgtF4, which is in accordance with the observation that F1b is the most prevalent in the new infections in Argentina. In summary, we present a method aimed to evaluate HBV viral fitness which improve the analysis of the relative frequency of viral variants during the HBV infection process.

Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases.

Aim: In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections)., Results: Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896., Discussion: HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype.

Background: Endovenous radiofrequency ablation (RFA) is a safe and effective treatment for varicose veins caused by saphenous reflux. Deep venous thrombosis (DVT) is a known complication of this procedure. The purpose of this study is to describe the frequency of DVT after RFA and the associated predisposing factors., Methods: A retrospective analysis was performed using prospectively collected data from December 2008 to December 2011; a total of 277 consecutive office-based RFA procedures were performed at a single institution using the VNUS ClosureFast catheter (VNUS Medical Technologies, San Jose, CA). Duplex ultrasonography scans were completed 2 weeks postprocedure in all patients. Risk factors assessed for the development of DVT included: great versus small saphenous vein (SSV) treated, right versus left side treated, number of radiofrequency cycles used, hypercoagulable state, history of DVT, tobacco use, medications (i.e., oral contraceptives, aspirin, warfarin, and clopidogrel), and vein diameter at the junction of the superficial and deep systems., Results: Seventy-two percent of the patients were women, 56% were treated on the right side, and 86% were performed on the great saphenous vein (GSV). The mean age was 54 ± 14 years (range: 23-88 years). Three percent of patients had a preprocedure diagnosis of hypercoagulable state, and 8% had a history of previous DVT. On postprocedural ultrasound, thrombus protrusion into the deep system without occlusion (endovenous heat-induced thrombosis) was present in 11 patients (4%). DVT, as defined by thrombus protrusion with complete occlusion of the femoral or popliteal vein, was identified in 2 patients (0.7%). Previous DVT was the only factor associated with postprocedural DVT (P = 0.018). Although not statistically significant, there was a trend toward a higher risk of DVT in SSV-treated patients. Factors associated with endovascular heat-induced thrombosis alone were male sex (P = 0.02), SSV treatment (P = 0.05), aspirin use (P = 0.008), and factor V Leiden deficiency (P = 0.01)., Conclusions: The use of RFA to treat patients with symptoms caused by saphenous reflux involves a small but definite risk of DVT. This study shows that the risk of post-RFA DVT is greater in patients with previous DVT, with a trend toward an increased risk in patients having treatment of the SSV. Periprocedural anticoagulation may be considered in this subset to reduce the risk of DVT after RFA. Thrombus protrusion without DVT was found to be more likely in patients with hypercoagulability, male sex, SSV treatment, and aspirin use. Additional prospective studies are required to analyze these and other factors that may predict thrombotic events after endovenous RFA., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The intrahepatic cholestasis of pregnancy (ICP) is a multifactorial liver disorder which pathogenesis involves the interplay among abnormal bile acid (BA) levels, sex hormones, environmental factors, and genetic susceptibility. The dynamic nature of ICP that usually resolves soon after delivery suggests the possibility that its pathobiology is under epigenetic modulation. We explored the status of white blood peripheral cells-DNA methylation of CpG-enriched sites at the promoter of targeted genes (FXR/NR1H4, PXR/NR1I2, NR1I3, ESR1, and ABCC2) in a sample of 88 ICP patients and 173 healthy pregnant women in the third trimester of their pregnancies. CpG dinucleotides at the gene promoter of nuclear receptors subfamily 1 members and ABCC2 transporter were highly methylated during healthy pregnancy. We observed significant differences at the distal (-1890) and proximal promoter (-358) CpG sites of the FXR/NR1H4 and at the distal PXR/NR1I2 (-1224) promoter, which were consistently less methylated in ICP cases when compared with controls. In addition, we observed that methylation at FXR/NR1H4-1890 and PXR/NR1I2-1224 promoter sites was highly and positively correlated with BA profiling, particularly, conjugated BAs. Conversely, methylation level at the proximal FXR/NR1H4-358 CpG site was significantly and negatively correlated with the primary cholic and secondary deoxycholic acid. In vitro exploration showed that epiallopregnanolone sulfate, a reported FXR inhibitor, regulates the transcriptional activity of FXR/NR1H4 but seems to be not involved in the methylation changes. In conclusion, the identification of epigenetic marks in target genes provides a basis for the understanding of adverse liver-related pregnancy outcomes, including ICP.

Cyclodextrin glucanotransferase (CGTase, EC 2.4.1.9) is an unique enzyme capable of converting starch and related substrates into cyclodextrins (CDs). In this paper, we report an one step gel purification method of CGTase from Bacillus sp. and later enzyme characterization. The Bacillus sp. strain was isolated from a Colocacia esculenta rizospheric soil sample and the CGTase production was carried out in alkaline medium (pH=10). The CGTase purification from the culture supernatant was performed by gel filtration. The enzyme was purified in one step with a recovery of 87.3% activity and 40-fold purification for specific enzymatic activity of 2.24 U/mg. Optimal activity was observed at pH 5.0 in citrate-phosphate buffer, and the enzyme retained almost 100 % of its activity between pH 5.5 and 10 after incubation for 1 h at 4°C. The enzyme exhibited maximum activity at 55°C and showed a T(50%) of 70°C. The ratio of α:β:γ CD formed by the enzyme was 0.74:1:0.61 for soluble starch and 0.29:1:0.85 for cocoyam starch.

Objective: currently, 12% of the Spanish population is foreign-born, and a third of newly diagnosed HIV-infected patients are immigrants. We determined whether being an immigrant was associated with a poorer response to antiretroviral treatment., Methods: historical multicenter cohort study of naïve patients starting HAART. The primary endpoint was time to treatment failure (TTF) defined as virological failure (VF), death, opportunistic disease, treatment discontinuation (D/C), or missing patient. Secondary endpoints were TTF expressed as observed data (TFO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/C not due to VF). A multivariate analysis was performed to control for confounders., Results: a total of 1090 treatment-naïve HIV-infected patients (387 immigrants and 703 autochthonous) from 33 hospitals were included. Most immigrants were from Sub-Saharan Africa (28.3%) or South-Central America/Caribbean (31%). Immigrants were significantly younger (34 y vs. 39 y), more frequently female (37.5% vs. 24.6%), with less HCV coinfection than autochthonous patients (7% vs. 31.3%). There were no differences in baseline viral load (4.95 Log(10) vs. 4.98 Log(10)), CD4 lymphocyte count (193.5/µL vs. 201.5/µL), late initiation of HAART (56.4% vs. 56.0%), or antiretrovirals used. Cox-regression analysis (HR; 95%CI) did not show differences in TTF (0.89; 0.66-1.20), TFO (0.95; 0.66-1.36), or TVF (1.00; 0.57-1.78) between immigrants and autochthonous patients. Losses to follow-up were more frequent among immigrants (17.8% vs. 12.1; p=0.009). Sub-Saharan African patients and immigrant females had a significantly shorter TTF., Conclusions: the response to HAART among immigrant patients was similar to that of autochthonous patients, although they had a higher rate of losses to follow-up. Sub-Saharan Africans and immigrant females may need particular measures to avoid barriers hindering antiviral efficacy.

In animal and plant cells, mitotic chromatin locally generates microtubules that self-organize into a mitotic spindle, and its dimensions and bipolar symmetry are essential for accurate chromosome segregation. By immobilizing microscopic chromatin-coated beads on slide surfaces using a microprinting technique, we have examined the effect of chromatin on the dimensions and symmetry of spindles in Xenopus laevis cytoplasmic extracts. While circular spots with diameters around 14-18 microm trigger bipolar spindle formation, larger spots generate an incorrect number of poles. We also examined lines of chromatin with various dimensions. Their length determined the number of poles that formed, with a 6 x 18 microm rectangular patch generating normal spindle morphology. Around longer lines, multiple poles formed and the structures were disorganized. While lines thinner than 10 mum generated symmetric structures, thicker lines induced the formation of asymmetric structures where all microtubules are on the same side of the line. Our results show that chromatin defines spindle shape and orientation. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.

Comparisons of nematode communities among ecosystems have indicated that, unlike many organisms, nematode communities have less diversity in the tropics than in temperate ecosystems. There are, however, few studies of tropical nematode diversity on which to base conclusions of global patterns of diversity. This study reports an attempt to estimate nematode diversity in the lowland tropical rainforest of La Selva Biological Research Station in Costa Rica. We suggest one reason that previous estimates of tropical nematode diversity were low is because habitats above the mineral soil are seldom sampled. As much as 62% of the overall genetic diversity, measured by an 18S ribosomal barcode, existed in litter and understorey habitats and not in soil. A maximum-likelihood tree of barcodes from 360 individual nematodes indicated most major terrestrial nematode lineages were represented in the samples. Estimated 'species' richness ranged from 464 to 502 within the four 40 x 40 m plots. Directed sampling of insects and their associated nematodes produced a second set of barcodes that were not recovered by habitat sampling, yet may constitute a major class of tropical nematode diversity. While the generation of novel nematode barcodes proved relatively easy, their identity remains obscure due to deficiencies in existing taxonomic databases. Specimens of Criconematina, a monophyletic group of soil-dwelling plant-parasitic nematodes were examined in detail to assess the steps necessary for associating barcodes with nominal species. Our results highlight the difficulties associated with studying poorly understood organisms in an understudied ecosystem using a destructive (i.e. barcode) sampling method.

Because of lacking ventilatory stimulation by sex hormones in postmenopausal women (PW), one might expect a lowered arterial oxygen saturation (S(O(2))) in hypoxia and therefore a stronger erythropoietic reaction than in young women (YW). Nine untrained (UTRPW) and 11 trained (TRPW) postmenopausal altitude residents (2600 m) were compared to 16 untrained (UTRYW) and 16 trained young women (TRYW) to check this hypothesis and to study the combined response to hypoxia and training. S(O(2)) was decreased in PW (89.2% +/- 2.2 vs. 93.6 +/- 0.7% in YW, p < 0.01). Hb mass, however, was similar in UT (UTRYW: 9.2 +/- 0.9 g/kg(1), UTRPW: 8.7 +/- 1.0 g/kg). But if body fat rise with age was excluded by relation to fat-free mass, Hb mass was increased in UTRPW (+1.2 g/kg, p < 0.05) compared to UTRYW. Training caused a similar rise of Hb mass in PW and YW (0.3 g/kg per mL/kg x min(1) rise in V(O(2peak))). There was no difference in erythropoietin among the groups. Ferritin was higher in PW than YW. The results show that female hormones and fitness level have to be considered in studies on erythropoiesis at altitude. The role of erythropoietin during chronic hypoxia still has to be clarified.