Miracle-dz/UniFAR-FTUs huggingface dataset:
Alzheimer's disease & metals: therapeutic opportunities

Alzheimer's disease (AD) is the most common age related neurodegenerative disease. Currently, there are no disease modifying drugs, existing therapies only offer short‐term symptomatic relief. Two of the pathognomonic indicators of AD are the presence of extracellular protein aggregates consisting primarily of the Aβ peptide and oxidative stress. Both of these phenomena can potentially be explained by the interactions of Aβ with metal ions. In addition, metal ions play a pivotal role in synaptic function and their homeostasis is tightly regulated. A breakdown in this metal homeostasis and the generation of toxic Aβ oligomers are likely to be responsible for the synaptic dysfunction associated with AD. Therefore, approaches that are designed to prevent Aβ metal interactions, inhibiting the formation of toxic Aβ species as well as restoring metal homeostasis may have potential as disease modifying strategies for treating AD. This review summarizes the physiological and pathological interactions that metal ions play in synaptic function with particular emphasis placed on interactions with Aβ. A variety of therapeutic strategies designed to address these pathological processes are also described. The most advanced of these strategies is the so‐called ‘metal protein attenuating compound’ approach, with the lead molecule PBT2 having successfully completed early phase clinical trials. The success of these various strategies suggests that manipulating metal ion interactions offers multiple opportunities to develop disease modifying therapies for AD.
Antiretroviral adherence and treatment outcomes among adult Ethiopian patients

ABSTRACT Developing appropriate strategies to sustain optimal medication adherence among the increasing number of HIV-positive patients taking antiretroviral therapy (ART) in sub-Saharan Africa is a major challenge. The objective of this study was to determine patient, regimen, disease, patient-provider, and healthcare-related factors associated with adherence with ART over a one-year period, and assess the impact of adherence on treatment outcomes. We performed a prospective, observational study among 246 patients who were initiated on ART in Ethiopia. Of 172 who completed follow-up, 130 (75.6%) had ≥95% adherence. In the multivariate analyses, a higher baseline BMI (OR, 1.2; 95% CI 1.0, 1.4) and use of reminder devices (OR, 9.1; 95% CI 2.0, 41.6) remained positively associated with adherence, while a higher HIV symptom and adverse drug reaction distress score was an independent negative predictor of adherence (OR, 0.90; 95% CI 0.9, 1.0) CD4 count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months (159 cells/µL [interquartile range (IQR), 72–324 cells/µL] vs. 132 cells/µL [IQR, 43–190 cells/µL]; p = 0.026). Our findings indicate that interventions aimed at improving adherence and thereby treatment outcomes in patients initiated on ART should promote the use of reminder devices, and monitor HIV symptoms and adverse reaction distress and nutritional status.
Assembly studies of six intestinal intermediate filament (IF) proteins B2, C1, C2, D1, D2, and E1 in the nematode C. elegans

The dimerisation properties of six intestine‐expressed intermediate filament (IF) proteins (B2, C1, C2, D1, D2, E1) were analysed in blot overlay assay on membranes containing all of the eleven recombinant C. elegans IF proteins (A1, A2, A3, A4, B1, B2, C1, C2, D1, D2, and E1). The interactions detected in the blot assays exclusively comprise intestine‐expressed IF proteins and the protein A4, which is found in the dauer larva intestine. About 86% of these interactions are heterotypic, while the remaining interactions relate to C1, C2, and D2 homodimers. These multiple modes of interaction were also supported by calculations of the numbers of possible interchain ionic interactions derived from the individual rod sequences. The results predict that the six B2, C1, C2, D1, D2, and E1 IF proteins are able to form as many as eleven different heteropolymeric and three homopolymeric IFs in the C. elegans intestine. This simple model of the intestinal IF meshwork enables us to speculate that our previously reported triple RNAi worms arrested or decreased their growth because of feeding reduction due to morphological defects of the mechanically compromised intestine.
Sex‐dependent control of murine emotional‐affective behaviour in health and colitis by peptide YY and neuropeptide Y

BACKGROUND AND PURPOSE Peptide YY (PYY) and neuropeptide Y (NPY) are involved in regulating gut and brain function. Because gastrointestinal inflammation is known to enhance anxiety, we explored whether experimental colitis interacts with genetic deletion (knockout) of PYY and NPY to alter emotional‐affective behaviour.
The case for peripheral CB1 receptor blockade in the treatment of visceral obesity and its cardiometabolic complications

In this review, we consider the role of endocannabinoids and cannabinoid‐1 (CB1) cannabinoid receptors in metabolic regulation and as mediators of the thrifty phenotype that underlies the metabolic syndrome. We survey the actions of endocannabinoids on food intake and body weight, as well as on the metabolic complications of visceral obesity, including fatty liver, insulin resistance and dyslipidemias. Special emphasis is placed on weighing the relative importance of CB1 receptors located in peripheral tissues versus the central nervous system in mediating the metabolic effects of endocannabinoids. Finally, we review recent observations that indicate that peripherally restricted CB1 receptor antagonists retain efficacy in reducing weight and improving metabolic abnormalities in mouse models of obesity without causing behavioural effects predictive of neuropsychiatric side effects in humans.
Agonist‐selective patterns of µ‐opioid receptor phosphorylation revealed by phosphosite‐specific antibodies

BACKGROUND AND PURPOSE Morphine activates the µ‐opioid receptor without causing its rapid endocytosis. In contrast, full agonists such as [d‐Ala2‐MePhe4‐Gly‐ol]enkephalin (DAMGO) or etonitazene stimulate a rapid and profound internalization. However, the detailed molecular events underlying the differential regulation of receptor trafficking by distinct opioid agonists remain incompletely understood.
Mindfulness-Based Cognitive Therapy Reduces Symptoms of Depression in People With a Traumatic Brain Injury: Results From a Randomized Controlled Trial

Objective:We sought to determine if we could reduce symptoms of depression in individuals with a traumatic brain injury using mindfulness-based cognitive therapy. Setting:The study was conducted in a community setting. Participants:We enrolled adults with symptoms of depression after a traumatic brain injury. Design:We conducted a randomized controlled trial; participants were randomized to the 10-week mindfulness-based cognitive therapy intervention arm or to the wait-list control arm. Main Measures:The primary outcome measure was symptoms of depression using the Beck Depression Inventory-II. Results:The parallel group analysis revealed a greater reduction in Beck Depression Inventory-II scores for the intervention group (6.63, n = 38,) than the control group (2.13, n = 38, P = .029). A medium effect size was observed (Cohen d = 0.56). The improvement in Beck Depression Inventory-II scores was maintained at the 3-month follow-up. Conclusion:These results are consistent with those of other researchers that use mindfulness-based cognitive therapy to reduce symptoms of depression and suggest that further work to replicate these findings and improve upon the efficacy of the intervention is warranted.
Einfluss der Zentrifugationsmethode auf die Qualität und Kryokonservierung von Hengstsamen

Das Ziel der vorliegenden Studie war es, den Einfluss von verschiedenen Zentrifugationsmethoden auf Spermienverlust und Gefriersamenqualitat abzuklaren. Dazu wurden je drei Ejakulate von 8 gekorten Warmbluthengsten des Nationalgestuts Avenches gewonnen, und zur Entfernung des Seminalplasmas nach drei verschiedenen Methoden zentrifugiert. Bei Methode I (Referenzmethode) erfolgte die Zentrifugation bei einer relativen Zentrifugalbeschleunigung von 600 x g wahrend 10 Minuten. Bei Methode II wurde bei 1000 x g wahrend 2 Minuten und bei Methode III bei 2000 x g wahrend 2 Minuten zentrifugiert. Nach der Zentrifugation wurden jeweils 90% des Uberstandes abpipettiert und darin die Anzahl Samenzellen (Spermienverlust) bestimmt. Nach Resuspension mit Gefrierverdunner erfolgte die Bestimmung der funktionellen Membranintegritat mittels HOS-Test sowie die Beurteilung der Motilitat. Im aufgetauten Samen pruften wir die Motilitat, die Vitalitat (SYBR-14/PI), die funktionelle Membranintegritat (HOS-Test) und den Akrosoms.
Epidermal growth factor receptor tyrosine kinase regulates the human inward rectifier potassium KIR2.3 channel, stably expressed in HEK 293 cells

BACKGROUND AND PURPOSE The detailed molecular modulation of inward rectifier potassium channels (including the KIR2.3 channel) is not fully understood. The present study was designed to determine whether human KIR2.3 (KIR2.3) channels were regulated by protein tyrosine kinases (PTKs).
Low sustainability, poor governance, and other challenges encountered by grassroots non-governmental organizations targeting HIV prevention for men who have sex with men in China – a nation-wide study

ABSTRACT Grassroots non-governmental organizations (NGOs) played pivotal roles in HIV prevention among men who have sex with men (MSM) in China. Their governance and sustainability issues were under-studied. This nation-wide study surveyed leaders of 202 of the HIV related NGOs in China.58. 4% of the leaders believed that their NGO would last for ≤5 years; which was negatively associated with perceived good relationship with CDC. 65.3% mentioned ≥3 non-sustainability issues; associated factors included perceived inadequacies in prevention skills, management skills, policy support, technical support, operational support, and CDC’s support; a reverse association was found for frequent collaboration with organizations in China. 30.6% of the leaders mentioned ≥7 governance issues; a stepwise model found a positive association with having no office and negative associations with number of full-time staff and core volunteers. These problems would severely limit the effectiveness of HIV prevention among MSM. Related improvements and support are warranted.
Stigma, medical mistrust, and perceived racism may affect PrEP awareness and uptake in black compared to white gay and bisexual men in Jackson, Mississippi and Boston, Massachusetts

ABSTRACT Gay and bisexual men and other men who have sex with men (MSM) account for more than two thirds of new HIV infections in the U.S., with Black MSM experiencing the greatest burden. Antiretroviral pre-exposure prophylaxis (PrEP) can reduce MSM’s vulnerability to HIV infection. Uptake of PrEP has been limited, particularly among racial and ethnic minority MSM. Four semi-structured focus groups with gay and bisexual men and other MSM at risk for HIV infection were convened in Boston and Jackson in late 2013. The analysis plan utilized a within-case, across-case approach to code and analyze emerging themes, and to compare results across the two cities. Participants recruited in Jackson were primarily Black gay men, while Boston participants were mostly non-Hispanic White gay men. Participants in both sites shared concerns about medication side effects and culturally insensitive health care for gay men. Jackson participants described stronger medical mistrust, and more frequently described experiences of anti-gay and HIV related stigma. Multiple addressable barriers to PrEP uptake were described. Information about side effects should be explicitly addressed in PrEP education campaigns. Providers and health departments should address medical mistrust, especially among Black gay and bisexual men and other MSM, in part by training providers in how to provide affirming, culturally competent care. Medicaid should be expanded in Mississippi to cover low-income young Black gay and bisexual men and other MSM.
Interview with a Quality Leader: Madeleine Leininger on Transcultural Nursing and Culturally Competent Care

adeleine Leininger, PhD LHD DS RN CTN M FAAN FRCNA, is professor emeritus, Wayne State University (Detroit) and adjunct professor of the University of Nebraska Medical Center (Omaha) College of Nursing. She is the founder and leader of the academic field of transcultural nursing, with a focus o n comparative human care theory and research. She spearheaded establishing the Transcultural Nursing Society in 1974; in 1989 she initiated the Journal of Transcultural Nursing and served as editor until 1995. Dr. Leininger was dean and professor of the schools of nursing at the University of Washington and the University of Utah. She was the first full-time president of the American Association of Colleges of Nursing. In 1998, she was honored as a Living Legend of the American Academy of Nursing. Recently she was honored as a fellow of the Royal College of Nursing, Australia. Dr. Leininger is the author and editor of 28 books and more than 200 articles and has given approximately 1,500 public lectures in the United States and overseas. She was the first graduate professional nurse to complete a doctorate in anthropology and conducted the first transcultural nursing research study in the Eastern Highlands of New Guinea. Since then she has studied 15 cultures in the United States and overseas and has served as a mentor to more than 100 graduate students researching transcultural nursing and healthcare. She coined the term and concept of culturally congruent care in the 1960s with her theory of culture care diversity and universality.
Effects of antiretroviral treatment and nadir CD4 count in progression to cardiovascular events and related comorbidities in a HIV Brazilian cohort: a multi-stage approach

ABSTRACT The use of highly active antiretroviral therapy has resulted in changes of comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS-related events. The occurrence of cardiovascular events is greater in PLHIV, but the mechanism responsible for it is still controversial. This article aimed to investigate factors associated with the progression to cardiovascular events in PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio de Janeiro-Brazil. Clinical progression was stratified in five states: No comorbidities (s1), arterial hypertension (s2), lipid abnormalities (s3), hypertension and lipid abnormalities (s4) and major cardiovascular events (stroke, coronary artery disease, thrombosis or death) (s5). Semi-Markov models evaluated the effects of cardiovascular traditional factors, treatment and clinical covariates on transitions between these states. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided. In addition to traditional factors (age, sex, educational level and skin color), the development of one comorbidity (lipid abnormalities or hypertension) increased in patients with low nadir CD4 (<50 cells/mm3), (HR = 1.59, CI 1.11–2.28 and 1.36, CI 1.11–1.66, respectively). The risk to experience a second comorbidity (s3→s4) increased 75% with low nadir CD4. Age was the only factor that increased the risk of major cardiovascular events once having lipid abnormalities with or without hypertension (s3,s4→s5). The prolonged use of certain antiretroviral drugs (abacavir, didanosine, ritonavir, lopinavir, amprenavir and fosamprenavir) increased the risk of direct transition (s1→s5) to major cardiovascular events (HR = 5.29, CI 1.16–24.05). This analysis suggests that prolonged use of certain antiretroviral drugs led directly to major cardiovascular events, while low nadir CD4 only affected the occurrence of lipid abnormalities and hypertension. Management strategies, including rational use of complex exams (such as, computed-tomography angiography), statins and antihypertensives, should be developed based on the distinct roles of antiretroviral use and of HIV infection itself on the progression to cardiovascular events.
Neoadjuvant Chemoradiation in Patient with Localy Advanced Rectal Cancer

Abstract Introduction. Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinoma. Aim of the study is to analyze efficacy of neoadjuvant CRT and survival rates in patients with locally advanced rectal cancer. Materials and methods. Retrospective study of 60 locally advanced rectal cancer patients who underwent neoadjuvant radiotherapy with or without addition of neoadjuvant chemotherapy in Clinic of Oncology of Pauls Stradiņš Clinical University Hospital from 2007 to 2012 was done. Results. Long-course radiotherapy (45-50.4 Gy) received 52 patients. Median time from diagnosis to radiotherapy was 35.8 days. Median time to surgery was 47.7 days. Pathological complete remission (pCR) of the primary rectal cancer was not observed. Distribution by pathologic staging was as follows: 28.8% Stage I (7.7% T1N0M0), 32.7% Stage II and 38.5% Stage III. Downstaging occurred in 93.7% in concomitant chemoradiation with Ftorafur, 61.9% in combination with 5FU/LV, and 53.3% in radiation without chemotherapy. Median PFS and OS were not met. In median follow up of 22.6 month overall survival was 90.3%, and PFS - 88%. Conclusions. Addition of chemotherapy to neoadjuvant radiotherapy is increasing tumor downstaging rate. Ftorafur in concomitant neoadjuvant chemoradiation showed increased downstaging compared to standard 5FU therapy. Response to preoperative therapy improves survival in patient with locally advanced rectal cancer.
SALIVARY GLANDS - AN OVERVIEW

The glands are divided into major and minor salivary gland categories. The major salivary glands are parotid, submandibular and sublingual glands. The minor glands are dispersed throughout the upper aero-digestive submucosa. Saliva is the watery substance produced in the mouths of humans and other animals . Saliva is a component of oral fluid . Human saliva is composed of 98% water , while the other 2% consists of other compounds such as electrolytes , mucus , antibacterial compounds and various enzymes . A review of some patents on salivary glands is also provided that summarizes the recent technical advancements taken place in this area.
REPAIR MECHANISM OF RETINAL PIGMENT EPITHELIAL TEARS IN AGE-RELATED MACULAR DEGENERATION

Purpose: To investigate repair mechanisms of retinal pigment epithelial (RPE) tears in age-related macular degeneration. Methods: The authors retrospectively studied 10 eyes with age-related macular degeneration that developed RPE tears during follow-up or after treatment with an anti-vascular endothelial growth factor drug or photodynamic therapy combined with ranibizumab. After development of the RPE tears, all follow-ups exceeded 13 months. Spectral domain or swept-source optical coherence tomography have been used to examine consecutive retinal changes where the RPE tears developed and attempted to determine the repair mechanisms. Results: Retinal pigment epithelial tears developed during the natural course (n = 4) after ranibizumab treatment (n = 2) and after photodynamic therapy and ranibizumab (n = 4). Subretinal fluid persisted for more than 6 months after the RPE tears developed (n = 4), with the area where the RPE was lost found to be covered with thickened proliferative tissue. In 6 eyes where the subretinal fluid was absorbed within 2 months, optical coherence tomography showed the outer retina appeared to be directly attached to Bruch membrane, and there was attenuation of the normal hyperreflective band attributable to normal RPE during follow-up. Conclusion: Results suggest that two repair processes may be present in the area where RPE tears developed. Persistent subretinal fluid may lead to repair with thick proliferative tissue, while the outer retina appears to attach to Bruch membrane when there is early subretinal fluid resolution after RPE tear development.
Alternative Certified Teachers and Children at Risk

Special education programs that serve at-risk students are facing very real personnel needs that colleges and universities alone cannot meet. Alternative certification programs (ACP) may help meet these needs. Effective university-school district partnership programs that include critical teaching training components may offer an attractive alternative to traditional teacher training programs. Teacher retention and increased student learning are probable outcomes resulting from quality model ACP.
Daily living: Does this matter for people with mental illness?

Structuring their daily life is an important problem for many individuals with chronic mental disorder. Therefore day structuring services are considered as constituent parts of modern mental healthcare systems. In this paper the theoretical and empirical basis for the implementation and evaluation of day structuring services will be discussed from a social science perspective. Recent work in the field of cultural sociology shows that the social framework of everyday behaviour in modern societies provides a great variety of opportunities to create and practice individual lifestyles. The potential to take advantage of these opportunities is related to individual competencies and resources. The few existing qualitative studies on the everyday behaviour of individuals with chronic mental disorders in the community reveal that increased freedom of choice is often combined with an objective or subjective lack of resources and competencies to make use of this variety of opportunities. Therefore, beyond providing a structure for daily life, day structuring services should help empower individuals with chronic mental disorder to make their choices among behavioural alternatives bearing in mind both illness-related limitations and their strengths and resources.
Hydrogen sulphide‐releasing diclofenac derivatives inhibit breast cancer‐induced osteoclastogenesis in vitro and prevent osteolysis ex vivo

BACKGROUND AND PURPOSE Hydrogen sulphide (H2S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non‐steroidal anti‐inflammatory drugs (NSAIDs) and H2S donors exhibit anti‐inflammatory and anti‐tumour properties. H2S‐releasing diclofenac (S‐DCF) derivatives are a novel class of NSAIDs combining the properties of a H2S donor with those of a conventional NSAID.
Krüppel‐like factor 4 is induced by rapamycin and mediates the anti‐proliferative effect of rapamycin in rat carotid arteries after balloon injury

BACKGROUND AND PURPOSE The transcription factor, Krüppel‐like factor 4 (KLF4), plays an important role in regulating the proliferation of vascular smooth muscle cells. This study aimed to examine the effect of rapamycin on the expression of KLF4 and the role of KLF4 in arterial neointimal formation.
Clinical considerations on the use of concomitant therapy in the treatment of acne

Acne is a disease that affects millions of people worldwide and requires prompt and effective management of both the physical and psychological sequelae that an individual may experience. The ultimate goal of treatment is to address as many of the pathogenic factors of acne as possible while minimizing side effects. Numerous therapeutic options are available; however, most current treatment options address only one or two of these factors. For this reason, combining single therapies has been the practice since the mid‐1970s, beginning with the concomitant use of treatments such as topical vitamin A with systemic tetracyclines or topical benzoyl peroxide. As additional therapeutic options have emerged, dermatologists have also begun to utilize these treatments concomitantly based on their synergistic and multifactorial effects on the different pathogenic factors of acne. This review provides an update of recent advances and data regarding the concomitant use of various anti‐acne agents.