Miracle-dz/UniFAR-FTUs huggingface dataset:
The targeting of β‐cells by T lymphocytes in human type 1 diabetes: clinical perspectives

This review focuses on genes that control β‐cell targeting in autoimmune, type 1‐dependent, diabetes (T1D) and on insulin as the major autoantigen recognized by T lymphocytes throughout the disease process. T1D associates with multiple gene variants. Beyond genes that predispose to general failure of immune tolerance to self, loci identified by the analysis of crosses between non‐obese diabetic (NOD) and conventional mouse strains harbour genes that control β‐cell targeting or the deviation of autoimmunity towards other tissues. We report here the role of genes encoding co‐activation molecules involved in the activation of T lymphocytes, ICOS and ICOS ligand (B7RP1). NOD mice which are deficient in either of these two molecules are protected from diabetes, but instead develop a neuromuscular autoimmune disease. We also report the characterization in humans of T lymphocytes that are specific for major β‐cell autoantigens, especially insulin. This opens the way towards new bioassays in the diagnosis of autoimmunity and towards autoantigen‐specific immunotherapy in T1D. In order to develop a new preclinical model of T1D that would allow testing insulin epitopes to induce immune tolerance in vivo, we developed a mouse that is deficient in endogenous major histocompatibility complex class I and class II genes and deficient for the two murine insulin genes and that express human class I, class II and insulin genes.
Targeting inflammation in the treatment of type 2 diabetes

Islets of patients with type 2 diabetes display the typical features of an inflammatory process characterized by the presence of cytokines, chemokines, immune cell infiltration, impaired function and tissue destruction with fibrotic areas. Functional studies have shown that targeting inflammation may improve insulin secretion and sensitivity. In particular clinical proof of concept studies using modulators of the interleukin‐1β (IL‐1β)—nuclear factor‐κB (NF‐κB) pathway demonstrated the role of the innate immune system in type 2 diabetes. This programme has now entered the phase 3 of clinical development. Other targets such as tumour necrosis factor α (TNFα) may be equally important but have been neglected based on poorly designed studies. In this article we discuss the mechanisms of islet inflammation in type 2 diabetes and review the opportunity of clinical translation.
Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis.

Importance The use of palliative care programs and the number of trials assessing their effectiveness have increased. Objective To determine the association of palliative care with quality of life (QOL), symptom burden, survival, and other outcomes for people with life-limiting illness and for their caregivers. Data Sources MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL to July 2016. Study Selection Randomized clinical trials of palliative care interventions in adults with life-limiting illness. Data Extraction and Synthesis Two reviewers independently extracted data. Narrative synthesis was conducted for all trials. Quality of life, symptom burden, and survival were analyzed using random-effects meta-analysis, with estimates of QOL translated to units of the Functional Assessment of Chronic Illness Therapy-palliative care scale (FACIT-Pal) instrument (range, 0-184 [worst-best]; minimal clinically important difference [MCID], 9 points); and symptom burden translated to the Edmonton Symptom Assessment Scale (ESAS) (range, 0-90 [best-worst]; MCID, 5.7 points). Main Outcomes and Measures Quality of life, symptom burden, survival, mood, advance care planning, site of death, health care satisfaction, resource utilization, and health care expenditures. Results Forty-three RCTs provided data on 12 731 patients (mean age, 67 years) and 2479 caregivers. Thirty-five trials used usual care as the control, and 14 took place in the ambulatory setting. In the meta-analysis, palliative care was associated with statistically and clinically significant improvements in patient QOL at the 1- to 3-month follow-up (standardized mean difference, 0.46; 95% CI, 0.08 to 0.83; FACIT-Pal mean difference, 11.36] and symptom burden at the 1- to 3-month follow-up (standardized mean difference, -0.66; 95% CI, -1.25 to -0.07; ESAS mean difference, -10.30). When analyses were limited to trials at low risk of bias (n = 5), the association between palliative care and QOL was attenuated but remained statistically significant (standardized mean difference, 0.20; 95% CI, 0.06 to 0.34; FACIT-Pal mean difference, 4.94), whereas the association with symptom burden was not statistically significant (standardized mean difference, -0.21; 95% CI, -0.42 to 0.00; ESAS mean difference, -3.28). There was no association between palliative care and survival (hazard ratio, 0.90; 95% CI, 0.69 to 1.17). Palliative care was associated consistently with improvements in advance care planning, patient and caregiver satisfaction, and lower health care utilization. Evidence of associations with other outcomes was mixed. Conclusions and Relevance In this meta-analysis, palliative care interventions were associated with improvements in patient QOL and symptom burden. Findings for caregiver outcomes were inconsistent. However, many associations were no longer significant when limited to trials at low risk of bias, and there was no significant association between palliative care and survival.
Fat‐free mass loss generated with weight loss in overweight and obese adults: what may we expect?

There is concern that intentional weight loss may generate excessive loss of fat‐free mass (FFM). Idealists target minimal loss of FFM, while others consider that FFM loss of up to 25% of weight loss is acceptable. In a cross‐sectional study of 275 weight‐stable, overweight or obese adults, we used whole‐body dual‐energy X‐ray absorptiometry to measure FFM. A range of models was used to estimate the expected ΔFFM/Δweight ratio required to attain the body composition of a weight‐stable individual at a lower body mass index (BMI). Higher BMI was associated linearly with higher FFM in men and women. Proportional ΔFFM/Δweight was influenced by sex, BMI and age. Direct scatter plot analysis, quadratic curve fit modelling and linear FFM–BMI modelling provided similar estimates for each model of ΔFFM/Δweight ratio, with 40% for men and 33% for women. These results show that the 25% rule is inappropriate and our estimates are higher than those generally reported after intentional weight loss indicating favourable preservation of FFM.
Fear of rejection--monitoring the heart-transplant recipient.

Among patients undergoing heart transplantation, a fundamental clinical concern is the risk of rejection of the new organ. Although modern immunosuppressive regimens have reduced the incidence of rejection substantially, about one quarter of recipients will still have a rejection episode requiring treatment during the first year after transplantation.1 Acute rejection is the cause of 12% of deaths occurring between 1 month and 1 year after transplantation.1 There is no established noninvasive marker of rejection available for heart-transplant recipients; instead they must undergo serial endomyocardial biopsies with histologic evaluation of myocardial tissue to monitor for rejection. Endomyocardial biopsy is an invasive .
Polypharmacy and inappropriate drug prescribing in elderly nursing home residents.

Background Polypharmacy and inappropriate drug use are common in nursing home residents, who are therefore at increased risk for potential adverse drug effects and drug interactions. In Slovenia, this is the first study of drug prescribing in elderly nursing home residents. Zdrav Vestn 2009; 78: 231–40 232 Zdrav Vestn 2009; 78 Methods This study was cross-sectional, including 2040 elderly nursing home residents in 12 nursing homes in Slovenia. 2003 Beers criteria and ten most common drug interactions were used to determine potentially inappropriate prescriptions. Results The mean age was 82.0 years (SD 7.7 years), 1597 (78 %) were female patients. The mean number of regularly prescribed drugs was 5.8, 1032 (50.6 %) of patients were taking more than 6 drugs at once. Higher number of drugs were more often prescribed to female patients. Patients with dementia and fully dependant patients were prescribed less, and patients with depression and those who were partially dependent in their daily activities were prescribed more drugs. 455 (22.3 %) residents had at least one inappropriately prescribed drug or combination of drugs. Male patients (p = 0.008), residents partially dependent on daily activities (p = 0.001) and patients with more prescribed drugs (p < 0.001) were more likely to have an inappropriate prescription. The most common inappropriate prescriptions were cyclooxigenase 2 non-selective nonsteroid anti-inflammatory drugs (NSAID), a prescription of NSAID, dipyridamole, ticlopidine or clopidogrel in patients with blood-clotting disorders or patients taking anticoagulants, a prescription of the combination of digoxine and amiodarone, and the combination of an ACE inhibiting drugs and spironolactone. Conclusions Obtained results about number of drugs and inappropriate drugs or drug combinations show that the situation in Slovenia is similar to the the situation in western European countries and better than in eastern Europe, but still half of the elderly nursing home residents in Slovenia are exposed to polypharmacy and one fifth to inappropriate drug prescribing.
Blood pressure‐lowering effect of the sodium glucose co‐transporter‐2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension

This study compared the blood pressure‐lowering effect of ertugliflozin (1, 5, 25 mg), hydrochlorothiazide (HCTZ; 12.5 mg) and placebo in 194 patients with type 2 diabetes mellitus and hypertension for 4 weeks using ambulatory blood pressure monitoring. Endpoints (change from baseline to week 4) were: 24‐h mean systolic blood pressure (SBP; primary); daytime, night‐time, seated predose SBP, 24‐h, daytime, night‐time, seated predose diastolic blood pressure, 24‐h urinary glucose excretion and fasting plasma glucose (FPG; secondary). Safety and tolerability were monitored. Significant decreases in placebo‐corrected 24‐h mean SBP (−3.0 to −4.0 mmHg) were recorded for all doses of ertugliflozin (for HCTZ, this was −3.2 mmHg). Daytime, but not night‐time SBP was consistently reduced. Ertugliflozin produced dose‐dependent significant decreases in FPG and increases in urinary glucose excretion. No notable changes in plasma renin activity or urinary aldosterone were seen. The most common adverse events were urinary tract infection, genital fungal infection, upper respiratory tract infection and musculoskeletal pain.
By Word of Mouth: A Qualitative Approach to Understanding the Integration of Preventive Dental Health in Primary Care Settings

Background: Substantial racial, ethnic, and socioeconomic dental disparities exist among children and adolescents in the United States. The inclusion of oral health messages during primary care visits may be a way to promote positive oral health behaviors of child and adolescent patients and reduce disparities in oral health. The Quality through Technology & Innovation in Pediatrics (QTIP) demonstration project is a promising approach to integrate preventive dental health in primary care pediatric practices. Purpose: To conduct a retrospective process evaluation to examine the extent and how primary care pediatric practices (n=18) integrated preventive dental health based on their participation in the QTIP demonstration project. Methods: We conducted a process evaluation to identify how participants engaged with and integrated oral health within their practices using a qualitative approach by directed content analysis. Results: We identified the extent to which QTIP practices’ integrated preventive dental health in their medical settings as result of the QTIP demonstration project through preventive dental health training and development and QTIP participants adherence to demonstration project objectives. QTIP practices also demonstrate through Plan-DoStudy-Act (PDSA) reports how they included preventive dental health practices within their medical settings. 1 Nelson JD, Spencer SM, Blake CE, Moore JB and Martin AB. To be submitted to Journal for Healthcare Quality.
La Nutrición en el Antiguo Perú

At the suggestion of my teacher Professor Carlos Monge, I have the honor to participate is this interesting Anthropology Conference. Dedicated exclusively to Biochemistry understood that my historical knowledge is scarce, when they had earned some references from people who have dealt with these issues, particularly those published by Professor Juan B. Lastres, to treat it entirely from the nutritional point of view .
Management of cases suffering from atypical myopathy: Interpretations of descriptive, epidemiological and pathophysiological findings. Part 1: First aid, cardiovascular, nutritional and digestive care

Summary Atypical myopathy is highly fatal, but about a quarter of affected horses survive. This highlights the need for provision of supportive treatment for these cases. This review is a practical guideline for equine practitioners and includes suggestions for close monitoring of involved organ systems and discusses options of supportive treatment based on current knowledge of the condition.
Bevacizumab versus ranibizumab for AMD.

For 5 years, patients and clinicians have wrestled with the choice between two drugs for the treatment of neovascular age-related macular degeneration (AMD), a common cause of irreversible blindness among the elderly worldwide. Vision loss results from the abnormal growth and leakage of blood vessels in the macula, a specialized portion of the retina responsible for the best visual acuity. Without this macular vision, patients become legally blind. Vascular endothelial growth factor (VEGF), the cytokine primarily responsible for blood-vessel growth, is inhibited when anti-VEGF drugs are injected repeatedly into the eye, and blindness is prevented in most patients. The majority .
Novel factors modulating human β‐cell proliferation

β‐Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β‐cells, and an understanding of the cellular mechanism(s) that regulate β‐cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β‐cell proliferation is one potential approach to restore β‐cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β‐cell replication in animal models or cell lines, promoting effective human β‐cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β‐cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5‐IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK‐3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF‐kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes.
Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance

Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'. In the last two decades, numerous high-risk (HiR) MDR and XDR K. pneumoniae sequence types have emerged showing superior ability to cause multicontinent outbreaks, and continuous global dissemination. The data highlight the complex evolution of MDR and XDR K. pneumoniae, involving transfer and spread of ARGs, and epidemic plasmids in highly disseminating successful clones. With the worldwide catastrophe of antibiotic resistance and the urgent need to identify the main pathogens that pose a threat on the future of infectious diseases, further studies are warranted to determine the epidemic traits and plasmid acquisition in K. pneumoniae. There is a need for future genomic and translational studies to decipher specific targets in HiR clones to design targeted prevention and treatment.
The yin and yang of interleukin-2-mediated immunotherapy.

In this issue of the Journal, the findings of two case series suggest that in vivo treatment with interleukin-2 can suppress immune-mediated diseases. In one study, Koreth et al.1 found that low-dose interleukin-2 was associated with reversal of glucocorticoid-refractory chronic graft-versus-host disease (GVHD) in patients who had undergone allogeneic hematopoietic stem-cell transplantation (HSCT) for the treatment of lymphomas and leukemias. The control of chronic GVHD was not accompanied by the relapse of cancer in any patient.1 In a second small case series, Saadoun et al.2 found that treatment of patients with hepatitis C virus (HCV)–related vasculitis with low-dose interleukin-2 led .
Inflammation in multiple sclerosis--sorting out the gray matter.

In this issue of the Journal, Lucchinetti and colleagues report a high prevalence of cortical gray-matter inflammation and demyelination on tissue obtained at biopsy from patients with multiple sclerosis of new onset.1 Although several prior studies have documented demyelinating lesions in the gray matter of persons with multiple sclerosis,2,3 none of these investigations analyzed tissues from more than one newly diagnosed patient. The findings of the study by Lucchinetti et al. are provocative and provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of multiple sclerosis. Specifically, they found cortical .
A watershed moment in the treatment of hepatitis C.

More than 170 million persons harbor chronic infection with hepatitis C virus (HCV), the leading indication for liver transplantation worldwide. For more than 20 years, treatment of chronic hepatitis C infection has relied on the use of the nonspecific antiviral cytokine interferon alfa, which induces hundreds of genes that collectively generate an antiviral state. In the early 1990s, treatment with interferon alfa resulted in a sustained virologic response in very few patients. The next two decades witnessed steady improvement; combining pegylated interferon alfa (peginterferon alfa) with ribavirin produced overall rates of sustained virologic response of 54 to 56%,1,2 with .
Which is more enduring--FAME or COURAGE?

Since the advent of percutaneous coronary intervention (PCI) in 1977,1 visual assessment of the severity of coronary stenosis has been used to guide revascularization in patients with coronary artery disease. Almost 20 years ago, however, a technique was developed to directly measure the functional stenosis severity with the use of an intracoronary pressure wire to quantify the transstenotic pressure gradient before and after PCI.2,3 Subsequently, pressure-derived fractional flow reserve (FFR) was evaluated in the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial, in which patients were randomly assigned to conventional, angiographically directed PCI or FFR-guided PCI (with .
Ponatinib for chronic myeloid leukemia.

The treatment of patients with chronic myeloid leukemia (CML) must be ranked as one of the great medical success stories of the past 30 years. The demonstration that the Philadelphia (Ph) chromosome carries a fusion gene formed by the juxtaposition of BCR and ABL genetic sequences focused attention on the possibility that the tyrosine kinase activity of ABL might be greatly enhanced by fusion with BCR such that the BCR-ABL oncoprotein could be the primary cause of CML. If it were so, then pharmacologic inactivation of the oncoprotein might be clinically useful, and so it proved. In 1996, Druker et .
Relación del tipo de alimentación con algunas variables del crecimiento, estado nutricional y morbilidad del lactante (Relationship of the type of feeding with some infant’s growth, nutritional state and mobility variables)

Antecedentes: Las recomendaciones actuales para alimentación del niño durante el primer año de vida es iniciar la lactancia materna tan pronto como sea posible y evitar el uso de cualquier tipo de alimentos o líquidos distintos a la leche de pecho durante los primeros cuatro a seis meses de vida. Objetivo: Determinar si el patrón de alimentación en las etapas iniciales de la vida postnatal influyen en las características del crecimiento y el desarrollo del lactante durante el primer año de la vida. Pacientes y métodos: Se estudiaron 77 lactantes pertenecientes a 14 consultorios del médico de la familia del Policlínico Docente Bejucal en la provincia de La Habana. De ellos 27 lactaron de forma exclusiva por 4 meses y 50 iniciaron la alimentación complementaria antes del cuarto mes. A todos los lactantes se les realizó un estudio clínico y antropométrico, al mes, tres, cinco, nueve y doce meses del nacimiento. El análisis estadístico incluyó las variaciones de los estadígrafos descriptivos (media, desviación estándar, e intervalos de confianza a 95%) así como un análisis de observaciones repetidas para conocer si las variaciones de la evolución dependen del tiempo de lactancia materna exclusiva. Resultados: Se pudo apreciar que no existen variaciones en la evolución de los valores de la media del peso hasta el noveno mes del desarrollo. Las variaciones de la talla no muestran diferencias en su patrón de ganancia entre los grupos en todas las etapas del desarrollo estudiadas. Hay diferencias en las cifras de morbilidad sobre todo en lo referente a las enfermedades respiratorias y diarreicas. Conclusiones: No se evidencian diferencias importantes relacionadas con la evolución del peso y la talla durante el primer año de vida. La morbilidad se ve influida por el tipo de alimentación que se reciba durante el primer año de vida.