Miracle-dz/UniFAR-FTUs huggingface dataset:
Human immunosenescence: is it infectious?

Summary: Morbidity and mortality due to infectious disease is greater in the elderly than in the young, at least partly because of age‐associated decreased immune competence, which renders individuals more susceptible to pathogens. This susceptibility is particularly evident for novel infectious agents such as in severe acute respiratory syndrome but is also all too apparent for common pathogens such as influenza. Many years ago, it was noted that the elderly possessed oligoclonal expansions of T cells, especially of CD8+ cells. At the same time, it was established that cytomegalovirus (CMV) seropositivity was associated with many of the same phenotypic and functional alterations to T‐cell immunity that were being reported as biomarkers associated with aging. It was discovered that CMV was the prime driving force behind most of the oligoclonal expansions and altered phenotypes and functions of CD8 cells. Independently, longitudinal studies of a free‐living population of the very old in Sweden over the past decade have led to the emerging concept of an ‘immune risk phenotype’ (IRP), predicting mortality, which was itself found to be associated with CMV seropositivity. These findings support our hypothesis that the manner in which CMV and the host immune system interact is critical in determining the IRP and hence is predictive of mortality. In this sense, then, we suggest that immunosenescence is contagious.
Dexmedetomidine and cardiac protection for non‐cardiac surgery: a meta‐analysis of randomised controlled trials

We conducted a systematic review of the effects of dexmedetomidine on cardiac outcomes following non‐cardiac surgery. We included prospective, randomised peri‐operative studies of dexmedetomidine that reported mortality, cardiac morbidity or adverse drug events. A PubMed Central and EMBASE search was conducted up to July 2007. The reference lists of identified papers were examined for further trials. Of 425 studies identified, 20 were included in the meta‐analysis (840 patients). Dexmedetomidine was associated with a trend towards improved cardiac outcomes; all‐cause mortality (OR 0.27, 95% CI 0.01–7.13, p = 0.44), non‐fatal myocardial infarction (OR 0.26, 95% CI 0.04–1.60, p = 0.14), and myocardial ischaemia (OR 0.65, 95% CI 0.26–1.63, p = 0.36). Peri‐operative hypotension (26%, OR 3.80, 95% CI 1.91–7.54, p = 0.0001) and bradycardia (17%, OR 5.45, 95% CI 2.98–9.95, p < 0.00001) were significantly increased. An anticholinergic did not reduce the incidence of bradycardia (p = 0.43). A randomised placebo‐controlled trial of dexmedetomidine is warranted.
The development of a blood‐brain barrier mechanism in foetal sheep

1. The penetration of a metabolically inert, small molecular radius lipid insoluble substance ([13C] and [4H]sucrose), from blood into brain and c.s. f. , has been studied in developing sheep from 50 days gestation (term, 150 days) through to the new‐born stage. Around 50 days gestation sucrose accumulated rapidly into brain and c.s. f. , and reached a steady‐state level in brain of about 12% of the plasma level by 3 hr. By 60 days sucrose penetrated less freely into brain and c.s. f. ; the brain steady‐state level was 10% by 4½ hr. A large decrease in sucrose penetration occurred by 70 days gestation, and by 123 days (just before the time when a foetal lamb becomes viable) both the rate of penetration and the brain steady‐state level of sucrose were similar to those of the adult of other species.
The Influence of an Experimentally-Induced Malocclusion On Vertebral Alignment in Rats: A Controlled Pilot Study

Abstract There is a growing interest in the relationship between occlusion and posture because of a greater incidence of neck and trunk pain in patients with occlusal dysfunction. The study was designed to verify whether an alteration of the spinal column alignment may be experimentally induced in rats as a consequence of altering dental occlusion and also to investigate whether the spinal column underwent any further changes when normal occlusion was then restored. Thirty rats were divided into two groups. Fifteen (15) rats (test group) wore an occlusal bite pad made of composite resin on the maxillary right first molar for a week (T1). The same rats wore a second composite bite pad for another week on the left first molar in order to rebalance dental occlusion (T2). Fifteen rats were included in an untreated control group. All the rats underwent total body radiographs at T0 (before the occlusal pad was placed), at T1 (one week after application of a resin occlusal bite pad on the maxillary left first molar) and at T2 (one week after application of a second resin occlusal bite pad on the maxillary right first molar). A scoliotic curve developed in all the test rats at T1. There were no alterations of spinal position observed in any of the control rats. Additionally, the spinal column returned to normal condition in 83% of the test rats when the balance in occlusal function was restored. The alignment of the spinal column seemed to be influenced by the dental occlusion.
Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with peritoneal hepatocellular carcinoma

The benefit of Sorafenib is not well described in patients with peritoneal hepatocellular carcinoma (HCC). Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown favorable outcomes in certain malignancies, their role in peritoneal HCC remains unknown. We present a series of patients with peritoneal HCC treated with CRS +/− HIPEC and evaluate their clinicopathologic characteristics and outcomes.
Six year Trend in Cataract Surgical Techniques in Iran

Purpose To determine the cataract surgery techniques performed in Iran from 2000 to 2005. Materials and Methods This study was part of the Iranian Cataract Surgery Survey (ICSS) which was a retrospective cross-sectional study. All major ocular surgery units and 10% of randomly selected minor units throughout Iran were included. Excluding the 2 week Iranian New Year holiday, 1 week per season between 2000 and 2005 (a total of 24 weeks) was selected for each center, and data on all cataract surgeries performed during these weeks were collected by reviewing patient records. The ANOVA repeated measure test was performed to determine longitudinal changes with a P<0.05 denoting statistical significance. Results Phacoemulsification with intraocular lens (IOL) implantation has become the surgical method of choice in Iran, increasing from less than 7% in 2000 to 57% in 2005 (P<0.0001). Extracapsular cataract extraction showed a reverse trend compared to phacoemulsification, decreasing from greater than 91% in 2000 to 41% in 2005 (P<0.0001). Intracapsular cataract extraction and lensectomy were rarely performed without significant changes over time (P>0.05). Conclusion Phacoemulsification with IOL implantation has become the preferred cataract surgery method in Iran during recent years.
. Desmoid tumor of the neck: CT and angiographic

The term desmoid tumor (Greek desmos = band) was coined to designate tumors of a tendon-or ligamentlike consistency. They are derived from musculoaponeurotic sup porting tissues and are histologically benign fibroblastic tu mors. These rare lesions constitute only 0.03% of all neo plasms. Because of their predilection for the anterior abdom inal wall, desmoid tumors have been categorically linked with "abdominal wall tumors" [1 , 2]. Nevertheless, they are known to occur in virtually all parts of the body.
Anaerobic regulation of the Escherichia coli dmsABC operon requires the molybdate‐responsive regulator ModE

Expression of the Escherichia coli dmsABC operon that encodes a molybdenum‐containing DMSO/TMAO reductase is increased in response to anaerobiosis and repressed by nitrate. These changes are mediated by the transcription factors Fnr and NarL respectively. Interestingly, modC strains that are defective in molybdate uptake exhibit impaired anaerobic induction and no nitrate‐dependent repression of the dmsABC operon. To determine if the molybdate‐responsive transcription factor ModE is involved in this process, a set of dmsA–lacZ operon fusions were constructed and analysed. The pattern of dmsA–lacZ expression in response to anaerobiosis and nitrate addition was identical in both modC and modE strains, thus suggesting a regulatory role for ModE. In vitro studies confirmed that ModE bound the dmsA promoter at a high‐affinity site typical of other E. coli ModE operator sites. Mutations in this site abolished ModE binding in vitro and displayed the same phenotype as a modE mutation. In contrast to previously characterized ModE operator sites, which either overlap or are located immediately upstream of the ModE‐regulated promoter, the ModE site is centred 52.5 bp downstream of the major dmsA transcript start site. We identified a putative integration host factor (IHF) binding site in the intervening sequence, and in vitro studies confirmed that IHF bound this site with high affinity. Using himA mutants, we confirmed that IHF plays a role in the molybdate‐dependent regulation of dmsA–lacZ expression in vivo. This study provides the first example in which ModE affects gene regulation in concert with another transcription factor.
Methanol-related deaths in Ontario.

OBJECTIVE Methanol poisoning accounts for several deaths annually in the province of Ontario. Our study was aimed at identifying the associated epidemiological factors for fatal outcomes following methanol poisoning in order to develop preventative strategies. METHODS The records of the Ontario Provincial Coroner's Office were reviewed retrospectively for all poison-related, alcohol-related, and chronic alcohol use-related deaths for the period of January 1, 1986 to December 31, 1991. Age, gender, reason for ingestion (accidental or intentional), and source of methanol for each victim were recorded. RESULTS There were 43 fatalities during this period, 39 males and 4 females with a mean age of 45 years (range 18-80). Suicide attempts accounted for 21 (49%) cases while the remaining 22 (51%) deaths were classified as accidental. Fourteen (64%) of these 22 patients consumed products labeled as methyl alcohol or wood alcohol as a substitute for ethanol. In 3 cases, the accidental ingestion was the direct result of methanol being improperly stored in containers normally associated with ethanol. The remaining 5 patients were poisoned through the consumption of liquor from illicit sources. CONCLUSIONS Over half of the methanol-related deaths in Ontario are accidental and potentially preventable. Possible preventative strategies include mandatory product relabeling to eliminate the word alcohol, enhanced public education, and the addition of aversive agents to methanol-containing commercial products.
Categorized hospital charges of acute ischemic stroke according to trial of org 10172 in acute stroke treatment classification.

BACKGROUND Previous studies have shown that the cost of hospitalization due to stroke is significantly associated with the length of stay, stroke severity and other clinical characteristics, as well as various socio-demographic factors. However, these studies have been rather inconsistent with regard to the influence of stroke subtypes on costs. AIMS This study was examined and compared hospital charges of in-patients with acute ischemic stroke according to the Trial of Org 10172 in Acute Stroke Treatment classification. MATERIALS AND METHODS The costs of case of 749 patients with first ever ischemic stroke who were admitted to an academic medical center between January 2006 and December 2008 were analyzed. The hospital charges were compared among the stroke subtypes using Analysis of Variance. Multiple regression analyses were further performed to test the significance of the impact of the stroke subtype after controlling for other variables. RESULTS The stroke subtype turned out to be a statistically significant factor influencing both the total charge and several categorized charges even after controlling for other contributing factors such as hospital length of stay and stroke severity. CONCLUSIONS This study concludes that the stroke subtype should be included when considering in-patient medical expenses of acute ischemic stroke.
Ultrasound Morphology of the Achilles in Asymptomatic Patients With and Without Diabetes

Background: The prevalence of tendinopathies is increased in subjects with diabetes mellitus. However, there are few data on the structural abnormalities of Achilles tendons in asymptomatic diabetic patients. The aim of the study was to assess the morphologic characteristics of the Achilles tendon in subjects with diabetes in comparison with controls without diabetes. Methods: Participants were consecutively recruited from an outpatient population. Ultrasound longitudinal and transverse scans were performed bilaterally along the full length of Achilles tendon from the musculotendinous junction to the insertion. Degenerative features (abnormal fibrillar pattern, hypo-hyperechoic areas), signs of enthesopathy (bony erosion, enthesophytes, and bursitis), and intratendinous neovessel formation were recorded. Results: Asymptomatic sonographic abnormalities (ASA) were significantly increased in subjects with diabetes (35/136 [25.7%] vs 32/273 [11.7%], P = .0003). Sixty tendons with ASA were observed in the first group and 45 in the latter because ASA were bilateral in 25 and in 13 subjects, respectively. ASA were more frequently localized at the enthesis (32/60 [53.3%] vs 9/45 [20%], P = .0005) in the diabetes group, whereas, on the contrary, they were more prevalent at the midportion in controls (38/45 [84.4%] vs 36/60 [60%], P < .006). Conclusion: Diabetes may predispose to Achilles tendinopathy and particularly to Achilles enthesopathy. Longitudinal studies, evaluating the progression of the lesions not only in the midportion of the tendon but also at the insertion are needed to support this conclusion. Level of Evidence: Level III, comparative series.
Voltage-Gated Ion Channels in Human Pancreatic β-Cells: Electrophysiological Characterization and Role in Insulin Secretion

OBJECTIVE— To characterize the voltage-gated ion channels in human β-cells from nondiabetic donors and their role in glucose-stimulated insulin release. RESEARCH DESIGN AND METHODS— Insulin release was measured from intact islets. Whole-cell patch-clamp experiments and measurements of cell capacitance were performed on isolated β-cells. The ion channel complement was determined by quantitative PCR. RESULTS— Human β-cells express two types of voltage-gated K+ currents that flow through delayed rectifying (KV2.1/2.2) and large-conductance Ca2+-activated K+ (BK) channels. Blockade of BK channels (using iberiotoxin) increased action potential amplitude and enhanced insulin secretion by 70%, whereas inhibition of KV2.1/2.2 (with stromatoxin) was without stimulatory effect on electrical activity and secretion. Voltage-gated tetrodotoxin (TTX)-sensitive Na+ currents (NaV1.6/1.7) contribute to the upstroke of action potentials. Inhibition of Na+ currents with TTX reduced glucose-stimulated (6–20 mmol/l) insulin secretion by 55–70%. Human β-cells are equipped with L- (CaV1.3), P/Q- (CaV2.1), and T- (CaV3.2), but not N- or R-type Ca2+ channels. Blockade of L-type channels abolished glucose-stimulated insulin release, while inhibition of T- and P/Q-type Ca2+ channels reduced glucose-induced (6 mmol/l) secretion by 60–70%. Membrane potential recordings suggest that L- and T-type Ca2+ channels participate in action potential generation. Blockade of P/Q-type Ca2+ channels suppressed exocytosis (measured as an increase in cell capacitance) by >80%, whereas inhibition of L-type Ca2+ channels only had a minor effect. CONCLUSIONS— Voltage-gated T-type and L-type Ca2+ channels as well as Na+ channels participate in glucose-stimulated electrical activity and insulin secretion. Ca2+-activated BK channels are required for rapid membrane repolarization. Exocytosis of insulin-containing granules is principally triggered by Ca2+ influx through P/Q-type Ca2+ channels.
Radiosurgery for Cushing's disease after failed transsphenoidal surgery.

OBJECT Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery. METHODS The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications. Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3-48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract. CONCLUSIONS Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.
Identification of two novel loss‐of‐function SIM1 mutations in two overweight children with developmental delay

Several deletions of chromosome 6q, including SIM1, were reported in obese patients with developmental delay. Furthermore, rare loss‐of‐function SIM1 mutations were shown to contribute to severe obesity, yet the role of these mutations in developmental delay remained unclear. Here, SIM1 in children with neurodevelopmental abnormalities was screened and the functional effect of the identified mutations was investigated.
Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells

Acinetobacter baumannii is an important opportunistic pathogen responsible for nosocomial infection. Despite considerable clinical and epidemiological data regarding the role of A. baumannii in nosocomial infection, the specific virulence factor or pathogenic mechanism of this organism has yet to be elucidated. This study investigated the molecular mechanism of apoptosis on the infection of human laryngeal epithelial HEp‐2 cells with A. baumannii and examined the contribution of outer membrane protein 38 (Omp38) on the ability of A. baumannii to induce apoptosis of epithelial cells. A. baumannii induced apoptosis of HEp‐2 cells through cell surface death receptors and mitochondrial disintegration. The Omp38‐deficient mutant was not as able to induce apoptosis as the wild‐type A. baumannii strain. Purified Omp38 entered the cells and was localized to the mitochondria, which led to a release of proapoptotic molecules such as cytochrome c and apoptosis‐inducing factor (AIF). The activation of caspase‐3, which is activated by caspase‐9, degraded DNA approximately 180 bp in size, which resulted in the appearance of a characteristic DNA ladder. AIF degraded chromosomal DNA approximately 50 kb in size, which resulted in large‐scale DNA fragmentation. These results demonstrate that Omp38 may act as a potential virulence factor to induce apoptosis of epithelial cells in the early stage of A. baumannii infection.
Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch–Belgian Haemato‐Oncology Co‐operative Group (HOVON) and Swiss Group for Clinical Cancer Research 

The question as to whether autologous stem cell transplantation (SCT) after consolidation chemotherapy improves the probability of survival of patients with acute myeloid leukaemia (AML) in first remission has not been settled. Here, we present the results of a phase III study conducted in newly diagnosed adult AML patients aged <60 years. Patients who had reached a complete remission (CR) after two courses of induction chemotherapy and who were not eligible for a human leucocyte antigen‐matched sibling SCT (n = 130), were randomized after a third consolidation cycle of chemotherapy between high‐dose cytotoxic treatment and autologous bone marrow transplantation or no further treatment. No significant differences in disease‐free survival and overall survival were observed between the two treatment arms. A slightly better overall survival in the no further treatment arm was because of fewer deaths in the first CR and a significantly better overall survival after the first relapse. The results are discussed in relation to the generic problems of applying autologous transplantation and in the perspective of the limited statistical power of this and other previously published studies.
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy and other primary immunodeficiency diseases help to resolve the nature of protective immunity against chronic mucocutaneous candidiasis

Purpose of reviewThis review summarizes and discusses the most recent and important publications describing Mendelian diseases associated with susceptibility to chronic mucocutaneous candidiasis (CMC) as a means of gaining insight into the pathogenesis of this immunodeficiency. Recent findingsImpairment to T helper 17 (Th17) cell-associated signalling pathways are common in immunodeficiency syndromes associated with CMC infections. Mutations in CARD9, STAT3, IL17RA, IL17F, STAT1, and IL12RB and polymorphisms in Dectin 1 and interleukin-22 (IL-22) encoding genes have been shown to impair the development or function of Th17 cells and are associated with susceptibility to candidiasis. Studies on autoimmune polyendocrinopathy candidiasis ectodermal dystrophy have revealed autoimmunity to Th17 cytokines and cells as the basis for CMC. IL-17A, IL-17F, and IL-22 induce production of antimicrobial peptides and chemoattractants that recruit neutrophils in response to invading fungi. Th17 cell-associated cytokines may play a role in shaping the host's microbiome (that competes with C. albicans) preventing overgrowth of this pathogen. Recent evidence also suggests that IL-22 together with IL-17F might be the most important Th17 cytokine in protection against Candida. SummaryDissection of critical molecular and immunological mechanisms will allow the development of new treatments for primary and secondary immunodeficiency disorders resulting in chronic Candida infections.