Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes.

CONTEXT Human leukocyte antigen (HLA) DQ haplotypes have the strongest genetic association with type 1 diabetes (T1DM) risk. OBJECTIVE The objective of the study was to analyze whether HLA DQ alleles influence the development of antiislet autoantibodies, the progression to T1DM among autoantibody-positive relatives, or both. DESIGN The Diabetes Prevention Trial-1 screened more than 90,000 nondiabetic relatives of patients for cytoplasmic islet-cell autoantibody (ICA) expression between 1994 and 2002. SETTING The study was conducted in the general community. PARTICIPANTS The Diabetes Prevention Trial-1 found 2817 ICA-positive relatives who were tested for biochemical autoantibodies (GAD65, ICA512, and insulin) and HLA-DQ haplotypes, and 2796 of them were followed up for progression to diabetes for up to 8 yr (median, 3.6 yr). MAIN OUTCOME MEASURE Progression to T1DM was measured. RESULTS High-risk DQ haplotypes and genotypes were associated with a higher percentage of relatives expressing multiple biochemical autoantibodies and higher T1DM risk (e.g., respectively, 59 and 36% at 5 yr for carriers of the DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype). The number of autoantibodies expressed significantly increased T1DM risk and across different DQ genotypes, autoantibody positivity directly correlated with diabetes risk. However, multivariate analyses indicated that the influence of most genotypes on T1DM risk was not independent from autoantibody expression, with the possible exception of DQA1*0102-DQB1*0602. Specific genotypic combinations conferred 5-yr diabetes risks significantly lower (e.g. 7%-DQA1*0201-DQB1*0201/DQA1*0501-DQB1*0201 and 14%-DQA1*0301-DQB1*0301/DQA1*0501-DQB1*0201) than when those haplotypes were found in other combinations. CONCLUSION HLA DQ alleles determine autoantibody expression, which is correlated with diabetes progression. Among autoantibody-positive relatives, most HLA DQ genotypes did not further influence T1DM risk.
Cell cycle arrest and gene expression profiling of testis in mice exposed to fluoride

Exposure to fluoride results in low reproductive capacity; however, the mechanism underlying the impact of fluoride on male productive system still remains obscure. To assess the potential toxicity in testis of mice administrated with fluoride, global genome microarray and real‐time PCR were performed to detect and identify the altered transcriptions. The results revealed that 763 differentially expressed genes were identified, including 330 up‐regulated and 433 down‐regulated genes, which were involved in spermatogenesis, apoptosis, DNA damage, DNA replication, and cell differentiation. Twelve differential expressed genes were selected to confirm the microarray results using real‐time PCR, and the result kept the same tendency with that of microarray. Furthermore, compared with the control group, more apoptotic spermatogenic cells were observed in the fluoride group, and the spermatogonium were markedly increased in S phase and decreased in G2/M phase by fluoride. Our findings suggested global genome microarray provides an insight into the reproductive toxicity induced by fluoride, and several important biological clues for further investigations. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1558–1565, 2017.
Outcomes after antiretroviral therapy during the expansion of HIV services in Haiti

Background We report patient outcomes after antiretroviral therapy (ART) initiation in a network of HIV facilities in Haiti, including temporal trends and differences across clinics, during the expansion of HIV services in the country. Methods We assessed outcomes at 12 months after ART initiation (baseline) using routinely collected data on adults (≥15 years) in 11 HIV facilities from July 2007-December 2013. Outcomes include death (ascertained from medical records), lost to follow-up (LTF) defined as no visit > 365 days from ART initiation, and retention defined as being alive and attending care ≥ 365 days from ART initiation. Outcomes were compared across calendar year of ART initiation and across facilities. Risk factors for death and LTF were assessed using Cox proportional hazards and competing risk regression models. Results Cumulatively, 9,718 adults initiated ART with median age 37 years (IQR 30–46). Median CD4 count was 254 cells/uL (IQR 139–350). Twelve months after ART initiation, 4.4% (95% CI 4.0–4.8) of patients died, 21.7% (95% CI 20.9–22.6) were LTF, and 73.9% (95% CI 73.0–74.8) were retained in care. Twelve-month mortality decreased from 13.8% among adults who started ART in 2007 to 4.4% in 2013 (p<0.001). Twelve-month LTF after ART start was 29.2% in 2007, 18.7% in 2008, and increased to 30.1% in 2013 (p<0.001). Overall, twelve-month retention after ART start did not change over time but varied widely across facilities from 61.1% to 86.5%. Conclusion Expansion of HIV services across Haiti has been successful with increasing numbers of patients initiating ART and decreasing twelve-month mortality rates. However, overall retention has not improved, despite differences across facilities, suggesting additional strategies to improve engagement in care are needed.
Role for the microtubule-associated protein tau variant p.A152T in risk of α-synucleinopathies

Objective: To assess the importance of MAPT variant p.A152T in the risk of synucleinopathies. Methods: In this case-control study, we screened a large global series of patients and controls, and assessed associations between p.A152T and disease risk. We included 3,229 patients with clinical Parkinson disease (PD), 442 with clinical dementia with Lewy bodies (DLB), 181 with multiple system atrophy (MSA), 832 with pathologically confirmed Lewy body disease (LBD), and 2,456 healthy controls. Results: The minor allele frequencies (MAF) in clinical PD cases (0.28%) and in controls (0.2%) were not found to be significantly different (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.63–2.98, p = 0.42). However, a significant association was observed with clinical DLB (MAF 0.68%, OR 5.76, 95% CI 1.62–20.51, p = 0.007) and LBD (MAF 0.42%, OR 3.55, 95% CI 1.04–12.17, p = 0.04). Additionally, p.A152T was more common in patients with MSA compared to controls (MAF 0.55%, OR 4.68, 95% CI 0.85–25.72, p = 0.08) but this was not statistically significant and therefore should be interpreted with caution. Conclusions: Overall, our findings suggest that MAPT p.A152T is a rare low penetrance variant likely associated with DLB that may be influenced by coexisting LBD and AD pathology. Given the rare nature of the variant, further studies with greater sample size are warranted and will help to fully explain the role of p.A152T in the pathogenesis of the synucleinopathies.
The effect of channel spatial correlation on physical layer security in multi-antenna scenarios

Information-theoretic security at the physical layer has been proposed to increase the privacy of wireless communications due to its achievable characteristics: unbreakability, provability, and quantifiability. An accurate and powerful analytical framework aimed at deriving the achievable security level provided by Gaussian channels is presented and validated. Its accuracy is assessed by mean of a narrowband fading scenario simulator with multi-antenna transceivers. The impact on the security level of a number of aspects, such as the Eavesdropper's distance as well as the number and distance of antennas in MIMO systems is finally discussed.
Using state‐dependency of transcranial magnetic stimulation (TMS) to investigate letter selectivity in the left posterior parietal cortex: a comparison of TMS‐priming and TMS‐adaptation paradigms

The state‐dependency of transcranial magnetic stimulation (TMS) can be used to investigate the neural properties of subregions of the stimulated region. The objective of the present study was to determine whether state‐dependency can reveal letter selectivity in the left posterior parietal cortex (PPC), a region known to contain letter‐selective neurons. In two experiments, we used visual priming and adaptation to modulate the initial activation state of the left PPC prior to application of TMS. In the priming experiment, TMS was applied over the left PPC during the delay between the prime and the target stimulus on each experimental trial. Left PPC TMS reversed the effects of priming by facilitating the detection of non‐primed letters, whereas detection of primed letters was unaffected. As neurons tuned to non‐primed letters were less active at the time of TMS application than neurons tuned to the primed letters, this finding demonstrates that TMS preferentially facilitates the detection of attributes encoded by the less active neural populations. A similar facilitation of the less active neural populations was observed when adaptation was used to suppress letter‐selective neurons prior to application of TMS. Our study demonstrates that TMS‐priming and TMS‐adaptation paradigms can reveal letter selectivity in the left PPC and thus be useful in the study of language processes. Our results also show that the state‐dependent TMS effects obtained with visual priming are similar to those found with TMS adaptation: in both cases, attributes encoded by the less active neural populations are preferentially facilitated.
Surgical management of prosthetic vascular graft infection: comparative retrospective analysis of 30 consecutive cases.

BACKGROUND Graft infection after vascular prosthetic reconstruction for the treatment of peripheral arterial occlusive disease (PAOD) is a rare but severe complication with poor outcome. The options for surgical treatment are not uniformly accepted and remain controversial. PATIENTS AND METHODS We retrospectively analyzed the histories of 30 patients treated for prosthetic graft infection (Szilagyi grade III) in our hospital between 1994 and 1999 to determine which forms of treatment were best suited for which types of patient. In the majority of cases the initial treatment was lower-extremity bypass surgery. The most frequent location of infection was the groin (73%). Staphylococci (13% of which were methicillin resistant) were the most common type of bacteria. The overall incidence of prosthetic infection was 2.3%. RESULTS After confirmation of the infection by computed tomography (CT) or white blood cell scintigraphy, one of the following 5 forms of surgical treatment was performed: 1. Removal of the infected prosthesis and its simultaneous replacement by an autologous vein bypass. 2. Bypass removal and secondary replacement by an autologous vein. 3. Extra-anatomical replacement. 4. Graft removal and primary amputation. 5. Local therapy with debridement and secondary wound healing. In some patients primary amputation after graft infection was necessary to prevent further deterioration with fulminant sepsis. The overall mortality was 17%, the amputation rate was 60%. CONCLUSIONS The best results were achieved by early complete removal of the alloplastic material and one-step replacement by either an autologous vein or extra-anatomic bypass. This resulted in a limb salvage rate of 54% and 40% and mortality rates of 9% and 0%, respectively.
The non-operative management of hand fractures

Most hand fractures can be treated non-operatively. Some hand fractures, such as open injuries or markedly displaced intra-articular fractures, are almost always treated operatively. The treatment of many fractures, such as proximal interphalangeal joint fracture subluxations or spiral phalangeal fractures, is unclear. The aim of this review is to establish those injuries where the outcome of non-operative treatment is unlikely to be improved with surgery. This may help to prevent unnecessary surgery, concentrate work on finding the sub-groups that may benefit from surgery and to establish which injuries do so well with non-operative treatment that the only valuable clinical research in future will be large cohort studies of non-operative treatment or randomized controlled trials comparing operative and non-operative treatments. The relevant fractures are spiral metacarpal fractures, transverse metacarpal shaft and neck (boxer’s) fractures, base of proximal phalanx avulsion fractures, thumb metacarpophalangeal joint ulnar and radial collateral ligament injuries and bony mallet injuries. For the majority of these injuries, current knowledge suggests that the outcome of non-operative treatment cannot reliably be improved upon with surgery. Level of evidence IV
Immune function in patients with acute pancreatitis

Background: The aim of this study was to clarify the relationship between the balance of T‐helper (Th)1 and Th2 cytokines, and the numbers of CD4+ T and CD8+ T‐cells, and was investigated, together with the plasma concentration of the antigen, an apoptosis marker, in patients with mild and acute pancreatitis (AP).
DIAGNOSTIC TESTING PATTERNS OF RENIBACTERIUM SALMONINARUM IN SPAWNING SALMONID STOCKS IN MICHIGAN

Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum, is a slowly progressing disease that threatens salmon conservation and restoration programs in North America. The purpose of this study was to track naturally occurring R. salmoninarum infection in representative, Michigan, USA, salmonid stocks using nested polymerase chain reaction (nPCR), quantitative enzyme-linked immunosorbent assay (Q-ELISA), and culture. The Q-ELISA test detected 67.6% infection prevalence, which is lower than culture (77.2%) or nPCR (94.2%), yet it provided semiquantitative data on infection intensity. The disagreement in results among the three assays may reflect the different phases of R. salmoninarum infection at the time of sampling. The testing results demonstrated the presence of six patterns, with each of the patterns representing a probable stage along the course of natural R. salmoninarum infection. Findings also suggest that fish stocks tested in this study were not uniform in the distribution of the diagnostic patterns and that, from studying such patterns, one can determine the course of BKD infection in a particular population.
Paradox of sonic hedgehog (SHH) transcriptional regulation: Alternative transcription initiation overrides the effect of downstream promoter DNA methylation

Recently, DNA methylation has been suggested as a potential mechanism involved in the transcriptional regulation of SHH gene expression in cancer. However, detailed analyses on the underlying transcriptional mechanisms of SHH expression have not been presented so far and were therefore the focus of this study. We found that the genomic region of SHH contains two different transcriptional start sites and four CpG islands spread from the 5' promoter region to the 3' end of the SHH gene. Based on this CpG island topology we analyzed the influence of DNA methylation within the promoter region as well as in exon 2 and exon 3 on SHH mRNA expression in a large set (n = 14) of benign and malignant human cell lines, and further elucidated the functionality of the two identified SHH transcription initiation sites. Methylation-specific PCR (MSP) clearly showed that SHH is expressed independently of DNA methylation within exon 2 and exon 3 of its genomic region, while methylation of the promoter region is able to abrogate SHH expression. Most interesting, we found activation of the upstream SHH promoter in several breast cancer cell lines when the downstream SHH promoter is methylated. These observations lead us to propose a transcriptional model for the SHH gene, in which combined mechanisms of DNA methylation and alternative promoter usage coordinate the transcriptional activity of this important developmental gene.
Profiling of Alzheimer’s disease patients in Puerto Rico: A comparison of two distinct socioeconomic areas

Objective: The Latino/Hispanic community in the United States is at higher risk of developing Alzheimer’s disease than other ethnic groups. Specifically, Caribbean Hispanics showed a more severe Alzheimer’s disease symptomatology than any other ethnic group. In a previous study, we demonstrated that the mortality rate associated with Alzheimer’s disease in Puerto Rico is higher than that reported in the United States. Moreover, the mortality rate associated with Alzheimer’s disease was higher among Puerto Rican living in Puerto Rico than those in the mainland United States. There is also a differential geographical distribution of mortality rate associated with Alzheimer’s disease in Puerto Rico, which may be associated with differential socioeconomic status and/or access to healthcare. However, there is no information regarding the clinical profile of Alzheimer’s disease patients in Puerto Rico. Methods: Here, we present the results of a retrospective study directed to profile Alzheimer’s disease patients clustered into two groups based on areas previously determined with low (Metro Region) and high (Northwest-Central Region) mortality rate associated with Alzheimer’s disease in Puerto Rico. Results: Significant difference in the age-at-diagnosis and years of education was found among patients within the two studied regions. Despite these differences, both regions showed comparable levels of initial and last Mini Mental State Examination scores and rate of cognitive decline. Significant difference was also observed in the occurance of co-morbidities associated with Alzheimer’s disease. Conclusions: The differential profile of Alzheimer’s disease patients correlated with differences in socioeconomic status between these two regions, suggesting that covariant associated with social status may contribute to increased risk of developing Alzheimer’s disease. Further studies should be conducted to determine the role of socioeconomic factors and healthy living practices as risk factors for Alzheimer’s disease.
Health Care Savings Attributable to Integrating Guidelines-based Asthma Care in the Pediatric Medical Home

Objective. To estimate savings to health care system of a best-practice asthma intervention in primary care for inner-city children. Methods. Data were analyzed from National Heart, Lung and Blood Institute (NHLBI) Guidelines-based initial (n=244) and follow-up (n=202) asthma assessments of patients who received enhanced treatment in primary care. Savings were calculated using cost-of-illness model and compared with program cost. Results. Patients were about equally distributed between African American and Hispanic children (mean age = 7 years; range 36 months-19 years). Of those with persistent asthma, 36% had been prescribed a controller medication. This significantly improved on follow-up (p<.01). There were significant reductions in asthma severity (p<.05) and emergency department use (p<.01), and near-significant reduction in asthma hospitalizations (p=.059). Conclusion. Total annual savings attributable to clinical outcomes was $4,202,813 or $4,525 per patient with asthma. Total annual cost of the implementation was $390,169 or $420 per asthma patient. Conservatively estimated savings exceeded cost of intervention by nearly 11 to 1.
What do medical students learn from dissection?

Dissection has long been the accepted method for teaching anatomy to medical students. More recently, some educators have suggested that easier, cheaper, alternative methods are just as effective. But what do the students think? This paper aimed to identify what undergraduate medical students learn, how they cope, and what effects participating in dissection has on them as individuals. A cohort of 267 second year medical students at Otago Medical School were invited to complete three online surveys; before their first dissection laboratory class, after their first musculoskeletal system dissection and following the last semester of studying anatomy. Open‐ended questions showcasing the attitudes, beliefs, and opinions on what dissection had taught the medical students over years two and three were analyzed. A general inductive approach was used and common emergent themes were identified. In total, 194 students completed the second, and 108 students completed the third questionnaire. Students commonly conveyed dissection as an appropriate and valuable educational tool, useful for teaching and learning anatomical knowledge and relationships, appreciating the body in three‐dimension, teamwork, and how to cope with death/dead bodies. The noted effects of personal growth while participating in dissection were highly varied, but in general, impacted positively on the majority of students. This study shows that at Otago Medical School the students also believe that dissection is not only a useful tool to learn anatomy but also that it fosters teamwork, assists professional development and helps them come to terms with death and dying. Anat Sci Educ 11: 325–335. © 2017 American Association of Anatomists.
Comparative In Vitro Susceptibility of a Tetracycline‐Resistant Chlamydia trachomatis Strain Isolated in Toulouse (France)

Background and Objectives: We recently reported the first isolation of a tetracycline‐resistant Chlamydia trachomatis strain in Toulouse from a woman treated with tetracycline. To characterize this isolate, its in vitro susceptibility was compared with those of 34 other C. trachomatis isolates recovered in Toulouse. Study Design: The susceptibilities of C. trachomatis strains were determined in terms of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) using McCoy cells in 96‐well microdilution plates, with an inoculum of 5.103 to 1.104 inclusion‐forming units/ml. The antimicrobial agents tested were tetracycline, azithromycin, erythromycin, ofloxacin, and pristinamycin. Results: No difference was observed between the MICs and MBCs except for the tetracycline. Tetracycline‐resistant strain MIC and MBC were >64 μg/ml, although <1% of the bacterial population showed resistance. For the other isolates, the MIC of tetracycline was ≤0.25 μg/ml. The antibiotics other than tetracycline were active in vitro against all strains. Conclusions: These results show that the tetracycline resistance observed in Toulouse differs from the “heterotypic resistance” described previously in the United States in multiresistant C. trachomatis isolates. They confirm that the resistance we observed may be a new phenomenon.