Miracle-dz/UniFAR-FTUs huggingface dataset:
A Clinicocytological Appraisal of Vesiculobullous and Noduloulcerative Lesions of Skin.

Introduction: Cytopathology has proven to be of great help in the diagnosis of various skin lesions, however, studies relating to histopathological and cytological correlation are few. The objective of this study was to evaluate cytology as an early diagnostic tool in comparison to histopathology in various vesiculobullous and noduloulcerative lesions of skin. Material and methods: The study material constituted 50 cases of vesiculobullous and noduloulcerative lesions of skin. A detailed history of the patients was taken and complete physical and dermatological examination findings including clinical diagnosis ,were recorded. Cytological examination (Tzanck/FNAC/Scrapings) and histopathological examination (incisional/ excisional/punch biopsy) were done in each case. Clinicocytological evaluation was done and results were correlated with histopathological findings. However, in case of vesiculobullous lesions, immunofluorescence findings were also correlated for further confirmation of the diagnosis Result: Overall, the sensitivity of cytology in diagnosing vesiculobullous and noduloulcerative lesions of skin was 89.36% Conclusion: Cytology has been proven as a reliable and informative tool in the diagnosis of various vesiculobullous and noduloulcerative lesions of skin. In comparison to biopsy techniques; it is a non traumatic, inexpensive, safe, well tolerated and a rapid diagnostic tool.
Long‐term outcome of multiple joint procedures in haemophilia

In elderly people with haemophilia (PWH), surgery of more than one joint of the lower extremities might be needed. Multiple joint procedures (MJP) were introduced in 1995, defined as any combination of Total Knee or Total Hip Arthroplasty or Ankle Arthrodesis during one in‐hospital stay. The expectation is that by means of such procedures this specific population is able to physically function better for an extended period of time. Thus, they will participate in their society in an optimal way. In this study, we tried to describe an outcome after MJP, including pre‐ and post‐operative pain and range of motion (ROM), and recommend measurement tools. 22 of 37 PWH who underwent MJP between 1995 and 2012 were available for assessment. Pain (WFH score) and range of motion were compared pre and postoperatively. Current outcome was described by VAS per joint, nocturnal and overall pain, MACTAR, Hemophilia Activity List, SF36, and EQ‐5D. Mean age at surgery was 50, 3 years (SD 8, 3); mean follow‐up 12 years (1–18 years). Pain (VAS) decreased post‐surgery (Median 1 – 1, 5), but moderate pain remained. Extension of knees slightly increased, but both knee flexion and ankle plantar and dorsal flexion decreased. PWH reported the ability to stand longer but also pointed at specific problems, e.g. riding a bike (MACTAR). The HAL showed limited activities (functional domains), especially in the ‘complex lower extremity’ (22, 8/100). The SF36 and EQ‐5D showed a mix of physical problems of our population, while experiencing moderate pain and reasonable physical functioning. This led us to the conclusion that adequate follow‐up is needed: ROM of all joints, VAS of all joints as well as nocturnal and overall pain, HAL, SF36 and EQ5D. Performance based activities and participation need further attention.
Presence of Type I-F CRISPR/Cas systems is associated with antimicrobial susceptibility in Escherichia coli

Background Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their associated cas genes are sequence-specific DNA nuclease systems found in bacteria and archaea. CRISPR/Cas systems use RNA transcripts of previously acquired DNA (spacers) to target invading genetic elements with the same sequence, including plasmids. In this research we studied the relationship between CRISPR/Cas systems and multidrug resistance in Escherichia coli . Methods The presence of Type I-E and Type I-F CRISPR systems was investigated among 82 antimicrobial-susceptible and 96 MDR clinical E. coli isolates by PCR and DNA sequencing. Phylogrouping and MLST were performed to determine relatedness of isolates. RT-PCR was performed to ascertain the expression of associated cas genes. Results Type I-F CRISPR was associated with the B2 phylogroup and was significantly overrepresented in the susceptible group (22.0%) compared with the MDR group (2.1%). The majority of CRISPR I-F-containing isolates had spacer sequences that matched IncF and IncI plasmids. RT-PCR demonstrated that Type I-F cas genes were expressed and therefore potentially functional. Conclusions The CRISPR I-F system is more likely to be found in antimicrobial-susceptible E. coli . Given that the Type I-F system is expressed in WT isolates, we suggest that this difference could be due to the CRISPR system potentially interfering with the acquisition of antimicrobial resistance plasmids, maintaining susceptibility in these isolates.
Major role of pKpQIL-like plasmids in the early dissemination of KPC-type carbapenemases in the UK

Objectives Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae were first seen in the UK in 2003 and have been increasingly reported since 2010, largely owing to an ongoing outbreak in North-West England. We examined the role of clonal spread and plasmid transmission in their emergence. Methods Isolates comprised KPC-positive K. pneumoniae ( n = 33), Escherichia coli ( n = 7) and Enterobacter spp. ( n = 4) referred to the national reference laboratory between 2008 and 2010 from 17 UK centres, including three in North-West England. Isolates were typed by MLST. Plasmids were transferred by electroporation and characterized by PCR or sequencing. PCR screening assays were developed to distinguish plasmid pKpQIL variants. Results The K. pneumoniae isolates included 10 STs, of which three belonged to clonal group (CG) 258. CG258 ( n = 19) isolates were detected in 13 centres but accounted for only 7/19 (36.8%) of those from North-West England. Most KPC-producers (37/44, 84.1%), including 16/19 CG258 K. pneumoniae , carried bla KPC on IncFII K2 plasmids. Sequencing of a subset of these plasmids ( n = 11) revealed similarities with published pKpQIL. One variant, pKpQIL-UK [identified in K. pneumoniae CG258 ( n = 5) and ST468 ( n = 1) isolates from distinct centres] had only a few nucleotide changes from classical pKpQIL, whereas pKpQIL-D1 ( n = 1) and pKpQIL-D2 ( n = 4), from isolates of various species in the North-West, harboured large variations, reflecting replacement of the partitioning and replication functions and potentially thereby facilitating spread. PCR revealed that 36/37 (97.3%) IncFII K2 -type plasmids in KPC-positive isolates had pKpQIL markers. Conclusions pKpQIL-like plasmids played a major role in the early dissemination of KPC enzymes in the UK.
Better adherence to prescribed treatment regimen is related to less chronic pain among adolescents and young adults with moderate or severe haemophilia

Little data exist, especially for adolescent and young adult (AYA) persons with haemophilia (PWH), about the relationship between adherence to prescribed treatment regimen and chronic pain. We examined this relationship among PWH (moderate or severe) aged 13–25 via cross‐sectional survey. Adherence was assessed using the Validated Hemophilia Regimen Treatment Adherence Scale (VERITAS)‐Pro and VERITAS‐PRN for prophylactic and on‐demand participants respectively. VERITAS scores range from 24 (most adherent) to 120 (least adherent). Chronic pain was measured using the FPS‐R and was dichotomized as high for FPS‐R scores ≥4 and low for <4. Logistic regression models were constructed to assess factors associated with having high (vs. low) chronic pain. Of 80 AYA respondents (79 men), most had severe disease (91%), infused prophylactically (86%) and had haemophilia A (91%). Fifty‐one per cent were aged 13–17 and most were white (76%), non‐Hispanic (88%) and never married (93%). Chronic pain was reported as high for 35% of respondents. Mean VERITAS‐Pro scores for those with high and low chronic pain were 53.6 ± 12.3 vs. 47.4 ± 12.9, P = 0.05. VERITAS‐PRN scores were similar across chronic pain status. Logistic regression revealed that for each 10‐point reduction (i.e. increase in adherence) in the combined VERITAS (Pro and PRN) and VERITAS‐Pro scores there was a 35% (OR = 0.65; 95%CI = 0.44, 0.96; P = 0.03) and 39% (OR = 0.61; 95%CI = 0.39, 0.96; P = 0.03) reduction in odds of having high chronic pain respectively. Among AYA PWHs, better adherence was associated with significantly lower odds of having high chronic pain. Moreover, non‐whites were >4 times as likely as whites to report high chronic pain.
Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life

Objectives: Data quantifying outcomes of recurrent Clostridium difficile infection (rCDI) are lacking. We sought to determine the UK hospital resource use and health‐related quality of life (HRQoL) associated with rCDI hospitalizations. Patients and methods: A non‐interventional study in six UK acute hospitals collected retrospective clinical and resource use data from medical records of 64 adults hospitalized for rCDI and 64 matched inpatient controls with a first episode only (f)CDI. Patients were observed from the index event (date rCDI/fCDI confirmed) for 28 days (or death, if sooner); UK‐specific reference costs were applied. HRQoL was assessed prospectively in a separate cohort of 30 patients hospitalized with CDI, who completed the EQ‐5D‐3L questionnaire during their illness. Results: The median total management cost (post‐index) was £7539 and £6294 for rCDI and fCDI, respectively (cost difference, P = 0.075); median length of stay was 21 days and 15.5 days, respectively (P = 0.269). The median cost difference between matched rCDI and fCDI cases was £689 (IQR=£1873‐£3954). Subgroup analysis demonstrated the highest median costs (£8542/patient) in severe rCDI cases. CDI management costs were driven primarily by hospital length of stay, which accounted for >85% of costs in both groups. Mean EQ‐5D index values were 46% lower in CDI patients compared with UK population values (0.42 and 0.78, respectively); EQ visual analogue scale scores were 38% lower (47.82 and 77.3, respectively). Conclusions: CDI has considerable impact on patients and healthcare resources. This multicentre study provides a contemporaneous estimate of the real‐world UK costs associated with rCDI management, which are substantial and comparable to fCDI costs.
Pretreatment HIV drug resistance results in virological failure and accumulation of additional resistance mutations in Ugandan children

Background: Pretreatment HIV drug resistance (PDR) can impair virological response to ART, jeopardizing effective treatment for children. Methods: Children aged ≤12 years initiated first‐line ART in Uganda during 2010–11. Baseline and 6 monthly viral load (VL) and genotypic resistance testing if VL >1000 copies/mL was done. The 2015 IAS‐USA mutation list and Stanford algorithm were used to score drug resistance mutations (DRMs) and susceptibility. Virological failure (VF) was defined as two consecutive VLs >1000 copies/mL or death after 6 months of ART. Factors associated with failure and acquired drug resistance (ADR) were assessed in a logistic regression analysis. Results: Among 317 children enrolled, median age was 4.9 years and 91.5% received NNRTI‐based regimens. PDR was detected in 47/278 (16.9%) children, of whom 22 (7.9%) had resistance against their first‐line regimen and were therefore on a partially active regimen. After 24 months of follow‐up, 92/287 (32.1%) had experienced VF. Children with PDR had a higher risk of VF (OR 15.25, P<0.001) and ADR (OR 3.58, P = 0.01). Conclusions: Almost one‐third of children experienced VF within 24 months of NNRTI‐based first‐line treatment. PDR was the strongest predictor of VF and ADR, and therefore presents a major threat in children. There is a need for ART regimens that maximize effectiveness of first‐line therapy for long‐term treatment success in the presence of PDR or incorporation of routine VL testing to detect VF and change treatment in time, in order to prevent clinical deterioration and accumulation of additional drug resistance. Children ≤3 years should be initiated on a PI‐based regimen as per WHO guidelines.
Using metagenomics to investigate human and environmental resistomes

Antibiotic resistance is a global health concern declared by the WHO as one of the largest threats to modern healthcare. In recent years, metagenomic DNA sequencing has started to be applied as a tool to study antibiotic resistance in different environments, including the human microbiota. However, a multitude of methods exist for metagenomic data analysis, and not all methods are suitable for the investigation of resistance genes, particularly if the desired outcome is an assessment of risks to human health. In this review, we outline the current state of methods for sequence handling, mapping to databases of resistance genes, statistical analysis and metagenomic assembly. In addition, we provide an overview of important considerations related to the analysis of resistance genes, and recommend some of the currently used tools and methods that are best equipped to inform research and clinical practice related to antibiotic resistance.
Detección de bacteriemia en los pacientes dados de alta en urgencias: estudio de 61 episodios

BACKGROUND: To know the prevalence, the clinical and microbiological characteristics of bacteremia episodes detected on discharged patients at the emergency unit, as well as the accordance of diagnostics and the predicting factors. PATIENTS AND METHODS: We analysed the cases with bacteria detected on discharged patients during 2 years (1995-1996) in an university hospital. We reported: age, sex isolated organism in blood cultures, bacteremia source, leukocytes count, presence of underlying conditions, and accordance between initial and final diagnosis. We compared the characteristics of the groups with bacteremia without apparent origin and the ones with evident clinical source. RESULTS: We detected 61 cases, the mean age was 55 years (SD = 21), and 54% were males. The most commonly isolated agent was E. coli (50%). The leukocytes count was higher 10 x 10(9)/l in 15%. The source of bacteremia was: urinary tract infection (54%) no clinical focus (31%), respiratory tract (11%) and biliary duct (3%). The 90% of urinary tract and the 71% of respiratory infections were correctly diagnosed. However only the 5% of bacteremias without apparent source was correctly diagnosed. We found these differences statistically a significant (p < 0.001 and p = 0.002). Underlying conditions were detected in the 84% of cases in bacteremia without apparently source: AIDS (22%), cirrhosis (22%), parenteral drugs addiction (17%) and venous catheter (17%). Comparing both groups, with apparent focus and without it, we found that the presence of underlying condition is the only independent factor which predispose to bacteremia (p = 0.000; RR = 4.6; IC 95% = 1.9-11.8). CONCLUSIONS: The prevalence of bacteremia detected in discharged patients at the emergency unit seems acceptable. However those results suggest that we could decrease the number of patients with bacteremia without apparently source, because this group shows up to be the less successful in diagnosis. In patients with fever and no clinical focus in the emergency unit, it is useful to consider the presence of underlying factors to decide its management.
Diyabetli Hastalarda Hastalık Algısını Etkileyen Faktörlerin İncelenmesi

Arastirma, diyabetli hastalarda hastalik algisini etkileyen faktorlerin incelenmesi amaciyla yapilmistir. Arastirmaya dort farkli hastanenin uc farkli kliniginden 218 diyabet hastasi katilmistir. Veri, hastalara tanitici bilgi formu ve Hastalik Algisi Olcegi uygulanarak toplanmistir. Diyabet hastalarinda yasin, cinsiyetin, medeni durumun, egitim durumunun, calisma durumunun, sosyo-ekonomik durumun, diyet durumunun, hastalikla ilgili egitim alma durumunun, psikolojik destek alma durumunun, hastalikla ilgili bilgi sahibi olma durumunun, diyabet tipi ve tani konma suresinin hastalik algisini etkiledigi belirlenmistir. Katilimcilarin cogunlugunun, hastaliklariyla ilgili oldugunu dusundukleri semptomlar yasadiklari, hastaliklarini kronik olarak algiladiklari, fiziksel, sosyal, psikolojik islevlerine hastaligin etkisi oldugunu dusundukleri, tedavilerinin etkin olduguna inandiklari ve hastaliklarindan duygusal olarak etkilendikleri saptanmistir.
A pilot randomized control trial to evaluate the feasibility of an Internet‐based self‐management and transitional care program for youth with haemophilia

Adolescents with haemophilia must assume responsibility for their health and management of their disease. An online self‐management program was developed to support adolescents during this transition. To determine the feasibility of the program using a randomized control trial (RCT) design in terms of accrual/attrition rates, willingness to be randomized, compliance with the program/outcome measures and satisfaction. Adolescents, ages 13–18, were enrolled in a pilot RCT (NCT01477437) and randomized to either the intervention (8‐week program with telephone coaching) or the control arm (no access to the website, weekly telephone call as attention‐strategy). All participants completed pre/postoutcome measures. Twenty‐nine teens participated (intervention n = 16, control n = 13). Participants in the intervention arm spent an average of 50 min on the website per week and completed the modules in an average of 14 weeks (SD = 4.9). Attrition was higher in the control group compared to the intervention group (54% vs. 25%). 17/18 (94%) who completed the program also completed the poststudy measures. Teens on the intervention arm showed significant improvement in disease‐specific knowledge (P = 0.004), self‐efficacy (P = 0.007) and transition preparedness (P = 0.046). There was a statistically significant improvement in knowledge in the intervention group when compared to the control group (P = 0.01). Overall, the teens found the website to be informative, comprehensive and easy to use and were satisfied with the program. This pilot RCT study suggests benefit to the program and indicates an RCT design to be feasible with minor adjustments to the protocol.
The Isolation and Characterization of Murine Macrophages

Macrophages are mononuclear phagocytes that are widely distributed throughout the body. These cells can contribute to development and homeostasis and participate in innate and adaptive immune responses. The physiology of macrophages can vary tremendously depending on the environment in which they reside and the local stimuli to which they are exposed. Macrophages are prodigious secretory cells, and in that role can promote and regulate immune responses and contribute to autoimmune pathologies. Macrophages are highly phagocytic, and in this capacity have long been considered to be essential immune effector cells. The important roles of macrophages in maintaining homeostasis and in contributing to tissue remodeling and wound healing is sometimes overlooked because of their vital role in host defense. Curr. Protoc. Immunol. 83:14.1. 1‐14.1. 14. © 2008 by John Wiley & Sons, Inc.
Risk factors for severe acute malnutrition in Central India

Aim: To identify risk factors for severe malnutrition in children <5 years age. Background: Severe acute malnutrition (SAM) is a major cause of childhood morbidity and mortality in our country. However, little information is available on determinants of SAM. Materials and Methods: This was a prospective study done over a period of one year at a tertiary care hospital. Children under five years of age with SAM were enrolled, and the risk factors leading to malnutrition were identified. Results: The risk factors contributing to malnutrition were poor socioeconomic status, parental illiteracy, overcrowding, lack of immunization, lack of awareness among caregivers regarding appropriate child feeding practices. Conclusion: To decrease the prevalence of malnutrition, it is essential to provide education to caregivers about appropriate feeding practices.
Prompt immune tolerance induction at inhibitor diagnosis regardless of titre may increase overall success in haemophilia A complicated by inhibitors: experience of two US centres

Current guidelines recommend delaying the start of immune tolerance induction (ITI) until the inhibitor titre is <10 Bethesda units (BU) to improve success. This study was conducted to evaluate ITI outcome relative to time to start ITI from inhibitor detection irrespective of inhibitor titre. Data were retrospectively collected from two US haemophilia treatment centres (HTCs) on subjects with severe/moderate factor VIII (FVIII) deficiency with inhibitors who underwent ITI. Outcomes were defined pragmatically: success – negative inhibitor titre and ability to use FVIII concentrate for treatment/bleed prevention; partial success – inhibitor titre 1 to <5 BU with ability to use FVIII concentrate for treatment of bleeding; failure – ITI ongoing >3 years without achieving success/partial success, or ITI discontinuation. Fifty‐eight subjects were included; 32 of 39 (82%) with high‐responding inhibitor (HRI) achieved success, 7 failed. HRI subjects were subdivided based on ITI start time: 23/39 subjects started within 1 month of detection and 22/23 (96%) achieved success. Of these 23, 13 started ITI with an inhibitor titre ≥10 BU; all were successes. Eleven of 39 HRI subjects had an interval >6 months until ITI start; 7 (64%) achieved success. Time from inhibitor detection to ITI start may play a critical role in outcome. A titre ≥10 BU at ITI start did not influence outcome in subjects when ITI was initiated within 1 month of detection. Prompt ITI should be considered a viable therapeutic option in newly identified patients with inhibitors regardless of current inhibitor titre.
Strategies for Genotyping

The identification of genomic loci linked to or associated with human disease has been greatly facilitated by the evolution of genotyping strategies and techniques. The success of these strategies continues to be based upon clear clinical assessment, accurate sample handling, and careful data management, but also increasingly upon experimental design. Technological advances in the field of genotyping have permitted increasingly complex and large population studies to be performed. An understanding of publicly available genetic variation databases, including an awareness of the limitations of these data, and an appreciation of the strategic approaches that should be used to exploit this information will provide tremendous insight for researchers are aiming to utilize this accessible technology. As genome‐wide association studies (GWAS) and Next Generation (NextGen) sequencing become the mainstays of genetic analyses, it is important that their technical strengths and limitations, as well as their impact on study design, be understood before use in a linkage or genetic association study. Curr. Protoc. Hum. Genet. 68:1.3. 1‐1.3. 22 © 2011 by John Wiley & Sons, Inc.
Classification and regression tree analysis vs. multivariable linear and logistic regression methods as statistical tools for studying haemophilia

Haemophilia is a rare genetic haemorrhagic disease characterized by partial or complete deficiency of coagulation factor VIII, for haemophilia A, or IX, for haemophilia B. As in any other medical research domain, the field of haemophilia research is increasingly concerned with finding factors associated with binary or continuous outcomes through multivariable models. Traditional models include multiple logistic regressions, for binary outcomes, and multiple linear regressions for continuous outcomes. Yet these regression models are at times difficult to implement, especially for non‐statisticians, and can be difficult to interpret.