Miracle-dz/UniFAR-FTUs huggingface dataset:
Amyloid neuropathy: a retrospective study of 35 peripheral nerve biopsies

Abstract We performed a retrospective study of 35 peripheral nerve biopsies (PNBs) with amyloid deposits in the endoneurium. In every case, nerve lesions were studied on paraffin‐embedded fragments (PEFs) and by ultrastructural examination (USE). In addition, muscle fragments were taken and embedded in paraffin. Immunohistochemistry was performed with anti‐transthyretin (TTR) serum on 19 nerve and 15 muscle PEFs. Direct immunofluorescence with anti‐light‐chain sera was performed on frozen nerve fragments in 19 cases. Endoneurial amyloid deposits were easily identified on routine PEF in 26 cases, after Congo red or thioflavine staining in three, and by USE in six. A dramatic myelinated fiber loss was evidenced in 34 cases (77–2970 per mm2), and features of axonal degeneration were present in every case. Segmental demyelination was observed in 10 cases. A mutation in the TTR gene was present in 14 cases, with Met30 mutation in 10 and Ala49 in four members of the same family. Amyloid deposits were strongly marked by the anti‐TTR serum in 11 other cases, twice in the endoneurium, five around muscle fibers, and four in both locations. In eight patients, light‐chain positivity was evidenced in endoneurial deposits, lambda in six and kappa in two. Two other patients with monoclonal gammopathy did not present any light‐chain fixation. In 17 cases, amyloidosis was disclosed by PNB and 13 had a TTR pathology; eight of them, over 65 years old, correspond to a late‐onset form of familial amyloid polyneuropathy which is an underdiagnosed condition.
Time to Death after Terminal Withdrawal of Mechanical Ventilation: Specific Respiratory and Physiologic Parameters May Inform Physician Predictions.

BACKGROUND Discussions about withdrawal of life-sustaining therapies often include family members of critically ill patients. These conversations should address essential components of the dying process, including expected time to death after withdrawal. OBJECTIVES The study objective was to aid physician communication about the dying process by identifying predictors of time to death after terminal withdrawal of mechanical ventilation. METHODS We conducted an observational analysis from a single-center, before-after evaluation of an intervention to improve palliative care. We studied 330 patients who died after terminal withdrawal of mechanical ventilation. Predictors included patient demographics, laboratory, respiratory, and physiologic variables, and medication use. RESULTS The median time to death for the entire cohort was 0.58 hours (interquartile range (IQR) 0.22-2.25 hours) after withdrawal of mechanical ventilation. Using Cox regression, independent predictors of shorter time to death included higher positive end-expiratory pressure (per 1 cm H2O hazard ratio [HR], 1.07; 95% CI 1.04-1.11); higher static pressure (per 1 cm H2O HR, 1.03; 95% CI 1.01-1.04); extubation prior to death (HR, 1.41; 95% CI 1.06-1.86); and presence of diabetes (HR, 1.75; 95% CI 1.25-2.44). Higher noninvasive mean arterial pressure predicted longer time to death (per 1 mmHg HR, 0.98; 95% CI 0.97-0.99). CONCLUSIONS Comorbid illness and key respiratory and physiologic parameters may inform physician predictions of time to death after withdrawal of mechanical ventilation. An understanding of the predictors of time to death may facilitate discussions with family members of dying patients and improve communication about end-of-life care.
Epidemiology of hepatitis C virus among long-term dialysis patients: a 9-year study in an Italian region.

BACKGROUND Monitoring hepatitis C virus (HCV) antibodies (anti-HCV) in long-term dialysis patients is an important issue of public health. The aim of the study is to analyze the prevalence, seroconversion rate, and impact of HCV-positive serological test results on survival. METHODS We studied 6,412 patients starting long-term dialysis therapy reported to Lazio Dialysis Registry (Italy) between 1995 and 2003. HCV serological status was assessed by using second- or third-generation assays. Patients who were seronegative at the beginning of a period who became seropositive at the end of the same period are defined as seroconverters. RESULTS In 1995 to 2003, the overall prevalence of anti-HCV among long-term dialysis patients decreased from 30.6% to 15.1%; we did not observe a decrease in prevalence of anti-HCV in those starting dialysis treatment. After a decrease in the first year, HCV seroconversion rates remained stable at approximately 2 cases/100 person-years. Survival at 9 years was lower for both HCV seroconverters and those already anti-HCV positive at dialysis therapy initiation compared with HCV-negative subjects (log-rank test, P < 0.001). Results of a multiple Cox model showed that subjects who were or became anti-HCV positive had a hazard ratio of 1.29 (95% confidence interval, 1.15 to 1.44) compared with HCV-negative patients. CONCLUSION We did not observe a significant decrease in HCV seroconversion rates in 1995 to 2003. The overall decrease in anti-HCV prevalence could be related to the lower survival probability for both HCV seroconverters and those already HCV positive at long-term dialysis therapy initiation compared with HCV-negative subjects. Our findings confirm that additional efforts should be made to minimize the risk for HCV infection before and during long-term dialysis treatment.
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.

BACKGROUND Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. METHODS This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. RESULTS Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)
Sensitivity of the ISO 6579:2002/Amd 1:2007 Standard Method for Detection of Salmonella spp. on Mesenteric Lymph Nodes from Slaughter Pigs

ABSTRACT The ISO 6579:2002/Amd 1:2007 (ISO) standard has been the bacteriological standard method used in the European Union for the detection of Salmonella spp. in pig mesenteric lymph nodes (MLN), but there are no published estimates of the diagnostic sensitivity (Se) of the method in this matrix. Here, the Se of the ISO (SeISO) was estimated on 675 samples selected from two populations with different Salmonella prevalences (14 farms with a ≥20% prevalence and 13 farms with a <20% prevalence) and through the use of latent-class models in concert with Bayesian inference, assuming 100% ISO specificity, and an invA-based PCR as the second diagnostic method. The SeISO was estimated to be close to 87%, while the sensitivity of the PCR reached up to 83.6% and its specificity was 97.4%. Interestingly, the bacteriological reanalysis of 33 potential false-negative (PCR-positive) samples allowed isolation of 19 (57.5%) new Salmonella strains, improving the overall diagnostic accuracy of the bacteriology. Considering the usual limitations of bacteriology regarding Se, these results support the adequacy of the ISO for the detection of Salmonella spp. from MLN and also that of the PCR-based method as an alternative or complementary (screening) test for the diagnosis of pig salmonellosis, particularly considering the cost and time benefits of the molecular procedure.
Seroepidemiology of hepatitis C virus infection in Taiwan

The prevalence of antibody to hepatitis C virus among Chinese subjects in Taiwan was evaluated using a commercially available enzyme immunoassay. The overall prevalence of antibody to hepatitis C virus was 0.28% among 1,419 healthy subjects, 0.8% among 500 unselected paid blood donors and 0.4% among 793 pregnant women. The three offspring of the mothers positive for antibody to hepatitis C virus were all found to be positive for antibody to hepatitis C virus at birth but all became negative by the age of 6 mo. Among healthy subjects, none of 1,000 school children and young adolescents had antibody to hepatitis C virus. Among patients in selected “high‐risk” groups, antibody to hepatitis C virus was detected in 100% of 9 hemophiliac patients who were positive for antibody to human immunodeficiency virus, in 53% of 115 intravenous drug abusers, in 34.4% of 96 hemodialysis patients and in 15.8% of 19 homosexual men who were positive for antibody to human immunodeficiency virus. Only 7.1% of 196 prostitutes, 5.9% of 34 spouses of patients positive for antibody to hepatitis C virus and 0.5% of 201 brothelgoers had antibody to hepatitis C virus. These findings suggest that hepatitis C virus is transmitted mainly by the parenteral route in Taiwan. Transmission from mother to infant is not an important mode of spread of hepatitis C virus. (HEPATOLOGY 1991;13:830–833.)
Effect of Water Salinity on Some Blood Parameters of Common Carp (Cyprinus carpio)

This study was conducted to investigate the effect of high salinity on the blood parameters of common carp (Cyprinus carpio) which gradually exposed to salt concentrations of 5, 10 and 15g/liter, as well as tap water (control 0.1g/liter). 80 fish were randomly distributed to four salinity treatments with 2 replicates /treatment (10 fish / replicate) at average weight of 15 ± 3 g to study the effect of salinity on the blood parameters, which included packed cells volume(PCV), red blood cells (RBC), white blood cells (RBC) and hemoglobin (Hb). Results showed an increase in the (PCV) to 36.17, 40.15 to and 45.30% when the salinity increased to 5, 10 and 15g/l respectively, compared with the control treatment (33.14%). Hb reached 13.34, 14.56 and 15.80 mg/100 ml at the concentration of 5, 10 and 15 respectively, compared with the control treatment (12.15 mg/100ml). RBC reached 2.80, 2.93 and 3.1 × 106 cells/mm3 respectively, in comparison with control (0.1 g/l), while the WBC increased to 12.88, 15.23 and 10.55 × 103 cells/mm3 when the salt concentrations were 5, 10 and 15g/l respectively, compared with control (10.44 × 103 cells/mm3).
Automated quantitative analysis of nocturnal jejunal motor activity identifies abnormalities in individuals and subgroups of patients with slow transit constipation

OBJECTIVE:Small bowel dysmotility has previously been demonstrated in some patients with slow transit constipation (STC), suggesting a generalized intestinal disorder. However, no study has addressed whether the incidence of small intestinal dysfunction differs between subgroups of patients in this heterogeneous population. Using appropriate methodology, we aimed to determine prospectively the proportion of individuals with abnormal small bowel motility, and to assess whether heterogeneity in terms of pattern of colonic transit delay (based on 111In diethylene-triamine-pentaacetic acid (DTPA) isotope scintigraphy), or mode of onset (based on clinical history) is of importance.METHODS:Thirty-seven patients with STC underwent 24-h ambulatory jejunal manometry; data were compared with those obtained in 38 healthy controls. Automated quantitative analysis of seven variables of the nocturnal migrating motor complex was performed, to assess whether differences existed between groups, and whether individual patients had evidence of small intestinal dysmotility, defined as two or more measures of migrating motor complex variables outside the normal range.RESULTS:Four variables differed significantly between STC patients and controls: in phase III, propagation was slower, duration was longer, and contraction amplitude was higher; in phase II, contraction frequency was increased. Seven of 24 patients with a generalized pattern of colonic transit delay had abnormal small bowel motility compared with none of 13 with a left-sided delay (p < 0.04). These included four patients with chronic idiopathic symptoms and three with acquired symptoms.CONCLUSIONS:Approximately one third of patients with a generalized delay in colonic transit had evidence of jejunal enteric neuromuscular dysfunction. Individual patients with a left-sided colonic delay did not satisfy the criteria for nocturnal small bowel dysmotility, but as a group, some differences were noted from controls. In contrast to previous reports, evidence of generalized enteric dysmotility may be present irrespective of the mode of onset.
Long-term impact on alcohol-involved crashes of lowering the minimum purchase age in New Zealand.

OBJECTIVES We assessed the long-term effect of lowering the minimum purchase age for alcohol from age 20 to age 18 years on alcohol-involved crashes in New Zealand. METHODS We modeled ratios of drivers in alcohol-involved crashes to drivers in non-alcohol-involved crashes by age group in 3 time periods using logistic regression, controlling for gender and adjusting for multiple comparisons. RESULTS Before the law change, drivers aged 18 to 19 and 20 to 24 years had similar odds of an alcohol-involved crash (P = .1). Directly following the law change, drivers aged 18 to 19 years had a 15% higher odds of being in an alcohol-involved crash than did drivers aged 20 to 24 years (P = .038). In the long term, drivers aged 18 to 19 years had 21% higher odds of an alcohol-involved crash than did the age control group (P ≤ .001). We found no effects for fatal alcohol-involved crashes alone and no trickle-down effects for the youngest group. CONCLUSIONS Lowering the purchase age for alcohol was associated with a long-term impact on alcohol-involved crashes among drivers aged 18 to 19 years. Raising the minimum purchase age for alcohol would be appropriate.
Single thyroid tumour showing multiple differentiated morphological patterns and intramorphological molecular genetic heterogeneity

Aims A 49-year-old man presented with a single thyroid tumour that showed a combination of conventional papillary carcinoma, follicular variant of papillary carcinoma, clear cell papillary carcinoma, columnar cell carcinoma and poorly differentiated carcinoma. As all of the morphologies have been associated with papillary carcinoma in the literature, we wished to determine if they contained identical or different molecular abnormalities. Methods Targeted next generation sequencing (NGS) of each morphological component and metastases was performed. Results NGS revealed a BRAF p.K601E mutation in both the clear cell papillary carcinoma and poorly differentiated carcinoma and a KRAS p.G12R mutation in the papillary carcinoma, follicular variant. Two different areas of columnar cell variant were tested, with one showing a KRAS p.G12D mutation but no mutation in the other area. A KRAS p.G12R mutation was seen in the metastatic clear cell variant. Two different lymph nodes had metastatic columnar cell carcinoma, one negative for mutations but the other with a compound KRAS p.G12R and KRAS p.G12V mutation on different alleles. No mutations including BRAF and KRAS were seen in the conventional papillary carcinoma. Conclusions Although all of the morphological patterns in this tumour have been reported as having aetiological or other association with one another, there was only partial concordance with their molecular signatures. There was significant molecular discordance, however, even with identical morphologies.
Enhancement of Dendritic Cell Antigen Cross-Presentation by CpG DNA Involves Type I IFN and Stabilization of Class I MHC mRNA1

Dendritic cells (DCs) internalize exogenous Ags and process them for cross-presentation by class I MHC (MHC-I) to CD8+ T cells. This processing can occur by transporter for Ag presentation (TAP)-dependent or TAP-independent mechanisms. We observed that CpG DNA enhanced cross-presentation of Ags by Flt-3L-cultured bone marrow-derived murine DCs by a type I IFN (IFN-αβ)-dependent mechanism. Myeloid DCs provided cross-presentation function in this system. Both TAP1 knockout and wild-type DCs showed enhanced cross-presentation when treated with CpG DNA at 26°C, demonstrating that TAP is not essential to this regulatory mechanism, although TAP is an important determinant of MHC-I expression. Enhancement of cross-processing by CpG DNA did not involve increased Ag uptake or proteolysis but did correlate with IFN-αβ-dependent increases in expression of MHC-I mRNA and protein. Increased MHC-I mRNA levels resulted in part from stabilization of MHC-I mRNA, a novel posttranscriptional mechanism for regulation of MHC-I expression. Thus, a major mechanism by which CpG oligodeoxynucleotide increase cross presentation by DCs appears to be an IFN-αβ-mediated increase in MHC-I synthesis.
Sphincter pharyngoplasty: Speech outcome and complications

Objectives: To assess the speech outcomes and complications in children who had undergone sphincter pharyngoplasty (SP) for management of velopharyngeal insufficiency (VPI). Study Design: Retrospective chart review. Methods: Charts from patients who had sphincter pharyngoplasty between January 1993 and June 1996 were reviewed. Syndrome diagnosis and presence of repaired cleft palate were reviewed. Preoperative speech assessment, videofluoroscopic and nasopharyngoscopic evaluations, age at time of surgery, and postoperative speech assessments were reviewed for all patients. Postoperative videofluoroscopy and nasopharyngoscopy were performed for those patients who had persistent VPI. Obstructive sleep symptoms were also assessed. Results: Thirty patients were identified; six patients had no follow‐up evaluation, leaving 24 patients included in this study. Average follow‐up was 11.7 months (range, 2–35 mo). Velocardiofacial syndrome (VCFS) was the most commonly identified syndrome. Postoperatively, 15 of 24 patients (62.5%) had complete resolution of their VPI; five of 24 (20.8%) had significant improvement; one of 24 (4.2%) had minimal to no change; and three of 24 (12.5%) were hyponasal. Of the six patients with some degree of persistent VPI, three underwent revision surgery. All three patients had complete resolution of their VPI after revision surgery, resulting in an overall success rate of 18 of 24 (75%). Conclusions: Sphincter pharyngoplasty has wide application in the management of children with VPI, including those with VCFS. The procedure is readily modified to accommodate an individual patient's needs as determined by preoperative VPI evaluation. A modification of the procedure is described to minimize the risk of postoperative airway obstruction and hyponasality, both regarded as airway complications of sphincter pharyngoplasty.
The Menstrual Cycle and Raynaud's Phenomenon

Fluctuations in female sex hormones may be responsible for the high prevalence of Raynaud's phenomenon (RP) observed in premenopausal women. These hormones are known to act on central and peripheral thermoreceptors. In an attempt to establish whether cold sensitivity is altered during the menstrual cycle 50 premenopausal women were investigated. Of these, 26 had primary RP and 24 acted as controls. Each subject was exposed to environmental heating and cooling at three stages of the menstrual cycle to coincide with peaks and troughs in hormone levels. These stages were menstruation, periovulation, and during the midluteal phase. Finger hemodynamics was assessed by means of venous occlusion strain gauge plethysmography and fingertip temperature. Core temperature was assessed with an oral thermocouple. The results show that cold sensitivity was altered during the menstrual cycle in both groups with the fastest finger rewarming pattern during menstruation. Moreover, a significant difference was observed in core temperature between the two groups during the midluteal phase. As a group, subjects with RP failed to show a significant rise in core temperature following ovulation. The authors conclude that the menstrual cycle is associated with changes in the effect of cold on digital blood flow.
Early climbing fiber interactions with Purkinje cells in the postnatal mouse cerebellum

The time and place of initial contacts between afferent axons and their target cells are not known for most regions of the mammalian CNS. To address this issue, we have selectively visualized afferent climbing fiber axons together with their synaptic targets, Purkinje cells, in postnatal mouse cerebellum. Climbing fibers were orthogradely labeled by injection of rhodamine isothiocyanate into their brainstem source, the inferior olivary nucleus. Purkinje cells were localized with an antibody to a calcium‐binding protein, calbindin D‐28k(CaBP), in the same section or in adjacent sections.
Peripheral Nerve Society Guideline on processing and evaluation of nerve biopsies

Nerve biopsy is often the final step in the diagnostic work‐up of neuropathies of unknown origin. The aim of this guideline was to prepare an evidence‐based guideline on the methods for performing and evaluating nerve biopsy. The panel performed a search of MEDLINE, hand search of bibliographies of the references retrieved, review of the evidence, and reached agreement by consensus. There were not enough formal studies of diagnostic test accuracy to allow evidence‐based recommendations of levels A–C for most questions. The panel summarized the class IV evidence and reached agreement by consensus on the following recommendations: (1) Nerve biopsy should not be performed before adequate clinical, electrophysiological, and laboratory investigation and only be performed with appropriate informed consent. (2) An interactive working relationship with the relevant disciplines involved and the provision of sufficient clinical information is encouraged. (3) Biopsies should be processed and read by professionals with adequate training and experience. (4) Optimal analysis of nerve biopsy is best performed by laboratories that have the facilities and expertise to prepare and evaluate frozen and fixed sections (cryostat, paraffin, and epoxy sections). (5) Immunohistochemistry, teased fiber analysis, electron microscopy, and morphometry may help clarify the diagnosis in some conditions and should be considered as additional studies.