Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemical characterization of molecular subtypes of invasive breast cancer: a study from North India

In recent years breast cancer has been classified on the basis of its molecular characteristics by gene expression profiling. A similar classification using immunohistochemistry has been identified so that it has a wider application. This study was designed to define the precise prevalence of molecular subtypes of invasive breast carcinoma using immunohistochemistry in patients from north India and to correlate it with known clinical and histological prognostic factors. Based on ER/PR/Her2/neu expression, 100 cases of invasive breast cancer were categorized into: ER+ and ⁄ or PR+ and Her2/neu− (47%), ER+ and⁄or PR+ and Her2/neu+ (15%), ER− and ⁄ or PR− and Her2/neu+ (Her2/neu overexpressing, 21%), ER−, PR− and Her2/neu− (Triple negative, 17%). All cases demonstrated positivity for the luminal Cytokeratins 8/18. In addition, 10% of these tumours showed expression of the basal markers (CK4/14, CK5/6). Among the 17 triple negative cases, eight cases were positive for one of the basal markers and two cases with basal marker expression were Her2/neu overexpressing. The basal markers showed significant correlations only with histological grade and ER negative status. On the basis of hormone receptor, Her‐2/neu and cytokeratin expressions, distinct subclasses of breast cancer have been identified which show significant differences in relation to histological grade and ER status. Expression of basal markers is needed to define basal‐like breast cancer.
Need for strengthening of internship (rotatory housemanship) training in India.

Introduction: Internship is a problematic phase in the training of doctors in India. At the end of their one-year Internship, students are not formally examined for proficiency, rarely a student is not given a satisfactory completion certificate and training is sometimes not supervised. Students are required to spend three months of this Internship in Primary Health Centres at rural postings. During this period the students often prepare for the written exams that would allow them to pursue post-graduate studies. Method: In a personal reflection, this situation is described in the current article. The author suggests several approaches to improve this unwanted situation, so that the rural postings could be taken more seriously by the students. Outcomes: Suggestions range from a post-internship examination, via the introduction of compulsory rural postings after graduation to an increase of the avenues for post- graduate training to include a course in family medicine and general practice. Conclusions: The objective of providing excellent training during internship periods cannot be achieved unless interns actively participate. If the current situation does not change, for example according to the suggested solutions, this valuable component of medical training will remain problematic, thereby hindering the optimal preparation of doctors for the entire spectrum of necessary health care in India.
Early clinical exposure in medical curricula across Europe: An overview

Background: Many faculties of medicine now include programmes using early clinical exposure (ECE) to introduce medical students to important topics in medicine. Objective: To sketch the landscape of ECE in Europe, describing existing courses. Methods: A survey questionnaire was developed by the Basic Medical Education Committee of the European Academy of Teachers in General Practice (EURACT). This survey used the key informant interviews method, with EURACT Council members serving as key informants by filling in the questionnaire and gathering descriptive data on ECE programmes in their own countries. Results: We asked representatives of 32 EURACT member countries to complete the questionnaire in 2006. We received responses from 21 countries, and the programmes of 40 medical schools from 16 countries were included in the study. Thirty-two medical schools implemented ECE starting in the first year. The duration of ECE programmes ranged from 2 weeks to 2 years. The length of each session varied from 2 hours to a full day. Primary care played an important role in ECE. ECE programmes were implemented with a wide range of objectives. Conclusion: ECE is a new and rewarding trend in European medical schools, and general practice/family medicine (GP/FM) departments are widely involved in these teaching activities. This could help establish GP/FM departments in some countries that still do not have them in their medical schools.
Oral Tacrolimus for the Treatment of Refractory Inflammatory Bowel Disease in the Biologic Era

Background:Patients with inflammatory bowel disease who are refractory to standard therapies frequently require surgery. The long-term efficacy of tacrolimus in patients who fail standard immunosuppressive and antitumor necrosis factor &agr; therapy is unknown. Methods:Thirty-five patients (11 Crohn’s disease and 24 ulcerative colitis) with medication-resistant disease were treated with oral tacrolimus and reviewed retrospectively. Patients were commenced on tacrolimus 0.1 mg/kg/day, with a trough level targeted between 8 and 12 ng/mL. Clinical response or remission at 30 days, 90 days, and 1 year was assessed. The overall risk of requiring surgery and predictive factors were also assessed. Results:All patients had failed a thiopurine, 5 (14%) had also failed methotrexate, while 90% had a primary or secondary nonresponse, or an incomplete response, to an antitumor necrosis factor &agr; agent. The proportions that achieved a clinical response at 30 days, 90 days, and 1 year was 65.7%, 60%, and 31.4%, respectively, whereas the corresponding proportions in remission were 40%, 37.1%, and 22.9%. The cumulative risk of requiring surgery was 40.4% at 1 year and 59.3% at 2 years with a median time to surgery of 22 months (range, 0.5–84 months). Patients who were steroid refractory, or dependent, before starting tacrolimus were more likely to have surgery (P = 0.006), whereas patients who were able to achieve or maintain a clinical response with tacrolimus by 90 days were less likely (P = 0.004). Conclusions:Tacrolimus is able to induce a clinical response in a third and remission in a fifth of medically refractory patients with inflammatory bowel disease at 1 year. A 90-day therapeutic trial is worthwhile in difficult to treat patients.
The Embryonic Human Brain: An Atlas of Developmental Stages

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A feasibility study evaluating an in situ formed synthetic biodegradable membrane for guided bone regeneration in dogs.

PURPOSE The aim was (1) to evaluate the soft-tissue reaction of a synthetic polyethylene glycol (PEG) hydrogel used as a barrier membrane for guided bone regeneration (GBR) compared with a collagen membrane and (2) to test whether or not the application of this in situ formed membrane will result in a similar amount of bone regeneration as the use of a collagen membrane. MATERIAL AND METHODS Tooth extraction and preparation of osseous defects were performed in the mandibles of 11 beagle dogs. After 3 months, 44 cylindrical implants were placed within healed dehiscence-type bone defects resulting in approximately 6 mm exposed implant surface. The following four treatment modalities were randomly allocated: PEG+autogenous bone chips, PEG+hydroxyapatite (HA)/tricalcium phosphate (TCP) granules, bioresorbable collagen membrane+autogenous bone chips and autogenous bone chips without a membrane. After 2 and 6 months, six and five dogs were sacrificed, respectively. A semi-quantitative evaluation of the local tolerance and a histomorphometric analysis were performed. For statistical analysis, repeated measures analysis of variance (ANOVA) and subsequent pairwise Student's t-test were applied (P<0.05). RESULTS No local adverse effects in association with the PEG compared with the collagen membrane was observed clinically and histologically at any time-point. Healing was uneventful and all implants were histologically integrated. Four out of 22 PEG membrane sites revealed a soft-tissue dehiscence after 1-2 weeks that subsequently healed uneventful. Histomorphometric measurement of the vertical bone gain showed after 2 months values between 31% and 45% and after 6 months between 31% and 38%. Bone-to-implant contact (BIC) within the former defect area was similarly high in all groups ranging from 71% to 82% after 2 months and 49% to 91% after 6 months. However, with regard to all evaluated parameters, the PEG and the collagen membranes did not show any statistically significant difference compared with sites treated with autogenous bone without a membrane. CONCLUSION The in situ forming synthetic membrane made of PEG was safely used in the present study, revealing no biologically significant abnormal soft-tissue reaction and demonstrated similar amounts of newly formed bone for defects treated with the PEG membrane compared with defects treated with a standard collagen membrane.
Vitamin A deficiency due to bi-allelic mutation of RBP4: There’s more to it than meets the eye

ABSTRACT Vitamin A deficiency is the leading cause of preventable blindness in children worldwide and results in a well-recognized ocular phenotype. Herein we describe a patient presenting to the eye clinic with a retinal dystrophy and ocular colobomata. This combination of clinical signs and consanguineous pedigree structure suggested a genetic basis for the disease, a hypothesis that was tested using whole genome sequencing. Bi-allelic mutations in RBP4 were identified (c.248+1G>A), consistent with a diagnosis of inherited vitamin A deficiency. We describe a constellation of signs that appear to be characteristic for this disease, increasing clinical awareness of this rare condition.
Examining the Time to Improvement of Sleep Interference With Pregabalin in Patients With Painful Diabetic Peripheral Neuropathy and Postherpetic Neuralgia

Pregabalin has been shown to be a safe, effective treatment for neuropathic pain associated with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN), with average time to reduction in pain of 2 days. Pain-related sleep interference is commonly reported in both painful DPN and PHN. These post hoc analyses examined the time to improvement in sleep with pregabalin in patients with painful DPN or PHN, measured by reduction in daily sleep interference (DSI) scores on an 11-point numeric rating scale. A total of 4527 patients from 16 placebo-controlled trials of pregabalin for treatment of painful DPN or PHN were included in the analysis. In these trials, there were a total of 16 pregabalin treatment arms for painful DPN (75–600 mg/d), 10 for PHN (150–600 mg/d), and 3 for painful DPN/PHN (150–600 mg/d). Time to improvement in DSI scores was calculated for all treatment arms that demonstrated statistically significant reductions in DSI scores during the first 14 days of treatment compared with placebo (23 of 29; 79.3%) and was defined as the first day DSI scores for that day and the following day were significantly lower than placebo (P < 0.001). Mean (SD) time to improvement in DSI scores was 1.6 (1.3) days. Sustained improvement (≥1-point improvement in mean DSI score) was seen significantly earlier for pregabalin DSI responders than patients receiving placebo. These findings demonstrate that statistically significant and sustained improvement in sleep occurs rapidly (within 1 day for some patients) in response to treatment with pregabalin.
Acellular dermal matrix as a barrier in guided bone regeneration: a clinical, radiographic and histomorphometric study in dogs.

OBJECTIVES The purpose of this study was to evaluate the effectiveness of the acellular dermal matrix (ADM) as a membrane for guided bone regeneration (GBR), in comparison with a bioabsorbable membrane. MATERIAL AND METHODS In seven dogs, the mandibular pre-molars were extracted. After 8 weeks, one bone defect was surgically created bilaterally and the GBR was performed. Each side was randomly assigned to the control group (CG: bioabsorbable membrane made of glycolide and lactide copolymer) or the test group (TG: ADM as a membrane). Immediately following GBR, standardized digital X-ray radiographs were taken, and were repeated at 8 and 16 weeks post-operatively. Before the GBR and euthanasia, clinical measurements of the width and thickness of the keratinized tissue (WKT and TKT, respectively) were performed. One animal was excluded from the study due to complications in the TG during wound healing; therefore, six dogs remained in the sample. The dogs were sacrificed 16 weeks following GBR, and a histomorphometric analysis was performed. Area measurements of new tissue and new bone, and linear measurements of bone height were performed. RESULTS Post-operative healing of the CG was uneventful. In the TG membrane was exposed in two animals, and one of them was excluded from the sample. There were no statistically significant differences between the groups for any histomorphometric measurement. Clinically, both groups showed an increase in the TKT and a reduction in the WKT. Radiographically, an image suggestive of new bone formation could be observed in both groups at 8 and 16 weeks following GBR. CONCLUSION ADM acted as a barrier in GBR, with clinical, radiographic and histomorphometric results similar to those obtained with the bioabsorbable membrane.
Image analyses of collagen types and thickness in oral sub mucous fibrosis stained with picrosirius red under polarizing microscope

Context: Oral submucous fibrosis (OSF) is a potentially malignant oral disorder leading to increased fibrosis in the sub-epithelial layer. The collagen in the condition has been a subject of intense scrutiny in an attempt to understand the pathogenesis of the disease. Aim: The present study aims to quantify and qualify the collagen fibers in different histological grades of OSF using picrosirius red stain under the polarizing microscope. The quantification of the fibrosis was carried out using image analysis software and the fibers were graded according to staining hue and intensity into their respective subtypes. Comparison was done with normal mucosa, scar/keloid tissue samples. Materials and Methods: The present study included OSF (n = 50) of differing histological grades, keloid/scar (n = 4) and normal mucosa (n = 6) as control cases. Histological assessment was performed on hematoxylin and eosin stained sections. Picrosirius red stained slides were observed under a polarizing microscope for assessment of collagen subtypes. Quantification of collagen was done under polarizing microscope and image parameters were analyzed using ProReg® Capture Pro 2.8. 8 (Lawrence and Mayo India Pvt Ltd, 2011) image analysis software. Results: The epithelial thickness in OSF, scar and keloid is less than that of normal mucosa and progressive decrease in the epithelial thickness is seen in the successive stages of OSF. The fibrosis increases with increasing grades of OSF, was higher in scar and keloid and was highly statistically significant. Type I collagen was more predominant in all stages of OSF, in normal oral mucosa and scar/keloid tissue samples as compared with type III. Though quantitative analysis of the collagen types I and III is possible, with picrosirius red qualitative analysis is an arduous task. The specificity of detection of collagen subtypes was acceptable with the picrosirius red stain, but the sensitivity left a lot to be desired.
Dimensional ridge alterations following immediate implant placement in molar extraction sites: a six-month prospective cohort study with surgical re-entry.

AIM To assess dimensional ridge alterations following immediate implant placement in molar extraction sites. MATERIAL AND METHODS Twelve subjects received 12 immediate transmucosal implants in molar extraction sites. Peri-implant defects were treated according to the principles of Guided Bone Regeneration by means of a deproteinized bone substitute and a bioresorbable collagen membrane. Changes in vertical (IS-BD, CREST-BD) and horizontal distances (EC-I, IC-I) of alveolar bony walls to the bottom of the defects (BD) and to the implant surfaces (I) were compared between implant placement and surgical re-entry at 6 months. RESULTS The implant survival rate at 6 months was 100%. Statistically significant differences (P<0.01) were observed in the mean changes in vertical distances IS-BD and CREST-BD between baseline and re-entry. At re-entry, all peri-implant marginal defects assessed from the internal socket wall to the implant surface (IC-I) were healed. The residual combined thickness of the buccal wall with the newly formed peri-implant bone at sites with an initial thickness of 1 mm was statistically significantly smaller (P<0.05) compared with that of sites with an initial buccal thickness of 2 mm (2.50 +/- 0.76 vs. 4+/-0 mm). CONCLUSIONS The marginal defects around immediate implants placed in molar extraction sites were completely filled after 6 months of healing through de novo bone formation. Bone resorption was observed from the external aspects of the buccal and oral socket walls. Dimensional changes of the external socket walls were mostly pronounced at the buccal aspects.
beta-Tricalcium phosphate in the early phase of socket healing: an experimental study in the dog.

OBJECTIVES The aim of this experiment was to analyze processes involved in the incorporation of beta-tricalcium phospate (TCP) particles in host tissue during healing following tooth extraction and grafting. MATERIAL AND METHODS Five beagle dogs were used. Four premolars in the maxilla ((3)P(3), (2)P(2)) were hemi-sected, the distal roots were removed and the fresh extraction socket filled with TCP. The tooth extraction and grafting procedures were scheduled in such a way that biopsies representing 1 and 3 days, as well as 1, 2, and 4 weeks of healing could be obtained. Tissue elements such as cells, fibers, vessels, leukocytes and mineralized bone were determined. In deparaffinized sections structures and cells that expressed Tratarate resistant acid phosphate, alkaline phosphatase, and osteopontin were identified by the use of markers. RESULTS The porosities of the TCP particles were initially filled with erythrocytes that subsequently were replaced with mineralized bone. Some of the graft material was invaded by mesenchymal and inflammatory cells and disintegrated. Thus, small membrane bound granules appeared in the granulation tissue and the provisional matrix. In the process of hard tissue formation, partly mineralized (modified) TCP particles became surrounded by ridges of woven bone. CONCLUSIONS It was demonstrated that the early healing of an extraction socket that had been grafted with beta-TCP involved (i) the formation of a coagulum that was (ii) replaced with granulation tissue and a provisional matrix in which (iii) woven bone could form. In this process the biomaterial was apparently involved.
Long-term, retrospective evaluation (implant and patient-centred outcome) of the two-implant-supported overdenture in the mandible. Part 2: marginal bone loss.

OBJECTIVE In part 2 of this long-term, retrospective study on the two-implant-supported overdenture in the mandible, the annual marginal bone loss was evaluated in detail and parameters, with a significant effect on the annual bone loss, were verified. MATERIAL AND METHODS For all 495 patients with an overdenture in the mandible at least 5 years in function, data up to their last follow-up visit had been collected, including long-cone radiographs (taken at the abutment connection and after years 1, 3, 5, 8, 12 and 16 of loading) and probing data at their last evaluation. General information (medical history, implant data, report on surgery) was retrieved from the patient's file. Two hundred and forty-eight patients had been clinically examined recently. For the others, information on bone level and probing depths were retrieved from the patient's files, as all patients had been enrolled in our annual follow-up schedule. RESULTS The mean annual bone loss on a site level (without considering the first year of bone remodelling) after 3 years of loading was 0.08 mm/year (SD=0.22, n=1105), after 5 years of loading 0.07 mm/year (SD=0.14, n=892), after 8 years of loading 0.06 mm/year (SD=0.12, n=598), after 12 years 0.04 mm/year (SD=0.07, n=370) and 0.05 mm/year (SD=0.05, n=154) after 16 years of loading. Ongoing bone loss was seen in a number of implants (n=26) with the annual bone loss exceeding 0.2 mm. Some factors clearly showed a significant impact on bone loss: smoking (> or =10 cigarettes/day), GBR, the presence of dehiscence and bone quantity(the latter only during the first year). The probing data showed a favourable condition, with <1.2% of the approximal pockets being > or =6 mm, and 4.1%=5 mm. CONCLUSIONS The mean annual bone loss over the study period was <0.1 mm/year after the first year of loading. However, a small number (2.5%) of the implants showed continuing bone loss.
Perception of Temporal Order: The Effects of Age, Sex, and Cognitive Factors

ABSTRACT The present paper investigates the effects of age, sex, and cognitive factors on temporal-order perception. Nine temporal-order tasks were employed using two and four stimuli presented in the auditory and visual modalities. Significantly increased temporal-order thresholds (TOT) in the elderly were found for almost all tasks, while sex differences were only observed for two tasks. Multiple regression analyses show that the performance on most temporal-order tasks can be predicted by cognitive factors, such as speed of fluid reasoning, short-term memory, and attention. However, age was a significant predictor of TOT in three tasks using visual stimuli. We conclude (1) that age-related differences can often be attributed to cognitive factors involved in temporal-order perception, and (2) that the concept of temporal-order perception is more complex than implied by the current models.