Miracle-dz/UniFAR-FTUs huggingface dataset:
Total pregnancy‐associated plasma protein A—a first trimester maternal serum marker for Down's syndrome: clinical and technical assessment of a poly‐monoclonal enzyme immunoassay

Pregnancy‐associated plasma protein A (PAPP‐A) is a maternal serum marker of fetal chromosomal disease and a risk marker for adverse outcome. PAPP‐A in the circulation exists both as a 2:2 complex (PAPP‐A/proMBP) with the proform of eosinophil major basic protein (proMBP) and as dimeric PAPP‐A. Non‐PAPP‐A containing proMBP complexes constitute the bulk of proMBP in maternal serum. We developed and characterized a sandwich enzyme immunoassay for PAPP‐A using a polyclonal rabbit anti‐PAPP‐A/proMBP antibody (SSI 6823) and a monoclonal murine anti‐PAPP‐A/proMBP antibody (HYB 234‐3), reactive with the PAPP‐A part of PAPP‐A/proMBP. The assay range was 2 mIU/L–500 mIU/L, intra‐ and inter‐assay coefficients of variation <10%. The immunoreactivity eluted ahead of thyroglobulin, Mr 669 kDa, in gel filtration and bound to a heparin column. Serum concentrations of PAPP‐A were determined in gestational weeks 5–13 in 167 pregnant women with normal fetuses and 39 women with Down's syndrome (DS) fetuses. The median PAPP‐A MoM (multiples of the median in normal controls) in DS pregnancies was 0.30 (quartile range: 0.17–0.54). The PAPP‐A logMoMs in DS pregnancies were normally distributed with a mean of −0.5927 and SD of 0.3639. When simulating the performance of PAPP‐A and age as markers for DS in population screening a detection rate (DR) of 62% was found for a screen positive rate (SPR) of 5%. Together with β‐HCG and nuchal translucency, two other first trimester markers for fetal DS, a DR 90% could be obtained for an SPR of 5%.
Circadian alterations of reproductive functional markers in male rats exposed to 1800 MHz radiofrequency field

In this study, we explored the circadian effects of daily radiofrequency field (RF) exposure on reproductive functional markers in adult male Sprague–Dawley rats. Animals in circadian rhythm (as indicated by melatonin measurements), were divided into several groups and exposed to 1800 MHz RF at 205 μw/cm2 power density (specific absorption rate 0.0405 W/kg) for 2 h/day for 32 days at different zeitgeber time (ZT) points, namely, ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20. Sham-exposed animals were used as controls in the study. From each rat, testicular and epididymis tissues were collected and assessed for testosterone levels, daily sperm production and sperm motility, testis marker enzymes γ-GT and ACP, cytochrome P450 side-chain cleavage (p450cc) mRNA expression, and steroidogenic acute regulatory protein (StAR) mRNA expression. Via these measurements, we confirmed the existence of circadian rhythms in sham-exposed animals. However, rats exposed to RF exhibited a disruption of circadian rhythms, decreased testosterone levels, lower daily sperm production and sperm motility, down-regulated activity of γ-GT and ACP, as well as altered mRNA expression of cytochrome P450 and StAR. All of these observations were more pronounced when rats were exposed to RF at ZT0. Thus, our findings indicate potential adverse effects of RF exposure on male reproductive functional markers, in terms of both the daily overall levels as well as the circadian rhythmicity.
Microbial Keratitis in Kingdom of Bahrain: Clinical and Microbiology Study

Background: Microbial keratitis is a potentially vision threatening condition worldwide. Knowing the predisposing factors and etiologic microorganism can help control and prevent this problem. This is the first study of its kind in Kingdom of Bahrain. Objective: To study the profile of microbial keratitis in Bahrain with special focus on risk factors, clinical outcome and microbilogical results. Methods: A retrospective analysis of all patients admitted in Salmaniya Medical Complex over a period of three years from January 2005 to January 2007 was performed. A total of 285 patients with keratitis were analysed. Non infectious corneal ulceration were excluded. Data collected from medical records were demographic features, predisposing factors, history of corneal trauma, associated ocular conditions, visual acuity at the time of presentation and the clinical course. Predisposing risk factors measured were contact lens use, presence of blepharitis, diabetes, lid abnormalities, dry eyes, keratoplasty and refractive surgery. For contact lens wearers any contact lens related risk factors that can lead to keratitis were measured. Pearson's chi-square test was used to carry out statistical analysis wherever required. Results: Contact lens wear, as a risk factor for microbial keratitis, formed 40% of the total study population. Other risk factors identified were dry eyes 24 cases (8%), 10 blepharitis (3%), 22 trauma (8%), abnormal lid position 14 cases (5%). 6 patients keratitis in a graft (2%), 3 had refractive surgery (1%). The most common causative organism isolated was pseudomonas aeroginosa (54%) followed by streptococcus 12%, staph 10%, other organisms 6%. 95% of contact lens wearers had pseudomonas Aeroginosa. This was statistically significant (p< 0.0001). The vast majority, 92% healed with scarring. 1% needed therapeutic keratoplasty and 7% lost to follow up. Risk factors in contact lens wearers were; 41 patients (36%) slept with the contact lenses. 12 (8%) had contact lens related trauma and 8 (7%) had poor hygiene. Sleeping with the contact lenses was statistically significant (p< 0.0001). Conclusion & Recommendation: Contact lens wear is the major risk factor for microbial keratitis in Bahrain. Pseudomonas aeroginosa was the commonest bacteria isolated. Sleeping with the contact lenses is the major risk factor among contact lens wearers. Majority of keratitis patients resulted in permanent scarring on the cornea. Educating the public, especially on contact lens care and precaution, can help reduce this visual morbidity.
Clinical and Magnetic Resonance Imaging Outcomes After Surgical Repair of Complete Proximal Hamstring Ruptures

Background: The use of validated outcome questionnaires and magnetic resonance imaging (MRI) when assessing outcomes after surgical treatment of proximal hamstring avulsions has been limited. Purpose: To comprehensively evaluate clinical, functional, and radiological outcomes in patients treated with surgical repair for complete proximal hamstring avulsions. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review of 15 consecutive patients was performed. Outcome measures included the Single Assessment Numeric Evaluation (SANE), visual analog scale (VAS) for pain, Proximal Hamstring Injury Questionnaire, Lower Extremity Functional Scale (LEFS), Harris Hip Score (HHS), and Tegner Activity Scale (TAS). Physical examination was performed by an independent sports medicine fellow. Magnetic resonance imaging of the lower extremity was used to assess tendon healing and muscle quality after repair. Results: Thirteen of 15 (87%) eligible patients were available for follow-up at a mean 36.9 months (range, 27-63 months), including 8 men and 6 left-sided injuries. The average age was 44.6 years (range, 26-58 years). Twelve of 13 patients underwent surgical repair within 60 days of injury. Mean (± standard deviation) postoperative functional outcome scores were as follows: LEFS, 74.9 ± 7.8 (range, 59-80); HHS, 90.7 ± 13.9 (range, 67-100); SANE, 93.6 ± 7.5 (range, 75-100); VAS for pain, 1.3 ± 1.9 (range, 0-5); and TAS, 4.6 ± 2.3 (range, 1-7). All 11 patients who participated in sports before surgery were able to return to sport, but 45% reported a decrease in their current level of activity. Isokinetic muscle testing demonstrated that injured hamstring strength recovered up to 78% ± 6.1% (range, 74%-88%) of the contralateral side. The MRI examinations revealed that 100% of patients had a healed proximal hamstring repair, with signs of tendinopathy and mild atrophy in 3 of 12 patients. Conclusion: The current findings indicate that surgical repair of complete hamstring ruptures provides reliable pain relief, good functional outcomes, high satisfaction rates, and excellent healing rates (MRI) but does not fully restore hamstring function and sports activity to preinjury levels.
Prognostic Value of ERCC1, Thymidylate Synthase, and Glutathione S-Transferase &pgr; for 5-FU/Oxaliplatin Chemotherapy in Advanced Colorectal Cancer

Background:The aim of this study was to determine whether the expression of the excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS) and glutathione S-transferase &pgr; (GST&pgr;) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy. Methods:The study population consisted of 70 patients with advanced colorectal cancer (median age, 54 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on days 1 plus leucovorin (LV) 20 mg/m2 over 10 minutes, followed by 5-FU bolus 400 mg/m2 and a 22-hour continuous infusion of 600 mg/m2 from day 1 to 2. Treatment was repeated at 2-week intervals. The expression of ERCC1, TS, and GST&pgr; in primary tumors was examined using immunohistochemistry. Results:ERCC1, TS, and GST&pgr; were positive in 55.7%, 68.6%, and 71.4% of cases, respectively. Patients without TS expression were more likely to respond to chemotherapy (P = 0.009). There were no significant differences between response to treatment and the ERCC1 or GST&pgr; expression pattern (P = 0.768, P = 0.589, respectively). The median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0474). Patients who were ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GST&pgr; positive had a poor OS (P = 0.0017, P = 0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted OS (hazard ratio 1.72, P = 0.023). Conclusion:Immunohistochemical study of ERCC1 and TS may be useful for the prediction of clinical outcome in patients with advanced colorectal cancer treated with 5-FU and oxaliplatin.
How does the pharmaceutical industry influence prescription? A qualitative study of provider payment incentives and drug remunerations in hospitals in Shanghai

Abstract Over-prescription has become one major problem in China’s health care sector. Incorporating interview data from hospitals in Shanghai, this paper provided empirical evidence on how the process of over-prescription was carried out in day-to-day clinical settings, and demonstrates various mechanisms that allow over-prescription to continue vigorously in the context of the Chinese health care system. In particular, this study identified four levels of incentives that over-prescription was carried out: hospital, medical department, doctors and pharmaceutical companies. Due to the insufficient funding from the government and rising operational costs, hospitals had to rely on the sales of drugs and provision of medical services to survive. This funding pressure then transferred to specific revenue targets for medical departments. A combination of incentives, including drug remunerations, bonus system, low pay and high workloads motivated over-prescription at doctor level. At pharmaceutical company level, high profits of pharmaceuticals products as well as lack of emphasis on efficacy of drugs led to under-table payments and illicit drug remunerations. The study argued that the way that the Chinese health care system operates was based on the profit-seeking principle rather than on fulfilling its social functions, and called for a systematic reform of provider incentives to eradicating the problem of over-prescription.
Phonation after cervical spinal cord injury (CSCI): Prospective case examinations of the acute and sub-acute stages of recovery

Abstract The aim of the investigation was to examine the changes in phonation and related quality-of-life in the acute and sub-acute stages of recovery post-cervical spinal cord injury (CSCI). A prospective examination of phonation was conducted using perceptual and instrumental measures of respiratory and laryngeal functioning alongside a quality-of-life rating scale. Change was present across measures for both cases at each time point. Overall, a general pattern of recovery was seen, although some areas deteriorated between 6–12 months. Severity of impairments, extent of change, and impact on quality-of-life differed between the cases. Measures varied in sensitivity to change in function. Phonation can be impaired following both complete and incomplete CSCI, with type and severity of impairment/s undergoing change throughout the acute and sub-acute period post-injury. Spontaneous physiological recovery does not necessarily result in improved phonation and/ or quality-of-life. Potential exists for targeted speech-language therapy in this population, throughout recovery, to best capitalize on the physical changes that are occurring and to maximize functional application of skills to improve quality- of-life. Further research is warranted to examine this recovery period on a larger scale.
Recovery of nuclear matrix ultrastructure of interphase CHO cells after heat shock

Heat shock induces changes in G1 CHO cell nuclear matrix (NM) ultrastructure that may be related to heat‐induced nuclear protein accumulation (Wachsberger and Coss, 1993, J. Cell. Physiol., 155:615–634). The present study quantitates recovery of alterations in NM fine structure in CHO cells heated in G1 and compares structural recovery with recovery of bulk RNA synthesis and surviving fraction (SF). Morphology of NM preparations was quantified 30 min and 20 hr following heat shock by 1) measurement of the number of fiber anastomosing points per unit area per NM, and 2) measurement of the length of fibers between points of anastomoses within individual NMs. Architectural recovery was nearly complete within 20 hr in cells heated at 43°C or 45°C with SFs of 0.27 or greater. No recovery of architecture was observed in heated cells with SFs of approximately 0.01 or less. The residual damage to NMs was associated with RNA‐containing fiber networks as determined by means of RNase gold labeling. Recovery from inhibition of RNA synthesis following heat shock was related to recovery of NM architecture. It is suggested that 1) repair of NM architecture does not require full recovery of bulk RNA synthesis, and 2) partial or complete irreversible collapse of the NM may be responsible, in part, for heat‐induced, interphase cell death. © 1994 Wiley‐Liss, Inc.
Dietary procyanidins selectively modulate intestinal farnesoid X receptor-regulated gene expression to alter enterohepatic bile acid recirculation: elucidation of a novel mechanism to reduce triglyceridemia.

SCOPE Understanding the molecular basis by which dietary procyanidins modulate triglyceride and cholesterol homeostasis has important implications for the use of natural products in the treatment and prevention of cardiovascular disease. METHODS To determine whether modulation of bile acid (BA) homeostasis contributes to the hypotriglyceridemic action of grape seed procyanidin extract (GSPE) we examined the effect on genes regulating BA absorption, transport and synthesis in vitro, in Caco-2 cells, and in vivo, in wild type (C57BL/6) and farnesoid x receptor knockout (Fxr(-/-)) mice. RESULTS We provide novel evidence demonstrating that GSPE is a naturally occurring gene-selective bile acid receptor modulator (BARM). Mechanistically, GSPE down-regulates genes involved in intestinal BA absorption and transport in an Fxr-dependent manner, resulting in decreased enterohepatic BA recirculation. This correlates with increased fecal BA output, decreased serum triglyceride and cholesterol levels, increased hepatic cholesterol 7α-hydroxylase (Cyp7a1), and decreased intestinal fibroblast growth factor 15 (Fgf15) expression. GSPE also increased hepatic HmgCoA reductase (Hmgcr) and synthase (Hmgcs1) expression, while concomitantly decreasing sterol regulatory element-binding protein 1c (Srebp1c). CONCLUSION GSPE selectively regulates intestinal Fxr-target gene expression in vivo, and modulation of BA absorption and transport is a critical regulatory point for the consequential hypotriglyceridemic effects of GSPE.
Consensus Recommendations on Estrogen Receptor Testing in Breast Cancer By Immunohistochemistry

Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomarker that determines breast cancer prognosis after treatment with endocrine therapy. Although immunohistochemistry has been widely viewed as the gold standard methodology for ER testing in breast cancer, lack of standardized procedures, and lack of regulatory adherence to testing guidelines has resulted in high rates of “false-negative” results worldwide. Standardized testing is only possible after all aspects of ER testing—preanalytical, analytical, and postanalytical, have been closely controlled. A meeting of the “ad-hoc committee” of expert pathologists, technologists, and scientists, representing academic centers, reference laboratories, and various agencies, issued standardization testing recommendations, aimed at optimization of clinical ER testing environment, as a step toward improved standardized testing.
Transforming Growth Factor-b1 Stimulates Protein Kinase A in Mesangial Cells*

We recently demonstrated that transforming growth factor-b (TGF-b) stimulates phosphorylation of the type I inositol 1,4,5-trisphosphate receptor (Sharma, K., Wang, L., Zhu, Y., Bokkala, S., and Joseph, S. (1997) J. Biol. Chem. 272, 14617–14623), possibly via protein kinase A (PKA) activation in murine mesangial cells. In the present study, we evaluated whether TGF-b stimulates PKA activation. Utilizing a specific PKA kinase assay, we found that TGF-b increases PKA activity by 3-fold within 15 min of TGF-b1 treatment, and the enhanced kinase activity was completely reversed by the inhibitory peptide for PKA (PKI; 1 mM). In mesangial cells transfected with a PKI expression vector, enhanced PKA activity could not be demonstrated with TGF-b1 treatment. TGF-b1 was also found to stimulate translocation of the a-catalytic subunit of PKA to the nucleus by Western analysis of nuclear protein as well as by confocal microscopy. TGF-b1-mediated phosphorylation of cAMP response element-binding protein was completely reversed by H-89 (3 mM), a specific inhibitor of PKA. Stimulation of fibronectin mRNA by TGF-b1 was also attenuated in cells overexpressing PKI. We thus conclude that TGF-b stimulates the PKA signaling pathway in mesangial cells and that PKA activation contributes to TGF-b stimulation of cAMP response elementbinding protein phosphorylation and fibronectin expression.
A polyclonal CD4+ and CD8+ lymphocytosis in a patient doubly infected with HTLV‐I and HIV‐1: A clinical and molecular analysis

HTLV‐I is associated with adult T‐cell leukemia/ lymphoma (ATL) characterized by monoclonal expansions of CD4+ T‐lymphocytes. In this report we describe a histologically benign, polyclonal HTLV‐I infection in a patient exhibiting both an absolute CD4+ and CD8+ lymphocytosis. Three T‐cell lines containing integrated HTLV‐I proviral copies established from this patient were initially polyclonal, but with time all grew out the same two clones as determined by analysis of their T‐cell antigen receptor beta chain gene rearrangements. The patient subsequently developed pulmonary and nasopharyngeal nodules containing HTLV‐I infected cells. Restriction analysis of the patient's HTLV‐I provirus revealed no differences from prototype HTLV‐I and the tax gene was normally expressed in vivo and in vitro. The patient's T‐lymphocytosis and HTLV‐I+ pulmonary tract nodules were put into a complete clinical remission by treatment with alkylating agents and steroids. Subsequently, the patient developed a severe immunodeficiency state and expired. Retrospective serologic and gene amplification assays for HIV‐1 demonstrated that he had been doubly infected from the time of presentation. Postmortem analysis by polymerase chain reaction revealed the presence of both HTLV‐I and HIV‐1 in lymphatic tissues and the testes; HIV‐1 was also detected in brain tissue.
Comparison of arbitrarily primed-polymerase chain reaction and plasmid profiles typing of Pseudomonas aeruginosa strains from burn patients and hospital environment.

OBJECTIVE To identify the strengths and weakness of arbitrary primed-polymerase chain reaction (AP-PCR) and plasmid profiles for typing of Pseudomonas aeruginosa (P. aeruginosa) and tracking of source of infections. METHODS Seventy-four strains of P. aeruginosa were isolated from burn patients and hospital environment between January to April 2003 in Ghotbadden Burn Hospital, Shiraz, Iran. The strains were classified by photo Capt Mw program, similarity and clustering of strains were assessed using NTSYS-PC version 2.02K software. RESULTS Based on 50% and 64.7% and 67.5% similarity on the plotted dendrogram, 38 plasmid profiles were classified into: 2, 3 and 5 clusters, respectively. Photo Capt Mw program categorized AP-PCR products to 47 different types of 6 to 12 bands between 0.376 to 3.7 kb. Based on dendrogram pattern 3 levels (62 %, 81% and 84.6%) of similarity were selected. Using these criteria 2, 5 and 11 clusters were obtained, respectively. CONCLUSION As compared with plasmid profiles, AP-PCR analysis protocol is rapid, reproducible and differentiated the isolates with higher discrimination power. These results suggest that during admission of patients in burn center a limited number of common strains cross-contaminate burn victims. However, transmissions of infection from hospital environment to patients also occur in the minority of the victims. To control cross-contamination of the patient wounds with antibiotics resistant isolates, strong disinfection of patients' bathroom after scrubbing of each patient wounds is mandatory.
Weight Change and the Risk of Total Hip Replacement

Background: We examined the effect of adult weight change on risk for total hip replacement resulting from primary osteoarthritis, using a prospective study design. Methods: We linked data on body mass index and body weight from 3 screening surveys in 3 Norwegian counties (mean ages at screenings 34, 43, and 47 y; n = 38,868) with follow-up data on total hip replacement (n = 572). Mean age at the start of follow up was 55 years, and mean duration of follow up was 9 years. For each participant we calculated a rate of weight change (weight slope) by linear regression of body weight versus time from the first through the third screening. Results: Among men, mean weight change from first to last screening was +9.8 kg in the highest quartile and −3.7 kg in the lowest quartile. In women, the corresponding figures were +9.5 kg in the highest quartile and −5.2 kg in the lowest quartile. There was no association of weight slope, absolute weight change, or relative weight change between screenings with later total hip replacement resulting from primary osteoarthritis. We saw no change in the association between body mass index and later hip arthroplasty as the participants’ age increased from 34 to 47 years at the 3 screenings. Conclusion: The risk for later total hip replacement resulting from primary osteoarthritis was unaffected by weight change during the fourth and fifth decades of life. The dose-response association between adult body mass index and later total hip replacement was similar across these age groups.