Miracle-dz/UniFAR-FTUs huggingface dataset:
99MTc-mibi Radio-guided Surgery in Primary Hyperparathyroidism: A Prospective Study of 128 Patients

Aims and study design We investigated the role of an intraoperative gamma probe (IGP) technique in 128 patients with primary hyperparathyroidism (HPT). The patients were evaluated before surgery by 99mTcO4/MIBI scintigraphy and neck ultrasound and then operated on by the same surgical team. The IGP technique consisted of the injection of a low dose (37 MBq) of 99mTc-MIBI in the operating room shortly before the start of surgery. Quick parathyroid hormone (QPTH) was routinely measured during the operation. Results In 94/97 patients (96.9%) with a preoperative diagnosis of solitary parathyroid adenoma (PA) minimally invasive radioguided surgery (MIRS) was successfully performed; in the other 3/97 patients (3.1%) conversion to bilateral neck exploration (BNE) was required because of the intraoperative diagnosis of parathyroid carcinoma in two cases and multiglandular disease (MGD) in one. MIRS was successfully performed also in 23 patients who had undergone previous thyroid or parathyroid surgery. In 31 patients with a preoperative diagnosis of MGD (n = 5) or concomitant nodular goiter (n = 26) the IGP technique was used during a bilateral neck exploration. Among these patients IGP was useful in localizing an ectopic parathyroid gland in the thymus in one case of MGD and a PA located deep in the neck (n = 2) or ectopic at the carotid bifurcation (n = 1) in three cases with nodular goiter. However, in several other patients with nodular goiter it was difficult for the probe to distinguish intraoperatively between thyroid nodules and PA located close to the thyroid gland. Conclusions It can be concluded that a) in primary HPT patients with a high likelihood (according to scintigraphic and ultrasound findings) of being affected by a single PA and with a normal thyroid gland, the IGP technique appears useful in MIRS; b) a 99mTc-MIBI dose as low as 37 MBq appears to be adequate to perform MIRS; c) the measurement of QPTH is strongly recommended in HPT patients selected for MIRS to confirm the radicality of parathyroidectomy; d) MIRS can be useful also in HPT patients who underwent previous parathyroid or thyroid surgery to limit the surgical trauma of reoperation and minimize complications; e) with the exception of PAs located at ectopic sites or deep in the neck, the IGP technique does not seem to be recommendable in HPT patients with concomitant nodular goiter.
Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects

Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation. Male Wistar rats were subjected to forced swimming test and given N-acetylcysteine and fluoxetine immediately after the pre-test session, 5 h later and 1 h before the test session of the forced swimming test. N-acetylcysteine decreased immobility time (P < 0.05), serum corticosterone (P < 0.001), and hydrogen peroxide (P < 0.001), while restored glutathione concentration. Treatment of the rats with N-acetylcysteine produced significant (P < 0.001) down-regulation of STAT3 mRNA expression and protein phosphorylation. On the other hand, N-acetylcysteine significantly (P < 0.001) increased SOCS3 gene expression; however, SOCS3 protein was not changed. In conclusion, our study suggests that modulation of the JAK/STAT pathway might mediate the antidepressant-like effects of N-acetylcysteine. Therefore, depression research may target the JAK/STAT signaling pathway to provide a novel effective therapy.
The five most commonly used intact parathyroid hormone assays are useful for screening but not for diagnosing bone turnover abnormalities in CKD-5 patients.

BACKGROUND/AIMS Assessment of bone turnover for management of renal osteodystrophy is part of routine care in chronic kidney disease Stage 5 (CKD-5) patients. Measurement of intact parathyroid hormone (iPTH) is the most commonly used surrogate marker for bone turnover in these patients. The current study was conducted to evaluate the predictive value of the five most commonly used iPTH assays for bone turnover. METHODS In a cross-sectional study, 84 CKD-5 patients underwent bone biopsy and blood drawings for determination of iPTH and total serum alkaline phosphatase (AP). RESULTS Histologically, patients presented with a broad range of bone turnover abnormalities as determined by activation frequency and bone formation rate/bone surface. Results of the five iPTH assays in each patient correlated but were significantly different. There were also significant differences between iPTH measurements at the same bone turnover level. Using Kidney Disease Outcome Quality Initiative recommended iPTH ranges, all assays showed comparably poor diagnostic performance. At 80% specificity, cut-off values of the 5 iPTH assays for low bone turnover varied from 165 to 550 pg/ml and for high bone turnover from 404 to 1,003 pg/ml. Sensitivities at these cutoffs remained below acceptable standards. Addition of AP measurements to iPTH did not improve diagnostic accuracy. CONCLUSIONS Precise assessment of bone turnover will require utilization of established and novel bone markers reflecting effects of bone turnover rather than measuring only iPTH or other effectors.
Factors associated with chronic renal failure in HIV-infected ambulatory patients

Objective: Renal disease is an increasingly common manifestation among HIV-positive persons, particularly during late stages of HIV disease. We performed a cohort-based, nested case–control study to examine the role of several factors in developing HIV-related chronic renal disease, including HIV viral load and CD4+ cell count. Design: Incident cases of chronic renal disease were identified from a cohort of 6361 prospectively followed HIV-1 positive persons. Controls were selected using incidence density sampling and matched 4 : 1 on age, race/ethnicity, and gender. Methods: Odds ratios (OR) and 95% confidence intervals (CI) were obtained using conditional logistic regression. Results: One hundred and eight cases of chronic renal disease were identified; 80 (74.1%) were eligible for the current analysis. Nadir CD4+ cell count < 200 × 106 cells/l (OR = 4.3; 95% CI, 2.1–8.7), highly active antiretroviral therapy (HAART) use for 56 days or more (OR = 0.5; 95% CI, 0.3–1.0), and hypertension [treated with angiotensin-converting enzyme (ACE) inhibitors: OR = 4.6; 95% CI, 1.8–11.6; treated with non-ACE inhibitors: OR = 2.5; 95% CI, 1.0–6.2; not treated: OR = 4.2; 95% CI, 0.8–21.6] were associated with disease. HAART use for 56 days or more modified the associations for nadir CD4+ cell count and hypertension. Conclusions: Our findings suggest that advanced HIV-disease, as indicated by low CD4+ cell count, is associated with subsequently developing chronic renal disease and treatment with HAART may reduce the risk of developing chronic renal disease.
Clinicohistological pattern of ovarian tumours in Peshawar region.

BACKGROUND Ovarian tumours are one of the major health problems confronting the general practitioners in general and gynaecologists in particular. Ovarian tumours may either be asymptomatic, found on the routine ultrasound examination or symptoms may be vague till the patient has an acute emergency like torsion or rupture of a benign cyst. The worst is late presentation of a malignant ovarian tumour. There is marked variation in the presentation of the tumour as well as in histological types. This study was undertaken to analyse modes of presentation and various histopathological patterns of ovarian tumours. METHODS This study was conducted from 1st January, 2002 to 31st December, 2002, in Gynaecology 'A' Unit, Lady Reading Hospital (LRH) Peshawar. After admitting patients with ovarian tumours a detailed case history was taken followed by thorough clinical examination. All the relevant details were recorded using the questionnaire. Patients were investigated after performing various surgical procedures; the specimens of ovarian tumours were subjected to Histopathological examination in the histopathology section, Lady Reading Hospital, Peshawar. RESULTS Amongst the total numbers of 5732 gynaecological admissions during study period the total numbers of ovarian tumours were sixty-eight. Out of which benign ovarian tumours were 61 (89.71%) and malignant ovarian tumours were 7 (10.29%) There were no tumours with borderline malignancy. The commonest histological pattern observed in the study was epithelial tumours (76.5%) including both benign and malignant tumours. The commonest benign tumour was serous cyst adenoma (24%) followed by mature cystic teratoma (18%). Common malignant ovarian tumours were granulosa cell tumours and Endometriod carcinoma (each 28.5%). CONCLUSION Epithelial tumours are the commonest variety of ovarian tumours followed by Germ cell tumours. The histological type of ovarian tumour correlates with the prognosis of the tumour.
Replication control of plasmid pLS1: efficient regulation of plasmid copy number is exerted by the combined action of two plasmid components, CopG and RNA II

Two elements, the products of genes copG and rnall, are involved in the copy‐number control of plasmid pLS1. RNA II is synthesized in a dosage‐dependent manner. Mutations in both components have been characterized. To determine the regulatory role of the two genes, we have cloned copG, rnall or both elements at various gene dosages into pLS1‐compatible plasmids. Assays of incompatibility towards wild‐type or mutant pLS1 plasmids showed that: (i) the rnall gene product, rather than the DNA sequence encoding it, is responsible for the incompatibility, and (ii) CopG and RNA II act in trans and are able to correct up fluctuations in pLS1 copy number. A correlation between the gene dosage at which the regulatory elements were supplied and the incompatibility effect on the resident plasmid was observed. The entire copG‐rnall circuit has a synergistic effect when compared with any of its components in the correction of pLS1 copy‐number fluctuations, indicating that, in the homoplasmid steady‐state situation, the control of pLS1 replication is exerted by the co‐ordinate action of CopG and RNA II.
Murine Double Minute Clone 2 309T/G and 285G/C Promoter Single Nucleotide Polymorphism as a Risk Factor for Breast Cancer: A Polish Experience

Background Breast cancer is a multifactorial disease caused by complex interactions between genetic and environmental factors. Recently, a functional polymorphism, MDM2 285G>C (rs117039649), has been discovered. This polymorphism antagonizes the effect of the 309T>G (rs2279744) polymorphism on the same gene, resulting in decreased MDM2 transcription. Methods The MDM2 285G>C and 309T>G polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis in women with breast cancer (n=468) and controls (n=550). Results The odds ratio (OR) for breast cancer patients with the MDM2 285C/C and 285G/C genotypes was 0.4768 (95% confidence interval [CI] 0.2906–0.7824; p=0.0033, pcorr=0.0066). We also found a significantly lower frequency of the MDM2 285C allele in patients with breast cancer than in controls: the OR for the C allele in patients with breast cancer was 0.4930 (95% CI=0.3059–0.7947, p=0.0031, pcorr=0.0062). The p value of the chi-square test for the trend observed for the MDM2 285G>C polymorphism was statistically significant (ptrend=0.0036). The statistical power of this study amounted to 85% for the G/C or C/C genotypes and 85% for the C allele. However, we did not observe significant differences between the distribution of MDM2 309T>G genotypes and alleles in patients with breast cancer and healthy controls. Conclusion In a sample of the Polish population, we observed that the MDM2 285C gene variant may be a significant protective factor against breast cancer.
Cell‐mediated cytotoxicity in recovery from poxvirus infections

The availability of mutant and gene targeted knockout mice with defects in components of cellular cytotoxicity mediated by either the Fas or the exocytosis pathway permitted an analysis of their role in recovery from poxvirus infections. Ectromelia (EV), a natural mouse pathogen causing mousepox, the closely related orthopoxviruses cow pox (CPV) and vaccinia virus (VV), each encode serpins that inhibit Fas mediated apoptosis and lysis of target cells. Nevertheless, distinct differences were seen when the three viruses were inoculated into perforin‐;deficient mice: highly resistant C57Bl/6 mice became susceptible to low doses of EV; resistance to CPV increased whereas there was no effect on VV infections. Absence of the cytolytic granule associated granzymes (gzm) A and B rendered C57Bl/6 mice increasingly more susceptible to EV infections. Lack of both gzms rendered them as susceptible as perforin deficient mice, despite the presence of functionally active perforin. Elevated EV titres in liver and spleen of gzmA×B deficient mice, early after infection and before cytotoxic T cells were detectable, strongly suggests that these two gzms exert an antiviral effect by a mechanism distinct from effector molecules of NK and cytotoxic T cells. Copyright © 2003 John Wiley & Sons, Ltd.
Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons

1 Simultaneous whole‐cell voltage and Ca2+ fluorescence measurements were made from the distal apical dendrites and the soma of thick tufted pyramidal neurons in layer 5 of 4‐week‐old (P28–32) rat neocortex slices to investigate whether activation of distal synaptic inputs can initiate regenerative responses in dendrites. 2 Dual whole‐cell voltage recordings from the distal apical trunk and primary tuft branches (540–940 μm distal to the soma) showed that distal synaptic stimulation (upper layer 2) evoking a subthreshold depolarization at the soma could initiate regenerative potentials in distal branches of the apical tuft which were either graded or all‐or‐none. These regenerative potentials did not propagate actively to the soma and axon. 3 Calcium fluorescence measurements along the apical dendrites indicated that the regenerative potentials were associated with a transient increase in the concentration of intracellular free calcium ([Ca2+]i) restricted to distal dendrites. 4 Cadmium added to the bath solution blocked both the all‐or‐none dendritic regenerative potentials and local dendritic [Ca2+]i transients evoked by distal dendritic current injection. Thus, the regenerative potentials in distal dendrites represent local Ca2+ action potentials. 5 Initiation of distal Ca2+ action potentials by a synaptic stimulus required coactivation of AMPA‐ and NMDA‐type glutamate receptor channels. 6 It is concluded that in neocortical layer 5 pyramidal neurons of P28–32 animals glutamatergic synaptic inputs to the distal apical dendrites can be amplified via local Ca2+ action potentials which do not reach threshold for axonal AP initiation. As amplification of distal excitatory synaptic input is associated with a localized increase in [Ca2+]i these Ca2+ action potentials could control the synaptic efficacy of the distal cortico‐cortical inputs to layer 5 pyramidal neurons.
Long-term Outcomes After Ulnar Collateral Ligament Reconstruction in Competitive Baseball Players

Background: Ulnar collateral ligament reconstruction (UCLR) has afforded baseball players with excellent results; however, previous studies have described only short-term outcomes. Purpose: To evaluate long-term outcomes after UCLR in baseball players. Study Design: Case series; Level of evidence, 4. Methods: All UCLRs performed on competitive baseball players with a minimum 10-year follow-up were identified. Surgical data were collected prospectively and patients were surveyed by telephone follow-up, during which scoring systems were used to assess baseball career and post–baseball career outcomes. Results: Of 313 patients, 256 (82%) were contacted at an average of 12.6 years; 83% of these baseball players (90% pitchers) were able to return to the same or higher level of competition in less than 1 year, but results varied according to preoperative level of play. Baseball career longevity was 3.6 years in general and 2.9 years at the same or higher level of play, but major and minor league players returned for longer than did collegiate and high school players after surgery (P < .001). Baseball retirement typically occurred for reasons other than elbow problems (86%). Many players had shoulder problems (34%) or surgery (25%) during their baseball career, and these occurrences most often resulted in retirement attributable to shoulder problems (P < .001). For post–baseball career outcomes, 92% of patients were able to throw without pain, and 98% were still able to participate in throwing at least on a recreational level. The 10-year minimum follow-up scores (mean ± standard deviation) for the Disabilities of the Arm, Shoulder and Hand (DASH), DASH work module, and DASH sports module were 0.80 ± 4.43, 1.10 ± 6.90, and 2.88 ± 11.91, respectively. Overall, 93% of patients were satisfied, with few reports of persistent elbow pain (3%) or limitation of function (5%). Conclusion: Long-term follow-up of UCLRs in baseball players indicates that most patients were satisfied, with few reports of persistent elbow pain or limitation of function. During their baseball career, most of these athletes were able to return to the same or higher level of competition in less than 1 year, with acceptable career longevity and retirement typically for reasons other than the elbow. According to a standardized disability and outcome scale, patients also had excellent results after UCLR during daily, work, and sporting activities.
Cautions on the Use of Multiple Imputation When Selecting Between Latent Categorical versus Continuous Models for Psychological Constructs

Clinical psychology researchers studying adolescents and young adults long have been interested in characterizing the latent categorical (classes/profiles) versus continuous (factors) nature of psychological syndromes. To inform this debate, researchers sometimes compare the fit of finite mixture versus factor analysis models to symptom data. This study explains and evaluates how missing data handling methods can impact results of this important model fit comparison. Via simulation, we assess three missing data-handling methods previously recommended to researchers fitting these models: multiple imputation using a saturated multivariate normal imputation model, multiple imputation using a hypothesized model, or full information maximum likelihood using the EM algorithm (FIML-EM). Results show that, under certain conditions, the method used to handle missing data can interfere with clinical psychologists' ability to accurately discriminate latent classes from continua. For instance, certain imputation methods increase the chance of selecting latent continua when latent classes truly exist. FIML-EM performed best overall. Recommendations for practice are discussed.
The management of radial scars of the breast - does core biopsy help?

PURPOSE To compare the effectiveness of fine needle aspiration cytology (FNAC) with core biopsy (CB) in the pre-operative diagnosis of radial scar (RS) of the breast. PATIENTS AND METHODS A retrospective analysis was made of all radial scars diagnosed on surgical histology over an 8-year period. Comparison was made between the results of different preoperative needle biopsy techniques and surgical histology findings. RESULTS Forty of 47 patients with a preoperative radiological diagnosis of radial scar were included in this analysis. Thirty-eight patients had impalpable lesions diagnosed on mammography and two presented with a palpable lump. FNAC (n=17) was inadequate in 47% of patients, missed two co-existing carcinomas found in this group, and gave a false positive or suspicious result for malignancy in 4 patients. CB (n=23) suggested a RS in 15 patients, but only diagnosed 4 out of 7 co-existing carcinomas found in this group. CONCLUSION CB is more accurate than FNAC in the diagnosis of RS. However, these data demonstrate that CB may offer little to assist in the management of patients with RS. In summary, this paper advocates the use of CB in any lesion with a radiological suspicion of carcinoma and diagnostic excision of all lesions thought to be typical of RS on mammography.
Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort1

Fever has a major impact on immune responses by modulating survival, proliferation, and endurance of lymphocytes. Lymphocyte persistence in turn is determined by the equilibrium between death and survival-promoting factors that regulate death receptor signaling in these cells. A potential integrator of death receptor signaling is the caspase-8 inhibitor c-FLIP, the expression of which is dynamically regulated, either rapidly induced or down-regulated. In this study, we show in activated primary human T lymphocytes that hyperthermia corresponding to fever triggered down-regulation of both c-FLIP-splicing variants, c-FLIPshort (c-FLIPS) and c-FLIPlong, with consequent sensitization to apoptosis mediated by CD95 (Fas/APO-1). The c-FLIP down-regulation and subsequent sensitization was specific for hyperthermic stress. Additionally, we show that the hyperthermia-mediated down-regulation was due to increased ubiquitination and proteasomal degradation of c-FLIPS, the stability of which we have shown to be regulated by its C-terminal splicing tail. Furthermore, the induced sensitivity to CD95 ligation was independent of heat shock protein 70, as thermotolerant cells, expressing substantially elevated levels of heat shock protein 70, were not rescued from the effect of hyperthermia-mediated c-FLIP down-regulation. Our findings indicate that fever significantly influences the rate of lymphocyte elimination through depletion of c-FLIPS. Such a general regulatory mechanism for lymphocyte removal has broad ramifications for fever-mediated regulation of immune responses.
Computational prediction and analysis of the DR6–NAPP interaction

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that involves a devastating clinical course and that lacks an effective treatment. A biochemical model for neuronal development, recently proposed by Nikolaev et al., that may also have implications for AD, hinges on a novel protein–protein interaction between the death cell receptor 6 (DR6) ectodomain and an N‐terminal fragment of amyloid precursor protein (NAPP), specifically, the growth factor‐like domain of NAPP (GFD NAPP). Given all of this, we used a pure computational work‐flow to dock a binding competent homology model of the DR6 ectodomain to a binding competent crystal structure of GFD NAPP. The DR6 homology model was built according to a template supplied by the neurotrophin p75 receptor. The best docked model was selected according to an empirical estimate of the binding affinity and represents a high quality model of probable structural accuracy, especially with respect to the residue‐level contribution of GFD NAPP. The final model was tested and verified against a variety of biophysical and theoretical data sets. Particularly, worth noting is the excellent observed agreement between the theoretically calculated DR6–GFD NAPP binding free energy and the experimental quantity. The model is used to provide a satisfying structural and energetic interpretation of DR6–GFD NAPP binding and to suggest the possibility of and a mechanism for spontaneous apoptosis. The evidence suggests that the DR6–NAPP model proposed here is of probable accuracy and that it will prove useful in future studies, modeling work, and structure‐based AD drug design. Proteins 2011. © 2010 Wiley‐Liss, Inc.