Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute and long‐term effects of MK‐801 on direct cortical input evoked homosynaptic and heterosynaptic plasticity in the CA1 region of the female rat

We analysed acute and long‐term effects of the N‐methyl‐d‐aspartate receptor antagonist MK‐801 on long‐term heterosynaptic population spike depression (LTHPSD) evoked by high‐frequency stimulation of the direct cortical input in female rat hippocampal slices to understand disturbances in cognitive functions associated with an acute phencyclidine‐induced psychosis. High‐frequency stimulation (HFS) of the direct cortical input (dCI) to cornu ammonis area 1 (CA1) induced homosynaptic long‐term potentiation (LTP) while simultaneously evoking LTHPSD at the Schaffer collateral input. Animals treated with a single intraperitoneal application of MK‐801 (5 mg/kg body weight) showed severe behavioural alterations for 24 h, although histological examination of CA1 did not reveal any morphological changes. However, after application of MK‐801, homosynaptic LTP of the dCI was suppressed for up to 7 days and recovered within 4 weeks. Likewise, LTHPSD in response to HFS of the dCI to CA1 was abolished for at least 1 week post‐treatment, with partial recovery occurring after 4 weeks. Homosynaptic LTP, induced by HFS of Schaffer collaterals, was also disturbed for at least 24 h, with recovery after 7 days. Remarkably, bath application of MK‐801 (50 µm) converted LTHPSD, induced by dCI HFS, into persistent heterosynaptic long‐term enhancement of stratum radiatum‐evoked responses. The acute effects of MK‐801 on synaptic plasticity seen in this study may contribute to the observed severe behavioural alterations and long‐term effects and may explain some of the long‐lasting symptoms remaining after an acute psychotic episode in humans.
Cigarette smoking and adenomatous polyps: a meta-analysis.

BACKGROUND & AIMS Through the past 2 decades, a consistent association between cigarette smoking and colorectal adenomatous polyps, recognized precursor lesions of colorectal cancer, has been shown. We performed a meta-analysis to provide a quantitative pooled risk estimate of the association, focusing on the different characteristics of the study populations, study designs, and clinical feature of the polyps. METHODS We performed a comprehensive literature search of studies linking cigarette smoking and adenomas. We used random effects models to evaluate pooled relative risks and performed dose-response, heterogeneity, publication bias, and sensitivity analyses. RESULTS Forty-two independent observational studies were included in the analysis. The pooled risk estimates for current, former, and ever smokers in comparison with never smokers were 2.14 (95% confidence interval [CI], 1.86-2.46), 1.47 (95% CI, 1.29-1.67), and 1.82 (95% CI, 1.65-2.00), respectively. The association was stronger for high-risk adenomas than for low-risk adenomas. Studies in which all controls underwent full colonoscopy showed a higher risk compared with studies in which some or all controls underwent partial colon examination. CONCLUSIONS This meta-analysis provides strong evidence of the detrimental effect of cigarette smoking on the development of adenomatous polyps. Smoking is important for both formation and aggressiveness of adenomas.
Incidence of uveal melanoma in Sweden from 1960 to 1998.

PURPOSE To investigate the incidence of uveal melanoma in Sweden during the period from 1960 to 1998, with respect to age distribution, gender, and changes in incidence over time. METHODS The Swedish Cancer Registry was searched for patients with uveal melanoma and cross-checked against hospital files over patients where an eye-sparing treatment had been applied, to ensure inclusion in the Registry even when no histologic specimen was available. The crude and age-standardized incidence was estimated separately for each gender. The Swedish population of 1970 to 1974 was used as a standard, and the annual change in incidence was calculated by using a regression model with logarithmic incidence numbers. RESULTS In total, 2997 patients met the criteria, of whom 1542 were males and 1455 females. During the 39-year period, the age-standardized incidence of uveal melanoma declined significantly in the male population, from 11.7 cases/million to 8.4 cases/million (P = 0.002). The trend toward reduced incidence in females, from 10.3 to 8.7 cases/million did not reach statistical significance (P = 0.108). The annual relative change in incidence was 1% (95% CI, 0.8%-1.2%) in males and 0.7% (95% CI, 0%-1.3%) in females. The age-specific incidence revealed a significantly higher incidence among men older than 45 years (23.5 cases/million) compared with the incidence in women of the same age group (19.2 cases/million; P < 0.001). CONCLUSIONS A Swedish national survey performed to establish the incidence of uveal melanoma during the period from 1960 to 1998 revealed a decreasing incidence in the male and a stable incidence in the female population.
Gastric emptying and postprandial glucose excursions in adolescents with type 1 diabetes

Abstract: Because amylin is co‐secreted with insulin from beta cells, patients with type 1 diabetes (T1DM) are deficient in both insulin and amylin. Amylin delays gastric emptying and suppresses glucagon in the postprandial period. Hence, we hypothesized that children with complication‐naive T1DM have accelerated gastric emptying in response to a mixed meal because of amylin deficiency. Amylin, glucagon, insulin, glucose, and gastric emptying were measured in seven T1DM and in eight control subjects without diabetes. Subjects with T1DM had markedly elevated glucose concentrations when compared with controls (p < 0.0001). Amylin concentrations as predicted were lower in T1DM compared with those in controls (p < 0.0001). Insulin did not peak in the immediate postprandial period in T1DM when compared with controls (p < 0.0001). Glucagon concentrations did not significantly differ between groups. Interestingly, gastric velocity was delayed in patients with T1DM compared with controls (p < 0.01). In conclusion, subjects with T1DM do have amylin deficiency but this is not associated with accelerated gastric emptying as we had hypothesized but rather with delayed gastric emptying. Factors other than amylin play a role in control of gastric motility in T1DM. Subcutaneous insulin delivery fails to reach adequate concentrations in the postprandial period to curtail peak glucose concentration in T1DM.
Interscalene regional anesthesia for shoulder surgery.

BACKGROUND Despite a trend toward the use of regional anesthesia for orthopaedic procedures, there has been resistance to the use of interscalene regional block for shoulder surgery because of concerns about failed blocks and potential complications. METHODS We retrospectively reviewed the cases of 568 consecutive patients who had shoulder surgery under interscalene regional block in a tertiary-care, university-based practice with an anesthesiology residency program. The blocks were performed by a group of anesthesiologists who were dedicated to the concept of regional anesthesia in their practice. Complete anesthetic and orthopaedic records were available for 547 patients. The surgical procedure, planned type of anesthesia, occurrence of block failure, and the presence of complications were noted. RESULTS Of the 547 patients, 295 underwent an arthroscopic procedure and 252 (including eighty who had an arthroplasty) underwent an open procedure. General anesthesia was the initial planned choice for sixty-nine patients because of the complexity or duration of the procedure, the anatomic location, or patient insistence. Thirty-four of the sixty-nine patients also received an interscalene regional block. Interscalene regional block alone was planned for 478 patients. A total of 462 patients (97%) had a successful block whereas sixteen required general anesthesia because the block was inadequate. The success of the block was independent of the type or length of the surgery. No patient had a seizure, pneumothorax, cardiac event, or other major complication. Twelve (2.3%) of the 512 patients who had a block had minor complications, which included sensory neuropathy in eleven patients and a complex regional pain syndrome that resolved at three months in one patient. For ten of the eleven patients, the neuropathy had resolved by six months. CONCLUSIONS Interscalene regional block provides effective anesthesia for most types of shoulder surgery, including arthroplasty and fracture fixation. When administered by an anesthesiologist committed to and skilled in the technique, the block has an excellent rate of success and is associated with a relatively low complication rate.
Teaching parents advanced clinical skills

The management of haemophilia, in common with many other inherited, chronic disorders, has witnessed enormous advances and improvements. The quality of life enjoyed by children with haemophilia is excellent. To realize these benefits, however, expectations are placed on parents to administer intravenous treatment at home. The frequency of required treatment can be as often as alternate days.
Quantitative imaging of green fluorescent protein in cultured cells: Comparison of microscopic techniques, use in fusion proteins and detection limits

To determine the application limits of green fluorescent protein (GFP) as a reporter gene or protein tag, we expressed GFP by itself and with fusion protein partners, and used three different imaging methods to identify GFP fluorescence. In conventional epifluorescence photomicroscopy, GFP expressed in cells could be distinguished as a bright green signal over a yellow‐green autofluorescence background. In quantitative fluorescence microscopy, however, the GFP signal is contaminated by cellular autofluorescence. Improved separation of GFP signal from HeLa cell autofluorescence was achieved by the combination of confocal scanning laser microscopy using 488‐nm excitation, a rapid cut‐on dichroic mirror and a narrow‐bandpass emission filter. Two‐photon excitation of GFP fluorescence at the equivalent of ≅ 390 nm provided better absorption than did 488‐nm excitation. This resulted in increased signal/background but also generated a different autofluorescence pattern and appeared to increase GFP photobleaching. Fluorescence spectra similar to those of GFP alone were observed when GFP was expressed as a fusion protein either with glutathione‐S‐transferase (GST) or with glucokinase. Furthermore, purified GST•GFP fusion protein displayed an extinction coefficient and quantum yield consistent with values previously reported for GFP alone. In HeLa cells, the cytoplasmic GFP concentration must be greater than ≅ 1 μM to allow quantifiable discrimination over autofluorescence. However, lower expression levels may be detectable if GFP is targeted to discrete subcellular compartments, such as the plasma membrane, organelles or nucleus.
Purification and Characterization of the AAA+ Domain of Sinorhizobium meliloti DctD, a σ54-Dependent Transcriptional Activator

ABSTRACT Activators of σ54-RNA polymerase holoenzyme couple ATP hydrolysis to formation of an open complex between the promoter and RNA polymerase. These activators are modular, consisting of an N-terminal regulatory domain, a C-terminal DNA-binding domain, and a central activation domain belonging to the AAA+ superfamily of ATPases. The AAA+ domain of Sinorhizobium meliloti C4-dicarboxylic acid transport protein D (DctD) is sufficient to activate transcription. Deletion analysis of the 3′ end of dctD identified the minimal functional C-terminal boundary of the AAA+ domain of DctD as being located between Gly-381 and Ala-384. Histidine-tagged versions of the DctD AAA+ domain were purified and characterized. The DctD AAA+ domain was significantly more soluble than DctD( Δ 1-142), a truncated DctD protein consisting of the AAA+ and DNA-binding domains. In addition, the DctD AAA+ domain was more homogeneous than DctD( Δ 1-142) when analyzed by native gel electrophoresis, migrating predominantly as a single high-molecular-weight species, while DctD( Δ 1-142) displayed multiple species. The DctD AAA+ domain, but not DctD( Δ 1-142), formed a stable complex with σ54 in the presence of the ATP transition state analogue ADP-aluminum fluoride. The DctD AAA+ domain activated transcription in vitro, but many of the transcripts appeared to terminate prematurely, suggesting that the DctD AAA+ domain interfered with transcription elongation. Thus, the DNA-binding domain of DctD appears to have roles in controlling the oligomerization of the AAA+ domain and modulating interactions with σ54 in addition to its role in recognition of upstream activation sequences.
Surgical management of endoscopically unresectable duodenal gangliocytic paraganglioma in a patient with partial upper gastrointestinal obstruction

Context: Gangliocytic paragangliomas are unusual and often misunderstood tumors that occur almost exclusively in the second portion of the duodenum, although they have been described in other sites such as the urinary bladder, spermatic cord, prostate, urethra, uterus and scalp. We describe our experience with the surgical management of an endoscopically unresectable gangliocytic paraganglioma located in the third part of the duodenum causing a partial upper gastrointestinal obstruction. Case Report: A fifty-two-year-old male presented to the Geisinger clinic with a four-year history of postprandial projectile vomiting associated with epigastric discomfort. Computed tomography scan revealed an oval-shaped filling defect in the third part of the duodenum. Endoscopic ultrasonography showed a 22 × 16 × 35 mm submucosal mass that was not amenable to an endoscopic resection. Exploratory laparotomy revealed an absence of extraduodenal involvement. A long-stalked tumor was successfully excised and extruded through a longitudinal duodenotomy. The pathology report showed a gangliocytic paraganglioma with negative lymph nodes. Conclusions: In patients presenting with prolonged recurrent attacks of vomiting, diagnostic workup to exclude anatomic causes is mandatory. Gangliocytic paraganglioma must be considered in the differential diagnosis of an intraduodenal tumor.
Plasma proinsulin in first-degree relatives of type 2 diabetic subjects.

Glucose intolerant relatives of Type 2 diabetic subjects have impaired insulin secretory responses to glucose but their proinsulin secretion has not been assessed. Plasma intact proinsulin was measured in 101 normoglycaemic and glucose intolerant first-degree relatives of Type 2 diabetic subjects both fasting and one hour after an infusion of glucose of 5 mg glucose.kg ideal weight.min-1. Geometric mean (+/- SD) plasma proinsulin increased from 2.4 (+2.5-1.2) and increased to 4.5 (+4.2-2.1) pmol/l at 1 hour (p less than 0.001). Linear regression revealed no relationship of fasting or achieved proinsulin with sex or obesity and a non-significant trend towards increasing fasting and achieved proinsulin with age and fasting plasma glucose. Proinsulin was assessed as a ratio to the simultaneous plasma C-peptide to estimate the relative amounts of insulin and proinsulin secreted by the beta-cells. Analysis of partial correlation coefficients, controlling for age and obesity, showed that the Achieved Proinsulin/Achieved C-peptide ratio was related to both fasting (r = 0.27, p = 0.004) and achieved plasma glucose (r = 0.25, p = 0.008). Glucose intolerant relatives (n = 37) had a small but significant increase in relative proinsulin secretion compared with normoglycaemic relatives (n = 64) (Achieved Proinsulin/Achieved C-peptide 0.07 +/- 0.05 vs 0.04 +/- 0.02 p less than 0.01). This is in accord with abnormal beta cell function being an early feature of Type 2 diabetes but does not distinguish between a primary beta-cell abnormality and a secondary effect of mild hyperglycaemia.
Hypothermia Does Not Alter Somatosensory Evoked Potential Amplitude and Global Cerebral Oxygen Extraction during Marked Sodium Nitroprusside–induced Arterial Hypotension

Background To prevent neurologic damage, monitoring cerebral function by somatosensory evoked potentials is used in selected settings. Excision of intraocular melanoma provides a unique opportunity to assess independently during anesthesia the effects on median nerve somatosensory evoked potentials (MN-SSEPs) and cerebral oxygen extraction of sodium nitroprusside–evoked arterial hypotension with and without hypothermia. Methods Median nerve somatosensory evoked potentials, arterial pressure, jugular venous bulb oxygen saturation (Sjo2) and lactate concentration, and arterial–jugular bulb oxygen content difference were assessed during propofol–remifentanil anesthesia under sodium nitroprusside–evoked arterial hypotension (mean arterial pressure, 40 mmHg) with and without surface hypothermia (32°C) in 11 otherwise healthy patients undergoing resection of choroidal melanoma. Results Hypothermia alone did not affect peak-to-peak amplitude of N20/P25 but prolonged cortical latency of N20 (22.6 ± 2.2 vs. 25.9 ± 2.5 ms, P < 0.05), cervical latency of N13 (14.3 ± 1.2 vs. 15.7 ± 1.6 ms, P < 0.05), and central conduction time (8.3 ± 1.4 vs. 10.2 ± 1.6 ms, P < 0.05). Evoked arterial hypotension did not depress MN-SSEP N20/P25 amplitude either with or without hypothermia (−0.31 vs. −0.28 &mgr;V, P > 0.05) or alter latency (0.08 vs. 0.1 ms, P > 0.05). Furthermore, hypotension with or without hypothermia did not change Sjo2, arterial–jugular bulb oxygen content difference, or lactate concentration. Conclusions Thus, hypothermia to 32°C does not alter MN-SSEP amplitude and global cerebral oxygen extraction during marked sodium nitroprusside–induced arterial hypotension with a mean arterial pressure of 40 mmHg but prolongs MN-SSEP latencies during propofol–remifentanil anesthesia in individuals without cerebrovascular disease.
Beyond rose colored glasses: the adaptive role of depressive and anxious symptoms among individuals with heart failure who were evaluated for transplantation

The prospect of and the evaluative period for transplantation can be stressful for individuals with heart failure (HF). Little is known about the impact of psychosocial factors on service utilization and health outcomes. The current study examined the impact of depression, dysthymia, and anxiety on two‐yr hospitalization and mortality among 96 individuals with HF who were evaluated for transplantation. Results revealed that only a small percentage of individuals endorsed sufficient symptomatology to meet criteria for a psychiatric, Axis I disorder (3.1% = anxiety; 2.1% = depression; 1.0% = dysthymia) although a significant proportion of the sample was prescribed an antidepressant or an anxiolytic (37%). Multivariable regression analysis was conducted to examine the association between significant independent demographic, medical, and psychiatric predictors and total duration of hospitalizations; logistic regression analysis was used to examine the relation between predictors and mortality. An increase in anxious symptoms was associated with a decrease in total number of days hospitalized during the two‐yr period following the initial evaluation. Similarly, as depressive symptoms increased, risk of two‐yr mortality decreased. Future research should assess communication between the patient and providers to further elucidate the potential relationship between psychiatric symptoms, service utilization/hospitalization, and mortality in this patient population.
Developing nomogram to estimate birth weight from head circumference and mid-upper arm circumference.

BACKGROUND Despite the huge proportion of the babies in the developing world being born low birthweight, only about half of the newborns are weighed at birth as weighing scales often tend to be either non-available or defective. OBJECTIVE Designing a nomogram for estimation of birthweight from head circumference (HC) and mid-upper arm circumference (MUAC). METHOD Birthweight, HC and MUAC of 500 newborns who were admitted in the baby nursery of Medical College and Hospital, Kolkata between July 2010 to December 2010 were measured. RESULTS Multiple linear regression equation for prediction of birth weight from MUAC and HC was derived and a nomogram was constructed from the same. CONCLUSION The birthweight estimation nomogram is an inexpensive and convenient tool for use in the community setting where weighing machines may not be always available and may thus allow prompt and early referral.
Stroke rehabilitation information for clients and families: Assessing the quality of the StrokEngine-Family website

Purpose. This study: (i) Identified the availability of scientifically-based information on the internet regarding stroke rehabilitation intended for those who have experienced a stroke and their families; and, (ii) assessed the usability of a newly created website on stroke rehabilitation for laypersons, StrokEngine-Family. Method. First, an extensive systematic search was undertaken to identify and appraise existing stroke rehabilitation websites. Seventeen websites met specific inclusion/exclusion criteria. Although some addressed stroke rehabilitation interventions in layperson language, none discussed the numerous treatment options based on scientifically based information. Thus, StrokEngine-Family was developed and its usability assessed with individuals who had experienced a stroke and family members. Results. Seven respondents aged 43 – 68 years participated in the pilot testing of the newly developed StrokEngine-Family. All except one indicated overall satisfaction with the website: The one respondent rated it as somewhat user-friendly mainly for aesthetic reasons including the need for darker colors and larger font. In addition, respondents requested specific information regarding emotional support and local community referrals to this type of support. Based on the feedback, minor changes were made including a greater use of short phrases, bulleted notations and the addition of a depression module. Conclusions. The systematic review provided support for the development of StrokEngine-Family. In pilot testing, StrokEngine-Family was easy to use and valuable in content.
Effects of estrogen depletion on angiogenesis in estrogen-receptor-positive breast carcinoma – an immunohistochemical study of vasohibin-1 and CD31 with correlation to pathobiological response of the patients in neoadjuvant aromatase inhibitor therapy

Objectives: Tumor–stroma interactions, including angiogenesis, are pivotal in breast cancer. Changes of angiogenesis during endocrine therapy have not been reported in breast cancer patients. Vasohibin-1 (VASH-1) is a recently identified endothelium-derived negative feedback regulator of angiogenesis. Vasohibin-1 positive ratio (VPR) is proposed as an indicator of neovascularization of the tissues. Methods: The status of neovascularization, based on VPR before and after steroidal aromatase inhibitor (AI) exemestane (EXE) treatment, was evaluated in 54 post-menopausal Asian patients. VPR changes were correlated with the pathobiological response of the patients using Ki67 labeling index (LI) changes. Results: When using a decrement of more than 40% in post-treatment Ki67 LI as the definition of response, significant inverse correlation was detected between Ki67 LI and VPR changes in responders. Significant increment in neovascularization, as demonstrated by elevated VPR, was only detected in responders (p = 0.039). Increased angiogenesis detected in responders to neoadjuvant therapy may represent a stromal response to dying/dead cells, as part of tumor–stroma interaction following estrogen depletion. Conclusions: VPR could be a potential surrogate marker for predicting neoadjuvant endocrine therapy response, incorporating features of both carcinoma and stromal cells, in the early stage of neoadjuvant endocrine therapy before any discernible clinical and/or histopathological changes became apparent.