Miracle-dz/UniFAR-FTUs huggingface dataset:
U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication

Bisheteroarylpiperazines are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). We describe a novel bisheteroarylpiperazine, U-90152 [1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4-[3-(1-methyl eth yl-amino)pyridinyl]piperazine], which inhibited recombinant HIV-1 RT at a 50% inhibitory concentration (IC50) of 0.26 microM (compared with IC50s of > 440 microM for DNA polymerases alpha and delta). U-90152 blocked the replication in peripheral blood lymphocytes of 25 primary HIV-1 isolates, including variants that were highly resistant to 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine, with a mean 50% effective dose of 0.066 +/- 0.137 microM. U-90152 had low cellular cytotoxicity, causing less than 8% reduction in peripheral blood lymphocyte viability at 100 microM. In experiments assessing inhibition of the spread of HIV-1IIIB in cell cultures, U-90152 was much more effective than AZT. When approximately 500 HIV-1IIIB-infected MT-4 cells were mixed 1:1,000 with uninfected cells, 3 microM AZT delayed the evidence of rapid viral growth for 7 days. In contrast, 3 microM U-90152 totally prevented the spread of HIV-1, and death and/or dilution of the original inoculum of infected cells prevented renewed viral growth after U-90152 was removed at day 24. The combination of U-90152 and AZT, each at 0.5 microM, also totally prevented viral spread. Finally, although the RT amino acid substitutions K103N (lysine 103 to asparagine) and Y181C (tyrosine 181 to cysteine), which confer cross-resistance to several nonnucleoside inhibitors, also decrease the potency of U-90152, this drug retains significant activity against these mutant RTs in vitro (IC50s, approximately 8 microgramM).
Anatomical variation of sciatic nerve: a case report of high division and unusual anastomosis with the posterior femoral cutaneous nerve

The posterior femoral cutaneous nerve is a sensitive nerve that rises from S1-S3, usually giving off cutaneous branches for the gluteal region, perineum, the posterior region of the thigh and leg. The sciatic nerve is the largest nerve in the human body, rising from L4-S3, and divides into the tibial and common fibular nerves, innervating the muscles from the posterior compartment of the thigh. Anastomosis between the sciatic nerve and the posterior femoral cutaneous nerve is rare. During dissection of the right gluteal region on a male cadaver fixed with 10% formalin, we observed an anastomosis between both nerves, while the common fibular nerve perforated the piriformis muscle, dividing it in two muscle slips. Both nerves trajectories were within the regular pattern after this communication. Our aims were to describe this unusual case of anastomosis and perform a literature review on the variations of the sciatic nerve, while also discussing their clinical significance.
The Adaptive Response to Dietary Zinc in Mice Involves the Differential Cellular Localization and Zinc Regulation of the Zinc Transporters ZIP4 and ZIP5*

The ZIP5 gene encodes a protein closely related to ZIP4, a zinc transporter mutated in the human genetic disorder acrodermatitis enteropathica. Herein, we demonstrate that mouse ZIP5 and ZIP4 genes are co-expressed in several tissues involved in zinc homeostasis (intestine, pancreas, embryonic yolk sac). However, unlike expression of the ZIP4 gene, which is induced during periods of zinc deficiency, ZIP5 gene expression is unaltered by dietary zinc. Immunohistochemistry localizes ZIP5 to the basolateral surfaces of enterocytes, acinar cells, and visceral endoderm cells in mice fed a zinc-adequate diet. However, this protein is removed from these cell surfaces and internalized during dietary zinc deficiency. In contrast, ZIP4 is induced and recruited to the apical surface of enterocytes and endoderm cells during zinc deficiency. In the pancreas, ZIP4 is expressed in β-cells, whereas ZIP5 is expressed in acinar cells. These results suggest that the function of ZIP5 is antagonistic to that of ZIP4 in the control of zinc homeostasis; rather than functioning in the acquisition of dietary zinc, as does ZIP4, ZIP5 may function in the removal of zinc from the body. Thus, during periods when dietary zinc is replete, ZIP5 may function to remove zinc from the blood via the pancreas and intestine, the major sites of zinc excretion in mammals, whereas the acquisition of dietary zinc by intestinal ZIP4 would be minimal. In contrast, during periods of dietary zinc deficiency when secretion of zinc by the pancreas and intestine is minimized, ZIP5 is removed from the cell surface, and the intestinal uptake of zinc is augmented by induction of ZIP4.
Lack of Size‐Related Differential Sensitivity to Equilibrium Conduction Block among Mammalian Myelinated Axons Exposed to Lidocaine

This study sought to evaluate the sensitivity of individual, relatively thick myelinated axons of mammalian nerve to equilibrium conduction block by lidocaine, and to compare this to the incidence of conduction block previously measured in individual thinner myelinated axons. The incidence of conduction block by lidocaine 0.3 and 0.6 mM (8.1–16.2 mg/dl) was determined on 35 individual axons in dissected filaments of rabbit recurrent laryngeal nerve (RLN) in which the control conduction velocity ranged from 28 to 77 m/sec. Thirty-four axons (97%) remained excitable in lidocaine 0.3 mM; 2 axons (6%) remained excitable in lidocaine 0.6 mM. These proportions did not differ significantly (P > 0.2) from those in thinner axons of vagus, either in comparisons with previous data from extracellular recordings or with new data from filament recordings. The results imply that differential blocks observed under clinical conditions probably depend-on factors other than a size-related difference in the minimal equilibrium blocking concentration among myelinated axons. Equilibrium depression of the amplitude of RLN compound action potentials by lidocaine 0.3 and 0.6 mM was disproportionately great relative to the incidence of equilibrium conduction block in individual axons, confirming that depression of the compound action potential is not a reliable measure of nerve conduction block.
Malabsorption and systemic lupus erythematosus.

(Continued from p 1900.) To the Editor. —In reference to Rustgi and Peppercorn's article appearing in the July 1988 issue of theArchivesdealing with gluten-sensitive enteropathy (GSE) and systemic lupus erythematosus (SLE),1we wish to point out some inaccuracies. A MEDLINE search of the literature yields eight cases of concomitant occurrence of intestinal malabsorption with typical changes of celiac disease on intestinal biopsy and SLE2-8(Table), not four cases, as cited in Rustgi and Peppercorn's article. They seem to ignore four other cases.2-5Among these four cases, a gluten-free diet (GFD) was not tried in two,2,3and was ineffective in one5; in one case4celiaclike changes occurred in a patient with SLE and dermatitis herpetiformis (DH), without clinical aspects of malabsorption, and with normal small-bowel function (because of the high incidence of celiac disease in DH). A GFD was tried, but there is
Intratumoural chemotherapy with 5‐fluorouracil for palliation of bronchial cancer in patients with severe airway obstruction

Patients with tracheal or major airway obstruction owing to inoperable carcinomas are at risk of developing respiratory failure or postobstructive pneumonia. In such cases, there is an urgency to restore the airway. Bronchoscopic interventional procedures for palliation of malignant airway obstruction are becoming more common in clinical practice. However, as current interventional methods may be unavailable or are contraindicated, we have investigated the use of direct intratumoural injection with 5‐fluorouracil for tumour regression to open the airway. In this study, 65 patients who presented with greater than 50% obstruction of at least one major airway were treated with 5‐fluorouracil injection directly into the endobronchial tumour or area of infiltrated bronchial mucosa through a flexible fiber‐optic bronchoscope. The pretreatment luminal opening for this cohort of 65 patients ranged from 0% (totally obstructed) to 40%, with an overall mean luminal opening of 22% (78% occlusion). There was a positive response to intratumoural injection in 56 of 65 patients, and a large reduction in the size of tumours by endoscopic evaluation in the majority of cases. Overall, the mean pretreatment luminal opening of 22.0% was significantly improved to a mean post‐treatment luminal opening of 58.5%, an increase in the opening of the airways of 36.5%. The increase in the diameter of the airway lumen was more than 50% for 34 of 65 patients, and 23 showed a 25–50% improvement. The results were of obvious immediate clinical benefit. Statistical analysis of all patient data by a Wilcoxon matched‐pairs/sign‐ranked test confirmed the significant benefit achieved (P < 0.001). The therapy was well tolerated, with no systemic side‐effects or any serious complications. The results of this study suggest that in patients with life‐threatening airway obstruction, intratumoural injection of anticancer drugs should be regarded as an important new therapeutic approach and an integral part of interventional bronchoscopic management. This study further encourages more general consideration of intratumoural drug injection as a minimally invasive therapeutic method for the treatment of lung cancer and various inoperable cancers.
Interleukin‐1β: a bridge between inflammation and excitotoxicity?

Interleukin‐1 (IL‐1) is a proinflammatory cytokine released by many cell types that acts in both an autocrine and/or paracrine fashion. While IL‐1 is best described as an important mediator of the peripheral immune response during infection and inflammation, increasing evidence implicates IL‐1 signaling in the pathogenesis of several neurological disorders. The biochemical pathway(s) by which this cytokine contributes to brain injury remain(s) largely unidentified. Herein, we review the evidence that demonstrates the contribution of IL‐1β to the pathogenesis of both acute and chronic neurological disorders. Further, we highlight data that leads us to propose IL‐1β as the missing mechanistic link between a potential beneficial inflammatory response and detrimental glutamate excitotoxicity.
High prevalence of male infertility in southeastern Nigeria

Three hundred and fourteen Nigerian couples were evaluated thoroughly for the cause of their infertility in our clinics located at Nnewi and Awka in Southeastern Nigeria. Two hundred and four (65.0%) of them had primary infertility and 110 (35%) had secondary infertility. The median duration of the infertility was 5 years and majority of the female patients (67.2%) were aged between 25 and 34 years. A positive male factor alone was found in 133 (42.4%) couples and female factor alone in 81 (25.8%) couples (P < 0.01). Sixty-five (20.7%) couples had a combination of male and female factors, while the cause of infertility was unexplained in 35 (11.1%) couples. Oligozoospermia (35.9%) and asthenozoospermia (32.3%) were the most common aetiological factors responsible for male infertility. Tubual occlusion (49.0%) was the most common cause of female infertility. Genital tract infection resulting from sexual promiscuity and poorly treated sexual transmitted diseases were responsible for these abnormalities. In this part of the world, the wife is commonly blamed whenever there is infertility. However, this study has revealed the greater contribution of male factors to infertility. More attention should be paid to male partners whenever a couple presents for infertility. Men should also be a major target of any intervention aim at prevention.
Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men.

BACKGROUND Skeletal muscle fat infiltration (myosteatosis) increases with aging, and has been associated with poor metabolic and musculoskeletal health, independent of overall adiposity. Studies examining the relationship of myosteatosis and mortality among older individuals recruited without regard to their health status are sparse. METHODS We evaluated the association of peripheral computed tomography measured calf myosteatosis (intermuscular fat and muscle density as a measure of intramuscular fat) with mortality in 1,063 community-dwelling older men. Cox proportional hazards models were used to estimate the risk of mortality independent of potential confounders. RESULTS During a mean follow-up of 7.2 years, 317 participants died. After adjustment for potential covariates and additional adjustment for whole body fat, lower skeletal muscle density was associated with increased all-cause mortality and cardiovascular disease mortality (hazard ratio [95% confidence interval] per standard deviation lower skeletal muscle density: 1.24 [1.09-1.41] and 1.46 [1.15-1.86], respectively), and to some extent with noncardiovascular disease mortality (1.18 [1.0-1.38], p = .053). After adjusting for trunk fat in a separate multivariable model, the association between skeletal muscle density and all-cause and cardiovascular disease mortality remained significant (both p < .01), while its association with noncardiovascular disease mortality became of borderline significance (p = .085). No other measures of adiposity, including calf intermuscular fat, were associated with mortality. CONCLUSION Our study reveals an independent association between skeletal muscle density and mortality in a community-based sample of older, predominantly Caucasian men. Further studies are needed to establish if this association is independent of other ectopic fat depots, and to identify the biological mechanisms underlying this relationship.
ASPECTOS DA SONOPLASTIA NO TEATRO

Desde a inauguracao do seculo XX, como o seculo das teorias de interpretacao e da encenacao como um sistema organizado de elementos teatrais, o espetaculo teatral vem recebendo cuidadosa atencao, essencialmente voltada para a integracao efetiva entre a organizacao de seus elementos e a comunicacao pretendida, de acordo com a realidade socio-cultural em que esta inserido. Pouco depois dos meados do seculo XX, a Semiotica alcancou uma dimensao de aplicabilidade no estudo dos elementos do teatro (signos do teatro), possibilitando, assim, estudos mais detalhados de especificidades desses signos. O resultado dessas pesquisas vem contribuindo sobremaneira para praticas teatrais cada vez mais eficazes em seus propositos esteticos e comunicativos.
Effect of an intubation dose of rocuronium on Spectral Entropy and Bispectral Index responses to laryngoscopy during propofol anaesthesia.

BACKGROUND The spectral entropy of the electroencephalogram has been proposed to monitor the depth of anaesthesia. State Entropy (SE) reflects the level of hypnosis. Response Entropy (RE), computed from electroencephalogram and facial muscle activity, reflects the response to nociceptive stimulation. We evaluated the effect of rocuronium on Bispectral Index (BIS) and entropy responses to laryngoscopy. METHODS A total of 25 patients were anaesthetized with propofol using a target-controlled infusion. At steady state, they randomly received 0.6 mg kg(-1) rocuronium (R) or saline (S). After 3 min, a 20 s laryngoscopy was applied. BIS, RE and SE were recorded continuously and averaged over 1 min during baseline, at steady state, 2 min after R or S administration (R/S+2) and 0, 1, 2 and 3 min after laryngoscopy (L0, L1, L2, L3). RESULTS At R/S+2, the RE-SE gradient was higher in Group S than in Group R. Laryngoscopy provoked an increase in BIS, RE and SE. Comparing R/S+2 and L0 values in Groups R and S, BIS increased from 43 (6) to 49 (8) and 42 (9) to 51 (15), SE increased from 43 (7) to 50 (8) and 41 (10) to 55 (12), and RE increased from 46 (8) to 54 (9) and 47 (12) to 66 (15), respectively. BIS and SE did not differ between groups. At L0, RE and RE-SE were higher in Group S [66 (15) and 11 (4), respectively] than in Group R [54 (9) and 4 (2), respectively]. CONCLUSIONS Rocuronium alters the RE-SE gradient and the RE and RE-SE responses to laryngoscopy. Muscle relaxation may confound interpretation of entropy monitoring.
The bedside chest radiograph in the evaluation of incipient heart failure.

Ninety-four patients had chest radiographs made on admission to a coronary care unit and daily thereafter for 1 days. Studies were carried out at bedside, in the postero-anterior projection, at 6 ft. (1.8 m) target-film distance, with the patient sitting. Thirty-one patients had radiographic evidence of congestive heart failure without clinical signs. In 23 of these, clinically evident failure subsequently developed. A “subclinical failure” group could thus be identified with a noninvasive technique. No useful information was obtained by filming patients clinically in failure, nor those in subclinical failure beyond day one. The most common sign of failure was distension of upper lobe vessels.
Stroke in Northern Sweden

Background: Stroke is one of the most common causes of death and long-term disability worldwide. Although stroke mortality has decreased in most industrialized countries, there are populations, particularly in East Europe, in which the mortality has increased. The WHO initiated, 20 years ago, the MONICA Project. The aim of the study was to measure trends in coronary heart disease and stroke and to assess the extent to which these were related to changes in known risk factors. Design: The Northern Sweden MONICA stroke study started in 1985 and is still ongoing. All individuals with an acute stroke in the age group 25 - 74 years have been included in the stroke register. Death certificates, discharge records, and GPs' records are screened and validated using strict MONICA criteria. Results: Stroke event rates (first ever and recurrent stroke) per 100,000 and year in the age group 25 - 74 years varied little over the years. Between 1985 and 1998 the annual incidence varied between 318 and 372 in men and between 195 and 240 in women, with no secular trends at all. The 28-day case fatality decreased in both men and women, from 19% to 11%. Logistic regression analyses showed a risk reduction in dying from stroke to 0.55 (p<0.0001) the last year compared with the first, with an absolute annual reduction in case fatality of 3%, in both men and women. In international comparison Northern Sweden shows an intermediately high incidence and one of the lowest case fatality rates of all participating populations. The incidence in subarachnoid haemorrhage was among the highest. Conclusion: The ongoing decline in stroke mortality in Sweden is driven exclusively by declining case fatality, whereas event rates (first ever and recurrent stroke) have remained the same since 1985. This, together with more people entering advanced, stroke-prone age groups, implies that the burden of stroke will continue to increase in Sweden.
Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis

Hepatic stellate cells (HSC) play a central role in the pathogenesis of liver fibrosis. Following liver injury, these cells proliferate and are activated to a profibrogenic myofibroblastic phenotype. In addition to increased matrix protein synthesis, there is evidence to indicate that these cells are able to regulate matrix degradation. In the early phases of their cellular activation, HSC release matrix metalloproteinases with the ability to degrade the normal liver matrix. When HSC are fully activated, there is a net down‐regulation of matrix degradation mediated by increased synthesis and extracellular release of tissue inhibitors of metalloproteinase (TIMP)‐1 and ‐2. These studies in cell culture have been complemented by in vivo studies of hepatic TIMP‐1 and TIMP‐2 gene expression. In advanced human liver disease of various aetiologies, there is increased TIMP‐1‐mRNA and protein and increased TIMP‐2‐mRNA in fibrotic liver compared with control liver. Temporal studies of progressive rat liver fibrosis caused by bile duct ligation or by carbon tetrachloride, indicate an important role for increased TIMP‐1 and TIMP‐2 expression in pathogenesis. Moreover, in a rat model of reversible liver fibrosis, matrix remodelling and resolution of liver fibrosis is closely associated, temporally, with a marked decrease in TIMP‐1 and TIMP‐2 expression. These combined cell culture and in vivo findings have led us to investigate the mechanisms of regulation of TIMP‐1 gene expression in hepatic stellate cells. Our recent data indicate that transcriptional regulation of TIMP‐1 gene expression in HSC is mediated via a mechanism which differs considerably from that previously identified in skin fibroblasts. We conclude that increased TIMP‐1 and TIMP‐2 expression by HSC plays an important role in the pathogenesis of liver fibrosis. This may represent an important therapeutic target in the design of anti‐fibrotic strategies for chronic liver disease.
Bringing Data-Driven Process Analysis into Surgical Practice : The Surgical Process Analyzer

The growing number of connected medical devices in the operating room and electronic health records provide valuable data to analyze surgical processes for workflow optimization, context-aware assistance systems and prediction of adverse events. In this area of surgical data science, i.e. surgical process analysis, a key challenge is to combine methods from computer science and statistics with surgical knowledge about processes and data, such as standard operating procedures, surgical guidelines, uncertainty and quality of data. We propose a novel framework that integrates handling of data, knowledge models and data analysis with an intuitive user interface for data visualization, process analytics and knowledge capturing. A key goal of this so called “Surgical Process Analyzer” is to empower surgical domain experts to perform process analysis in their surgical practice. As a result we expect to advance research in surgical data science by addressing real-world use-cases with collaboration of surgeons and data scientists that provides benefit for patients.
Swapping the Gene-Specific and Regional Silencing Specificities of the Hst1 and Sir2 Histone Deacetylases

ABSTRACT Sir2 and Hst1 are NAD+-dependent histone deacetylases of budding yeast that are related by strong sequence similarity. Nevertheless, the two proteins promote two mechanistically distinct forms of gene repression. Hst1 interacts with Rfm1 and Sum1 to repress the transcription of specific middle-sporulation genes. Sir2 interacts with Sir3 and Sir4 to silence genes contained within the silent-mating-type loci and telomere chromosomal regions. To identify the determinants of gene-specific versus regional repression, we created a series of Hst1::Sir2 hybrids. Our analysis yielded two dual-specificity chimeras that were able to perform both regional and gene-specific repression. Regional silencing by the chimeras required Sir3 and Sir4, whereas gene-specific repression required Rfm1 and Sum1. Our findings demonstrate that the nonconserved N-terminal region and two amino acids within the enzymatic core domain account for cofactor specificity and proper targeting of these proteins. These results suggest that the differences in the silencing and repression functions of Sir2 and Hst1 may not be due to differences in enzymatic activities of the proteins but rather may be the result of distinct cofactor specificities.