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BACKGROUND: Recent studies have correlated surgical skill measured by video-based assessment with improved clinical outcomes. Certain automated measures of operative performance in robotic surgery can be gathered beyond video review called objective performance indicators (OPIs). We explore the relationship between OPIs, surgeon experience, and postoperative recovery, hypothesizing that more efficient dissection will be associated with experience. METHODS: Fifty-six robotic cholecystectomies between February 2022 and March 2023 were recorded at a large tertiary referral center. Surgeon experience and clinical outcomes data from the EMR were obtained for all 56 cases with 10 completing the QOL survey. Two steps of robotic cholecystectomies were reviewed: dissection of Calot's triangle (DCT) and dissection of the gallbladder from the liver (DGL). Postoperative recovery was measured using the SF-36 well-being survey. Univariate analysis was conducted using Pearson's coefficient. RESULTS: Increased operative experience was associated with more efficient camera and instrument movements. DCT had 7 and DGL had 31 of 41 OPIs that correlated with experience. With respect to DGL, more experienced surgeons had reduced step duration and instrument path length and increased camera and instrument speeds. CONCLUSIONS: Several OPIs correlate with surgical experience and may form the basis of more instructive feedback for trainees and less experienced surgeons in improving intraoperative technique.
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Procedimentos Cirúrgicos Robóticos , Cirurgiões , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Projetos Piloto , Fenômenos Biomecânicos , Qualidade de Vida , Colecistectomia , Competência ClínicaRESUMO
A green approach for the synthesis of electrophilic alkenes has been developed via Knoevenagel condensation between active methylene compounds and carbonyl compounds using Mg powder under aqueous conditions. In this strategy, Mg(OH)2 acts as a catalyst, which was generated in situ by the reaction between metallic Mg (20 mol %) and water. Mg was found to be an efficient, nontoxic, and inexpensive metal catalyst system for producing a range of electrophilic alkenes in excellent yields (≤98%). A gram-scale synthesis of electrophilic alkenes has been developed, and Mg metal was recovered and recycled up to three times without an appreciable loss of catalytic activity. A catalytic cycle was proposed, and the reaction mechanism was investigated using density functional theory. The key steps are enolization of ethyl cyanoacetate, C-C bond formation, and then regeneration of the catalyst via metathesis with H2O. The overall reaction occurs easily with a maximum ΔG°â§§ value of 7.9 kcal/mol for the rate-determining C-C bond formation step. Our protocol has several advantages and can be further extended to one-pot sequential Knoevenagel condensation and Michael addition, and one-pot sequential Knoevenagel condensation and chemoselective reduction can be used for the synthesis of valuable precursors of pharmaceutical products under green and aqueous conditions.
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Background and Aims: Opioids are conventionally used for post-thyroidectomy pain, regional anesthesia is becoming popular due to its feasibility and efficacy in minimizing use of opioids and hence its side effects. This study compared analgesic efficacy of bilateral superficial cervical plexus block (BSCPB) using perineural and parenteral dexmedetomidine with 0.25% ropivacaine in thyroidectomy patients. Material and Methods: In this double-blind study, 60 American Society of Anesthesiologists (ASA) physical status I and II thyroidectomy patients, aged 18-65 years were randomized into two groups. Group A (n = 30) received BSCPB with 0.25% ropivacaine, 10 mL on each side with dexmedetomidine 0.5 µg/kg IV infusion. Group B (n = 30) received 0.25% ropivacaine plus dexmedetomidine 0.5 µg/kg, ten mL on each side. Duration of analgesia by measuring pain visual analog scores (VAS), total dose of analgesic requirement, Haemodynamics parameters and adverse events were recorded for 24 h. Categorical variables were analyzed using Chi-square test and continuous variables were computed as mean with standard deviation and analyzed using independent sample t-test. Mann-Whitney U test was used for analysis of ordinal variables. Results: Time to rescue analgesia was longer in Group B (18.6 ± 3.27 h) as compared to Group A (10.2 ± 2.11 h) (P < 0.001). Total analgesic dose required was also found to be lesser in Group B (50.83 ± 20.37 mg) as compared to Group A (73.33 ± 18.27 mg) (P < 0.001). No significant hemodynamic changes or side effects were observed in both groups; (P > 0.05). Conclusion: Perineural dexmedetomidine with ropivacaine in BSCPB significantly prolonged the duration of analgesia with reduced rescue analgesic requirement.
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The site frequency spectrum (SFS) is an important statistic that summarizes the molecular variation in a population, and is used to estimate population-genetic parameters and detect natural selection. Here, we study the SFS in a randomly mating, diploid population in which both the population size and selection coefficient vary periodically with time using a diffusion theory approach, and derive simple analytical expressions for the time-averaged SFS in slowly and rapidly changing environments. We show that for strong selection and in slowly changing environments where the population experiences both positive and negative cycles of the selection coefficient, the time-averaged SFS differs significantly from the equilibrium SFS in a constant environment. The deviation is found to depend on the time spent by the population in the deleterious part of the selection cycle and the phase difference between the selection coefficient and population size, and can be captured by an effective population size.
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Genética Populacional , Modelos Genéticos , Densidade Demográfica , Seleção GenéticaRESUMO
Many experimental and field studies have shown that adaptation can occur very rapidly. Two qualitatively different modes of fast adaptation have been proposed: selective sweeps wherein large shifts in the allele frequencies occur at a few loci and evolution via small changes in the allele frequencies at many loci. Although the first process has been thoroughly investigated within the framework of population genetics, the latter is based on quantitative genetics and is much less understood. Here we summarize results from our recent theoretical studies of a quantitative genetic model of polygenic adaptation that makes explicit reference to population genetics to bridge the gap between the two frameworks. Our key results are that polygenic adaptation may be a rapid process and can proceed via subtle or dramatic changes in the allele frequency depending on the sizes of the phenotypic effects relative to a threshold value. We also discuss how the signals of polygenic selection may be detected in the genome. Although powerful methods are available to identify signatures of selective sweeps at loci controlling quantitative traits, the development of statistical tests for detecting small shifts of allele frequencies at quantitative trait loci is still in its infancy.
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Adaptação Fisiológica/genética , Genética Populacional/métodos , Herança Multifatorial/genética , Aclimatação/genética , Alelos , Evolução Biológica , Evolução Molecular , Frequência do Gene/genética , Genética Populacional/estatística & dados numéricos , Modelos Genéticos , Locos de Características Quantitativas/genética , Seleção Genética/genéticaRESUMO
In an adapted population of mutators in which most mutations are deleterious, a nonmutator that lowers the mutation rate is under indirect selection and can sweep to fixation. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large population of asexual mutators. We show that when beneficial mutations are absent, the fixation probability is a nonmonotonic function of the mutation rate of the mutator: it first increases sublinearly and then decreases exponentially. We also find that beneficial mutations can enhance the fixation probability of a nonmutator. Our analysis is relevant to an understanding of recent experiments in which a reduction in the mutation rates has been observed.
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Taxa de Mutação , Reprodução Assexuada , Seleção Genética , Escherichia coli/genética , Evolução Molecular , Modelos Teóricos , ProbabilidadeRESUMO
We study a continuous time model for the frequency distribution of an infinitely large asexual population in which both beneficial and deleterious mutations occur and fitness is additive. When beneficial mutations are ignored, the exact solution for the frequency distribution is known to be a Poisson distribution. Here we include beneficial mutations and obtain exact expressions for the frequency distribution at all times using an eigenfunction expansion method. We find that the stationary distribution is non-Poissonian and related to the Bessel function of the first kind. We also provide suitable approximations for the stationary distribution and the time to relax to the steady state. Our exact results, especially at mutation-selection equilibrium, can be useful in developing semi-deterministic approaches to understand stochastic evolution.
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Aptidão Genética/genética , Modelos Genéticos , Reprodução Assexuada/genética , Seleção Genética , Genética Populacional , Mutação/genéticaRESUMO
We study the stationary state of a population evolving under the action of random genetic drift, selection and recombination in which both deleterious and reverse beneficial mutations can occur. We find that the equilibrium fraction of deleterious mutations decreases as the population size is increased. We calculate exactly the steady state frequency in a nonrecombining population when population size is infinite and for a neutral finite population, and obtain bounds on the fraction of deleterious mutations. We also find that for small and very large populations, the number of deleterious mutations depends weakly on recombination, but for moderately large populations, recombination alleviates the effect of deleterious mutations. An analytical argument shows that recombination decreases disadvantageous mutations appreciably when beneficial mutations are rare as is the case in adapting microbial populations, whereas it has a moderate effect on codon bias where the mutation rates between the preferred and unpreferred codons are comparable.
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Deriva Genética , Taxa de Mutação , Mutação/genética , Recombinação Genética , Seleção Genética , Densidade DemográficaRESUMO
We consider a one-dimensional classical ferromagnetic Ising model when it is quenched from a low temperature to zero temperature in finite time using Glauber or Kawasaki dynamics. Most of the previous work on finite-time quenches assume that the system is initially in equilibrium and focuses on the excess mean defect density at the end of the quench, which decays algebraically in quench time with Kibble-Zurek exponent. Here we are interested in understanding the conditions under which the Kibble-Zurek scalings do not hold and in elucidating the full dynamics of the mean defect density. We find that depending on the initial conditions and quench time, the dynamics of the mean defect density can be characterized by coarsening and/or the standard finite-time quench dynamics involving adiabatic evolution and Kibble-Zurek dynamics; the timescales for crossover between these dynamical phases are determined by coarsening time and stationary state relaxation time. As a consequence, the mean defect density at the end of the quench either is a constant or decays following coarsening laws or Kibble-Zurek scaling. For the Glauber chain, we formulate a low-temperature scaling theory and find exact expressions for the final mean defect density for various initial conditions. For the Kawasaki chain where the dynamic exponents for coarsening and stationary state dynamics are different, we verify the above findings numerically and examine the effect of unequal dynamic exponents.
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BACKGROUND: Molecular testing guides the management of cytologically indeterminate thyroid nodules. We evaluated the real-world clinical benefit of a commercially available thyroid mutation panel plus microRNA risk classifier in classifying RAS-mutated nodules. METHODS: We performed a subgroup analysis of the results of molecular testing of Bethesda III/IV nodules using the ThyGenX/ThyGeNEXT-ThyraMIR platform at 3 tertiary-care centers between 2017 and 2021, defining a positive result as 10% or greater risk of malignancy. RESULTS: We identified 387 nodules from 375 patients (70.7% female, median age 59.3 years) who underwent testing. Positive nodules (32.3%) were associated with increased surgical intervention (74.4% vs 14.9%, P < .0001) and carcinoma on surgical pathology (46.4% vs 3.4%, P < .0001) compared to negative modules. RAS mutations were the most common mutations, identified in 71 of 380 (18.7%) nodules, and were classified as ThyraMIR- (28 of 71; 39.4%) or ThyraMIR+ (43 of 71; 60.6%). Among RAS-mutated nodules, there was no significant difference in operative rate (P = .2212) or carcinoma diagnosis (P = .6277) between the ThyraMIR+ and ThyraMIR- groups, and the sensitivity, specificity, negative predictive value, and positive predictive value of ThyraMIR were 64.7%, 34.8%, 40.0%, and 59.5%, respectively. CONCLUSION: Although testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.
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Carcinoma , MicroRNAs , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/cirurgia , MicroRNAs/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Mutação , Estudos RetrospectivosRESUMO
Although many phenotypic traits are determined by a large number of genetic variants, how a polygenic trait adapts in response to a change in the environment is not completely understood. In the framework of diffusion theory, we study the steady state and the adaptation dynamics of a large but finite population evolving under stabilizing selection and symmetric mutations when selection and mutation are moderately large. We find that in the stationary state, the allele frequency distribution at a locus is unimodal if its effect size is below a threshold effect and bimodal otherwise; these results are the stochastic analog of the deterministic ones where the stable allele frequency becomes bistable when the effect size exceeds a threshold. It is known that following a sudden shift in the phenotypic optimum, in an infinitely large population, selective sweeps at a large-effect locus are prevented and adaptation proceeds exclusively via subtle changes in the allele frequency; in contrast, we find that the chance of sweep is substantially enhanced in large, finite populations and the allele frequency at a large-effect locus can reach a high frequency at short times even for small shifts in the phenotypic optimum.
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Objectives: Previous reports on association of autoantibodies with histological severity in nonalcoholic fatty liver disease (NAFLD) have revealed inconsistent results. Therefore, this study was undertaken to find the impact of autoantibodies on histological severity of NAFLD. Methods: All cases with histological diagnosis of NAFLD during January 2016 to January 2021 were included in the study. Laboratory parameters were recorded, and histological assessment was done. The positivity of autoimmune markers was defined as presence of either antinuclear antibody (ANA; titer >1:80), anti-smooth muscle antibodies (ASMA), or anti-liver-kidney-microsomal antibodies (LKM-1; titer >1:40). Serum levels of CK18 - M30 and PIIINP were evaluated to assess the subtle changes in necroinflammatory activity and fibrosis in the liver. Results: Autoantibodies were present in 281/683 (41.1%, 95% CI 37.4-44.9) patients. ANA, ASMA, ANA + ASMA was seen in 20.9% (95% CI 17.9-24.2); 14.5% (95% CI 11.9-17.4); and 5.7% (95% CI 4.1-7.7) cases, respectively. No significant difference was noted between the two groups in terms of age and metabolic tests. No significant difference was noted in the histological parameters between groups with autoantibodies positivity and no-positivity. Mean value of CK18-M30 between cases with negative autoantibody; ANA positivity; ASMA positivity; and combined positivity of autoantibody were 178.2 ± 81.8, 161.6 ± 63.7, 153.2 ± 70.3 and 169.8 ± 42.9, respectively (P = 0.57). However, CK18-M30 and PIIINP showed a rising trend with NAFL, NASH, NASH + AIH (P < 0.001). Conclusions: Autoantibodies noted in 41% NAFLD cases. No significant necroinflammatory activity or fibrosis associated with presence of antibodies in NAFLD cases. However, CK-18-M30 showed a rising trend from NAFL to NASH to NASH + AIH.
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Background: Bladder cancer, the most common malignancy of the urinary tract is a leading cause of morbidity and mortality. But cystoscopy, which is till now the mainstay of screening, is an invasive, high-cost method with low sensitivity especially for flat lesions. Aim: To find a non-invasive and effective screening method with liquid-based cytology (LBC) using The Paris System (TPS) and CK20 immunocytochemistry. Materials and Methods: It was a prospective study including the patients with clinical or cystoscopic diagnosis of urinary bladder space occupying lesions (SOL). Both conventional (CC) and liquid-based cytology slides were prepared from urine samples. Slides were evaluated by two trained pathologists and categorized according to TPS guidelines. CK20 immunocytochemistry (ICC) was also performed. Consequent formalin-fixed paraffin embedded sections were blindly examined by another pathologist and was taken as gold standard for comparison. Statistical Analysis: All the statistical analysis were done using MedCalc version 15.8 [Mariakerke, Belgium: MedCalc Software 2015]. Results: The study included 150 cases with a mean age of 62.4 years. Five cases revealed unsatisfactory smears. Rest of the cases were categorized as the following: 18.1% as NH-GUC, 8% as LGUN, 22.1% as AUC, 15.4% as SH-GUC, 32.9% as HGUC. Kappa value of CC and LBC were strong (0.854). LBC alone showed very low specificity (58%) and PPV (74.8%) which improved on application of ICC (specificity: 97.4%, PPV: 96.3%). Conclusion: We conclude that CK20 ICC offers potential for accurate, non-invasive detection and surveillance of bladder cancer and is a better tool when combined with liquid-based cytology, reported using The Paris System.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Estudos Prospectivos , Citologia , Citodiagnóstico/métodos , Urina , Urotélio/patologiaRESUMO
Background and Aims: The bilateral superficial cervical plexus block (BSCPB) is efficacious for post-operative analgesia in thyroid surgeries. We assessed the analgesic efficacy of dexmedetomidine and dexamethasone administered as adjuvants with 0.25 percent ropivacaine in BSCPB for thyroidectomy under general anaesthesia with regard to the duration of analgesia, total amount of rescue analgesic requirement, changes in intra- and post-operative haemodynamic parameters, VAS scores, and adverse events, if any. Methods: A prospective double-blind trial was planned with 80 adults undergoing thyroidectomy, randomized into two equal groups and given BSCPB with 20 ml 0.25% ropivacaine with adjuvants as either dexmedetomidine 50mg (group A) or dexamethasone 4mg (group B), 10 ml on each side, after the induction of general anaesthesia. Post-operative pain was monitored using the visual analog scale and the duration of analgesia was measured by time to first rescue analgesia. Post-operative haemodynamics and any adverse events were recorded. Results: The mean duration of analgesia was slightly prolonged in group A but statistically non-significant as compared to group B (1037 ± 97 vs. 1004 ± 122 minutes; P0.18). The post-operative median VAS scores and vital parameters were relatively comparable for both groups (P > 0.05) for the first 24h. There was a significant reduction in the incidence of PONV (P < 0.05) in group B. Conclusion: Although dexamethasone offers a slight advantage of decreased incidence of PONV, BSCPB using ropivacaine with either dexmedetomidine or dexamethasone as an adjuvant imparted adequate analgesia with stable haemodynamics and may be used as a pre-emptive analgesic technique in thyroid surgeries.
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BACKGROUND: Multiple myeloma (MM) results from clonal expansion of immunoglobulin secreting, heavy chain class-switched, terminally differentiated B-lymphocytes (plasma cells), resulting in radiologic or biochemical evidence of end-organ damage. Though neurological manifestations (peripheral neuropathies, spinal radiculopathies, cranial nerve palsies, and metabolic encephalopathies) can occur during the disease course, direct central nervous system (CNS) infiltration by malignant plasma cells (CNS-MM) is very rare (~1%) and has a dismal prognosis (survival of <6 months). METHODOLOGY: Clinico-laboratory profile and outcome of CNS-MM patients diagnosed and treated at a tertiary cancer care hospital were retrospectively analyzed. RESULTS: On scrutinizing 500 consecutive myeloma case records, 4 patients with CNS-MM were identified. All these patients were diagnosed during myeloma relapse, and all had deceased within 1 week and 12 months of developing CNS infiltration. Our experience with CNS-MM patients is similar to the experiences documented across major world literature. CONCLUSION: Our manuscript reinforces that CNS-MM should be considered in any myeloma patient presenting with unexplainable CNS manifestations. As there are no prospective studies to recommend optimal treatment strategies, CNS-MM still remains a dismal complication of myeloma.
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Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland.
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Carcinoma de Células Acinares , Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Tumores Neuroendócrinos , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Patologistas , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Acinares/patologia , Carcinoma de Células Grandes/patologia , Inquéritos e QuestionáriosRESUMO
Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as diabetic retinopathy and retinopathy of prematurity. Thus far, mediators of nitrative stress have been poorly characterized. We recently described that trans-arachidonic acids are major products of NO(2)(*)-mediated isomerization of arachidonic acid within the cell membrane, but their biological relevance is unknown. Here we show that trans-arachidonic acids are generated in a model of retinal microangiopathy in vivo in a NO(*)-dependent manner. They induce a selective time- and concentration-dependent apoptosis of microvascular endothelial cells in vitro, and result in retinal microvascular degeneration ex vivo and in vivo. These effects are mediated by an upregulation of the antiangiogenic factor thrombospondin-1, independently of classical arachidonic acid metabolism. Our findings provide new insight into the molecular mechanisms of nitrative stress in microvascular injury and suggest new therapeutic avenues in the management of disorders involving nitrative stress, such as ischemic retinopathies and encephalopathies.
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Apoptose/fisiologia , Ácidos Araquidônicos/toxicidade , Angiopatias Diabéticas/metabolismo , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Vasos Retinianos/citologia , Trombospondina 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ácidos Araquidônicos/metabolismo , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Primers do DNA , Marcação In Situ das Extremidades Cortadas , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Vasos Retinianos/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sus scrofa , Sais de Tetrazólio , TiazóisRESUMO
The clinical course after liver transplantation (LT) in progressive familial intrahepatic cholestasis type 1 (PFIC1) is complicated by intractable diarrhoea, growth failure, graft steatosis and cirrhosis. Recent evidence from Japan suggests the role of genotype to predict outcome after LT. We report a case with pathogenic frameshift mutation who had failed partial external biliary diversion, underwent LT and his post-LT course has been complicated by intractable diarrhoea, growth failure, steatosis and fibrosis. This case highlights the fact that homozygous frameshift p.Gly197LeufsTer10 mutation in ATP8B1 is associated with poor outcome and genetic evaluation should be mandatory before subjecting the patient to LT.
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BACKGROUND: An upsurge in cases of rhinosinusitis with or without associated orbital and/or cerebral involvement by mucormycosis has been observed in post-COVID-19 patients. Our objective is to evaluate the clinical and histopathology features of these patients to determine the severity and develop a scoring on the extent on tissue invasion. METHOD: We prospectively enrolled and analyzed 95 post-COVID-19 patients who presented with the invasive mucormycosis of the head and neck region. Clinical and histology details were noted in predesigned forms. Various histology variables were graded from I to III to propose a scoring system for the severity of the disease. RESULTS: Mucormycosis was common in males with a mean age of 46.8 ± 11 years. Facial pain was the most common presenting complaint and 77% of the patients were diabetic. Most cases (n = 59) showed a moderate degree of neutrophilic infiltrate with ⩾50% tissue necrosis and angioinvasion in three or more vessels with a fungal load of 2+/3+. Histology severity grade III was observed in patients who died from cerebral mucormycosis (n = 3) and septicemia (n = 2) and in patients who had undergone orbital exenteration (n = 6). CONCLUSION: The histopathology and severity score classification was directly correlated with the outcome of the patients. Further evaluation and a larger study will help to validate the proposed scoring for its clinical use in all forms and causes of mucormycosis.
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INTRODUCTION: Early diagnosis of sepsis and its severity is essential for appropriate treatment to improve patient survival, especially in resource-limited settings. The aim of the present study was to study the role of red blood cell distribution (RDW) as a biomarker for the early detection of severe sepsis defined clinically and also in the prediction of mortality from sepsis. METHODS: The cross-sectional study included a total of 175 subjects who met the inclusion criteria for the diagnosis of severe sepsis. After a thorough clinical examination, blood samples were taken from all patients within 3 hours of presenting the disease. The RDW values and other investigations were studied on the day of admission compared to other severity markers with the mortality index of 30 days. RESULT: The RDW value was significantly higher in patients with severe sepsis and in non-survivor patients than in survivors (P < .0001). There was a strong correlation between the SOFA score and RDW in predicting the disease outcome with the Pearson correlation coefficient of r = .46. The area under the receiver operating characteristic curve was found to be 0.852 at a CI of 95% (0.796-0.909) with RDW 17.15, sensitivity was 88.6% and specificity was 63.5%. There was a positive correlation with Pearson's correlation coefficient of r = .46 between RDW and the SOFA score. CONCLUSIONS: RDW can be used as a potential marker for the early detection of severe sepsis and in the prediction of the outcome. Large multicenter prospective studies can confirm the utility of this routinely available marker for patients with sepsis.