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Deinococcus species, noted for their exceptional resistance to DNA-damaging environmental stresses, have piqued scientists' interest for decades. This study dives into the complex mechanisms underpinning radiation resistance in the Deinococcus genus. We have examined the genomes of 82 Deinococcus species and classified radiation-resistance proteins manually into five unique curated categories: DNA repair, oxidative stress defense, Ddr and Ppr proteins, regulatory proteins, and miscellaneous resistance components. This classification reveals important information about the various molecular mechanisms used by these extremophiles which have been less explored so far. We also investigated the presence or lack of these proteins in the context of phylogenetic relationships, core, and pan-genomes, which offered light on the evolutionary dynamics of radiation resistance. This comprehensive study provides a deeper understanding of the genetic underpinnings of radiation resistance in the Deinococcus genus, with potential implications for understanding similar mechanisms in other organisms using an interactomics approach. Finally, this study reveals the complexities of radiation resistance mechanisms, providing a comprehensive understanding of the genetic components that allow Deinococcus species to flourish under harsh environments. The findings add to our understanding of the larger spectrum of stress adaption techniques in bacteria and may have applications in sectors ranging from biotechnology to environmental research.
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Deinococcus , Estresse Oxidativo , Deinococcus/efeitos da radiação , Deinococcus/genética , Deinococcus/metabolismo , Filogenia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Genoma Bacteriano , Reparo do DNARESUMO
BACKGROUND: When deep brain stimulation (DBS) infections are identified, they are often too advanced to treat without complete hardware removal. New objective markers to promptly identify DBS infections are needed. We present a patient with GPi (globus pallidus interna) DBS for dystonia, where the electrode impedance unexpectedly increased 3-months post-operatively, followed by serologic and hematologic markers of inflammation at 6-months, prompting explantation surgery. We recreated these conditions in a laboratory environment to analyze the pattern of changing of electrical impedance across the contacts of a DBS lead following Staphylococcus biofilm formation. METHODS: A stainless-steel culture chamber containing 1 % brain heart infusion agar was used. A DBS electrode was dipped in peptone water containing a strain of S. aureus and subsequently introduced into the chamber. The apparatus was incubated at 37 °C for 6 days. Impedance was measured at 24hr intervals. A control experiment without S. Aureus inoculation was used to determine changes in impedance over a period of 6-days. RESULTS: The mean monopolar impedance on day-1 was 751.8 ± 23.8 Ω and on day-3 was 1004.8 ± 68.7 Ω, a 33.7 % rise (p = 0.007). A faint biofilm formation could be seen around the DBS lead by day-2 and florid growth by day-3. After addition of the linezolid solution, a 15.9 % decrease in monopolar impedance was observed from day 3-6 (p = 0.003). CONCLUSION: This study gives insight into impedance trends following a hardware infection in DBS. Increased impedance outside expected norms may be valuable for early prediction of infection. Furthermore, timely management using antibiotics might reduce the frequency of infection-related explant surgeries.
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Estimulação Encefálica Profunda , Distúrbios Distônicos , Humanos , Impedância Elétrica , Staphylococcus aureus , Eletrodos , Globo Pálido/fisiologia , Resultado do TratamentoRESUMO
Skull reconstruction using cranial implants is often required for repairing skull defects caused due to trauma, diseases, or malignancy to protect intracranial structures. For relieving Intracranial Pressure (ICP) surgeons restore cranial defects either using natural bones or fabricated custom cranial implants. With the increase in Traumatic Brain Injuries (TBI) and challenges faced by TBI patients to regain normalcy, it is imperative to analyse the mechanical behaviour of skull-implant assemblies under some Head Injury Criteria (HIC). Medical grade materials including Titanium Alloys (Ti-6Al-4V) and Polyether-ether-ketone (PEEK) are used by fabricating Patient-Specific Implants (PSI) manufactured using 3D imaging, modelling and printing techniques. 3D technologies are preferred over conventional manufacturing methods, as they enable fabrication of custom shapes, sizes and properties for these PSI. For an effective attachment of PSI with a defective skull, a stable joint and plate arrangement as fixture plates is necessary at their interface. These fixtures can have variable numbers, design shapes, materials and location arrangements. This paper presents the Finite Element Method/Analysis (FEM/FEA) study of PSI attached to a defected skull for reconstruction, with linear shaped fixture configuration, when subjected to an external dynamic loading at 5 m/s, strain rate of 10s-1 to 243s-1 and ICP of 15mm Hg from three sides of the skull faces. Three different materials as Neoprene (soft), Concrete (medium rigid) and E-Glass (highly rigid) have been used, in the form of a rectangular thin cuboidal wall structure, at an angle of 45° with the skull face. Four linear shaped fixture plates which were simplest to design, were used to attach the PSI-skull assembly, to ensure that weight of the PSI-fixation assembly on the patient remains minimal, overall assembly has symmetrical fixations and efforts required by a surgeon for fitment of these plates remain minimal. Placement of these fixture plates has been optimized to encompass the complete PSI-skull interface section, due to which the stresses within all the assembly components (PSI, fixture plate and skull) reduced by nearly 2.5 times than the initial design and remained within yielding limits, thereby, averting any failure under heavy external dynamic loading.
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Crânio , Titânio , Humanos , Titânio/química , Crânio/cirurgia , Polímeros , Polietilenoglicóis/química , Cetonas/química , Análise de Elementos Finitos , Estresse MecânicoRESUMO
OBJECTIVES: We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. DESIGN: Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015-2020, n=110; All India Institute of Medical Sciences, New Delhi 2018-2020, n=62). RESULTS: In the 2015-2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992-1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992-1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%-11%. CONCLUSIONS: Emergency colectomy rates for ASC have halved in 25 years to 8%-15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.
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Produtos Biológicos , Colite Ulcerativa , Colite , Adulto , Humanos , Prognóstico , Ciclosporina/uso terapêutico , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Corticosteroides/uso terapêutico , Esteroides/uso terapêutico , Proteína C-Reativa/metabolismo , Colite/tratamento farmacológico , Albuminas/uso terapêutico , Índice de Gravidade de Doença , Colectomia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Background The closure of the appendiceal stump is a crucial step during an appendectomy. The purpose of this study is to evaluate the LigaSure Vessel Sealing System in laparoscopic appendectomy (LA) for sealing and dividing the base of the appendix. Material and methods Laparoscopic appendectomy was performed using the 5-mm LigaSure Vessel Sealer in 53 patients, and the mesoappendix along with the base of the appendix was divided by LigaSure. Patient demographic details, operative time, return to oral feed, duration of hospital stay, and postoperative complications were recorded, and statistical analysis was done. Results Out of 53 patients (24 women and 29 men), no complications occur in 51 patients. The mean age and standard deviation (SD) were 26.50 ± 10.46 years. The mean operative time for 53 appendectomies by LigaSure was 27.8 ± 6.72 minutes. The mean duration of hospital stay after surgery was 3.3 ± 0.72 days. One patient developed mild subcutaneous emphysema over the abdomen (1.8%), and surgical site infection occurred in one patient (1.8%). Conclusion This study demonstrated that sealing and dividing the base of the appendix by the LigaSure Vessel Sealing System is safe and feasible. It is associated with low complication rate and may help in simplifying the operative procedure.
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BACKGROUND: Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000 µg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort. METHODS: IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission. RESULTS: Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6 years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000 µg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000 µg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2-196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1-80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria. CONCLUSION: AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%).
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Colite Ulcerativa , Índice de Gravidade de Doença , Esteroides , Adulto , Colectomia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Feminino , Humanos , Infliximab/uso terapêutico , Complexo Antígeno L1 Leucocitário , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esteroides/uso terapêutico , Falha de Tratamento , Adulto JovemRESUMO
Background: Metastasis of the lymph node is one of the most significant prognostic factors for breast cancer (BC). Aim: To predict positivity of the lymph node in BC patients with help of USG and USG-guided FNAC and thus to prevent unnecessary morbidity. Methods: 50 patients of incisional/true cut biopsy-proven BC patients were included. All were subjected to mammography, USG and FNAC of the lump breast. USG-guided FNAC of the axillary lymph node was done in 25 of these patients. These findings were assessed by histological examination following dissection of the axillary lymph node. Results: Axillary lymph node (ALN) metastasis was present in 42 patients on histopathology; 21 patients suspicious of malignancy on preoperative USG were confirmed by HPE. Out of 88 confirmed lymph nodes evaluated on ultrasonography, 4 were benign, 18 were indeterminate and 66 were suspicious. The most promising features were tumour length/depth ratio of <1.5 in 81, absent fatty hilum in 73% and hypoechoic cortex in 74%. Assessment of axilla with USG had a sensitivity of 50%, a specificity of 100%, a PPV of 100%, an NPV of 27.59% and a diagnostic accuracy of 58%. Preoperative USG-guided FNAC had a sensitivity of 91.67%, a specificity of 100%, a PPV of 100%, an NPV of 33.33% and a diagnostic accuracy of 92%. Conclusion: USG can detect non-palpable axillary lymph nodes and FNAC can increase the sensitivity and specificity of this technique, which makes this procedure very promising in detecting axillary metastases in BC patients.
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Cysticercosis is caused by the larvae of Taenia solium and is a significant health problem. Disseminated cysticercosis is an infrequent manifestation of the same. A woman in her 30s presented to us with a history of seizures, outward protrusion of both eyes and multiple soft-tissue swellings over the face and tongue for 3 years. Imaging studies revealed multiple cystic lesions in the brain parenchyma, extraocular muscles, subcutaneous tissue, muscles of mastication and tongue. A high index of suspicion and a planned therapeutic approach is required in such cases.
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Cisticercose , Encéfalo/patologia , Protocolos Clínicos , Cisticercose/diagnóstico por imagem , Cisticercose/tratamento farmacológico , Feminino , Humanos , Músculos Oculomotores/patologia , Convulsões/etiologiaRESUMO
BACKGROUND: Tight junction proteins (TJPs) play an important role in gut-barrier dysfunction in cirrhosis and its complications such as acute variceal bleed (AVB). However, the dynamics of TJPs expression after AVB, its relation to bacterial translocation, and impact on clinical outcome is largely unknown. AIMS: The aim of this study was to study the expression of TJPs in cirrhosis and assess its dynamic changes in AVB. In addition, the relation of TJP expression to endotoxemia and clinical outcomes was assessed. METHODS: In this prospective pilot study, 17 patients of cirrhosis with AVB, 59 patients of cirrhosis without AVB (non-AVB cirrhosis), and 20 controls were assessed for claudin-2 and claudin-4 expression in the duodenal biopsy. In the AVB-cirrhosis group, additional biopsies were obtained after 3 weeks. Endotoxemia was assessed by measuring IgG anti-endotoxin antibody levels. Claudin expression was correlated with a 6-month survival. RESULTS: Claudin-2 expression was downregulated in patients with AVB and non-AVB cirrhosis in villi (P < 0.001 and 0.013) and crypts (P < 0.001 and 0.012), respectively, compared with the controls. Claudin-4 expression was similar in villi (P = 0.079), but lower in crypts (P = 0.007) in patients with cirrhosis. Claudin-2 expression was upregulated on serial biopsies in both villi and crypts (P = 0.003 and 0.001, respectively) in AVB-cirrhosis with postbleed expression comparable with those with non-AVB cirrhosis. IgG anti-endotoxin antibody levels were elevated in cirrhosis with no correlation with claudin-2/4 expression. Claudin-2 expression independently predicted survival at 6 months. CONCLUSION: Both claudin-2 and claudin-4 expression are downregulated in cirrhosis. AVB is associated with dynamic changes in TJPs expression. Gut-barrier dysfunction might predict outcomes independent of bacterial endotoxemia in cirrhosis.
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BACKGROUND/AIMS: Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC. METHODS: Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS' index (ulcerative colitis index of severity > 6 at day 1+fecal calprotectin > 1,000 µg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome. RESULTS: Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0-2,700,000] vs. 116 copies/mg [0-27,220]; P< 0.01). On multivariable analysis, mucosal CMV DNA load > 2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6-39.7; P< 0.01) and AIIMS' index (OR, 39.8; 95% CI, 4.4-364.4; P< 0.01) were independent predictors of steroid-failure and need for colectomy. The combination correctly predicted outcomes in 84% of patients with ASUC. CONCLUSIONS: High mucosal CMV DNA ( > 2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.
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The outbreak of coronavirus disease 2019 (COVID-19) that started in Wuhan, China, in December 2019 has spread worldwide, emerging as a global pandemic. The severe respiratory pneumonia caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far claimed more than 0.38 million lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 virus displays high transmission rates, the underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries, suggesting that its spread is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nonstructural protein 13 (nsp13), nsp14, nsp15, and nsp16 (ORF1b polyproteins) and in the S-protein within 10 viral isolates from the United States. These viral proteins are involved in RNA replication and binding with the human receptors, indicating that the viral variants that are circulating in the population of the United States are different from those circulating in the populations of other countries. In addition, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of a U.S. isolate (GenBank accession no. MT188341.1) leading to a shift in the amino acid frame from position 2540 onward. Through comparative structural analysis of the wild-type and mutant proteins, we showed that this addition of a phenylalanine residue renders the protein in the mutant less stable, which might affect mRNA cap-1 methyltransferase function. We further analyzed the SARS-CoV-2-human interactome, which revealed that the interferon signaling pathway is targeted by orf1ab during infection and that it also interacts with NF-κB-repressing factor (NKRF), which is a potential regulator of interleukin-8 (IL-8). We propose that targeting this interaction may subsequently improve the health condition of COVID-19 patients. Our analysis also emphasized that SARS-CoV-2 manipulates spliceosome machinery during infection; hence, targeting splicing might affect viral replication. In conclusion, the replicative machinery of SARS-CoV-2 is targeting interferon and the notch signaling pathway along with spliceosome machinery to evade host challenges.IMPORTANCE The COVID-19 pandemic continues to storm the world, with over 6.5 million cases worldwide. The severity of the disease varies with the territories and is mainly influenced by population density and age factor. In this study, we analyzed the transmission pattern of 95 SARS-CoV-2 genomes isolated from 11 different countries. Our study also revealed several nonsynonymous mutations in ORF1b and S-proteins and the impact on their structural stability. Our analysis showed the manipulation of host system by viral proteins through SARS-CoV-2-human protein interactome, which can be useful to understand the impact of virus on human health.
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BACKGROUND: Hydatid cyst disease, commonly caused by Echinococcus granulosus, rarely occurs in paraspinal muscles. Among the few reported cases, the current case is the largest paraspinal hydatid cyst disease ever reported in literature with a review of management of such large lesions. CASE DESCRIPTION: A 38-year-old male presented with lower back swelling for 1 year. Ultrasonography and magnetic resonance imaging scans suggested hydatidosis, following which the patient was taken up for surgery after preoperative medical therapy. En bloc resection was done, and histopathologic examination of the resected specimen confirmed the diagnosis. Postoperative albendazole was also used, and no recurrence was noted at 24 months post operation. CONCLUSIONS: Hydatid disease should be kept as one of the differential diagnoses for back swelling, especially in endemic regions. Giant-sized hydatid cysts of paraspinal muscles, though rare, cannot be ruled out on clinical ground alone. Thorough history taking and detailed examination should be aided with radiologic investigations like magnetic resonance imaging for an accurate diagnosis. En bloc excision of the cyst combined with preoperative and postoperative medical therapy is an effective method of treating this condition and significantly reducing complication rates.
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Equinococose/cirurgia , Região Lombossacral/cirurgia , Recidiva Local de Neoplasia/cirurgia , Músculos Paraespinais/cirurgia , Adulto , Albendazol/uso terapêutico , Diagnóstico Diferencial , Equinococose/diagnóstico , Humanos , Região Lombossacral/patologia , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia/diagnósticoRESUMO
Introduction: Laparoscopic appendectomy is a commonly performed procedure. The base of appendix is secured by various techniques (suture, LigaSure, endoloop, or hamlock clip). Harmonic scalpel (HS) may be used to seal the base of the appendix. The study was conducted to assess the efficacy of HS in laparoscopic appendectomy for sealing the base of the appendix. Materials and Methods: The patients were divided into two groups: group 1 in which base was secured by endoloop and group 2 in which base of the appendix was sealed by HS in a stepwise manner. We made a record of patients' age and gender, and operative time. The patients were followed for a period of 3 months from the time of discharge. Results: During the study period of 4.5 years, 102 patients were in group 1 and 108 patients in group 2. Both groups were age and gender matched. Mean operating time for group 1 was 43.34 ± 6.7 minutes and that for group 2 was 28.46 ± 7.19 minutes (P < .0001). Complications included postoperative ileus (group 1 = 8, group 2 = 10) and surgical site infection (group 1 = 4, group 2 = 4, P > .05). Conclusion: It appears that use of HS for laparoscopic appendectomy is feasible and safe. Its results appear to be comparable with other methods of laparoscopic appendectomy. Complications are minimal. Further studies at other centers may substantiate our efforts.
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Apendicectomia/instrumentação , Apendicite/cirurgia , Laparoscopia/instrumentação , Técnicas de Sutura , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Estudos Retrospectivos , Adulto JovemRESUMO
Serrated polyps are considered precursor lesions that account for 15% to 30% of colorectal cancers, and they are overrepresented as a cause of interval cancers. They are difficult to detect and resect comprehensively; however, recent data suggest that high definition endoscopy, chromoendoscopy (via spray catheter, pump or orally), narrow band imaging, split-dose bowel preparation and a slower withdrawal (>6 minutes) can all improve detection. Cold snare resection is effective and safe for these lesions, including cold snare piecemeal endoscopic mucosal resection, which is likely to become the standard of care for lesions >10 mm in size. Sessile serrated lesions ≥10 mm in size, those exhbiting dysplasia, or traditional serrated adenomas increase the chance of future advanced neoplasia. Thus, a consensus is emerging: a surveillance examination at 3 years should be recommended if these lesions are detected. Serrated lesions likely carry equivalent risk to adenomas, so future guidelines may consider serrated class lesions and adenomas together for risk stratification. Patients with serrated polyposis syndrome should undergo surveillance every 1 to 2 years once the colon is cleared of larger lesions, and their first degree relatives should undergo screening every 5 years starting at age 40.
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Pólipos do Colo , Neoplasias Colorretais , Adenoma , Colonoscopia , Humanos , Imagem de Banda EstreitaRESUMO
Spirometry based measurement of lung function is a global initiative for chronic obstructive lung disease (GOLD) standard to diagnose chronic obstructive pulmonary disease (COPD), one of the leading causes of mortality worldwide. The environmental and behavioural risk factors for COPD includes tobacco smoking, air pollutants and biomass fuel exposure, which can induce one or more abnormal lung function patterns. While smoking remains the primary risk factor, only 15-20% smokers develop COPD, indicating that the genetic factors are also likely to play a role. According to the study of Global Burden of Disease 2015, â¼174 million people across the world have COPD. From a comprehensive literature search conducted using the 'PubMed' and 'GWAS Catalogue' databases, and reviewing the literature available, only a limited number of studies were identified which had attempted to investigate the genetics of COPD and lung volumes, implying a huge research gap. With the advent of genomewide association studies several genetic variants linked to lung function and COPD, like HHIP, HTR4, ADAM19 and GSTCD etc., have been found and validated in different population groups, suggesting their potential role in determining lung volume and risk for COPD. This article aims at reviewing the present knowledge of the genetics of lung function and COPD.
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Doença Pulmonar Obstrutiva Crônica/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Pulmão/patologia , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Transdução de Sinais , Fumar/efeitos adversos , EspirometriaRESUMO
In the present study, we report the draft genome sequence of an obligate thermophile Geobacillus thermoleovorans strain RL isolated from Manikaran hot water spring located atop the Himalayan ranges, India. Strain RL grew optimally at 70 °C but not below 45 °C. The draft genome (3.39 Mb) obtained by Illumina sequencing contains 138 contigs with an average G + C content of 52.30%. RAST annotation showed that amino acid metabolism pathways were most dominant followed by carbohydrate metabolism. Genome-wide analysis using NCBI's Prokaryotic Genome Annotation Pipeline revealed that strain RL encodes for a cocktail of industrially important hydrolytic enzymes glycoside hydrolase, α-and ß-glucosidase, xylanase, amylase, neopullulanase, pullulanase and lipases required for white biotechnology. In addition, the presence of genes encoding green biocatalyst multicopper polyphenol oxidase (laccase) and an anticancer enzyme l-glutaminase reflects the significance of strain RL in gray and red biotechnology, respectively. Strain RL is a thermophilic multi-enzyme encoding bacterium which could be the source for the recombinant production of biotechnologically significant enzymes. In, addition whole cells of strain RL may be used in bioremediation studies.
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Linear echoendoscopes with large instrument channels enable EUS-guided interventions in organs and anatomical spaces in proximity to the gastrointestinal tract. Novel devices and tools designed for EUS-guided transluminal interventions allow various new applications and improve the efficacy and safety of these procedures. New-generation biopsy needles provide higher histology rates and require less passes. Specially designed stents and stent insertion devices enable intra- and extra-hepatic bile and pancreatic duct stenting as well as gallbladder drainage. Currently, EUS-guided biliary drainage in obstructive jaundice due to malignant distal bile duct obstruction is feasible and safe when ERCP has failed. It might replace ERCP as first choice intervention in future. EUS-guided transmural stenting is regarded as the preferred intervention in the management of symptomatic peripancreatic fluid collections. Creating a new anastomosis between different organs such as gastrojejunostomy has also become possible with lumen-apposing stents. EUS-guided creation of a gastrogastrostomy is a promising novel technique to access the excluded stomach to facilitate conventional ERCP in patients with Roux-en-Y gastric bypass anatomy. The role of EUS in tumor ablation and targeted angiotherapy is also constantly expanding. In this review, we report on the newest developments of therapeutic EUS within the past 4 years.