Biodegradation of nitenpyram (neonicotinoid insecticide) by endophytic bacterium, Bacillus thuringiensis strain NIT-2, isolated from neonicotinoid-treated plant samples.

Nitenpyram (neonicotinoid insecticide) is commonly used for crop protection from pests. Currently, due to its widespread use, the nitenpyram accumulation in the environment is anticipated to be high. Hence, the removal of nitenpyram residue from the environment is essential. However, the biodegradation of nitenpyram by endophytes is still unreported. Therefore, we aimed to isolate and identify a bacterial strain capable of degrading nitenpyram. We isolated approximately 300 endophytic strains from Brassica rapa var. perviridis that had been exposed to different neonicotinoid insecticides. After 14 days of incubation, a bacterial strain, NIT-2, with nitenpyram degradation capability (approximately 65%) was found. Via 16S rRNA gene sequencing, the strain was identified as Bacillus thuringiensis. In addition, metabolites, 2-[N-(6-chloro-3-pyridylmethyl)-N-ethyl]amino-2-methyliminoacetic acid, N-(6-chloro-3-pyridilmethyl)-N-ethyl-N-methylformamidine (CPMF), and N-(6-chloro-3-pyridilmethyl)-N-ethylformamide (CPF), were identified during the degradation. Moreover, CPMF and CPF were further degraded 71% and 18%, respectively by NIT-2. Thus, B. thuringiensis strain NIT-2 is the first reported endophytic bacterium capable of degrading nitenpyram.

Activin A levels in metabolic dysfunction-associated steatotic liver disease associates with fibrosis and the PNPLA3 I148M variant.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition worldwide. There is an urgent need to develop new biomarkers to assess disease severity and to define patients with a progressive phenotype. Activin A is a new promising biomarker with conflicting results about liver fibrosis. In this study we investigate levels of Activin A in patients with biopsy proven MASLD. We assess levels of Activin A in regard to fibrosis stage and genetic variant I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3). METHODS: Activin A levels were assessed in plasma samples from patients with biopsy-proven MASLD in a cross-sectional study. All patients were clinically evaluated and the PNPLA3 I148M genotype of the cohort was assessed. FINDINGS: 41 patients were included and 27% of these had advanced fibrosis. In MASLD patients with advanced fibrosis, Activin A levels was higher (p < 0.001) and could classify advanced fibrosis with an AUROC for activin A of 0.836 (p < 0.001). Patients homozygous for PNPLA3 I148M G/G had higher levels of activin A than non-homozygotes (p = 0.027). CONCLUSIONS: Circulating activin A levels were associated with advanced fibrosis and could be a potential blood biomarker for identifying advanced fibrosis in MASLD. Patients with the risk genotype PNPLA3 I148M G/G had higher levels of activin A proposing activin A as a contributor of the transition from simple steatosis to a fibrotic phenotype.

Experience of percutaneous closure of small to large patent ductus arteriosus with Nit-Occlud® device in a tertiary referral hospital in Colombia.

Background: The decision to close patent ductus arteriosus should always be individualized and taken together with the child's family once the risks and benefits of both choices have been exposed. Objective: This study aims to report the experience and outcomes in patients undergoing endovascular closure of small to medium-size PDA with a Nit-Occlud® device in a tertiary referral hospital in Colombia. Methods: Longitudinal descriptive study, which included all patients under 18 years of age who underwent percutaneous ductal closure with Nit-Occlud® device between January 1, 2011, and February 1, 2023. Patients with associated complex congenital heart disease requiring surgical management, pregnant patients, and patients with incomplete data regarding studied variables were excluded from the study. Results: Eighty-seven patients were documented, with a mean age, weight, and height at closure of 51 months, 14 kg, and 95.83 cm, respectively. About 70% of the patients (n = 61) were female, 76% were under 6-years-old and only one patient was over 15. The average size of the ductus at the pulmonary end was 2 mm. Four of the total number of patients did not achieve PDA closure during the procedure. Of the remaining 83, complete immediate closure was achieved in 81 patients. A device exchange for a larger device was required during the same procedure in one of the cases. Two patients presented residual shunt of 0.5 mm during follow-up, and one required a new procedure for device closure 10 months later. Only one device presented repeatedly embolization to the aorta, requiring surgical removal. As a technical difficulty, one device presented repeated passage into the aorta, so it was decided to remove it before releasing it to avoid complications, and given the complex anatomy of the ductus, surgical closure was indicated. Among the complications, one patient presented a hematoma of the subcutaneous tissue in the right thigh, which improved with medical management, and no deaths related to the procedure were registered. Conclusions: Using the Nit-Occlud® device to close small to moderate-sized ductus remains a safe and effective strategy with successful closure rates at 1-year follow-up irrespective of age, weight, height, or whether it involves a small or medium-sized duct. Despite our limitations, results concerning adverse effects are comparable to those observed in multicentric studies conducted in other regions.

Antecdentes: La decisión de cerrar el conducto arterioso permeable (CAP) siempre debe ser individualizada y tomada en conjunto con la familia del niño una vez expuestos los riesgos y beneficios de ambas opciones. Objetivo: Este estudio tiene como objetivo informar la experiencia y los resultados en pacientes sometidos a cierre endovascular del CAP de tamaño pequeño a mediano con un dispositivo Nit-Occlud® en un hospital de tercer nivel de referencia en Colombia. Método: Estudio descriptivo longitudinal, que incluyó a todos los pacientes menores de 18 años a quienes se les realizó cierre ductal percutáneo con dispositivo Nit-Occlud® entre el 1 de enero de 2011 y el 1 de febrero de 2023. Se excluyeron: pacientes con cardiopatía congénita compleja asociada que requirieron manejo quirúrgico, pacientes embarazadas y pacientes con datos incompletos sobre las variables estudiadas. Resultados: Se documentaron 87 pacientes, con edad, peso y talla promedio al cierre de 51 meses, 14 kg y 95.83 cm, respectivamente. El 70% de los pacientes (n = 61) eran mujeres, el 76% tenían menos de seis años y solo un paciente tenía más de 15 años. El tamaño medio del conducto en el extremo pulmonar fue de 2 mm. Cuatro del total de pacientes no lograron el cierre del CAP durante el procedimiento. De los 83 restantes, se logró el cierre inmediato completo en 81 pacientes. En uno de los casos fue necesario cambiar el dispositivo por uno más grande durante el mismo procedimiento. Dos pacientes presentaron shunt residual de 0.5 mm durante el seguimiento y uno requirió un nuevo procedimiento para cierre del dispositivo diez meses después. Solo un dispositivo presentó embolización repetida en la aorta, requiriendo extracción quirúrgica. Como dificultad técnica, un dispositivo presentó paso repetido hacia la aorta, por lo que se decidió retirarlo antes de liberarlo para evitar complicaciones y dada la compleja anatomía del ductus se indicó cierre quirúrgico. Entre las complicaciones, un paciente presentó un hematoma del tejido subcutáneo en el muslo derecho, que mejoró con el manejo médico, y no se registraron muertes relacionadas con el procedimiento. Conclusiones: El uso del dispositivo Nit-Occlud® para cerrar conductos de tamaño pequeño a moderado sigue siendo una estrategia segura y eficaz con tasas de cierre exitoso al año de seguimiento, independientemente de la edad, el peso, la altura o si se trata de un conducto de tamaño pequeño o mediano. A pesar de nuestras limitaciones, los resultados sobre los efectos adversos son comparables a los observados en estudios multicéntricos realizados en otras regiones.

Bi-allelic NIT1 variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage.

PURPOSE: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). METHODS: We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. RESULTS: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C>T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C>T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. CONCLUSION: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.

Metabolic Dysfunction-Associated Fibrosis 5 (MAF-5) Score Predicts Liver Fibrosis Risk and Outcome in the General Population With Metabolic Dysfunction.

BACKGROUND & AIMS: There is an unmet need for noninvasive tests to improve case-finding and aid primary care professionals in referring patients at high risk of liver disease. METHODS: A metabolic dysfunction-associated fibrosis (MAF-5) score was developed and externally validated in a total of 21,797 individuals with metabolic dysfunction in population-based (National Health and Nutrition Examination Survey 2017-2020, National Health and Nutrition Examination Survey III, and Rotterdam Study) and hospital-based (from Antwerp and Bogota) cohorts. Fibrosis was defined as liver stiffness ≥8.0 kPa. Diagnostic accuracy was compared with FIB-4, nonalcoholic fatty liver disease fibrosis score (NFS), LiverRisk score and steatosis-associated fibrosis estimator (SAFE). MAF-5 was externally validated with liver stiffness measurement ≥8.0 kPa, with shear-wave elastography ≥7.5 kPa, and biopsy-proven steatotic liver disease according to Metavir and Nonalcoholic Steatohepatitis Clinical Research Network scores, and was tested for prognostic performance (all-cause mortality). RESULTS: The MAF-5 score comprised waist circumference, body mass index (calculated as kg / m2), diabetes, aspartate aminotransferase, and platelets. With this score, 60.9% was predicted at low, 14.1% at intermediate, and 24.9% at high risk of fibrosis. The observed prevalence was 3.3%, 7.9%, and 28.1%, respectively. The area under the receiver operator curve of MAF-5 (0.81) was significantly higher than FIB-4 (0.61), and outperformed the FIB-4 among young people (negative predictive value [NPV], 99%; area under the curve [AUC], 0.86 vs NPV, 94%; AUC, 0.51) and older adults (NPV, 94%; AUC, 0.75 vs NPV, 88%; AUC, 0.55). MAF-5 showed excellent performance to detect liver stiffness measurement ≥12 kPa (AUC, 0.86 training; AUC, 0.85 validation) and good performance in detecting liver stiffness and biopsy-proven liver fibrosis among the external validation cohorts. MAF-5 score >1 was associated with increased risk of all-cause mortality in (un)adjusted models (adjusted hazard ratio, 1.59; 95% CI, 1.47-1.73). CONCLUSIONS: The MAF-5 score is a validated, age-independent, inexpensive referral tool to identify individuals at high risk of liver fibrosis and all-cause mortality in primary care populations, using simple variables.

Method for assessing the content of molybdenum enzymes in the internal organs of fish.

Molybdenum enzymes (Mo-enzymes) contain a molybdenum cofactor (MoCo) in the active site. These enzymes are potentially interesting for studying the survival mechanism of fish under hypoxic water conditions. This is because Mo-enzymes can synthesize nitric oxide from nitrates and nitrites, which are present in high concentrations under hypoxic water conditions. However, there is currently no method for assessing the Mo-enzymes content in the fish internal organs. Methods capable of determining Mo-enzymes content in the fish are of major importance. For this purpose, a method for quantitative determination of MoCo from plant tissues was modified. We demonstrated the Mo-enzyme content assessment by isolated MoCo from the fish's internal organs and the Neurospora crassa nit-1 extract containing inactive NADPH nitrate reductase. The Mo enzyme content was calculated using a calibration curve in nM of nitrites as a product of restored NADPH reductase activity after complementation with MoCo. Here we present a robust laboratory method which can be used to assess the content of Mo-enzymes in the internal organs of fish.•Mo-enzymes play a crucial role in detoxifying toxic compounds. Therefore, it is important to develop a method to accurately determine the amount of Mo-enzymes present. Notably, the method demonstrated the efficiency and accuracy as detected high content of Mo-enzymes in the liver and intestines (P < 0.0001). The obtained data on the distribution of Mo-enzymes in the internal organs of this species correspond to that of other vertebrates. Here, we present a rapid, sensitive, accurate and accessible method.•The developed method is simple and easy to use. Importantly, the protocol does not require complex manipulations, and the equipment used is available in most laboratories. The article provides step-by-step instructions for reproducing the method.

IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.

Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate in vitro that incubation with IL-32ß protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.

Identification of clinical phenotypes associated with poor prognosis in patients with nonalcoholic fatty liver disease via unsupervised machine learning.

BACKGROUND AND AIMS: Both fibrosis status and body weight are important for assessing prognosis in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify population clusters for specific clinical outcomes based on fibrosis-4 (FIB-4) index and body mass index (BMI) using an unsupervised machine learning method. METHODS: We conducted a multicenter study of 1335 biopsy-proven NAFLD patients from Japan. Using the Gaussian mixture model to divide the cohort into clusters based on FIB-4 index and BMI, we investigated prognosis for these clusters. RESULTS: The cohort consisted of 223 cases (16.0%) with advanced fibrosis (F3-4) as assessed from liver biopsy. Median values of BMI and FIB-4 index were 27.3 kg/m2 and 1.67. The patients were divided into four clusters by Bayesian information criterion, and all-cause mortality was highest in cluster d, followed by cluster b (P = 0.001). Regarding the characteristics of each cluster, clusters d and b presented a high FIB-4 index (median 5.23 and 2.23), cluster a presented the lowest FIB-4 index (median 0.78), and cluster c was associated with moderate FIB-4 level (median 1.30) and highest BMI (median 34.3 kg/m2 ). Clusters a and c had lower mortality rates than clusters b and d. However, all-cause of death in clusters a and c was unrelated to liver disease. CONCLUSIONS: Our clustering approach found that the FIB-4 index is an important predictor of mortality in NAFLD patients regardless of BMI. Additionally, non-liver-related diseases were identified as the causes of death in NAFLD patients with low FIB-4 index.

Fast and sensitive detection of nitroxynil using a chalcone-based supramolecular fluorescent sensor.

Nitroxynil as a veterinary drug has been widely used for treatment of parasitic worms in food-producing sheep and cattle. However, the residual nitroxynil in edible animal products can lead to severe adverse effects on human health. Thus, development of an effective analytical tool for nitroxynil is of great significance. In the present study, we designed and synthesized a novel albumin-based fluorescent sensor, which was capable of detecting nitroxynil with the fast response (<10 s), high sensitivity (limit of detection ∼8.7 ppb), high selectivity, and excellent anti-interference property. The sensing mechanism was clarified by using the molecular docking technique and mass spectra. Moreover, this sensor showed the detection accuracy comparable to standard HPLC method, and meanwhile exhibited much shorter response time and higher sensitivity. All the results demonstrated that this novel fluorescent senor could serve as a practical analytical tool for determination of nitroxynil in real food samples.

Histological confinement of transglutaminase-mediated nit sheath crosslinking is essential for proper oviposition and egg coating in the human head louse, Pediculus humanus capitis.

BACKGROUND: Head louse females secrete liquid gel, which is mainly composed of the louse nit sheath protein 1 (LNSP1) and LNSP2, when they lay eggs. The gel is crosslinked by transglutaminase (TG) to form the nit sheath, which covers most of the egg except the top operculum area where breathing holes are located. Knowledge on the selective mechanism of nit sheath solidification to avoid uncontrolled crosslinking could lead to designing a novel method of louse control, but no information is available yet. METHODS: To elucidate the crosslinking mechanisms of nit sheath gel inside the reproductive system of head louse females, in situ hybridization in conjunction with microscopic observation of the oviposition process was conducted. RESULTS: Histochemical analysis revealed that LNSP1 and LNSP2 are expressed over the entire area of the accessory gland and uterus, whereas TG expression site is confined to a highly localized area around the opening of posterior oviduct. Detailed microscopic observations of oviposition process uncovered that a mature egg is positioned in the uterus after ovulation. Once aligned inside the uterus, the mature egg is redirected so that its operculum side is tightly held by the ventral end of the uterus being positioned toward the head again and its pointed bottom end being positioned toward the dorsal end of the uterus, which functions as a reservoir for the nit sheath gel. CONCLUSIONS: Physical separation of the TG-mediated crosslinking site from the ventral end of the uterus is necessary to avoid uncontrolled crosslinking inside the uterus and to ensure selective crosslinking over only the lower part of egg without any unwanted crosslinking over the operculum during oviposition.

The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.

In previous studies, we have identified the tumor suppressor proteins Fhit (fragile histidine triad) and Nit1 (Nitrilase1) as interaction partners of ß-catenin both acting as repressors of the canonical Wnt pathway. Interestingly, in D. melanogaster and C. elegans these proteins are expressed as NitFhit fusion proteins. According to the Rosetta Stone hypothesis, if proteins are expressed as fusion proteins in one organism and as single proteins in others, the latter should interact physically and show common signaling function. Here, we tested this hypothesis and provide the first biochemical evidence for a direct association between Nit1 and Fhit. In addition, size exclusion chromatography of purified recombinant human Nit1 showed a tetrameric structure as also previously observed for the NitFhit Rosetta Stone fusion protein Nft-1 in C. elegans. Finally, in line with the Rosetta Stone hypothesis we identified Hsp60 and Ubc9 as other common interaction partners of Nit1 and Fhit. The interaction of Nit1 and Fhit may affect their enzymatic activities as well as interaction with other binding partners.

Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice.

Background & Aims: Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings. Methods: A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas. Results: There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan®, 21% of respondents used a single liver stiffness cut-off: 8 kPa in 50%, while the rest used 7.2 kPa, 7.8 kPa and 8.7 kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10 kPa and >7.5 to >20 kPa, respectively). Conclusions: The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management. Lay summary: Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.

Performance of Noninvasive Tests of Fibrosis Among Asians, Hispanic, and non-Hispanic Whites in the STELLAR Trials.

BACKGROUND & AIMS: The effect of race on routinely available noninvasive tests of fibrosis is incompletely understood. This study evaluated the performance of noninvasive tests among white and Asian patients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH). METHODS: Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and 4 noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF], and liver stiffness by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves with 5-fold cross-validation repeated 100 times. RESULTS: Among 3207 patients screened with evaluable liver histology, 2281 were whites and 762 were Asians. Seventy-two percent of whites and 67% of Asians had advanced fibrosis. The areas under the receiver operating characteristics curves of the noninvasive tests for advanced fibrosis were similar in whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for liver stiffness, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the 2 groups. However, the sensitivities of NFS, FIB-4, and ELF were low in both white and Asian patients younger than 40 years. CONCLUSIONS: In the global phase III STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between white and Asian patients.

Population structure of an Antarctic aquatic cyanobacterium.

BACKGROUND: Ace Lake is a marine-derived, stratified lake in the Vestfold Hills of East Antarctica with an upper oxic and lower anoxic zone. Cyanobacteria are known to reside throughout the water column. A Synechococcus-like species becomes the most abundant member in the upper sunlit waters during summer while persisting annually even in the absence of sunlight and at depth in the anoxic zone. Here, we analysed ~ 300 Gb of Ace Lake metagenome data including 59 Synechococcus-like metagenome-assembled genomes (MAGs) to determine depth-related variation in cyanobacterial population structure. Metagenome data were also analysed to investigate viruses associated with this cyanobacterium and the host's capacity to defend against or evade viruses. RESULTS: A single Synechococcus-like species was found to exist in Ace Lake, Candidatus Regnicoccus frigidus sp. nov., consisting of one phylotype more abundant in the oxic zone and a second phylotype prevalent in the oxic-anoxic interface and surrounding depths. An important aspect of genomic variation pertained to nitrogen utilisation, with the capacity to perform cyanide assimilation and asparagine synthesis reflecting the depth distribution of available sources of nitrogen. Both specialist (host specific) and generalist (broad host range) viruses were identified with a predicted ability to infect Ca. Regnicoccus frigidus. Host-virus interactions were characterised by a depth-dependent distribution of virus type (e.g. highest abundance of specialist viruses in the oxic zone) and host phylotype capacity to defend against (e.g. restriction-modification, retron and BREX systems) and evade viruses (cell surface proteins and cell wall biosynthesis and modification enzymes). CONCLUSION: In Ace Lake, specific environmental factors such as the seasonal availability of sunlight affects microbial abundances and the associated processes that the microbial community performs. Here, we find that the population structure for Ca. Regnicoccus frigidus has evolved differently to the other dominant phototroph in the lake, Candidatus Chlorobium antarcticum. The geography (i.e. Antarctica), limnology (e.g. stratification) and abiotic (e.g. sunlight) and biotic (e.g. microbial interactions) factors determine the types of niches that develop in the lake. While the lake community has become increasingly well studied, metagenome-based studies are revealing that niche adaptation can take many paths; these paths need to be determined in order to make reasonable predictions about the consequences of future ecosystem perturbations. Video Abstract.

Prevalence and Antimicrobial Resistance of Bacterial Uropathogens Isolated from Dogs and Cats.

Bacterial urinary tract infection (UTI) is a common diagnosis in companion animal practice and is one of the leading reasons for antimicrobial prescriptions. We analysed 1862 samples from the urinary tract of dogs and cats, submitted to a veterinary microbiological diagnostic laboratory in 2019 and 2020 in Germany. Susceptibility of 962 uropathogenic isolates to 15 antimicrobials, suggested as first- and second-line treatment options for UTI, was determined according to CLSI recommendations. Bacterial growth of uropathogens was detected in 43.9% of dog and in 38.5% of cat samples. Escherichia (E.) coli was the most frequently isolated pathogen (48.4%), followed by Enterococcus spp. (11.9%) and coagulase-positive staphylococci (CoPS; 11.5%). Females were more likely to exhibit a positive microbiological culture. Regarding first-line antibiotics, 93.4% of the most commonly isolated uropathogenic species were susceptible to the first-line antibiotics amoxicillin/clavulanic acid (AMC) and 87.6% to trimethoprim-sulfamethoxazole (SXT), while 76.1% showed decreased susceptibility to ampicillin (AMP). Multidrug resistance (MDR) was detected in 11.9% of E. coli, 50.4% of enterococci, and 42.7% of CoPS; 90.6% of these isolates were susceptible to nitrofurantoin (NIT). Our data indicate that empiric treatment of UTI with AMC or SXT could be recommended and is preferable to treatment with AMX. NIT should be considered for the treatment of MDR uropathogens.

Nonalcoholic Fatty Liver Disease-A Concise Review of Noninvasive Tests and Biomarkers.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with a continuously growing prevalence. The pathophysiology of the disease is complex and includes several mechanisms, with metabolic syndrome and insulin resistance playing a major role. It is crucial to diagnose NAFLD before it advances to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, presented by its complications which include ascites, portal hypertension, bleeding varices and encephalopathy. Another important complication of NAFLD and cirrhosis is hepatocellular carcinoma (HCC), a cancer with increasing incidence and poor prognosis. Even with the growing prevalence of NAFLD, diagnosis via liver biopsies is unrealistic, considering the costs and complications. Noninvasive tests, including serum biomarkers and elastography, are cost-effective and convenient, thereby replacing liver biopsies in diagnosing and excluding liver fibrosis. However, currently, these noninvasive tests have several limitations, such as variability, inadequate accuracy and risk factors for error. The limitations and variability of these tests comet the investigator to propose combining them in diagnostic algorithms to produce more accurate tools. Identifying patients with significant fibrosis is important for targeted therapies to prevent disease progression. Effective screening using noninvasive tests can be crucial for patient risk stratification and early diagnosis.

Factors Associated With Non-invasive Oxygen Therapy Failure in COVID-19 Pneumonia: A Single Center, Retrospective Study in a Tertiary Hospital in North India.

BACKGROUND: Non-invasive oxygen therapy (NIT) consists of high-flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP). NIT is routinely being used for the management of acute respiratory failure secondary to coronavirus disease-2019 (COVID-19) with variable outcomes. However, previously published studies show that NIT failure might delay endotracheal intubation and invasive mechanical ventilation and results in worse outcomes in patients with hypoxemic respiratory failure. Early prediction of failure of NIT, will help in early decision-making in initiating invasive mechanical ventilation. We retrospectively studied the predictors for NIT failure in patients with moderate to severe COVID-19. METHODS: Adult patients (>18 years) admitted to the intensive care unit (ICU) with moderate to severe COVID-19 ARDS and received NIT [HFNO and CPAP non-invasive ventilation (NIV)] were included in this study. Baseline clinical and laboratory data were collected retrospectively from the electronic hospital information system. NIT failure was defined as the need for invasive mechanical ventilation after the initiation of NIT in the ICU. Univariate and multivariate logistic regression analyses were used to find out the possible predictors of NIT failure. RESULTS: Out of 254 patients admitted to ICU, 127 patients were initiated NIT at admission to ICU. During the course of the ICU stay, 33 (26%) patients subsequently required invasive mechanical ventilation (NIT failure). Respiratory rate-oxygenation index (ROX index) of <2.97 at two hours and <3.63 at six hours of ICU admission predicted NIT failure in our cohort of patients with a high positive predictive value. CONCLUSION: Patient selection is crucial for successful NIT in COVID-19. Application of ROX index measured in the first six hours of ICU admission helps in the identification of patients at risk of NIT failure with moderate to severe COVID-19 ARDS.

A comprehensive review on the pretreatment and detection methods of neonicotinoid insecticides in food and environmental samples.

In recent years, the residues of neonicotinoid insecticide in food and environmental samples have attracted extensive attention. Neonicotinoids have many adverse effects on human health, such as cancer, chronic disease, birth defects, and infertility. They have substantial toxicity to some non-target organisms (especially bees). Hence, monitoring the residues of neonicotinoid insecticides in foodstuffs is necessary to guarantee public health and ecological stability. This review aims to summarize and assess the metabolic features, residue status, sample pretreatment methods (solid-phase extraction (SPE), Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS), and some novel pretreatment methods), and detection methods (instrument detection, immunoassay, and some innovative detection methods) for neonicotinoid insecticide residues in food and environmental samples. This review provides detailed references and discussion for the analysis of neonicotinoid insecticide residues, which can effectively promote the establishment of innovative detection methods for neonicotinoid insecticide residues.

Long-term Consequences of Ventricular Septal Defect Closure Using Nit-Occlud Le VSD Coil Device: A Systematic Review and Meta-Analysis.

Background: The successful management of ventricular septal defect (VSD) has been possible through the development of advanced techniques. In this regard, percutaneous VSD closure by employing different types of occluders as an alternative for surgery can help to achieve the most desirable postprocedural consequences. However, the studies reported contradictory results on the use of different brands of VSD occluders. Herein, we performed a systematic review and meta-analysis of published studies to assess pooled long-term success rate and potential complications of using the Nit-Occlud Lê VSD coil for VSD closure. Materials and Methods: Two reviewers began to deeply search the various databases for all eligible studies in accordance with the considered keywords. The inclusion criterion for retrieving the studies was to describe the mid-term or long-term consequences of VSD closing by the Nit-Occlud Lê VSD coil device. In the final, eight articles were eligible for the analysis. The follow-up time of the studies ranged from 6 months to 5 years. Results: The success rate of the procedure ranged from 87.0% to 100% considering the weight of each study, the pooled success rate of VSDs closure by Nit-Occlud Lê VSD coil device was 93.1% (95% confidence interval [CI]: 89.9% to 95.5%). The pooled prevalence of postprocedural residual shunt was estimated to be 9.6% (95%CI: 6.8% to 13.4%). The corrected pooled prevalence of trivial mild aortic regurgitation (AR) was 2.9% (95%CI: 1.5% to 5.4%); however, moderate-to-severe AR and complete heart block or right bundle branch block were shown to be rare. Conclusion: VSD closure using a Nit-Occlud Lê VSD coil device can lead to a high success rate with low rates of residual shunt, cardiac conductive or vascular disturbances.

Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701).

Background & Aims: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. Methods: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. Results: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index ≥0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (≤1%), and the model had a competitive performance compared with the Baveno VII criteria. Conclusions: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. Lay summary: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.