NDT-C11 as a viable novel detergent for single particle cryo-EM.

Single particle cryo electron microscopy (cryo-EM) is now the major method for the determination of integral membrane protein structure. For the success of a given project the type of membrane mimetic used for extraction from the native cell membrane, purification to homogeneity and finally cryo-grid vitrification is crucial. Although small molecule amphiphiles - detergents - are the most widely used membrane mimetic, specific tailoring of detergent structure for single particle cryo-EM is rare and the demand for effective detergents not satisfied. Here, we compare the popular detergent lauryl maltose-neopentyl glycol (LMNG) with the novel detergent neopentyl glycol-derived triglucoside-C11 (NDT-C11) in its behavior as free detergent and when bound to two types of multisubunit membrane protein complexes - cyanobacterial photosystem I (PSI) and mammalian F-ATP synthase. We conclude that NDT-C11 has high potential to become a very useful detergent for single particle cryo-EM of integral membrane proteins.

[Syphilis infection and related factors among HIV-infected patients in Zhejiang Province].

Objective: To investigate syphilis infection and related factors among HIV-infected patients being followed up for more than one year in Zhejiang Province. Methods: Data were collected from the China Disease Control and Prevention Information System, and information such as demographic characteristics, viral load levels, and syphilis serologic test results was collected from HIV-infected persons who were diagnosed with HIV more than 1 year, aged ≥15 years with a current address in Zhejiang Province through December 31, 2022. The logistic regression model analyzed the prevalence of syphilis and the related factors. The SPSS 19.0 software was used for statistical analysis. Results: A total of 33 734 HIV-infected patients, with the prevalence of syphilis was 5.6% (1 879/33 734). Among the syphilis cases, the prevalence of syphilis was 6.4% (1 774/27 934) of males, 7.5% (640/8 543) of 25-34 years old age group, 7.6% (1 025/13 423) of unmarried, 8.3% (1 239/14 862) of homosexual transmission, 6.9% (214/3 080) with a non-local registered residence and 9.6% (602/6 267) with a history of STD before the HIV diagnosis. Multivariate Logistic regression analysis showed that participants who were male (aOR=2.19, 95%CI:1.77-2.72), 25-34 years old age group (aOR=1.80, 95%CI:1.47-2.20), homosexual transmission (aOR=1.67, 95%CI:1.49-1.88), with other provinces registered residence (aOR=1.26, 95%CI:1.09-1.47), and with a history of sexually transmitted disease (STD) before the HIV diagnosis (aOR=1.98, 95%CI:1.78-2.20) were associated with increased risk of syphilis. Being married (aOR=0.79, 95%CI:0.68-0.92) was associated with a decreased risk of syphilis. Conclusions: Syphilis infections were high in HIV-infected patients followed up more than one year in Zhejiang Province. It is recommended that syphilis surveillance and screening frequency should be strengthened among HIV-infected persons with characteristics such as male, homosexual transmission, and STD history.

Structural insights into thermophilic chaperonin complexes.

Group I chaperonins are dual heptamer protein complexes that play significant roles in protein homeostasis. The structure and function of the Escherichia coli chaperonin are well characterized. However, the dynamic properties of chaperonins, such as large ATPase-dependent conformational changes by binding of lid-like co-chaperonin GroES, have made structural analyses challenging, and our understanding of these changes during the turnover of chaperonin complex formation is limited. In this study, we used single-particle cryogenic electron microscopy to investigate the structures of GroES-bound chaperonin complexes from the thermophilic hydrogen-oxidizing bacteria Hydrogenophilus thermoluteolus and Hydrogenobacter thermophilus in the presence of ATP and AMP-PNP. We captured the structure of an intermediate state chaperonin complex, designated as an asymmetric football-shaped complex, and performed analyses to decipher the dynamic structural variations. Our structural analyses of inter- and intra-subunit communications revealed a unique mechanism of complex formation through the binding of a second GroES to a bullet-shaped complex.

Influencia del sexo en los resultados de la cirugía retrógrada intrarrenal (CRIR). Datos obtenidos del Flexible Ureteroscopy Outcomes Registry (FLEXOR) / Does gender influence retrograde intrarenal surgery (RIRS) outcomes? Data from the Flexible Ureteroscopy Outcomes Registry (FLEXOR)

Introducción y objetivos Si bien la ureteroscopia flexible es una técnica establecida, a día de hoy no existen datos sobre la influencia del sexo del paciente en los resultados y complicaciones. El objetivo de este estudio es evaluar el papel que desempeña el sexo en la realización de la ureteroscopia flexible a partir de una serie grande de pacientes.MétodosEste estudio analizó retrospectivamente los datos del registro multicéntrico FLEXOR de los pacientes tratados de cálculos renales con CRIR desde enero de 2018 hasta agosto de 2021. Se analizaron los datos demográficos, las características de los cálculos, los hallazgos perioperatorios, los resultados y las complicaciones, y se compararon entre grupos estratificados según el sexo.ResultadosUn total de 6.669 pacientes fueron incluidos, el 66,1% eran varones y el 33,9% mujeres. Las características de los cálculos eran comparables entre los grupos. Las mujeres presentaron tasas significativamente más elevadas de fiebre y urocultivo positivo (12 frente a 8% y 37 frente a 34%). Además, las mujeres tuvieron una estancia hospitalaria ligeramente más larga (3,8 vs. 3,5 días; p < 0,001) y más fragmentos residuales después del procedimiento (23,03 vs. 20,97; p = 0,032). Las complicaciones globales fueron ligeramente superiores en las mujeres (15,74 frente a 14%; p = 0,042), debido principalmente a las tasas de fiebre (6,9 frente a 5,7%); el riesgo de sepsis fue similar en ambos grupos. Según un análisis multivariante, los cálculos de mayor tamaño, múltiples y localizados en el polo inferior parecen tener un efecto negativo en la incidencia de los cálculos residuales y las complicaciones.ConclusiónNuestro estudio de la vida real a nivel mundial refleja que el sexo femenino puede estar correlacionado con unas tasas ligeramente mayores de fragmentos residuales y complicaciones generales de bajo grado. ... (AU)

Introduction and objectives As well established flexible ureteroscopy (RIRS). There is still no evidence if gender can have any influence on the outcomes and complication when performing This study aims to evaluate the role that gender has in performing flexible ureteroscopy from a large series of patients.MethodsThis study retrospectively analyzed patients who underwent RIRS for renal stones from January 2018 to August 2021 within the multicentric FLEXOR registry. Demographics, stone characteristics, perioperative findings, results and complications were analyzed and compared between gender groups.ResultsA total of 6669 patients were included, 66.1% were male and 33.9% were female. Stone characterictis was comparable between groups. Female patients had significant higher fever and positive urine culture rates (12% vs. 8% and 37% vs. 34%). Also, females had a slight longer hospital stay (3.8 vs. 3.5 days; P < 0.001) and more residual fragments after the procedure (23.03% vs. 20.97 (P = 0.032). Overall complications were slightly significantly higher in women (15.74% vs. 14% (P = 0.042)) mainly at the expense of fever rates (6.9% vs. 5.7%) whereas the risk of sepsis was similar in both groups. A multivariate analysis showed that larger stone size, multiple and lower pole stones seem to have a negative impact in the incidence of residual stones and complications.ConclusionOur real life global study reflects that female gender may have a correlation with a slightly increased residual fragment rate and overall low grade complications. However, women can safely be treated with RIRS with no increased the rate of sepsis with appropriate care. (AU)

Deep learning driven de novo drug design based on gastric proton pump structures.

Existing drugs often suffer in their effectiveness due to detrimental side effects, low binding affinity or pharmacokinetic problems. This may be overcome by the development of distinct compounds. Here, we exploit the rich structural basis of drug-bound gastric proton pump to develop compounds with strong inhibitory potency, employing a combinatorial approach utilizing deep generative models for de novo drug design with organic synthesis and cryo-EM structural analysis. Candidate compounds that satisfy pharmacophores defined in the drug-bound proton pump structures, were designed in silico utilizing our deep generative models, a workflow termed Deep Quartet. Several candidates were synthesized and screened according to their inhibition potencies in vitro, and their binding poses were in turn identified by cryo-EM. Structures reaching up to 2.10 Å resolution allowed us to evaluate and re-design compound structures, heralding the most potent compound in this study, DQ-18 (N-methyl-4-((2-(benzyloxy)-5-chlorobenzyl)oxy)benzylamine), which shows a Ki value of 47.6 nM. Further high-resolution cryo-EM analysis at 2.08 Å resolution unambiguously determined the DQ-18 binding pose. Our integrated approach offers a framework for structure-based de novo drug development based on the desired pharmacophores within the protein structure.

[Efficacy and safety of endoscopic diaphragm incision in children with congenital duodenal diaphragm].

Objective: To explore the efficacy and safety of endoscopic diaphragm incision in pediatric congenital duodenal diaphragm. Methods: Eight children with duodenal diaphragm treated by endoscopic diaphragm incision in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from October 2019 to May 2022 were enrolled in this study. Their clinical data including general conditions, clinical manifestations, laboratory and imaging examinations, endoscopic procedures and outcomes were retrospectively analyzed. Results: Among the 8 children, 4 were males and 4 females. The diagnosis was confirmed at the age of 6-20 months; the age of onset was 0-12 months and the course of disease was 6-18 months. The main clinical manifestations were recurrent non-biliary vomiting, abdominal distension and malnutrition. One case complicated with refractory hyponatremia was first diagnosed with atypical congenital adrenal hyperplasia in the endocrinology department. After treatment with hydrocortisone, the blood sodium returned to normal, but vomiting was recurrent. One patient underwent laparoscopic rhomboid duodenal anastomosis in another hospital but had recurred vomiting after the operation, who was diagnosed with double duodenal diaphragm under endoscope. No other malformations were found in all the 8 cases. The duodenal diaphragm was located in the descending part of the duodenum, and the duodenal papilla was located below the diaphragm in all the 8 cases. Three cases had the diaphragm dilated by balloon to explore the diaphragm opening range before diaphragm incision; the other 5 had diaphragm incision performed after probing the diaphragm opening with guide wire. All the 8 cases were successfully treated by endoscopic incision of duodenal diaphragm, with the operation time of 12-30 minutes. There were no complications such as intestinal perforation, active bleeding or duodenal papilla injury. At one month of follow-up, their weight increased by 0.4-1.5 kg, with an increase of 5%-20%. Within the postoperative follow-up period of 2-20 months, all the 8 children had duodenal obstruction relieved, without vomiting or abdominal distension, and all resumed normal feeding. Gastroscopy reviewed at 2-3 months after the operation in 3 cases found no deformation of the duodenal bulbar cavity, and the mucosa of the incision was smooth, with a duodenal diameter of 6-7 mm. Conclusion: Endoscopic diaphragm incision is safe, effective and less invasive in pediatric congenital duodenal diaphragm, with favorable clinical applicability.

Does gender influence retrograde intrarenal surgery (RIRS) outcomes? Data from the Flexible Ureteroscopy Outcomes Registry (FLEXOR).

INTRODUCTION AND OBJECTIVES: As well established flexible ureteroscopy (RIRS). There is still no evidence if gender can have any influence on the outcomes and complication when performing. This study aims to evaluate the role that gender has in performing flexible ureteroscopy from a large series of patients. METHODS: This study retrospectively analyzed patients who underwent RIRS for renal stones from January 2018 to August 2021 within the multicentric FLEXOR registry. Demographics, stone characteristics, perioperative findings, results and complications were analyzed and compared between gender groups. RESULTS: A total of 6669 patients were included, 66.1% were male and 33.9% were female. Stone characteristics was comparable between groups. Female patients had significant higher fever and positive urine culture rates (12% vs. 8% and 37% vs. 34%). Also, females had a slight longer hospital stay (3.8 vs. 3.5 days; P < 0.001) and more residual fragments after the procedure (23.03% vs. 20.97 (P = 0.032). Overall complications were slightly significantly higher in women (15.74% vs. 14% (P = 0.042)) mainly at the expense of fever rates (6.9% vs. 5.7%) whereas the risk of sepsis was similar in both groups. A multivariate analysis showed that larger stone size, multiple and lower pole stones seem to have a negative impact in the incidence of residual stones and complications. CONCLUSION: Our real life global study reflects that female gender may have a correlation with a slightly increased residual fragment rate and overall low grade complications. However, women can safely be treated with RIRS with no increased the rate of sepsis with appropriate care.

Methylprednisolone in severe COVID-19 with acute respiratory distress syndrome - less is more?

INTRODUCTION: Corticosteroids, particularly methylprednisolone, are part of the treatment for severe COVID-19 with acute respiratory distress syndrome (ARDS). In this study, we aimed to compare the mortalities of patients treated with higher versus lower doses of methylprednisolone. Secondary outcomes included oxygenation, need for mechanical ventilation, length of stay in intensive care unit (ICU), secondary infection, improvement of PaO2/FiO2 (PF) ratio, and inflammatory response as expressed by C-reactive protein (CRP). MATERIALS AND METHODS: A retrospective cohort study conducted at Sarawak General Hospital from 1st June to 30th September 2021. Patients who received intravenous methylprednisolone for severe COVID-19 in the ICU were identified and divided into two groups: higher dose (cumulative dose more than 10 mg per kg) and lower dose (cumulative dose less than 10 mg per kg). RESULTS: Out of a total of 165 patients, 40 (24.2%) patients received higher dose methylprednisolone. There was no significant difference in socio-demographic characteristics (age, gender, body mass index), COVID-19 vaccination status, laboratory parameters (lymphocyte count, CRP, lactate dehydrogenase, D-dimer), or usage of immunomodulator therapy between the groups. Overall mortality was 23.6%. Mortality in the higher dose group was twice as high compared to lower dose group (37.5% versus 19.2%) (OR 3.79, 95% CI 1.24-11.59, p<0.05). In addition, the higher dose cohort developed more secondary infections (87.5%) and had longer stays in ICU (median 11 days, IQR 8- 15). No significant difference was found between both cohorts in terms of CRP reduction, improvement of PF ratio, or the need for mechanical ventilation post methylprednisolone. CONCLUSION: In this study, the use of higher dose methylprednisolone in COVID-19 with ARDS was not associated with better clinical outcomes. A lower dose of methylprednisolone might be sufficient in treating severe COVID-19 with ARDS.

Moving from long case to scenario-based clinical examination: Proposals for making it feasible.

INTRODUCTION: Our faculty used one long case (LC) and three short cases for the clinical component of the final professional examinations. During the COVID-19 pandemic, the LC had to be replaced with scenario-based clinical examination (SBCE) due to the impracticability of using recently hospitalised patients. While keeping the short case component as usual, the LC had to be replaced with SBCE in 2020 for the first time at a short notice. To evaluate the positive and negative aspects of SBCE and LC to determine the feasibility of replacing LC with SBCE in future examinations. MATERIALS AND METHODS: We compared the LC scores of three previous years with those of the SBCE and studied the feedback of the three stakeholders: students, examiners, and simulated patients (SPs), regarding their experience with SBCE and the suitability of SBCE as an alternative for LC in future examinations. RESULTS: The SBCE scores were higher than those of the LC. Most of the examiners and students were not in favour of SBCE replacing LC, as such. The SPs were more positive about the proposition. The comments of the three stakeholders brought out the plus and minus points of LC and SBCE, which prompted our proposals to make SBCE more practical for future examinations. CONCLUSION: Having analysed the feedback of the stakeholders, and the positive and negative aspects of LC and SBCE, it was evident that SBCE needed improvements. We have proposed eight modifications to SBCE to make it a viable alternative for LC.

Frontiers in metalloprotein crystallography and cryogenic electron microscopy.

Metalloproteins comprise at least a third of all proteins that utilize redox properties of transition metals on their own or as parts of cofactors. The development of third generation storage ring sources and X-ray free-electron lasers with femtosecond pulses in the first decade of the 21st century has transformed metalloprotein crystallography. In the past decade, cryogenic-electron microscopy single-particle analysis, which does not require crystallization of biological samples has been extensively utilized, particularly for membrane-bound metalloprotein systems. Here, we explore recent frontiers in metalloprotein crystallography and cryogenic electron microscopy, organized for convenience under three metalloprotein-centered biological cycles, focusing on contributions from each technique, their synergy and the ability to preserve metals' redox states when subjected to a particular probe.

[Epidemiological characteristics of COVID-19 caused by 2019-nCoV Delta variant in Shangyu district, Shaoxing of Zhejiang province].

Objective: To investigate the epidemiological characteristics of COVID-19 caused by 2019-nCoV Delta variant in Shangyu district, Shaoxing of Zhejiang province in 2021, and provide evidence for the improvement of COVID-19 control and prevention measures. Methods: The incidence data of COVID-19 in Shangyu from December 7 to 21, 2021 was obtained from Shangyu District Center for Disease Control and Prevention. The epidemiological characteristics of the cases, i.e. the population, time and space distributions, were analyzed, and the incubation period and time-varying reproduction numbers (Rt) were calculated. Results: From December 7 to 21, 2021, a total of 380 COVID-19 cases caused by 2019-nCoV Delta variant were detected in Shangyu, the median age of the cases was 52 years, M (Q1，Q3: 38, 61). The male to female ratio of the cases was 1∶1.25, and the cases were mainly workers (36.58%) and farmers (27.63%). The epidemic affected 9 townships (or community) of Shangyu, especially Caoe and Baiguan communities with the cases accounting for 57.10% and 31.53% respectively. The median incubation period of cases was 4.00 days, M (Q1，Q3: 3.00, 5.75). The basic reproduction number (R0) was 4.06, and the Rt was 5.62 in early phase of the outbreak (the highest) and continuously decreased to less than 1.00 within 10 days after the detection of the outbreak. The number of COVID-19 cases decreased to 0 within 14 days after the outbreak (December 7-21), and the main detection methods were screening in centralized isolation (55.53%) and home isolation (40.00%). The infection rates of close contacts and secondary close contacts were 2.06% and 0.46% respectively. Conclusion: The epidemic of COVID-19 in Shangyu characterized by short incubation period, large number of infected people, and case clustering, suggesting the strong transmission of Delta variant (B.1.617.2). Comprehensive prevention and control measures, such as management of close contacts and secondary close contacts, and high-risk area, are essential for the rapid control of the epidemic.

[Application value of BIS and S100ß combined with Copeptin in patients with acute severe carbon monoxide poisoning].

Objective: To explore the application value of bispectral index(BIS) , specific protein 100ß(S100ß) combined with Copeptinin patients with acute severe carbon monoxide poisoning (ASCMP). Methods: A total of 256 patients with acute carbon monoxide poisoning admitted to Hengshui People's Hospital from June 2018 to June 2020 were collected, and they were divided into 30 mild cases, 40 moderate cases and 186 severe cases according to the degree of poisoning. Among them, patients with severe carbon monoxide poisoning were divided into a poor prognosis group (20 cases) and a good prognosis group (166 cases) according to whether adverse events occurred. The changes of creatine kinase isoenzyme (CK-MB) , N-terminal precursor B-type brain natriuretic peptide (NT-proBNP) , BIS, S100ß, and Copeptin in poisoned patients were measured. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the significance of relevant indicators for ASCMP patients. Results: Compared with the mild-to-moderate group, CK-MB, NT-proBNP, S100ß, Copeptin increased, and BIS value decreased in the severe group (P< 0.05). 24 hours after admission, compared with the good prognosis group, CK-MB, NT-proBNP, S100ß, Copeptin in the poor prognosis group increased, and the BIS value decreased (P<0.05). In the poor prognosis group, CK-MB, NT-proBNP, S100ß, and Copeptin at 72 hours after admission were all lower than those at 24 hours after admission, and the BIS value was higher than that at 24 hours after admission (P<0.05). Logistic regression analysis showed that ASCMP patients with increased S100ß, Copeptin, and decreased BIS values had an increased risk of adverse events (P<0.05). The ROC curve showed that the area under the curve of the combined detection of BIS, S100ß and Copeptin was 0.859, which had a great predictive value for the prognosis of ASCMP patients. Conclusion: BIS, S100ß combined with Copeptin detection is of great value for early assessment of ASCMP disease and prognosis prediction.

Dropping the non-core subjects from undergraduate final professional examination: How it would impact the results.

INTRODUCTION: Observing the dearth of distinctions in the two decades of final professional medical examinations (FPE) caused concern. Multiple True False (MTF) tests with penalty scoring pulling down the scores was considered one reason. Another possible reason was having too many subjects covered in the MTF and Best Answer Question (BAQ) papers. This study aimed to explore the impact of dropping the non-core subjects with minimal inputs from MTF and BAQ papers and the students' views in this regard. MATERIALS AND METHODS: We examined the students' performance in the core and non-core subjects in MTF and BAQ papers and the impact of dropping the non-core subjects' contribution to the students' scores of the recent four final professional examinations. We also surveyed the opinions of the students, who took the FPE in the year 2000. RESULTS: The failure rates were significantly higher in noncore than core subjects (p < 0.001) except in one MTF paper. The mean scores were significantly lower in non-core than core subjects in all the four FPEs (p < 0.05) except in one MTF paper. Dropping the non-core subject items from MTF and BAQ showed an improvement in the scores of MTF, theory total, and most grand totals resulting in two more students reaching distinction status. A mere 3.8% of the students could thoroughly revise the non-core subjects before the FPE. Two-fifth of them believed that non-core subjects had a significant impact on theory performance. Only 31.5% favoured dropping the non-core subjects, and an equal number preferred a status quo, while the rest suggested a reduction in their weightage. CONCLUSION: Most of the students considered the non-core subjects important in their career. However, very few of them could revise these subjects for the professional examination. The study demonstrated that dropping the non-core subjects from MTF and BAQ improved the students' final scores and helped more students to attain distinction status.

Large Culprit Plaque and More Intracranial Plaques Are Associated with Recurrent Stroke: A Case-Control Study Using Vessel Wall Imaging.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic plaque features are potential factors associated with recurrent stroke, but previous studies only focused on a single lesion, and few studies investigated them with perfusion impairment. This study aimed to investigate the association among whole-brain plaque features, perfusion deficit, and stroke recurrence. MATERIALS AND METHODS: Patients with ischemic stroke due to intracranial atherosclerosis were retrospectively collected and categorized into first-time and recurrent-stroke groups. Patients underwent high-resolution vessel wall imaging and DSC-PWI. Intracranial plaque number, culprit plaque features (such as plaque volume/burden, degree of stenosis, enhancement ratio), and perfusion deficit variables were recorded. Logistic regression analyses were performed to determine the independent factors associated with recurrent stroke. RESULTS: One hundred seventy-five patients (mean age, 59 [SD, 12] years; 115 men) were included. Compared with the first-time stroke group (n = 100), the recurrent-stroke group (n = 75) had a larger culprit volume (P = .006) and showed more intracranial plaques (P < .001) and more enhanced plaques (P = .003). After we adjusted for other factors, culprit plaque volume (OR, 1.16 per 10-mm3 increase; 95% CI, 1.03-1.30; P = .015) and total plaque number (OR, 1.31; 95% CI, 1.13-1.52; P < .001) were independently associated with recurrent stroke. Combining these factors increased the area under the curve to 0.71. CONCLUSIONS: Large culprit plaque and more intracranial plaques were independently associated with recurrent stroke. Performing whole-brain vessel wall imaging may help identify patients with a higher risk of recurrent stroke.

Comparing CxBladder to Urine Cytology as Adjunct to Cystoscopy in Surveillance of Non-muscle Invasive Bladder Cancer-A Pilot Study.

Purpose: Guidelines advocate cystoscopy surveillance (CS) for non-muscle invasive bladder cancer (NMIBC) post-resection. However, cystoscopy is operator dependent and may miss upper tract lesions or carcinoma in-situ (CIS). Urine cytology is a common adjunct but lacks sensitivity and specificity in detecting recurrence. A new mRNA biomarker (CxBladder) was compared with urine cytology as an adjunct to cystoscopy in detecting a positive cystoscopy findings during surveillance cystoscopy in our center. Materials and Methods: Consented patients older than 18, undergoing CS for NMIBC, provide paired urine samples for cytology and CxBladder test. Patients with positive cystoscopy findings would undergo re-Trans Urethral Resection of Bladder Tumor (TURBT). Results: Thirty-five patients were enrolled from April to June 2019. Seven contaminated urine samples were excluded. The remaining cohort of 23 (82%) and 5 (18%) females had a mean age of 66.69 (36-89). Eight (29%) patients with positive cystoscopy finding underwent TURBT. All 8 patients also had positive CxBladder result. This shows that CxBladder has a sensitivity and negative predictive value (NPV) of 100%, specificity of 75% and positive predictive value (PPV) of 62% in predicting a positive cystoscopy finding. TURBT Histo-pathological findings showed Low-grade Ta NMIBC in one patient (4%), and 7 (25%) patients had inflammatory changes. Urine cytology was only positive in one patient with a positive cystoscopy finding. This led to a sensitivity of merely 13% and NPV of 74%, while specificity and PPV was 100% in predicting a positive cystoscopy finding. Conclusion: CxBladder had high NPV and sensitivity which accurately predicted suspicious cystoscopy findings leading to further investigation. It has great potential for use as adjunct to cystoscopy for surveillance of NMIBC.

24-hr observation unit is safe location for rapid glucose control in uncomplicated severe hyperglycaemia.

BACKGROUND: Uncomplicated hyperglycaemia is a common presentation in the emergency department (ED). Rapid glucose control is associated with the risk of iatrogenic hypoglycaemia. We sought to determine the safety of a rapid glucose control protocol delivered in a 24-h emergency department observation unit (OU). METHODS: This is a retrospective chart review of patients admitted to the OU for hyperglycaemia where the assessing clinician deemed there was no other reason for medical admission apart from hyperglycaemia; and that the patient could be safely discharged provided their hyperglycaemia was adequately treated. The rapid glucose control protocol consists of 4-6 hourly glucose monitoring and insulin injections according to a sliding scale. We report the demographics, reduction in glucose values and the incidence of hypoglycaemia in the OU. We also determine the rate of discharge from OU and the rate of hospital admission at 30 days. RESULTS: We included 101 patients. The mean age was 53.5 years (95% CI 50.4-56.6) and 64% of patients were male. The mean HbA1c value was 12.8% (95% CI 12.3-13.3). The mean admission and discharge glucose values were 27.2 (95% CI 26.3-28.1) and 13.9 (95% CI 13.2-14.6) mmols/l respectively. There was no incidence of hypoglycaemia in the OU. We successfully discharged 90.1% of the patients from the OU, of which 3 (3.3%) patients were admitted to the hospital within 30 days of discharge. CONCLUSION: ED OU is a safe location to deliver effective management for patients presented with uncomplicated severe hyperglycaemia.

The active form of quinol-dependent nitric oxide reductase from Neisseria meningitidis is a dimer.

Neisseria meningitidis is carried by nearly a billion humans, causing developmental impairment and over 100 000 deaths a year. A quinol-dependent nitric oxide reductase (qNOR) plays a critical role in the survival of the bacterium in the human host. X-ray crystallographic analyses of qNOR, including that from N. meningitidis (NmqNOR) reported here at 3.15 Šresolution, show monomeric assemblies, despite the more active dimeric sample being used for crystallization. Cryo-electron microscopic analysis of the same chromatographic fraction of NmqNOR, however, revealed a dimeric assembly at 3.06 Šresolution. It is shown that zinc (which is used in crystallization) binding near the dimer-stabilizing TMII region contributes to the disruption of the dimer. A similar destabilization is observed in the monomeric (∼85 kDa) cryo-EM structure of a mutant (Glu494Ala) qNOR from the opportunistic pathogen Alcaligenes (Achromobacter) xylosoxidans, which primarily migrates as a monomer. The monomer-dimer transition of qNORs seen in the cryo-EM and crystallographic structures has wider implications for structural studies of multimeric membrane proteins. X-ray crystallographic and cryo-EM structural analyses have been performed on the same chromatographic fraction of NmqNOR to high resolution. This represents one of the first examples in which the two approaches have been used to reveal a monomeric assembly in crystallo and a dimeric assembly in vitrified cryo-EM grids. A number of factors have been identified that may trigger the destabilization of helices that are necessary to preserve the integrity of the dimer. These include zinc binding near the entry of the putative proton-transfer channel and the preservation of the conformational integrity of the active site. The mutation near the active site results in disruption of the active site, causing an additional destabilization of helices (TMIX and TMX) that flank the proton-transfer channel helices, creating an inert monomeric enzyme.

Data on the effect of electrospinning parameters on the morphology of the nanofibrous poly(3-hydroxybutyrate-co-4-hydroxybutyrate) scaffolds.

Electrospinning is a promising approach to fabricate desirable electropsun nanofibrous scaffold that could be applied in the medical fields. In this study, bacterial copolymer poly(3-hydroxybutyrate-co-68 mol% 4-hydroxybutyrate) [P(3HB-co-68mol% 4HB)] copolymer produced was fabricated into electrospun nanofibers using various combination of electrospinning parameters including the polymer solution, applied voltage and injection speed. The morphology of the fabricated scaffolds were observed using scanning electron microscope (SEM). The SEM images were analysed for the fibre diameter distribution of the scaffolds using Image Analyser. The results revealed that the 8 wt% of polymer solution, 25 kV/cm of the applied voltage and 1.5 mL/h of the injection speed was the most suitable combination. This electrospinning parameters combination fabricated nanofibrous P(3HB-co-4HB) scaffold with smooth, beadles and uniform nanofibers with small fibre diameter distribution.

LncRNA ITGB1 promotes the development of bladder cancer through regulating microRNA-10a expression.

OBJECTIVE: This study aims to investigate the expression level of lncRNA ITGB1 both in bladder cancer (BCa) tissue and cell lines, as well as to evaluate its function and potential mechanism in the progression of BCa. PATIENTS AND METHODS: The expressions of lncRNA ITGB1 in 36 BCa tissues samples (and corresponding adjacent normal ones) and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection of sh-ITGB1 in BCa cell lines, the effect of ITGB1 on the proliferation of BCa cells was examined by cell counting kit-8 (CCK-8) assay and colony formation assay. Subsequently, qRT-PCR was used to examine microRNA-10a expression in BCa tissues and cells after ITGB1 was silenced. At the same time, the correlation between ITGB1 and microRNA-10a expression was analyzed. Finally, cell recovery experiment was applied for the in-depth study of the interaction between ITGB1 and microRNA-10a and its underlying mechanism. RESULTS: LncRNA ITGB1 was found upregulated in BCa tissues and cell lines. Knockdown of lncRNA ITGB1 remarkably inhibited cell proliferation. The expression levels of ITGB1 and microRNA-10a in BCa tissues were negatively correlated. ITGB1 downregulation was found to be able to enhance microRNA-10a expression, suggesting that microRNA-10a may be a potential target for ITGB1 in BCa. In addition, cell reverse experiment also verified that ITGB1 could regulate the expression of microRNA-10a, and their interaction affected the malignant progression of BCa. CONCLUSIONS: LncRNA ITGB1 level is upregulated in BCa tissues and associated with the pathological stage of BCa, which could be used as a new predictor of BCa patients' prognosis. In addition, ITGB1 might promote BCa cell proliferation via regulating microRNA-10a expression.