Insulin resistance, and not ß-cell impairment, mediates association between Mycobacterium tuberculosis sensitization and type II diabetes mellitus among US adults.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (M.tb) by mechanisms that remain to be fully explained. We evaluated association between M.tb sensitization and T2DM among U.S adults and, via formal mediation analysis, the extent to which this association is mediated by insulin resistance and/or ß-cell failure. These evaluations accounted for demographic, socio-economic, behavioral and clinical characteristics. T2DM was assessed by fasting plasma glucose, 2-hour oral glucose tolerance testing and HbA1c; homoeostasis model assessment 2 (HOMA2) was used to estimate ß-cell dysfunction (HOMA2-B) and insulin resistance (HOMA2-IR); while M.tb sensitization status was ascertained by tuberculin skin testing (TST). Exposure to M.tb was associated with increased risk for T2DM, likely driven by an increase in insulin resistance. Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Research in Context: What is already known about this subject?: Accumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure to Mycobacterium tuberculosis ( M.tb ) via mechanisms that remain to be unraveled What is the key question?: To what extent do insulin resistance and ß-cell failure mediate the association between M.tb sensitization with T2DM among US adults? What are the new findings?: M.tb sensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG) Insulin resistance, and not ß-cell impairment, likely independently mediate the observed diabetogenic effects of M.tb sensitization How might this impact on clinical and/or public health practice in the foreseeable future?: If corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomesThis will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM.

Time toxicity associated with early phase clinical trial participation.

BACKGROUND: Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation. PATIENTS AND METHODS: A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work. RESULTS: A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n = 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy. CONCLUSIONS: Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

Elevated plasma matrix metalloproteinases associate with Mycobacterium tuberculosis blood stream infection and mortality in HIV-associated tuberculosis.

Mortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality and Mycobacterium tuberculosis (Mtb) blood stream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10 and procollagen III N-terminal propeptide (PIIINP) associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.

Lost in Follow-Up: Predictors of Patient No-Shows to Clinic Follow-Up After Abdominal Injury.

BACKGROUND: The aim of this study is to evaluate risk factors for non-attendance to post-discharge, hospital follow-up appointments for traumatically injured patients who underwent exploratory laparotomy. METHODS: This is a retrospective chart review of patients who underwent exploratory laparotomy for traumatic abdominal injury at an urban, Midwestern, level I trauma center with clinic follow-up scheduled after discharge. Clinically, relevant demographic characteristics, patients' distance from hospital, and the presence of staples, sutures, and drains requiring removal were collected. Descriptive statistics of categorical variables were calculated as totals and percentages and compared with a chi-squared test or Fisher's exact when appropriate. RESULTS: The sample included 183 patients who were largely assaultive trauma survivors (68%), male (80%), and black (53%) with a mean age of 35.4 ± 14.9 years. Overall, 18.5% no-showed for their follow-up appointment. On multivariate analysis for clinic no-show; length of stay (odds ratio = 0.92 [0.84-0.99], P = 0.04) and the need for suture, staple, or drain removal were protective for clinic attendance (odds ratio = 5.59 [1.07-7.01], P = 0.04). Overall, 12 patients (6.4%) were readmitted. Forty patients (18.3%) had their follow-up in the emergency department (ED). On multivariate regression of risk factors for ED visits, the only statistically significant factors (P < 0.05) were clinic appointment no-show (OR = 2.81) and self-pay insurance (OR = 4.78). CONCLUSIONS: Abdominal trauma patients are at high risk of no-show for follow-up appointments and no-show visits are associated with ED visits. Future work is needed evaluating interventions to improve follow-up.

The longitudinal relationship between child emotional disorder and parental mental health in the British Child and Adolescent Mental Health surveys 1999 and 2004.

BACKGROUND: Research suggests parental psychopathology has an adverse effect on child mental health. However, due to the interactional nature of parent-child relationships and with a high rate of emotional disorders reported in school-age children, it is important to know whether the effect is reciprocal. METHODS: We explored the longitudinal relationship between child and parent mental health in the British Child and Adolescent Mental Health Surveys (N=7,100 child-parent dyads) and their three-year follow-ups. The Development and Well-Being Assessment with DSM-IV diagnostic criteria was used to measure child psychiatric diagnoses, while parental mental health was assessed using the General Health Questionnaire. Multivariable logistic regression was used to explore the longitudinal association between child emotional disorder and parent mental health. RESULTS: Parents of children who had an emotional disorder at baseline were more likely to have poor mental health three years later compared with parents whose children had no psychiatric diagnosis (33.3% versus 16.7%; crude odds ratio=2.52; adjusted odds ratio=2.19, 95% CI=1.58 to 3.05, p<0.001). Children of parents with poor mental health at baseline were more likely to develop an emotional disorder three years later compared with children whose parents had good mental health (5.2% versus 2.5%; crude odds ratio=2.08; adjusted odds ratio=1.63, 95% CI=1.18 to 2.25, p=0.003). LIMITATIONS: The findings of this research are limited by the survey data collected, the measures used and survey dropout. CONCLUSIONS: We detected a bi-directional relationship between child and parent mental health, suggesting that effective intervention for one individual may benefit other family members.

A realist evaluation of a collaborative model to support research co-production in long-term care settings in England: the ExCHANGE protocol.

BACKGROUND: Collaborative working between academic institutions and those who provide health and social care has been identified as integral in order to produce acceptable, relevant, and timely research, and for outputs to be useful and practical to implement. The ExCHANGE Collaboration aims to bring together researchers and people working, living in and visiting care homes to build capacity, share and mobilise knowledge, and identify key areas for future research. This paper describes an embedded, formative, realist and theory-driven evaluation which aims to gather information about how successful the ExCHANGE Collaboration is perceived to be in achieving its aims. An existing realist programme theory from the literature - Closer Collaboration - will be supplemented by two substantive theories: Co-production and Knowledge Brokering. This will result in an initial programme theory which will be tested by this formative evaluation to refine understanding of how the ExCHANGE Collaboration works. METHODS: The evaluation will employ mixed qualitative methods, including: analysis of documents such as feedback forms, Knowledge Broker journal/diary, event attendance records, risk and issues logs and other relevant paperwork gathered as part of project delivery; observations of events/activities; and interviews with care home providers and staff, care home residents, residents' family members, and researchers who are involved in the project (both project design/delivery, and also attendance or involvement in project activities/events). Framework Analysis will be used to interpret the data collected; analysis will be strategic, by focusing on particular key areas of importance in the developing theory of how the ExCHANGE Collaboration might achieve change. RESULTS: The results of this study are expected to be published in 2022. DISCUSSION: This evaluation will investigate how successful the ExCHANGE Collaboration is perceived to be in achieving its aims, in what way, in which contexts, and how this may differ for those involved. It will do this by testing an initial programme theory about how the collaboration works, for whom, under which circumstances, and in what way. Findings will be shared through written publication, an end of project learning event for those involved/interested in the project, and a lay summary to be made publically available.

Complications from Needle Thoracostomy: Penetration of the Myocardium.

We report a rare but serious complication of needle thoracostomy, penetration of the myocardium. Needle thoracostomy is typically performed in the prehospital setting or upon arrival in the emergency department for suspected tension pneumothorax. Needle decompression is generally taught and done anteriorly, in the 2nd intercostal space on the midclavicular line (MCL). An alternative approach is laterally, along the anterior axillary line (AAL) in the 4th intercostal space. Our case supports prior literature that the anterior MCL location has a low rate of efficacy to decompress the chest, as well as a high rate of complications. We recommend performing needle decompression laterally at the AAL whether in the field or in the emergency department.

The geometry of the toxicity of silver nanoparticles to freshwater mussels.

The question about the influence of the geometry of silver nanoparticle (nAg) towards toxicity in aquatic organisms is largely unanswered. The purpose of this study was to examine if different geometries of nAg could initiate biophysical stress in the soft tissues of mussels. Freshwater Dreissenna bugensis mussels were exposed for 48 h at 15 °C to 10 and 50 µg/L of ionic Ag and to 3 forms of polyvinylpyrrolidone (PVP)-coated nAg of similar size: sphere, cube and prism. At the end of the exposure period, mussels were allowed to depurate overnight and the post-mitochondrial fraction of the soft tissues were analyzed for the levels of liquid crystals (LCs), changes in the activity and fractal dimensions of pyruvate kinase-lactate dehydrogenase (PK-LDH), F-actin and protein-ubiquitin (UB) levels. The data revealed that exposure to nAg forms lead to increased formation of LCs in increasing order of intensity: prismatic > cubic > spherical nAg. The activity in PK-LDH was decreased by all forms of nAg but not by ionic Ag+ (as with the following effects). Fractal kinetics of the PK-LDH system revealed that the nAg forms increased the spectral dimension (sD) in increasing order: spherical > cubic > prismatic nAg. A decrease in the fractal diffusion rate (fDR) with small changes in the fractal dimension (fD) was also obtained. The levels of F-actin and protein-UB were significantly affected for most forms of nAg and followed a pattern similar to LCs levels. In conclusion, the geometry of nAg could influence the formation of LCs, alter the fractal kinetics of the PK-LDH system, F-actin levels and protein damage in the soft tissues of freshwater mussels.

Nonrestorative sleep scale: a reliable and valid short form of the traditional Chinese version.

PURPOSE: Previous research has suggested the essential unidimensionality of the 12-item traditional Chinese version of the Nonrestorative Sleep Scale (NRSS). This study aimed to develop a short form of the traditional Chinese version of the NRSS without compromising its reliability and validity. METHODS: Data were collected from 2 cross-sectional studies with identical target groups of adults residing in Hong Kong. An iterative Wald test was used to assess differential item functioning by gender. Based on the generalized partial credit model, we first obtained a shortened version such that further shortening would result in substantial sacrifice of test information and standard error of measurement. Another shortened version was obtained by the optimal test assembly (OTA). The two shortened versions were compared for test information, Cronbach's alpha, and convergent validity. RESULTS: Data from a total of 404 Chinese adults (60.0% female) who had completed the Chinese NRSS were gathered. All items were invariant by gender. A 6-item version was obtained beyond which the test performance substantially deteriorated, and a 9-item version was obtained by OTA. The 9-item version performed better than the 6-item version in test information and convergent validity. It had discrimination and difficulty indices ranging from 0.44 to 2.23 and - 7.58 to 2.13, respectively, and retained 92% of the test information of the original 12-item version. CONCLUSION: The 9-item Chinese NRSS is a reliable and valid tool to measure nonrestorative sleep for epidemiological studies.

Perspectives on the fellowship training in cardiac, thoracic, and vascular anesthesia and critical care in Europe from program directors and educational leads around europe

ABSTRACT:This article reviews fellowship training in adult cardiac, thoracic, and vascular anesthesia and critical care from the perspective of European program initiators and educational leaders in these subspecialties together with current training fellows. Currently, the European Association of Cardiothoracic Anaesthesiology (EACTA) network has 20 certified fellowship positions each year in 10 hosting centers within 7 European countries, with 2 positions outside Europe (São Paulo, Brazil). Since 2009, 42 fellows have completed the fellowship training. The aim of this article is to provide an overview of the rationale, requirements, and contributions of the fellows, in the context of the developmental progression of the EACTA fellowship in adult cardiac, thoracic, and vascular anesthesia and critical care from inception to present. A summary of the program structure, accreditation of host centers, requirements to join the program, teaching and assessment tools, certification, and training requirements in transesophageal electrocardiography is outlined. In addition, a description of the current state of EACTA fellowships across Europe, and a perspective for future steps and challenges to the educational program, is provided. (AU)

The influence of surface coatings on the toxicity of silver nanoparticle in rainbow trout.

Silver nanoparticles (nAg) are often produced with different coatings that could influence bioavailability and toxicity in aquatic organisms. The purpose of this study was to examine the influence of 4 surface coatings of nAg of the same core size towards bioavailability and toxicity in juvenile rainbow trout (Oncorhynchus mykiss). Juveniles were exposed to 50 µg/L of 50 nm diameter nAg for 96 h at 15 °C with the following coatings: branched polyethylenimine (bPEI), citrate, polyvinylpyrrolidone (PVP) and silicate (Si). The data revealed that the coatings influenced hepatic Ag loadings in the following trend PVP > citrate > bPEI and Si with estimated bioavailability factors of 28, 18, 6 and 2 L/kg respectively. Hepatic Ag levels were significantly associated with DNA damage and inflammation as determined by arachidonate cyclooxygenase activity. The bPEI and citrate-coated nAg consistently produced the observed effects above in addition to increased mitochondrial electron transport activity and glutathione S-transferase activity. The absence of metallothionein and lipid peroxidation suggests that mechanisms other than the liberation of Ag+ were at play. In conclusion, surface coatings were shown to significantly influence bioavailability and toxic properties of nAg to rainbow trout juveniles.

Pelvic organ prolapse: An unusual cause of small bowel obstruction.

We present the rare case of a small bowel obstruction secondary to pelvic organ prolapse (POP). A 77-year-old female presented with four days of abdominal pain, nausea, and vomiting. She had a history of abdominal hysterectomy with bilateral salpingo-opherectomy and a mildly symptomatic cystocele. She was found to have an enterocele causing small bowel obstruction. The enterocele was manually reduced and subsequently managed non-operatively with a pessary. Prior case reports of small bowel obstructions secondary to POP required emergent surgical intervention. Post-menopausal women should be asked about symptoms or presence of pelvic organ prolapse and in the correct patient population, pelvic examination can be important for diagnosis and treatment of small bowel obstruction. If the enterocele is manually reduced non-operative management can be safe and effective.

The Risk of Post-operative Complications in Super-Super Obesity Compared to Super Obesity in Accredited Bariatric Surgery Centers.

BACKGROUND: The prevalence of super obesity (SO, BMI > 50.0 kg/m2) and super-super obesity (SSO, BMI > 60 kg/m2) is increasing. Current data are limited and discrepant on the relationship between SSO and post-bariatric surgery complication risk. We hypothesized there would be increased complications for both laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG) in SSO compared to SO, but the relative risk (RR) would support the use of LSG in SSO patients. METHODS: Metabolic and Bariatric Surgery Accreditation and Quality Improvement 2016 data were queried for SO and SSO patients undergoing LRYGB or LSG. Thirty-day post-operative complications were calculated. Univariate analyses were performed with a χ2 or Student's t test. Comparisons between multiple groups were performed using a one-way ANOVA. Statistical significance was defined as p < 0.05. RESULTS: A total of 5723 patients with SSO and 24,940 with SO were included for analysis. Patients with SSO had more co-morbidities. Patients with SSO had a higher likelihood of complications compared to SO patients (15.2% vs 12.6%, p < 0.0005). SSO patients, and specifically SSO RYGB, were significantly more likely to experience an unplanned intubation, prolonged ventilation, and unplanned ICU admission. Compared to SO LRYGB, the RR for complications in SSO LRYGB and LGS were 1.19 and 0.76 respectively (p < 0.0005). DISCUSSION: We found SSO patients had increased 30-day post-operative complications after both LRYGB and LSG compared to SO patients. LSG may be the preferred procedure for this high-risk population.

Nonrestorative sleep scale: reliable and valid for the Chinese population.

PURPOSE: To conduct a linguistic and psychometric evaluation of a Chinese version of the Nonrestorative Sleep Scale (NRSS). METHODS: The Chinese NRSS was created from a standard forward-backward translation and trialed on 10 Chinese adults. Telephone interviews were then conducted with 100 adults, who completed the Chinese NRSS, the Pittsburgh Sleep Quality Index (PSQI), the Athens Insomnia Scale (AIS), the Center for Epidemiological Studies Depression Scale (CES-D), and the Toronto Hospital Alertness Test (THAT). A household survey was conducted with 20 subjects, followed by a confirmatory factor analysis (CFA), and a bifactor model was developed to evaluate the reliability and validity of the NRSS. RESULTS: The bifactor model had the root mean square error of approximation (RMSEA), standardized root mean square residual (SRMR), and comparative fit index (CFI) of 0.06, 0.06, and 0.97, respectively. Convergent validity was shown from the moderate associations with PSQI (r = - 0.66, P < 0.01), AIS (r = - 0.65, P < 0.01), CES-D (r = - 0.54, P < 0.01), and THAT (r = 0.68, P < 0.01). The coefficient omega (0.92), omega hierarchical (0.81), factor determinacy (0.93), H value (0.91), explained common variance (0.63), and percentage of uncontaminated correlations (0.80) derived from the bifactor CFA supported the essential unidimensionality of NRSS. CONCLUSIONS: The Chinese NRSS is a valid and reliable essential unidimensional tool for the assessment of nonrestorative sleep in the Chinese population.

The influence of surface waters on the bioavailability and toxicity of zinc oxide nanoparticles in freshwater mussels.

The release of engineered nanoparticles in the aquatic environment could pose a threat to the biota. The purpose of the study was to examine the influence of surface water characteristics on zinc oxide nanoparticles (nZnO) and ZnS04 toxicity to the freshwater mussel Dreissena polymorpha. Mussels were exposed to an equivalent concentration of 25 µg/L Zn as either nZnO or ZnSO4 for 96 h at 15 °C in 4 types of surface waters: green water (high conductivity and pH with low natural organic matter content), brown water (low conductivity and pH with high natural organic matter content), diluted municipal effluent (high conductivity and pH with high urban organic matter content) and aquarium water (treated green water with organic matter removed). After the exposure period, mussels were analyzed for air-time survival, total and labile Zn levels in tissues, lipid metabolism (phospholipase A2, triglycerides levels) and oxidative stress (glutathione S-transferase, arachidonate cyclooxygenase, lipid peroxidation). The data revealed that mussels exposed to ZnSO4 in controlled aquarium water accumulated more total and labile Zn tissues, decreased oxidative stress and triglycerides and increased air time survival. While nZnO had few effects in aquarium water, oxidative stress was enhanced and total Zn in tissues were decreased in brown water and diluted municipal effluent and triglycerides were higher in nZn-exposed mussels in brown water. Air-time survival was decreased in mussels kept in green water and nZnO. It was also decreased in mussels exposed to ZnSO4 in green water and diluted municipal effluent. In conclusion, the fate and toxic effects of Zn could be influenced by both the chemical form (nanoparticles or ionic Zn) and surface water properties in freshwater mussels.

Delivery of lethal dsRNAs in insect diets by branched amphiphilic peptide capsules.

Development of new and specific insect pest management methods is critical for overcoming pesticide resistance and collateral off-target killings. Gene silencing by feeding dsRNA to insects shows promise in this area. Here we described the use of a peptide nano-material, branched amphiphilic peptide capsules (BAPCs), that facilitates cellular uptake of dsRNA by insects through feeding. The insect diets included dsRNA with and without complexation with BAPCs. The selected insect species come from two different orders with different feeding mechanisms: Tribolium castaneum and Acyrthosiphon pisum. The gene transcripts tested (BiP and Armet) are part of the unfolded protein response (UPR) and suppressing their translation resulted in lethality. For Acyrthosiphon pisum, ingestion of BiP-dsRNA associated with BAPCs led to the premature death of the aphids (t1/2=4-5days) compared to ingestion of the same amounts of free BiP-dsRNA (t1/2=11-12days). Tribolium castaneum was effectively killed using a combination of BiP-dsRNA and Armet-dsRNA complexed with BAPCs; most dying as larvae or during eclosion (~75%). Feeding dsRNA alone resulted in fewer deaths (~30%). The results show that complexation of dsRNA with BAPCs enhanced the oral delivery of dsRNA over dsRNA alone.

Triple-Negative Breast Cancer: Who Should Receive Neoadjuvant Chemotherapy?

Progress in the treatment of triple-negative breast cancer remains an important challenge. Given the aggressive biology and high risk of distant recurrence, systemic chemotherapy is warranted in most patients. Neaodjuvant chemotherapy benefits patients with locally advanced disease by downsizing the tumor and increasing the probability of breast-conserving surgery. Clinical and pathologic responses provide important prognostic information, which makes neoadjuvant therapy an attractive approach for all patients with triple-negative breast cancer. Clinical research in the neoadjuvant setting is focused on improvement in pathologic complete response rates and outcomes of patients with residual disease.