Ambient fine particulate pollution associated with diabetes mellitus among the elderly aged 50 years and older in China.
The linkage between ambient air pollution exposure and occurrence of diabetes mellitus is not well defined. This study examined the association between exposure to fine particles (PM2.5) and the prevalence of diabetes among Chinese elderly people. We surveyed 11,504 adults aged ≥50 years in China, estimated the annual concentrations of ambient PM2.5 using a satellite-based model of aerosol optical depth information. We employed a generalized mixed effects model to examine the association between PM2.5 and the prevalence of diabetes and explored potential effect modifiers. We estimated diabetes burden attributable to ambient PM2.5 if the observed association is indeed causal. The diabetes prevalence among the participants was 6.5% (n = 745). Our analysis found a statistically significant association between PM2.5 and diabetes. The adjusted odds ratio was 1.27 (95% confidence interval (CI), 1.12, 1.43) for each 10 μg/m3 increment in ambient PM2.5. Stratified analyses found a lower association among the participants with higher consumption of fruit. We estimated that 22.02% (95% CI: 8.59%, 43.29%) of the diabetes cases could be ascribable to ambient PM2.5. Our finding suggests that PM2.5 exposures could increase the risk of diabetes, and if causal, could be responsible for substantial burden of diabetes among the Chinese elderly; and higher intakes of fruit might reduce the harmful effects of PM2.5, however, due to the limitation of the cross-sectional study design, more studies are warranted to confirm this observation.


Service for the Pseudonymization of Electronic Healthcare Records Based on ISO/EN 13606 for the Secondary Use of Information.
The availability of electronic health data favors scientific advance through the creation of repositories for secondary use. Data anonymization is a mandatory step to comply with current legislation. A service for the pseudonymization of electronic healthcare record (EHR) extracts aimed at facilitating the exchange of clinical information for secondary use in compliance with legislation on data protection is presented. According to ISO/TS 25237, pseudonymization is a particular type of anonymization. This tool performs the anonymizations by maintaining three quasi-identifiers (gender, date of birth, and place of residence) with a degree of specification selected by the user. The developed system is based on the ISO/EN 13606 norm using its characteristics specifically favorable for anonymization. The service is made up of two independent modules: the demographic server and the pseudonymizing module. The demographic server supports the permanent storage of the demographic entities and the management of the identifiers. The pseudonymizing module anonymizes the ISO/EN 13606 extracts. The pseudonymizing process consists of four phases: the storage of the demographic information included in the extract, the substitution of the identifiers, the elimination of the demographic information of the extract, and the elimination of key data in free-text fields. The described pseudonymizing system was used in three telemedicine research projects with satisfactory results. A problem was detected with the type of data in a demographic data field and a proposal for modification was prepared for the group in charge of the drawing up and revision of the ISO/EN 13606 norm.


Barriers and Enablers of Older Patients to Deprescribing of Cardiometabolic Medication: A Focus Group Study.
Deprescribing has been recommended for managing polypharmacy but deprescribing preventive medication in older patients is still uncommon. We aimed to investigate older patients' barriers to and enablers of deprescribing cardiometabolic medication. Two focus groups were conducted among patients ≥70 years with polypharmacy, including cardiometabolic medication. Purposive sampling through four community pharmacies was used in two regions in the Netherlands. A topic list was developed using literature and the theoretical domains framework (TDF). The meetings were audio recorded, transcribed verbatim and coded using thematic coding, attribute coding and the TDF. In addition, patients were categorized on attitudes towards medication and willingness to stop. The meetings were attended by 17 patients and 1 caregiver (71 to 84 years). In total 15 barriers and 13 enablers were identified within four themes, partly related to beliefs, fears and experiences regarding using or stopping medication, and partly related to the relationship with the health care professional and the conditions to stop. Some patients attributed their wellbeing to their medication and were therefore unwilling to stop. Reducing cardiometabolic medication because of less strict treatment targets confused some patients and was a barrier to deprescribing. Having options to monitor clinical measurements and restart medication were enablers. Patients were only willing to stop cardiometabolic medication when this was proposed by a HCP they trusted. Patients with a positive attitude towards medication varied in their willingness to stop cardiometabolic medication. Patients with a negative attitude towards medication were generally willing to stop medication but still perceived several barriers and may consider some medication as being essential. Fears, beliefs, and experiences regarding using and stopping medication as well as trust in the HCP influence willingness to have medication deprescribed. Attitudes towards medication in general do not necessarily translate into willingness or unwillingness to stop specific medication. For deprescribing cardiometabolic medication, patient involvement when setting new treatment targets and monitoring the effects on short-term outcomes are important.


Cross finger flaps.
Proper fingertip reconstruction requires good skin and soft tissue coverage, preservation of function and as normal an appearance as possible. The cross finger flap results in negligible joint stiffness, minimal morbidity and little work-time loss. An important factor is the conservation of finger length permitted by this technique. This method of repair is underutilized. It is indicated in several types of fingertip amputations where bone shortening would be detrimental.


Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma.
We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p < 0.001) differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001) and perilipin A in luminal A-type IDC (p = 0.007). Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004) and acyl-CoA oxidase 1 positivity (p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.


Improving preemptive transplant education to increase living donation rates: reaching patients earlier in their disease adjustment process.
Patients who receive a preemptive kidney transplant before starting dialysis avoid the medical complications related to dialysis and have the highest graft success and lowest mortality rates. Because only 2.5% of incident patients receive kidney transplants preemptively, improved psychosocial education may assist more patients in accessing preemptive transplant. This article outlines (1) unique psychosocial issues affecting patients with chronic kidney disease stage 4 (glomerular filtration rates > 20 mL/min per 1.73 m2) and (2) how an educational program about preemptive living donor transplant should be designed and administered to increase access to this treatment option. Early referral patients may be overwhelmed in coping with and learning about their disease and, therefore, not ready to make a treatment decision, or they may be highly motivated to obtain a transplant to avoid dialysis and return to a normal life. An education program that defines the quality-of-life and health benefits possible with early transplant is outlined. The program is focused on minimizing the disruption of starting 2 treatment techniques and maximizing early transplant health, graft survival, employability, and retention of insurance coverage. Once the benefits of preemptive living donor transplant are outlined, educators can focus on demystifying the living donor evaluation process and assisting interested patients in planning how to find a living donor. To reach all patients, especially racial minorities, education about preemptive transplant should be available in primary-care physicians' and community nephrologists' offices, at dialysis centers, and through other kidney organizations.


Etiology of Down syndrome: Evidence for consistent association among altered meiotic recombination, nondisjunction, and maternal age across populations.
Down syndrome caused by meiotic nondisjunction of chromosome 21 in humans, is well known to be associated with advanced maternal age, but success in identifying and understanding other risk factors has been limited. Recently published work in a U.S. population suggested intriguing interactions between the maternal age effect and altered recombination patterns during meiosis, but some of the results were counter-intuitive. We have tested these hypotheses in a population sample from India, and found that essentially all of the results of the U.S. study are replicated even in our ethnically very different population. We examined meiotic recombination patterns in a total of 138 families from the eastern part of India, each with a single free trisomy 21 child. We genotyped each family with a set of STR markers using PCR and characterized the stage of origin of nondisjunction and the recombination pattern of maternal chromosome 21 during oogenesis. Our sample contains 107 maternal meiosis I errors and 31 maternal meiosis II errors and we subsequently stratified them with respect to maternal age and the number of detectable crossover events. We observed an association between meiosis I nondisjunction and recombination in the telomeric 5.1 Mb of chromosome 21. By contrast, in meiosis II cases we observed preferential pericentromeric exchanges covering the proximal 5.7 Mb region, with interaction between maternal age and the location of the crossover. Overall reduction of recombination irrespective of maternal age is also evident in meiosis I cases. Our findings are very consistent with previously reported data in a U.S. population and our results are the first independent confirmation of those previous reports. This not only provides much needed confirmation of previous results, but it suggests that the genetic etiology underlying the occurrence of trisomy 21 may be similar across human populations.


Treatment of posttransplantation recurrence of hepatitis C with interferon and ribavirin: lessons on tolerability and efficacy.
Recurrence of hepatitis C virus (HCV) infection after orthotopic liver transplantation is a major cause of graft failure. The aim of our study was to determine the safety, efficacy, and tolerability of combination therapy with interferon and ribavirin in the treatment of recurrent hepatitis after liver transplantation. Twenty-six patients (18 men) with histologically established HCV recurrence after liver transplantation for cirrhosis secondary to chronic HCV infection were treated with a combination of interferon alfa-2b (3 million units three times weekly) and ribavirin (800 to 1,000 mg/d). Dosage modifications were according to a standard protocol incorporating laboratory values and clinical side effects. Fifty percent of patients completed 1 year or more of therapy. On an intention-to-treat basis, nine patients (35%) showed an end-of-treatment virological response. Six of these nine patients completed greater than 6 additional months of follow-up, and all have had sustained virological responses. A histological response (decrease in histological activity index > or = 2) was seen in 75% of virological responders and 67% of nonresponders. Adverse events requiring dose modification or cessation of therapy occurred in 66% of patients. Adjuvant therapies used to support hemoglobin levels included erythropoietin and red blood cell transfusions. There were no independent pretreatment predictors of a virological response, perhaps because of the small sample size. Combination therapy with interferon and ribavirin may be beneficial in patients with recurrent HCV after liver transplantation. The majority of patients require dose modifications because of side effects. Histological response is common in virological nonresponders.


Distribution and Diffusion of Macromolecule Delivery to the Brain via Focused Ultrasound using Magnetic Resonance and Multispectral Fluorescence Imaging.
Focused ultrasound (FUS), in combination with microbubble contrast agents, can be used to transiently open the blood-brain barrier (BBB) to allow intravascular agents to cross into the brain. Often, FUS is carried out in conjunction with magnetic resonance imaging (MRI) to evaluate BBB opening to gadolinium-based MRI contrast agents. Although MRI allows direct visualization of the distribution of gadolinium-based contrast agents in the brain parenchyma, it does not allow measurements of the distribution of other molecules crossing the BBB. Therapeutic molecules (e.g., monoclonal antibodies) are much different in size than MRI contrast agents and have been found to have different distributions in the brain after FUS-mediated BBB opening. In the work described here, we combined in vivo MRI and ex vivo multispectral fluorescence imaging to compare the distributions of MRI contrast and dextran molecules of different molecular weights (3, 70 and 500 kDa) after FUS-mediated BBB opening through a range of ultrasound pressures (0.18-0.46 MPa) in laboratory mice. The volume of brain exposed was calculated from the MRI and fluorescence images and was significantly dependent on both molecular weight and ultrasound pressure. Diffusion coefficients of the different-molecular-weight dextran molecules in the brain parenchyma were also calculated from the fluorescence images and were negatively correlated with the molecular weight of the dextran molecules. The results of this work build on a body of knowledge that is critically important for the FUS technique to be used in clinical delivery of therapeutics to the brain.


Human adenosine deaminase 2 deficiency: A multi-faceted inborn error of immunity.
Human adenosine deaminase 1 deficiency was described in the 1970s to cause severe combined immunodeficiency. The residual adenosine deaminase activity in these patients was attributed to adenosine deaminase 2. Human adenosine deaminase type 2 deficiency (DADA2), due to biallelic deleterious mutations in the ADA2 gene, is the first described monogenic type of small- and medium-size vessel vasculitis. The phenotype of DADA2 also includes lymphoproliferation, cytopenia, and variable degrees of immunodeficiency. The physiological role of ADA2 is still enigmatic hence the pathophysiology of the condition is unclear. Preliminary data showed that in the absence of ADA2, macrophage differentiation is skewed to a pro-inflammatory M1 subset, which is detrimental for endothelial integrity. The inflammatory phenotype responds well to anti-TNF therapy with etanercept and that is the first-line treatment for prevention of severe vascular events including strokes. The classic immunosuppressive drugs are not successful in controlling the disease activity. However, hematopoietic stem cell transplantation (HSCT) has been shown to be a definitive cure in DADA2 patients who present with a severe cytopenia. HSCT can also cure the vascular phenotype and is the treatment modality for patients' refractory to anti-cytokine therapies. In this review, we describe what is currently known about the molecular mechanisms of DADA2. Further research on the pathophysiology of this multifaceted condition is needed to fine-tune and steer future therapeutic strategies.


Estimating blurless and noise-free Ir-192 source images from gamma camera images for high-dose-rate brachytherapy using a deep-learning approach.
Objective. Precise monitoring of the position and dwell time of iridium-192 (Ir-192) during high-dose-rate (HDR) brachytherapy is crucial to avoid serious damage to normal tissues. Source imaging using a compact gamma camera is a potential approach for monitoring. However, images from the gamma camera are affected by blurring and statistical noise, which impact the accuracy of source position monitoring. This study aimed to develop a deep-learning approach for estimating ideal source images that reduce the effect of blurring and statistical noise from experimental images captured using a compact gamma camera.Approach. A double pix2pix model was trained using the simulated gamma camera images of an Ir-192 source. The first model was responsible for denoising the Ir-192 images, whereas the second model performed super resolution. Trained models were then applied to the experimental images to estimate the ideal images.Main results. At a distance of 100 mm between the compact gamma camera and the Ir-192 source, the difference in full width at half maximum (FWHM) between the estimated and actual source sizes was approximately 0.5 mm for a measurement time of 1.5 s. This difference has been improved from approximately 2.7 mm without the use of DL. Even with a measurement time of 0.1 s, the ideal images could be estimated as accurately as in the 1.5 s measurements. This method consistently achieved accurate estimations of the source images at any position within the field of view; however, the difference increased with the distance between the Ir-192 source and the compact gamma camera.Significance. The proposed method successfully provided estimated images from the experimental images within errors smaller than 0.5 mm at 100 mm. This method is promising for reducing blurring and statistical noise from the experimental images, enabling precise real-time monitoring of Ir-192 sources during HDR brachytherapy.


Converging effects of a Bifidobacterium and Lactobacillus probiotic strain on mouse intestinal physiology.
Evidence has grown to support the efficacy of probiotics in the management of gastrointestinal disorders, many of which are associated with dysregulated fluid and electrolyte transport. A growing body of evidence now suggests that the host microbiota and probiotics can influence intestinal ion transport and that these effects often occur in a strain-dependent manner. In this study, we sought to investigate the effects of two therapeutically relevant organisms, Bifidobacterium infantis 35,624 and Lactobacillus salivarius UCC118, on small intestinal transit, fecal output and water content, transepithelial resistance (TER), and colonic secretomotor function. Mice fed either strain displayed significantly reduced small intestinal transit in vivo, though neither strain influenced fecal pellet output or water content. Colon from mice fed both organisms displayed increased colonic TER, without a concomitant change in the gene expression of the tight junction proteins claudin 1 and occludin. However, L. salivarius UCC118 selectively inhibited neurally evoked ion secretion in tissues from animals fed this particular probiotic. Consistent with this finding, the neurotoxin tetrodotoxin (TTx) significantly inhibited the short-circuit current response induced by L. salivarius UCC118 following addition to colonic preparations in Ussing chambers. Responses to B. infantis 35,624 also displayed sensitivity to TTx, although to a significantly lesser degree than L. salivarius UCC118. Both strains similarly inhibited cholinergic-induced ion transport after addition to Ussing chambers. Taken together, these data suggest that B. infantis 35,624 and L. salivarius UCC118 may be indicated in disorders associated with increased small intestinal transit, and, in particular for L. salivarius UCC118, neurally mediated diarrhea.


Reflection of plane-polarized light by the retina.
Experiments are described in which retinal reflectance was measured as a function of wavelength for three subjects. Two components of the reflected light were studied: that which retained polarization and that which was depolarized. Both components were found to be present at all visible wavelengths and to have magnitudes which rose at the red end of the spectrum, although the fraction of the reflected light which retained polarization was then lower. The results are compared with those of earlier studies. While there is qualitative agreement on the form of the wavelength-dependence of retinal reflectance, the magnitudes of the values deduced by different authors vary considerably. The influence of ocular birefringence on polarized-light studies of the retina is discussed, together with possible locations from the structures responsible for the observed reflectances.


Analysis of K+ and Na+ transport and intracellular contents during and after heat shock and their role in protein synthesis in rat hepatoma cells.
Heat shock at 42 degrees caused a rapid inhibition of protein synthesis in Reuber H35 hepatoma cells. Inhibition was maximal within 5 min after the temperature was increased. After heat shock at 42 degrees for 30 min, protein synthesis was restored in 4 to 5 hr. Heat shock did not inhibit amino acid transport or cause a decrease of cellular amino acid pools, excluding a direct effect of these parameters on the inhibition of protein synthesis. The same heat shock caused a stimulation of Na+-K+ pump activity, as monitored by ouabain-sensitive Rb+ influx, but the activity returned rapidly to pretreated levels after heat shock. Similar effects were observed in the passive K+ efflux. Furthermore, heating did not affect the intracellular K+ and Na+ contents. A clear difference in the effect of temperature on protein synthesis and active K+ and Na+ influx was observed. In an Arrhenius plot, a sharp break for protein synthesis was observed at 40 degrees (D. H. J. Schamhart et al., Radiat. Res., in press, 1984), while no discontinuity was observed in the Arrhenius plot for active K+ and Na+ influxes. The results demonstrate that, during and after heat shock and at various temperatures, the K+ and Na+ balances are in a continuous steady state. Experimental modification of the intracellular K+ and Na+ contents by using ouabain or the Na+ ionophore monensin revealed that, within large limits of intracellular cation contents, protein synthesis is unimpaired. These results exclude any direct involvement of K+ and Na+ in the effects of heat shock on protein synthesis in Reuber H35 hepatoma cells.


Species differences in the 5-hydroxytryptamine-induced contraction in the isolated distal ileum.
We investigated the mechanism of 5-hydroxytryptamine (5-HT)-induced contraction in the longitudinal muscle of isolated distal ileum from ferrets, piglets and rats. 5-HT and 5-methoxytryptamine concentration-dependently contracted the ileum of ferrets, piglets and rats. 2-Methyl-5-HT and m-chlorophenylbiguanide concentration-dependently contracted the ferret ileum, whereas they had no effect in piglets and rats. In ferrets, the 5-HT-induced contraction was inhibited by methysergide and by ramosetron, but not by ketanserin or GR113808. Atropine and tetrodotoxin suppressed contractions elicited by 5-HT, 2-methyl-5-HT and m-chlorophenylbiguanide in ferrets, but not that elicited by 5-methoxytryptamine. In piglets, 5-HT-induced contraction was inhibited by methysergide and by tetrodotoxin, but not by ketanserin, ramosetron, GR113808 or atropine. In rats, 5-HT-induced contraction was inhibited by methysergide and by ketanserin, but not by ramosetron or tetrodotoxin. In contrast, GR113808 enhanced contractions elicited by 5-HT or 5-methoxytryptamine. These results suggest that 5-HT-induced contraction in ferrets is mediated via 5-HT1 receptors on the muscle and by release of acetylcholine via 5-HT3 receptors. In piglets, 5-HT-induced contraction appears to be mediated by release of neurotransmitters other than acetylcholine via 5-HT1 receptors. 5-HT-induced contraction in rats is evoked via 5-HT1 and 5-HT2 receptors on the muscle. Furthermore, 5-HT4 receptors may participate in the relaxation elicited by 5-HT in rats.


Global research trends of diabetes remission: a bibliometric study.
Research on diabetes remission has garnered prominence in recent years. However, to date, no pertinent bibliometric study has been published. This study sought to elucidate the current landscape and pinpoint potential new research directions through a bibliometric analysis of diabetes remission. We perused relevant articles on diabetes remission from January 1, 2000, to April 16, 2023, in the Web of Science. We utilized CiteSpace software and VOSviewer software to construct knowledge maps and undertake analysis of countries, institutional affiliations, author contributions, journals, and keywords. This analysis facilitated the identification of current research foci and forecasting future trends. A total of 970 English articles were procured, and the annual publication volume manifested a steady growth trend. Most of the articles originated from America (n=342, 35.26%), succeeded by China and England. Pertaining to institutions, the University of Newcastle in England proliferated the most articles (n=36, 3.71%). Taylor R authored the most articles (n=35, 3.61%), and his articles were also the most co-cited (n=1756 times). Obesity Surgery dominated in terms of published articles (n=81, 8.35%). "Bariatric surgery" was the most prevalently used keyword. The keyword-clustering map revealed that the research predominantly centered on diabetes remission, type 1 diabetes, bariatric surgery, and lifestyle interventions. The keyword emergence and keyword time-zone maps depicted hotspots and shifts in the domain of diabetes remission. Initially, the hotspots were primarily fundamental experiments probing the feasibilities and mechanisms of diabetes remission, such as transplantation. Over the course, the research trajectory transitioned from basic to clinical concerning diabetes remission through bariatric surgery, lifestyle interventions, and alternative strategies. Over the preceding 20 years, the domain of diabetes remission has flourished globally. Bariatric surgery and lifestyle interventions bestow unique advantages for diabetes remission. Via the maps, the developmental milieu, research foci, and avant-garde trends in this domain are cogently portrayed, offering guidance for scholars.


[Evolution of kidney function and progression factors in nephrectomised patients].
Data recorded from external visit in hospitals, reflects high number of nephrectomized patients. Most of these patients were remitted after any surgery or deteriorizated renal function or any other associated pathology. Several studies of nephrectomized patients are reported in literature concerning both healthy patients and comorbidity factors, and renal function and its evolution are evaluated. However, obtained results present a wide variability, which needs to be assessed. In this study we present a retrospective observational study of 92 one-kidney surgical patients, visited in Nephrology surgery of University Clinic Hospital. Patients presented an average age of 67 years old (range 22-89 years old), and a post-surgery monitoring of 21 years. Population was divided in two groups according with their glomerular filtration (FG). Before surgery, group 1 presented FG < 60 ml/min and group 2 > 60 ml/min, respectively. Group 1 patients (a total of 24 patients) presented an FG average of 48 ml/min, 8% had proteinuria and 63% presented high blood pressure. 21% of them needed an average of 20 years (10-30 years) to reach E4 and E5 steps and in general, most of them progressed to insufficient renal chronic disease. Five cases achieved renal therapy replacement. Group 2 patients, composed of a total of 68 patients, had an FG average of 76.5 ml/min, and 10% of patients presented proteinuria and 34% HTA; however, 80% of group 2 patients achieve E3 step with average age of 17 years, and a post-surgery of 47 years (1-48 years). A total of 19.1 % presented an FG higher 60 ml/min with an average development of 22 years along their evolution. According to the results obtained it is suggested that monorrenal surgical patients present a low progression of renal disease and it is also observed a progressive tendency to the chronic renal failure due to emerging of proteinuria.


Activation two-dimensional semiconductors for photocatalysis: a cross-dimensional strategy.
The emerging 2D semiconductors substantially extend materials bases for versatile applications such as semiconductor photocatalysis demanding semiconductive matrices and large surface areas. The dimensionality, while endowing 2D semiconductors the unique properties to host photocatalytic functionality of pollutant removal and hydrogen evolution, hurdles the activation paths to form heterogenous photocatalysts where the photochemical processes are normally superior over these on the mono-compositional counterparts. In this perspective, we present a cross-dimensional strategy to employ the nD (n=0-2) clusters or nanomaterials as activation partners to boost the photocatalytic activities of the 2D semiconductors. The formation principles of heterogenous photocatalysts are illustrated specifically for the 2D matrices, followed by selection criteria of them among the vast 2D database. The computer investigations are illustrated in the density functional theory route and machine learning benefitted from the vast samples in the 2D library. Synthetic realizations and characterizations of the 2D heterogenous systems are introduced with an emphasis on chemical methods and advanced techniques to understand materials and mechanistic studies. The perspective outlooks cross-dimensional activation strategies of the 2D materials for other applications such as CO2 removal, and materials matrices in other dimensions which may inspire incoming research within these fields.


Prognostic and clinicopathological features of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D1 expression in human esophageal squamous cell carcinoma.
To investigate the expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. Expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. The reduced expression rate of E-cadherin, alpha-catenin, beta-catenin and gamma-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression rate was 56.5%. Expression of gamma-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (chi(2) = 4.183 and chi(2) = 5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (chi(2) = 5.769, P<0.05). Reduced expression of E-cadherin and gamma-catenin was associated with poor differentiation of tumor, reduced expression of gamma-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and gamma-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and in reduced expression one and were 78% and 48% in gamma-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of alpha-catenin correlated with that of E-cadherin and beta-catenin (P<0.05). The reduced expression of E-cadherin and gamma-catenin, but not alpha-catenin, beta-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.


Proteinuria in mild to moderate hypertension: results of the VA cooperative study of six antihypertensive agents and placebo. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.
The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.


Hepatic arterial supply in 1297 CT-angiographies.
Analysis, evaluation and classification of hepatic arterial supply variants and determination of their frequency distribution in CT-angiographies. CT-angiographies of 1,568 patients were evaluated retrospectively for the period between January 1, 2010 and August 30, 2012. The hepatic arterial anatomy was assessed and categorized according to Michels's classification. So far unclassified variants were considered separately. CT-angiographies of 1297 patients were included in the study. Type I according to Michels was seen in 937 cases (72.2 %), followed by type V in 114 patients (8.8 %) and type III in 83 patients (6.4 %). Type X could not be found in any of the patients. Not yet classified variants were discovered in 26 patients. The most frequent variant in this connection was a right hepatic artery originating from the superior mesenteric artery with the left hepatic artery originating from the left gastric artery (n = 10). Michels's classification could be largely confirmed on the basis of a radiologically examined patient population. Not yet classified variants were categorized into subgroups of the existing classification. Imaging of hepatic arterial supply variants using CT-angiography. Distribution of variations of arterial liver supply in a general patient population. Expansion of Michels's classification to include new variations of the arterial liver supply.


Prophylactic treatment of premature babies with artificial surfactant (ALEC).
Artificial surfactant (ALEC) made from DPPC and uPG 7:3 w/w has been given at birth to babies under 30 weeks of gestation in three trials. The first trial enrolled 62 resuscitated babies: 28 treated with 25 mg ALEC powder and 34 controls. The mortality fell from 41 to 7% (p = 0.0005). In the second trial babies were randomized to receive 1 ml of 100 mg ALEC suspension into the pharynx at birth and up to 3 more endotracheal doses in 24 h. Controls received 1 ml of saline. There were 69 ALEC-treated babies and 67 controls. The mortality due to complications of respiratory distress syndrome (RDS) fell from 31 to 9% (p less than 0.01); periventricular haemorrhage was reduced from 40 to 19% (p less than 0.01). The third trial involved 328 babies randomized in 10 centres. ALEC treatment reduced the neonatal mortality from 27 to 14% (p less than 0.002); intracerebral haemorrhages fell from 24 to 16% (p = 0.06) and severe RDS by 27% (p less than 0.03). Regression analysis showed a significant reduction in hours receiving ventilation and greater than 30% oxygen during the first 10 days.


Vacuolar H+-ATPase subunit Vma1p functions as the molecular ligand in the vacuole-targeting fungicidal activity of polymyxin B.
Polymyxin B (PMB) is a cationic cyclic peptide that can selectively inhibit the growth of Gram-negative bacteria by disrupting the outer membrane permeability barrier through binding to lipopolysaccharide (LPS). Here, a fluorescent PMB derivative (PMB-Ds) was applied to visually confirm the vacuole as a direct lethal target of PMB against fungal cells, which lack LPS. PMB-Ds could be visualized in the normal rounded vacuolar membrane of Saccharomyces cerevisiae cells, suggesting the presence of a molecular ligand assisting the vacuole-targeting mobilization of the peptide in the organism. Vma1p, a cytoplasmic subunit constituent of the yeast vacuolar-type ATPase, was identified as one of the PMB-binding proteins by means of mass spectrometry. Mutant cells carrying a deletion of Vma1p but not those with deletions in two separate PMB-binding proteins were shown to be resistant to the vacuolar membrane disruptive action of PMB. Furthermore, the mutant cells were resistant to PMB lethality even when treated with PMB in combination with allicin, an allyl sulfur compound, which can selectively enhance the vacuole-targeting fungicidal activity of the peptide. In contrast, the parent cells were not made resistant to the vacuolar membrane disruptive action of PMB even if cells were pre-treated with bafilomycin A1, a specific inhibitor of the yeast vacuolar-type H+-ATPase. However, the parent cells were rendered more resistant to PMB consequent to Vma1p-GFP localization in the cytoplasm. These findings suggested a role for Vma1p in the vacuole-targeting fungicidal activity of PMB comparable to that of LPS in the outer membrane of Gram-negative bacteria.


Effect of Smoking on Short-term Postoperative Complications After Elective Upper Extremity Surgery.
Background: There is a paucity of literature exploring the impact of smoking on short-term complications, readmissions, and reoperations after elective upper extremity surgery using a large multicenter national database. We hypothesized that smokers will have an increased rate of complications, readmissions, and reoperations compared with a cohort of nonsmokers undergoing elective upper extremity surgery. Methods: Patient data were collected from the American College of Surgeons National Surgical Quality Improvement Program database between the years 2012 and 2017. Patients were included if they underwent elective surgery of the upper extremity using 338 predetermined Current Procedural Terminology codes. The data collected were divided into patient demographics, comorbidities, perioperative variables, and 30-day complications. Current smoking status was defined as smoking within 1 year prior to surgery. The incidence of surgical complications, reoperations, and readmissions was compared between the 2 cohorts using multivariable regression analysis. Results: Of the 107 943 patients undergoing elective surgeries of the upper extremity, 73 806 met the inclusion criteria. Of these, 57 986 (78.6%) were nonsmokers in the year prior to surgery, and 15 820 (21.4%) were current smokers. Between these groups, current smokers were younger (P < .001), more often men (P < .001), had lower body mass index (P < .001), and more often underwent procedures that involved bone manipulation (P < .001). Multivariate regression analysis defined current smoking as significantly associated with overall surgical site complications, superficial surgical site infections, deep surgical site infections, reoperation, and readmission. Conclusion: Current smoking was significantly associated with an increase in all surgical site complications, readmissions, and reoperations after elective upper extremity surgery. Surgeons should consider smoking a modifiable risk factor for postoperative complications and appropriately counsel patients on outcomes and complications given the elective nature of upper extremity surgery.


Quantitative analysis of Escherichia coli metabolic phenotypes within the context of phenotypic phase planes.
In silico models of Escherichia coli metabolism have been developed to predict metabolic behavior and propose experimentally testable hypotheses. However, a thorough assessment of the metabolic phenotype requires well-designed experimentation and reproducible experimental techniques. A method for the quantitative analysis of E. coli metabolism in vivo within the framework of in silico phenotypic phase plane analysis is presented. Using this approach, we have quantitatively studied E. coli metabolism in various environmental conditions and nutritional media. Our experimental methodology, in combination with steady-state metabolic models, can be used to study biological properties and evaluate the metabolic capabilities of microbes.


Anterior segment manifestations of human immunodeficiency virus/acquired immune deficiency syndrome.
Ocular complications are known to occur as a result of human immunodeficiency virus (HIV) disease. They can be severe leading to ocular morbidity and visual handicap. Cytomegalovirus (CMV) retinitis is the commonest ocular opportunistic infection seen in acquired immune deficiency syndrome (AIDS). Though posterior segment lesions can be more vision-threatening, there are varied anterior segment manifestations which can also lead to ocular morbidity and more so can affect the quality of life of a HIV-positive person. Effective antiretroviral therapy and improved prophylaxis and treatment of opportunistic infections have led to an increase in the survival of an individual afflicted with AIDS. This in turn has led to an increase in the prevalence of anterior segment and adnexal disorders. Common lesions include relatively benign conditions such as blepharitis and dry eye, to infections such as herpes zoster ophthalmicus and molluscum contagiosum and malignancies such as squamous cell carcinoma and Kaposi's sarcoma. With the advent of highly active antiretroviral therapy, a new phenomenon known as immune recovery uveitis which presents with increased inflammation, has been noted to be on the rise. Several drugs used in the management of AIDS such as nevirapine or indinavir can themselves lead to severe inflammation in the anterior segment and adnexa of the eye. This article is a comprehensive update of the important anterior segment and adnexal manifestations in HIV-positive patients with special reference to their prevalence in the Indian population.


Single-filament kinetic studies provide novel insights into regulation of actin-based motility.
Polarized assembly of actin filaments forms the basis of actin-based motility and is regulated both spatially and temporally. Cells use a variety of mechanisms by which intrinsically slower processes are accelerated, and faster ones decelerated, to match rates observed in vivo. Here we discuss how kinetic studies of individual reactions and cycles that drive actin remodeling have provided a mechanistic and quantitative understanding of such processes. We specifically consider key barbed-end regulators such as capping protein and formins as illustrative examples. We compare and contrast different kinetic approaches, such as the traditional pyrene-polymerization bulk assays, as well as more recently developed single-filament and single-molecule imaging approaches. Recent development of novel biophysical methods for sensing and applying forces will in future allow us to address the very important relationship between mechanical stimulus and kinetics of actin-based motility.


Is the exogenous orienting of spatial attention truly automatic? Evidence from unimodal and multisensory studies.
The last decade has seen great progress in the study of the nature of crossmodal links in exogenous and endogenous spatial attention (see [Spence, C., McDonald, J., & Driver, J. (2004). Exogenous spatial cuing studies of human crossmodal attention and multisensory integration. In C. Spence, & J. Driver (Eds.), Crossmodal space and crossmodal attention (pp. 277-320). Oxford, UK: Oxford University Press.], for a recent review). A growing body of research now highlights the existence of robust crossmodal links between auditory, visual, and tactile spatial attention. However, until recently, studies of exogenous and endogenous attention have proceeded relatively independently. In daily life, however, these two forms of attentional orienting continuously compete for the control of our attentional resources, and ultimately, our awareness. It is therefore critical to try and understand how exogenous and endogenous attention interact in both the unimodal context of the laboratory and the multisensory contexts that are more representative of everyday life. To date, progress in understanding the interaction between these two forms of orienting has primarily come from unimodal studies of visual attention. We therefore start by summarizing what has been learned from this large body of empirical research, before going on to review more recent studies that have started to investigate the interaction between endogenous and exogenous orienting in a multisensory setting. We also discuss the evidence suggesting that exogenous spatial orienting is not truly automatic, at least when assessed in a crossmodal context. Several possible models describing the interaction between endogenous and exogenous orienting are outlined and then evaluated in terms of the extant data.


Superior orbital fissure syndrome as a presenting symptom in hepatocellular carcinoma.
A patient with superior orbital fissure syndrome caused by metastatic hepatocellular carcinoma is reported. She had painful ophthalmoplegia and decreased sensation along the first branch of the trigeminal nerve. Histological confirmation was done by biopsy of sternal metastases. The awareness of various neurological presentations apart from hepatic failure in this malignancy is emphasized.


Structure and activity of JAC1 J-domain implicate the involvement of the cochaperone activity with HSC70 in chloroplast photorelocation movement.
Chloroplast photorelocation movement towards weak light and away from strong light is essential for plants to adapt to the fluctuation of ambient light conditions. In the previous study, we showed that blue light receptor phototropins mediated blue light-induced chloroplast movement in Arabidopsis by regulating short actin filaments localized at the chloroplast periphery (cp-actin filaments) rather than actin cables in the cytoplasm. However, the signaling pathway for the chloroplast photorelocation movement is still unclear. We also identified JAC1 (J-domain protein required for chloroplast accumulation response 1) as an essential component for the accumulation response and dark positioning in Arabidopsis. We recently determined the crystal structure of the J-domain of JAC1. The JAC1 J-domain has a positively charged surface, which forms a putative interface with the Hsc70 chaperone by analogy to that of bovine auxilin. Furthermore, the mutation of the highly conserved HPD motif in the JAC1 J-domain impaired the in vivo activity of JAC1. These data suggest that JAC1 cochaperone activity with HSC70 is essential for chloroplast photorelocation movement.


Early versus late tracheostomy in patients with severe traumatic head injury.
A majority of patients with severe traumatic brain injury (TBI) need ventilatory support and require endotracheal intubation. There has been substantial debate regarding the timing of tracheostomy. We reviewed our data to determine the impact of early tracheostomy on our resources. Retrospective review of a consecutive series of patients with severe TBI treated at a Level II trauma center. All 55 patients admitted to the surgical intensive care unit (ICU) with severe TBI from January, 2002 through September, 2005 were reviewed through the trauma registry. The inclusion criteria were severe TBI with a Glasgow Coma Scale (GCS) score < or = eight points at the time of admission and expected survival for longer than three days. All of these patients required mechanical ventilation and subsequently underwent tracheostomy. According to the timing of tracheostomy, subjects were classified as early group (< or = 7 days; N = 27) or late group (> 7 days; N = 28). The Wilcoxon rank sum test, the log-rank test, and Fisher exact tests were used to compare these groups. The average time of the tracheostomy procedure was 5.5 +/- 1.8 (SD) days in the early group and 11.0 +/- 4.3 days in the late group. There were no significant differences between the groups in terms of age, proportion of female sex, GCS, Injury Severity Score, or need for blood transfusion. However, patients in the early group had a significantly shorter stay in the ICU than patients in the late group (19.0 +/- 7.7 vs. 25.8 +/- 11.8 days; P = 0.008). There was no difference between the groups in ventilator days (15.7 +/- 6.0 vs. 20.0 +/- 16.0 days; p = 0.57). There were no significant differences between the groups regarding overall mortality (15% vs. 4%; p = 0.19), incidence of pneumonia prior to tracheostomy (41% vs. 50%; p = 0.59), median total hospital length of stay (24 days vs. 28 days; p = 0.42), discharged to rehabilitation (74% vs. 82%; p = 0.53), or median total hospital cost (292,329 dollars vs. 332,601 dollars; p = 0.26). Early tracheostomy was beneficial, resulting in a shorter ICU stay.


Dynamic change of mitral annular geometry and motion in ischemic mitral regurgitation assessed by a computerized 3D echo method.
In patients with ischemic mitral regurgitation (IMR), we assessed dynamic changes in mitral annular geometry and motion during the cardiac cycle, and examined their association with the severity of IMR, using our computerized three-dimensional (3D) echo method. Real-time 3D echo was performed in 12 normal controls and 25 patients with IMR. The saddle-shaped annulus was reconstructed in every 3D volume/frame during a cardiac cycle. For each 3D volume/frame, we assessed the mitral annular area (MAA) and the annular contraction that was expressed as the percentage of the largest MAA accounted for by the change in MAA from largest to smallest calculated value. In IMR patients, the minimum MAA occurred in late-systole, while it occurred in early-systole in the controls. IMR patients had a larger minimum MAA (6.7 ± 1.3 vs. 3.6 ± 0.8 cm², P < 0.001) and reduced annular contraction (23.0 ± 6.5 vs. 42.6 ± 7.0%, P < 0.001) when compared to controls. Both minimum MAA and annular contraction had significant correlations with IMR severity (r = 0.67 and r = 0.78, P < 0.001 for both). The contraction of the dilated mitral annulus occurred in late-systole in patients with IMR. The alterations of annular geometry and motion may be associated with the development of IMR.


Effects of surface treatments on repair bond strength of a new CAD/CAM ZLS glass ceramic and two different types of CAD/CAM ceramics.
We evaluated the effects of three different surface treatments and two different bonding procedures on shear bond strength of resin composites to different computer-aided design/manufacturing (CAD/CAM) ceramics with or without thermocycling. The test specimens were prepared from three different CAD/CAM ceramics (Group A, IPS e.max CAD; Group B, IPS e.max ZirCAD; Group C, Vita Suprinity). They were divided into eight subgroups according to the surface treatment and bonding procedures. After resin composite was applied to the surfaces of all test specimens, they were stored in distilled water for 24 h at 37°C. Next, half of the test specimens were subjected to a thermocycling procedure, and the other half were stored in distilled water at 37°C throughout thermocycling. The shear bond strength was performed using a universal testing machine. Statistical analysis revealed that the ceramic types (P > 0.0031) and thermocycling (P > 0.0021) did not, but the surface treatment technique did significantly affect the shear bond strength values (P < 0.05; except group C). Higher bond strength values were observed with HF etching in Groups A and C compared with the other tested surface treatments.


Relationship between movement disorders and obsessive-compulsive disorder: beyond the obsessive-compulsive-tic phenotype. A systematic review.
Obsessive-compulsive disorder (OCD) and symptoms (OC symptoms) are associated with tic disorders and share an aetiological relationship. The extent to which OCD/OC symptoms are correlated with other hyperkinetic movement disorders is unclear. The aim of this review was to investigate this co-occurrence and the extent to which OCD/OC symptoms and hyperkinetic movement disorders share a neurobiological basis. A systematic review was performed, specifically searching for OCD/OC symptom comorbidity in hyperkinetic movement disorders using case control studies, longitudinal studies and family based studies. The literature search was conducted using PubMed and PsycINFO databases. Heterogeneity of measurement instruments to detect OCD diagnosis and OC symptoms decreased comparability between studies. The most convincing evidence for a relationship was found between the choreas (Huntington's disease and Sydenham's chorea) and OCD/OC symptoms. Furthermore, elevated frequencies of OC symptoms were found in small case control series of dystonias. Small family based studies in dystonia subtypes modestly suggest shared familial/genetic relationships between OC symptoms and dystonia. Current data indicate a relationship between OCD/OC symptoms and the choreas. As OCD and the choreas have been associated with dysfunctional frontal-striatal circuits, the observed relationships might converge at the level of dysfunctions of these circuits. However, paucity of longitudinal and family studies hampers strong conclusions on the nature of the relationship. The relationship between OCD and movement disorders needs further elaboration using larger family based longitudinal studies and sound instruments to characterise OC symptomatology. This could lead to better understanding of the shared pathology between OCD and hyperkinetic movement disorders.


Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure.
We report findings from our investigation of the world's second clinical isolate of vancomycin-resistant Staphylococcus aureus (VRSA). An elderly man was hospitalized with an infected chronic heel ulcer and osteomyelitis. Before hospital admission, he received multiple courses of antibiotic therapy but, notably, no vancomycin. Numerous cultures of ulcer specimens (performed on an outpatient basis) grew methicillin-resistant, vancomycin-susceptible S. aureus and vancomycin-resistant Enterococcus species. At admission, an additional culture of a specimen from the heel ulcer grew S. aureus that was identified as VRSA (minimal inhibitory concentration for vancomycin [by broth-microdilution], 32 microg/mL). Further evaluation confirmed the presence of the vanA gene mediating vancomycin resistance. To assess VRSA transmission, we performed a carriage study of 283 identified contacts and an environmental survey of the patient's home; no VRSA isolates were recovered. This case illustrates that recent exposure by patients to vancomycin is not necessary for development of vanA-containing VRSA. For clinical and public health reasons, it is essential that microbiology laboratories adequately test for vancomycin-resistance in S. aureus.


Air pollution and COVID-19: Is the connect worth its weight?
Primary route of transmission of SARS-CoV-2 among humans is droplets and direct contact. Airborne transmission of this virus is not established conclusively and so is the role of airborne particulate matter. This commentary examines the existing evidence about the role of particulate matter pollutants in SARS-CoV-2 transmission. PM2.5and other small particulate matter have been shown to carry viable virus particles in the air and incriminated in spread of measles and SARS coronavirus. Empirical evidence has been provided regarding role of air pollution in accelerated transmission of SARS-CoV-2 in Italy as well as Wuhan. Lockdown-related reduction in PM2.5levels in ambient air may have contributed to reduce transmission of SARS-CoV-2. High PM2.5levels in the past might have added to SARS-CoV-2 related mortality due to air pollution relate comorbidities. Post-lockdown increase in PM2.5levels may accelerate covid-19 transmission and can add to the burden of COVID-19 morbidity and mortality.


Effect of alcohol, tobacco, and cannabis co-use on gray matter volume in heavy drinkers.
Alcohol, tobacco, and cannabis are the three most frequently used drugs in the United States and co-use is common. Alcohol, tobacco, and cannabis use has been separately associated with altered brain structure, and alcohol and tobacco co-use results in decreases in gray matter volume. Less is known about the effect of alcohol and cannabis co-use, and alcohol, tobacco, and cannabis tri-use. Therefore, this study examined the effect of co- and tri-use on gray matter volume, a measure of brain cell density, in heavy drinkers. Heavy drinkers (n = 237; 152m/85f; age = 32.52; white = 111; black = 28; Latino = 9; American Indian = 2; Pacific Islander = 4; Asian = 59; mixed = 15; other = 9) were classified into four groups based on their alcohol, tobacco, and cannabis use: alcohol only users (n = 70), alcohol and tobacco co-users (n = 90), alcohol and cannabis co-users (n = 35), and alcohol, tobacco, and cannabis tri-users (n = 42). All participants completed a structural MRI scan. Voxel-based morphometry was conducted to evaluate the effect of co-use on gray matter volume, with alcohol only users as the reference group. Age, sex, and scanner were included as covariates. Alcohol and tobacco co-users had significantly decreased left orbitofrontal gray matter volume relative to alcohol only users (Cohen's d = .79). There were no differences in gray matter volume between the alcohol only and alcohol and cannabis co-users, or between the alcohol only and tri-user groups. The additive effect of tobacco co-use on gray matter volumes in heavy drinkers was limited and localized. The effect of tri-use of alcohol, tobacco, and cannabis may have interacted, such that overlapping cannabis and tobacco use masked volume differences present in separate co-using groups. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Multimodality therapy is recommended for limited-stage combined small cell esophageal carcinoma.
Limited-stage combined small cell esophageal carcinoma (LS-C-SCEC) is a rare, poorly understood, underdiagnosed disease, with components of both small cell esophageal cancer and non-small cell esophageal cancer. We investigated the optimal treatment strategy and prognostic factors in patients with LS-C-SCEC. LS-C-SCEC patients included in the analysis (from our hospital and the literature) were treated between January 1966 and December 2013. Patient treatment strategies included surgery (S), chemotherapy (CT), and radiation therapy (RT). The primary end point was overall survival (OS); the secondary end points included tumor complete response rates, patterns of failure, and toxicity. Kaplan-Meier curves were compared with the log-rank test. Univariate and multivariate analyses were used to determine prognosticators for OS. A total of 72 patients were included in the analysis: 24 (33%) from our hospital and 48 (67%) from the literature. The median OS of all patients was 15.0 months. Patients who received CT had a significantly longer median OS than did those who did not (OS 22.8 months vs 10.0 months) (P=0.03). Patients treated with multimodality therapy (including RT+CT [18%], S+CT [40%], or S+RT+CT [17%]) vs monotherapy (typically, S [18%]) had significantly improved OS (15.5 months vs 9.3 months) (P=0.02) and complete response rates. On multivariate analysis, tumor location (upper third of the esophagus) and type of treatment (monotherapy) were the only factors predictive of poor OS. Multimodality therapy (including RT+CT, S+CT, or S+RT+CT) improves OS for patients with LS-C-SCEC compared with monotherapy (typically, S). Additional studies are necessary to personalize multimodal treatment approaches to individual patients.


Change in muscle force following electrical stimulation. Dependence on stimulation waveform and frequency.
Change in muscle force in healthy subjects due to electrical stimulation was accomplished with rectangular and sinusoidal currents. The pulse width of rectangular stimuli was 0.3 ms and repetition frequency was 25 Hz. The frequency of sinusoidal stimuli was 2 500 Hz, chopped by a 25 Hz rectangular signal. Thirteen healthy subjects were involved in the study and divided into three groups. The first group (A) had stimulation with rectangular impulses, the second (B) with sinusoidal impulses and the third (C) was a control group. The quadriceps muscle was stimulated daily for 10 minutes for 3 weeks. The maximal voluntary isometric torque increased for 25% in group A and 13% in group B, while there was no significant difference in group C. Different patterns of fatigue occurred with different stimuli. The presence of fatigue during the high frequency sinusoidal stimulation diminished the strengthening effects.


Aqueous peat extract exposes rhizobia to sub-lethal stress which may prime cells for improved desiccation tolerance.
Inoculation of legume seed with rhizobia is an efficient and cost-effective means of distributing elite rhizobial strains to broad-acre crops and pastures. However, necessary drying steps after coating seed expose rhizobia to desiccation stress reducing survival and limiting potential nitrogen fixation by legumes. Rhizobial tolerance to desiccation varies with strain and with growth conditions prior to drying. Cells grown in peat generally survive desiccation better than cells grown in liquid broth. We aimed to identify peat-induced proteomic changes in rhizobia that may be linked to desiccation tolerance. Proteins expressed differentially after growth in peat extract when compared with a minimal defined medium were measured in four rhizobial strains. Proteins showing the greatest increase in abundance were those involved in amino acid and carbohydrate transport and metabolism. Proteins involved in posttranslational modification and cell defence mechanisms were also upregulated. Many of the proteins identified in this study have been previously linked to stress responses. In addition, analysis using nucleic acid stains SYTO9 and propidium iodide indicated that membranes had been compromised after growth in peat extract. We targeted the membrane repair protein PspA (ΔRL3579) which was upregulated in Rhizobium leguminosarum bv. viceae 3841 after growth in peat extract to validate whether the inability to repair membrane damage after growth in peat extract reduced desiccation tolerance. The ΔRL3579 mutant grown in peat extract had significantly lower survival under desiccation stress, whereas no difference in survival between wild-type and mutant strains was observed after growth in tryptone yeast (TY) or minimal medium (JMM) media. Staining mutant and wild-type strains with SYTO9 and propidium iodide indicated that membranes of the mutant were compromised after growth in peat extract and to a lesser extent in TY. This study shows that growth in peat extract causes damage to cell membranes and exposes rhizobia to sub-lethal stress resulting in differential expression of several stress-induced proteins. The induction of these proteins may prime and protect the cells when subjected to subsequent stress such as desiccation. Identifying the key proteins involved in desiccation tolerance and properties of peat that stimulate this response will be important to inform development of new inoculant technology that maximises survival of rhizobia during delivery to legume crops and pastures.


Exploring health advice by dental professionals in USA: A secondary data analysis of NHANES (2015-2018).
To examine socioeconomic and ethnic variations in the provision of health advice by dental professionals. Data were from the National Health and Examination Survey (NHANES) (2015-2018). Socioeconomic position (Poverty-income ratio and education) and ethnicity were the main exposures. The outcome variable of interest was whether participants received health advice regarding the "benefits of quitting cigarettes," "benefits of monitoring blood sugar levels," and "importance of oral cancer screening". Logistic regression analysis was used to examine the relationship between socioeconomic factors/ethnicity, and health advice after adjusting for covariates. The analysis included a total of 5524 people aged eighteen and above who had complete data. Black and Hispanic individuals had higher odds of receiving advice on smoking (OR = 1.49, 95% CI: 1.04-2.12 and OR = 1.48, 95% CI: 1.05-2.07, respectively) and glucose monitoring (OR = 3.00, 95% CI: 2.03-4.43 and OR = 3.14, 95% CI: 2.04-4.82, respectively), but no significant difference for cancer screening advice.Higher poverty-income ratios (PIR) were associated with lower odds of receiving smoking advice (OR = 0.91, 95% CI: 0.84-0.98), but no significant associations were observed for glucose monitoring or cancer screening advice. The study's findings reveal a social gradient in the provision of cancer advice, with individuals having higher education levels, particularly university education (OR = 1.69, 95% CI: 1.24-2.31), showing significantly higher odds of receiving cancer screening advice CONCLUSION: The study highlights significant variations in health advice provision in dental settings, with education level, ethnicity, and smoking status playing prominent roles, emphasizing the need for targeted interventions to promote equity and cultural competence in delivering health advice in dental settings. The results emphasize the importance of strong policies and ongoing education for dental professionals to ensure optimal treatment and prevention.


Metabolic syndrome: An independent risk factor for erectile dysfunction.
The objective was to determine the role of various components of metabolic syndrome (MetS) as independent risk factor for erectile dysfunction (ED). A total of 113 subjects of MetS, as recommended by recent IDF and AHA/NHLBI joint interim statement were selected for study who presented for ED. After doing Anthropometric examination, fasting laboratory assay for fasting plasma glucose (FPG), fasting insulin, hemoglobin A1c, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 2 h oral glucose tolerance test (OGTT) was done. Erectile function was assessed by completing questions one through five of the International Index of Erectile Function (IIEF-5). A multiple linear regression analysis was carried out on 66 subjects with IIEF-5 score as dependent variable and components of MetS FPG, 2 h OGTT, TG, HDL, and waist circumference as independent variables. Using a multiple linear regression analysis, we observed that presence of the various components of MetS was associated with ED and a decrease IIEF-5 score and this effect was greater than the effect associated with any of the individual components. Of the individual components of the MetS, HDL (B = 0.136; P = 0.004) and FPG (B = -0.069; P = 0.007) conferred the strongest effect on IIEF-5 score. However, overall age had most significant effect on IIEF-5 score. It is crucial to formulate strategies and implement them to prevent or control the epidemic of the MetS and its consequences. The early identification and treatment of risk factors might be helpful to prevent ED and secondary cardiovascular disease, including diet and lifestyle interventions.


Estrogen receptor beta polymorphism is associated with prostate cancer risk.
After cloning of the second estrogen receptor, estrogen receptor beta (ERbeta) in 1996, increasing evidence of its importance in prostate cancer development has been obtained. ERbeta is thought to exert an antiproliferative and proapoptotic effect. We examined whether sequence variants in the ERbeta gene are associated with prostate cancer risk. We conducted a large population-based case-control study (CAncer Prostate in Sweden, CAPS) consisting of 1,415 incident cases of prostate cancer and 801 controls. We evaluated 28 single nucleotide polymorphisms (SNP) spanning the entire ERbeta gene from the promoter to the 3'-untranslated region in 94 subjects of the control group. From this, we constructed gene-specific haplotypes and selected four haplotype-tagging SNPs (htSNP: rs2987983, rs1887994, rs1256040, and rs1256062). These four htSNPs were then genotyped in the total study population of 2,216 subjects. There was a statistically significant difference in allele frequency between cases and controls for one of the typed htSNPs (rs2987983), 27% in cases and 24% in controls (P = 0.03). Unconditional logistics regression showed an odds ratio of 1.22 (95% confidence interval, 1.02-1.46) for men carrying the variant allele TC or CC versus the wild-type TT, and an odds ratio of 1.33 (95% confidence interval, 1.08-1.64) for localized cancer. No association of prostate cancer risk with any of the other SNPs or with any haplotypes were seen. We found an association with a SNP located in the promoter region of the ERbeta gene and risk of developing prostate cancer. The biological significance of this finding is unclear, but it supports the hypothesis that sequence variation in the promoter region of ERbeta is of importance for risk of prostate cancer.


Interpersonal Change During Inpatient CBASP Treatment: Focus on Group Therapy.
Background: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) has been tailored specifically to the demands of patients with persistent depressive disorder (PDD). According to the CBASP model, PDD patients are supposed to live perceptually disconnected from their social environment, which consequently maintains depression. While initially developed as an individual treatment modality, the adaptation for group therapy yields an important interpersonal space. However, little is known about the specific factors that contribute to patients' benefit from the CBASP group modality. Methods: The analyzed sample comprised N = 87 PDD patients who completed a 12 week multimodal inpatient treatment including 2 weekly CBASP-specific individual and group sessions, respectively, as well as CBASP-unspecific medical contacts, pharmacotherapy and complementary therapies. Group sessions included trainings in situational analysis and interpersonal skills. Interpersonal change over therapy was examined based on the patients' self-perceived interpersonal problems (IIP) and the impact messages as perceived by their individual therapists (IMI). Pre and post-treatment data were compared using within-sample t-tests. Additionally, patients evaluated CBASP group therapy on a feedback form. They were invited to reflect on individual benefits and its helpful and unhelpful aspects. Qualitative content analysis with inductive category development was used to analyze feedback. Inter-rater reliability was computed to confirm categories before summarizing the frequencies of reported factors. Results: Self-perceived interpersonal distress significantly decreased over therapy. Patients reported reduced interpersonal problems and therapists reported more friendly and dominant impact messages. Interestingly, patients who showed a significant depressive symptom reduction described higher change scores. Regarding qualitative data, patients reported five main benefits from group therapy: Gain in social competence, self-confidence, self-reflection, interpersonal dynamics, and optimism/universality. Patients responding to CBASP identified significantly more factors than non-responders. Conclusions: Compared to studies with individual CBASP only, the present findings suggest that CBASP group therapy may contribute to the improvement of interpersonal behavior. Group therapy is discussed as a potential boosting effect for individual CBASP. However, as the present data were collected in a multimodal inpatient setting without competitor, randomized controlled trials are warranted that investigate the specific benefits of the group modality or the combined individual and group therapy over individual CBASP only.


Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy.
Application of coordination chemistry in nanotechnology is a rapidly developing research field in medicine. Bismuth complexes have been widely used in biomedicine with satisfactory therapeutic effects, mostly in Helicobacter pylori eradication, but also as potential antimicrobial and anti-leishmanial agents. Additionally, in recent years, application of bismuth-based compounds as potent anticancer drugs has been studied extensively. Search for data connected with recent trends on bismuth compounds in cancer chemo- and radiotherapy was carried out using web-based literature searching tools such as ScienceDirect, Springer, Royal Society of Chemistry, American Chemical Society and Wiley. Pertinent literature is covered up to 2016. In this review, based on 213 papers, we highlighted a number of current problems connected with: (i) characterization of bismuth complexes with selected thiosemicarbazone, hydrazone, and dithiocarbamate classes of ligands as potential chemotherapeutics. Literature results derived from 50 papers show that almost all bismuth compounds inhibit growth and proliferation of breast, colon, ovarian, lung, and other tumours; (ii) pioneering research on application of bismuth-based nanoparticles and nanodots for radiosensitization. Results show great promise for improvement in therapeutic efficacy of ionizing radiation in advanced radiotherapy (described in 36 papers); and (iii) research challenges in using bismuth radionuclides in targeted radioimmunotherapy, connected with choice of adequate radionuclide, targeting vector, proper bifunctional ligand and problems with 213Bi recoil daughters toxicity (derived from 92 papers). This review presents recent research trends on bismuth compounds in cancer chemo- and radiotherapy, suggesting directions for future research.


[Change in the renin-angiotensin-aldosterone system in aging. 1].
Data are provided that testify to a changed reactivity of the RAAS in old age: Higher sensitivity of this system to the regulatory influences of the sympathico-adrenal and of the hypothalamus-hypophysis system as well as restriction of the functional facilities and reduction of reactivity. The obtained results indicate an aging-dependent reduction of the degree of reliability of the RAAS in stress situations.


Combined theoretical and experimental analysis of the bonding in the heterobimetallic cubane-type Mo(3)NiS(4) and Mo(3)CuS(4) core clusters.
X-ray structural data for the cubane-type clusters [Mo3CuS4(dmpe)3Cl4](+) and Mo3NiS4(dmpe)3Cl4 (dmpe = 1,2-bis(dimethylphosphino)ethane) with 16 metal electrons have been compared with optimized structural parameters calculated using "ab initio" methodologies. Compound Mo3NiS4(dmpe)3Cl4 crystallizes in the cubic noncentrosymmetric space group P213 with a Mo-Ni distance of 2.647 Angstrom, that is 0.2 Angstrom shorter than the Mo-Cu bond length in the isoelectronic copper cluster. The best agreement between theory and experiments has been obtained using the B3P86 method. In order to validate the B3P86 results, accurate infrared and Raman spectra have been acquired and the vibrational modes associated to the cubane-type Mo3M'S4 (M' = Cu or Ni) unit have been assigned theoretically. The electronic changes taking place when incorporating the M' into the Mo3S4 unit have been analyzed from a theoretical and experimental perspective. The bond dissociation energies between M'-Cl and Mo3S4 fragments show that formation of [Mo3CuS4(dmpe)3Cl4](+) is 135 kcal/mol energetically less favorable than the Ni incorporation. The more robust nature of the Mo3NiS4 fragment has been confirmed by mass spectrometry. The X-ray photoelectron spectroscopy (XPS) spectra of the trimetallic and tetrametallic complexes have been measured and the obtained binding energies compared with the computed electronic populations based on topological approaches of the electron localization function (ELF). The energies and shapes of the Cu 2p and Ni 2p lines indicate formal oxidation states of Cu(I) and Ni(II). However, the reductive addition of nickel into [Mo3S4(dmpe)3Cl3](+) causes a small decrease in the Mo 3d binding energies. This fact prevents an unambiguous assignment of an oxidation state in a conventional way, a circumstance that has been analyzed through the covariance of the electronic populations associated to the C(M') core and V(Mo3Ni) and V(S(2)') valence basins where Mo3NiS4 is a particularly electronically delocalized chemical entity.


Medical education resources initiative for teens program in baltimore: A model pipeline program built on four pillars.
Less than 6% of U.S. medical school applicants are African-American. The lack of diversity among physicians, by race as well as other measures, confers a negative impact on the American healthcare system because underrepresented minority (URM) physicians are more likely to practice in underserved communities and deliver more equitable, culturally competent care. MERIT (Medical Education Resources Initiative for Teens) is a nonprofit organization based in Baltimore, Maryland, USA. MERIT prepares URM high school students for health careers by providing a holistic support system for seven consecutive years. The program model, which utilizes weekly Saturday sessions, summer internships, and longitudinal mentoring, is built on four foundational pillars: (1) Ignite the Fire, (2) Illuminate the Path, (3) Create the Toolkit, and (4) Sustain the Desire. Since 2011, MERIT has supported 51 students in the Baltimore City Public School System. For the past two years, 100% (n = 14) of MERIT seniors enrolled in universities, compared to only 20.2% of Baltimore City students overall. While it is too early to know whether MERIT alumni will realize their goals of becoming healthcare professionals, they are currently excelling in universities and over 75% (n = 17) are still planning to pursue graduate degrees in health-related fields. After piloting an effective program model, MERIT now has three key priorities moving forward: (1) Creating a sustainable and thriving organization, (2) increasing the number of scholars the program supports in Baltimore, and (3) expanding MERIT to other cities.


Multilocus genotypes determined by enzyme electrophoresis of Neisseria meningitidis isolated from patients with systemic disease and from healthy carriers.
Variation in nine enzymes in 152 isolates of Neisseria meningitidis from Norway (118 from blood or cerebrospinal fluid of patients with systemic disease and 34 from the pharynx of healthy carriers) was analysed by starch-gel electrophoresis. All nine enzymes were polymorphic and the number of allozymes (electromorphs) identified per locus ranged from 3 to 12, with a mean of 6.1. Among the 152 isolates, 55 unique combinations of electromorphs (electrophoretic types, ETs) were distinguished. Twenty ETs were represented among the carrier isolates and 37 among the systemic isolates; hence, only two ETs were found in both groups of isolates. ET-5 was identified 67 times among the 118 systemic isolates (58%), indicating an association of this ET with invasiveness; ET-5 was also the most common type among the carrier isolates (18%). Genetic similarity between ETs was analysed by pairwise comparison of all 55 ETs with respect to the number of electromorphs by which they differed. No evidence of a general genetic difference between carrier and case isolates was found. Two well-defined clusters of ETs were observed, each including one of the two most common ETs identified among the systemic isolates (ET-5 and ET-37), together with isolates differing from them only at one or two loci. All isolates of ET-5 and ET-37, as well as their closely related variants defined by the similarity matrix, were resistant to sulphonamide, independent of their antigenic characteristics and isolation site. The extensive allozyme variation among isolates of the same serogroup demonstrated the limited value of serogrouping as an epidemiological tool. All but one isolate of serotype 15:P1.16 were electrophoretically similar, as were all the 2a:P1.2 isolates. The 15:P1.15 isolates, however, were genetically heterogeneous. The distribution of alleles in genotypes identified among the systemic isolates indicated that genetic recombination may occur in natural populations of N. meningitidis.


Validation of the modified TNM-Izumi classification for hepatocellular carcinoma.
The clinical value of the UICC TNM classification and the Izumi TNM modification regarding prognosis after hepatic resection was evaluated. Between January 1993 and December 1998, survival and disease-free survival were analyzed in 53 cirrhotic patients (40 males, 13 females; mean age, 65 years; range, 43-81) who underwent hepatic resection for HCC. The 1-, 3-, and 5-year overall survivals were: 89%, 54%, and 50%, with disease-free survivals of 70%, 38%, and 28%, respectively. The difference between stages 1 and 2 or stages 3 and 4A using the UICC TNM classification was not significant with respect to survival or disease-free survival. Conversely, the Izumi TNM modification showed a significant difference between each stage with respect to survival and disease-free survival. In a multivariate analysis the lack of micro/macro vascular invasion was predictive of long-term outcome. Our results show that the UICC TNM classification for hepatocellular carcinoma is inadequate. The Izumi modified TNM staging system is superior in assessing prognosis for surgical HCC patients.


Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach. Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m2 ). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein-protein interaction (PPI) data. At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3-5.6, P = 3.2 × 10-8 ) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling. The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling.


Advances in plasmid gene delivery and expression in skeletal muscle.
One of the most striking recent advances for plasmid delivery in vivo has been that of electropermeabilization, commonly referred to as electroporation. This physical process exposes a muscle tissue to a brief, high intensity electric field that induces temporary and reversible breakdown of the plasma membrane. During the period of membrane destabilization, a variety of molecules, including plasmids, gain intracellular access. Electroporation has been shown to improve the efficiency of plasmid gene delivery to skeletal muscle of small animals by as much as two-orders of magnitude to levels comparable to that of adenoviral gene delivery. This technology will allow the muscle to be used as a bioreactor for the secretion of therapeutic proteins into the circulation. This method of gene delivery, which is simple, efficient and reproducible, has become valuable for basic research, with great potential for gene therapy and DNA vaccination. Moreover, significant progress has been made using a variety of molecular designs to achieve regulation of gene expression by low molecular weight drugs. The enhanced efficiency of plasmid delivery by electroporation and the resultant durability of transgene expression, combined with the effectiveness of drug-dependent transgene regulation systems, provide a powerful set of tools that will be broadly applicable to the development of plasmid-based gene therapies for the treatment of human disease.


Muscle-strengthening and conditioning activities and risk of type 2 diabetes: a prospective study in two cohorts of US women.
It is well established that aerobic physical activity can lower the risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are beneficial for the prevention of T2D is unclear. This study examined the association of muscle-strengthening activities with the risk of T2D in women. We prospectively followed up 99,316 middle-aged and older women for 8 years from the Nurses' Health Study ([NHS] aged 53-81 years, 2000-2008) and Nurses' Health Study II ([NHSII] aged 36-55 years, 2001-2009), who were free of diabetes, cancer, and cardiovascular diseases at baseline. Participants reported weekly time spent on resistance exercise, lower intensity muscular conditioning exercises (yoga, stretching, toning), and aerobic moderate and vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression with adjustment for major determinants for T2D was carried out to examine the influence of these types of activities on T2D risk. During 705,869 person years of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted models including aerobic MVPA, the pooled relative risk (RR) for T2D for women performing 1-29, 30-59, 60-150, and >150 min/week of total muscle-strengthening and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women reporting no muscle-strengthening and conditioning activities (p<0.001 for trend). Furthermore, resistance exercise and lower intensity muscular conditioning exercises were each independently associated with lower risk of T2D in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening activities had substantial risk reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29-0.38]). Limitations to the study include that muscle-strengthening and conditioning activity and other types of physical activity were assessed by a self-administered questionnaire and that the study population consisted of registered nurses with mostly European ancestry. Our study suggests that engagement in muscle-strengthening and conditioning activities (resistance exercise, yoga, stretching, toning) is associated with a lower risk of T2D. Engagement in both aerobic MVPA and muscle-strengthening type activity is associated with a substantial reduction in the risk of T2D in middle-aged and older women.


Design of a freeform varifocal panoramic optical system with specified annular center of field of view.
A new zoom mechanism was proposed for the realization of a freeform varifocal panoramic annular lens (PAL) with a specified annular center of the field of view (FOV). The zooming effect was achieved through a rotation of the varifoal PAL around an optical axis, which is different from a conventional zooming method by moving lenses back and forth. This method solves the problem of FOV deviation from the target scope during the zooming process, since the optical axis was not taken as the zooming center of the FOV. The conical surface corresponding to a certain acceptance angle was specified as the annular center of the FOV, and it was adopted as the reference surface of zooming for the FOV. As an example, the design principle and optimization process of a freeform varifocal PAL was discussed in detail. The annular center of the FOV was specified at the acceptance angle of 90°. The absolute FOV in the direction of acceptance angles is relative to the specified annular center, with cosine deviation from ±20° at 0° rotational angle to ±10° at ±180° rotational angle on both sides around optical axis. An X-Y polynomial (XYP) was used for the representation of freeform surfaces for its simple form and convergence efficiency. The correction for irregular astigmatism and distortion and the position offset of an entrance pupil caused by an irregular aperture spherical aberration are also discussed. The results from the analysis of the modulus of the optical transfer function (MTF) and f-theta distortion show that the zooming method by a rotation of the varifocal freeform PAL is feasible.


An approach to aliphatic 1,8-stereocontrol: diastereoselective syntheses of (±)-patulolide C and (±)-epipatulolide C.
The tin(iv) bromide promoted reaction of 7-hydroxy-7-phenylhept-2-enyl(tributyl)stannane 11 with benzaldehyde gave a mixture of the epimeric 1,8-diphenyloct-3-ene-1,8-diols 12 and so indirect methods were developed for aliphatic 1,8-stereocontrol to complete diastereoselective syntheses of (±)-patulolide C 1 and (±)-epipatulolide C 40. (5Z)-3,7-syn-7-(2-Trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was prepared from the tin(iv) chloride promoted reaction of 4-(2-trimethylsilylethoxy)methoxypent-2-enyl(tributyl)stannane 16 with acrolein (1,5-syn : 1,5-anti = 96 : 4). An Ireland-Claisen rearrangement of the corresponding benzoyloxyacetate 21 with in situ esterification of the resulting acid using trimethylsilyldiazomethane gave methyl (4E,7Z)-2,9-anti-2-benzyloxy-9-(2-trimethylsilylethoxy)methoxydeca-4,7-dienoate 22 together with 10-15% of its 2,9-syn-epimer 26, the 2,9-syn- : 2,9-anti-ratio depending on the conditions used. An 88 : 12 mixture of esters was taken through to the tert-butyldiphenylsilyl ether 38 of (±)-patulolide C 1 together with 6% of its epimer 39, by reduction, a Wittig homologation and deprotection/macrocyclisation. Following separation of the epimeric silyl ethers, deprotection of the major epimer 38 gave (±)-patulolide C 1. The success of 2,3-Wittig rearrangements of allyl ethers prepared from (5Z)-3,7-syn-7-(2-trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was dependent on the substituents on the allyl ether. Best results were obtained using the pentadienyl ether 56 and the cinnamyl ether 49 that rearranged with >90 : 10 stereoselectivity in favour of (1E,5E,8Z)-3,10-syn-1-phenyl-10-(2-trimethylsilylethoxy)methoxyundeca-1,5,8-trien-3-ol 50. This product was taken through to the separable silyl ethers 38 and 39, ratio 7 : 93 by regioselective epoxidation and alkene reduction using diimide, followed by deoxygenation, ozonolysis, a Wittig homologation and selective deprotection/macrocyclisation. Deprotection of the major epimer 39 gave (±)-epipatulolide C 40.


Does the National Immunisation Register stack up? Quantifying accuracy when compared to parent-held health record books.
The National Immunisation Register (NIR), which is derived from general practice management systems, is an important tool for the provision of clinical services, national immunisation programme evaluation and immunisation research in New Zealand. However, the accuracy of the NIR data has not yet been quantified. This study aimed to examine, describe and quantify the extent of discrepancy in the NIR compared to Well Child Tamariki Ora parent-held health record books (Health Books). Immunisation data for vaccinations given between birth and four years old for children born between 2006 and 2019 were compared between the Health Books and the NIR. Health Book records were used as the reference standard to calculate performance measures: sensitivity, specificity, positive and negative predictive values for the NIR. Overall, NIR performance was high: sensitivity ranged from 90% to 93%, specificity from 78% to 85%, the positive predictive value from 91% to 94% and the negative predictive value from 77% to 84%. NIR performance was higher for National Immunisation Schedule (NIS) vaccines compared with non-NIS vaccines. This study indicates the NIR data accuracy generally performs well compared with international equivalents, especially for NIS vaccine records. Further work is required to ascertain why discrepancies between the Health Books and NIR continue to occur, with particular attention to important subgroups and translating records across from migrant populations. Also, future work is required to understand the accuracy of vaccination records for groups who experience lower-quality healthcare and a higher burden of infectious diseases.


The small heat-shock proteins IbpA and IbpB reduce the stress load of recombinant Escherichia coli and delay degradation of inclusion bodies.
BACKGROUND: The permanently impaired protein folding during recombinant protein production resembles the stress encountered at extreme temperatures, under which condition the putative holding chaperones, IbpA/IbpB, play an important role. We evaluated the impact of ibpAB deletion or overexpression on stress responses and the inclusion body metabolism during production of yeast alpha-glucosidase in Escherichia coli. RESULTS: Deletion of ibpAB, which is innocuous under physiological conditions, impaired culture growth during alpha-glucosidase production. At higher temperatures, accumulation of stress proteins including disaggregation chaperones (DnaK and ClpB) and components of the RNA degradosome, enolase and PNP, was intensified. Overexpression of ibpAB, conversely, suppressed the heat-shock response under these conditions. Inclusion bodies of alpha-glucosidase started to disaggregate after arrest of protein synthesis in a ClpB and DnaK dependent manner, followed by degradation or reactivation. IbpA/IbpB decelerated disaggregation and degradation at higher temperatures, but did hardly influence the disaggregation kinetics at 15 degrees C. Overexpression of ibpAB concomitant to production at 42 degrees C increased the yield of alpha-glucosidase activity during reactivation. CONCLUSIONS: IbpA/IbpB attenuate the accumulation of stress proteins, and - at high temperatures - save disaggregated proteins from degradation, at the cost, however, of delayed removal of aggregates. Without ibpAB, inclusion body removal is faster, but cells encounter more intense stress and growth impairment. IbpA/IbpB thus exert a major function in cell protection during stressful situations.