The effect of mild traumatic brain injury on peripheral nervous system pathology in wild-type mice and the G93A mutant mouse model of motor neuron disease.
Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. Mild-TBI did not alter the lifespan of G93A mice or age of onset; however, rotarod performance was impaired in G93A verses wild-type mice. Grip strength was reduced only in G93A mice after mild-TBI. Increased electromyography (EMG) abnormalities and markers of denervation (AchR, Runx1) indicate that mild-TBI may result in peripheral effects that are exaggerated in G93A mice. Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice.


Intervening on impostor phenomenon: prospective evaluation of a workshop for health science students using a mixed-method design.
Unaddressed impostor feelings that impede developing interest in science and self-efficacy in conducting research have a dispiriting effect that perpetuates unsatisfactory diversity in the health science workforce when such feelings are experienced more by those historically underrepresented in the workforce. This warrants effective interventions to reduce the impact of impostor feelings and related factors that diminish career resilience. We examined the effects of a 90-minute workshop on impostor perceptions and growth mindset to raise awareness of impostor phenomenon (IP) and develop skills to manage IP successfully for students attending a 10-week summer research experience program. Using a convergent mixed-methods design, data were analyzed from 51 racially and ethnically diverse students who participated in an interactive IP workshop. Using students' half-way and final progress reports about their summer experiences and pre- and post-summer online surveys, we identified how the workshop changed awareness of IP and helped students develop coping strategies. Students strongly endorsed the workshop, remarking that its content and personal stories from peers validated their own IP experiences and relieved anxiety by revealing how common the experience was. Many reported applying mindset-changing solutions, including positive self-talk, focusing their thinking on facts about themselves and situation, and grounding themselves firmly against potentially persuasive and confidence-eroding impostor feelings. While students reported end-of-summer impostor feelings at levels similar to before the program, they described being able to manage their feelings better and persist towards goals and challenging tasks. One measure of IP appeared to be addressed through students' activation of a growth mindset, potentially explaining a specific mechanism for intervention. Discrepancies between qualitative responses and quantitative IP measures demand additional work on IP instruments. A brief, theory-based IP workshop administered by research training programs, including those as short as 10-weeks, can have positive impact on subsequent IP experience and its successful management, with potential long-term impact on retention of a diverse biomedical research workforce.


Nanoformulations of small molecule protein tyrosine kinases inhibitors potentiate targeted cancer therapy.
Protein tyrosine kinases (PTKs) are closely related to tumor development and usually participate in apoptosis, DNA repair, and cell proliferation by activating signaling pathways. Therefore, PTKs have become the most promising targets for cancer therapy. In recent years, a large number of studies on the mechanism of tyrosine kinase activation have indicated that tyrosine kinase inhibitors (TKIs) have important clinical significance and application prospects as targeted anticancer drugs because they can effectively block certain cellular signaling pathways, inhibit tumor metastases and reduce tumor proliferation. Although the increasing emergence of anticancer drug resistance limits the clinical application of TKIs, emerging nanotechnology has made it possible to solve this problem. In this work, the state-of-art of small molecule protein tyrosine kinase inhibitors and the applications of drug delivery systems for TKIs are reviewed, and the potentials and challenges for future research of small molecule TKIs are addressed.


Effects of Single Vs. Multiple Sets during 10 Weeks of Water-based Resistance Training on Neuromuscular Adaptations in Young Women.
This study aims to analyze the neuromuscular adaptations of sedentary young women between water-based resistance training performed with single and multiple sets. 66 women (24.72±4.33 years old) were randomly divided into 2 training groups: SS (single set of 30 s) and MS (3 sets of 30 s). Both groups performed 2 sessions per week for 10 weeks. One repetition maximal test (1RM), muscle endurance test (maximal repetitions at 60% 1RM) and muscle power test (squat and countermovement jump performance) were evaluated at pre- and post-training. To compare neuromuscular variables, a repeated measures ANOVA with a group factor (α=0.05) was used. Both groups showed significant increases in 1RM (SS: 14.59%; MS 14.86%), in 60% 1RM (SS: 31.23%; MS: 37.37%), in SJ (SS: 10.9%; MS: 8.3%) and CMJ (SS: 9.1%; MS: 6.8%), without difference between groups. There can be concluded that young and sedentary women presented improvements in different expressions of strength after 10 weeks of training, regardless the volume of training.


DNA-induced 2'3'-cGAMP enhances haplotype-specific human STING cleavage by dengue protease.
The cytosolic DNA sensor cGMP-AMP synthase (cGAS) synthesizes the noncanonical cyclic dinucleotide 2'3'-cGAMP to activate the adaptor protein stimulator of IFN genes (STING), thus awakening host immunity in response to DNA pathogen infection. However, dengue virus (DENV), an RNA virus without a DNA stage in its life cycle, also manipulates cGAS-STING-mediated innate immunity by proteolytic degradation of STING. Here, we found that the sensitivity of STING to DENV protease varied with different human STING haplotypes. Exogenous DNA further enhanced DENV protease's ability to interact and cleave protease-sensitive STING. DNA-enhanced STING cleavage was reduced in cGAS-knockdown cells and triggered by the cGAS product 2'3'-cGAMP. The source of DNA may not be endogenous mitochondrial DNA but rather exogenous reactivated viral DNA. Cells producing 2'3'-cGAMP by overexpressing cGAS or with DNA virus reactivation enhanced STING cleavage in neighboring cells harboring DENV protease. DENV infection reduced host innate immunity in cells with the protease-sensitive STING haplotype, whose homozygote genotype frequency was found significantly reduced in Taiwanese people with dengue fever. Therefore, the human STING genetic background and DNA pathogen coinfection may be the missing links contributing to DENV pathogenesis.


Fructans, but not the sucrosyl-galactosides, raffinose and loliose, are affected by drought stress in perennial ryegrass.
The aim of this study was to evaluate the putative role of the sucrosyl-galactosides, loliose [alpha-D-Gal (1,3) alpha-D-Glc (1,2) beta-D-Fru] and raffinose [alpha-D-Gal (1,6) alpha-D-Glc (1,2) beta-D-Fru], in drought tolerance of perennial ryegrass and to compare it with that of fructans. To that end, the loliose biosynthetic pathway was first established and shown to operate by a UDP-Gal: sucrose (Suc) 3-galactosyltransferase, tentatively termed loliose synthase. Drought stress increased neither the concentrations of loliose and raffinose nor the activities of loliose synthase and raffinose synthase (EC 184.108.40.206). Moreover, the concentrations of the raffinose precursors, myoinositol and galactinol, as well as the gene expressions of myoinositol 1-phosphate synthase (EC 184.108.40.206) and galactinol synthase (EC 126.96.36.199) were either decreased or unaffected by drought stress. Taken together, these data are not in favor of an obvious role of sucrosyl-galactosides in drought tolerance of perennial ryegrass at the vegetative stage. By contrast, drought stress caused fructans to accumulate in leaf tissues, mainly in leaf sheaths and elongating leaf bases. This increase was mainly due to the accumulation of long-chain fructans (degree of polymerization > 8) and was not accompanied by a Suc increase. Interestingly, Suc but not fructan concentrations greatly increased in drought-stressed roots. Putative roles of fructans and sucrosyl-galactosides are discussed in relation to the acquisition of stress tolerance.


Enhanced infectivity of strains of Helicobacter pylori isolated from children compared with parental strains.
Intra-familial infection, mother-to-child infection, is considered to be one of the main routes of transmission for Helicobacter pylori, in developed countries such as Japan. A major role for intra-familial spread in the pathogenicity of H. pylori is now beyond controversy, although the major route of transmission remains poorly understood. We performed this study to clarify the factors determining intra-familial transmission. We used several H. pylori strains isolated from family members to compare infectivity. H. pylori K21 and K22 strains were isolated from the father and mother, and the K25 strain was isolated from the third child of the family. Mongolian gerbils were inoculated with H. pylori strains and the infectivity of three strains was compared in each experiment. In addition, the whole genome sequence, adhesion to gastric epithelial cells and the growth of static condition or continuous flow culture among three strains of H. pylori were analysed.Results/Key findings. Most of the colonies were determined as the same molecular type K25 in all of the four grouped animals and H. pylori K25 was observed as the dominant strain. The stronger adhesion capacity of the K25 strain was observed in comparison with the other two strains through in vitro analysis. By assessing the genomic profiles of H. pylori isolates from three strains, identified TnPZ regions were detected only in the K25 strain. The infectivity of H. pylori isolates intra-familial infection and animal infection were prescribed by the adhesion capacity and molecular type of each strain.


Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor.
Fabry disease is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal alpha-galactosidase A (alpha-Gal A), resulting in renal failure along with premature myocardial infarction and strokes. No effective treatment of this disorder is available at present. Studies of residual activities of mutant enzymes in many Fabry patients showed that some of them had kinetic properties similar to those for normal alpha-Gal A, but were significantly less stable, especially in conditions of neutral pH (refs. 3-5). The biosynthetic processing was delayed in cultured fibroblasts of a Fabry patient, and the mutant protein formed an aggregate in endoplasmic reticulum, indicating that the enzyme deficiency in some mutants was mainly caused by abortive exit from the endoplasmic reticulum, leading to excessive degradation of the enzyme. We report here that 1-deoxy-galactonojirimycin (DGJ), a potent competitive inhibitor of alpha-Gal A, effectively enhanced alpha-Gal A activity in Fabry lymphoblasts, when administrated at concentrations lower than that usually required for intracellular inhibition of the enzyme. DGJ seemed to accelerate transport and maturation of the mutant enzyme. Oral administration of DGJ to transgenic mice overexpressing a mutant alpha-Gal A substantially elevated the enzyme activity in some organs. We propose a new molecular therapeutic strategy for genetic metabolic diseases of administering competitive inhibitors as 'chemical chaperons' at sub-inhibitory intracellular concentrations.


Shared thoughts and practices on some modifiable cancer risk factors.
Numerous cancer-causing factors are inversely correlated with health literacy. The current study's objective was to evaluate the Saudi community's knowledge, attitude, and behavior regarding certain carcinogens. To perform this descriptive study, a cross-sectional survey was carried out in Hail City, Northern Saudi Arabia, between September 2020 and November 2020. In the city of Hail, about 450 volunteers have expressed interest in taking part in the study. A total of 165 individuals smoked cigarettes and drank alcohol, respectively (67%) and 42 (9%). Negative attitudes toward cigarette smoking, alcohol consumption, radiation exposure, genetic predisposition, some viruses, some bacterial infection, some parasites, and fungi were 85/450 (19%), 209/450 (46.4%), 206/450 (45.8%), 322/450 (71.6%), 297/450 (66%), 375/450 (83.3%), 403/450 (89.6%), and 405/450 (90%), in that order. Some cancer-causing substances are widely used in the Saudi community. Lack of understanding and a negative attitude toward some carcinogens are widespread, necessitating immediate interventions at the community and health affairs levels.


Factors related to breast abscess after delivery: a population-based study.
To investigate whether there are underlying factors, other than breastfeeding behaviours, which may contribute to the development of breast abscess during the year following delivery. A population-based study. In Sweden. The 1,454,068 singleton deliveries during 1987-2000. Methods Data retrieval from two national patient registers: the Medical Birth Registry and the National Discharge Register. Stratified Mantel-Haenszel analysis. Odds ratios with 95% confidence intervals for possible risk factors for breast abscess in the year following delivery. During the year following delivery 1401 women had surgery because of a breast abscess. This gives a rate of 0.1%. Sixty-five percent of cases occurred between three and eight weeks postpartum. An annual increase in the odds ratio (OR) was found between 1993 and 1999. Lowest risk was found among mothers who were < or =24 years and a significantly increased risk among mothers > or =30 years. There was a 3.6-fold increased risk for breast abscess associated with primiparity and OR for post-maturity (>41 weeks) was 5. Primiparous women appear to be at a greater risk for the development of breast abscess during lactation than multiparous women. Mothers over the age of 30 years and those who give birth post-maturely are also at a significantly increased risk. Primiparous women and women over 30 years could be targeted for extra information in preparation for parenthood classes about how to avoid over distension of the breasts during breastfeeding. Further research is needed to understand the role of post-maturity and to investigate why some women recover spontaneously from inflammatory processes of the breast.


The obesity-mortality paradox in elderly patients with angiographic coronary artery disease: a report from the ET-CHD registry.
The body mass index (BMI)-mortality paradox has been well known in patients with obstructive coronary artery disease (CAD). However, this phenomenon has rarely been described among elderly patients over a 5-year follow-up. We studied a cohort of 722 elderly patients (age 65 years) with angiographic CAD from the ET-CH D registry during 1997-2003 in eastern Taiwan. To evaluate the BMI effect on mortality, the elderly subjects were categorized into 5 groups by BMI (kg/m2): underweight and normal-low weight (< 21), normal-high weight (21-23.9) overweight (24-26.9), mild obesity (27-29.9) and moderate/severe obesity (30). At a maximal 10-year follow-up, cardiac and all-cause deaths were the primary end points. After multivariate analysis, patients from the category of under weight and normal-low weight in reference to those from the normal-high weight category had a significantly higher risk of cardiac and all-cause mortality (hazard ratio (HR): 1.68 (95% CI: 1.04-2.70) and 2.02 (95% CI: 1.42-2.87), respectively) following a median of 5.4 years. Obese elderly patients tended to have the lowest risk of all-cause death across all the study BMI categories in the early stage. However, after 5 years, mortality increased in the obese patients surviving beyond 5 years, and was higher than that in overweight patients. The obesity-mortality paradox was present in elderly patients with angiographic CAD in Taiwan and the risk of death was significantly higher in those with a BMI < 21 kg/n2. However, a J-shaped relationship between mortality and BMI developed after 5 years of follow-up.


Comparison between Angiographic Findings of Coronary Artery Disease in STEMI and NSTEMI Patients of Bangladesh.
Coronary Angiogram (CAG) has been used to detect coronary artery disease in myocardial infarction (both STEMI and NSTEMI) patients. The purpose of this study was to compare the degree of coronary artery disease among STEMI and NSTEMI patients. Among acute coronary syndrome in NSTEMI we found more widespread coronary artery disease other than STEMI. Lack of documentations encouraged us to perform this study in our center. In this retrospective observational study we summarized all myocardial infarction (MI) patients who underwent coronary angiography (CAG) from August 2013 to August 2014 at Enam Medical College Hospital, Dhaka, Bangladesh and data of degree of coronary artery disease were recorded. Data of 100 consecutive MI patients who underwent CAG during that period were recorded. Among them 50 patients having STEMI as Group I (male 45, female 5) & other 50 patients sustained NSTEMI as Group II (male 38, female 12). Among NSTEMI patient group 80% were having multi-vessel disease and in STEMI patient group 80% having single vessel disease and remaining having multi-vessel disease. The degree of coronary artery disease is extensive in NSTEMI patients than in STEMI group. Coronary angiogram can visualize the degree of coronary artery involvement and is a useful screening modality to compare disease extent in MI patients.


Embryonal rhabdomyosarcoma of the nose in an elderly patient, case report and review of the literature.
Embryonal rhabdomyosarcoma of the head and neck is very rare in adults. We report on an embryonal rhabdomyosarcoma of the nose, occuring in a 74-year-old female patient presenting with nasal congestion as the only clinical symptom. Suspected to be an amelanotic melanoma, further biopsies and histological examinations provided the correct diagnosis. She first underwent a course of chemotherapy which led to a partial shrinkage of the tumor mass which was followed by a complete resection of the residual tumor mass. Biologic behaviour of this tumor must be fully appreciated as treatment is interdisciplinary. Rhabdomyosarcoma should be considered in the differential diagnosis of tumors of the nose and paranasal sinuses not only in children, but also in adults.


Prosthesis-patient mismatch due to small ring annuloplasty in patients with degenerative mitral insufficiency.
Avoidance of prosthesis-patient mismatch (PPM) is important when selecting a mitral valve prosthesis. This study investigated the effect of PPM after small ring mitral valve annuloplasty on postoperative hemodynamics and the clinical course. This study retrospectively reviewed 227 patients with symptomatic severe mitral insufficiency (MI) who underwent mitral valve repair for degenerative MI using an Edwards ring or band (size: 26-32mm) between 2003 and 2012. Echocardiography was performed postoperatively and at follow-up to evaluate cardiac function, including residual MI, mean transmitral pressure gradient, left atrial diameter (LAD), and tricuspid regurgitant pressure gradient (TRPG). There were no operative deaths. Actuarial freedom from major adverse cardiac events was 91% at 10 years. The postoperative MI grade was not significantly different between different sizes of prosthesis (26mm, 0.67±0.8; 28mm, 0.73±0.9; 30mm, 0.85±0.9; 32mm, 0.3±0.6). LAD and TRPG were significantly lower for each size of prosthesis at follow-up (all p<0.05). Patients with a smaller body surface area received a significantly smaller prosthesis (p<0.05). The transmitral pressure gradient was significantly higher in patients with a 26-mm prosthesis than in patients with a larger size of prosthesis. Thirty-three patients had a follow-up transmitral pressure gradient ≥5mmHg. The follow-up LAD was larger in patients with a transmitral pressure gradient <5mmHg than in patients with that ≥5mmHg (43.2±9.4mm vs 47.1±9.6mm, p<0.05). Mitral valve repair results in excellent clinical outcomes with significant reductions in MI, LAD, and TRPG for all sizes of prosthesis. However, use of a smaller prosthesis may result in a higher mean transmitral pressure gradient, and may inhibit reverse remodeling of the left atrium. Therefore, PPM should be avoided.


Assessing the quality of life in infants with deformational plagiocephaly.
This was a parent-reported outcome study on the impact of helmet therapy on the quality of life of infants with deformational plagiocephaly and their caregivers. Using survey-based analysis, we compared the quality of life in infants with deformational plagiocephaly with a cohort of their healthy peers. In addition, we compared infant quality of life before and after helmet therapy to evaluate the impact of this mainstay therapy for deformational plagiocephaly. Our results demonstrated that infants with plagiocephaly and their caregivers had a significantly decreased quality of life compared with healthy controls. This reframes our understanding of deformational plagiocephaly and emphasizes the need for therapeutic intervention in these individuals. A common therapeutic option - helmet remolding therapy - was shown to have no negative impact on quality of life, underscoring this as an appropriate therapeutic option. These data will allow us to counsel our future parents more effectively regarding the impact of deformational plagiocephaly and helmet therapy.


Cultural, social, and healthcare access factors associated with delays in gastric cancer presentation, diagnosis, and treatment: A cross-sectional study.
The aim of this study was to identify the time intervals between the demand for health services and the initiation of cancer treatment, and to explore the associated factors, in gastric cancer patients being treated in an oncology hospital in northern Brazil. This cross-sectional study. Gastric cancer patients receiving treatment in a northern Brazil reference hospital were interviewed. A Mann-Whitney test was used to verify associations between the time intervals of access to treatment and socioeconomic factors, clinical variables, and patient difficulties, adopting a 0.05 significance level. The average time intervals were 471.3 days between symptom onset and primary health service request and 180.9 days between diagnosis and treatment. The average time between the onset of symptoms and the treatment of gastric cancer was 747.8 days. Patients using herbal home remedies showed the longest times before seeking primary health care (p = 0.04). Delays between diagnosis and treatment were associated with unemployment (p = 0.03). High average times until oncologist appointments were related to the absence of comorbidities (p = 0.004). Personal difficulties and a lack of hospital beds were associated with long time intervals to specialist appointments and between diagnosis and treatment. Personal difficulties were associated with long time intervals between the onset of symptoms and the treatment of gastric cancer. Gastric cancer patients faced delays and healthcare access barriers in a region with high mortality for this disease. Appropriate interventions are necessary to reduce delays and better control the disease. In this paper we have explored the barriers to access to diagnosis and treatment for patients with gastric cancer in a major cancer centre in Northern Brazil. The results will inform strategies for improving timely access to critical cancer services.


Abnormal expression of truncated CRMP-1 protein in the brain cortex of MPSIIIB mice.
Mucopolysaccharidosis IIIB is a lysosomal disease characterized by a severe neurological deterioration, the pathophysiological mechanisms of which are poorly understood. Recently FGF pathway was shown to be altered leading us to explore a downstream target involved in brain development: the collapsin response mediator protein-1 (CRMP-1). CRMP-1 transcript level was normal but a cleavage of CRMP-1 was observed with an abnormal expression of the truncated form until adult age. This truncated CRMP-1 protein could play a role in post-natal cortex maturation and be involved in neuronal alterations occurring in lysosomal diseases.


Target temperature management of 33 degrees C exerts beneficial haemodynamic effects after out-of-hospital cardiac arrest.
Accumulating evidence indicates that target temperature management (TTM) is beneficial in patients resuscitated after cardiac arrest since it appears to improve neurological outcome. However, the optimal cooling method (surface vs. intravascular) has not yet been specified. Substantial heart disease is present in most of these patients and therefore haemodynamic effects of cooling need to be considered very carefully. We analysed the haemodynamic response to TTM in patients treated with surface versus intravascular cooling following out-of-hospital cardiac arrest. In this observational study 63 consecutive subjects presenting to the hospital after successful resuscitation following of out-of-hospital cardiac arrest received an intravascular (40 patients) or external cooling device (23 patients) to induce TTM. While with intravascular cooling the target temperature of 33 degrees C was reached after 159 minutes, the minimum temperature achieved with surface cooling was about 35 degrees C after 437 minutes. Haemodynamic parameters were recorded in a 4-hour rhythm for the first 12 hours after induction of hypothermia. Generally, TTM of 33 degrees C resulted in a higher systemic vascular resistance index (749 vs. 467 dyn*sec/cms/m2; P= 0.04) but also in a marked reduction of heart rate (67.70 vs. 100.00 bpm; P < 0.001), a higher mixed venous oxygen saturation (76 vs. 68%; P = 0.016), and a higher stroke volume index (45 vs. 33 mI/m2; P = 0.036). TTM additionally resulted in a higher cardiac power index (0.55 vs. 0.46 Watt/m2; P = 0.024). TTM of 33 degrees C compared to 35 degrees C exerts beneficial haemodynamic effects and might be viewed as an adjunct inotropic therapy avoiding the undesired side effects of vasoactive substances.


Mechanism of antitumor activity of bone marrow natural suppressor cells.
Co-culturing of P-815 tumor cell strain and intact mouse bone marrow cells nonadherent to plastic resulted in the appearance of soluble mediators with antitumor activity. Bone marrow cells start releasing these antiproliferative factors only after signal exchange with the target tumor cells. The cell-cell contact is an important factor for the induction of antitumor activity. Antitumor activity of bone marrow cells (similarly as immunosuppressive activity) is realized through suppressor factors; the appearance of these factors is induced by target tumor cells.


Completing Baseline Mapping of Trachoma in Nepal: Results of 27 Population-Based Prevalence Surveys Conducted in 2013 and 2014.
Trachoma is endemic in parts of Nepal; implementation of the surgery, antibiotics, facial cleanliness, environmental improvement (SAFE) strategy started in 2002. Some suspected-endemic districts had not previously been mapped. We aimed to estimate the prevalences of trachomatous inflammation-follicular (TF) and trichiasis in those districts. Population-based prevalence surveys were undertaken in 27 districts. In each of those districts, two-stage cluster sampling was used to select a sample of 2000 children aged 1-9 years and 4000 adults aged ≥15 years from a total of 40 wards (clusters), drawn evenly from two subdistricts. Consenting eligible participants were examined for trachoma by Global Trachoma Mapping Project (GTMP)-certified graders, using the World Health Organization simplified grading system. Data were analyzed at district level using GTMP methods. A total of 43,200 households were surveyed, and 162,094 people were examined for trachoma. District-level TF prevalence in 1-9-year-olds ranged from 0% to 4.3% (95% confidence interval [CI] 2.4-6.2). Among adults aged ≥15 years, trichiasis prevalence ranged from 0% to 0.33% (95% CI 0.08-0.65). TF was not a public health problem in any of the 27 districts surveyed; thus, antibiotic mass drug administration is not needed. In two districts (Dhanusa and Gorkha), trichiasis prevalence in adults aged ≥15 years was ≥0.2%; thus, further trichiasis surgery interventions at public health level are warranted to achieve elimination. These findings will facilitate planning for elimination of trachoma as a public health problem in Nepal.


The potential of the ovine udder as a model to determine the pathogenicity of bovine ureaplasmas.
Various methods of inducing mastitis in the ovine mammary gland with two bovine ureaplasma strains were investigated. The most successful method was by inoculation of fresh broth cultures on two successive days, 24 h apart. Eight more bovine strains were inoculated by this means and three successfully infected the glands.


Quantitative SEM characterisation of ceramic target prior and after magnetron sputtering: a case study of aluminium zinc oxide.
Till now electron microscopy techniques have not been used to evaluate the plasma-target interactions undergone during the magnetron sputtering process. The destructive nature of this interaction severely alters the target microstructure. Utilising quantitative microscopy techniques can shed light on the complex plasma and solid-state processes involved which can ultimately lead to improved functional thin film deposition. As a representative functional material, aluminium-doped-zinc oxide (AZO) is an upcoming alternative to conventional transparent electrode wherein the process optimisation is of great importance. In this paper, we evaluate the pre- and post-sputter field emission scanning electron microscopy (FESEM) data for ceramic AZO target fabricated at three final sintering temperatures (1100°C, 1200°C and 1300°C). In all cases, grain boundaries are merged in addition to a visible reduction in the secondary phases which makes segmentation-based image analysis challenging. Through surface statistics (i.e. fractal dimension, autocorrelation length, texture aspect ratio and entropy) as a function of magnification we can quantify the electron microscopy image of the microstructure. We show that the plasma-microstructure interaction leads to an increase in autocorrelation length, texture aspect ratio and entropy for the optimum AZO ceramic sputtering target sintered at 1200°C. Furthermore, a maximum reduction in fractal dimension span (as determined by exponential regression) is also observed for 1200°C. In addition to the evaluation of plasma effects on sintering, our approach can provide a window towards understanding the underlying thin film growth mechanisms. We believe that this technique can be applied to the defect characterisation of a wide range of polycrystalline ceramic sputtering targets (e.g. ITO, CZTS, GAZO and so on) with the ultimate goal of improving the magnetron sputtering process and the resulting functional thin film. LAY DESCRIPTION: Magnetron sputtering allows scientists to make functional thin films on the order of the nanoscale. In this technique, atoms are plucked from a 'target' then placed onto a substrate forming a thin nanometric film: all thanks to magnets, a special power supply and the fourth state of matter (plasma). Understanding what is going on and how to make a 'good' thin film is important for making better light emitting diodes, solar cells and light sensors. Scientists use electron microscopy to see what is going on in the microstructure of the sputtered thin films to fine tune the sputtering recipe. Here, for the first time, we have applied electron microscopy to see the surface of the microstructure before and after magnetron sputtering. This will help us understanding the plasma-microstructure interaction allowing us to make more informed decisions when fine-tuning the sputtering process to get improved thin films. This is a case study of aluminium-doped zinc oxide (AZO) target that could potentially replace indium tin oxide (ITO), which is widely used as a transparent electrode in devices involving light and electricity. In this case, improved characteristics would be lower electrical resistivity and higher transmission of light. We show that it is possible to use a mathematical description (e.g. the fractal dimension) of the scanning electron microscopy picture to show a link between the target surface and the functional properties. Simple explanation of fractal dimensions by Sixty Symbols ○ https://www.youtube.com/watch?v=cmBljeC79Ls Experimental demonstration of magnetron sputtering by The Thought Emporium ○ https://www.youtube.com/watch?v=Cyu7etM-0Ko Introductory video on magnetron sputtering by Applied Science ○ https://www.youtube.com/watch?v=9OEz_e9C4KM Demonstration of AZO target fabrication and sputtering by Pradhyut Rajjkumar ○ https://www.youtube.com/watch?v=kTLaTJfNX3c Simple explanation of a DIY SEM by Applied Science ○ https://www.youtube.com/watch?v=VdjYVF4a6iU.


Expression of manganese superoxide dismutase in esophageal and gastric cancers.
The tumor-killing activity of radiotherapy and chemotherapy for cancer is closely associated with the production of active oxygen, and the relation between therapeutic resistance and active oxygen scavengers produced by the tumor itself is gaining more attention. It is considered that manganese superoxide dismutase (MnSOD) protects host cells from oxidative stress, in synergy with other antioxidant enzymes. In this study, we used a quantitative polymerase chain reaction assay to measure MnSOD mRNA in resected specimens from patients with esophageal and gastric cancers. In both esophageal and gastric cancers, the level of MnSOD mRNA was significantly elevated in cancer tissue compared to non-cancer tissue (P < 0.01). In gastric cancer tissue, the MnSOD mRNA level was significantly higher than in esophageal cancer tissue (P < 0.01). The significance of MnSOD in cancer tissue was investigated further by measuring MnSOD content in resected specimens using an enzyme-linked immunosorbent assay, and by examining its location by an immunohistochemical method. Upregulation of MnSOD in cancer tissue most likely serves as a protective mechanism against anti-cancer therapies known to produce superoxide radicals as a key component of their tumor-killing activity.


Estradiol Membrane-Initiated Signaling in the Brain Mediates Reproduction.
Over the past few years our understanding of estrogen signaling in the brain has expanded rapidly. Estrogens are synthesized in the periphery and in the brain, acting on multiple receptors to regulate gene transcription, neural function, and behavior. Various estrogen-sensitive signaling pathways often operate in concert within the same cell, increasing the complexity of the system. In females, estrogen concentrations fluctuate over the estrous/menstrual cycle, dynamically modulating estrogen receptor (ER) expression, activity, and trafficking. These dynamic changes influence multiple behaviors but are particularly important for reproduction. Using the female rodent model, we review our current understanding of estradiol signaling in the regulation of sexual receptivity.


A novel lncRNA-miRNA-mRNA competitive endogenous RNA network for uveal melanoma prognosis constructed by weighted gene co-expression network analysis.
Uveal melanoma (UM) is the most common and aggressive intraocular tumor in adults, and long-term survival of UM patients remains poor. Abnormal competitive endogenous RNA (ceRNA) networks promote the initiation and progression of many tumors and may thus serve as useful prognostic indicators. Here, we do a comprehensive analysis of long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA ceRNA networks as prognostic markers for UM. The Cancer Genome Atlas UM dataset was used to identify survival-related mRNA and lncRNA modules through weighted gene co-expression network analysis (WGCNA). Prognostic miRNAs were identified using univariate Cox proportional hazard regression. We then used Cox and least absolute shrinkage and selection operator regression to screen for prognostic hub mRNAs and establish a hub ceRNA network. A nomogram of five hub mRNAs was constructed and Kaplan-Meier survival analysis performed. Six mRNA modules were constructed, two of which involved 1490 mRNAs that significantly correlated with survival. Among the three lncRNA modules constructed, one involved 199 survival-related lncRNAs. Five hub prognostic mRNAs were identified and a hub ceRNA network constructed, consisting of six lncRNAs, four miRNAs, and five mRNAs, with high prognostic value. We describe a hub ceRNA network of survival-associated lncRNAs, miRNAs, and mRNA that may underlie a critical post-translational regulatory mechanism determining UM aggression. These hub RNAs may be valuable prognostic markers and therapeutic targets in UM.


Breaking barriers in cardiac donation after circulatory death.
Heart transplant (HT) from controlled donation after circulatory death (cDCD) is an emerging strategy that is rapidly expanding and may help increase the heart donor pool. The use of thoracoabdominal normothermic regional perfusion with extracorporeal membrane oxygenation device has allowed to perform HT after cDCD in our country. We present a successful case of heart transplantation using a graft from cDCD with 201 min cold ischemia time. HT from cDCD could be a good alternative to brain dead donation. This experience suggests than nonlocal cardiac from cDCD could tolerate long periods of cold ischemia time and break the main barriers with this technique.


Nephropathic cystinosis with central nervous system involvement.
Nephropathic cystinosis is associated with end-stage renal failure, retinal damage, and hypothyroidism. Patients may now survive past the first decade of life with the use of dialysis and renal transplantation. Examination of a 24-year-old woman with this disorder revealed ovarian failure, mildly abnormal results on a glucose tolerance test, intermittent confusion, short-term memory loss, and cerebral atrophy on computerized axial tomography. Autopsy examination at age 25 years revealed cystine storage in multiple tissues including the atrophic ovaries, pancreatic islet cells, the aorta, and the brain. Dysfunction of multiple organ systems may develop in patients with cystinosis who survive into adulthood. This emphasizes the need for a systemic therapy for cystinosis.


A possible mechanism of immunoregulation produced by alpha 2-macroglobulin.
Most of the plasma suppressive activity was associated with alpha 2M in both normal subjects and cancer patients. alpha 2M binding to physiological levels of proteases was associated with an increase in the ability to suppress lymphocyte reactivity in the TEEM test. alpha 2M binding to proteases released a peptide that was a component of the alpha 2M; this peptide suppressed lymphocyte reactivity to mitogenic, antigenic, and allogenic stimuli in the TEEM test and in the lymphocyte transformation assay. Physically and biologically similar peptides have been found in the plasma of cancer patients and patients with thermal burns, uremia, and acute pancreatitis.


Metabolic aspects of HIV: associated wasting.
Despite recent progress in the treatment of human immunodeficiency virus (HIV) infection, wasting syndrome (WS) is now one of the major aspects of acquired immunodeficiency syndrome (AIDS). Malnutrition in HIV infected patients is characterised by a predominant loss of body cell mass (BCM), the amount of functional protoplasm in non-adipose tissue. This loss of BCM is correlated with a higher risk of AIDS events and a greater risk of mortality. If anorexia plays a major role in the development of the WS, some abnormalities in the metabolism drive the predominant loss of BCM. In the stable state, the resting energy expenditure (REE) is increased by about 10%. The REE is significantly correlated with the whole body protein turn over as measured by C13 leucine. This particular and only metabolic situation is associated with an increased insulin sensitivity and a high level in de novo hepatic lipogenesis. During periods of secondary infections, patients had a striking average weight loss, resulting from the combination of anorexia and dramatic elevated REE.


A fluorometric assay for acetylcholine with picomole sensitivity.
A sensitive fluorogenic assay for acetylcholine is described. The assay is based upon the reactions: (1) hydrolysis of acetylcholine to choline and acetate, catalyzed by acetylcholinesterase. (2) Oxidation of choline to betaine and hydrogen peroxide by choline oxidase. (3) Oxidation of p-hydroxyphenylacetic acid by hydrogen peroxide to a fluorescent product, catalyzed by peroxidase. With a sensitivity comparable to chemiluminescence procedures, the assay should find application to those situations requiring the persistence of a fluorescence signal or the necessity of assaying small volumes.


Place cell maps slowly develop via competitive learning and conjunctive coding in the dentate gyrus.
Place cells exhibit spatially selective firing fields that collectively map the continuum of positions in environments; how such activity pattern develops with experience is largely unknown. Here, we record putative granule cells (GCs) and mossy cells (MCs) from the dentate gyrus (DG) over 27 days as mice repetitively run through a sequence of objects fixed onto a treadmill belt. We observe a progressive transformation of GC spatial representations, from a sparse encoding of object locations and spatial patterns to increasingly more single, evenly dispersed place fields, while MCs show little transformation and preferentially encode object locations. A competitive learning model of the DG reproduces GC transformations via the progressive integration of landmark-vector cells and spatial inputs and requires MC-mediated feedforward inhibition to evenly distribute GC representations, suggesting that GCs slowly encode conjunctions of objects and spatial information via competitive learning, while MCs help homogenize GC spatial representations.


The 9-year clinical course of depressive and anxiety disorders: New NESDA findings.
In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity. Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes. Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered. 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant. Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of subthreshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research.


Number of Regularly Prescribed Drugs and Intrapatient Tacrolimus Trough Levels Variability in Stable Kidney Transplant Recipients.
High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant time of 6.0 ± 3.1 years. The coefficient of variation (CV) as a measure of IPV was calculated in each individual patient. Data concerning the type and number of currently prescribed medications were collected. The participants were divided into four groups, based on the number of regularly prescribed drugs (≤3, 4-6, 7-9, ≥10 drugs, respectively). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (interquartile range, 0.08-0.14), group 2: 0.14 (0.01-0.17), group 3: 0.17 (0.14-0.23), group 4: 0.17 (0.15-0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503, p < 0.001] independently influenced the tacrolimus IPV. Concomitant steroid or diuretics use increased IPV only in Advagraf-treated KTRs, whereas proton-pump inhibitor or statin use increased IPV in the Prograf group but not in the Advagraf group. A large number of concomitant medications significantly increases the tacrolimus IPV in stable KTRs.


Involutive morphological modifications in the rat adrenal glomerular zone after a low-sodium diet.
We have studied glomerular zone involution in the rat's adrenal gland after a period of hyperfunction brought about by a low-sodium diet. The changes observed in this zone effect those organoids that are more directly involved in steroid genesis; mitochondria, smooth endoplasmic reticulum and liposomes. The Golgi complexes appear very developed, often, showing, a positive acid phosphatase activity. Lysosomes suffered a considerable increase in their number, and carried out their digestive function on liposomes. All those changes discussed here are seen as an accomodation of this zone to the new normofunctional situation.


Protective treatments for copper alloy artworks: preliminary studies of sodium oxalate and limewater effectiveness against bronze disease.
Nantokite (CuCl) locked inside subsurface micro-pits has been recognised as the driving force to the form of corrosion called bronze disease. The use of the traditional corrosion inhibitor benzotriazole is questioned because of toxicity. So there is a need for alternative conservation treatments. This work is focused on the experimental design to test the effectiveness of sodium oxalate followed by treatment with limewater to face bronze disease on outdoor bronzes. A number of foundry bronze coupons were exposed to weathering at Genoa Experimental Marine Station (GEMS) exposure site and sprayed twice a week with a 5% NaCl solution for the first 124 days. After 562 days of natural weathering, the patinas on coupons were characterised with non-destructive techniques (NDT) and the presence of nantokite was verified. We designed a workflow, as similar as possible to conservation treatments on real artworks, to test a 3% w/v sodium oxalate treatment with two different application times, with or without limewater, on the coupons. The effectiveness of the treatments was analysed by comparison of surface properties by several NDT measurements. A statistical approach and XRD measurements directly on the corroded bronze surfaces are suggested as an effective way to characterise and compare the overall behaviour of bronze disease treatments for conservation.


Determination of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine in biological samples by HPLC.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all isoforms of nitric oxide synthase, the enzyme that synthesizes nitric oxide from arginine. Elevated plasma concentrations of ADMA are associated with hypertension and other risk factors for cardiovascular disease. Symmetric dimethylarginine (SDMA), a stereoisomer of ADMA that does not inhibit nitric oxide synthase, is also present in plasma in concentrations that are almost equal to ADMA concentrations. Any analytical method used for the determination of ADMA should therefore be able to discriminate between ADMA and SDMA. In this chapter a high-performance liquid chromatography (HPLC) method for the simultaneous analysis of arginine, ADMA, and SDMA is described. Solid-phase extraction is used to isolate all basic amino acids. Subsequently, amino acids are converted into relatively stable adducts by derivatization with o-phthalaldehyde reagent containing mercaptopropionic acid. Derivatives are then separated by reversed-phase HPLC using isocratic elution and fluorescence detection. The method requires only 0.05-0.2 mL of sample, allowing the analysis of plasma from small laboratory animals. Because of its high precision, this method is particularly suited to detect small concentration differences between samples, e.g., in the assessment of ADMA metabolism at the organ level by measurement of arterio-venous concentration differences.


A polymer membrane tethered with a cycloruthenated complex for colorimetric detection of Hg2+ ions.
A new cyclometallated ruthenium complex (Ru1) involving a 2-(2-thienyl)pyridine and a benzo[e]indolium block connected with a hexanoic acid was successfully synthesized and characterized, which exhibited the high sensitivity and selectivity to Hg2+ over other common metal ions with the detection limit of as low as 0.053 μM in aqueous system. Then, it was grafted onto a polymer membrane to afford a Hg2+-sensitive membrane (sensor 1), which was characterized by FT-IR, SEM and XPS spectra, respectively. When sensor 1 was dipped into the aqueous solution of Hg2+ ions, the color of the membrane changed from dark-red to yellow, which could be observed by naked eyes easily. It should be noted that the membrane can absorb Hg2+ ions well in aqueous solution and the adsorption capacity of this polymer membrane for Hg2+ ions was determined by atomic absorption spectroscopy, indicating that it also could be used as a potential material for removal of Hg2+ ions.


Downregulation of serine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells.
Serine/arginine-rich splicing factor 3 (SRSF3) likely has wide-ranging roles in gene expression and facilitation of tumor cell growth. SRSF3 knockdown induced G1 arrest and apoptosis in colon cancer cells (HCT116) in association with altered expression of 833 genes. Pathway analysis revealed 'G1/S Checkpoint Regulation' as the most highly enriched category in the affected genes. SRSF3 knockdown did not induce p53 or stimulate phosphorylation of p53 or histone H2A.X in wild-type HCT116 cells. Furthermore, the knockdown induced G1 arrest in p53-null HCT116 cells, suggesting that p53-dependent DNA damage responses did not mediate the G1 arrest. Real-time reverse transcription-polymerase chain reaction and western blotting confirmed that SRSF3 knockdown reduced mRNA and protein levels of cyclins (D1, D3 and E1), E2F1 and E2F7. The decreased expression of cyclin D and E2F1 likely impaired the G1-to-S-phase progression. Consequently, retinoblastoma protein remained hypophosphorylated in SRSF3 knockdown cells. The knockdown also induced apoptosis in association with reduction of BCL2 protein levels. We also found that SRSF3 knockdown facilitated skipping of 81 5'-nucleotides (27 amino acids) from exon 8 of homeodomain-interacting protein kinase-2 (HIPK2) and produced a HIPK2 Δe8 isoform. Full-length HIPK2 (HIPK2 FL) is constantly degraded through association with an E3 ubiquitin ligase (Siah-1), whereas HIPK2 Δe8, lacking the 27 amino acids, lost Siah-1-binding ability and became resistant to proteasome digestion. Interestingly, selective knockdown of HIPK2 FL induced apoptosis in various colon cancer cells expressing wild-type or mutated p53. Thus, these findings disclose an important role of SRSF3 in the regulation of the G1-to-S-phase progression and alternative splicing of HIPK2 in tumor growth.


Nitrous Oxide-Induced Metaphase Arrest: A Technique for Somatic Chromosome Analysis.
Procedures to arrest metaphase chromosomes are used for determining chromosome numbers, chromosomal aberrations, and natural chromosome variation, as well as chromosome sorting. Here is described a technique of nitrous oxide gas treatment of freshly harvested root tips that is highly effective at producing an excellent mitotic index together with well-spread chromosomes. The details of the treatment and equipment used are provided. The metaphase spreads can be used directly for determining chromosome numbers or for in situ hybridization to reveal chromosomal features.


The effect of low-level diode laser therapy on early differentiation of osteoblast via BMP-2/TGF-β1 and its receptors.
The objective of this study was to determine the effect of LLDL therapy on the gene expression of osteoblast markers of growth and differentiation. The MG-63 cell line was exposed to diode laser (ezLase) of 940 nm at 1-1.5 W and 3-4 J, and gene expressions (Runx-2, alkaline phosphatase [ALP], type I collagen [Col-I], osterix [OSX], osteocalcin [OSC], osteoprotegerin [OPG], bone morphogenetic protein [BMP]-2 and -7, transforming growth factor-β1 [TGF-β1], and TGF-β receptors [TGF-β R1, TGF-β R2; TGF-β R3]) were evaluated by quantitative RT-PCR. LLDL treatment stimulated the expression of osteoblast differentiation markers ALP, Col-I, Runx-2, and OSX in relation to the doses applied (P < 0.05), but no changes were detected in OSC, OPG, or BMP-7 at any study dose. This effect may be mediated by TGF-β1 and BMP-2, given that the treatment increased their expression and that of TGF-β receptors R1, R2, and R3 (P < 0.001). These results suggest that the biostimulatory effect of laser therapy on osteoblasts may be attributable to the release of autocrine factors in response to the irradiation. A clinical trial is warranted to test its therapeutic usefulness in bone tissue regeneration and to define a treatment protocol.


Terahertz spectroscopic detection of amino acid molecules under magnetic field.
Terahertz (THz) waves can cover the characteristic spectra of substances such as plasma, organisms, and biomolecules, whereas THz photons have low energy and do not damage biological tissues. Therefore, its absorption characteristics in the THz region can be used to characterize the internal structure of biomolecules. In this study, we designed a microfluidic chip and combined it with THz technology. The spectral intensity in descending order was found to be deionized water, phenylalanine, histidine, glycine and glutamic acid by observing the THz wave transmission in the range of 0.1-1.0 THz, comparing the frequency domain spectra of four amino acid solutions with volume fraction of 2% and deionized water. It is inferred that different molecular structures of amino acids resulted in different numbers of hydrogen bonds formed between them and water molecules, leading to different degrees of absorption of THz waves. In addition, magnetic fields parallel to the THz wave transmission were used to study the variation of different amino acids with magnetic field intensity. It is found that increasing the magnetic field strength decrease the transmission of THz waves. This is because under the action of the magnetic field, on the one hand, the hydrogen bonds formed by water molecules are strengthened and the absorption of THz waves is enhanced; on the other hand, amino acid molecules aggregate and the radius of molecular clusters increases, thus blocking the transmission of THz waves. Finally, we also calculated the electric conductivity of the solutions to prove the accuracy of the experimental results from a theoretical point of view.


Association of patients' pre-therapy strengths and alliance in outpatient psychotherapy: A multilevel growth curve analysis.
Meta-analytic evidence showed robust associations between the alliance in psychotherapeutic dyads and treatment outcomes. Recent studies have indicated that facets of positive mental health are additionally relevant predictors of both the alliance and success of psychotherapy. However, the impact of patients' pre-therapy strengths on the alliance at the beginning and during treatment has been scarcely examined. 428 patients (62.4% female, Mage = 40.79), treated by 41 therapists, underwent cognitive behavioral therapy in a German outpatient training and research center. Alliance from patients' perspectives was assessed at the beginning and during treatment. Data were analyzed with multilevel growth curve modeling. Alliance increased during psychotherapy, with a quadratic trajectory best representing this trend on average, p < .001. Pre-therapy strengths were positively related to alliance intercept, b = 0.0537, p < .001. No interaction was found between the included time variables and pre-therapy strengths in the prediction of the alliance slope. Positive mental health facets should be considered in psychotherapy research and practice. Future studies may focus on the parallel development of patients' strengths with other process factors in treatment.


Steroids linked with amide bond-extended cholesterol.
New type of linear cholesterol-like molecules based on cholesterol extended by attachment of etienic acid derivatives was designed and oligosteroids with two to four units were synthesized. Amide bond was used for inter steroid connections and 1-hydroxybenzotriazole active ester method was adapted for their formations. Use of disteroids as larger building blocks was applied.


Visible light-driven electron transfer and hydrogen generation catalyzed by bioinspired [2Fe2S] complexes.
Complexes [{(mu-SCH2)2NCH2C6H5}{Fe(CO)2L(1)}{Fe(CO)2L(2)}] (L(1) = CO, L(2) = P(Pyr) 3, 2; L(1) = L(2) = P(Pyr)3, 3) were prepared, which have the lowest reduction potentials for the mono- and double-CO-displaced diiron complexes reported so far. Hydrogen evolution, driven by visible light, was successfully observed for a three-component system, consisting of a ruthenium polypyridine complex, the biomimetic model complex 2 or 3, and ascorbic acid as both electron and proton donor in CH3CN/H2O. The electron transfer from photogenerated Ru(bpy)3(+) to 2 or 3 was detected by laser flash photolysis. Under optimal conditions, the total turnover number for hydrogen evolution was 4.3 based on 2 and 86 based on Ru(bpy)3(2+) in a three-hour photolysis.


Differential sensitivities of the vascular K(ATP) channel to various PPAR activators.
Several agonists of the peroxisome proliferator-activated receptors (PPARs) are currently used for the treatment of metabolic disorders including diabetes. We have recently shown that one of them, Rosiglitazone, inhibits the vascular ATP-sensitive K⁺ (K(ATP)) channel and compromises the coronary vasodilation by the β-adrenoceptor agonist. Here, we show evidence for the channel inhibition by various PPAR agonists, information that may be useful for finding new therapeutical agents with less cardiovascular side-effects and more selective K(ATP) channel blockers targeting at the K(ir)6.1 subunit. Structural comparison of these PPAR agonists may shed insight into the critical chemical groups for the channel inhibition. K(ir)6.1/SUR2B channel was expressed in HEK293 cells and studied in whole-cell voltage clamp. The K(ir)6.1/SUR2B channel was strongly inhibited by several PPAR(γ) agonists with potencies similar to, or higher than, that of Rosiglitazone, while other PPAR(γ) agonists barely inhibited the channel. The K(ir)6.1/SUR2B channel was also inhibited by PPAR(α) and PPAR(β/δ) agonists with intermediate potencies. The structure necessary for the channel inhibition appears to include the thiazole linked to an aromatic or furan ring. Additions of side groups such as small aliphatic chain increased the potency for channel inhibition, while additions of aromatic rings reduced it. These results indicate that the PPAR(γ) agonists with weak K(ATP) channel inhibition may be potential candidates as therapeutical agents, and those with strong channel inhibition may be used as selective K(ATP) channel blockers. The structural information of the PPAR agonists may be useful for the development of new therapeutical modalities with less cardiovascular side-effects.


GLP-1 receptor agonist, liraglutide, protects podocytes from apoptosis in diabetic nephropathy by promoting white fat browning.
Glucagon like peptide-1 receptor agonists (GLP-1RAs) belong to the class of incretin drugs. Incretin is a hormone secreted into blood by intestinal cells after food stimulation that induces insulin secretion. Liraglutide is a long-acting GLP-1RA that can reduce blood pressure, blood lipids, and inflammation. Previous studies showed that liraglutide can promote white fat browning and improve renal outcomes in patients with type 2 diabetes mellitus. However, no studies have linked white fat browning to kidney damage. The objective of this study was to investigate the effects of liraglutide-induced white fat browning on podocyte apoptosis in diabetic nephropathy. We also aimed to determine whether podocytes express glucagon like peptide-1 receptor (GLP-1R) and if liraglutide directly affects podocytes via GLP-1R. We assessed fat and renal function in db/db and wild-type mice and the effects of adipocyte conditioned medium on cultured podocytes. Liraglutide (400 mg/kg/d) was subcutaneously injected for 8 weeks. Liraglutide promoted white fat browning in vivo. During adipogenic differentiation of 3T3-L1 cells in vitro, liraglutide also upregulated expression of peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC1α) and uncoupling protein 1 (UCP1), which can induce white fat browning in vitro. Furthermore, we found that supernatant from 3T3-L1 cells stimulated by liraglutide reduced podocyte apoptosis. The inhibitory effect of liraglutide on apoptosis was eliminated by exogenous TNF-α. Finally, podocytes express GLP-1R. In vivo and in vitro studies showed that the apoptosis of podocytes in diabetic nephropathy may be related to the effect of liraglutide on promoting white lipid browning. Similarly, liraglutide may directly affect podocytes via GLP-1R.


Limbal allergic granulomatosis.
Four limbal diseases characterised by granuloma formation as part of an allergic response are discussed. A series of histological specimens from patients with Wegener's granulomatosis were re-examined. Genuine granulomatous disease at the limbus is rare, only occurring in two patients, whilst secondary, more non-specific limbal active chronic inflammation was more common. Comparisons between this disease, Churg Strauss allergic angiitis, some varieties of Mooren's ulcer and allergic granulomatous nodules were made. The role of the mast cell in promoting this eosinophilic leucocytic mediated group of disease is discussed briefly.


Molecular detection of porcine parvovirus 1-associated reproductive failure in southern India.
This study used 56 aborted and stillborn fetuses from organized swine farms in Tamil Nadu and Kerala, southern states of India. All samples were screened by using a PCR assay that targets the NS1 gene for PPV. Furthermore, the PCR positive samples were subjected to amplification of the VP2 gene of PPV1 with designed primers and sequenced for further study. The PCR screening of 56 samples found that 14.3% (n = 8) were positive for PPV genome. According to VP2 gene-based PCR for PPV1, 897 bp specific amplicons were detected in all eight of the samples. Two of the eight positive samples (L17 and T5) were sequenced and annotated randomly. The BLAST analysis of contig sequence INDTNCHN-T5 revealed 100% sequence homology with Chinese PPV1genome, whereas sequence from INDTNCHN-L17 revealed 99.43% sequence homology with Spain, Chinese, and German. PPV1 sequences and both the sequences INDTNCHN-T5 and INDTNCHN-L17 were submitted to the GenBank under the accession numbers MW822566 and MW822567 respectively. A phylogenetic analysis of the sequences in this study revealed specific grouping along with PPV1 strains in cluster E. Amino acid analysis of both isolated sequences in addition to the reference sequence from PPV1 showed variations in position 215 (I to T) in both the isolates, variation at position 228 (Q to E) in T5 isolate and variations at position 59 (L to M) and 314 (K to E) in L17 isolate. This study represents the first report of PPV1 cluster E in Tamil Nadu, southern India.


Are grunting respirations a sign of serious bacterial infection in children?
To assess the significance of grunting respirations in children and their potential association with serious bacterial infections, and to identify characteristics unique to this patient group. A prospective case-control design was used. Data were collected on all children who were hospitalized with grunting respirations in our department of paediatrics over a 13-month period. The enrolled patients were divided into three groups: previously healthy children aged 3 months or less, previously healthy children aged more than 3 months and children with chronic illness at any age. The findings were compared to matched controls hospitalized for similar symptoms but without grunting respirations. Grunting respirations were documented in 149 of the 3334 admissions (4.5%) during the period of study. The incidence was higher in children aged 3 months or less (7.5%) and lower in children older than 3 months (3.9%). Fever and respiratory symptoms were common (83.9% and 65.1%, respectively). Heart rate was the only vital sign that was significantly different between the study and control groups. Serious bacterial infection occurred more frequently in the study group (31.5% vs. 14.8%, p < 0.001, OR 2.14, 95% CI 1.36-3.36). Comparisons between the groups showed that grunting respirations were a sign of serious bacterial infection in previously healthy children older than 3 months (p = 0.007, OR 1.95, 95% CI 1.21-3.13) and in children with a chronic disease of any age (p = 0.033, OR 7.0, 95% CI 1.0-49.7 respectively), but not in previously healthy children younger than 3 months (p = 1). The incidence and importance of grunting respirations in hospitalized children depend on patient's age and previous medical status. A finding of grunting respirations in a previously healthy child aged over 3 months or in a chronically ill child should alert the physician to seek further evidence of bacterial infection, especially pneumonia.


Characteristics of dehydroepiandrosterone as a peroxisome proliferator.
Treatment of rats with dehydroepiandrosterone (300 mg/kg body weight, per os, 14 days) caused a remarkable increase in the number of peroxisomes and peroxisomal beta-oxidation activity in the liver. The activities of carnitine acetyltransferase, microsomal laurate 12-hydroxylation, cytosolic palmitoyl-CoA hydrolase, malic enzyme and some other enzymes were also increased. The increases in these enzyme activities were all greater in male rats than in female rats. Immunoblot analysis revealed remarkable induction of acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme in the liver and to a smaller extent in the kidney, whereas no significant induction of these enzymes was found in the heart. The increase in the hepatic peroxisomal beta-oxidation activity reached a maximal level at day 5 of the treatment of dehydroepiandrosterone and the increased activity rapidly returned to the normal level on discontinuation of the treatment. The increase in the activity was also dose-dependent, which was saturable at a dose of more than 200 mg/kg body weight. All these features in enzyme induction caused by dehydroepiandrosterone correlate well with those observed in the treatment of clofibric acid, a peroxisome proliferator. Co-treatment of dehydroepiandrosterone and clofibric acid showed no synergism in the enhancement of peroxisomal beta-oxidation activity, suggesting the involvement of a common process in the mechanism by which these compounds induce the enzymes. These results indicate that dehydroepiandrosterone is a typical peroxisome proliferator. Since dehydroepiandrosterone is a naturally occurring C19 steroid in mammals, the structure of which is novel compared with those of peroxisome proliferators known so far, this compound could provide particular information in the understanding of the mechanisms underlying the induction of peroxisome proliferation.


Xenon arc and argon laser photocoagulation in the treatment of diabetic disc neovascularization. Part 1. Effect on disc vessels, visual fields, and visual acuity.
Xenon arc and argon laser photocoagulation are equally effective in producing regression of disc neovascularization and maintaining visual acuity. Xenon has more destructive effects on the visual field and electroretinogram, but is more comfortable because retrobulbar anaesthesia is used and more convenient to the patient because fewer treatment sessions are needed.


Hepatoprotective effects of prostacyclins on CCl4-induced liver injury in rats.
Certain biochemical parameters of acute liver injury induced by carbon tetrachloride were investigated in rats treated with prostacyclin (PGI2) and two of its derivatives. Serum glutamate oxalacetate transaminase elevation and both triglyceride accumulation and reduction of glycogen content in liver were significantly suppressed by PGI2, 7-oxo-PGI2, and 20-methyl-13,14-didehydro-2,4-m-interphenylene-PGI2 48 hr after the injury. Prostacyclins partially restored some of the parameters of injury even in doses of 10 micrograms/kg ip. When the compounds were given 24 hr after CCl4 intoxication, much more pronounced protection was observed than in the case of treatments 1 hr before administration of the hepatotoxin. Thus, all tested prostacyclins exerted significant protective effects on acute liver damage which is obtained mainly in the second phase of the injury.


Aortic root replacement with anomalous origin of the coronary arteries.
Coronary arteries with anomalous origin from the aorta can be at risk during aortic valve procedures. We report a case of origin of the circumflex and left coronary artery from the proximal right coronary artery in a patient with a bicuspid aortic valve and aortic root aneurysm. Attention to the anatomic relationship of the anomalous arteries to the aorta allowed safe aortic root replacement.


Laparoscopic T-tube feeding jejunostomy as an adjunct to staging laparoscopy for upper gastrointestinal malignancies: the technique and review of outcomes.
In recent years, staging laparoscopy has gained acceptance as part of the assessment of resectability of upper gastrointestinal (UGI) malignancies. Not infrequently, we encounter tumours that are either locally advanced; requiring neoadjuvant therapy or occult peritoneal disease that requires palliation. In all these cases, the establishment of enteral feeding during staging laparoscopy is important for patients' nutrition. This review describes our technique of performing laparoscopic feeding jejunostomy and the clinical outcomes. The medical records of all patients who underwent laparoscopic feeding jejunostomy following staging laparoscopy for UGI malignancies between January 2010 and July 2015 were retrospectively reviewed. The data included patient demographics, operative technique and clinical outcomes. Fifteen patients (11 males) had feeding jejunostomy done when staging laparoscopy showed unresectable UGI maligancy. Eight (53.3%) had gastric carcinoma, four (26.7%) had oesophageal carcinoma and three (20%) had cardio-oesophageal junction carcinoma. The mean age was 63.3 ± 7.3 years. Mean operative time was 66.0 ± 7.4 min. Mean postoperative stay was 5.6 ± 2.2 days. Laparoscopic feeding jejunostomy was performed without intra-operative complications. There were no major complications requiring reoperation but four patients had excoriation at the T-tube site and three patients had tube dislodgement which required bedside replacement of the feeding tube. The mean duration of feeding tube was 127.3 ± 99.6 days. Laparoscopic feeding jejunostomy is an important adjunct to staging laparoscopy that can be performed safely with low morbidity. Meticulous attention to surgical techniques is the cornerstone of success.


High-dose therapy and autologous hematopoietic stem-cell transplantation does not increase the risk of second neoplasms for patients with Hodgkin's lymphoma: a comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem-cell transplantation.
To determine the incidence of second malignancies among patients with Hodgkin's lymphoma (HL) treated with autologous hematopoietic stem cell transplantation (AHSCT) compared with patients receiving conventional therapy alone and to identify potential risk factors for their occurrence. We analyzed data on 1,732 consecutive patients with HL treated at the British Columbia Cancer Agency from 1976 to 2001, including 202 patients undergoing AHSCT. The median follow-up duration was 9.8 years for the whole cohort, 9.7 years for those patients treated with conventional therapy, and 7.8 years from AHSCT. The cumulative incidence of developing any second malignancy 15 years after therapy for HL was 9% (risk ratio = 3.5; P < .001); however, the incidence did not differ between those patients receiving conventional therapy alone compared with those undergoing AHSCT (10% and 8%, respectively; P = .48). In multivariate analysis, the only factor significantly associated with an increased risk of developing any second neoplasm or solid tumor was age > or = 35 years (P < .0001). An increased risk of therapy-induced acute myeloid leukemia and therapy-induced myelodysplastic syndrome was seen for patients aged > or = 35 years (P = .03) and stage III/IV (P = .04). Patients with HL are at increased risk of developing a second neoplasm. However, those patients undergoing AHSCT do not seem to be at greater risk compared with those patients receiving conventional therapy alone, at least during the first decade after therapy.


Anionic bio-flocculants from sugarcane for purification of sucrose: An application of circular bioeconomy.
In sugar production, polyacrylamide-based anionic flocculants are added for juice treatment, the main objective being to remove impurities that affect the quality of the sugar. However, if they remain in the final product, those polymers can present carcinogenic and neurotoxic actions besides contaminating the soils where the waste is discharged. To overcome this problem, the present study proposes, for the first time, natural flocculants based on cellulose obtained from sugarcane bagasse (residue from sugarcane processing) as substitutes for the flocculants based on polyacrylamide, normally used in sugar cane juice purification. Additionally, cellulose-based flocculants obtained from Acacia wood, developed in a previous study, have also been tested for sugar juice treatment. Acacia wood and sugarcane bagasse were first treated with a choline chloride/levulinic acid solution in a molar ratio of 1:2, at 160 °C, for 4 h. Subsequently, the cellulose-rich samples were modified by a two-stage process (oxidation with sodium periodate followed by reaction with sodium metabisulfite), and polyelectrolytes with different characteristics were produced. The final products obtained were characterized, and their performance in the treatment of sugarcane juice, at different concentrations (10, 50, 100, 250, and 500 mg kg-1), was evaluated and compared to the synthetic commercial flocculant (Flonex, based on polyacrylamide) usually used by the sugarcane industry in Brazil. The substitution of petrol-based flocculants by natural-based ones, obtained from sugarcane residues, is presented for the first time in this study, with very relevant performance of the new flocculants. Overall, it was possible to produce anionic flocculants, modifying the cellulose obtained from different raw materials, which showed good results in the purification of sucrose, when compared with the commercial polyacrylamide normally used. It is also important to stress that, for the first time, a residue from sugarcane industry could be used with success in the purification of the sugar juice itself, which constitutes a major novelty.


Central nervous system involvement in non-Hodgkin's lymphoma.
Fifty-eight Hong Kong Chinese patients with CNS lymphoma were reviewed (primary seven, secondary 51). The incidence of secondary CNS lymphoma in patients with non-Hodgkin's lymphoma was estimated to be 9.4%. The Working Formulation separated subtypes which had a special propensity to involve the CNS. Significant proportions of our patients with secondary CNS lymphoma had other features which were known to be associated with a high risk of CNS disease including stage IV (48/51, 91.4%), bone marrow (26/51, 50.9%), peripheral blood (7.51, 13.7%), nasal (7/51, 13.7%), orbital (3/51, 5.9%), testicular (2/51, 3.9%) and bulky retroperitoneal (6/51, 11.8%) disease. 82% of patients with secondary CNS lymphoma had concurrent systemic disease and a further 12% had systemic relapse shortly afterward. CNS lymphoma is associated with poor prognosis and only 29% and 14% of the patients with primary and secondary CNS lymphoma respectively survived beyond 1 year. Patients responding to therapy had significantly better survival. 69.9% of the deaths were related to progressive systemic disease.


Sex-specific associations of arsenic exposure with global DNA methylation and hydroxymethylation in leukocytes: results from two studies in Bangladesh.
Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk-is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hmC has not been widely studied. We evaluated associations of As in drinking water, urine, and blood with global %5-mC and %5-hmC in two studies of Bangladeshi adults: (i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity study (n = 196; 49% male, 19-66 years); and (ii) peripheral blood mononuclear cell DNA in the Folate and Oxidative Stress study (n = 375; 49% male, 30-63 years). Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (P for interaction < 0.01). Analyses examining interactions by elevated plasma total homocysteine (tHcys), an indicator of B-vitamin deficiency, found that tHcys also modified the association between As and global %5-hmC (P for interaction < 0.10). In two samples, we observed associations between As exposure and global %5-hmC in blood DNA that were modified by sex and tHcys. Our findings suggest that As induces sex-specific changes in 5-hmC, an epigenetic mark that has been associated with cancer. Future research should explore whether altered %5-hmC is a mechanism underlying the sex-specific influences of As on skin lesion and cancer outcomes.


Metal oxide Perovskite-Carbon composites as electrocatalysts for zinc-air batteries. Optimization of ball-milling mixing parameters.
Zn-air batteries (ZABs) are promising electrochemical devices to store energy. Metal oxide perovskites mixed with carbon materials are highlighted as interesting materials for this application because of their appropriate bifunctional performance in oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The interaction between both components of the electrocatalyst is important in the bifunctional electrocatalytic activity, and the mixing method plays an important role in this interaction. Then, different mixing methods have been studied in this work (ball-milling, mortar and manual shaking). The use of different physicochemical techniques such as temperature programmed desorption (TPD), temperature programmed reduction (TPR) and X-ray photoelectron spectroscopy (XPS) in the materials characterization, allows us to conclude that the mixing method strongly influences the particle size and the interaction between both components, which determine the final electrocatalytic activity. The materials prepared by ball-milling displayed the best performance. Herein, the experimental conditions were optimized to obtain electrocatalysts with enhanced electrocatalytic activity for ORR and OER. Low rotating speed, air atmosphere and low ball-milling time generate electrocatalysts with a small nanoparticle size, more homogeneous and with a higher interaction between both components, which enhances electron transfer, and consequently, the overall oxygen-involved reactions. The best electrocatalyst obtained was studied as air-electrode in a Zn-air battery and it was compared to a commercial Pt/C electrocatalyst, obtaining higher cyclability (55.2 vs 51.7 %) for 30 h, and higher energy density at 5 mA/cm2 (764 mAh/g vs 741 mAh/g).


Clinical features and nigrostriatal dysfunction in patients with combined postural and resting tremors.
The characteristics of clinical features and nigrostriatal dopaminergic dysfunction in patients with combined postural and resting tremors have been less clearly reported. The present study examined 43 patients with a visible persistent bilateral postural tremor and a unilateral/bilateral resting tremor involving the hands and forearms. The patients had experienced tremors for more than 3 years, with no evidence of Parkinson's disease or other parkinsonian disorders. Visual and quantitative analyses of [18F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET in 36 patients were performed. Seventeen age-matched normal controls were also studied. On visual analysis, 28 patients (78%) showed normal [18F] FP-CIT uptake and eight (22%) showed significantly reduced uptake, suggesting nigrostriatal dopaminergic neuronal degeneration. The reduced [18F] FP-CIT uptake was significantly associated with earlier age-at-onset of tremor and asymmetric presentation of resting tremor. On quantitative analysis, there were statistically significant differences in the [18F] FP-CIT uptake ratio in the posterior putamen between patients with reduced uptake (2.37 ± 1.83) and patients with normal uptake (6.39 ± 1.35) (P < 0.001). However, posterior putamen uptake levels in patients with normal [18F] FP-CIT uptake on visual analysis were similar to those in normal controls (7.22 ± 1.29) (P = 0.291). The nigrostriatal dopaminergic dysfunction in patients with combined postural and resting tremors may be associated with earlier age-at-onset of tremor and asymmetric pattern of resting tremor, which might help to correctly diagnose patients with mixed tremors.


A Sortase A Programmable Phage Display Format for Improved Panning of Fab Antibody Libraries.
Phage display of combinatorial antibody libraries is a versatile tool in the field of antibody engineering, with diverse applications including monoclonal antibody (mAb) discovery, affinity maturation, and humanization. To improve the selection efficiency of antibody libraries, we developed a new phagemid display system that addresses the complication of bald phage propagation. The phagemid facilitates the biotinylation of fragment of antigen binding (Fab) antibody fragments displayed on phage via Sortase A catalysis and the subsequent enrichment of Fab-displaying phage during selections. In multiple contexts, this selection approach improved the enrichment of target-reactive mAbs by depleting background phage. Panels of cancer cell line-reactive mAbs with high diversity and specificity were isolated from a naïve chimeric rabbit/human Fab library using this approach, highlighting its potential to accelerate antibody engineering efforts and to empower concerted antibody drug and target discovery.


Clinical Application of Fiber Visualization with LIC Maps Using Multidirectional Anisotropic Glyph Samples (A-Glyph LIC).
Recently, a fiber visualization method for high-angular resolution diffusion-weighted magnetic resonance imaging (MRI) data was proposed using a multiple-kernel line integral convolution (LIC) algorithm and an anisotropic spot pattern. This processing routine leads to high contrast color-coded LIC maps that are capable of visualizing local anisotropy information and regional fiber architecture. In this paper, we evaluate and validate this method by applying it to simulated datasets and to in vivo diffusion MRI data of children and adults with different disease conditions and healthy volunteers. Compared to routine clinical fiber visualization (color-coded fractional anisotropy, FA maps, and fiber tractography), it has the advantage of visualizing complex local fiber architecture in a fully automated way. The results indicate that this method is capable of reliably delineating normal fiber architecture and fibers infiltrated, displaced, or disrupted by lesions and is therefore a promising tool in the clinical context.


The influence of group values and behavior on adolescent male perceptions of and use of homophobic language.
The pervasive and derogatory use of homophobic language is a threat to safe, respectful, and inclusive school environments. Group membership has been shown to influence how students use homophobic language. Previous qualitative studies have largely approached the use of this language from the theoretical framework of hegemonic masculinity. In contrast, the current study actively challenged all assumptions about the use of this language. This study was conducted in a public high school located in a rural conservative Christian community in the Intermountain West (USA). Using hermeneutic qualitative methodology to assess individual perceptions of homophobic language, 20 randomly selected 12th-grade male students (17-18 years of age) were individually interviewed. Three distinct groups emerged during our interviews: students on the debate team, students who strongly identified with a conservative religion, and students on popular athletic teams. Membership in specific peer groups influenced how students participated in or abstained from using homophobic language. Contrary to the prevailing research that pairs religiosity with negatively biased attitudes toward LGBTQIA, in this study, participants' religious beliefs appeared to be associated with respecting others' feelings and a decreased likelihood of using homophobic language. After summarizing this study's findings, we conclude with implications for practice. To more effectively deter the use of homophobic language, we encourage school-based interventions that target specific groups of adolescents and consider the social context in which homophobic language occurs.


Gamma entrainment frequency affects mood, memory and cognition: an exploratory pilot study.
Here we provide evidence with an exploratory pilot study that through the use of a Gamma 40 Hz entrainment frequency, mood, memory and cognition can be improved with respect to a 9-participant cohort. Participants constituted towards three binaural entrainment frequency groups: the 40 Hz, 25 Hz and 100 Hz. Participants attended a total of eight entrainment frequency sessions twice over the duration of a 4-week period. Additionally, participants were assessed based on their cognitive abilities, mood as well as memory, where the cognitive and memory assessments occurred before and after a 5-min binaural beat stimulation. The mood assessment scores were collected from sessions 1, 4 and 8, respectively. With respect to the Gamma 40 Hz entrainment frequency population, we observed a mean improvement in cognitive scores, elevating from 75% average to 85% average upon conclusion of the experimentation at weak statistical significance ([Formula: see text] = 0.10, p = 0.076). Similarly, memory score improvements at a greater significance ([Formula: see text] = 0.05, p = 0.0027) were noted, elevating from an average of 87% to 95%. In pertinence to the mood scores, a negative correlation across all populations were noted, inferring an overall increase in mood due to lower scores correlating with elevated mood. Finally, correlation analysis revealed a stronger R[Formula: see text] value (0.9838) within the 40 Hz group between sessions as well as mood score when compared across the entire frequency group cohort.


Hsa_circ_0041150 serves as a novel biomarker for monitoring chemotherapy resistance in small cell lung cancer patients treated with a first-line chemotherapy regimen.
To explore the potential of circRNAs as biomarkers in non-invasive body fluids for monitoring chemotherapy resistance in SCLC patients. CircRNAs were screened and characterized using transcriptome sequencing, Sanger sequencing, actinomycin D treatment, and Ribonuclease R assay. Our study involved 174 participants, and serum samples were collected from all chemotherapy-resistant patients (n = 54) at two time points: stable disease and progressive disease. We isolated and identified serum extracellular vesicles (EVs) from the patients using ultracentrifugation, transmission electron microscopy, nanoflow cytometry, and western blotting analysis. The expression levels of serum and serum EVs circRNAs were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The impact of circRNA on the function of SCLC cells was assessed through various assays, including proliferation assay, scratch assay, transwell assay, and cisplatin resistance assay. Hsa_circ_0041150 was found to be upregulated in chemoresistant SCLC cells and played a role in promoting proliferation, invasion, migration, and cisplatin resistance. Furthermore, the expression levels of hsa_circ_0041150 in serum and serum EVs increased when SCLC patients developed resistance after a first-line chemotherapy regimen. When combined with NSE, the monitoring sensitivity (70.37%) and specificity (81.48%) for chemotherapy resistance significantly improved. Moreover, the expression level of hsa_circ_0041150 showed significant associations with time to progression from SD to PD, and high hsa_circ_0041150 levels after drug resistance were more likely to cause chemotherapy resistance. Additionally, hsa_circ_0041150 demonstrated valuable potential in monitoring the progression from initial diagnosis to chemotherapy resistance in SCLC patients. Thus, EVs hsa_circ_0041150 holds promise as a biomarker for monitoring chemotherapy resistance in SCLC patients.


Chronic kidney disease and risk for presenting with acute myocardial infarction versus stable exertional angina in adults with coronary heart disease.
The aim of this study was to examine whether kidney dysfunction is associated with the type of clinical presentation of coronary heart disease (CHD). Reduced kidney function increases the risk for developing CHD, but it is not known whether it also influences the acuity of clinical presentation, which has important prognostic implications. A case-control study was conducted of subjects whose first clinical presentation of CHD was either acute myocardial infarction or stable exertional angina between October 2001 and December 2003. Estimated glomerular filtration rate (eGFR) before the incident event was calculated using calibrated serum creatinine and the abbreviated MDRD (Modification of Diet in Renal Disease) equation. Patient characteristics and use of medications were ascertained from self-report and health plan databases. Multivariable logistic regression was used to examine the association of reduced eGFR and CHD presentation. A total of 803 adults with incident acute myocardial infarctions and 419 adults with incident stable exertional angina who had baseline eGFRs ≤130 ml/min/1.73 m(2) were studied. Mean eGFR was lower in subjects with acute myocardial infarctions compared with those with stable angina. Compared with eGFR of 90 to 130 ml/min/1.73 m(2), a strong, graded, independent association was found between reduced eGFR and presenting with acute myocardial infarction, with adjusted odds ratios of 1.36 (95% confidence interval: 0.99 to 1.86) for eGFR 60 to 89 ml/min/1.73 m(2), 1.55 (95% confidence interval: 0.92 to 2.62) for eGFR 45 to 59 ml/min/1.73 m(2), and 3.82 (95% confidence interval: 1.55 to 9.46) for eGFR <45 ml/min/1.73 m(2) (p < 0.001 for trend). An eGFR <45 ml/min/1.73 m(2) is a strong, independent predictor of presenting with acute myocardial infarction versus stable angina as the initial manifestation of CHD.


Industry payments to US physicians for cancer therapeutics: An analysis of the 2016-2018 open payments datasets.
Many oncologists who lead guidelines and clinical trials have financial conflicts of interest (fCOI) with industry. However, the extent to which fCOI reaches all cancer care providers is not known. Here we describe industry payments across all cancer care specialties by specific drug. This observational, retrospective cohort study used Open Payments to describe general payments (i.e. consulting fees, meals, travel) to all US physicians for any cancer medicine during 2016-2018. Endpoints included number and value of payments by specialty, drug, and year. During 2016-2018, industry made general payments to 52 441 physicians for 137 unique cancer drugs. Annual number of payments (465 655 in 2018) and total value ($98.5 million in 2018) increased over the study period (20 % and 31 % increase since 2016). Medical/hematologic oncologists, surgical oncologists and radiologists received the highest total value of payments, accounting for $65.7 million (67 % of total), $13.4 million (14 % of total) and $10.8 million (11 % of total) in 2018. In 2018, 5 % of physicians (n = 1660) received >$10 000 in annual payments and 0.6 % (n = 209) received >$100 000. Pembrolizumab and Nivolumab, were associated with the highest total payment in each year, accounting for 12 % and 6 % (2018) of total value, respectively. While prior work has identified fCOIs among oncology leaders, these data suggest that payments extend across the cancer system. Pre-existing data suggest a strong relationship between industry payments and physician prescribing. The current study demonstrates that fCOIs among oncology prescribers are pervasive. The oncology community must consider the extent to which these relationships influence clinical practice and regulatory policies.


A non-toxic recombinant Clostridium septicum α toxin induces protective immunity in mice and rabbits.
Clostridium septicum alpha toxin (CSA) plays significant roles in ruminant's braxy. Genetically engineered CSA has been shown to function as a potential vaccine candidate in the prevention of the disease caused by Clostridium septicum. In the present study, we synthesized a non-toxic recombinant, rCSAm4/TMD by introducing four amino acid substitutions (C86L/N296A/H301A/W342A) and 11-amino-acid deletion (residues 212 to 222). Compared to recombinant CSA, rCSAm4/TMD showed no cytotoxicity to MDCK cells and was not fatal to mice. Moreover, rCSAm4/TMD could protect immunized mice against 5 × mouse LD100 (100% lethal dose) of crude CSA without obvious pathological change. Most importantly, rabbits immunized with rCSAm4/TMD produced high titers of neutralizing antibodies which protected the rabbits against crude CSA challenge. These data suggest that genetically detoxified rCSAm4/TMD is a potential subunit vaccine candidate against braxy.


The value of live three-dimensional echocardiography in an adult patient with aortico-left ventricular tunnel.
Aortico-left ventricular tunnel (ALVT) is a rare cardiac abnormality. This article presents an adult case of ALVT with aortic ostium lying above the left-noncommissure which was diagnosed with live three-dimensional echocardiography (3DE). Live 3DE has shown its value in providing more detailed information.


Neothelaxespileata, a new species from China (Hemiptera, Sternorrhyncha, Aphididae, Thelaxinae).
Neothelaxespileata Qiao sp. nov., found on Pileamartinii (Urticaceae) in China, is described and illustrated. Neothelaxes Chakrabarti & Quednau is also a new generic record for China.


Comparison of two clomiphene citrate dosage regimens for follicular recruitment in an in vitro fertilization program.
Clomiphene citrate (CC) (150 mg/day) is used in most clinical in vitro fertilization and embryo transfer (IVF-ET) programs to induce maturation of several preovulatory follicles rather than the one characteristic of the unstimulated cycle. This study examines whether a reduced dosage of CC will induce the maturation of a similar number of follicles. The advantage of the reduced dosage should be a decrease in the dose-dependent antiestrogenic effects of CC. Normally ovulating women undergoing treatment in an IVF-ET program received CC on cycle days 5 to 9. Thirty-six patients received 150 mg/day, and 60 patients received 50 mg/day. There were no significant differences between the groups in the number or the size of follicles as measured by ultrasonography on the day of human chorionic gonadotropin administration. All seven clinical pregnancies were in the 50 mg group (P less than 0.05). These data suggest that there is no advantage to the 150 mg/day dosage of CC as compared with 50 mg/day with respect to enhanced follicular recruitment, and the higher dosage may have a detrimental effect on pregnancy establishment.