A pH-responsive ratiometric fluorescence system based on AIZS QDs and azamonardine for urea detection.
Herein, a ratiometric fluorescent nanoprobe was strategically fabricated using pH-sensitive azamonardine (Aza) as a pH indicator and pH-insensitive AIZS QDs as a reference fluorescence signal for urea activity determination and pH sensing. As the pH changed from 9.7 to 11.7, the resorcinol could react with dopamine to form the cyclization product (Aza), producing a fluorescence signal at 455 nm. Meanwhile, the fluorescence intensity of AIZS QDs at 566 nm remained unchanged. Thus, the ratio of the fluorescence intensity (F455/F566) was able to quantify pH value. Our designed pH-sensing platform showed a linear respond to pH values in the range of 9.7 to 11.7 at intervals of 0.2. In addition, the hydrolysis of urea by urease caused an increase of the system pH value, which can be used to measure the concentration of urea. The developed method for urea determination exhibited a good linear relationship from 0.02 to 20 mM and the limit of detection was 0.0103 mM. Moreover, the practical application was confirmed by urea analysis in real water sample with high feasibility and accuracy, indicating the great application prospects of this sensing platform for urea activity analysis.


Quantitative immunodetection of key elements of polyphosphoinositide signal transduction in osteoblasts from arthritic patients shows a direct correlation with cell proliferation.
Phosphoinositides play an essential role in diverse cellular functions such as cell proliferation, cytoskeletal regulation, intracellular vesicle trafficking, motility, cell metabolism and death. Alteration of these pathways is common to many diseases. In this study, we show that osteoblasts from patients affected by osteoarthritis (OA) and by rheumatoid arthritis (RA) present a decreased cell proliferation and a reduced expression of the key elements of polyphosphoinositide signal transduction such as phosphatidylinositol-3-kinase (PI 3K), phospholipase C gamma1 (PLCgamma1), and protein kinase C zeta (PKCzeta) compared to the post-traumatic (PT) patients. Our results suggest that a correlation may exist between the reduced osteoblast proliferation observed in OA and RA patients and the lowered expression of PI 3K, PLCgamma1, and PKCzeta enzymes. The reduced proliferation rate of osteoblasts in response to these signal transduction effectors could counteract the evolution of arthritic disease.


Piezoelectric surgery: twenty years of use.
The use of ultrasonic vibrations for the cutting of bone was first introduced two decades ago. Piezoelectric surgery is a minimally invasive technique that lessens the risk of damage to surrounding soft tissues and important structures such as nerves, vessels, and mucosa. It also reduces damage to osteocytes and permits good survival of bony cells during harvesting of bone. Piezoelectric surgery was first used by oral and maxillofacial surgeons for osteotomies, but recently some specific applications in neurosurgery and orthopaedics have been proposed. We review the different applications of piezoelectric surgery.


Designer glycopeptides for cytotoxic T cell-based elimination of carcinomas.
Tumors express embryonic carbohydrate antigens called tumor-associated carbohydrate antigens (TACA). TACA-containing glycopeptides are appealing cytotoxic T cell (CTL)-based vaccines to prevent or treat cancer because the same sugar moieties are expressed in a variety of tumors, rendering a vaccination strategy applicable in a large population. Here we demonstrate that by using glycopeptides with high affinity for the major histocompatibility complex and glycosylated in a position corresponding to a critical T cell receptor (TcR) contact, it is possible to induce anti-TACA CTL in vivo. In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (beta-Gal-[1-->3]-alpha-GalNAc-O-serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. The fine specificity of the TF-specific CTL repertoire indicates that the TcR recognize the glycosylated amino acid residue together with TF in a conventional major histocompatibility complex class I-restricted fashion. These results have high potential for immunotherapy against a broad range of tumors.


Bilateral chorea associated with caudate nuclei lacunar infarcts. A case report.
A woman with ischaemic heart disease, hypertension and diabetes, who presented with bilateral chorea associated with lacunar infarcts in the caudate nuclei, is described.


Comparative analysis of the chemical constituents of two varieties of Pueraria candollei.
A high-performance liquid chromatography (HPLC) method was developed to determine the contents of miroestrol and deoxymiroestrol in the tubers of Pueraria candollei var. mirifica and P. candollei var. candollei. The linear detection ranges were 0.78-25.00 μg/mL for miroestrol and 1.56-25.00 μg/mL for deoxymiroestrol. The limit of detection (LOD) and limit of quantification (LOQ) were 0.2 and 0.78 μg/mL, respectively, for miroestrol and 0.78 and 1.56 μg/mL, respectively, for deoxymiroestrol. Our results suggest that both varieties of P. candollei can produce miroestrol and deoxymiroestrol and that the developed HPLC method can be applied for quality control of plants and their products.


The environmental impact on air quality and exposure to carbon monoxide from charcoal production in southern Brazil.
Black wattle silviculture is an important activity in southern Brazil. Much of the wood is used in the production of charcoal and the pyrolysis products impacts on air quality. This paper estimates the level of atmospheric contamination from the production of charcoal in one region of Brazil. We describe a low-cost charcoal kiln that can capture condensable gases and we estimate the levels of exposure of kiln workers to carbon monoxide. The latter results indicated that exposure to carbon monoxide can be reduced from an average of 950 ppm to 907 ppm and the mass of gases reduced by 16.8%.


Molecular characterization of Camelpox virus isolates from Bikaner, India: Evidence of its endemicity.
Camelpox is an important viral disease of camels, which may produce mild skin lesions or severe systemic infections. Camelpox virus (CMLV) isolates retrieved from an incidence of camelpox in camels at Bikaner, India were characterized on the basis of genotype and pathotype. Histopathological examination of the CMLV scab revealed intracytoplasmic-eosinophilic inclusion bodies. The phylogenetic analysis of all eight CMLV isolates for C18L gene nucleotide sequence revealed its clustering with its strains M-96 from Kazakhstan and CMS from Iran. The study will help to understand the transmission chain, pathobiology, and epidemiology of circulating CMLV strains. The full genome sequencing of some of the exemplary samples of CMLV is recommended in order to plan and implement a suitable control strategy.


Human interleukin 10 suppresses production of inflammatory mediators by LPS-stimulated equine peritoneal macrophages.
To investigate the ability of recombinant human interleukin 10 (rhuIL-10) to suppress the release of inflammatory mediators from lipopolysaccharide (LPS)-stimulated equine macrophages, rhuIL-10 was added to equine peritoneal macrophage monolayers at concentrations of 0, 0.1, 1, 10, or 100 ng/ml. Thirty minutes later, LPS (E. coli O55:B5) was added at final concentrations of 0, 1, 10, 100 ng/ml. Macrophages were incubated for 16 h at 37 degrees C, then supernates were harvested and assayed for tumor necrosis factor (TNF) activity (L929 cytotoxicity), interleukin-6 (IL-6) activity (B9 proliferation), prostaglandin E2 concentration (ELISA), and nitric oxide (Griess reaction for nitrite). Preincubation of LPS-stimulated peritoneal macrophages with rhuIL-10 caused significant (P<0.05) reduction in secretion of TNF, IL-6, and PGE2, in a dose-dependent manner. Of the inflammatory mediators, TNF was most sensitive to the effects of rhuIL-10. At concentrations of rhuIL-10> or =1 ng/ml, TNF activity in the supernate was inhibited significantly at all concentrations of LPS. At one or more LPS concentrations, there was significant inhibition of each mediator in the presence of 1 ng rhuIL-10/ml and, at 100 ng/ml, rhuIL-10 significantly inhibited production of each mediator at all LPS concentrations tested. When data were expressed as a percentage of control values and pooled across all LPS concentrations, both PGE2 and TNF values were significantly reduced at rhuIL-10 concentrations of > or =1 ng/ml, whereas IL-6 was inhibited significantly at concentrations of > or =10 ng rhuIL-10/ml. Tumor necrosis factor production was more completely suppressed (7.8% of control) by the highest concentration of rhuIL-10(100 ng/ml) than was PGE2 (27.2%) or IL-6 (43.8%). Nitrite was not detected in any supernate from peritoneal macrophage monolayers.


Histopathological Study of Left and Right Atria in Isolated Rheumatic Mitral Stenosis With and Without Atrial Fibrillation.
Mitral stenosis (MS) has the highest incidence of atrial fibrillation (AF) in chronic rheumatic valvular disease. There are very few studies in isolated MS comparing histopathological changes in patients with sinus rhythm (SR) and AF. To analyze the histological changes associated with isolated MS and compare between changes in AF and SR. This was a prospective study in patients undergoing valve replacement surgery for symptomatic isolated MS who were divided into 2 groups, Group I AF (n = 13) and Group II SR (n = 10). Intra-operative biopsies performed from 5 different sites from both atria were analyzed for 10 histopathologic changes commonly associated with AF. On multivariate analysis, myocytolysis (odds ratio [OR]: 1.48, P = 0.05) was found to be associated with AF, whereas myocyte hypertrophy (OR: 0.21, P = 0.003), and glycogen deposition (OR: 0.43, P = 0.002) was associated with SR. Interstitial fibrosis the commonest change was uniformly distributed across both atria irrespective of the rhythm. In rheumatic MS, SR is associated with myocyte hypertrophy whereas AF is associated with myocytolysis. Endocardial inflammation is more common in left atrial appendage irrespective of rhythm. Interstitial fibrosis is seen in >90% of patients distributed in both the atria and is independent of the rhythm. Amyloid and Aschoff bodies are uncommon and the rest of the changes are uniformly distributed across both the atria.


Does spinal anesthesia lead to postoperative urinary retention in same-day urogynecology surgery? A retrospective review.
Spinal anesthesia has been reported to be a risk factor for postoperative urinary retention (POUR) in various surgical specialties. We hypothesized that spinal anesthesia was a risk factor for POUR after outpatient vaginal surgery for pelvic organ prolapse (POP). This was a retrospective review of an urogynecology database for all outpatient POP vaginal surgeries performed in 2014 to evaluate the risk of POUR after general versus spinal anesthesia. A standardized voiding trial was performed by backfilling the bladder with 300 ml of saline. A successful trial was achieved if the patient voided two-thirds of the total volume instilled, confirmed by bladder ultrasound. Our primary outcome was to compare POUR requiring discharge with a Foley catheter between spinal and general anesthesia. Multivariate logistic regression was performed for variables with significance at p < 0.1 at the bivariate level. A total of 177 procedures were included, 126 with general and 51 with spinal anesthesia. The overall POUR rate was 48.9%. Type of anesthesia was not a risk factor for POUR. Multivariate logistic regression demonstrated that age < 55 years (adjusted odds ratio [OR] 3.73; 95% confidence interval [CI], 1.31-11.7), diabetes (adjusted OR 4.18, 95% CI 1.04-21.67), and having a cystocele ≥ stage 2 (adjusted OR 4.23, 95% CI 1.89-10) were risk factors for developing POUR. Acute urinary retention after outpatient vaginal pelvic floor surgery can vary by procedure, but overall is 48.9%. Spinal anesthesia does not contribute to POUR, but rates are higher in those women that are younger than 55 years of age, have a cystocele ≥ stage 2 preoperatively, and a history of diabetes.


Brain and retinal microglia in health and disease: an unrecognized target of the renin-angiotensin system.
Microglia are the resident immune cells within the brain and retina, commonly known as the macrophages of the central nervous system (CNS). Microglia survey the surrounding milieu to eliminate invading microbes, clear cellular debris and enforce programmed cell death by removing apoptotic cells. Complementary to their 'house-keeping' role, microglia are capable of releasing brain-derived neurotrophic factor (BDNF), as well as various anti-inflammatory cytokines that sustain and support neuronal survival. Although microglia are essential for maintaining a healthy CNS, paradoxically they may undergo phenotypic changes to influence numerous neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Understanding the underlying mechanisms that determine whether microglia are supportive or toxic could elucidate novel and more effective therapeutic targets to treat an array of neurological and retinal diseases. Although relatively little is known about the influences that evoke phenotypic changes in the microglial population, there is accumulating evidence illustrating an interaction with the renin-angiotensin system (RAS). The angiotensin AT1 and AT2 receptors may have differential roles in mediating the activity of microglia. Understanding the actions of these angiotensin receptors will be important in defining whether microglia are an important therapeutic target for RAS blockade in brain and ocular diseases.


Electrocardiographic patterns of proximal left anterior descending artery occlusion in ST-elevation myocardial infarction may be modified by 3-vessel coronary artery disease.
The electrocardiographic (ECG) pattern of ST-segment deviation in myocardial infarction is integral to the proper assessment of the location, extent, and functional significance of the infarct but may be modified by the underlying coronary artery anatomy. We describe the ECG findings in 2 cases of proximal left anterior descending (LAD) artery occlusion in ST-elevation myocardial infarction (STEMI) associated with 3-vessel coronary artery disease. Both patients had atypical ECG patterns of ST-segment elevation in leads V(2), I, and aVL and ST-segment depression with positive T waves suggestive of extensive subendocardial ischemia in leads II, III, aVF, and V(3) through V(6); acute proximal LAD occlusion and concomitant 3-vessel coronary artery disease were observed angiographically. Electrocardiographic changes in proximal LAD STEMI may be modified by the presence of significant atherosclerotic disease elsewhere in the coronary vasculature. Recognition of this ECG pattern may aid the clinician in the rapid identification of high-risk STEMI.


Integration analysis of metabolome and transcriptome profiles revealed the age-dependent dynamic change in chicken meat.
To explore the chemical composition of chicken meat during different growth and development periods, the dynamic alterations of the metabolite composition were determined using LC-MS/MS-based metabolomics. Together, 573 metabolites were identified in chicken meat from five age stages. Generally, pentadecanoic acid, stearic acid, creatine, carnosine, IMP, L-histidine and L-isoleucine presented an upward trend with age, while anserine, DHA, L-aspartic acid, LPA 18:1 and LPI 18:1 decreased with age. The main pathways of chicken meat metabolism affected by age were fructose and mannose metabolism, arachidonic acid metabolism, steroid hormone biosynthesis, riboflavin metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. Using transcriptomic profiling data, we conducted Pearson correlation analysis between gene expression and metabolite profile data in each age comparison. Integration analysis of metabolome and transcriptome would be helpful to understand the biological processes underlying the development of meat quality and explore valuable biomarkers for specific metabolite accumulation.


Machine learning augmented near-infrared spectroscopy: In vivo follow-up of cartilage defects.
To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints.


Utilization of dental care among adult populations: a scoping review of applied models.
The timely and appropriate utilization of dental health care is essential to the prevention and accurate treatment of oral diseases. Therefore, it is crucial that managers, health professionals and healthcare providers be fully aware of the predictors encouraging the utilization of dental services and reduce social inequalities. In this scoping review, we aimed to analyze the published articles and reports to find out the factors associated with dental services utilization and the comprehensiveness of the applied models among general adult populations. This scoping study was based on the 5-steps of Arksey and O'Malley framework. Keywords were selected under two main concepts: determinants of dental care utilization and the concept of the applied models. Searches were conducted in some electronic databses including PubMed, Google Scholar and Scopus with variations, and a combination of the keywords under the two main afore-mentioned concepts. All the relevant articles reporting the utilization of dental care and its potential predictors among adult populations were chosen. No restrictions involving terms of study time, location or methodological aspects of oral health utilization were considered. Using tables and charts mapping, we tried to group the studies based on the year of their publication, geographic distribution, the range of included indices and the type of their measurement. Also, a directed content analysis method was used to investigate the comprehensiveness of the studies in regard to considering the determinant factors at different levels suggested by the Andesen model. Fifty-two articles were included in the analysis. Thirty-six (69%) had been published between 2016 and 2020. The United States had conducted the most research in this scope. About 30% of studies had mentioned all three domains of demographics, social structure and beliefs, simultaneously. To evaluate the enabling factors, in 84.61% and 59.61% of studies, the income levels and insurance feature were assessed, respectively. 57.69% of the retrieved studies considered the perceived need features and 38.46% referred to the evaluated ones. The dental services utilization, in terms of the last visit during the "past 12 months", was assessed more commonly. Only 11.54% of studies did evaluate the contextual characteristics and about 71.15% of articles were relatively comprehensive. Overall, it seems that in most of the studies, not all of the determinant factors at different levels of the Andersen model have been considered. In order to discover the conceptual linkages and feedback loops of the model, it is essential to conduct more comprehensive research in the future.


Identification of fetuin in human and rat fetuses and in other species.
The fetal protein, fetuin, has previously only been identified in species belonging to the order Artiodactyla. Samples of fetal, newborn and adult human (Homo sapiens) and rat (Rattus norvegicus) plasma and tissues have been studied using three techniques: (a) crossed immunoelectrophoresis of plasma against each of four different anti-fetuin antisera (two anti-cattle, one anti-pig and one anti-sheep); (b) the peroxidase-antiperoxidase technique applied to agarose gels containing plasma spots; (c) the indirect immunoperoxidase technique applied to human fetal tissue sections. In human fetal samples all three methods gave evidence for the presence of fetuin except late in gestation and in the newborn. Adult plasma was negative. In rat fetuses only plasma was tested, by methods (a) and (b). Positive reactions were obtained for both fetal and adult samples; the fetal samples cross-reacted with several of the anti-fetuins, adult samples reacted with only one. All the fetal and embryonal plasma samples tested with the peroxidase-antiperoxidase method were positive for fetuin except for the chicken. Thus fetuin appears to be distributed in at least five mammalian orders (Artiodactyla, Primates, Rodentia, Carnivora and Perissodactyla).


Two adjacent cysteine residues in the C-terminal cytoplasmic fragment of bovine rhodopsin are palmitylated.
Covalent coupling of bovine rhodopsin to CPG-thiol glass was used for separation of CNBr peptides. It is shown that cysteine residues 322 and 323 in the C-terminal cytoplasmic fragment of rhodopsin are modified with palmitic acid.


Optimising the use of proteins from rich meat co-products and non-meat alternatives: Nutritional, technological and allergenicity challenges.
An exponential growth in the global demand for high quality proteins over the next 20 years is expected, mainly due to global population growth and the increasing awareness toward protein rich foods for more nutritive diets. Coupled with this, is the pressing need for more sustainable approaches within a bio-economy mindset. Although meat production is expected to increase to address this rising demand, a better use of the currently available resources provided by the food, and specially, the meat industry is required. In this regard, despite the high-quality proteins and other nutrients found in meat co-products; they are currently underused and their valorisation needs to be revisited. Also, emerging protein sources need to be investigated to alleviate the environmental pressure coming from the meat industry. In this review, the main focus was attributed to (i) the current and forthcoming challenges for the use of meat co-products as meat replacers to produce a new range of meat derived products (with high nutritional value, improved technological properties and better consumer acceptance); (ii) their performance regarding to the non-animal origin proteins currently used as meat protein replacers; and (iii) the allergenicity of the proteins that might fall into the category of novel protein sources.


Cholesterol levels in young adults: screen and intervene?
Early intervention is cost-effective over the long term: The cost of cholesterol-lowering drugs is easily offset by savings in the treatment of cardiovascular disease. Besides, most interventions are dietary, not pharmacologic.


Influence of solvents in the preparation of cobalt sulfide for supercapacitors.
In this study, cobalt sulfide (CoS) electrodes are synthesized using various solvents such as water, ethanol and a combination of the two via a facile chemical bath deposition method on Ni foam. The crystalline nature, chemical states and surface morphology of the prepared CoS nanoparticles are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy and transition electron microscopy. The electrochemical properties of CoS electrodes are also evaluated using cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy. When used as an electrode for a supercapacitor, CoS prepared with ethanol as a solvent exhibits a capacitance of 41.36 F g-1 at 1.5 A g-1, which is significantly better than that prepared using water and water/ethanol-based solvents (31.66 and 18.94 F g-1 at 1.5 A g-1, respectively). This superior capacitance is attributed to the ideal surface morphology of the solvent, which allows for easy diffusion of electrolyte ions into the inner region of the electrode. High electrical conduction enables a high rate capability. These results suggest that CoS nanoparticles are highly promising for energy storage applications as well as photocatalysis, electrocatalysis, water splitting and solar cells, among others. These results show that CoS is a promising positive electrode material for practical supercapacitors.


Optimization of manganese peroxidase and laccase production in the South American fungus Fomes sclerodermeus (Lév.) Cke.
Fomes sclerodermeus produces manganese peroxidase (MnP) and laccase as part of its ligninolytic system. A Doehlert experimental design was applied in order to find the optimum conditions for MnP and laccase production. The factors studied were Cu(2+), Mn(2+) and asparagine. The present model and data analysis allowed us not only to define optimal media for production of both laccase and MnP, but also to show the combined effects between the factors. MnP was strongly influenced by Mn(2+), which acts as an inducer. Under these conditions Cu(2+) negatively affected MnP activity. At 13 days of growth 0.75 U ml(-1) were produced in the optimized culture medium supplemented with 1 mM MnSO(4) and 4 g l(-1) asparagine. The laccase titer under optimized conditions reached maximum values at 16 days of growth: 13.5 U ml(-1) in the presence of 0.2 mM CuSO(4), 0.4 mM MnSO(4) and 6 g l(-1) asparagine. Mn(2+) promoted production of both enzymes. There were important interactions among the nutrients evaluated, the most significant being those between Cu(2+) and asparagine.


Production of butyrate from lysine and the Amadori product fructoselysine by a human gut commensal.
Human intestinal bacteria produce butyrate, which has signalling properties and can be used as energy source by enterocytes thus influencing colonic health. However, the pathways and the identity of bacteria involved in this process remain unclear. Here we describe the isolation from the human intestine of Intestinimonas strain AF211, a bacterium that can convert lysine stoichiometrically into butyrate and acetate when grown in a synthetic medium. Intestinimonas AF211 also converts the Amadori product fructoselysine, which is abundantly formed in heated foods via the Maillard reaction, into butyrate. The butyrogenic pathway includes a specific CoA transferase that is overproduced during growth on lysine. Bacteria related to Intestinimonas AF211 as well as the genetic coding capacity for fructoselysine conversion are abundantly present in colonic samples from some healthy human subjects. Our results indicate that protein can serve as a source of butyrate in the human colon, and its conversion by Intestinimonas AF211 and related butyrogens may protect the host from the undesired side effects of Amadori reaction products.


CTNNA3 genetic polymorphism may be a new genetic signal of type 2 diabetes in the Chinese Han population: a case control study.
Type 2 Diabetes (T2D) is the result of a combination of genes and environment. The identified genetic loci can only explain part of T2D risk. Our study is aimed to explore the association between CTNNA3 single nucleotide polymorphisms (SNPs) and T2D risk. We conducted a 'case-control' study among 1002 Chinese Han participants. Four candidate SNPs of CTNNA3 were selected (rs10822745 C/T, rs7920624 A/T, rs2441727 A/G, rs7914287 A/G), and logistic regression analysis was used to evaluate the association between candidate SNPs and T2D risk. We used single factor analysis of variance to analyze the differences of clinical characteristics among different genotypes. In this study, haplotype analysis was conducted by plink1.07 and Haploview software and linkage disequilibrium (LD) was calculated. The interaction of candidate SNPs in T2D risk was evaluated by multi-factor dimensionality reduction (MDR). Finally, we conducted a false-positive report probability (FPRP) analysis to detect whether the significant findings were just chance or noteworthy observations. The results showed that CTNNA3-rs7914287 was a risk factor for T2D ('T': OR = 1.33, p = 0.003; 'TT': OR = 2.21, p = 0.001; 'TT' (recessive): OR = 2.09, p = 0.001; Log-additive: OR = 1.34, p = 0.003). The results of subgroup analysis showed that rs7914287 was significantly associated with the increased risk of T2D among participants who were older than 60 years, males, smoking, drinking, or BMI > 24. We also found that rs2441727 was associated with reducing the T2D risk among participants who were older than 60 years, smoking, or drinking. In addition, rs7914287 was associated with T2D patients with no retinal degeneration; rs10822745 and rs7920624 were associated with the course of T2D patients. High density lipoprotein levels had significant differences under different genotypes of rs10822745. Under the different genotypes of rs7914287, the levels of aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase were also significantly different. We found that CTNNA3 genetic polymorphisms can be used as a new genetic signal of T2D risk in Chinese Han population. Especially, CTNNA3-rs7914287 showed an outstanding and significant association with T2D risk in both overall analysis and subgroup analysis.


Effects of prenatal alcohol exposure in a prospective sample of young adults: Mental health, substance use, and difficulties with the legal system.
Few studies have focused on the transition to adulthood in adults with prenatal alcohol exposure (PAE). In this study, we examine the occurrence of problem behavior at this transition, including mental health problems, substance use, and difficulties with the legal system. The sample is prospective and provides an opportunity to examine effects of a wide range of prenatal exposure. Adults with PAE were expected to show more problem behavior; the impact of level of exposure was examined as well. The sample was drawn from a predominantly low-income, African-American population. Mothers of the alcohol-exposed participants (n=123) and those in the non-exposed SES-Control group (CONT) (n=59) were recruited at a prenatal visit when information on alcohol and drug use during pregnancy was collected. A disability contrast group (n=54) was recruited at adolescence. The adults with PAE were assigned to three groups varying in physical and cognitive effects of exposure. This report is based on the adults' responses to interviews or questionnaires on problem behavior and laboratory tests related to substance use. Adults with PAE showed more problem behavior in all three areas than adults from the CONT group. For mental health problems, the exposed group showing cognitive, but not physical effects, had the highest scores; their scores were similar, however, to those of the disability contrast group on several scales. Results for outcomes on substance use and legal difficulties were less consistent, but, when significant effects occurred, the group that was exposed, but neither physically nor cognitively affected, was more likely to show negative outcomes. Males in this group were most involved in these behaviors. Effects of PAE continue into early adulthood and affect mental health problems, substance use, and interactions with the legal system. Adults who are exposed, but less physically affected, seem to be the most involved in problem behavior. More research is necessary to examine environmental effects in conjunction with PAE on these outcomes and to provide a basis for developing potential interventions.


The specific binding of a new 1,2,3-triazole to three blood proteins and it's appended rhodamine complex for selective detection of Hg2.
A synthesized compound, ethyl 2,5-diphenyl-2H-1,2,3-triazole-4- carboxylate (EDTC) was investigated on its physiochemical parameters and structural properties by using the quantum-chemical method. The results on the theoretical spectrum of EDTC were line with experimental fluorescence and absorption spectrum in large degree. Then EDTC was successfully synthesized to a novel rhodamine-based fluorescent probe (REDTC), which showed a distinct fluorescence enhancement upon the presence of Hg2+ in dimethyl formamide-water (DMF-H2O) buffer solution (pH 7.4). Meanwhile, the triazole appended colorless compound turns to pink upon complex formation with Hg2+ ions as 1:2 molar ratios and enables naked-eye detection. The chromogenic mechanism was determined by using spectroscopic measurements and TD DFT calculation. The fluorescence imaging experiments of Hg2+ in HeLa cell revealed that the probe REDTC could be labeled and it could be used in biological systems. Also, the intermediate EDTC was developed as a sensitive fluorescent probe for specific studies on the interactions to three kinds of blood proteins including human serum albumin (HSA), human immunoglobulin (HIg) and bovine hemoglobin (BHb) by using a series of spectroscopic methods and molecular docking under the simulative physiological conditions. The interactions between EDTC and these proteins led to the distinct fluorescence enhancement. The thermodynamic measured results further suggested that hydrophobic forces play a dominating role in stabilizing the complexes, which are in correspondence with the results from molecular docking. The UV-visible, synchronous, and three-dimensional (3D) fluorescence measurements demonstrated that EDTC influences the conformational of proteins and the microenvironment surrounding HSA, HIg, or BHb in aqueous solution.


Perceptions of autism spectrum disorder among the Swahili community on the Kenyan coast.
In high-income and Western societies there is great understanding and awareness of autism spectrum disorder (ASD); however, for many low-middle income countries, research and knowledge is notably lacking. In Africa, there is a growing prevalence of ASD due to increased diagnosis, yet it is still a poorly understood condition. Emerging literature has emphasised how cultural and societal beliefs underpin the level of understanding of ASD, and which typically results in lack of awareness and acceptance. As such it is important to investigate the cultural perceptions towards ASD within low-middle income communities of African culture, to further understand the challenges and barriers individuals with ASD face. The aim of the current study was to probe participants from the Swahili community, on the coast of Kenya, of their cultural views towards ASD. Semi-structured interviews were conducted with seven participants, and the data analysed using thematic analysis. Three key themes developed from the data; stigma, lack of awareness, and Government responsibility. Cultural perceptions negatively impacted awareness and are exacerbated by lack of directive from the Government in providing appropriate diagnostic and educational support.


A Computational Approach for the Discovery of Protein-RNA Networks.
Protein-RNA interactions play important roles in a wide variety of cellular processes, ranging from transcriptional and posttranscriptional regulation of genes to host defense against pathogens. In this chapter we present the computational approach catRAPID to predict protein-RNA interactions and discuss how it could be used to find trends in ribonucleoprotein networks. We envisage that the combination of computational and experimental approaches will be crucial to unravel the role of coding and noncoding RNAs in protein networks.


Urogenital problems in the neonatal foal.
The common conditions affecting the urogenital tract of the neonatal foal and their medical and surgical management are described. Early recognition and treatment of serious abnormalities are necessary for a successful outcome in the equine neonate.


HMB-45 (gp103) and MART-1 expression within giant cells in an atypical fibroxanthoma: a case report.
Atypical fibroxanthoma (AFX) is a cutaneous tumor that primarily occurs in the sun-damaged skin of the head and neck of adults. It is often a rapidly growing, solitary lesion that may clinically resemble squamous cell carcinoma, malignant melanoma, or lobular hemangioma. The histologic differential diagnosis primarily includes spindle cell squamous carcinoma and spindle cell melanoma, and immunohistochemical studies are often needed to establish the diagnosis. We report an unusual case of an AFX with aberrant HMB-45 and MART-1 (melanoma antigen recognized by T cells-1) immunohistochemical expression. Clinical information was obtained. Histologic examination and immunohistochemical studies were performed. A 54-year-old woman presented with a 1.5 cm posterior scalp lesion, which was excised. Microscopic examination revealed a dermal tumor composed of pleomorphic and spindled cells with numerous giant cells. The tumor cells expressed CD68 but did not express either keratin or S-100. In addition, there was focal gp100 (with HMB-45) and MART-1 expression limited to the large, multinucleated cells with vacuolated cytoplasm. A diagnosis of AFX was subsequently made. This is the first reported case of an AFX with HMB-45 and MART-1 reactivity.


Changes in patient health questionnaire (PHQ-9) scores in adults with medical authorization for cannabis.
Legal access to medical cannabis is increasing world-wide. Despite this, there is a lack of evidence surrounding its efficacy on mental health outcomes, particularly, on depression. This study assesses the effect of medical cannabis on Patient Health Questionnaire (PHQ-9) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada. An observational cohort study of medically authorized cannabis patients in Ontario and Alberta. Overall change in PHQ-9 scores from baseline to follow-up were evaluated (mean change) over a time period of up to 3.2 years. 37,338 patients from the cohort had an initial PHQ-9 score recorded with 5103 (13.7%) patients having follow-up PHQ-9 scores. The average age was 54 yrs. (SD 15.7), 46% male, 50% noted depression at baseline. The average PHQ-9 score at baseline was 10.5 (SD 6.9), following a median follow-up time of 196 days (IQR: 77-451) the average final PHQ-9 score was 10.3 (SD 6.8) with a mean change of - 0.20 (95% CI: - 0.26, - 0.14, p-value < 0.0001). Overall, 4855 (95.1%) had no clinically significant change in their PHQ-9 score following medical cannabis use while 172 (3.4%) reported improvement and 76 (1.5%) reported worsening of their depression symptoms. Although the majority showed no clinically important changes in PHQ-9 scores, a number of patients showed improvement or deteriorations in PHQ-9 scores. Future studies should focus on the parallel use of screening questionnaires to control for PHQ-9 sensitivity and to explore potential factors that may have attributed to the improvement in scores pre- and post- 3-6 month time period.


Behavioral plasticity: Role of neuropeptides in shaping feeding responses.
Behavioral plasticity refers to changes occurring due to external influences on an organism, including adaptation, learning, memory and enduring influences from early life experience. There are 2 types of behavioral plasticity: "developmental", which refers to gene/environment interactions affecting a phenotype, and "activational" which refers to innate physiology and can involve structural physiological changes of the body. In this review, we focus on feeding behavior, and studies involving neuropeptides that influence behavioral plasticity - primarily opioids, orexin, neuropeptide Y, and oxytocin. In each section of the review, we include examples of behavioral plasticity as it relates to actions of these neuropeptides. It can be concluded from this review that eating behavior is influenced by a number of external factors, including time of day, type of food available, energy balance state, and stressors. The reviewed work underscores that environmental factors play a critical role in feeding behavior and energy balance, but changes in eating behavior also result from a multitude of non-environmental factors, such that there can be no single mechanism or variable that can explain ingestive behavior.


In vitro simulated digestion and fecal fermentation of polysaccharides from loquat leaves: Dynamic changes in physicochemical properties and impacts on human gut microbiota.
The aim of this study was to well understand the dynamic changes of physicochemical properties of polysaccharides from loquat leaves (LLP) during in vitro simulated saliva-gastrointestinal digestion and fecal fermentation and its related impacts on human gut microbiota. Results showed that the contents of reducing sugar of LLP slightly increased during the gastrointestinal digestion, and its molecular weight also slightly decreased, suggesting that LLP could be slightly degraded under the gastrointestinal digestion conditions. Moreover, during the fecal fermentation, the molecular weight of the indigestible LLP (LLP-I) significantly decreased, and the molar ratio of constituent monosaccharides of LLP-I, such as glucuronic acid, galacturonic acid, galactose, and arabinose, significantly changed, indicating that LLP-I could be degraded and consumed by human gut microbiota. Indeed, some beneficial bacteria such as Megasphaera, Megamonas, Bifidobacterium, Phascolarctobacterium, and Desulfovibrio significantly increased, suggesting that LLP-I could change the composition and abundance of gut microbiota. LLP-I could also promote the production of health-promoting short chain fatty acids. Results from this study are benefical to well understand the in vitro digestion and fecal fermentation behaviors of LLP, and LLP can be developed as a potential prebiotic in the functional food industry.


The late onset of visual texture segmentation in kittens.
Texture segmentation was studied developmentally in kittens using a two-alternative forced choice jumping stand paradigm. None of 15 kittens tested solved a texture segmentation task based on orientation contrast prior to 83 days of age, despite their rapid acquisition age, despite their rapid acquisition of an analogous luminance-based image segmentation problem. However, three kittens showed rapid acquisition of the texture segmentation task when the textures were composed of non-oriented elements (dots and annuli), reaching criterion performance by 52-59 days of age. A control experiment demonstrated that kittens can discriminate between vertical and horizontal gratings comparable in line width to the oriented texture elements as early as 53 days of age. The surprisingly late appearance of orientation-based texture segmentation is considered in the context of current models of texture segmentation and is compared to recent reports of a similar finding in human infants [3,54].


Ozone washing decreases strawberry susceptibility to Botrytis cinerea while maintaining antioxidant, optical and sensory quality.
This work aimed to evaluate the effect of ozone washing (maximum concentration 3.5 mgL-1- 5 and 15 min) on Botrytis cinerea decay, physicochemical parameters, bioactive compounds, in vitro and in vivo antioxidant activity, and sensory properties of strawberries cv. Albion throughout refrigerated storage at 5 ± 1 °C. A 5 min long ozonation delayed the onset of B. cinerea infection by 4 days, and significantly reduced its incidence as storage progressed (~17 % lesser than in control at day 8), without impairing physicochemical parameters or sensory quality. This treatment did not affect the antioxidant activity of strawberry extracts neither in in vitro (ORAC and ABTS assays) or in vivo assays using Caenorhabditis elegans as a model organism. Higher ozone doses did not achieve greater reduction of B. cinerea decay throughout the storage period. This study demonstrated that exposing strawberries to a 5 min long aqueous ozone treatment could extend their storability at 5 °C.


Quantitative analyses of principal and secondary compound parieto-occipital feedback pathways in cat.
The purpose of our study was to quantify the magnitude of principal and secondary pathways emanating from the middle suprasylvian (MS) region of visuoparietal cortex and terminating in area 18 of primary visual cortex. These pathways transmit feedback signals from visuoparietal cortex to primary visual cortex. (1) WGA-HRP was injected into area 18 to identify inputs from visual structures. In terms of numbers of neurons, feedback projections to area 18 from MS sulcal cortex (areas PMLS, AMLS and PLLS) comprise 26% of inputs from all visual structures. Of these neurons, between 21% and 34.9% are located in upper layers 2-4 and the dominant numbers are located in deep layers 5 and 6. Areas 17 (11.8%) and 19 (11.2%) provide more modest cortical inputs, and another eight areas provide a combined total of 4.3% of inputs. The sum of neurons in all subcompartments of the lateral geniculate nucleus (LGN) accounts for another 34.8% of the input to area 18, whereas inputs from the lateral division of the lateral-posterior nucleus (LPl) account for the final 11.9%. (2) Injection of tritiated-((3)H)-amino acids into MS sulcal cortex revealed substantial direct projections from MS cortex that terminated in all layers of area 18, but with a markedly lower density in layer 4. Projections from MS cortex to both areas 17 and 19 are of similar density and characteristics, whereas those to other cortical targets have very low densities. Quantification also revealed minor-to-modest axon projections to all components of LGN and a massive projection throughout the LP-Pul complex. (3) Superposition of the labeled terminal and cell fields identified secondary, compound feedback pathways from MS cortex to area 18. The largest secondary pathway is massive and it includes the LPl nucleus. Much more modest secondary pathways include areas 17 and 19, and LGN. The relative magnitudes of the secondary pathways suggest that the one through LPl exerts a major influence on area 18, whereas the others exert more modest or minor influences. MS cortex in the contralateral hemisphere also innervates area 18 directly. These data are important for interpreting the impact of deactivating feedback projections from visuoparietal cortex on occipital cortex.


Gradual frequency rises in interacting black ghost knifefish, Apteronotus albifrons.
The present paper highlights the relationship between social status and production of gradual frequency rises in interacting Apteronotus albifrons. The gradual frequency rise production was mathematically inferred and a discrete classification deliberately avoided. The results showed little gradual frequency rise production before the hierarchy settlement. Afterwards, only the dominant fish kept this gradual frequency rise production at low levels, while the subdominant fish drastically increased it in all following interaction contexts. The hypothesis of gradual frequency rises being involved in communication as submissive signals was thus strengthened.


Brain and Cardiac Concomitant Localization of the Hydatid Cyst.
Hydatid cyst is a parasitic infestation that is usually observed in the liver and lungs. The localization in the brain and the heart is exceptional. Here, we report a 11-year-old boy who was diagnosed to have two large hydatid cysts of the heart and brain. We discuss this unusual presentation of hydatid cyst and its management.


Analysis of Relationships between DAT1 Polymorphism Variants, Personality Dimensions, and Anxiety in New Psychoactive Substance (Designer Drug) (NPS) Users.
The use of 'new psychoactive substances' appears to be increasingly common. The aim of this study was to examine biological and personality determinants in individuals who choose to use these substances, which may help in the prevention and treatment of psychoactive substance use disorders. The study group consisted of 374 male volunteers; all were users of 'new psychoactive substances' (NPS). The NPS users were recruited after they had abstained-for at least 3 months-from any substance of abuse in addiction treatment facilities. The NPS patients and the control subjects were examined by a psychiatrist using the Mini-International Neuropsychiatric Interview (M.I.N.I.), the NEO Five-Factor Personality Inventory (NEO-FFI), and the State-Trait Anxiety Inventory (STAI) scales. The real-time PCR method was used for genotyping. When we compared the controls with the study group, statistically significant interactions were found between DAT1 polymorphism, neuroticism, and NPS use. NPS use and DAT1 polymorphism were associated with a higher level of neuroticism on the NEO-FFI scale. The study group of NPS users showed a higher severity of anxiety symptoms, both in terms of trait and state, compared to the control group. The results may support the idea that neuroticism and anxiety correlate strongly with coping motives for using NPS.


Marine protected areas for demersal elasmobranchs in highly exploited Mediterranean ecosystems.
Marine ecosystems are complex socio-ecological systems where sustainable solutions can be best gained by satisfying both conservation and socioeconomic demands. Concretely, the Mediterranean Sea is facing a huge demand of resources and marine activities while hosting abundant and unique biodiversity. It is considered an important elasmobranch hotspot where seventy-two elasmobranch species are present in the basin. Despite the recognised importance of elasmobranchs as umbrella species, to date only a small number of marine protected areas have been designated towards their protection. The paucity of spatially-explicit abundance data on elasmobranchs often precludes the designation of these areas to protect these marine predators. Here, we aimed to identify marine areas to protect elasmobranch species by means of a systematic spatial planning approach. We first estimated the spatial distribution of five elasmobranch species (three sharks and two rays) in the western Mediterranean Sea and then applied Marxan decision support tools to find priority marine conservation areas. We found that the five elasmobranchs are distributed in coastal and slope areas of the southern waters of the study area while in the northern region they are abundant in the continental slope and towards offshore waters. Conservation priority areas were identified in the southern part of the western Mediterranean. Adding more complex cost layers and zoning to the analysis did not alter conservation priority areas, confirming such areas are highly consistent and highly important for elasmobranch protection. The marine conservation priority areas identified here can contribute to designate a proactive area-based protection strategy towards elasmobranch conservation, related species and the habitats that they depend in the western Mediterranean Sea.


Trends in Pediatric Primary Immunodeficiency: Incidence, Utilization, Transplantation, and Mortality.
Primary immunodeficiency disorders (PIDDs) describe a myriad of diseases caused by inherited defects within the immune system. As the number of identified genetic defects associated with PIDDs increases, understanding the incidence and outcomes of PIDD patients becomes imperative. To characterize the frequency of new diagnoses, patterns of health care utilization, rates of hematopoietic stem cell transplantation (HSCT), and mortality in pediatric patients with PIDDs. A retrospective cohort analysis of the Pediatric Health Information System database from 2004 to 2018 for pediatric inpatients with an International Classification of Diseases, Ninth and 10th Revisions (ICD-9/ICD-10). code associated with PIDD. A total of 17,234 patients with a PIDD were hospitalized from 2004 to 2018. There were 2.8 new PIDD diagnoses and 6.3 PIDD hospitalizations per 1,000 discharges; these metrics were unchanged during the study period. The number of new diagnoses for B-cell and antibody defects significantly increased over time. The number of new PIDD diagnoses significantly increased in adolescents or adults and decreased in infants. T-cell disorders had the highest number of intensive care unit admissions. There were 747 PIDD patients who underwent HSCT; complications of HSCT significantly decreased over time. Mortality rates significantly decreased in all PIDD patients and in patients receiving HSCT. The total hospitalizations and incidence of PIDDs within the hospitalized pediatric population were unchanged. There were significant changes in the class of PIDD diagnosed, the age at diagnosis, and health care utilization metrics. Mortality significantly decreased over time within the PIDD cohort.


Gastric emptying in mechanically ventilated critically ill patients: effect of neuromuscular blocking agent.
To assess gastrointestinal function in critically ill patients receiving muscle relaxant and to test clinical tolerance to enteral nutrition. Prospective study in an intensive care unit. 20 critically ill patients requiring sedation with muscle relaxant to obtain adequate mechanical ventilation. Patients were randomly selected to receive infusions of opioid sedation during the first session (session 1) and the same sedation with muscle relaxation (cisatracurium) during the second session (session 2). Gastric emptying was assessed by the paracetamol absorption technique. Following the paracetamol absorption 200 ml enteral feed was given, and the residual gastric volume was measured 1 and 2 h after feeding. The maximum plasma concentration (Cmax) was 14 mg/l (range 5-26) when patients received sedation, and 12 mg/l (range 5-30) when they received muscle relaxant. The target time for reaching the maximum plasma concentration (Tmax) was 30 min (range 20-60) and 35 min (range 20-60), respectively, in sessions 1 and 2. There was no significant difference between the two session as regards Tmax, Cmax, or AUC(0-120). The residual volumes were 110+/-65 ml (H1) and 95+/-76 ml (H2) during session 1 and 125+/-85 ml (H1) and 105+/-90 ml (H2) during session 2. Enteral feeding is one of the most effective methods of supporting nutritional needs in the critically ill patient. We conclude that in critically ill patients requiring sedation gastric emptying is not improved by neuromuscular blocking agent.


Multiple myeloma. A differential consideration for osteolysis surrounding total hip arthroplasties.
A diagnosis of multiple myeloma was made in a 77-year-old man based on the presence of focal periprosthetic osteolytic lesions surrounding a noncemented femoral component. The radiographic appearance of these lesions was remarkably similar to that of focal osteolytic lesions seen around stable prosthetic femoral components resulting from the localized accumulation of particulate debris. Multiple myeloma should be included in the differential diagnosis of osteolytic lesions around prosthetic components.


Socioeconomic and Demographic Characteristics of US Adults Who Purchase Prescription Drugs From Other Countries.
Little is known about the current use of imported drugs and the factors associated with individual purchase of medications outside the US. To evaluate the proportion of the US adult population that purchases medications in other countries and the patient factors associated with the behavior. This retrospective cross-sectional study used data from the 2015-2017 National Health Interview Survey. The study sample included 61 238 individuals 18 years or older who reported use of prescribed medication by a physician or other practitioner. Data analysis was performed in November 2019. Self-reported experience of purchasing prescription drugs from countries outside the US in the past 12 months. Internet use behaviors for health care included searches for health information and filling of a prescription online. Medication-taking behaviors included skipping or delaying filling a prescription and using alternative therapies to save money. Survey design-adjusted analysis was used to estimate and compare characteristics between those who purchased medications outside the US and those did not. Multivariable logistic regression was fitted to examine the association of medication purchases with internet use and medication-taking behavior factors. Among 61 238 US adults taking prescription medications (mean [SD] age, 50.5 [18.5] years; 56.5% female; 70.8% white), the estimated prevalence of purchasing of medication outside the US was 1.5% (95% CI, 1.4%-1.7%; 2.3 million US individuals). Those who purchased medications outside the US were more likely to be older (age >64 years; adjusted odds ratio [aOR], 1.68; 95% CI, 1.24-2.29), to be from Hispanic (aOR, 1.70; 95% CI, 1.23-2.35) or immigrant populations (aOR, 3.20; 95% CI, 2.44-4.20), and to have higher educational attainment (bachelor's degree; aOR, 1.79; 95% CI, 1.27-2.54), lower family income (low income; aOR, 1.41; 95% CI, 1.06-1.87), and lack of insurance (aOR, 3.14; 95% CI, 2.33-4.21). Data analyses indicated that online health information-seeking behavior (aOR, 1.62; 95% CI, 1.33-1.98) or use of an online pharmacy (aOR, 2.30; 95% CI, 1.83-2.90) was associated with a greater likelihood of medication purchases outside the US. Individuals who skipped medications (aOR, 3.86; 95% CI, 3.05-4.88) or delayed filling a prescription (aOR, 4.04, 95% CI, 3.23-5.06) also had higher odds of purchasing medication outside the US. The findings suggest that patients are not using prescription purchases outside the US to meet their medication needs. However, monitoring to promote safe administration of medications imported into the US should be continued.


Studies on the contraceptive efficacy of Praneem polyherbal cream.
Praneem polyherbal cream, a spermicidal formulation, has been developed at the National Institute of Immunology, which makes use of Praneem, a purified extract from the dried seeds of an ancient Indian plant Azadirachta indica (Neem), extract from the pericarp of fruits of Sapindus species and quinine hydrochloride. These ingredients have a synergistic spermicidal activity and an optimised formula was derived. The components were made into a water-soluble cream base prepared by using pharmaceutically acceptable base and stabilised by addition of IP grade antioxidant and preservatives. The cream is devoid of irritation and sensitization potential, as seen with standard Draize test on normal and abraded skin of rabbits and by 21-day cumulative skin sensitivity in human volunteers. The formulation was found to be safe under subacute toxicity studies in monkeys. The formulation has shown high contraceptive efficacy in rabbits and in monkeys after intravaginal application. The shelf-life of the cream at room temperature is estimated to be 18 months by accelerated stability studies.


Preliminary X-ray study of crystals of human C-reactive protein.
Two different crystal forms of human C-reactive protein have been grown from solutions of 2-methyl-2,4-pentanediol. Both crystal forms are tetragonal, the space group for form I is P4(1)22 (or P4(3)22), and that for form II is P4(2)22. The unit cell parameters for form I are a = b = 103.0(5) A, c = 308.5(7) A and for form II are a = b = 103.1(2) A, c = 312.7(6) A. The crystals of form II diffract to at least 3.0 A resolution, and are suitable for detailed structural studies.


Variation in the representation of human anatomy within digital resources: Implications for data integration.
Clinical informatics makes use of anatomical representation-particularly in the form of anatomical terms. But differences and ambiguities in naming anatomical structures and partitioning the body can complicate efforts to interlink anatomical resources and integrate clinical data. To better understand differences in representations of human anatomy, we compare five digital resources: a formal ontology, a terminology, and three 3D graphics applications. Because the graphics applications offer explicit representation of the boundaries and partitions of anatomical structures, they reveal the differences in modeling of anatomy that may not be apparent through text-based representations. The variations in these resources allow us to categorize differences in representations of anatomy and to highlight the importance of this topic in the context of clinical informatics.


A new dosing paradigm: high-dose, short-course fluoroquinolone therapy for community-acquired pneumonia.
The goals of optimal antimicrobial therapy are to treat infection effectively, to improve the clinical condition of the patient, and to prevent the emergence of resistant bacterial strains. For ideal drug usage the World Health Organization recommends administering the correct drug by the best route, in the right amount, at optimum intervals for the appropriate period, and after an accurate diagnosis. This article discusses the use of high-dose, short-course fluoroquinolone therapy as an effective option for patients with community-acquired pneumonia.


Characterization of luminal and peritubular membrane K+ selectivity in proximal tubular cells of frog kidney.
The functional significance of KCNQ1/KCNE1 K(+) secretory fluxes and the effects of 3 micromol/L Cd(2+) on the peritubular cell membrane potential and its potassium selectivity were investigated in proximal tubular cells of the frog kidney. Perfusing the lumen with l-phenylalanine plus/minus chromanol 293B, a specific blocker of KCNQ1, did not modify rapid depolarization and rate of slow repolarization of the peritubular cell membrane. Peritubular exposure to Cd(2+) led to a sustained, reversible hyperpolarization of the peritubular membrane, paralleled by an increase in fractional K(+) conductance. Peritubular barium blunted hyperpolarization of the peritubular cell membrane to Cd(2+). Thus, the KCNQ1/KCNE1 K(+) secretory fluxes are absent in proximal tubule of frog kidney, while Cd(2+) increases K(+) selectivity of the peritubular cell membrane.


Potential of minimally invasive procedures in the treatment of uterine fibroids: a focus on magnetic resonance-guided focused ultrasound therapy.
Minimally invasive treatment options are an important part of the uterine fibroid-treatment arsenal, especially among younger patients and in those who plan future pregnancies. This article provides an overview of the currently available minimally invasive therapy options, with a special emphasis on a completely noninvasive option: magnetic resonance-guided focused ultrasound (MRgFUS). In this review, we describe the background of MRgFUS, the patient-selection criteria for MRgFUS, and how the procedure is performed. We summarize the published clinical trial results, and review the literature on pregnancy post-MRgFUS and on the cost-effectiveness of MRgFUS.


The light-harvesting chlorophyll a/b-protein complex from barley thylakoid membranes. Polypeptide composition and characterization of an oligomer.
Electrophoretic analysis by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis showed that the light-harvesting chlorophyll a/b-protein complex of barley thylakoids contains only one polypeptide of apparent molecular weight 26 000. The barley mutant, deficient in chlorophyll b and this light-harvesting complex, lacks this polypeptide. The addition of a nonionic detergent, Triton X-100, to the sodium dodecyl solubilization buffer prior to SDS polyacrylamide tube gel electrophoresis, allowed separation of a relatively stable complex, characterized as an oligomeric form of the light-harvesting complex. The oligomer also contained a polypeptide with an apparent molecular weight of 26 000. The absorption and fluorescence spectral properties of the oligomer are similar to those of the monomer. It is suggested that the oligomer of the light-harvesting chlorophyll a/b-protein is closer to the in vivo form rather than the monomer.


Multidimensional liquid chromatography of opioid peptides: fluorogenic labelling, retention prediction and separation optimization.
The ultra-trace analysis of opioid peptides in biological samples can be achieved by multidimensional liquid chromatography with pre-column fluorogenic derivatization with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide ion. However, in order to take full advantage of the high sensitivity possible with detectors based on laser-induced fluorescence or chemiluminescence, each component of the analytical method must be carefully optimized. In this study, strategies are presented for the prediction of retention time and the optimization of separations of derivatized opioid peptides in multidimensional LC systems.


Identification of a novel cluster of PCV2 isolates from Meghalaya, India indicates possible recombination along with changes in capsid protein.
Documentation of the emergence of Porcine circovirus 2 (PCV2) infection and economic losses incurred due to high mortality has been reported worldwide. The prevalence and genetic diversity of the virus has been reported in Northeast India including the possible chances of Classical swine fever virus (CSFV) vaccine failure in pig population in this region resulting in major disease outbreak. Irrespective of the genetic variability, the emergence of a novel cluster (based on the ORF2 phylogeny) was reported last year. The present study describes a state-wide (Meghalaya, India) molecular epidemiological investigation of PCV2 strains in pig population by amplification, sequencing and undertaking phylogenetic analyses. The results indicate the identification of a novel cluster of PCV2 originating from the inter-genotypic recombination between PCV2c and PCV2d. Multiple sequence alignment of amino acids indicates possible substitution in the A, B and C domains of the capsid protein. Molecular structural modelling of the capsid protein of PCV2 indicated possible motif variations in the secondary structure including presence of a tunnel, encountered at the interface region on each chain facilitating in transportation of molecules and acting as an active site for attachment and penetration. The baseline data strengthens the existing control programme of PCV2 and is possibly helpful in the planning of active surveillance strategy in this region.


Detection of SARS-CoV-2 by bronchoscopy after negative nasopharyngeal testing: Stay vigilant for COVID-19.
Real-time polymerase chain reaction (RT-PCR) detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is required for diagnosis of coronavirus disease 2019 (COVID-19). Sensitivity of RT-PCR nasopharyngeal (NP) testing is presumed to be high, but there is no gold standard against which this has been determined. The objective was to determine whether lower respiratory tract infection (LRTI), detected in bronchoalveolar lavage fluid (BALF), occurs in the absence of upper respiratory tract infection with clinical testing of both specimen types. Between March 26, 2020 and April 17, 2020 at the University of Washington Medical Center all patients with BALF specimens clinically tested for SARS-CoV-2 were identified. We assessed the proportion of patients with positive RT-PCR for SARS-CoV-2 in BALF after negative NP testing. We describe 3 cases with positive testing in BALF. Among 16 patients with BALF samples, 3 cases (19%) had SARS-CoV-2 detected in BALF. In Case 1, negative NP testing occurred early in the infection and respiratory symptoms may have been missed due to neurologic injury. In Case 2, outpatient diagnosis was aspiration pneumonia, but clinical suspicion remained high for COVID-19 at hospitalization based on epidemiological and clinical features. All 3 cases involved older adults (age >65 years), one of whom was immunosuppressed in the setting of lung transplantation (Case 3). These data demonstrate that SARS-CoV-2 LRTI occurs in the presence of negative NP testing. NP testing may underestimate the prevalence of COVID-19 and has implications for spread of SARS-CoV2 in the community and healthcare setting.


Reevaluating the safety of fertility-sparing hormonal therapy for early endometrial cancer.
To evaluate the safety of fertility-sparing hormonal therapy for endometrial cancer in young patients. Six patients diagnosed with endometrial adenocarcinoma grade I and had undergone progestin treatment were reviewed. Four patients failed progestin treatment and were then found at surgery to have both endometrial and ovarian cancers. A clonality assay using the human androgen receptor gene as the X-linked polymorphic marker and immunohistochemistry for steroid hormone receptor expression were used to delineate the relation between the endometrial and ovarian lesions and to explore possible causes of treatment failure. The patients were followed for a mean of 48.8 months. Four of the six responded to the treatment at a mean of 3.5 months. Two of these patients had a recurrence within a mean of 4.5 months after their initial response. Two patients did not respond to progestin treatment. At surgery in those 4, both endometrial and ovarian tumors were found. All 6 are still alive, and 2 successfully delivered healthy infants. The clonality assay revealed an independent cell origin for the endometrial and ovarian lesions in 2 of the 4 women who failed progestin treatment. Progesterone receptors were absent in both endometrial and ovarian tumors in 2 of these 4 patients. The absence of progesterone receptors may relate to the failure of progestin treatment. The use of progestin treatment for well-differentiated early endometrial carcinoma should be cautious and requires very careful clinical evaluation before and after treatment.


Global climate change increases the impact of pollutant mixtures in the model species Paracentrotus lividus.
The goal of the present work is to study whether ocean- acidification (OA) and -warming (OW) could increase the toxicity of pollutants on P. lividus. We studied how model pollutants such as chlorpyrifos (CPF) and microplastics (MP), alone or in combination, impact the fertilisation process, and the development of larvae under conditions of OA (dissolved inorganic carbon increase of 126 × 10-6 mol per kg of sea water) and OW (temperature increase of 4 °C) predicted by FAO (Food and Agriculture Organization) for the next 50 years. Fertilisation was determined by microscopic examination after 1 h. Growth, morphology, and alteration level were measured after 48 h of incubation. Results showed that CPF has a marked effect on the growth of larvae, but less on the fertilisation rate. When larvae are exposed to both MP and CPF, the effect on fertilisation and growth is higher than when CPF is added alone. Larvae exposed to CPF tend to adopt a rounded shape which is detrimental to their buoyancy and the combination with other stressors aggravate this situation. The variables most influenced by CPF or its mixtures are those related to body length, body width, and higher levels of body abnormalities, which is consistent with the degenerative effects caused by CPF on sea urchin larvae. The PCA analysis showed that temperature has more influence when embryos or larvae are exposed to a combination of stressors, demonstrating that global climate change drastically increase the impact of CPF on aquatic ecosystems. Overall, in this work we demonstrated that global climate change conditions increase the sensitivity of embryos to MP and CPF. Our findings support the idea that global change conditions could have a severe impact on marine life, increasing the negative effect of toxic agents commonly present in the sea and their mixtures.


Efficacy and safety of aquatic exercise in knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.
To examine the efficacy and safety of aquatic exercise for people with knee osteoarthritis. PubMed, Web of Science, Embase, CENTRAL, CNKI and WanFang databases were searched from 1966 to September 2022. Randomized controlled trials evaluating aquatic exercise for people with knee osteoarthritis compared with no exercise and land-based exercise were included. The Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the certainty of evidence. Twenty-two studies with 1394 participants were included. Compared with no exercise (13 trials with 746 participants), low-to high-certainty evidence revealed that aquatic exercise yielded significant improvements in patient-reported pain (SMD -0.58, 95% CI -0.82 to -0.33), stiffness (SMD -0.57, 95% CI -1.03 to -0.11) and physical function (SMD -0.35, 95% CI -0.52 to -0.18) immediately postintervention. A sustained effect was observed only for pain at three months postintervention (SMD -0.48, 95% CI -0.91 to -0.06). The confidence intervals demonstrated that the pooled results do not exclude the minimal clinically important differences. There were no significant differences between the effects of aquatic exercise and land-based exercise (13 trials with 648 participants) on pain (SMD -0.12, 95% CI -0.29 to 0.04), stiffness (SMD -0.17, 95% CI -0.49 to 0.16) or physical function (SMD -0.13, 95% CI -0.28 to 0.02). No study reported a serious adverse event in relation to aquatic exercise. Aquatic exercise provides a short-term clinical benefit that is sustained for at least three months postintervention in terms of pain in people with knee osteoarthritis.


Observation: Three reasons to avoid having half of the trials be congruent in a four-alternative forced-choice experiment on sequential modulation.
Sequential modulation is the finding that the sizes of several selective-attention phenomena--namely, the Simon, flanker, and Stroop effects--are larger following congruent trials than following incongruent trials. In order to rule out relatively uninteresting explanations of sequential modulation that are based on a variety of stimulus- and response-repetition confounds, a four-alternative forced choice task must be used, such that all trials with any kind of repetition can be omitted from the analysis. When a four-alternative task is used, the question arises as to whether to have the proportions of congruent and incongruent trials be set by chance (and, therefore, be 25% congruent and 75% incongruent) or to raise the proportion of congruent trials to 50%, so that it matches the proportion of incongruent trials. In this observation, it is argued that raising the proportion of congruent trials to 50% should not be done. For theoretical, practical, and empirical reasons, having half of the trials be congruent in a four-alternative task aimed at providing unambiguous evidence of sequential modulation should be avoided.


Effect of preconditioning and postoperative hyperbaric oxygen therapy on colonic anastomosis healing with and without ischemia in rats.
To investigate the effect of hyperbaric oxygen therapy on colonic anastomosis healing with and without ischemia in rats. Forty female rats underwent segmental resection of 1 cm of the left colon followed by end-to-end anastomosis. They were randomly assigned to four groups (n=10 each), a sham group; two groups were submitted to Hyperbaric Oxygen therapy (HBOT) with and without induced ischemia and the induced ischemia group without HBOT. The HBOT protocol evaluated was 100% O2 at 2.4 Atmosphere absolute pressure (ATA) for 60 minutes, two sessions before as a preconditioning protocol and three sessions after the operation. Clinical course and mortality were monitored during all experiment and on the day of euthanasia on the fourth day after laparotomy. Macroscopic appearance of the abdominal cavity were assessed and samples for breaking strength of the anastomosis and histopathological parameters were collected. There was no statistically significant difference in mortality or anastomosis leak between the four experimental groups. Anastomosis breaking strength was similar across groups. The HBOT protocol tested herein at 2.4 ATA did not affect histopathological and biomechanical parameters of colonic anastomotic healing, neither the clinical outcomes death and anastomosis leak on the fourth day after laparotomy.


Oral delivery of proteins by biodegradable nanoparticles.
Successful administration of therapeutic proteins via the oral route has long eluded the drug delivery community; a variety of factors, both physical and physiological, have hindered the myriad approaches to increasing the bioavailability of orally administered therapeutic proteins, including: 1) pre-systemic degradation by enzymes and 2) poor penetration of the intestinal mucosa and epithelium. Even when bypassing the harsh, acidic environment of the stomach, the intestines pose significant obstacles to systemic uptake. For example, the lining of the gastrointestinal tract comprises a thick wall of epithelial cells covered by a layer of polysaccharides and mucus. In this review, we will discuss the biology underlying intestinal uptake of protein-containing, biodegradable nanoparticles, review insulin delivery as the most accepted model for oral delivery of proteins, and present a variety of new material systems enabling novel approaches to oral protein delivery which we believe will bring to bear the next therapeutic advances in our field.


The productivity measurement and enhancement system: a meta-analysis.
Meta-analytic procedures were used to examine data from 83 field studies of the Productivity Measurement and Enhancement System (ProMES). The article expands the evidence on effectiveness of the intervention, examines where it has been successful, and explores moderators related to its success. Four research questions were explored and results indicate that (a) ProMES results in large improvements in productivity; (b) these effects last over time, in some cases years; (c) the intervention results in productivity improvements in many different types of settings (i.e., type of organization, type of work, type of worker, country); and (d) moderator variables are related to the degree of productivity improvement. These moderator variables include how closely the study followed the original ProMES methodology, the quality of feedback given, whether changes were made in the feedback system, the degree of interdependence of the work group, and centralization of the organization. Implications based on these findings are discussed for future use of this intervention, and the system is discussed as an example for evidence-based management.


Serious Game for Teaching Undergraduate Medical Students in Cleft lip and Palate Treatment Protocol.
To develop and evaluate a serious game to deliver knowledge about the cleft lip with or without cleft palate (CL/P) protocol used in Craniofacial Center, Chiang Mai University. The game "Cleft Island" was developed then extensively evaluated using different criteria, including the measured knowledge gained by participants, and gameplay experience. A group of 53 fourth and fifth-year medical students (male: 24, female: 29) were recruited to take part in an experiment. They were from the Faculty of Medicine, Chiang Mai University, and had just rotated to the Department of Surgery. Three evaluations were conducted: 1) to test whether the players had competently gained CL/P knowledge; 2) to evaluate the usability of the game according to the System Usability Scale (SUS); and 3) to evaluate the game experience in terms of a Game Experience Questionnaire (GEQ) test. The results indicate a statistically significant improvement of medical students' knowledge after performing the Wilcoxon Signed-Ranks test (p < 0.5) between pre-test and post-test scores of the same medical student group; the acceptable average SUS score (M = 55.28) of the serious game; a moderate degree of experience of the GEQ components including positive affect (M = 2.64), competence (M = 2.49), and immersion (M = 2.21). Cleft Island can be used as an effective supplementary instructional material, which has the potential to provide significant knowledge of CL/P treatment protocol for the players. As far as the authors are aware, this is the first study to implement and assess a serious game for training in CL/P protocol.


Rotavirus and coronavirus-like particles in aboriginal and non-aboriginal neonates in Kalgoorlie and Alice Springs.
In a series of six-month surveys carried out in Kalgoorlie and Alice Springs Hospitals, rotavirus was infrequently detected both in Aboriginal and in non-Aboriginal neonates. Coronavirus-like particles were also detected infrequently, but they were found more often in Aboriginal than in non-Aboriginal neonates. The surveys did not detect any 28-nm virus-like particles.


In vivo antiviral activity of ribavirin/alpha-cyclodextrin complex: evaluation on experimental measles virus encephalitis in mice.
Intracranial injection of the rodent adapted CAM/RB strain of measles virus (MV) induces encephalitis in CBA/ca mice. It has already been shown that cyclodextrins can be used as carriers to increase the antiviral activity of ribavirin (RBV) against MV in cellular model. In this study, the antiviral activity of a RBV/alpha-cyclodextrin complex has been evaluated in vivo using the above model. CBA/ca mice were treated by intraperitoneal injection of free ribavirin (40 mg/kg) or a RBV/alpha-cyclodextrin complex (molar ratio 1:3). After 21 days, intracerebral injection of CAM/RB resulted in 100% mortality in the mock group. In contrast, mortality rates of 80% and 40%, respectively, were observed in RBV and RBV/alpha-CD-treated mice (p<0.05 and p=0.06 for distilled water and RBV, respectively). The viral load of MV in the mouse brain was monitored daily by real-time PCR until day 6 after infection, to compare virus production in treated and non-treated mice. This data shows that RBV complexation with alpha-cyclodextrin can increase the antiviral activity of ribavirin in a measles virus encephalitis model in mice.


High prevalence of sacroiliitis and early structural changes in the sacroiliac joint in children with enthesitis-related arthritis: findings from a tertiary centre in Hong Kong.
Epidemiological studies have demonstrated a wide, unexplained disparity in the prevalence of juvenile idiopathic arthritis (JIA) subtypes depending on geographical location, ethnicity and other factors. Enthesitis-related arthritis (ERA) is more prevalent in Southeast Asia. Axial involvement in ERA patients is increasingly recognised to occur early in the disease course. Inflammation in the sacroiliac joint (SIJ) observed on MRI seems highly predictive of subsequent structural radiographic progression. The resulting structural damage can have significant impacts on both functional status and spinal mobility. This study aimed to evaluate the clinical characteristics of ERA in a tertiary centre in Hong Kong. The primary objective of the study was to provide a comprehensive description of the clinical course and radiological findings of the SIJ among ERA patients. Paediatric patients diagnosed with JIA attending the paediatric rheumatology clinic from January 1990 to December 2020 were recruited from our registry based at the Prince of Wales Hospital. In our cohort, 101 children were included. The median age of diagnosis was 11 years, interquartile range (IQR) 8-15 years. The median follow-up duration was 7 years (IQR 2-11.5 years). ERA was the most prevalent subtype (40%), followed by oligoarticular JIA (17%). Axial involvement was frequently reported in our cohort of ERA patients. 78% demonstrated radiological evidence of sacroiliitis. Among those, 81% had bilateral involvement. The median duration from disease onset to confirmation of radiological sacroiliitis was 17 months (IQR 4-62 months). Among the ERA patients, 73% had structural changes of the SIJ. Alarmingly, 70% of these patients had already developed radiological structural changes when sacroiliitis was first detected on imaging (IQR 0-12 months). Erosion was the most common finding (73%), followed by sclerosis (63%), joint space narrowing (23%), ankylosis (7%) and fatty change (3%). The duration from symptom onset to diagnosis was significantly longer in ERA patients with SIJ structural changes (9 vs 2 months, p = 0.009), comparing with those without. We found that a high proportion of ERA patients had sacroiliitis and a significant number of them had radiological structural changes during early disease. Our findings illustrate the importance of prompt diagnosis and early treatment in these children.


In situ localization of small RNAs in plants by using LNA probes.
Small RNAs have crucial roles in numerous aspects of plant biology. Despite our current understanding of their biogenesis and mechanisms of action, the biological function of small RNAs, particularly miRNAs, remains largely unknown. To decipher small RNA function, knowledge about their spatiotemporal patterns of expression is essential. Here we report an in situ hybridization method for the precise localization of small RNAs in plants by using locked nucleic acid (LNA) oligonucleotide probes. This method has been adapted from protocols used to detect messenger RNAs in formaldehyde-fixed and paraffin-embedded tissue sections, but it includes essential optimizations in key prehybridization, hybridization and posthybridization steps. Most importantly, optimization of probe concentration and hybridization temperature is required for each unique LNA probe. We present the detailed protocol starting from sectioned tissues, and we include troubleshooting tips and recommended controls. This method has been used successfully in several plant species and can be completed within 2-6 d.


Possible specific chromosome changes in large bowel cancer.
Structural and numerical changes affecting chromosomes number 7 and number 12 were the most frequent karyotypic changes observed in 10 large bowel cancers. The findings are briefly discussed in relation to the development of this malignancy.


Decreased number of beta-adrenergic receptors in hypertensive vessels.
Responsiveness to inotropic agents is altered in hypertension and may contribute to its initiation and maintenance. A biochemical basis for this change was provided by the observation that the number of beta-adrenergic receptors, as reflected in specific [3H]dihydroalprenolol binding, was diminished in both arteries and veins of spontaneously hypertensive rats. There was no change in the affinity of dihydroalprenolol for the binding sites or in the capacity of isoproterenol to displace dihydroalprenolol. The decline in beta-adrenergic receptor numbers is not secondary to blood pressure elevation but may, instead, contribute to the pathogenesis of hypertension.


The AVRDC - The World Vegetable Center mungbean (Vigna radiata) core and mini core collections.
Large ex situ germplasm collections generally harbor a wide range of crop diversity. AVRDC--The World Vegetable Center is holding in trust the world's second largest mungbean (Vigna radiata) germplasm collection with more than 6,700 accessions. Screening large collections for traits of interest is laborious and expensive. To enhance the access of breeders to the diversity of the crop, mungbean core and mini core collections have been established. The core collection of 1,481 entries has been built by random selection of 20% of the accessions after geographical stratification and subsequent cluster analysis of eight phenotypic descriptors in the whole collection. Summary statistics, especially the low differences of means, equal variance of the traits in both the whole and core collection and the visual inspection of quantile-quantile plots comparing the variation of phenotypic traits present in both collections indicated that the core collection well represented the pattern of diversity of the whole collection. The core collection was genotyped with 20 simple sequence repeat markers and a mini core set of 289 accessions was selected, which depicted the allele and genotype diversity of the core collection. The mungbean core and mini core collections plus their phenotypic and genotypic data are available for distribution to breeders. It is expected that these collections will enhance the access to biodiverse mungbean germplasm for breeding.


Efficacy and toxicities of elective upper-neck irradiation versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: A meta-analysis.
This meta-analysis aimed to investigate the efficacy and radiation-related toxicities of upper-neck irradiation (UNI) over whole-neck irradiation (WNI) in patients with unilateral or bilateral node-negative nasopharyngeal carcinoma. We conducted a systematic review to identify studies comparing survival and toxicities between UNI and WNI by searching key databases up to Aug 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) for regional recurrence-free survival (RRFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were pooled using R 4.0.5. Risk ratios (RRs) for acute and late radiation-related toxicities were also pooled. Subgroup analyses according to nodal status, radiotherapy techniques, and study type were conducted. Eight studies enrolling 2568 patients were included. Patients who received UNI showed similar RRFS (HR 0.99, 95% CI 0.57-1.74, P = 0.975), LRFS (HR 0.86, 95% CI 0.53-1.41, P = 0.559), DMFS (HR 0.90, 95% CI 0.63-1.29, P = 0.581), PFS (1.10, 95% CI 0.73-1.67, P = 0.642), and OS (1.03, 95% CI 0.77-1.37, P = 0.866) compared with WNI. When stratified by nodal status, the pooled HRs for RRFS in patient subgroups with stage N0 disease, stage N1 with only retropharyngeal lymph nodes metastasis, and unilateral cervical lymph node metastasis were 0.46 (95% CI 0.04-5.16, P = 0.529), 1.12 (95% CI 0.29-4.38, P = 0.872), and 1.02 (95% CI 0.48-2.16, P = 0.968) respectively, none of which reached statistical significance. UNI was associated with lower incidences of grade 1-2 hypothyroidism (RR 0.75, 95% CI 0.57-0.97, P = 0.031) and grade 1-2 dysphagia (RR 0.58, 95% CI 0.42-0.80, P < 0.001) compared with WNI. UNI had similar efficacy and fewer toxicities compared with WNI for patients with unilateral or bilateral node-negative nasopharyngeal carcinoma. The lower-neck sparing of the uninvolved neck is a valid option for N0, N1, and even unilateral N3 diseases in nasopharyngeal carcinoma.


[First experiences with a new radiopharmaceutical for sentinel lymph node detection in malignant melanoma: (99m)Tc colloidal rhenium sulphide].
AIM of this study was to localize the sentinel lymph node by lymphoscintigraphy using technetium-99m colloidal rhenium sulphide (Nanocis), a new commercially available radiopharmaceutical. Due to the manufacturers' instructions it is licensed for lymphoscintigraphy. 35 consecutive patients with histologically proved malignant melanoma, but without clinical evidence of metastases, were preoperatively examined by injecting 20-40 MBq Nanocis with (mean particle size: 100 nm; range: 50-200 nm) intradermally around the lesion. Additionally blue dye was injected intraoperatively. A hand-held gamma probe guided sentinel node biopsy. During surgery, the preoperatively scintigraphically detected sentinel lymph nodes were identified in 34/35 (97%) patients. The number of sentinel nodes per patient ranged from one to four (mean: n = 1.8). Histologically, metastatic involvement of the sentinel lymph node was found in 12/35 (34%) patients; the sentinel lymph node positive-rate (14/63 SLN) was 22%. Thus, it is comparable to the findings of SLN-mapping using other technetium-99m-labeled nanocolloides. (99m)Tc-bound colloidal rhenium sulphide is also suitable for sentinel node mapping.


Electrical activity of the cingulate cortex. II. Cholinergic modulation.
The role of the cholinergic innervation in the modulation of cingulate electrical activity was studied by means of pharmacological manipulations and brain lesions. In the normal rat, an irregular slow activity (ISA) accompanied with EEG-spikes was recorded in the cingulate cortex during immobility as compared to walking. Atropine sulfate, but not atropine methyl nitrate, increased ISA and the frequency of cingulate EEG-spikes. Pilocarpine suppressed ISA and EEG-spikes during immobility, and induced a slow (4-7 Hz) theta rhythm. Unilateral or bilateral lesions of the substantia innominata and ventral globus pallidus area using kainic acid did not significantly change the cingulate EEG or its relation to behavior. Large electrolytic lesions of the medial septal nuclei and vertical limbs of the diagonal band generally decreased or abolished all theta activity in the cingulate cortex and the hippocampus. However, in 5 rats the cingulate theta rhythm increased while the hippocampal theta disappeared after a medial septal lesion. The large, postlesion cingulate theta, accompanied by sharp EEG-spikes during its negative phase, is an unequivocal demonstration of the existence of a theta rhythm in the cingulate cortex, independent of the hippocampal rhythm. Cholinergic afferents from the medial septum and diagonal band nuclei are inferred to be responsible for the behavioral suppression of cingulate EEG-spikes and ISA, and partially for the generation of a local cingulate theta rhythm. However, an atropine-resistant pathway and a theta-suppressing pathway, possibly coming from the medial septum or the hippocampus, may also be important in cingulate theta generation.


Effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients with type 2 diabetes mellitus.
Differences in the efficacy and safety of antidiabetic drugs among different ethnic groups are well documented. Metformin is widely used in the treatment of type 2 diabetes in Western countries, but high doses of metformin have been approved only recently for clinical use in Japan. The aim of the present study was to investigate the effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients. A total of 71 Japanese patients with type 2 diabetes were prospectively studied for the effects of dosage and dosing frequency on the efficacy and safety of metformin during hospitalization. Dose effects were studied in 27 patients treated with 0, 500, 1,000, 1,500 and 2,250 mg/day of metformin. The effect of dosing frequency was compared in 56 patients with 1,500 mg/day of metformin administered either two or three times per day. Significant dose-dependent improvement in daily profiles of blood glucose was observed with metformin dosages up to 1,500 mg/day, with a trend towards further improvement observed at 2,250 mg/day. The efficacy of 1,500 mg of metformin was comparable when the drug was administered either two or three times per day. The most frequently reported side-effects were gastrointestinal symptoms, which were not affected by the dosage or dosing frequency of metformin. These results show that the efficacy of high-dose metformin is dose-dependent in Japanese patients. The efficacy and safety of metformin were similar when the drug was administered either two or three times per day.


No evidence of "obesity paradox" after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry.
The aim of this study was to compare clinical outcomes among unselected patients stratified in categories of body mass index, who underwent percutaneous coronary intervention (PCI) with either sirolimus-eluting or paclitaxel-eluting stents. Overweight and obesity are often considered risk factors for cardiovascular events. However, recent studies have associated obesity with better outcomes after PCI with bare-metal stents. Data from routine clinical practice using drug-eluting stents (DES) focusing on this "obesity paradox" are not available. We used data from DES.DE (German Drug-Eluting Stent) registry to compare in-hospital and 1-year outcomes among unselected patients undergoing PCI with DES implantation. Primary endpoints were the rate of major adverse cardiac and cerebrovascular events (MACCE) (defined as the composite of death, myocardial infarction, and stroke) and target vessel revascularization (TVR). Between October 2005 and 2006, 1,436 normal weight, 2,839 overweight, and 1,531 obese patients treated with DES were enrolled at 98 sites. Baseline clinical parameters were more severe in overweight and obese patients; 1-year follow-up comparison between groups revealed similar rates of all-cause death (3.3% vs. 2.4% vs. 2.4%; p=0.17), MACCE (7.1% vs. 5.6% vs. 5.5%; p=0.09), and TVR in survivors (10.9% vs. 11.7% vs. 11.6%; p=0.56) in normal weight individuals compared with overweight or obese patients. Such results persisted after risk-adjustment for heterogeneous baseline characteristics of groups and were independent of the types of DES. DES.DE revealed no evidence of "obesity paradox" in a routine clinical practice using DES.