Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review.
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a clinical entity defined by rapid deterioration of IPF during the course of the disease that is not due to infections, pulmonary embolism, or heart failure. The condition needs to be differentiated from acute interstitial pneumonia (or Hamman-Rich syndrome), which occurs in patients with no underlying lung disease. The exact etiology and pathogenesis remain unknown, but the condition is characterized by diffuse alveolar damage (on a background of IPF) that probably occurs as a result of a massive lung injury due to some unknown etiologic agent. High-resolution computed tomography can help in prognostication and management of this condition. Once infections and other causes of worsening have been excluded, treatment involves enhanced immunosuppression with pulse doses of methylprednisolone and cytotoxic agents. Our systematic review shows that the outcome, however, is poor, with 1-month and 3-month mortality around 60% and 67%, respectively. Few studies have shown beneficial effects of cyclosporine, pirfenidone, and anticoagulants in the management and prevention of AE-IPF. The etiology, risk factors, pathogenesis, therapy, prognosis, and predictors need to be studied and the potential role of newer agents in the management and prevention of AE-IPF needs to be further clarified.


Syntheses of some α-cyclic tripeptides as potential inhibitors for HMG-CoA Reductase.
α-Cyclic tripeptides (CtPs) are the most rigid members of the cyclic peptide family. However, due to their synthetic difficulty, biological activity has remained undisclosed. The incorporation of side-chain-protected natural amino acids into functional CtPs was performed to explore the potential biological functions. Several novel CtPs that consist of protected serine (S(Bn)) and/or glutamate (E(OBn)) were prepared from corresponding linear tripeptides by chemical synthesis. There is a strong possibility for CtPs that contain 3 phenyl groups to correlate with atorvastatin structure. The binding effects in human HMG-CoA reductase (hHMGR) activities were first evaluated by molecular docking. High docking scores were received with these CtPs for enzyme. Therefore, enzymatic assays were carried out and the compound cyclo(S(Bn))3 was indeed able to moderately inhibit hHMGR (IC50 = 110 μM).


Chondroblastoma: varied histologic appearance, potential diagnostic pitfalls, and clinicopathologic features associated with local recurrence.
Chondroblastoma is a rare, benign bone tumor. Although it has distinctive clinicopathologic features, its wide morphologic spectrum may pose diagnostic problems. We present the clinicopathologic features of 42 patients (28 males, 14 females; age range, 8 to 66 years), with emphasis on unusual histologic features, potential diagnostic pitfalls, and factors associated with recurrence. Thirty-four tumors were in long bones, with the most common site being the proximal femur. Unusual histologic features included the presence of atypical, epithelioid, spindle, and foamy cells and necrosis and a diffuse basophilic myxoid matrix. Tumors with focal osteoclast-like giant cell rich areas (n = 11), prominent cystic change (n = 8) and extensive fibromyxoid areas (n = 3) resembled giant cell tumors, aneurysmal bone cysts, and chondromyxoid fibromas, respectively. The diagnosis of referring pathologists was inaccurate in 34% of cases. Six patients (14%) had local recurrence. The only clinical feature significantly associated with increased risk of local recurrence was duration of symptoms for less than 6 months (log rank P =.003). None of the histologic features was significantly associated with recurrence. These included worrisome features such as cellular atypia, necrosis, and mitoses. None of the patients had metastases. An increased awareness of the morphologic spectrum of chondroblastomas will enable pathologists to avoid diagnostic pitfalls. We emphasize the need for a combined clinical, radiologic and histologic approach to the diagnosis of chondroblastomas.


[Development of a conceptual model for interpretation of monitoring indicators of childhood obesity prevention from the Italian National Prevention Plan].
the Italian National Prevention Plan (PNP) posed the standard to be achieved by Regions for the prevention of obesity in childhood and adolescence. The PNP also set up a monitoring system to assess the impact of implemented policies. to develop a conceptual model to facilitate interpretation of variation in outcome indicators. after a systematic review, the DPSEEA («Driving forces», «Pressures», «State», «Exposure», «Effect», «Actions») was identified as the more appropriate framework to assess the results of preventive policies. Factors for each component of the framework were identified and indicators that allow measuring the changing of each of these factors were defined. the included «driving forces» were related to the profit-led food industry, to the nutrition environment at school, and to household-level factors. Among the «pressures», parenting behaviours, food provided by school canteens, sociocultural factors, social context, physical activity (PA), opportunities at school or after-school were included. In the State, the high consumption of processed food, the large quantities of high-calorie food easy available, the consumption of carbonated and sugar-sweetened beverages, the reduced social function of mealtimes in families, the early cessation of breastfeeding, the reduction of outdoors activity, active transportation, and PA at school for children were identified. The «exposure» factors were the reduced opportunities of doing PA and the over-consumption of calories that influence the «effect», described as the prevalence of children and adolescents affected by obesity. through the DPSEEA, a conceptual model was set up; it allows to place in the causal chain the «actions» and the mechanisms through which these actions should impact on the «exposure» (PA and over-consumption of calories), making the rationale of process and impact indicators explicit.


Maternal tamoxifen exposure leads to abnormal primordial follicle assembly.
Tamoxifen (TAM) is an accredited drug used for treatment and prevention of breast cancer. Due to the long-term taking and the trend for women to delay childbearing, inadvertent conception occasionally occurs during TAM treatment. To explore the effects of TAM on a fetus, pregnant mice at gestation day 16.5 were orally administrated with different concentrations of TAM. Molecular biology techniques were used to analyze the effects of TAM on primordial follicle assembly of female offspring and the mechanism. It was found that maternal TAM exposure affected primordial follicle assembly and damaged the ovarian reserve in 3 dpp offspring. Up to 21 dpp, the follicular development had not recovered, with significantly decreased antral follicles and decreased total follicle number after maternal TAM exposure. Cell proliferation was significantly inhibited; however, the cell apoptosis was induced by maternal TAM exposure. Epigenetic regulation was also involved in the process of TAM induced abnormal primordial follicle assembly. The changed levels of H3K4me3, H3K9me3, and H3K27me3 presented the function of histone methylation in the regulation of the effects of maternal TAM exposure on the reproduction of female offspring. Moreover, the changed level of RNA m6A modification and the changed expression of genes related to transmethylation and demethylation proved the role of m6A in the process. Maternal TAM exposure led to abnormal primordial follicle assembly and follicular development by affecting cell proliferation, cell apoptosis, and epigenetics.


The Polymerization Effect on Synthesis and Visible-Light Photocatalytic Properties of Low-Temperature β-BiNbO4 Using Nb-Citrate Precursor.
Low-temperature β-BiNbO4 powders (denoted as Low-β) were prepared by citrate and Pechini methods using homemade water-soluble niobium precursors. The addition of ethylene glycol and the resultant polymerization effect on the synthesis and visible-light photocatalytic performance of β-BiNbO4 powders were fully investigated. The polymerization effect is beneficial to lower the phase formation temperature and obtain smaller particle catalysts. Both methods can synthesize catalysts with excellent performance of visible-light degradation of methyl violet (MV). The Low-β BiNbO4 powder prepared by citrate method shows better degradation rate of about 1 h to decompose 80 % of MV and also displays good photocatalytic stability. The photodegradation of MV under the visible-light irradiation followed the pseudo-first-order kinetics according to the Langmuir-Hinshelwood model, and the obtained first-order rate constant and half-time are 2.85 × 10(-2) min(-1) and 24.3 min, respectively. The better photocatalytic performance of BiNbO4 powders prepared by citrate method can be attributed to its smaller band gap and better crystallinity.


Photo-Induced Microfluidic Production of Ultrasmall Glyco Gold Nanoparticles.
Ultra-small gold nanoparticles (UAuNPs) are extremely interesting for applications in nanomedicine thanks to their good stability, biocompatibility, long circulation time and efficient clearance pathways. UAuNPs engineered with glycans (Glyco-UAuNPs) emerged as excellent platforms for many applications since the multiple copies of glycans can mimic the multivalent effect of glycoside clusters. Herein, we unravel a straightforward photo-induced synthesis of Glyco-UAuNPs based on a reliable and robust microfluidic approach. The synthesis occurs at room temperature avoiding the use of any further chemical reductant, templating agents or co-solvents. Exploiting 1 H NMR spectroscopy, we showed that the amount of thiol-ligand exposed on the UAuNPs is linearly correlated to the ligand concentration in the initial mixture. The results pave the way towards the development of a programmable synthetic approach, enabling an accurate design of the engineered UAuNPs or smart hybrid nano-systems.


Utilization of Free Soft Tissue Grafts in Otoplasty: A Simple Yet Effective Way to Avoid Suture Extrusion.
Prominent ear deformity occurs in 5% of the general population and has been treated by otoplasty for many years to address the psychosocial challenges of having such a deformity. There is extensive literature but no consensus on the best method to address potential surgical complications, including suture extrusion. The aim of this article was to describe a surgical technique designed to reduce suture extrusion following otoplasty surgery by placing free soft tissue grafts between Mustardé sutures and postauricular skin. Two hundred and eleven patients who underwent otoplasties with soft tissue grafts between January 2017 and January 2020 were included in this study. All surgeries were performed by 2 facial plastic surgeons with more than 20 years of experience each, practicing in Toronto, Canada. Patients were followed up to assess for suture extrusion between 12 and 36 months (median, 21 months) postoperatively. The rates of suture complications and extrusion were compared with those previously reported in the literature. Only 2 patients out of 211 (0.47%) had unilateral suture extrusion and were treated with suture removal. This is dramatically lower than the upper values reported in the literature, which average 5.55% (range, 0%-22.2%). A soft tissue graft separating the Mustardé sutures and postauricular skin acts as a barrier, and can be used in conjunction with traditional surgical techniques. By adding this graft in the proposed manner, there is additional tissue reinforcing the suture repair, thereby reducing the rates of suture complications and extrusion without increasing the operative time.


Expression of mosquito-larvicidal toxin genes under the control of a native promoter in Enterobacter amnigenus An11.
Enterobacter amnigenus An11, that can colonize the gut of mosquito larva, is an alternative toxin-producing host to be used as a mosquito control since it is able to float in the feeding zone of mosquito larvae. To produce mosquito-larvicidal toxins in this bacterium, a native promoter has been identified from its genomic DNA. The promoter exhibited consensus sequences for -35 and -10 regions of bacterial promoters and constitutively drove the expression of gfp. This promoter was inserted into recombinant plasmids upstream of promoter-free cyt2Aa2 from Bacillus thuringiensis and mtx2 from Bacillus sphaericus. Results demonstrated that Cyt2Aa2 and Mtx2 are constitutively produced without induction. The recombinant E. amnigenus showed toxicity against mosquito larvae, demonstrating a potential to be applied in a mosquito control program.


A lateral flow dipstick combined with reverse transcription recombinase polymerase amplification for rapid and visual detection of the BVDV and BPIV3.
Bovine respiratory disease complex (BRDC) is a serious disease affecting feedlot cattle in China and likely other places worldwide. Bovine viral diarrhea virus (BVDV) and bovine parainfluenza virus type 3 (BPIV3) are principally responsible for causing BRDC, and are a major strain to the industrial economy. Eradication of these viruses/disease requires swift viral identification and treatment. Hence, this study established a fast and easy procedure of BVDV and BPIV3 identification that employs reverse transcription recombinase polymerase amplification (RT-RPA) and lateral flow dipstick (LFD), and uses primers and lateral flow (LF) probe targeting the 5'-UTR gene of BVDV and phosphoprotein P gene of BPIV3, respectively. Our assay was able to successfully amplify BVDV and BPIV3 RNA within 25 min at 35 °C using RT-RPA, with products visible on the LFD within 5 min at room temperature (RT). The lowest detection limits were 50 RNA molecules for BVDV and 34 RNA molecules for BPIV3 per reaction. We also demonstrated that the established dual RT-RPA LFD assay was precise and targeted, harboring excellent potential to become an onsite molecular diagnostic tool in the detection of BVDV and BPIV3. This method can detect BVDV (Pestivirus A, B) and BPIV3, and exhibit no cross-reaction with other viruses like the classical swine fever virus (CSFV) and infectious bovine rhinotracheitis virus (IBRV). The assay performance was further assessed with clinical samples, and demonstrated good performance in comparison to real-time RT-PCR (RT-qPCR). Moreover, the RT-RPA LFD assay was comparitively rapid and required minimal training.


High-level expression vectors for Caulobacter crescentus incorporating the transcription/translation initiation regions of the paracrystalline surface-layer-protein gene.
A number of plasmid vectors were constructed for high-level gene expression in the dimorphic gram-negative bacterium Caulobacter crescentus. These vectors incorporate the transcription and translation initiation regions of the C. crescentus CB15A rsaA gene, which codes for the abundantly synthesized protein comprising the bacterium's paracrystalline surface layer. The expression vectors are based on the broad-host-range IncQ plasmid RSF1010 (R300B) and incorporate the rsaA promoter and transcription start site. Some vectors also contain translation initiation information; these can result in the addition of as little as a single glycine residue to the protein encoded by the cloned segment. The vectors can be introduced into C. crescentus by electroporation at high frequency (ranging up to 10(6)-10(7) electroporants/micrograms DNA with surface-layer-deficient mutant C. crescentus CB2A) or conjugal transfer. They range in size from 10 to 12 kb, specify either chloramphenicol or kanamycin resistance, and possess the restriction sites EcoRI, BamHI, KpnI, and SstI for cloning genes downstream of the rsaA gene sequences. For a number of the vectors, the complete nucleotide sequence is known. A comparison was made between the expression of an endoglucanase gene from these plasmids in C. crescentus CB2A and CB15A and similar constructions under the control of lacZ alpha transcription and translation initiation signals carried on a pUC9 vector in an Escherichia coli host. The two expression systems compared favorably; cell lysates prepared from C. crescentus CB2A exhibited 40% of the endoglucanase activity of similarly prepared lysates from E. coli JM101. Lysates prepared from C. crescentus CB15A exhibited only 8% of the endoglucanase activity of E. coli lysates.


Impact of supragingival scaling on the outcomes of subgingival instrumentation completed after 1 week: a split-mouth randomized clinical trial.
To investigate the impact of supragingival scaling on the clinical outcomes of subgingival instrumentation completed after 1 week. In 27 patients with Stage II and Stage III periodontitis, pairs of contralateral quadrants were randomly assigned into test group 1 (single sitting scaling and root planing) and test group 2 (supragingival scaling followed by subgingival instrumentation after 1 week). Periodontal parameters were recorded at baseline, 2, 4, and 6 months; Gingival crevicular fluid vascular endothelial growth factor (VEGF) estimation was done at baseline in both groups and 7 days after supragingival scaling in test group 2. At 6 months, significantly better improvement in test group 1 at sites with periodontal probing depth (PPD) > 5 mm; (∆PPD = 2.32 mm vs 1.41 mm, P = .001; ∆clinical attachmen level [CAL] = 2.34 mm vs 1.39 mm, P = .001) was observed. Supragingival scaling resulted in significant reduction in gingival crevicular fluid VEGF (42.46 to 27.88 pg/site) after 1 week. Regression analysis explained 14% variance in VEGF to baseline PPD at sites with PPD > 4 mm; and 21% variance in CAL improvement to VEGF at sites with PPD > 5 mm. The percentage of sites with PPD = 5 to 8 mm reaching the clinical endpoint was 52% and 40% for test group 1 and test group 2, respectively. Better results were noticed in bleeding on pocket probing-positive sites in both groups. The sites with PPD > 5 mm where supragingival scaling was followed by subgingival instrumentation after 1 week resulted in less favourable treatment outcomes. (Clinical trial registry NCT05449964).


Spatially resolved multidimensional NMR spectroscopy within a single scan.
We have recently demonstrated that the spatial encoding of internal nuclear magnetic resonance (NMR) spin interactions can be exploited to collect multidimensional NMR spectra within a single scan. Such experiments rely on an inhomogeneous spatial excitation of the spins throughout the sample, and lead to indirect-domain peaks via a constructive interference among the spatially resolved spin-packets that are thus created. The shape of the resulting indirect-domain echo peaks approaches a Sinc function when the chemical's distribution is uniform, but will depart from this function otherwise. It is hereby shown that a Fourier analysis of either the diagonal- or the cross-peaks resolved in these single-scan two-dimensional (2D) NMR experiments can in fact provide a weighted spatial distribution of the analyte originating such peak, thus opening up the possibility of completing spatially resolved multidimensional NMR measurements within a fraction of a second. Principles of this new mode of analysis are discussed, and examples where the potential of spatially resolved ultrafast 2D NMR spectroscopy is brought to bear are presented. Potential extensions of this approach to higher dimensions are also briefly addressed.


Salmonella in broiler chickens in Thailand with special reference to contamination of retail meat with Salmonella enteritidis.
The present study was performed to assess the prevalence of Salmonella in chickens in Thailand. In 1997, 22 serovars of Salmonella were isolated from 72 of 100 chicken meat samples purchased from 10 retail markets in Bangkok and 20 of 200 chicken meat samples from one slaughterhouse for export and 19 of 285 chicken feces obtained from three farms located in the east region of Thailand. The most predominant serovar was S. Enteritidis, which was isolated from 28% of the retail chicken meat, 4.5% of the chicken meat from slaughterhouse, and 6.6% of chickens feces samples examined.


The effect of diminished oocyte reserve in younger women (age < or = 37) on pregnancy rates in natural cycles.
To determine the relative confounding effect of diminished oocyte reserve on the chance of successful pregnancy in non-in vitro fertilization-embryo transfer (IVF-ET) cycles. Matched controlled study comparing pregnancy outcome in women aged < or = 37 years with severely decreased oocyte reserve as manifested by a day 3 serum follicle stimulating hormone (FSH) > or = 15 mIU/ml compared to women with normal oocyte reserve (serum FSH < or = 8 mIU/ml). Couples were excluded if they did not have tubal patency or a semen analysis that required IVF-ET. Only couples that tried at least three natural cycles (unless pregnancy occurred first) were included. The live delivered pregnancy rates within a maximum of five cycles of luteal phase support with progesterone (P) or at most mild FSH stimulation, or intrauterine insemination for mild male factor or cervical factor was 33.3% (8/24) with increased day 3 FSH and 62.5% (16/24) for the normal group (p = 0.08, Fisher's exact test). Women with marked oocyte depletion are half as likely to conceive with assisted reproductive techniques compared to women with normal oocyte reserve.


Psychostimulants, madness, memory... and RGS proteins?
The ingestion of psychostimulant drugs by humans imparts a profound sense of alertness and well-being. However, repeated use of these drugs in some individuals will induce a physiological state of dependence, characterized by compulsive behavior directed toward the acquisition and ingestion of the drug, at the expense of customary social obligations. Drugs of abuse and many other types of experiences share the ability to alter the morphology and density of neuronal dendrites and spines. Dopaminergic modulation of corticostriatal synaptic plasticity is necessary for these morphological changes. Changes in the density of dendritic spines on striatal neurons may underlie the development of this pathological pattern of drug-seeking behavior. Identifying proteins that regulate dopaminergic signaling are of value. A family of proteins, the regulators of G protein signaling (RGS) proteins, which regulate signaling from G protein-coupled receptors, such as dopamine and glutamate, may be important in this regard. By regulating corticostriatal synaptic plasticity, RGS proteins can influence presynaptic activity, neurotransmitter release, and postsynaptic depolarization and thereby play a key role in the development of this plasticity. Pharmacological agents that modify RGS activity in humans could be efficacious in ameliorating the dependence on psychostimulant drugs.


Assessing service provision and outcomes at the Canberra Obesity Management Service: A retrospective chart review.
This study aimed to evaluate the multidisciplinary care model of the Canberra Obesity Management Service (COMS) with regard to patient demographics and clinical outcomes, particularly in comparison with previous COMS outcome reviews. A retrospective chart review was carried out on all patients attending an initial assessment at COMS between July 2018 and June 2019. Existing patients attending follow-up reviews were excluded so as to avoid repeating analyses of data from previous COMS reviews. Patient data were recorded and deidentified and underwent descriptive analyses. A total of 234 patients with a mean age of 45.6 (SD = 13.9) years, mean BMI of 50.1 kg/m2 (SD = 8.5), and a female majority (72.2%) were analyzed. Of the 165 patients who attended follow-up appointments, 27.9% experienced ≥10% weight loss (46/165). Sleeve gastrectomy was associated with the largest mean weight reduction (15.6% at 6 months [n = 18]). Compared with previous COMS studies, both the throughput and proportion of participants achieving clinically meaningful weight reduction were observed to have increased. Further studies assessing service cost-effectiveness, the development of standardized treatment pathways, and the use of a systematic data collection system would be valuable in allowing comparison between outcomes with similar obesity services in Australia and internationally.


Congenital amusia and academic performance among Colombian university students.
Congenital amusia is a rare neurogenetic and neuropsychological condition which hinders the ability to recognize variations in all aspects of a musical piece. Although previous studies have determined the prevalence of congenital amusia in the general population, few have studied its presence among university students. Findings regarding the association between this condition and academic performance are equivocal, although evidence suggests that musical training improves scholastic achievement. We conducted a cross-sectional study on a sample of 383 university students, all pursuing health-related degrees, comparing their class rank with their performance on the BRAMS Online Test for amusia. We found a prevalence of 0.52% for pitch-based amusia. When applying the Off-Scale test failure criterion for the definition of amusia in our sample, we found a prevalence of 4.4%. Logistic models showed an increase in risk of poor academic performance (lowest quartile) in subjects who failed the off-scale test (Odds Ratio: 7.14 95% CI 2.59-19.6) and who met any of the described definitions of amusia (Odds Ratio: 4.89 95% CI 2.24-10.7). Both musical training and self-report of musical ability significantly affected test results. Although musical education shows some effect over academic performance, further studies are required to determine if this is due to differential effects in subjects with and without amusia.


Application of proton magnetic resonance spectroscopy on substantia nigra metabolites in Parkinson's disease.
This study investigates changes in substantia nigra metabolites in Parkinson's disease (PD) using proton magnetic resonance spectroscopy ((1)H- MRS). Thirty patients with asymmetric PD and 20 normal controls were included in this study. Substantia nigra metabolites were detected in all subjects using 3D-multimer (1)H-MRS with a 3.0 T MRI scanner. The relative ratios of NAA/Cr, NAA/Cho, NAA/(Cho + Cr) in the substantia nigra were compared between two sides of asymmetric PD patients as well as between PD patients and controls. Significant differences in NAA/Cr, NAA/Cho, NAA/(Cho + Cr) were observed between PD patients and healthy controls (P < 0.05) as well as between the ipsilateral and contralateral of affected extremity in PD patients (P < 0.05). Significant differences in NAA/Cr, NAA/Cho, NAA/(Cho + Cr) were also observed between patients with mild and severe PD. Thus, we found that (1)H-MRS can be used to detect substantia nigra metabolites in PD patients, which may be useful for early diagnosis and evaluation of PD.


Infections and antibiotic use in early life, and obesity in early childhood: a mediation analysis.
Literature shows a positive association between antibiotics and obesity in childhood, but fails to account for confounding by indication. We evaluate the direct effect of infection on obesity and the indirect effect mediated by antibiotics by performing a mediation analysis of the infection-obesity association. A Medicaid cohort of children age 2-14 years old between 2015-2019 (n = 61,330) is used to perform mediation analysis of infections and antibiotic use in the first year of life, and obesity in childhood in Missouri, U.S.A. An additional infection increases the risk of obesity in childhood (aIRR = 1.050, p < 0.001); however, mediation by antibiotic use is clinically and statistically insignificant. If the number of infections is not considered in the analysis, then antibiotic use as a risk factor for obesity is overstated (aIRR = 1.037 vs. 1.013 p < 0.001). The number of infections exhibits a significant relationship with obesity and is a stronger risk factor for obesity than antibiotic use. In particular, a greater number of bronchitis, otitis media, and upper respiratory infections in the first year of life are associated with a significant increased risk of obesity in childhood. We find only weak evidence that an additional antibiotics claim increases the risk of obesity in childhood and this risk may not be clinically meaningful. Further research is needed to explore the association between early childhood infections, especially in the first 6 months of life, and obesity including the biological mechanism and environmental factor of early life infections associated with obesity.


Impact of Bariatric Surgery on Outcomes of Patients with Sickle Cell Disease: a Nationwide Inpatient Sample Analysis, 2004-2014.
With advances in disease-specific treatments and improved overall survival, obesity rates are rising among patients with sickle cell disease (SCD). The primary aim of this study was to evaluate the role of bariatric surgery on clinical outcomes among hospitalized obese patients with SCD. The United States Nationwide Inpatient Sample database was queried between 2004 and 2014 for discharges with co-diagnoses of morbid obesity and SCD. The primary outcome was in-hospital mortality. Secondary outcomes included vaso-occlusive crisis, acute chest syndrome, biliary-pancreatic complications, renal failure, urinary tract infection, malnutrition, sepsis, pneumonia, respiratory failure, thromboembolic events, strictures, wound infection, length of stay, and hospitalization costs. Using Poisson regression, adjusted incidence risk ratios (IRR) were derived for clinical outcomes in patients with prior-bariatric surgery compared to those without bariatric surgery. Among 2549 patients with a discharge diagnosis of SCD and morbid obesity, only 42 patients (1.7%) had bariatric surgery. On multivariable analysis, bariatric surgery did not influence mortality (P = 0.98). Bariatric surgery was not associated with increased risk for acute chest syndrome, sepsis, multi-organ failure, biliary-pancreatic, or surgery-related complications (all P > 0.05). Interestingly, bariatric surgery decreased risk of vaso-occlusive crises (IRR 0.21; 95% CI, 0.07-0.69; P = 0.01) in these patients and was associated with a shorter length of stay (P < 0.001) but higher hospitalization costs (P < 0.001). Bariatric surgery may lower rates of vaso-occlusive crises in morbidly obese sickle cell patients without significantly affecting mortality and other adverse outcomes. In spite of this, these weight loss surgeries are underutilized in this select population.


District and school physical education policies: implications for physical education and recess time.
The relationship between physical education (PE) policies and children's PE and recess time is not well understood. The purpose of this study is to assess the association of district and school PE policies, the PE environment, and PE and recess time. Key informants in 65 schools from 9 states completed instruments assessing district and school PE policies, the school PE environment, and time in PE and recess. Few significant associations were found between PE policies and PE or recess minutes; no policies were associated with both. A number of PE environmental variables were associated with both policies and time in PE and recess. PE policies, their implementation, and PE environmental variables can have important implications for recess time. Some school PE environment measures designed to improve PE may result in PE time limitations. Deficiencies in PE and recess time are not likely to be effectively addressed through policy adoption alone.


Studies on clinical isolates of coagulase-negative staphylococci resistant to methicillin. Evidence of cross-resistance between methicillin and cephalothin.
The in vitro susceptibility to cephalothin and cefuroxime of 195 isolates of methicillin-resistant coagulase-negative staphylococci was determined by the agar-diffusion test, using 7.5% NaCl-supplemented agar. The distribution of the inhibition zone diameters for isolates of S. epidermidis (S. biotype 1) as well as for S. haemolyticus (S. biotype 4) was trimodal. While 4% of the isolates were found susceptible to cefuroxime, 39% of the S. epidermidis/S. hominis (S. biotype 1) isolates and 34% of the S. haemolyticus (S. biotype 4) isolates were found susceptible to cephalothin by this method. Eight of these isolates (six S. epidermidis, two S. haemolyticus) were selected for susceptibility testing by the tube-dilution method, together with four isolates (three S. haemolyticus, one S. epidermidis) found resistant to cephalothin by the agar-diffusion test. The first-mentioned isolates were all found susceptible to cephalothin with MICs less than or equal to 2 micrograms/l, while the last-named all were resistant with MICs greater than or equal to 16 micrograms/ml. Population analyses revealed sub-populations of highly resistant bacteria in all methicillin-resistant isolates of S. epidermidis (S. biotype 1), as well as in all isolates of S. haemolyticus (S. biotype 4). We thus concluded that methicillin-resistance in isolates of coagulase-negative staphylococci implies resistance to cephalosporins and that the difference between S. epidermidis and S. haemolyticus as regards cephalosporin-susceptibility is quantitative and not qualitative. Eighty-nine per cent of the 195 methicillin-resistant isolates in this study were resistant to penicillin and at least one more antibiotic. We therefore think that resistance to penicillin and one or more non-beta-lactam antibiotics strongly suggests methicillin-resistance and that such isolates should be further tested on hypertonic media.


Toxicity assessment of the herbicides sulcotrione and mesotrione toward two reference environmental microorganisms: Tetrahymena pyriformis and Vibrio fischeri.
The potential toxicity of sulcotrione (2-[2-chloro-4-(methylsulfonyl)benzoyl]-1,3-cyclohexanedione) and mesotrione (2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione), two selective triketonic herbicides, was assessed using representative environmental microorganisms frequently used in ecotoxicology: the eukaryote Tetrahymena pyriformis and the prokaryote Vibrio fischeri. The aims were also to evaluate the toxicity of different known degradation products, to compare the toxicity of these herbicides with that of atrazine, and to assess the toxicity of the commercial herbicidal products Mikado and Callisto. Toxicity assays involved the Microtox test, the T. pyriformis population growth impairment test, and the T. pyriformis nonspecific esterase activity test. For each compound, we report original data (IC(50) values) on nontarget cells frequently used in ecotoxicology. Analytical standards sulcotrione and mesotrione showed no toxic effect on T. pyriformis population growth but a toxic influence was observed on nonspecific esterase activities of this microorganism and on metabolism of V. fischeri. Most of the degradation products studied and the two commercial formulations showed a greater toxicity than the parent molecules. Compared with the effect of atrazine, the toxicity of these triketonic herbicides was less than in T. pyriformis and greater than or the same as in V. fischeri. Additional work is needed to obtain a more accurate picture of the environmental impact of these herbicides. It will be necessary in future experiments to study the ecosystemic levels (aquatic and soil compartments) and to assess the potential toxicity of the newly discovered degradation products and of the additives accompanying the active ingredient in the commercial herbicidal formulations.


Reliable determination of furosine in human serum and dialysate proteins by high-performance liquid chromatography.
Furosine, formed by hydrolysis of 1-deoxy-fructosyl-lysine (fructose-lysine), is a product of the Amadori rearrangement of glucose and epsilon-NH2-lysine. Fructose-lysine can react further with tissue and circulating proteins to produce advanced glycation end-products (AGEs). Peritoneal dialysate used in the treatment of patients with end-stage renal failure contains high concentrations of glucose which may lead to intraperitoneal formation of AGEs. To quantitate the kinetics of formation and peritoneal clearance of glycated peritoneal dialysate proteins, we developed an effective approach to the measurement of furosine in clinical samples of serum and peritoneal dialysate.


The effect of longterm vs shortterm tutors on the quality of the tutorial process and student performance.
Small-group, problem- based learning can require a significant amount of individual faculty time when groups last as long as 10 weeks. One solution is to use two short-term (3-5 weeks) tutors instead of a single long-term (6-10 weeks) tutor. This study was performed to evaluate whether having short-term instead of a long-term tutors affected student performance and/or the quality of the tutorial process. The grade point averages for first and second year medical students in the classes of 2001 and 2002 were stratified by how many long-term tutors students had (2, 3, 4, 5, or 6) over a period of 17 months. In addition, students completed anonymously a 24-item tutor evaluation questionnaire utilizing a 5 point Likert scale (outstanding, good, satisfactory, marginal or unsatisfactory) at the mid-point and at the end of each tutorial. The evaluations were stratified by whether the tutor was short-term or long-term (to the mid-point or end of the tutorial, respectively). Statistical analysis was performed using analysis of variance. Grade point averages did not correlate with the number of long-term tutors that students had. Long-term tutors were rated significantly higher than short-term tutors in 17 of the 24 categories evaluated by the questionnaire, including development of students' critical thinking, information skills and self-learning skills; encouraging students to express themselves freely and to take responsibility for their own learning; helping students to balance basic science and clinical applications; and overall assessment. Short-term vs long-term tutors do not affect objective student performance as measured by grade point average. However, long-term tutors are ranked significantly higher by students in numerous areas related to the perceived quality of the tutorial process. Short-term tutoring may be less of a demand on an individual faculty's time, but may lessen the students' perceived quality of the tutorial process.


The use of psychophysical, structural, and electrodiagnostic parameters to identify glaucomatous damage.
Fifty-one patients with early glaucoma and 29 patients without the disease had their contrast sensitivity, colour vision, differential light threshold, neuroretinal rim area, retinal nerve fibre layer, pattern-reversal electrogram and visually evoked potential examined. A stepwise discriminant analysis found that the combination of the vertical cup disc ratio, the diffuse nerve fibre layer score and the localized nerve fibre layer score correctly identified 98% of the normals and 84% of the glaucoma patients. Single parameters and various combinations of parameters were also examined for their ability to discriminate between the two groups. Fifty-two glaucoma suspects were similarly examined and were classified into those whose discriminant functions were normal or abnormal.


Writing for the readerScientific Papers Made Easy Stuart West and Lindsay Turnbull Oxford University Press, 2023. 208 pp.
Clarity and brevity are key to readable research papers.


Interventions for Congenital Atrioventricular Valve Dysfunction: JACC Focus Seminar.
Innovation and creativity have led to tremendous advancements in the care and management of patients with congenital heart disease (CHD) that have resulted in considerably increased survival. Catheter-based interventions have contributed significantly to these advancements. However, catheter-based interventions for congenital lesions of the atrioventricular (AV) valves have been limited in scope and effectiveness mainly because of patient size and anatomical challenges. Thus, surgical repair and replacement for congenital AV valve lesions have remained the preferred therapy. However, the ongoing transcatheter heart valve revolution has led to techniques and technologies that are changing the landscape, particularly for adult CHD patients. Many devices for AV valve repair and replacement are being studied in adult patients without CHD, and translation of select practices to CHD patients has begun, with many more to come. Transcatheter AV valve interventions represent exciting opportunities for the growing numbers of adult CHD patients.


Trachoma.
Trachoma is the most common infectious cause of blindness. It is caused by ocular serovars of Chlamydia trachomatis. Transmission is favoured in poor communities, where crowding is common and access to water and sanitation inadequate. Repeated reinfection over many years causes dense scarring of the upper eyelid. The resultant inversion of the lashes abrades the eyeball, and the abrasion leads to corneal opacification and visual impairment. The host immune response is probably at least partly the cause of this process. The "SAFE" strategy is used for the control of trachoma: surgery for in-turned lashes, antibiotics for active disease, facial cleanliness, and environmental improvement. The demonstration that a single oral dose of the antibiotic azithromycin is as effective as 6 weeks of topical tetracycline was an important advance in trachoma control. By means of the SAFE strategy, WHO and its partners aim to eliminate trachoma as a public-health problem by the year 2020.


Human biomonitoring of eight trace elements in urine of residents living in rural areas along the Yangtze River, China.
The rapid economic development and industrialization have made heavy metal contamination a great public concern, especially in China. However, the levels of heavy metals in human body, especially those susceptible to the effect of industrial progression, are rarely explored. In this study, eight elements in 2643 urinary samples of individuals living in rural areas along the Yangtze River were determined through inductively coupled plasma optical emission spectrometry (As, Cr, Cu, Fe, Mn, Pb, and Zn) and TAS-990 atomic absorption spectrophotometry (Cd). Two-level regression model was applied to explore the potential factors associated with the level of the eight trace elements. After adjusting for urinary creatinine, the geometric means were 77.5, 10.98, 14.39, 13.00, 0.59, 1.51, 489.62, and 1.80 μg/g for As, Cr, Cu, Fe, Mn, Pb, Zn, and Cd, respectively. The level of eight elements varied among individual and familial characteristics. Compared with domestic and international results, the rural residents living in riverside areas had higher level of As, Cd, Cr, Fe, and Zn. Therefore, industrial progression followed by economic development has resulted in high body burden of heavy metals. Targeted public health policies should be made to improve the local environment and the recognition of potential risk factors.


Hybridization of TEDOR and NCX MAS solid-state NMR experiments for simultaneous acquisition of heteronuclear correlation spectra and distance measurements.
Magic angle spinning (MAS) solid-state NMR (ssNMR) spectroscopy is a major technique for the characterization of the structural dynamics of biopolymers at atomic resolution. However, the intrinsic low sensitivity of this technique poses significant limitations to its routine application in structural biology. Here we achieve substantial savings in experimental time using a new subclass of Polarization Optimized Experiments (POEs) that concatenate TEDOR and SPECIFIC-CP transfers into a single pulse sequence. Specifically, we designed new 2D and 3D experiments (2D TEDOR-NCX, 3D TEDOR-NCOCX, and 3D TEDOR-NCACX) to obtain distance measurements and heteronuclear chemical shift correlations for resonance assignments using only one experiment. We successfully tested these experiments on N-Acetyl-Val-Leu dipeptide, microcrystalline U-13C,15N ubiquitin, and single- and multi-span membrane proteins reconstituted in lipid membranes. These pulse sequences can be implemented on any ssNMR spectrometer equipped with standard solid-state hardware using only one receiver. Since these new POEs speed up data acquisition considerably, we anticipate their broad application to fibrillar, microcrystalline, and membrane-bound proteins.


Subcortical projections to the pontine nuclei in the cat.
In a systematic attempt to trace all projections from the brainstem and diencephalon to the pontine nuclei of the cat, implantations and injections of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) or Fluoro-Gold were placed in the pontine nuclei of 21 cats. In most of the cases there was no evidence of spread of tracer outside the pontine nuclei. Retrogradely labeled cells in the brainstem and diencephalon were carefully mapped and counted. The number labeled cells in the brainstem and diencephalon ranged from 24 in cases with very small implantations to 3,490 in cases with large injections in the pontine nuclei (counts from every fifth section). The labeled cells are located bilaterally with an ipsilateral preponderance. After large injections, 25-38% of the labeled cells were located in the brainstem reticular formation, 10-16% in the pretectal nuclei, 10-15% in the hypothalamus, 7-9% in the zona incerta, 3-9% in the fields of Forel, 4-5% in the nucleus locus coeruleus, 3-5% in the ventral lateral geniculate body, 2-4% in the superior colliculus, 3% in the periaqueductal gray, and 14-15% in other parts of the brainstem. Judging from cases with small tracer deposits entirely confined to the pontine nuclei, there appear to be two types of subcortical inputs: Projections from the reticular formation, the nucleus locus coeruleus, the periaqueductal gray, and the raphe nuclei are widespread, presumably reaching all parts of the pontine nuclei, while projections from a diversity of other sources are localized, reaching limited parts of the pontine nuclei only or predominantly.


Hospitalization and Some Sociodemographic Characteristics of Patients Registered with a Community Mental Health Center.
One of the most important indicators evaluating the effectiveness of community mental health centers is the decrease in hospitalization rates of registered patients. The aim of our study was to compare the annual hospitalization rates of patients receiving community mental health services before enrollment with the annual hospitalization rates after enrollment. The study included 400 patients with a registration period of at least 1 year as of the end of 2018. Wilcoxon signed rank test was used to test the significance of the difference between pre-registration and post-registration patients' annual hospitalizations. The annual hospitalization rates (0.32 ± 0.35) and the annual hospitalization rates (0.15 ± 0.35) before and after registration were found to be statistically significant (p < 0.001). Annual hospitalization rates decreased by 54.58%. Our Community Mental Health Center, which provides community-based mental health services, has led to a significant decrease in annual hospitalization rates thanks to the services provided.


A bone mineralization defect in the Pahenu2 model of classical phenylketonuria involves compromised mesenchymal stem cell differentiation.
Osteopenia is observed in some patients affected by phenylalanine hydroxylase (PAH) deficient phenylketonuria (PKU). Bone density studies, in diverse PKU patient cohorts, have demonstrated bone disease is neither fully penetrant nor uniform in bone density loss. Biochemical assessment has generated a muddled perspective regarding mechanisms of the PKU bone phenotype where the participation of hyperphenylalaninemia remains unresolved. Osteopenia is realized in the Pahenu2 mouse model of classical PKU; although, characterization is incomplete. We characterized the Pahenu2 bone phenotype and assessed the effect of hyperphenylalaninemia on bone differentiation. Employing Pahenu2 and control animals, cytology, static and dynamic histomorphometry, and biochemistry were applied to further characterize the bone phenotype. These investigations demonstrate Pahenu2 bone density is decreased 33% relative to C57BL/6; bone volume/total volume was similarly decreased; trabecular thickness was unchanged while increased trabecular spacing was observed. Dynamic histomorphometry demonstrated a 25% decrease in mineral apposition. Biochemically, control and PKU animals have similar plasma cortisol, adrenocorticotropic hormone, and 25-hydroxyvitamin D. PKU animals show moderately increased plasma parathyroid hormone while plasma calcium and phosphate are reduced. These data are consistent with a mineralization defect. The effect of hyperphenylalaninemia on bone maturation was assessed in vitro employing bone-derived mesenchymal stem cells (MSCs) and their differentiation into bone. Using standard culture conditions, PAH deficient MSCs differentiate into bone as assessed by in situ alkaline phosphatase activity and mineral staining. However, PAH deficient MSCs cultured in 1200 μM PHE (metric defining classical PKU) show significantly reduced mineralization. These data are the first biological evidence demonstrating a negative impact of hyperphenylalaninemia upon bone maturation. In PAH deficient MSCs, expression of Col1A1 and Rankl are suppressed by hyperphenylalaninemia consistent with reduced bone formation and bone turnover. Osteopenia is intrinsic to PKU pathology in untreated Pahenu2 animals and our data suggests PHE toxicity participates by inhibiting mineralization in the course of MSC bone differentiation.


Rate-limiting, diurnal activity of hepatic microsomal cholesterol-7 alpha-hydroxylase in pigeons with high serum cholesterol.
Efficiency of regulating serum cholesterol by cholesterol-7 alpha-hydroxylase was studied in pigeon strains hypo-(SR-39) and hypercholesterolemic (SR-37) with respect to dietary cholesterol. Diurnal hydroxylase activity in SR-37 was 10% of that in strain SR-39 adapted to a light-dark cycle and fed a non-cholesterol diet. Acrophase (6 p.m.) activity was 54-fold greater in SR-39 than in SR-37 pigeons. Dietary cholesterol elevated enzyme activity 2.8-fold in SR-37 pigeons. Dietary cholestyramine plus cholesterol increased hydroxylase activity 21-fold in SR-37 and 3-fold in SR-39 strain; yet, activity remained greater in SR-39. Cholestyramine feeding prevented elevated cholesterol levels in both groups. The circadian rhythms of hydroxylase and serum corticosterone were determined. The diurnal activity in SR-37 was 10% of that in SR-39 and acrophase activity was 34-fold greater in SR-39. Hormone levels were comparable. Programmed acrophase was asynchronous between strains. Hydroxylase activity was positively correlated with corticosterone levels and inversely correlated with serum cholesterol. A defect in the up-regulation of cholesterol-7 alpha-hydroxylase is proposed which limits the catabolism of cholesterol in strain SR-37.


Efficacy and safety of quinine loading dose in patients with severe falciparum malaria at a tertiary care hospital in Pakistan.
To compare the clinical outcomes of a loading dose regimen of quinine with a uniform dose regimen in patients with severe falciparum malaria. A retrospective chart review of 315 patients admitted with severe falciparum malaria and treated with quinine at a tertiary care teaching hospital of Karachi, Pakistan during 1999-2006 was conducted. Group A with 103 patients (32.7%) was given an initial loading dose of quinine while group B with 212 patients (67.3%) did not receive the loading dose. The two groups were compared in terms of reduction of parasite load, resolution of fever, recovery of consciousness and incidence of adverse effects. Outcome parameters were measured on the third day of therapy. More individuals in group A (62.1%) were afebrile as compared to group B (54.7%) at day 3 of therapy. Patients in group B showed greater reduction in parasitaemia (47.2% at baseline to 4.7% on day 3) as compared to group A (56.3 % at baseline to 9.7% on day 3). Following therapy, fewer patients in group B had altered consciousness (7.1% at baseline to 4.7% on day 3) as compared to patients in group A (7.8% at baseline to 5.8% on day 3). However, these associations were not statistically significant. The incidence of thrombocytopenia was higher in Group A (5.8%) as compared to Group B (0.9%). Although quinine loading dose may be more effective than uniform dose in rapid fever clearance; it also appears to be associated with higher toxicity. Uniform dose of quinine may be prescribed in severe falciparum malaria in view of its better safety profile.


Micronutrients Deficiencies in Candidates of Bariatric Surgery: Results from a Single Institution over a 1-Year Period.
Micronutrient deficiencies represent a common condition after bariatric surgery (BS). The prevalence of these nutritional disorders before BS is still debated. The aim of our study was to retrospectively evaluate the prevalence of micronutrient deficiencies in candidates for BS. A prospectively maintained database of our institution was searched to find all patients who underwent surgery between January and December 2021. The following data were collected: age, gender, body mass index (BMI), obesity-associated diseases, and preoperative serum levels of vitamin B12, folate, and vitamin D. A total of 174 patients were included in our study. Mean age and BMI were 39.2 ± 11.4 years and 44.3 ± 7.1 kg/m2, respectively. One hundred and thirty-nine patients (79.9%) had at least one preoperative micronutrient disorder, with vitamin D deficiency being the most common (116, 66.7%), followed by a deficit of folate (76, 43.7%) and vitamin B12 (10, 5.7%). Forty-seven (27%) individuals had insufficient levels of vitamin D. Comparison of deficiencies between sexes showed that vitamin B12 < 20 ng/ml was significantly more frequent in women (p = 0.03). DLP showed a mild significant effect on folate levels (p = 0.01), while the association of HNT and T2DM had a mild significant effect on vitamin B12 (p = 0.02). Preoperative micronutrient deficiencies were frequently found in candidates for BS. Approximately 90% of patients had deficient or insufficient serum levels of vitamin D preoperatively. Almost half of the patients had a preoperative deficit of folate, and vitamin B12 deficiency was significantly more frequent in the female population. It is mandatory to screen all patients undergoing BS for vitamin deficiencies before surgery.


Borderline personality disorder traits and mentalising ability: The self-other social cognition paradox.
Borderline personality disorder (BPD) is a psychiatric condition characterised by a pervasive pattern of impulsivity, low self-image, and interpersonal conflicts. Previous findings indicate a mixed relationship between BPD and social cognition; little research as investigated whether BPD traits influence performance on specific elements of social cognitive tasks, i.e., positive/negative valence. Community-based typical controls (n = 151; 51% female) were recruited through an online survey. Participants completed aspects of the Personality Assessment Inventory pertaining to BPD traits, the Interpersonal Reactivity Index, and measures of both emotion recognition and mentalising. Following group stratification into high/low BPD traits, participants with high BPD traits were observed to perform significantly better when identifying negative valence stimuli. Furthermore, high levels of affect instability was found to significantly influence negative valence recognition. This research highlights previous research which shows a paradox between higher performance on measures of social cognition, with a group of individuals who report significant interpersonal and relational difficulties. This research supports the assessment of social cognitive processes for people with BPD and/or high BPD traits to support clinical formulation of strengths and difficulties.


Population structure analysis using rare and common functional variants.
Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.


Optimality of group testing in the presence of misclassification.
Several optimality properties of Dorfman's (1943) group testing procedure are derived for estimation of the prevalence of a rare disease whose status is classified with error. Exact ranges of disease prevalence are obtained for which group testing provides more efficient estimation when group size increases.


The Arabidopsis F-box protein FOF2 regulates ABA-mediated seed germination and drought tolerance.
The phytohormone abscisic acid (ABA) plays a crucial role at various plant developmental stages, including seed germination and seedling development, and regulates stomatal aperture in response to drought. However, the underlying mechanisms are not well understood. Here, we showed that F-BOX OF FLOWERING 2 (FOF2) is induced by ABA and drought stress. Overexpression of FOF2 led to reduced ABA sensitivity during seed germination and early seedling development, whereas the fof2 mutant exhibited increased sensitivity to ABA. Molecular and genetic analyses revealed that FOF2 negatively affected ABA-mediated seed germination and early seedling development partially by repressing the expression of the ABA-signaling genes ABI3 and ABI5. Additionally, we found that FOF2-overexpressing plants exhibited increased ABA contents, enhanced ABA sensitivity during stomatal closure, and decreased water loss, thereby improving tolerance to drought stress, in contrast to the fof2 mutant. Consistent with a higher ABA content and enhanced drought tolerance, the expression of ABA- and drought-induced genes and the ABA-biosynthesis gene NCED3 was upregulated in the FOF2-overexpressing plants but downregulated in fof2 mutant in response to drought stress. Taken together, our findings revealed that FOF2 plays an important negative role in ABA-mediated seed germination and early seedling development, as well as a positive role in ABA-mediated drought tolerance.


Mechanism of proteasome gate modulation by assembly chaperones Pba1 and Pba2.
The active sites of the proteasome are housed within its central core particle (CP), a barrel-shaped chamber of four stacked heptameric rings, and access of substrates to the CP interior is mediated by gates at either axial end. These gates are constitutively closed and may be opened by the regulatory particle (RP), which binds the CP and facilitates substrate degradation. We recently showed that the heterodimeric CP assembly chaperones Pba1/2 also mediate gate opening through an unexpected structural arrangement that facilitates the insertion of the N terminus of Pba1 into the CP interior; however, the full mechanism of Pba1/2-mediated gate opening is unclear. Here, we report a detailed analysis of CP gate modulation by Pba1/2. The clustering of key residues at the interface between neighboring α-subunits is a critical feature of RP-mediated gate opening, and we find that Pba1/2 recapitulate this strategy. Unlike RP, which inserts at six α-subunit interfaces, Pba1/2 insert at only two α-subunit interfaces. Nevertheless, Pba1/2 are able to regulate six of the seven interfacial clusters, largely through direct interactions. The N terminus of Pba1 also physically interacts with the center of the gate, disrupting the intersubunit contacts that maintain the closed state. This novel mechanism of gate modulation appears to be unique to Pba1/2 and therefore likely occurs only during proteasome assembly. Our data suggest that release of Pba1/2 at the conclusion of assembly is what allows the nascent CP to assume its mature gate conformation, which is primarily closed, until activated by RP.


Resveratrol induces ordered domains formation in biomembranes: Implication for its pleiotropic action.
Resveratrol is a polyphenol compound with great value in cancer therapy, cardiovascular protection, and neurodegenerative disorders. The mechanism by which resveratrol exerts such pleiotropic effects is not yet clear and there is a huge need to understand the influence of this compound on the regulation of lipid domains formation on membrane structure. The aim of the present study was to reveal potential molecular interactions between resveratrol and lipid rafts found in cell membranes by means of Förster resonance energy transfer, DPH fluorescence quenching, and triton X-100 detergent resistance assay. Liposomes composed of egg phosphatidylcholine, cholesterol, and sphingomyelin were used as model membranes. The results revealed that resveratrol induces phase separation and formation of liquid-ordered domains in bilayer structures. The formation of such tightly packed lipid rafts is important for different signal transduction pathways, through the regulation of membrane-associating proteins, that can justify several pharmacological activities of this compound.


Socio-economic status and functioning in patients newly diagnosed with bipolar disorder and their unaffected siblings - Results from a cross-sectional clinical study.
Few studies have reported socio-economic status and functioning in patients newly diagnosed with bipolar disorder (BD) and their unaffected siblings (US). Socio-economic status and functioning were compared in a cross-sectional clinical study including 382 patients newly diagnosed with BD, 129 of their US, and 200 healthy control individuals (HC). Socio-economic status was lower in patients newly diagnosed with BD compared with HC within educational achievement, employment status, workability and relationship status (p < 0.001, OR between 0.02 and 0.53). Regarding US and HC, US had lower educational achievement (p < 0.001, OR = 0.27 [0.16; 0.46]), as the only affected socio-economic outcome. Functioning was substantially impaired according to the Functional Assessment Short Test (FAST) (p < 0.001, Cohen's d = 2.12) and Work and Social Adjustment Scale (WSAS) (p < 0.001, Cohen's d = 2.76) in patients newly diagnosed with BD compared with HC. US expressed the same pattern with impaired overall functioning. Within patients, the impaired functioning was associated with a longer illness duration. Patients had an illness duration of 10.5 [IQR: 6.1; 16.2] years, even though they were included shortly after a diagnosis of BD (0.3 [IQR: 0.1; 0.7] years), highlighting the obstacles of research in illness onset of BD. Patients newly diagnosed with BD, and to a lesser degree their US, exhibit lower socio-economic status and impaired overall functioning. These findings emphasise the importance of early diagnosis, treatment and focus on functional recovery and stress that intervention strategies and further research in high-risk individuals are needed.


Effect of lyophilization on the structure and phase changes of PEGylated-bovine serum albumin.
Poly (ethylene glycol) (PEG) conjugation masks the protein's surface and increases the molecular size of the polypeptide, thus preventing the approach of antibodies or antigen processing cells and reducing the degradation by proteolytic enzymes. Proteins are readily denatured by numerous stresses arising in solution (e.g., heating, agitation, freezing and pH changes) or by chemical reactions (e.g., hydrolysis and deamidation), many of which are mediated by water. Lyophilization is most commonly used to prepare dehydrated proteins, which, theoretically, should have the desired long-term stability at ambient temperatures. Through Raman spectroscopy, differential scanning calorimetry (DSC) associated with the determination of water content by Karl Fisher titration, it was observed that after the modification of BSA-PEG in a ratio of 1:0.25 showed lower degree of structural alterations and consequently lower variation on the physical-chemical characteristics when it was compared to BSA-PEG (1:0.5). Moreover, the BSA-PEG (1:0.25) optimizes the conditions during the lyophilization process and storage of the protein.


Modification of the existing maximum residue levels for 1,4-dimethylnaphthalene in potatoes.
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Dormfresh limited submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue level (MRL) for the active substance 1,4-dimethylnaphthalene in potatoes. The data submitted in support of the request were found to be sufficient to derive an MRL proposal. Adequate analytical methods for enforcement are available to control the residues of 1,4-dimethylnaphthalene in potatoes and residues of 1,4-dimethylnaphthalene, M23 and M23 conjugates in animal matrices. The data gaps identified during the MRL review relevant to the identity of metabolites found at significant levels in the processing studies and the analytical methods for enforcement in animal matrices were considered satisfactorily addressed. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of 1,4-dimethylnaphthalene according to the reported agricultural practice is unlikely to present a risk to consumer health.


[Effect of early high fat diet on pancreatic β cellularity and insulin sensibility in young rats].
To study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic β cellularity in young rats. Sixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope. The high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet β-cells were observed in the high fat group after 6 weeks. Early high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in β-cells may be an early sign of β-cell damage due to obesity.


Surgical treatment of erectile impotence with inflatable penile prosthesis.
Thirty-nine men with erectile impotence were treated with surgical implantation of an inflatable penile prosthesis. The patients were followed for 6 months to 2 years. Thirty-five patients (90 per cent) have expressed long-term satisfaction with the appearance and performance of the prosthesis. Major complications developed in 9 patients (23 per cent), requiring 12 subsequent operative procedures.


Evidence of An Association Between Cerebral Blood Flow and Microstructural Integrity in Normative Aging Using a Holistic MRI Approach.
Cerebral tissue integrity decline and cerebral blood flow (CBF) alteration are major aspects of motor and cognitive dysfunctions and neurodegeneration. However, little is known about the association between blood flow and brain microstructural integrity, especially in normal aging. To assess the association between CBF and cerebral microstructural integrity. Cross sectional. A total of 94 cognitively unimpaired adults (mean age 50.7 years, age range between 22 and 88 years, 56 Men). A 3 T; pseudo-continuous arterial spin labeling (pCASL), diffusion tensor imaging (DTI), Bayesian Monte Carlo analysis of multicomponent driven equilibrium steady-state observation of T1 and T2 (BMC-mcDESPOT). Lobar associations between CBF derived from pCASL, and longitudinal relaxation rate (R1 ), transverse relaxation rate (R2 ) and myelin water fraction (MWF) derived from BMC-mcDESPOT, or radial diffusivity (RD), axial diffusivity (AxD), mean diffusivity (MD) and fractional anisotropy (FA) derived from DTI were assessed. Multiple linear regression models were used using the mean region of interest (ROI) values for MWF, R1 , R2 , FA, MD, RD, or AxD as the dependent variable and CBF, age, age2 , and sex as the independent variables. A two-sided P value of <0.05 defined statistical significance. R1 , R2 , MWF, FA, MD, RD, and AxD parameters were associated with CBF in most of the cerebral regions evaluated. Specifically, higher CBF values were significantly associated with higher FA, MWF, R1 and R2 , or lower MD, RD and AxD values. These findings suggest that cerebral tissue microstructure may be impacted by global brain perfusion, adding further evidence to the intimate relationship between cerebral blood supply and cerebral tissue integrity. 4 TECHNICAL EFFICACY: Stage 4.


The future role of mesenchymal stem cells in the management of shoulder disorders.
Biologics may help to optimize the healing environment after rotator cuff repair. Mesenchymal stem cells (MSCs) may have the potential to regenerate a physiological enthesis, thereby improving healing at the repair site after rotator cuff repair. The PubMed database was searched in May 2013. Only in vivo and in vitro studies reporting on stem cell use in the rotator cuff of humans or animals were included. Exclusion criteria consisted of the following: Level V evidence, systematic reviews, and studies reporting preliminary results. This query resulted in 141 citations. Of these, 90 were excluded based on the title of the study. A final group of 17 studies was included in this review (9 in vivo animal studies, 5 in vitro human studies, 1 in vitro animal study, 1 study reporting in vitro human and in vivo animal results, and 1 study reporting on clinical outcomes of human patients). The current literature regarding therapeutic use of MSCs in shoulder surgery is limited. Although in vivo animal studies have shown some promising approaches to enhance tendon-to-bone healing, the use of MSCs for shoulder surgery should still be regarded as an experimental technique. Further basic and clinical research is needed until a procedure can be defined for the routine use of these cells in shoulder surgery.


In vitro evaluation of copper sulfide nanoparticles decorated with folic acid/chitosan as a novel pH-sensitive nanocarrier for the efficient controlled targeted delivery of cytarabine as an anticancer drug.
Nanoparticles (NPs) have gained more attention as drug delivery systems. Folic acid (FA)-chitosan (CS) conjugates, because of their biodegradability, low toxicity, and better stability, offer a pharmaceutical drug delivery tool. The aim of this work was to fabricate CuS NPs modified by CS followed by grafting FA as a nanocarrier for the delivery of cytarabine (CYT) as an anticancer drug. In this work, CuS NPs modified by CS and FA were successfully synthesized. The structural properties of the nanocarrier were characterized by using scanning electron microscopy, Fourier transform infrared, X-ray diffraction, thermogravimetric analysis, and Brunauer-Emmett-Teller. The adsorption mechanism of CYT by adsorption isotherms, kinetics, and thermodynamics was deliberated and modeled. The in vitro CYT release behavior for the nanocarrier was 99% and 61% at pH 5.6 and 7.4, respectively. The adsorption behavior of CYT by CuS NPs -CS-FA was well explored by pseudo-second-order kinetic and Langmuir isotherm models by the coefficient of determination (R2 > 0.99). Thermodynamic results showed that the uptake of CYT by CuS NPs-CS-FA was endothermic and spontaneous. The experimental results showed that CYT/CuS NPs -CS-FA can be proposed as an efficient nanocarrier for the targeted delivery of anticancer drugs.


[Histochemical characteristics of adrenergic myocardial and adrenal fibers in experimental narrowing of the aorta and pulmonary artery].
Ligation of the aorta or the pulmonary trunk was the method of experimental overloading of heart ventricles. Histochemical studies indicated activation of mediator chain of the sympatho-adrenal system. Catecholamines content in the nervous plexus of the overloaded ventricle did not change but there was an increase of their content in the medullary layer of the adrenals. Thus, chromaffin cells activity increases and desympathization of the heart muscle may be an important step in pathogenesis of heart failure in acute arterial hypertension.


Unusual association of epidemic dropsy with brachial neuritis and palatal palsy.
Epidemic dropsy (ED) results from accidental ingestion of adulterated mustard oil with argemone oil. Chief organs involved in this disease are heart, subcutaneous tissue, eyes and kidneys. Nervous system involvement is very rare. Objective manifestation of neurological involvement is even rarer. The authors report two cases from the same family, who were victims of epidemic dropsy along with their parents. One of them showed objective neurologic involvement in the form of brachial neuritis and another showed palatal palsy.


Microbial Etiologies of Otitis Media with Resistance Pattern in a Tertiary Care Hospital in North India.
The study aimed to evaluate the bacterial and fungal profiles in Otitis Media (OM), Acute Otitis Media (AOM), and Chronic Otitis Media (COM) and the sensitivity patterns to antibiotics available in our hospital settings. A total of 150 clinically diagnosed cases of OM (AOM or COM) with ear discharge were enrolled. Swabs were cultured for microbial flora. Drug susceptibility testing was conducted using the Kirby-Bauer disc diffusion method. The most common bacteria isolated in AOM was Streptococcus spp., and in COM it was Staphylococcus aureus. Among fungal isolates, Candida albicans dominate. The antimicrobial profile of the organisms revealed maximum sensitivity to Fluoroquinolones. Correct diagnosis and precise antibiotic prescription reduce the load of antibiotic resistance.


Synaptic contact number and size in stratum radiatum CA1 of APP/PS1DeltaE9 transgenic mice.
Synaptic changes occur early in the course of Alzheimer's disease and are key to understanding the initial events in associated neurodegenerative processes. The quantitative analysis of synaptic morphology in transgenic mouse models of Alzheimer's disease can provide important insights into these processes. To this end, the total number and the distribution of the diameters of synaptic contacts in the stratum radiatum of the CA1 region of the hippocampus of 12-month-old APP/PS1DeltaE9 transgenic mice and wild type littermates have been evaluated by applying design-based stereological methods to material prepared for electron microscopy. Although there were no differences in the size of the synaptic contacts, the total number of synaptic contacts was significantly larger in the transgenic mice, suggesting that the transgenic effect at this age is synaptotrophic and that the presence of amyloid plaques and an elevated Abeta42/40 ratio are not necessarily detrimental to populations of synapses. The potential of this type of data in evaluating synaptic changes related to Alzheimer's disease is discussed and the methodology described in detail.


A description of the lactic acid bacteria microbiota associated with the production of traditional fermented vegetables in Vietnam.
An important part of the daily nourishment in Vietnam constitutes of fermented vegetables. Bacteria and especially lactic acid bacteria play a central role in the production of many fermented vegetables. The current study was conducted to investigate the diversity of native lactic acid bacteria (LAB) populations in 'dua muoi' (mustard and beet fermentation) and 'ca muoi' (eggplant fermentation), three types of popular traditional fermented vegetables of Vietnamese origin. To this end a polyphasic approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and pheS gene sequence analysis was used. In addition, denaturing gradient gel electrophoresis was performed as a culture-independent method to complement the observed culturable diversity data. A total of 881 LAB isolates were recovered from 21 different samples. Predominant LAB associated with 'dua muoi' and 'ca muoi' were identified as Lactobacillus fermentum (56.6%), Lactobacillus pentosus (24.4%) and Lactobacillus plantarum (17.1%). Less abundant species were Pediococcus pentosaceus (1.0%) and Lactobacillus brevis (0.5%). Species present less than 0.1% included Lactobacillus paracasei, Lactobacillus pantheris and Pediococcus acidilactici. In contrast to fermented mustard and beet with the highest prevalence of L. fermentum, the species most recovered from fermented eggplant samples was L. pentosus. In addition, an important degree of genetic variability within the different predominant species was observed and strain dependency correlating with the type of fermented vegetable or location of production could be demonstrated using multivariate statistics. This research gives an extensive and detailed inventory of the LAB diversity associated with the production of diverse Vietnamese fermented vegetables and demonstrates the influence of type of raw material and/or production location and conditions on this diversity.


Comparative anti-thrombotic activity and haemorrhagic adverse effect of nattokinase and tissue-type plasminogen activator.
Anti-thrombotic activity and safety of nattokinase, an enzyme produced by Bacillus subtilis during soybean fermentation, were investigated in comparison with tissue-type plasminogen activator (t-PA). Carotid arterial thrombosis was produced with a FeCl3-soaked paper, followed by intravenous injection of nattokinase or t-PA. Nattokinase and t-PA delayed thrombus formation, near-fully (> 90%) inhibiting at 75 and 8.5 mg/kg, respectively. As adverse effects, t-PA induced petechial haemorrhage at 10 mg/kg in the lungs and thymus, and extensive bleeding at 20 mg/kg. Nattokinase also caused pulmonary haemorrhage from 300 mg/kg. Collectively, the standard safety margins (SSMs) for t-PA and nattokinase were calculated to be 1.2 and 4.0, respectively. Combinational treatment with dexamethasone (2 mg/kg) increased the efficacy and safety of t-PA and nattokinase, widening their SSMs to 2.4 and 8.0, respectively. The results indicate that nattokinase delayed thrombus formation and dissolved thrombi, and that nattokinase could be a good candidate anti-thrombotic agent with relatively-low haemorrhagic risk.


The optimal management of Seymour fractures in children and adolescents: a systematic review protocol.
Seymour fractures are open, displaced juxta-epiphyseal fractures of the distal phalanx, with an overlying nail bed laceration that occur in children and adolescents with an open physis. This fracture occurs rarely, but its potential consequences are clinically significant. Due to anatomical particulars and proximity to the growth plate, this open fracture may result in soft tissue infection and osteomyelitis, leading to growth arrest and persistent mallet deformity. At present, there is no consensus as to the optimal management of Seymour fractures. The objective of this study will be to systematically evaluate the existing evidence on the management of Seymour fractures in children and adolescents and to establish what are the most important factors pertaining to an uncomplicated recovery. We designed and registered a study protocol for a systematic review of randomised controlled trials and observational studies. A comprehensive literature search will be conducted (from inception to present) in MEDLINE, EMBASE, CINAHL and Cochrane Library databases. Grey literature will be identified through searching Open Grey and dissertation databases using an exhaustive search strategy. All clinical studies examining the management of Seymour fractures will be included. The interventions (irrigation and debridement; prophylactic antibiotics) and their timings (early vs late) will be compared to no antibiotics and no debridement. Primary outcome measures will be the incidence of superficial and deep infection. Secondary outcomes will include other adverse events such mal-union, non-union, need for re-operation, physeal disturbance and nail dystrophy/atrophy. Two independent reviewers will screen all citations, full-text articles, and abstract data. Conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using an appropriate tool. A narrative synthesis will be performed. If data permits, we will conduct random-effects meta-analysis where appropriate. This review will provide evidence for the management of Seymour fractures, based on a cumulation of existing smaller studies. Due to the rarity of this fracture pattern, included studies are expected to be mainly observational and prone to bias; however, there is value in summarising the evidence to guide clinicians. Systematic review registration: PROSPERO CRD42020153726.


Non-deforestation drivers of fires are increasingly important sources of aerosol and carbon dioxide emissions across Amazonia.
Deforestation rates have declined substantially across the Brazilian Legal Amazon (BLA) over the period from 2000-2017. However, reductions in fire, aerosol and carbon dioxide have been far less significant than deforestation, even when accounting for inter-annual variability in precipitation. Our observations and analysis support a decoupling between fire and deforestation that has exacerbated forest degradation in the BLA. Basing aerosol and carbon dioxide emissions on deforestation rates, without accounting for forest degradation will bias these important climate and ecosystem-health parameters low, both now and in the future. Recent increases in deforestation rate since 2014 will enhance such degradation, particularly during drought-conditions, increasing emissions of aerosol and greenhouse gases. Given Brazil's committed Nationally Determined Contribution under the Paris Agreement, failure to account for forest degradation fires will paint a false picture of prior progress and potentially have profound implications for both regional and global climate.


Interictal cytokine levels were correlated to seizure severity of epileptic patients: a retrospective study on 1218 epileptic patients.
Many aspects on the correlation between epilepsy and cytokine levels were unclear. This study aims to investigate the correlations between cytokine levels and severe epilepsy. Totally 1218 epileptic patients were grouped by types of epilepsy: TLE (temporal lobe epilepsy, n = 409), XLE (extra-temporal lobe epilepsy, n = 290) and IGE (idiopathic generalized epilepsy, n = 519). Two hundred healthy volunteers were as controls. Clinical findings and levels of 14 serum and CSF cytokines and 6 STAT members were collected, measured and analyzed. Analysis showed no differences in interictal cytokine levels among patients from TLE, XLE and IGE groups. Interictal serum levels of IL-1b, IL-1Ra, IL-6, IL-8, IFNγ, IFNλ3 and IL-17a were associated with seizure severity of epileptic patients, measured by seizure frequency, VA score or NHS3. Multivariate regression analysis indicated that interictal concentrations of serum IL-6, IFNγ, IL-17a, IFNλ3, and CSF IL-6, IL-17a, IFNλ3 were significant biomarkers for patients with severe epilepsy. mRNA levels of IL-6, IFNγ, IL-17a, and IFNλ3 were elevated in different types of epilepsy. Activation of all STATs was elevated in epilepsy, and STAT3 was activated 9-fold in average, which was the highest among all STATs. Interictal serum IL-6, IFNγ, IL-17a, IFNλ3, and CSF IL-6, IL-17a, IFNλ3 could be used as potential biomarkers for severe epilepsy. Activation of STATs, especially STAT3, was important in epilepsy. Our findings pointed out crucial roles of cytokine levels in epilepsy.


LncRNA THRIL promotes high glucose-induced proliferation and migration of human retina microvascular endothelial cells through enhancing autophagy.
Diabetes retinopathy (DR) is associated with retinal microvascular system injury induced by high glucose (HG). This study aims to explore the role and mechanism of long non-coding RNA THRIL in regulating cell proliferation and migration of human retina microvascular endothelial cells (hRMECs) under HG condition. The gene and protein expression were detetced by RT-PCR and western blot, respectively. Cell proliferation and migration of hRMECs were examined using MTT assay and Transwell assay, respectively. The interaction between miR-125b-5p and THRIL or autophagy-related gene 4D (ATG4D) was analyzed using luciferase activity assay. THRIL expression was induced by HG in hRMECs. THRIL overexpression enhanced the proliferation and migration of hRMECs induced by HG, whereas THRIL silencing yielded the opposite results. Furthermore, THRIL overexpression induced autophagy activation, and inhibition of autophagy by 3-methyladenine abrogated the promotory effects of THRIL overexpression on cell proliferation and migration of hRMECs. Mechanismly, THRIL inhibited miR-125b-5p to upregulate the expression of ATG4D (an important autophagy-related gene), thereby promoting autophagy. Moreover, miR-125b-5p overexpression or ATG4D silencing alone abolished the promoting effects of THRIL overexpression on HG-induced autophagy, proliferation and migration of hRMECs. THRIL promotes HG-induced cell proliferation and migration of hRMECs through activation of autophagy via the miR-125b-5p/ATG4D axis. THRIL may serve as a potential therapeutic target for DR.


Finite-size effects on the quasistatic displacement pulse in a solid specimen with quadratic nonlinearity.
There is an unresolved debate in the scientific community about the shape of the quasistatic displacement pulse produced by nonlinear acoustic wave propagation in an elastic solid with quadratic nonlinearity. Early analytical and experimental studies suggested that the quasistatic pulse exhibits a right-triangular shape with the peak displacement of the leading edge being proportional to the length of the tone burst. In contrast, more recent theoretical, analytical, numerical, and experimental studies suggested that the quasistatic displacement pulse has a flat-top shape where the peak displacement is proportional to the propagation distance. This study presents rigorous mathematical analyses and numerical simulations of the quasistatic displacement pulse. In the case of semi-infinite solids, it is confirmed that the time-domain shape of the quasistatic pulse generated by a longitudinal plane wave is not a right-angle triangle. In the case of finite-size solids, the finite axial dimension of the specimen cannot simply be modeled with a linear reflection coefficient that neglects the nonlinear interaction between the combined incident and reflected fields. More profoundly, the quasistatic pulse generated by a transducer of finite aperture suffers more severe divergence than both the fundamental and second order harmonic pulses generated by the same transducer.


Evaluation by electronic tongue and headspace-GC-IMS analyses of the flavor compounds in dry-cured pork with different salt content.
Traditional dry-cured pork, a meat product with a unique flavor and good chewability, occupies an important place in the Chinese market. However, the salt content of dry-cured pork is on the high side and long-term consumption of high-salt meat products is not good for human health. This study determined the role of salt in volatile organic substances and non-volatile taste components of dry-cured pork. Dry-cured pork samples with different salt content (0%, 1%, 3%, 5%, and 7%) were analyzed by electronic tongue for moisture content, pH, salt (NaCl) value, taste activity value, free amino acids, and taste components and by headspace-gas chromatography-ion mobility spectrometry for volatile organic components. The results showed that the moisture content of the tested samples decreased while the salt content increased. The highest amounts of free amino acids were found in dry-cured pork with 3% salt content (P < 0.05). The highest peak area of volatile organic compounds and the maximal taste indexes were found in dry-cured pork with 3% and 5% salt content.


Cultural Adaptation and Validation of the Barriers to HIV Testing Scale-Karolinska Version for Brazilian Men Who Have Sex With Men.
The aim of this study was to perform the cultural adaptation and validation of the Barriers to HIV testing scale-Karolinska version for Brazilian men who have sex with men. A methodological study was conducted for cultural adaptation and validation of the scale. Reliability analyses, exploratory factor analysis, confirmatory factor analysis, and convergent and discriminant validity tests were performed. Four factors were extracted: F1, personal consequences; F2, structural barriers; F3, confidentiality; F4, economic consequences and individual concerns. Good fit indexes were obtained: (χ 2 )/GL (2.71); goodness of fit index (0.94); root-mean-square error of approximation (0.052; 90% CI [0.045-0.059]); Tucker-Lewis index (0.94); normed fit index (0.93); IFI (0.95); comparative fit index (0.95). Convergent validity results were greater than 0.7 for the four factors. The adapted version of the scale showed satisfactory reliability and validity for assessing barriers to HIV testing among men who have sex with men.


Induction of the oscillatory current by low concentrations of caffeine in sheep cardiac Purkinje fibres.
The actions of low concentrations of caffeine (0.5-2 mmol/l) on the transient inward oscillatory current (Ios) and the inward tail current (Iex) were studied in sheep cardiac Purkinje fibres by means of a two microelectrode voltage clamp method. The following results were obtained. Caffeine: induced an Ios when this current was not already present; increased the amplitude (within limits) and consistently decreased the time to peak of an already present Ios; increased Iex upon which Ios may be superimposed; shifted the depolarizing threshold for the appearance of Ios to more negative and the repolarizing threshold to less negative values; increased the effects of strophanthidin of Ios and Iex; exaggerated the effects of high [Ca]o which by itself mimicked some of the actions of caffeine; had a small effect of Ios and Iex in low [Ca]o; 8. reversed the effect of norepinephrine on Iex; enhanced the effects of trains of clamps and of longer clamp steps on Ios and Iex. It is concluded that low concentrations of caffeine facilitate the manifestations of calcium overload thereby inducing or exaggerating the oscillatory and tail currents and that these effects are modulated by the cellular calcium load but are not mediated through adrenergic mechanisms.


Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis.
Human carcinomas arise through the acquisition of genetic changes that endow precursor cancer cells with a critical threshold of cancer-relevant genetic lesions. This complex genomic alterations confer upon precursor cancer cells the ability to grow indefinitely and to metastasize to distant sites. One important mechanism underlying a cell's tumorigenic potential is the status of its telomere. Telomeres are G-rich simple repeat sequences that serve to prevent chromosomal ends from being recognized as DNA double-strand breaks (DSBs). Dysfunctional telomeres resemble DSBs, leading to the formation of dicentric chromosomes that fuel high degrees of genomic instability. In the setting of an intact p53 pathway, this instability promotes cellular senescence, a potent tumor suppressor mechanism. However, rare cells that stochastically lose p53 function emerge from this sea of genomic instability and progress towards cancer. In this review, we describe the use of mouse models to probe the impact of dysfunctional telomeres on tumor initiation and suppression.


Understanding brain organisation in the face of functional heterogeneity and functional multiplicity.
Understanding the fundamental organisation of the brain in terms of functional specialisation and integration is one of the principal aims of imaging neuroscience. Many investigations into the functional organisation of the brain are predicated on parcellating the brain into patches of assumed piece-wise constant connectivity. There are, however, many brain areas where the assumption of piece-wise constant organisation is violated. Connectivity, and by extension function, often varies continuously across the grey matter according to multiple overlapping modes of change. The organisation is governed by functional heterogeneity (continuous change) as well as functional multiplicity (overlapping modes). Functional heterogeneity and multiplicity have important implications for how we can and should analyse our data and how we ought to interpret the results, both in the classical context of parcellated modes and under models that allow for overlapping modes of continuous change. The goal of this opinion paper is to raise awareness of these issues and highlight recent methodological developments toward accounting for these important fundamental features of brain organisation.


Modified-Malay Eating Behavior and Pattern Questionnaire (Malay-EBPQ): translation and validation among Malaysian women.
Eating behavior primarily depends on eating patterns which are largely influenced by interactions between physiology, environment, psychology, culture and socio-economic status. This study was designed to translate and validate the Eating Behavior Pattern Questionnaire (EBPQ) among Malaysian women. A cross-sectional study involving translation and validation of the English version of EBPQ. The original questionnaire, contained 51 items extracted into six domains was translated in Malay using forward and backward translation, pre-tested and validated among conveniently sampled female healthcare personnel. Vegetarians, pregnant ladies and women in confinement were excluded due to special daily dietary plans. Construct validity, reliability and feasibility were analyzed using Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). During translation, item modifications were made and subjected to field testing among 394 women. The original questionnaire was used as a reference to identify the positioning of items in constructs. Fifteen items were removed due to poor correlation with items within constructs. Seven factors were extracted using Varimax rotation with Kaiser-Meyer-Olkin (KMO) value range from 0.725-0.872 and significant Bartlett's test of Sphericity (p < 0.001). The item-loading of the items within the constructs ranged between 0.415-0.812 (explained variation = 62.7%). Cultural and lifestyle behavior was relabeled to lifestyle and behavioral eating, and snacking on sweets was relabeled as snacking pattern. Emotional eating was divided into two sub-factors as snacking behavior and emotional influence. CFA resulted with an acceptable fit with no presence of floor and ceiling effects. Intra-class correlation coefficient (ICC) for all the constructs were reported good and excellent. The overall internal consistency was reported as good. The modified 36-item Malay-EBPQ had moderate internal consistency, reliable and fit with multi-dimensional measures of eating behaviors and dietary patterns among women in the multi-racial population with cultural diversity.


Integrating novel systemic therapies for the treatment of mycosis fungoides and Sézary syndrome.
Novel systemic therapies are generally prescribed to patients with advanced-stage disease or those with early-stage disease refractory to skin-directed therapies. In general, systemic chemotherapy should be reserved for patients who fail to respond to biological agents. Such biological agents include interferon alfa, bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab vedotin and mogamulizumab. Extracorporeal photopheresis is particularly effective for patients with Sézary Syndrome. Allogeneic transplantation is becoming increasing used for younger patients. Novel agents in advanced development include the monoclonal antibody IPH4102,duvelisib,and the new modified formulation of denileukin diftitox. The choice of agents for patients is typically a balance of patient factors (age, co-morbidities, geographic location), relative efficacy and toxicity.