Laboratory reference values for healthy adults from southern Tanzania.
To define and discuss reference ranges for commonly determined laboratory parameters in healthy adults from southern Tanzania. A population-based sample of adult volunteers from Mbeya, Tanzania, who were not HIV positive or showing signs and symptoms of other diseases, participated in this study. We enrolled 145 women and 156 men between 19 and 48 years of age to determine clinical chemistry (CC), haematology and lymphocyte immunophenotyping (LIP) parameters using standard laboratory methods. Medians and nonparametric 95% reference ranges for each parameter were determined and compared with reference ranges from the USA, Europe and from other African countries. Agreement with ranges from developed countries was poor: for CC values the average concordance was 80.9% and 86.7% with values from two developed countries. Haematology ranges from the USA classified 86.3% of values correctly, whereas ranges from three different sub-Saharan Africa (SSA) sites classified between 82.5% and 94.5% of values correctly. The agreement of LIP reference ranges was 87.5% with values determined in Germany but between 91.7% and 95.8% compared with values determined at other sites in SSA. Clinical reference ranges determined in developed countries are inadequate for use in SSA. Laboratories in this region should either define their own or use values determined under similar conditions. The ranges reported here are more appropriate for use in SSA than ranges determined in developed countries.


Psychiatric comorbidity in different organic vertigo syndromes.
A high degree of psychiatric disorders has repeatedly been described among patients with organic vertigo syndromes and attributed to vestibular dysfunction. Yet almost no investigations exist which differentiate between various organic vertigo syndromes with regard to psychiatric comorbidity. The following prospective, interdisciplinary study was carried out to explore whether patients with different organic vertigo syndromes exhibit different psychological comorbidities. 68 patients with organic vertigo syndromes (benign paroxysmal positioning vertigo (BPPV) n = 20, vestibular neuritis (VN) n = 18, Menière's disease (MD) n = 7, vestibular migraine (VM) n = 23) were compared with 30 healthy volunteers. All patients and control persons underwent structured neurological and neuro-otological testing. A structured diagnostic interview (-I) (SCID-I) and a battery of psychometric tests were used to evaluate comorbid psychiatric disorders. Patients with VM and MD showed significantly higher prevalence of psychiatric comorbidity (MD = 57%, VM = 65%) especially with anxiety and depressive disorders, than patients with VN (22%) and BPPV (15 %) compared to normal subjects (20 %). These elevated rates of comorbidities resulted in significantly elevated odds-ratios (OR) for the development of comorbid psychiatric disorders in general (for VM OR = 7.5, for MD OR = 5.3) and especially for anxiety disorders (for VM OR = 26.6, for MD OR = 38.7). As a consequence, a structured psychological and psychometric testing and an interdisciplinary therapy should be proceeded in cases with complex and prolonged vertigo courses, especially in patients with VM and MD. Possible reasons of these unexpected results in VM and MD are discussed.


Franklin Mall, the first basic scientist of pediatric surgery.
Franklin Mall (1862-1917) made fundamental discoveries in the embryology of malrotation and the development of the diaphragm, pathological conditions basic to pediatric surgery. As the inaugural professor of anatomy at the new Johns Hopkins University School of Medicine when it opened in 1893, Mall was among the first fulltime researchers in basic medical science in American medical schools, a new role that came to characterize the modern academic medical center.


Beyond particulate matter: New evidence on the causal effects of air pollution on mortality.
The increasing demand for electricity worldwide has caused a corresponding rise in the consumption of coal, leading to an increase in sulfur dioxide (SO2) pollution levels. Despite the severity of the issue, there is a lack of conclusive evidence establishing a causal link between SO2 pollution and health, particularly in developing countries. We leverage a large national environmental regulation policy, implemented in China to reduce SO2 emissions, to estimate the impacts of SO2 pollution on mortality. We find that 1-μg/m3 reduction in SO2 concentrations leads to 18 fewer cardiovascular deaths per 100,000 people aged 60 years and above (0.9% decrease) and 2 fewer deaths per 100,000 children under the age of 5 (1.5% decrease) annually. A back-of-the-envelope calculation suggests that the total health benefits of the environmental policy outweigh its economic costs. The results are consistent across various robustness checks.


Identification of circulating microRNAs during the liver neoplastic process in a murine model of hereditary tyrosinemia type 1.
Hereditary tyrosinemia type 1 (HT1) is a severe inborn error of metabolism, impacting the tyrosine catabolic pathway with a high incidence of hepatocellular carcinoma (HCC). Using a HT1 murine model, we investigated the changes in profiles of circulating and hepatic miRNAs. The aim was to determine if plasma miRNAs could be used as non-invasive markers of liver damage in HT1 progression. Plasma and liver miRNAome was determined by deep sequencing after HT1 phenotype was induced. Sequencing analysis revealed deregulation of several miRNAs including let-7/miR-98 family, miR-21 and miR-148a, during manifestation of liver pathology. Three miRNAs (miR-98, miR-200b, miR-409) presenting the highest plasmatic variations among miRNAs found in both plasma and liver and with >1000 reads in at least one plasma sample, were further validated by RT-qPCR. Two of these miRNAs have protein targets involved in HT1 and significant changes in their circulating levels are detectable prior an increase in protein expression of alpha-fetoprotein, the current biomarker for HCC diagnosis. Future assessment of these miRNAs in HT1 patients and their association with liver neoplastic lesions might designate these molecules as potential biomarkers for monitoring HT1 damage progression, improving diagnosis for early HCC detection and the design of novel therapeutic targets.


Fungal allergens.
Many fungi are capable of causing IgE-mediated hypersensitivity in humans. However, the most predominant fungi implicated in allergy belong to the genera Aspergillus, Alternaria, Cladosporium, and Penicillium. Pure and relevant allergens are essential for diagnosis as well as for understanding the immunopathogenesis of the disease. Until recently, pure and standardizable antigens from fungi were not available. In recent years, many recombinant allergens have been produced by molecular cloning. Using these allergens, novel methods are being developed to improve diagnosis of mold-induced allergy. By understanding the immunopathogenesis of allergens, new avenues might open up leading to improved patient care, including immunotherapy and vaccination. This review covers the current status of fungal allergens, their role in reliable immunodiagnosis, and their probable use in immunotherapy and vaccination.


Doing good by writing well for JOSA A: editorial.
Editor-in-Chief P. Scott Carney gives his thoughts on good writing for scientific publication.


Factor V Leiden, prothrombin, MTHFR, and PAI-1 gene polymorphisms in patients with arterial disease: A comprehensive systematic-review and meta-analysis.
The role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic-review and meta-analysis of inherited thrombophilia in cerebrovascular (CVD), coronary heart (CHD), and peripheral artery disease (PAD) patients. MEDLINE and EMBASE were searched up to February 2022. Pooled prevalences (PPs) and odds ratios (ORs) with 95 % confidence intervals (95%CI) were calculated in a random-effects model. Factor V Leiden (G1691A), prothrombin (G20210A), MTHFR C677T/A1298C and PAI-1 4G/5G were evaluated. 377 studies for 98,186 patients (32,791 CVD, 62,266 CHD, 3129 PAD) and 108,569 controls were included. Overall, 37,249 patients had G1691A, 32,254 G20210A, 42,546 MTHFR C677T, 8889 MTHFR A1298C, and 19,861 PAI-1 4G/5G gene polymorphisms. In CVD patients, PPs were 6.5 % for G1691A, 3.9 % for G20210A, 56.4 % for MTHFR C677T, 51.9 % for MTHFR A1298C, and 77.6 % for PAI-1. In CHD, corresponding PPs were 7.2 %, 3.8 %, 52.3 %, 53.9 %, and 76.4 %. In PAD, PPs were 6.9 %, 4.7 %, 55.1 %, 52.1 %, and 75.0 %, respectively. Strongest ORs in CVD were for homozygous G1691A (2.76; 95 %CI, 1.83-4.18) and for homozygous G20210A (3.96; 95 %CI, 2.05-7.64). Strongest ORs in CHD were for homozygous G1691A (OR 1.68; 95%CI, 1.02-2.77) and G20210A (heterozygous 1.49 95%CI, 1.22-1.82; homozygous 1.54 95%CI, 0.79-2.99). The OR for PAI-1 4G/4G in PAD was 5.44 (95%CI, 1.80-16.43). Specific subgroups with higher PPs and ORs were identified according to age and region. Patients with arterial disease have an increased prevalence and odds of having some inherited thrombophilia. Some thrombophilia testing may be considered in specific subgroups of patients.


Evaluation of temperature-dependent fluctuations in skin microcirculation flow using a light-emitting diode based photoacoustic imaging device.
Skin microvessels maintain temperature homeostasis by contracting and dilating upon exposure to changes in temperature. Under general anesthesia, surgical invasiveness, including incisions and coagulation, and the effects of anesthetics may cause variations in the threshold temperature, leading to the constriction and dilation of cutaneous blood vessels. Therefore, studies on skin microvascular circulation are necessary to develop appropriate interventions for complications during surgery. We visualized and quantified skin microcirculatory fluctuations associated with temperature variations using a light-emitting diode photoacoustic imaging (LED-PAI) device. The hands of ten healthy volunteers were stressed with four different water temperatures [25℃ (Control), 15℃ (Cold1), 40℃ (Warm), and 15℃ (Cold2)]. The photoacoustic images of the fingers were taken under each condition, and the microvascular flow owing to temperature stress was quantified as the area of photoacoustic signal (S) in each image. The S values were compared with the variations in blood flow (Q) measured by laser Doppler flowmetry (LDF). The correlation between Q and S according to the 40 measurements was r = 0.45 (p<0.01). In addition, the values of S under each stress condition were as follows: Scontrol = 10,826 ± 3364 pixels, Scold1 = 8825 ± 2484 pixels, Swarm = 13,369 ± 3001 pixels, and Scold2 = 8838 ± 1892 pixels; the differences were significant. The LDF blood flow (Q) showed similar changes among conditions. These findings suggest that the LED-PAI device could be an option for evaluating microcirculation in association with changes in temperature.


[Progress in hepatitis C treatment].
Recent approval of new protease inhibitors (boceprevir and telaprevir) for the treatment of chronic hepatitis C, genotype 1, has meant a significant increase in the sustained viral response both in naive and previously treated patients. However, such efficacy increase has been accompanied by an increase in adverse events, sometimes serious, and new practical issues including different approaches to stop treatment and drug interactions that recommend a close follow-up of patients. The efficacy and safety of triple therapy in special populations such as cirrhotic and transplanted patients is less known and has some particulars, meaning that its administration requires an exhaustive monitoring.


Neurotoxic and hepatotoxic cyanotoxins removal by nanofiltration.
This study investigates the influence of chemical feed characteristics on nanofiltration performance for cyanotoxins removal, namely the neurotoxic anatoxin-a (alkaloid of 166 g/mol, positively charged) and the hepatotoxic microcystins (cyclic peptides of approximately 1,000 g/mol, negatively charged). Results indicate that NF membranes are an effective barrier against anatoxin-a and microcystins in drinking water. Anatoxin-a and especially microcystins were almost completely removed, regardless of the variations in feed water quality (natural organic matter and competitive toxin), the water recovery rate and the pH values. Anatoxin-a removal was governed by electrostatic interactions and steric hindrance, whereas for microcystins the latter was the main mechanism. In turn, fluxes were significantly impacted by background organics and, especially, inorganics (pH, calcium).


Simultaneous determination of enalapril maleate and nitrendipine in tablets using spectrophotometric methods manipulating ratio spectra.
A fixed dose combination of enalapril maleate (EN) and nitrendipine (NT) achieved satisfactory blood pressure control rather than monotherapy. Four accurate spectrophotometric methods utilizing ratio spectra were developed and validated for the simultaneous determination of EN and NT in combined pharmaceutical dosage form (Eneas® tablets). The first method was first derivative ratio spectrophotometric method (1DD) where the amplitudes maxima were measured at 219.2 nm and 233.4 nm for the determination of EN and NT, respectively. The second method was ratio difference spectrophotometric method where EN and NT were estimated by measuring the amplitudes difference between 213 nm and 225 nm on the ratio spectrum of EN and between 241 nm and 227 nm on the ratio spectrum of NT. The third method was ratio subtraction followed by extended ratio subtraction, EN was determined at 210 nm by subtraction of the constant values from the ratio spectrum then multiplication with the divisor (NT spectrum). An extended ratio subtraction method was then applied in order to determine NT at 235 nm by using the zero-order spectrum of EN (10 μg/ml) as a divisor. The fourth method was ratio subtraction coupled with constant multiplication methods. The zero- order absorption spectrum of the laboratory prepared mixture was divided by NT (12 μg/ml) spectrum, subsequently, the value of the constant was multiplied by the divisor to obtain the original spectrum of NT, followed by its subtraction from the laboratory prepared mixture to get the spectrum of EN. EN and NT were determined at 210 nm and 235 nm, respectively. Linearity was ascertained over the concentration ranges of (1-11 μg/ml) for EN and (2-14 μg/ml) for NT, for the first and second methods and (2-13 μg/ml) for EN and (3-20 μg/ml) of NT, for the third and fourth methods. Application of the methods to the determination of the cited drugs in Eneas® tablets gave satisfactory results. Methods validation confirmed their accuracy and selectivity. Statistical comparison of the results with the reported one showed no significant difference, regarding precision and accuracy. Routine analysis of the cited drugs in quality control laboratories could be performed using the developed methods.


Trends in the health status of older Manitobans, 1985 to 1999.
Trends in the health status of the entire senior population aged 65 years or older in Manitoba were examined over a 14-year period (1985-1999) using administrative data (about 50,000 individuals). Significant health gains were apparent for a number of important indicators, including acute myocardial infarction, stroke, cancer, and hip fractures, although some of these gains were restricted to urban areas. Improvements in these health indicators are significant, as they can have major implications for individuals' need for health services and ability to live independently. In contrast, chronic diseases were on the rise, with the prevalence of diabetes, hypertension, and dementia increasing substantially over the 14-year period. These trends suggest a need for a policy emphasis on prevention, such as reducing the prevalence of obesity, which is one risk factor for diabetes. Moreover, having sufficient care options in place for the growing number of individuals with dementia is an issue that will have to be addressed.


Conditions for hormone-stimulated expression of endogenous C57Bl strain-associated mammary tumor virus genome.
Full MMTV-Y gene expression can occur in dexamethasone-insulin-prolactin-stimulated cell cultured derived from C57Bl/10 mammary adenocarcinomas induced by syncarcinogenic action of chemical carcinogens (dimethylbenzanthracene), and mammotropic hormones (estrogen and prolactin). The rate of the hormone-stimulated virus production, as determined by biochemical, immunological and electron microscopical methods, was comparable to the level of spontaneous MMTV production by cells of established mouse mammary cancer cultures (CCL-51 and Mm5mt/cl). On the contrary, no virus production has been detected in hormone-stimulated cultures derived from C57Bl/10 mammary tumors induced by chemical carcinogen alone (urethan).


Mechanism of the glycine cleavage reaction. Properties of the reverse reaction catalyzed by T-protein.
T-protein, one of the components of the glycine cleavage system, catalyzes the synthesis of the H-protein-bound intermediate from methylenetetrahydrofolate, ammonia, and H-protein having a reduced lipoyl prosthetic group (Okamura-Ikeda, K., Fujiwara, K., and Motokawa, Y. (1982) J. Biol. Chem. 257, 135-139). Spectroscopic studies indicated that the utilization of methylenetetrahydrofolate occurred only in the presence of the three substrates, indicating the formation of a quaternary complex. The amount of methylenetetrahydrofolate consumed was equal to that of methylene carbon attached to H-protein. Steady-state kinetic studies show that the reaction proceeds through an Ordered Ter Bi mechanism. Reduced H-protein is the first substrate that binds T-protein followed by methylenetetrahydrofolate and ammonia. The order of release of products is tetrahydrofolate and the H-protein-bound intermediate. Km values for H-protein, methylenetetrahydrofolate, and ammonia are 0.55 microM, 0.32 mM, and 22 mM, respectively.


Applicability of massively parallel sequencing on monitoring harmful algae at Varna Bay in the Black Sea.
In this study the plankton diversity in 13 environmental samples from Varna Bay (in the western Black Sea) was analyzed using massively parallel sequencing (MPS). This preliminary study was undertaken to assess the potential of this technology for future implementation in monitoring programs in the Black Sea. Amplicon sequences of the 18S rRNA gene (V4-5 regions) were obtained using the Illumina MiSeq 250PE platform. A total of 1137 operational taxonomic units (OTUs) were obtained among which 242 OTUs with >0.990 BLAST top hit similarity (21.3% of all detected OTUs) closely related to sequences belonging to -protists. A large portion (175 OTUs=72.3%) was identified at the species levels, including species typical for the Bulgarian Black Sea plankton community, as well as many that haven't been reported earlier in the Bulgarian Black Sea coast (124 OTUs=51.2%). Dinoflagellates were represented by the highest species number (77 OTUs comprising 31.8% of protist species), with dominant genera Gyrodinium and Heterocapsa. The present survey revealed the presence of 12 species listed as harmful, some of which have been previously overlooked, such as Cochlodinium polykrikoides, Karenia bicuneiformis, and Karlodinium veneficum. Species identification was possible for 10.3-36.0% of the detected OTUs in the six major supergroups. The frequency in Rhizaria was significantly lower than that in other major groups (p<0.05-0.01), implying difficulties in the classification from morphology-based observations. The metagenetic data had an insufficient resolution of the 18S rRNA gene for species identification in many genera. These issues may hamper the implementation of MPS-based surveys for plankton monitoring, especially for detecting harmful algal blooms (HAB). The sequencing technology is steadily improving and it is expected that sequence length and quality issues will be resolved in the near future. The ongoing efforts to register taxonomic information and quality controls in the international nucleotide sequence databases (INSDs) will be essential for improving taxonomic identification power.


Bioaugmentation with a defined bacterial consortium: A key to degrade high molecular weight polylactic acid during traditional composting.
Polylactic acid (PLA) is commercialized as a compostable bio-thermoplastic. PLA degrades under industrial composting conditions where elevated temperatures are maintained for a long timeframe. However, these conditions cannot be achieved in a non-industrial compost pile. Therefore, this study aims to degrade high molecular weight PLA films by adding a PLA-degrading bacterial consortium (EAc) comprised of Nocardioides zeae EA12, Stenotrophomonas pavanii EA33, Gordonia desulfuricans EA63, and Chitinophaga jiangningensis EA02 during traditional composting. With EAc-bioaugmentation, PLA films (5-30% w/w) had complete disintegration (35 d), 77-82% molecular weight reduction (16 d), and higher CO2 liberation and mineralization than non-bioaugmented composting. Bacterial community analyses showed that EAc-bioaugmentation increased the relative abundance of Schlegelella, a known polymer degrader, and interacted positively with beneficial indigenous microbes like Bacillus, Schlegelella and Thermopolyspora. The bioaugmentation also decreased compost phytotoxicity. Hence, consortium EAc shows potential in PLA-waste treatment applications, such as backyard and small-scale composting.


Anaerobic detoxification of acetic acid in a thermophilic ethanologen.
The liberation of acetate from hemicellulose negatively impacts fermentations of cellulosic biomass, limiting the concentrations of substrate that can be effectively processed. Solvent-producing bacteria have the capacity to convert acetate to the less toxic product acetone, but to the best of our knowledge, this trait has not been transferred to an organism that produces ethanol at high yield. We have engineered a five-step metabolic pathway to convert acetic acid to acetone in the thermophilic anaerobe Thermoanaerobacterium saccharolyticum. The first steps of the pathway, a reversible conversion of acetate to acetyl-CoA, are catalyzed by the native T. saccharolyticum enzymes acetate kinase and phosphotransacetylase. ack and pta normally divert 30% of catabolic carbon flux to acetic acid; however, their re-introduction in evolved ethanologen strains resulted in virtually no acetic acid production. Conversion between acetic acid and acetyl-CoA remained active, as evidenced by rapid (13)C label transfer from exogenous acetate to ethanol. Genomic re-sequencing of six independently evolved ethanologen strains showed convergent mutations in the hfs hydrogenase gene cluster, which when transferred to wildtype T. saccharolyticum conferred a low acid production phenotype. Thus, the mutated hfs genes effectively separate acetic acid production and consumption from central metabolism, despite their intersecting at the common intermediate acetyl-CoA. To drive acetic acid conversion to a less inhibitory product, the enzymes thiolase, acetoacetate:acetate CoA-transferase, and acetoacetate decarboxylase were assembled in T. saccharolyticum with genes from thermophilic donor organisms that do not natively produce acetone. The resultant strain converted acetic acid to acetone and ethanol while maintaining a metabolic yield of 0.50 g ethanol per gram carbohydrate. Conversion of acetic acid to acetone results in improved ethanol productivity and titer and is an attractive low-cost solution to acetic acid inhibition.


The habitual nature of food purchases at the supermarket: Implications for policy making.
Supermarkets have become the most important provider of food products worldwide. However, empirical evidence about how consumers make their food purchase decisions in this environment is still scarce. The present field study aimed to: i) explore how people make their in-store food purchases, and ii) identify the information they search for when making those purchases. Consumers (n = 144) were intercepted when entering the facilities of three supermarkets in two Uruguayan cities. They were asked to wear a mobile eye-tracker while they made their purchases as they normally do. The great majority of the consumers bought at least one food product or beverage (92%) and, on average, examined products from 2.8 sections. In total, they investigated 37 categories within 13 self-service sections, corresponding to 26 categories of ultra-processed products. For 67% of the products, consumers went straight to the product they seemed to be looking for, grabbed it and put it in their shopping basket or cart, without making any comparison among products. A limited information search was observed. On average, consumers spent 22 s examining products within self-service sections and only 6.9 s were elapsed from the moment they grabbed a product until they put it in the shopping cart. These results provide empirical evidence of the habitual nature of supermarket food purchases in a context characterized by wide availability of ultra-processed products. Taken together, the findings suggest that policies and interventions aimed at reducing purchases of ultra-processed products should disrupt habitual decisions at the point of purchase. In this sense, policies targeted at introducing salient changes on food packages hold potential to disrupt food purchases and encourage consumers to establish new and more healthful food purchase habits.


Prevalence and factors associated with mental health problems of psychological distress and depression among rural Victorians - analysis of cross-sectional data (Crossroads II).
Research suggests that rates of mental illness are similar in rural and urban Australia, although there are significant workforce shortages in rural regions along with higher rates of chronic disease and obesity and lower levels of socioeconomic status. However, there are variations across rural Australia and limited local data on mental health prevalence, risk, service use and protective factors. This study describes the prevalence of self-reported mental health problems of psychological distress and depression, in a rural region in Australia and aims to identify the factors associated with these problems. The Crossroads II study was a large-scale cross-sectional study undertaken in the Goulburn Valley region of Victoria, Australia in 2016-18. Data were collected from randomly selected households across four rural and regional towns and then screening clinics from individuals from these households. The main outcome measures were self-reported mental health problems of psychological distress assessed by the Kessler 10 and depression assessed by Patient Health Questionnaire-9. Unadjusted odd ratios and 95% confidence intervals of factors associated with the two mental health problems were calculated using simple logistic regression with multiple logistic regression using hierarchical modelling to adjust for the potential confounders. Of the 741 adult participants (55.6% females), 67.4% were aged ≥ 55 years. Based on the questionnaires, 16.2% and 13.6% had threshold-level psychological distress and depression, respectively. Of those with threshold-level K-10 scores, 19.0% and 10.5% had seen a psychologist or a psychiatrist respectively while 24.2% and 9.5% of those experiencing depression had seen a psychologist or a psychiatrist, respectively in the past year. Factors such as being unmarried, current smoker, obesity, were significantly associated with a higher prevalence of mental health problems whereas physical activity, and community participation reduced the risk of mental health problems. Compared to rural towns, the regional town had higher risk of depression which was non-significant after adjusting for community participation and health conditions. The high prevalence of psychological distress and depression in this rural population was consistent with other rural studies. Personal and lifestyle factors were more relevant to mental health problems than degree of rurality in Victoria. Targeted lifestyle interventions could assist in reducing mental illness risk and preventing further distress.


Rabies antibody titres in vaccinated reindeer.
One dose of inactivated, adjuvanted rabies vaccine of cell culture origin (Rabisin) induced good but short-duration immunity in close to 100% of the 50 semi-domesticated reindeer (Rangifer tarandus tarandus L.) vaccinated. Most of the animals (44) had rabies virus antibody titre > or = 1.5 IU/ml at 38 days after vaccination. Five animals had titre 0.5 IU. Antibody titres were not, however, present 1 year after primary vaccination in most animals. About 1 year (360-413 days) after primary vaccination, 22 of the 39 reindeer that could be sampled had rabies virus antibody titre < 0.5 IU/ml.


Perceptions of Sexual Risk, PrEP Services, and Peer Navigation Support among HIV-Negative Latinx and Black Men who have Sex with Men (MSM) Residing in Western Washington.
HIV PrEP (pre-exposure prophylaxis) is underutilized among Latinx and Black men who have sex with men (MSM) in the United States. Although peer navigation approaches may increase PrEP uptake and adherence, it remains unclear what strategies work best for MSM of color. From July 2017 to August 2018, we conducted semi-structured in-depth interviews with 25 purposively sampled Latinx and Black cisgender MSM to evaluate how the intersectionality of race/ethnicity, sexual orientation, and other identities influenced men's views on PrEP in general and on peer navigation specifically. Thematic analysis was used to identify and analyze emergent themes. Emergent themes included: (1) awareness of vulnerability in intimate relationships; (2) barriers to PrEP initiation including perceived side effects, stigma, and financial concerns; (3) a wish to connect with other Latinx and Black MSM in a health and prevention space; and (4) the desire for peer matching based on identity considerations and lived experience. Younger men and Spanish-speaking Latinx men were most interested in peer navigation to access PrEP, while bisexual men had confidentiality concerns. In our study, Latinx and Black MSM viewed peer navigation services favorably, especially if they addressed men's desire to connect with other MSM of color. Developing culturally-congruent peer navigation programming could help improve PrEP uptake and care engagement for Latinx and Black MSM. Programs should recruit peers from the racial/ethnic minority communities most impacted by HIV and prioritize matching peers to clients based on identity concerns, needs, and preferences.


Imaging of the calcaneus.
The anatomy of the calcaneus is complex with multiple processes and grooves for support of related bony and soft tissue structures. With respect to imaging, the calcaneus and its articulations are a diagnostic challenge to radiologists and clinicians. This article focuses on the use of commonly employed radiologic modalities with respect to the anatomy of the calcaneus and some of the more common and challenging conditions that affect the calcaneus.


[Pneumonia in adults caused by the respiratory syncytial virus].
Respiratory syncytial virus (RSV) usually affects children but sometimes affects a certain group of adults. A case of an 81 year old female with idiopathic thrombocytopenic purpura who had pneumonia caused by RSV is presented. The literature is reviewed as well as the most frequent clinical manifestations, diagnosis methods and treatment.


Phase 1 Trial of MLN0128 (Sapanisertib) and CB-839 HCl (Telaglenastat) in Patients With Advanced NSCLC (NCI 10327): Rationale and Study Design.
There are currently no approved targeted therapies for lung squamous-cell carcinoma (LSCC) and KRAS-mutant lung adenocarcinoma (LUAD). About 30% of LSCC and 25% of KRAS-mutant LUAD exhibit hyperactive NRF2 pathway activation through mutations in NFE2L2 (the gene encoding NRF2) or its negative regulator, KEAP1. Preclinical data demonstrate that these tumors are uniquely sensitive to dual inhibition of glycolysis and glutaminolysis via mammalian target of rapamycin (mTOR) and glutaminase inhibitors. This phase 1 study was designed to assess safety and preliminary activity of the mTOR inhibitor MLN0128 (sapanisertib) in combination with the glutaminase inhibitor CB-839 HCl. Phase 1 dose finding will use the queue-based variation of the 3 + 3 dose escalation scheme with the primary endpoint of identifying the recommended expansion dose. To confirm the acceptable tolerability of the recommended expansion dose, patients will subsequently enroll onto 1 of 4 expansion cohorts (n = 14 per cohort): (1) LSCC harboring NFE2L2 or (2) KEAP1 mutations, or (3) LUAD harboring KRAS/(KEAP1 or NFE2L2) coalterations, or (4) LSCC wild type for NFE2L2 and KEAP1. The primary endpoint of the dose expansion is to determine the preliminary efficacy of MLN0128/CB-839 combination therapy. This phase 1 study will determine the recommended expansion dose and preliminary efficacy of MLN0128 and CB-839 in advanced non-small-cell lung cancer with a focus on subsets of LSCC and KRAS-mutant LUAD harboring NFE2L2 or KEAP1 mutations.


Genotoxicity of analgesic compounds assessed by an in vitro micronucleus assay.
Several analgesic compounds and mixtures of analgesics were examined for both cytotoxicity and ability to induce chromosomal damage in the normal rat-kidney cell line NRK-49F. Chromosomal damage was assessed using an in vitro micronucleus assay. Of all the compounds tested, only N-hydroxyparacetamol caused a high degree of cell death at the concentrations used. 4 analgesic compounds were found to be inducers of micronuclei in NRK cells; in order of decreasing potency these were: N-hydroxyparacetamol, N-hydroxyphenacetin, caffeine and paracetamol. An aspirin, phenacetin, caffeine mixture (APC) failed to induce micronuclei above the background level, and a paracetamol-codeine combination did not increase the level of micronuclei induction above that induced by paracetamol alone. This report suggests paracetamol and some related compounds are capable of inducing chromosomal damage in mammalian cells in vitro, which is consistent with recent reports of a possible paracetamol-DNA interaction.


Differential expression and serologically distinct subpopulations of human Ia antigens detected with monoclonal antibodies to Ia alpha and beta chains.
Studies with two monoclonal antibodies (DA6.147 and DA6.231) which react, respectively, with isolated human Ia alpha and beta chains are reported. Both antibodies detect epitopes expressed on all DR-heterozygous and DR-homozygous cell lines tested (n = 17) and bind to the Epstein-Barr virus-negative cell line Ramos. Ia subunit specificity of the antibodies was determined by an adaptation of an electroblot technique which transfers separated Ia chains from polyacrylamide gels to nitrocellulose paper. In radioimmunobinding assays, peripheral blood B cell-enriched fractions, phytohemagglutinin-activated T cells and pokeweed mitogen-activated cells gave strong reactions with DA6.231 (anti-Ia beta). In contrast, DA6.147 (anti-Ia alpha) reacted only weakly, if at all, with peripheral B cells, pokeweed mitogen blasts and activated T cells. However, both antibodies bound to isolated Ia from activated T cells and peripheral B cells after Nonidet-P40 solubilization of the cells and DA6.147+ antigens could be found in the cytoplasm of activated T cells by indirect immunofluorescence techniques. Results of serological inhibition procedures following fractionation of lymphoblastoid cell lysates on monoclonal antibody affinity columns showed that the DA6.147 alpha chain epitope is carried on only a minor subpopulation of human Ia.


Delivery of quercetin for breast cancer and targeting potentiation via hyaluronic nano-micelles.
Quercetin (QT) is a very effective anticancer drug in combating breast cancer. However, it has several disadvantages such as poor water solubility, low bioavailability and low targeting, which seriously restrict its clinical application. In this work, amphiphilic hyaluronic acid polymers (dHAD) were synthesized by grafting dodecylamine to hyaluronic acid (HA). The dHAD self-assembles with QT to form drug-carrying micelles (dHAD-QT). The dHAD-QT micelles possessed excellent drug-loading capacities (75.9 %) for QT and showed significantly improved CD44 targeting compared with unmodified HA. dHAD-QT micelles exhibited high cytotoxicity and apoptosis-inducing abilities, which were ascribed to the pH-sensitive dHAD-QT micelles accomplishing rapid drug release of QT under low pH condition. Importantly, in vivo experiments showed that dHAD-QT effectively inhibited tumor growth in tumor-bearing mice, with a tumor inhibition rate of 91.8 %. Furthermore, dHAD-QT prolonged the survival time of tumor-bearing mice and reduced the toxicity of the drug to normal tissues. These findings indicate that the designed dHAD-QT micelles have promising potential as efficient nano-drugs for breast cancer treatment.


Changes in serum and striatal free amino acids after Venezuelan equine encephalomyelitis virus infection.
The infection with the Venezuelan equine encephalomyelitis virus produced a significant increase in the concentration of alanine, arginine, asparagine, glutamine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine in the striatum of rats. On the contrary, the concentrations of aspartate, GABA, glutamate, and taurine were reduced. Arginine, aspartate, glycine, methionine, phenylalanine, taurine, and tyrosine concentrations were increased in the serum of infected rats. However, the modifications in the content of free amino acids in the striatum and serum of rats that survived the infection were qualitatively and quantitatively different from those detected during the acute phase of the infection.


[Dementia: Overview of Nomenclature and the Most Common Forms].
This article explains the nomenclature of dementia in common use and presents a brief overview of the typical symptoms and findings of the most common forms of dementia. A particular focus is placed on Lewy body dementia, which is often underdiagnosed.


Temperature dependence of quantum oscillations from non-parabolic dispersions.
The phase offset of quantum oscillations is commonly used to experimentally diagnose topologically nontrivial Fermi surfaces. This methodology, however, is inconclusive for spin-orbit-coupled metals where π-phase-shifts can also arise from non-topological origins. Here, we show that the linear dispersion in topological metals leads to a T2-temperature correction to the oscillation frequency that is absent for parabolic dispersions. We confirm this effect experimentally in the Dirac semi-metal Cd3As2 and the multiband Dirac metal LaRhIn5. Both materials match a tuning-parameter-free theoretical prediction, emphasizing their unified origin. For topologically trivial Bi2O2Se, no frequency shift associated to linear bands is observed as expected. However, the π-phase shift in Bi2O2Se would lead to a false positive in a Landau-fan plot analysis. Our frequency-focused methodology does not require any input from ab-initio calculations, and hence is promising for identifying correlated topological materials.


PPARgamma inhibition of cyclooxygenase-2, PGE2 synthase, and inducible nitric oxide synthase in cardiac myocytes.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. They regulate lipid metabolism, glucose homeostasis, cell proliferation, and differentiation and modulate inflammatory responses. We examined whether PPARgamma is functional in cultured neonatal ventricular myocytes and studied its role in inflammation. Western blots revealed PPARgamma in myocytes. When myocytes were transfected with a PPAR response element reporter plasmid (PPRE-TK-luciferase), the PPARgamma activator 15-deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) increased promoter activity, whereas cotransfection of a dominant negative PPARgamma inhibited it. To determine the role of 15dPGJ2 in expression of proinflammatory genes, we tested its effect on interleukin-1beta induction of cyclooxygenase-2 (COX-2). 15dPGJ2 decreased interleukin-1beta stimulation of COX-2 by 40% and PGE2 production by 73%. We next questioned whether 15dPGJ2 was modulating the expression of inducible prostaglandin E2 synthase (PGES) and found that it completely blocked interleukin-1beta induction of PGES. Use of a second PPARgamma agonist, troglitazone, and the selective PPARgamma antagonist GW9662 demonstrated that the effects seen were PPARgamma-dependent. In addition, we found that 15dPGJ2 blocked interleukin-1beta stimulation of inducible nitric oxide synthase (iNOS). We concluded that 15dPGJ2 may play an anti-inflammatory role in a PPARgamma-dependent manner, decreasing COX-2, PGES, and PGE2 production, as well as iNOS expression.


[Relationship between macronutrient and micronutrient intake and nutritional status of active older adults in Chillán, Chile].
Social participation by older adults is a health-protective element that promotes a normal nutritional status through the intake of appropriate nutrients that favour successful aging. A cross-sectional analytical study was performed on a sample of 118 older adults. Food intake was measured using a 24-h recall questionnaire. The body mass index was used to evaluate the nutritional status. The information was analysed using uni- and bivariate descriptive statistics. Given the abnormal distribution of the responses, the Mann-Whitney and Kolgomorov-Smirnov statistical test were used to compare data at the significance level α=0.05. More than half (55%) of the women and 61% of men had a normal nutritional status. The calories and macronutrient intake were within the recommended ranges and unrelated to the nutritional status (P>.05). The micronutrients showed significant differences in relation to the nutritional status, broken down by gender and age, in the majority of vitamins and minerals. (P>.01). The group between 75-90 years old accomplished the recommended dietary allowance in every case. The active participation in organised community groups, the educational level of the older adults, and higher income, could be key factors to explain the good nutritional status of the group, and appears to be a good indicator of healthy aging.


Dimensions of suicidal behavior according to patient reports.
Five factor analyses with limitations explored the Suicidal Intent Scale (SIS) subscales reflecting suicidal behavior dimensions. This larger sample study conducts an exploratory factor analysis of the SIS. Two large samples of suicide attempters (N= 435 and N= 252) from a general hospital were studied. The validity of SIS subscales obtained from the factor analysis was investigated by examining the association between the subscales and clinical variables. There were two factors: expected lethality and planning. In both samples, male gender and depression tended to be associated with higher scores in both subscales (small to medium effect sizes). Hospitalization was associated with higher scores in both SIS subscales (medium to large effects) suggesting that these subscales were reasonably good predictors of suicide attempt severity. Clinicians assessing patient reports to establish the severity of suicide attempts need to ask questions regarding both dimensions: expected lethality and planning.


Presenting symptoms of women with depression in an obstetrics and gynecology setting.
To describe the presenting symptoms of women with depression in two obstetrics and gynecology clinics, determine depression diagnosis frequency, and examine factors associated with depression diagnosis. Data were extracted from charts of women screening positive for depression in a clinical trial testing a collaborative care depression intervention. Bivariate and multivariable analyses examined patient factors associated with the diagnosis of depression by an obstetrician-gynecologist (ob-gyn). Eleven percent of women with depression presented with a psychologic chief complaint but another 30% mentioned psychologic distress. All others noted physical symptoms only or presented for preventive care. Ob-gyns did not identify 60% of women with a depression diagnosis. Depression severity was similar in women who were or were not diagnosed by their ob-gyns. Bivariate analyses showed four factors significantly associated with depression diagnosis: reporting a psychologic symptom as the chief complaint or associated symptom (72% compared with 18.6%, P<.001), younger age (35.5 years compared with 40.8 years, P<.005), being within 12 months postpartum (13.9% compared with 2.8%, P<.005), and a primary care-oriented visit (72% compared with 30%, P<.001). Multivariable analysis showed that reporting a psychologic symptom (adjusted odds ratio [OR] 8.90, 95% confidence interval [CI] 4.15-19.10, P<.001), a primary care oriented visit (adjusted OR 2.46, 95% CI 1.14-5.29, P=.03), and each year of increasing age (adjusted OR 0.96, 95% CI 0.93-0.96, P=.02) were significantly associated with a depression diagnosis. The majority of women with depression presented with physical symptoms; most women with depression were not diagnosed by their ob-gyn, and depression severity was similar in those diagnosed and those not diagnosed. III.


Hibiscus rosa-sinensis Forage as a Potential Feed for Animals: A Review.
This review summarized for the first time the nutritional benefits of Hibiscus rosa-sinensis in animal feed. the agronomic characteristics for the hyperproduction of Hibiscus rosa-sinensis were reported, as well as the chemical composition of the forage meal (leaves + petioles + stems), with emphasis on crude protein, amino acids, minerals, neutral detergent fiber, acid detergent fiber, lignin detergent acid, secondary metabolites, and metabolizable energy for ruminants and non-ruminants. Additionally, their medicinal properties such as antimicrobial, antifungal, antiparasitic, antioxidant, anti-inflammatory, antidiarrheal, and antipyretic properties were detailed. Its use as a source of protein in ruminant feeding is attractive and can be combined with grasses. In rabbits, fresh forage in high concentrations in the diets reduces the feed palatability, which causes a decrease in animal response, although it depends on the forage quality. In addition, limits for Hibiscus rosa-sinensis forage were recommended in diets or feeding systems for poultry, pigs, rabbits, goats, and sheep.


Graft size alone should not affect donors selection and be used to predict the prognosis of recipients after living donor liver transplantation.
Graft size is recognized as one of the most important factors that affect prognosis of the liver recipients. This study determines whether the graft to recipient weight ratio (GRWR) alone can be used to select the liver donor and as an outcome predictor before living donor liver transplantation (LDLT). LDLT patients (202) were divided into three groups according to the GRWR: Group S (n=46, GRWR <0.8); Group M (n=83, GRWR 0.8-1.0); Group L (n=73, GRWR >1.0). Recovery of graft function, incidence of small-for-size syndrome and rate of complications were compared among the three groups. There were no significant differences in the baseline characteristics in both the donors and recipients, nor in the intensive care unit stay hours, re-operation rate, hospital stay after operation, Clavien System score and recovery of graft function after transplantation, among the three groups. The small-for-size syndrome rates were 13%, 7.23% and 11% in Groups S, M and B, and no significant difference was noted among the three groups. GRWR may not be the only factor affecting recipient prognosis after LDLT. Local graft dysfunction such as impaired venous outflow, severity of disease and portal hyperperfusion in the recipient, and fatty liver in donor may influence the graft and thus the prognosis of transplantation.


Reconnecting with nature for sustainability.
Calls for humanity to 'reconnect to nature' have grown increasingly louder from both scholars and civil society. Yet, there is relatively little coherence about what reconnecting to nature means, why it should happen and how it can be achieved. We present a conceptual framework to organise existing literature and direct future research on human-nature connections. Five types of connections to nature are identified: material, experiential, cognitive, emotional, and philosophical. These various types have been presented as causes, consequences, or treatments of social and environmental problems. From this conceptual base, we discuss how reconnecting people with nature can function as a treatment for the global environmental crisis. Adopting a social-ecological systems perspective, we draw upon the emerging concept of 'leverage points'-places in complex systems to intervene to generate change-and explore examples of how actions to reconnect people with nature can help transform society towards sustainability.


Magnetic resonance imaging of head and neck tumors.
Magnetic resonance imaging has revolutionized the imaging of head and neck malignancies and is now rapidly replacing computed tomography as the study of choice in the majority of lesions in the head, neck, larynx, hypopharynx, oropharynx, paranasal sinuses, paranasopharynx, and skull base. CT scanning can be used in the same region; however, inflammation obtained in CT is not as clearly demonstrated and in some situations, such as malignancies of the tongue, the lesions may be missed entirely. There are still occasional difficult clinical problems when the two studies are complementary, but this situation will definitely be rare.


Pneumococcal meningitis in a pediatric intensive care unit: prognostic factors in a series of 49 children.
Despite advances in antibiotic therapy strategies and in pediatric intensive care, prognosis of Streptococcus pneumoniae meningitis remains very poor. However, few prognostic studies have been published, especially in pediatric populations. We conducted a prognostic study to determine the factors associated with hospital mortality of 49 children admitted in a single pediatric intensive care unit during a 12-yr period (1990-2002). Hospital mortality was 49% (24 of 49 patients), and neurologic sequels were observed in 47% of survivors. Among them, 90% had permanent sensory deafness. Based on univariable analyses, seven variables were associated with the outcome: Pediatric Risk of Mortality II score (p = .000005), Glasgow Coma Score of >8 (p = .001), use of mechanical ventilation (p = .001), platelet count (p = .007), white blood cells count (p = .002), cerebrospinal fluid glucose level (p = .02), and lack of corticosteroids use (p = .02). In multivariable analysis, only three factors were independently associated with in-hospital mortality: Pediatric Risk of Mortality II score (hazard ratio, 1.13; 95% confidence interval, 1.06-1.20; p = .0002), platelets count of >200 x 10/L (hazard ratio, 0.25; 95% confidence interval, 0.08-0.81; p = .021) and white blood cell count above 5 x 10/L (hazard ratio, 0.31; 95% confidence interval, 0.11-0.87; p = .026). S. pneumoniae meningitis remains a devastating childhood disease in developed countries. Three variables were independently associated with the in-hospital death in our series-high Pediatric Risk of Mortality II score, low white blood cells count, and low platelet count-reflecting the main importance of severe sepsis and neurologic presentation in establishing the prognosis of these patients.


Prognostic value of the expression of p53 and bcl-2 in patients with laryngeal carcinoma.
Previous studies have yielded inconsistent results on the prognostic significance of p53 and bcl-2 in head and neck cancer. The aim of this study was the evaluation of p53 and bcl-2 protein expression in laryngeal squamous cell carcinoma and to clarify the relationship between them. All patients with laryngeal carcinoma were treated during the period 1991-1993. In the present study p53 and bcl-2 expression in paraffin sections from 50 cases of laryngeal squamous cell carcinoma were analysed and correlated with routine clinico-pathological parameters. The expressions of p53 and bcl-2 were examined by immunohistochemical staining. Immunoreactivity for p53 was observed in 45 (90%) of carcinomas and bcl-2 immunoreactivity in 7 (14%). No significant correlation between the p53 or bcl-2 expression and patients' T- or N-stage, histological grading, or overall survival was found.


Adaptations in the mesoaccumbens dopamine system resulting from repeated administration of dopamine D1 and D2 receptor-selective agonists: relevance to cocaine sensitization.
The mesoaccumbens dopamine (DA) system is intricately involved in sensitization to the locomotor stimulant effects of cocaine. Among the adaptations implicated in cocaine sensitization are transient subsensitivity of impulse-regulating DA D2 autoreceptors on ventral tegmental area (VTA) DA neurons leading to hyperactivity of the mesoaccumbens DA pathway, and persistently enhanced DA D1 receptor responses of nucleus accumbens (NAc) neurons. We have tested the hypothesis that both of these adaptations are necessary to produce cocaine sensitization. We injected rats twice daily for 2 weeks with the selective DA D1 class receptor agonist SKF 38393, the DA D2 class receptor agonist quinpirole, or both. We then used single-cell recording procedures to determine possible alterations in VTA DA autoreceptor sensitivity and NAc D1 receptor sensitivity at three withdrawal times: 1 day, 1 week and 1 month. We also tested whether these treatments produced cross-sensitization to cocaine at each withdrawal time. Repeated quinpirole treatment produced a reduction in VTA autoreceptor sensitivity and cross-sensitization to cocaine, but these effects lasted for less than 1 week. Repeated SKF 38393 treatment produced enhanced NAc D1 responses which lasted for 1 week and cross-sensitization to cocaine which was only evident after 1 week of withdrawal. Repeated treatment with the combination of the two agonists transiently down-regulated autoreceptor sensitivity, enhanced and prolonged D1 receptor supersensitivity (lasting 1 month), and produced enduring cross-sensitization to cocaine. These results suggest that neuroadaptations within both the VTA and NAc may be necessary for the induction of enduring cocaine sensitization.


A 2000 gm tubal pregnancy.
A multigravid patient in Papua New Guinea had a fetal death at 33 weeks' gestation. After nine attempts at induction of labor failed, a laparotomy revealed that the 2000 gm fetus was enclosed in the midsegment of the left Fallopian tube.


Genetic diversity underlying capsaicin intake in the Mishima battery of mouse strains.
Capsaicin is the active substance responsible for the pungent sensation produced by red pepper. In order to approach the underlying genetic mechanism for preference of red pepper, we conducted a 12-h, 1-bottle intake test of capsaicin solution using both male and female animals from the Mishima battery of mouse strains: 10 wild-derived inbred strains (PGN2, BFM/2, HMI, CAST/Ei, NJL, BLG2, CHD, SWN, KJR, MSM), 1 strain derived from the so-called fancy mouse (JF1), and 3 widely used laboratory strains (C57BL/6J, DBA/1J and BALB/cAnN). The concentration of capsaicin was increased from 0.5 to 15 microM successively. Gender differences were not observed in this test, but we found striking strain differences in capsaicin intake. Relative to baseline water intake, C57BL/6J and DBA/1J consumed 10%, whereas two wild strains, KJR and MSM, ingested approximately 60% of the 15-microM capsaicin solution. In a 2-bottle fluid preference test, both C57BL/6J and MSM strains reject capsaicin fluid even at the 0.5-microM concentration, which indicates that the receptors for capsaicin in these strains recognize capsaicin at a similar level. Thus, the strain differences at higher capsaicin concentrations in the 1-bottle test may reflect differences in central nervous system response to the capsaicin solution. The genetic difference in intake of capsaicin observed in these strains may provide a useful tool for identifying genes underlying response to red pepper in mice and other mammalian species.


Wegener's granulomatosis: report of a case with rapidly progressive glomerulonephritis and diabetes mellitus.
A patient with the classic form of Wegener's granulomatosis with severe dabetes mellitus and rapidly progressive glomerulonephritis is described. This 61-year-old male presented with epistaxis and nasal pain and obstruction. The nasal cavities were filled with crusts covering eroded mucosa. The diagnosis was made by biopsy of nasal and bronchial mucosa, and laboratory data. The epistaxis was stopped by 10 Gy irradiation over the nasal cavities. The patient had severe diabetes mellitus. His blood sugar was not controlled by diet and insulin injection. His general condition worsened rapidly as the growth of granuloma in the nose and lung. Accordingly, prednisolone therapy reinitiated to suppress the granuloma although it has a reverse effect on diabetes mellitus. Approximately one month after admission, he died of acute renal failure. Autopsy was carried out. Granulomatous lesions were noted in the nasal cavities, lungs and spleen. Many petechiae were found macroscopically over the cortex of the kidney. Hyalinization or sclerosis with crescent formation was found microscopically in estimated 85% of the glomeruli. Immunohistologic analysis of the renal tissue demonstrated an irregular linear pattern deposition of IgG, IgA and C3 and a granular pattern deposition of IgM and C1q.


Microfat and Lipoconcentrate for the Treatment of Facial Scars.
Fat grafting is as a unique regenerative filler with soluble factors and progenitor cells that may remodel scar tissue in an easy yet effective way. A combination of microfat grafting, lipococoncentrate injection, scar subcision, and platelet-rich plasma supplementation may be used to treat the majority of facial scars. The lipoconcentrate technique condenses the lipoaspirate to a progenitor cell-rich fluid of low volume by a combination of centrifugation and emulsification steps. In this article, the authors' methods for scar treatment by fat grafting are discussed. Choice of technique for facial scars, precise indications, and contraindications are introduced.


Disease activity in women with ankylosing spondylitis remains higher under Tumour Necrosis Factor inhibitor treatment than in men: a five-year observational study.
To assess sex differences in response, level of disease activity, and drug survival in tumour necrosis factor inhibitor (TNFi)-naïve ankylosing spondylitis (AS) patients. Consecutive AS patients, fulfilling the modified New York criteria, were included in a prospective cohort study at initiation of the first TNFi and followed until this medication was stopped (drug survival). Disease activity scores [AS Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), and CRP] were measured at 3, 6, and 12 months, and every subsequent year, up to 5 years. The response was defined by the ASDAS-CRP response criteria (clinically important improvement: ASDAS-CRP decrease ≥ 1.1). Analyses included regression methods for repeated measurements and survival analyses. Overall, 356 patients were included (34% women, mean ± sd age 46 ± 12 years), with a median disease duration of 12 (interquartile range 6;20) years. Women were less likely than men to achieve a clinically important response after 6 months of TNFi treatment (47% vs 64%; relative risk 1.4, 95% confidence interval (CI) 1.1;1.9, p = 0.02], despite a lack of sex differences in mean ASDAS-CRP levels over 5 year follow-up. Adjusted models for BASDAI over 5 years showed that women had a 0.6 point higher BASDAI score than men (β = 0.6 0.1;1.1 <0.02). Numerically, more women than men discontinued treatment over a period of 5 years (hazard ratio = 1.5, 95% CI 0.9;2.5, p = 0.15). Female AS patients show a lower response to TNFi and a higher disease activity compared to men.


Highly sensitive and selective cartap nanosensor based on luminescence resonance energy transfer between NaYF4:Yb,Ho nanocrystals and gold nanoparticles.
Fluorescent detection is an attractive method for the detection of toxic chemicals. However, most chemosensors that are currently utilized in fluorescent detection are based on organic dyes or quantum dots, which suffer from instability, high background noise and interference from organic impurities in solution, which can also be excited by UV radiation. In the present research, we developed a novel NaYF4:Yb,Ho/Au nanocomposite-based chemosensor with high sensitivity (10 ppb) and selectivity over competing analytes for the detection of the insecticide cartap. This nanosensor is excited with a 970-nm laser instead of UV radiation to give an emission peak at 541 nm. In the presence of cartap, the nanocomposites aggregate, resulting in enhanced luminescence resonance energy transfer between the NaYF4:Yb,Ho nanocrystals and the gold nanoparticles, which decreases the emission intensity at 541 nm. The relative luminescence intensity at 541 nm has a linear relationship with the concentration of cartap in the solution. Based on this behavior, the developed nanosensor successfully detected cartap in farm produce and water samples with satisfactory results.


Endoscopic-Assisted Abdominoplasty.
Advantages of standard endoscopic surgery include diminished incidence of scarring, numbness, bleeding, and edema, making endoscopic surgery preferable to the conventional suprapubic approach. Endoscopic-assisted abdominoplasty can also treat diastasis recti deformity with minimal excess skin. For enhanced results, a learning curve is expected to achieve optimal technical expertise.


Eggplant (Solanum melongena L.) polyphenol oxidase multi-gene family: a phylogenetic evaluation.
Polyphenol oxidases (PPOs) in different Solanum species including eggplant have been studied. PPOs have been implicated in undesirable enzymatic browning of eggplant fruit and also in plant defense. The main objective of this study was to identify and accelerate the further functional characterization of additional eggplant PPOs that are involved in food biochemistry and defense-related functions. Eggplant PPOs identified earlier were used in "Basic local alignment search tool (BLAST)" search against expressed sequence tag and nucleotide databases. We have identified seven additional sequences which were almost complete in length. The sequences of the PPOs were aligned and their phylogenetic and evolutionary relationships established. The sequences are quite diverse, broadly falling into two major clusters; three PPOs form a separate branch/minor cluster. The thirteen sequences had conserved copper A binding sites but copper B binding sites differed considerably in two new PPO sequences (AFJ79642 and ACR61398). A third conserved 'Histidine-rich' region has been identified at the 'C' terminus of the eggplant PPOs. In addition, all the seven new PPOs exhibited at least one glycosylated sequon in the mature PPO sequence. Identification of additional PPO genes will further help in functional and biological characterization of these PPOs.


Functions of long non-coding RNA ROR in patient-derived glioblastoma cells.
Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer in adult patients. A variety of long non-coding RNAs play an important role in the pathogenesis of GBM, however the molecular functions of most of them still remain elusive. Here, we investigated linc-RoR (long intergenic non-protein coding RNA, regulator of reprogramming) using GBM neurospheres obtained from 12 different patients. We demonstrated that the highest level of this transcript is detected in cells with increased EGFR expression. According to our data, linc-RoR knockdown decreases cell proliferation, increases sensitivity to DNA damage, and downregulates the level of cancer stem cell (CSC) markers. On the other hand, linc-RoR overexpression promote cell growth and increases the proportion of CSCs. Analysis of RNA sequencing data revealed that linc-RoR affects expression of genes involved in the regulation of mitosis. In agreement with this observation, we have showen that the highest level of linc-RoR is detected in the G2/M phase of the cell cycle, when linc-RoR is localized on the chromosomes of dividing cells. Based on our results, we can propose that linc-RoR performs pro-oncogenic functions in human gliobalstoma cells, which may be associated with the regulation of mitotic progression and GBM stemness.


Metabolic and therapeutic assessment of gestational diabetes by two-hour and twenty-four-hour isocaloric meal tolerance tests.
Lean and obese women with gestational diabetes (GDM) were given two different isocaloric meal challenge tests to assess glucose and insulin responses. Forty-three pregnant women received a 400-kcal isocaloric breakfast meal tolerance test (mini-MTT). Twenty of the subjects were also given a 2000-kcal isocaloric diet with three meals and three snacks during a 24-h period (maxi-MTT). This was the first study to utilize the physiologic challenge of mixed meals to compare insulin and glucose responses of both obese and lean normal pregnant women and women with GDM around the clock. Normal obese pregnant women had higher integrated glucose and insulin values around the 24-h clock (P less than 0.003 and less than 0.03, respectively) than lean pregnant women. Lean and obese women with GDM also responded differently to the physiologic challenge of mixed meals. Some, but not all, obese diabetic subjects were markedly hyperinsulinemic in contrast to lean diabetic women who were relatively insulin deficient. One normoglycemic massively obese 18-yr-old pregnant woman was unexpectedly found to be severely hyperinsulinemic. The two meal tolerance tests clearly defined a delay in the release of insulin in women with GDM (lean and obese) and markedly different quantitative insulin responses to identical meal challenges in obese diabetic subjects. Maternal hyperinsulinemia was positively correlated with prepregnancy body mass index (kg/m2) and heavier infants, but not with plasma glucose levels. These studies provide evidence that GDM is a heterogeneous syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacokinetics of inhaled salbutamol in patients with cystic fibrosis versus healthy young adults.
We studied the disposition of inhaled salbutamol in adolescents with cystic fibrosis (CF) and compared it with the pharmacokinetics of the drug given by the intravenous and inhaled routes in healthy adults. After inhalation of salbutamol, CF patients had a significantly larger area under the concentration-time curve derived from amounts of drug in the systemic circulation. The differences in serum concentration of salbutamol were not reflected in differences in change of heart rate. We conclude that the rate and extent of pulmonary absorption of inhaled salbutamol in patients with CF differ from those in healthy adults.


Examining the value of body gestures in social reward contexts.
Brain regions associated with the processing of tangible rewards (such as money, food, or sex) are also involved in anticipating social rewards and avoiding social punishment. To date, studies investigating the neural underpinnings of social reward have presented feedback via static or dynamic displays of faces to participants. However, research demonstrates that participants find another type of social stimulus, namely, biological motion, rewarding as well, and exert effort to engage with this type of stimulus. Here we examine whether feedback presented via body gestures in the absence of facial cues also acts as a rewarding stimulus and recruits reward-related brain regions. To achieve this, we investigated the neural underpinnings of anticipating social reward and avoiding social disapproval presented via gestures alone, using a social incentive delay task. As predicted, the anticipation of social reward and avoidance of social disapproval engaged reward-related brain regions, including the nucleus accumbens, in a manner similar to previous studies' reports of feedback presented via faces and money. This study provides the first evidence that human body motion alone engages brain regions associated with reward processing in a similar manner to other social (i.e. faces) and non-social (i.e. money) rewards. The findings advance our understanding of social motivation in human perception and behavior.


Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.
Chloride channel-3 (ClC-3) Cl-/H+ antiporters and leucine-rich repeat-containing 8 (LRRC8) family anion channels have both been associated with volume-regulated anion currents (VRACs). VRACs are often altered in ClC-3 null cells but are absent in LRRC8A null cells. To explore the relationship between ClC-3, LRRC8A, and VRAC we localized tagged proteins in human epithelial kidney (HEK293) cells using multimodal microscopy. Expression of ClC-3-GFP induced large multivesicular bodies (MVBs) with ClC-3 in the delimiting membrane. LRRC8A-RFP localized to the plasma membrane and to small cytoplasmic vesicles. Co-expression demonstrated co-localization in small, highly mobile cytoplasmic vesicles that associated with the early endosomal marker Rab5A. However, most of the small LRRC8A-positive vesicles were constrained within large MVBs with abundant ClC-3 in the delimiting membrane. Dominant negative (S34A) Rab5A prevented ClC-3 overexpression from creating enlarged MVBs, while constitutively active (Q79L) Rab5A enhanced this phenotype. Thus, ClC-3 and LRRC8A are endocytosed together but independently sorted in Rab5A MVBs. Subsequently, LRRC8A-labeled vesicles were sorted to MVBs labeled by Rab27A and B exosomal compartment markers, but not to Rab11 recycling endosomes. VRAC currents were significantly larger in ClC-3 null HEK293 cells. This work demonstrates dependence of LRRC8A trafficking on ClC-3 which may explain the association between ClC-3 and VRACs.


Speciation: don't fly and diversify?
Loss of flight in Japanese carrion beetles is correlated with greater population subdivision and higher speciation rate. This reveals the complex relationship of trait evolution with dispersal power, range size and diversification.


State of the art and future prospects of the biological control of postharvest fruit diseases.
Synthetic fungicides are the primary means to control postharvest diseases of fruits. Biological control has emerged as one of the most promising alternatives to chemicals. During the last 20 years, several biological control agents have been widely investigated for use on different pathogens and fruit crops. Many biological control mechanisms have been suggested for use on fruit including antibiosis, parasitism, induced resistance in the host tissue and competition. With the aim of extending the use of the biofungicides, there have been many studies on the application of various combinations of control agents, and on the application integrated with chemical and physical means of protection. The formulation and application methods are key issues for the efficacy and successful outcome of the commercial product. Genetic engineering may provide a useful tool in the enhancement of the biological control efficacy. Since biofungicides are usually not as effective as pesticides, this approach should be viewed as an important component of an integrated disease management scheme given that a significant and permanent reduction of pesticide use is our goal.


Iatrogenic renal artery thrombosis.
Renal calculi were removed from 2 women--in 1 case by renal bisection and in the other by nephrolithotomy. In each case a small bulldog clamp was applied to the renal artery for less than 30 minutes. Both patients suffered renal artery thrombosis necessitating nephrectomy. When the histories of these patients were reviewed the common factor found was oral contraceptives, suggesting that oral contraceptives may predispose to renal artery thrombosis.


Explorative study on the expression of neuregulin-1 gene in peripheral blood of schizophrenia.
Neuregulin-1 (Nrg-1)(1) gene has been considered as a schizophrenia susceptibility gene. In order to observe the association of Nrg-1 gene with schizophrenia, the study was designed to investigate the effect of anti-psychotic treatment on the Nrg-1 mRNA expression in peripheral blood lymphocytes of the patients with a diagnosis of schizophrenia. The Nrg-1 mRNA expression in peripheral blood lymphocytes (PBLs) was measured by using semi-quantitative RT-PCR in 31 first-onset schizophrenia patients, 16 sibling controls and 31 no-sibship controls. Results showed that Nrg-1 mRNA expression in PBLs of patients was lower than that in other two control groups (F=6.722, P=0.002). However, as follow-up time extended, from the second week, Nrg-1 mRNA expression of PBLs in antipsychotic treated patients gradually increased and has obvious statistical significance compared the efficacy of taking anti-psychotic before and after therapy. These results demonstrated that Nrg-1 gene has association with schizophrenia. It is possible to select Nrg-1 mRNA expression of PBLs in schizophrenia patients as a potential therapeutic marker.


[Does measuring axillo-rectal temperature difference help in the diagnosis of acute appendicitis?].
The value of the axillorectal temperature difference in the diagnosis of acute appendicitis was estimated with the aid of statistical methods. The axillorectal temperature difference turned out to be of very low discriminant ability between acute appendicitis and non-acute conditions.


Uncovering the invisible-prevalence, characteristics, and radiomics feature-based detection of visually undetectable intraprostatic tumor lesions in 68GaPSMA-11 PET images of patients with primary prostate cancer.
Primary prostate cancer (PCa) can be visualized on prostate-specific membrane antigen positron emission tomography (PSMA-PET) with high accuracy. However, intraprostatic lesions may be missed by visual PSMA-PET interpretation. In this work, we quantified and characterized the intraprostatic lesions which have been missed by visual PSMA-PET image interpretation. In addition, we investigated whether PSMA-PET-derived radiomics features (RFs) could detect these lesions. This study consists of two cohorts of primary PCa patients: a prospective training cohort (n = 20) and an external validation cohort (n = 52). All patients underwent 68Ga-PSMA-11 PET/CT and histology sections were obtained after surgery. PCa lesions missed by visual PET image interpretation were counted and their International Society of Urological Pathology score (ISUP) was obtained. Finally, 154 RFs were derived from the PET images and the discriminative power to differentiate between prostates with or without visually undetectable lesions was assessed and areas under the receiver-operating curve (ROC-AUC) as well as sensitivities/specificities were calculated. In the training cohort, visual PET image interpretation missed 134 tumor lesions in 60% (12/20) of the patients, and of these patients, 75% had clinically significant (ISUP > 1) PCa. The median diameter of the missed lesions was 2.2 mm (range: 1-6). Standard clinical parameters like the NCCN risk group were equally distributed between patients with and without visually missed lesions (p < 0.05). Two RFs (local binary pattern (LBP) size-zone non-uniformality normalized and LBP small-area emphasis) were found to perform excellently in visually unknown PCa detection (Mann-Whitney U: p < 0.01, ROC-AUC: ≥ 0.93). In the validation cohort, PCa was missed in 50% (26/52) of the patients and 77% of these patients possessed clinically significant PCa. The sensitivities of both RFs in the validation cohort were ≥ 0.8. Visual PSMA-PET image interpretation may miss small but clinically significant PCa in a relevant number of patients and RFs can be implemented to uncover them. This could be used for guiding personalized treatments.


Techniques for epicardial mapping and ablation with a miniature robotic walker.
Present treatments for ventricular tachycardia have significant drawbacks. To ameliorate these drawbacks, it may be advantageous to employ an epicardial robotic walker that performs mapping and ablation with precise control of needle insertion depth. This paper examines the feasibility of such a system. This paper describes techniques for epicardial mapping and depth-controlled ablation with the robotic walker. The mapping technique developed for the current form of the system uses a single equivalent moving dipole model combined with the navigation capability of the walker. The intervention technique provides saline-enhanced radio frequency ablation, with sensing of needle penetration depth. The mapping technique was demonstrated in an artificial heart model with a simulated arrhythmia focus, followed by preliminary testing in the porcine model in vivo. The ablation technique was demonstrated in an artificial tissue model, and then in chicken breast tissue ex vivo. The walker located targets to within 2 mm using the SEMDM technique. No epicardial damage was found subsequent to the porcine trial in vivo. Needle insertion for ablation was controlled to within 2 mm of the target depth. Lesion size was repeatable, with diameter varying consistently in proportion to volume of saline injected. The experiments demonstrated the general feasibility of the techniques for mapping and depth-controlled ablation with the robotic walker.


[Congenital stenosis of interventricular foramina revealed by recurrent intracranial hypertension].
Non-tumoral stenosis of interventricular foramen is a rare clinical condition. It can be either unilateral, causing monoventricular hydrocephalus, or bilateral leading to biventricular hydrocephalus. The pathophysiology of this misdiagnosed entity remains controversial. The non-tumoral stenosis of interventricular foramen can be either acquired or congenital. The latter usually manifesting with a neonatal hydrocephalus. We report a case of congenital bilateral stenosis of interventricular foramen, in an 8-year-old girl, revealed by recurrent intracranial hypertension. Diagnosis was relied on 3D-CISS sequences MRI. The child showed full recovery after neuroendoscopic septal fenestration and ventriculo-peritoneal shunt.


Genome-Wide Analysis and Expression Profiling of DUF668 Genes in Glycine max under Salt Stress.
The DUF668 gene performs a critical role in mitigating the impact of abiotic stress factors. In this study, we identified 30 DUF668 genes in a soybean genome, distributed across fifteen chromosomes. The phylogenetic analysis classified the DUF668 genes into three groups (group I, group II, and group III). Interestingly, gene structure analysis illustrated that several GmDUF668 genes were without introns. Furthermore, the subcellular localization results suggested that GmDUF668 proteins were present in the nucleus, mitochondria, cytoplasm, and plasma membrane. GmDUF668 promoters were analyzed in silico to gain insight into the presence of regulatory sequences for TFs binding. The expression profiling illustrated that GmDUF668 genes showed expression in leaves, roots, nodules, and flowers. To investigate their response to salt stress, we utilized the RNA sequencing data of GmDUF668 genes. The results unveiled that GmDUF668-8, GmDUF668-20, and GmDUF668-30 genes were upregulated against salt stress treatment. We further validated these findings using qRT-PCR analysis. These findings provide a scientific basis to explore the functions of GmDUF668 genes against different stress conditions.


Ketamine promotes the amyloidogenic pathway by regulating endosomal pH.
Ketamine is an anesthetic and addictive drug that can cause cognitive dysfunction and neuroinflammation. Studies have shown that carboxy-terminal fragment derived from β-secretase (CTF-β) and amyloid beta (Aβ), the amyloidogenic products of amyloid precursor protein (APP), can also induce neuroinflammation and impair cognitive function. However, it remains unclear whether ketamine regulates the amyloidogenic pathway. In the endosome, APP is cleaved by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), whose activity is influenced by pH. Endosomal acidification is mainly regulated by sodium hydrogen exchanger 6 (NHE6), which leaks protons out of endosomes, and vacuolar proton translocating ATPases (V-ATPase), which pump protons into endosomes. Therefore, we hypothesized that ketamine lowers the endosomal pH by reducing the endosomal NHE6 protein level, and this hyperacidification promotes the amyloidogenic pathway. We set up C57BL/6 J mouse models using 10, 20, 40, 80, and 100 mg/kg ketamine administration and SH-SY5Y cell models using 1, 10, 100, and 1000 μM ketamine administration to investigate its effects on the amyloidogenic pathway at different doses. Western blotting results showed that 100 mg/kg ketamine treatment in vivo and 1000 μM ketamine treatment in vitro increased endosomal BACE1 and CTF-β protein levels and reduced endosomal NHE6 and APP protein levels. The endosomal accumulation of BACE1 caused by ketamine administration was also observed using confocal imaging. Moreover, flow cytometry indicated that ketamine treatment lowered the endosomal pH value of SH-SY5Y cells. Later, cells were pretreated with monensin to restore the endosomal pH. Monensin did not affect amyloidogenic-related proteins or NHE6 directly; therefore, ketamine-promoted endosomal amyloidogenic processing and BACE1 accumulation were depleted by restoring endosomal acidity through monensin pretreatment. Finally, knockdown of NHE6 promoted the amyloidogenic pathway similarly and prevented further enhancement by ketamine. These results indicated that the effects of ketamine on the amyloidogenic pathway were dependent on the reduction of NHE6 and endosomal pH.


Structural, optical, and cytotoxicity studies of laser irradiated ZnO doped borate bioactive glasses.
Borate glasses (BG) doped with different amounts of ZnO (0-0.6 mol%) were formed by the traditional melt quenching technique. The different glasses so made were characterized using different characterization techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and UV-Vis absorption optical properties. The XRD patterns showed an amorphous structure with one broad peak at 2θ = 29°, while the phonons bands were studied in terms of the FTIR bands. Optical properties of the glasses were studied using UV-Vis absorption spectra in the range 190-1100 nm, in which the prominent band lies at about 261.5 nm of peak position, from which the bandgab (Eg) was calculated from its edge using Tauc's plot, with Eg ~ 3.5 eV. The laser irradiation showed no significant changes in the absorption bands, despite a significant change observed in the amorphous behavior in the XRD pattern. The cell viability was performed for two samples of the BG and 0.6 mol% ZnO doped using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay method. The result showed better cell viability and low toxicity. So, ZnO doped BG can be used in various biomedical applications.


Alteration of dopamine metabolites in CSF and behavioral impairments induced by neonatal hippocampal lesions.
Alterations of monoamine metabolites in CSF and behavioral abnormalities were studied in rats with neonatal hippocampal lesions and controls. Lesions of the ventral hippocampus were produced bilaterally by ibotenic acid on postnatal day 7. Lesion-induced neurochemical alterations and behavioral impairments were examined concurrently when rats were 12 weeks old. CSF from the cisterna magna was sampled repeatedly from freely moving rats. The levels of free 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in CSF were determined. An exposure to a novel environment induced hyperexploratory behavior and elevated the level of free DOPAC in CSF in lesioned rats. Although a swim stress increased the levels of free DOPAC and 5-HIAA in CSF in both control and lesioned groups, rats with hippocampal lesions had a further elevation of free DOPAC in CSF and greater spontaneous activity relative to controls shortly after stress. Amphetamine (1.5 mg/kg, i.p.) induced hyperlocomotion in lesioned rats compared to controls. For the control group, the levels of the three monoamine metabolites in CSF were not significantly influenced by amphetamine. However, for the lesioned group, the level of DOPAC significantly decreased compared to preinjection of amphetamine. The results indicate that neonatal hippocampal lesion-induced impairments can be manifested by behavioral and neurochemical abnormalities. Alterations of monoamine metabolites in CSF may be determined quantitatively and used as indices for monitoring lesion-impaired monoaminergic function in the central nervous system.


Detection of Haemophilus influenzae in middle ear of otitis media with effusion by polymerase chain reaction.
Otitis media with effusion (OME) is one of the major causes of hearing loss in childhood. The pathogenesis still remains unclear, though it is closely related to acute otitis media with bacterial infections. It is known that Haemophilus influenzae is one of the most common bacteria isolated from middle ear effusions (MEEs). Recently, in vitro DNA amplification by polymerase chain reaction (PCR) is a new technology that has considerable implication for diagnosis of viral and bacterial infections because of its potentially precise specificity and sensitivity. In the present experiment polymerase chain reaction (PCR) was applied to the detection of DNA genome of H. influenzae contained in middle ear effusions. By Southern blot hybridization, two characteristic bands for H. influenzae DNA were detected at 273 b.p. and 550 b.p. position in 15 of 27 MEEs. However, no organism was cultured by conventional methods. Our results indicate the PCR technique is more specific and sensitive in detection of bacteria in middle ear effusion of OME, compared with conventional methods. It strongly suggests more involvement of the bacteria, especially H. influenzae, in OME onset.


Localization of enkephalins in adrenaline cells and the nerves innervating adrenaline cells in rat adrenal medulla.
The coexistence of met5- and leu5-enkephalin-like immunoreactivities with catecholamines in the rat adrenal medulla was studied with combined fluorescence microscopy and immunocytochemistry. Both met5- and leu5-enkephalin-like immunoreactivities were localized in few heavily stained adrenaline cells and in a population of nerves innervating adrenaline cells and as well as ganglion cells among the adrenaline cells. Only occasionally single noradrenaline cells exhibited light immunostaining for both enkephalins but no positive fibers could be found around the noradrenaline cells. In electron microscope the immunoreaction was seen in the granules of the adrenaline cells and in the large synaptic vesicles of the nerve terminals around the adrenaline cells. The present findings suggest that enkephalin-like immunoreactivity coexists mainly with adrenaline in rat adrenal medulla and that the enkephalin immunoreactive terminals regulate secretion of adrenaline from rat adrenal medulla.


Intermittent fasting could ameliorate cognitive function against distress by regulation of inflammatory response pathway.
Undesirable and desirable effects of stressors on the body are assigned to distress and eustress, respectively. Immune system and brain are the most susceptible parts to stressful conditions, whereas long-lasting alterations in putative immune proteins involved in tension such as corticosterone (CORT), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) can impact learning and memory. Intermittent fasting (IF) is a repeated regular cycle of dietary restriction with well-known beneficial properties on the body. The aim of this study was to identify the eustress effects of IF on cognitive function by assessing the critical inflammatory factors in chronic distress. Forty male mice were divided into four groups (n = 10/group). Distress and control normally received food and water, whereas IF and IF with distress groups were daily deprived of food and water for two hours. In the second week, the electrical foot shock was induced to distress and IF with distress groups. Finally, the cognitive functions of all mice were evaluated by Barnes maze, their blood samples were taken to determine the plasma level of CORT, IL-6 and TNF-α, and the removed brain and adrenal glands were weighed in the third week. A significant gain in plasma level of CORT, IL-6 and TNF-α with a considerable brain hypotrophy and adrenal hypertrophy was found in distress group, whereas IF caused a remarkable reduction of the plasma inflammatory factors, especially in IF with distress mice (P ≤ 0.05). In conclusion, IF could improve cognitive function and preserve the brain against distress by regulation of inflammatory response pathway.


Contrast-enhanced ultrasound of breast tumors: an initial experience.
The increase of neoadjuvant treatment for breast cancer creates a capacity challenge as response evaluation by magnetic resonance imaging (MRI) is a limited resource. Contrast-enhanced ultrasound (CEUS) has been proposed as an alternative imaging strategy. To get experience with examination of malignant breast tumors with CEUS and evaluate the potential for future use in response evaluation of neoadjuvant treatment. In this pilot study, the dynamic contrast-enhancement of ultrasound and MRI examinations were analyzed in 14 women with histologically verified breast cancer. Analysis of the time intensity curve of CEUS demonstrated the difference between tumor and normal tissue. The peak intensity was five times higher in tumor tissue (mean increase 397%, 95% CI 250-545). The curve was steeper for tumor tissue (mean 1.76, 95% CI 1.26-2.26) than for normal tissue (mean 0.43, 95% CI 0.24-0.62). CEUS is a feasible method of examining blood flow in malignant breast tumors.


Stress test to STEMI: Utility of coronary CTA in the diagnosis and management of anomalous right coronary artery from the left coronary cusp.
A 42-year-old woman presented to the emergency department with chest pain. Acute coronary syndrome was ruled out. During dobutamine stress echocardiography (DSE), she developed chest pain and inferior ST elevation. Emergent coronary angiography revealed no culprit lesions but did show an anomalous right coronary artery (RCA). Coronary CT angiography (CCTA) confirmed an anomalous RCA arising from the left coronary cusp with a slit-like ostium and interarterial course (ARCA-LCC-IA). Herein, we review the extant literature on ARCA-LCC-IA, its clinical presentation, the vital role of CTA and MRI in its diagnosis, as well as challenges and controversies surrounding management.


Nitric oxide levels in brain, liver, and gills of silver catfish (Rhamdia quelen) exposed to the antiparasitic eprinomectin.
Nitric oxide (NO) is a mediator and biomarker of pro- and anti-inflammatory processes. Excessive levels of NO for long periods have been associated with inflammation and tissue damage. The metabolism and synthesis of NO is usually measured indirectly, as metabolites and enzymes involved in reactions, often as the nitrite/nitrate (NOx) level. The aim of the present study was to measure the NOx levels in vital organs of juvenile silver catfish (Rhamdia quelen) exposed to various levels of eprinomectin in the water. The fish were exposed for 24 and 48 h to start concentration (0 h) of eprinomectin in water (0.0, 1.12, 1.80, and 3.97 μg/L). The eprinomectin concentrations in water were lower at 24 h (0.0, 0.85, 1.14, and 1.15 μg/L) and 48 h (0.0, 0.39, 0.69, and 1.28 μg/L), due to the process of eprinomectin metabolization. Subsequently, the fish were left for 48 h of recovery in eprinomectin-free water. NO levels were measured indirectly, as NOx levels in brain, liver, and gill tissue. Within 24 h of exposure, there was no significant increase in NOx levels in the organs evaluated at any of the concentrations tested. However, increases in NOx levels did occur at 48 h of exposure in all organs, particularly at the two highest concentrations of eprinomectin (1.80 and 3.97 μg/L). The transfer of fish to eprinomectin-free water did not result in reversal of NOx levels after 48 h of recovery, especially in fish that had been exposed to the two highest concentrations in the brain and liver tissues, and for the highest concentration in the gills. We conclude that silver catfish exposed to eprinomectin for up to 48 h present possible cerebral, hepatic, and branchial inflammatory process associated with increased tissue NOx levels, and that recovery for 48 h in water without antiparasitic is insufficient for the fish to recover from the poisoning.


A Stable Cyclic (R2 SnAu)3 Anion Having In-Plane σ-Möbius Aromaticity.
A cyclic (R2 SnAu)3 anion (3- , R2 Sn=2,2,5,5-tetrakis(trimethylsilyl)-1-stannacyclopentane-1,1-diyl) has been synthesized as a stable blue salt with K+ (THF)6 through the reaction of stable dialkylstannylene 1 with R'3 PAuCl (R'=Et, Ph) followed by the reduction with KC8 . Crystallographic and NMR analysis shows that the six-membered (SnAu)3 ring of 3- is planar and highly symmetric with an equal distance of six Au-Sn bonds. A UV/Vis spectrum of 3- in hexane reveals an intense absorption maximum at 598 nm. While cyclic Au3 - with four valence electrons is known as unstable anti-aromatic anion, 3- with three divalent tin ligands is stable σ aromatic anion with an unprecedented Möbius orbital array as predicted by the perturbation MO and CCSD analysis of 3- .


Design of novel tripeptides with macrophage migration-enhancing activity.
A new approach to the generation of biologically active peptides from non-peptide lead was demonstrated. C,N-termini protected Phe-Phe-His derivatives possessing macrophage migration-enhancing activity were designed on the basis of the structure of imidazoline derivative 1, and these structure-activity relationships were also described.


Direct determination of molecular ratios of peptides coupled via N-succinimidyl 3-(2-pyridyldithio)propionate to carrier proteins using high performance liquid chromatography.
A simple, rapid and reproducible method is presented for direct determination of the substitution ratio of a carrier protein with a synthetic nonradioactively labeled peptide. The peptide was covalently linked by a thiol group of a cysteine residue to the immunogenic carrier protein using the heterobifunctional reagent N-succinimidyl 3-(2-pyridyldithio)propionate. The substitution ratio was determined after reductive cleavage of the intermolecular disulfide bond between peptide and carrier and the amount of carrier and peptide quantitated directly by calibrated HPLC analysis within 15 min.


[Reconstructive measures for toe deformity after compartment syndrome].
Compartment syndrome of the lower extremities has various etiologies. Patients suffer from toe deformity due to incorrect healing following compartment syndrome. They are restricted in their mobility as a result, even though the primary causes of the compartment syndrome in the lower extremities have long since healed. The toe deformities cannot be specifically attributed to compartment syndrome. Instead, they are a typical response to biomechanical changes in the foot. Following compartment syndrome, they are the result of a relative shortening of the tendons and a loss of function and contraction of the muscle; in patients with splay foot and flat foot, the toe deformity is caused by bone and connective tissue pathology. Identical surgical measures are used.


Nonlinear least-squares fitting methods.
This chapter provides an overview of the techniques involved in "fitting equations to experimental data" with a particular emphasis on the what can be learned with these techniques, what are the requirements of the experimental data for these techniques, and what are the underlying assumptions of these techniques. The layout of this chapter is to start with a set of experimental data, and then walk the reader through the analysis of this set of data. The rigorous mathematical methods are referenced but not presented in detail.


Non-invasive Method for Collection of Clarias magur Spermatozoa for Breeding.
Induced spawning is more inefficient in Clarias magur than in other fish species such as cyprinids and salmonids. Ovulation can be induced in the female C. magur by using pituitary extract or synthetic hormones. However, milt from the male C. magur cannot be obtained by hand stripping because the volume of seminal fluid in the testes is extremely low. Notably, similar problems are observed in other male catfishes such as C. gariepinus and C. lazera. Because milt from the males cannot be obtained for use in artificial fertilization of eggs, males are invariably sacrificed, and the testicular tissue is excised and macerated to obtain spermatozoa.•We developed an alternative approach that allowed harvesting of C. magur spermatozoa through surgery for artificial fertilization without sacrificing male fish.•The surgically obtained spermatozoa were used to inseminate C. magur eggs; the cross resulted in healthy progeny with a fertilization rate of 80%-98% and hatching of up to 85% of fertilized embryos; similar to those obtained using the conventional sacrificial approach (hatching percentage range of 45%-85%) [1].•This indicated the viability of partial surgical harvest of testicular tissue in seed production in C. magur for aquaculture without sacrificing male fish.


Simultaneous determination of l‑DOPA, l‑tyrosine and uric acid by cysteic acid - modified glassy carbon electrode.
Electrochemical oxidation of l‑cysteine resulted in the formation of a film on glassy carbon electrode. In a solution of levodopa (l‑DOPA), l‑tyrosine (Tyr) and uric acid (UA), three separated intense anodic peaks were appeared in differential pulse voltammetry regime. Experimental conditions were optimized for simultaneous determination of the three compounds. All experiments were carried out in phosphate buffer solution (0.1 M, pH 8). Calibration curves were obtained in the presence of various concentrations of l‑DOPA, Tyr, and UA. Linear concentration ranges were 0.65-22 μM for l‑DOPA, 3.5-96 μM for Tyr, and 1.0-19 μM for UA. The limits of detection (LODs) were calculated as 0.2, 1.1 and 0.36 μM for l‑DOPA, Tyr, and UA, respectively. The electrochemical sensor was used successfully for the simultaneous determination of l‑DOPA, Tyr, and UA species in human blood serum samples.