Pentosidine levels in nonproteinuric diabetes associated with both low estimated glomerular filtration rate and cataract.
The main objective of this study was to investigate whether plasma pentosidine levels were associated with cataract and low estimated glomerular filtration rate (eGFR) in nonproteinuric type 2 diabetic patients. We characterized 888 nonproteinuric type 2 diabetic patients residing in Singapore according to their eGFR values. Proteinuria was excluded on the basis of multiple urinalyses. Patients with low renal function (cases, n = 125) and controls (n = 763) were defined as having eGFR < and ≥60 mL/min/1.73 m(2), respectively. Pentosidine levels were measured by enzyme-linked immunosorbent assay. Multinomial logistic regression was used to test the association between plasma pentosidine levels and the joint phenotype of cataract and low eGFR. Cases had higher triacylglycerol values, higher systolic blood pressure, and were more likely to be treated with two or more antihypertensive medications. In univariate analysis, cases were potentially more than twice as likely to have had a history of cataract compared with controls. This association persisted in multivariate analyses after adjusting for the significant covariates, hypertension and triacylglycerol, but was attenuated when age was included in the model. Plasma pentosidine levels were significantly higher in cases with low eGFR who also had a history of cataract. This association persisted in multivariate analyses that included the covariates, glycosylated hemoglobin, hypertension, and diabetic retinopathy, as well as age. Carbonyl stress, as reflected by pentosidine levels, is present in a subset of nonproteinuric diabetic patients. Clinically, this stress was associated with the joint presence of cataract and low eGFR.


Urban stormwater runoff drives denitrifying community composition through changes in sediment texture and carbon content.
The export of nitrogen from urban catchments is a global problem, and denitrifying bacteria in stream ecosystems are critical for reducing in-stream N. However, the environmental factors that control the composition of denitrifying communities in streams are not well understood. We determined whether denitrifying community composition in sediments of nine streams on the eastern fringe of Melbourne, Australia was correlated with two measures of catchment urban impact: effective imperviousness (EI, the proportion of a catchment covered by impervious surfaces with direct connection to streams) or septic tank density (which affects stream water chemistry, particularly stream N concentrations). Denitrifying community structure was examined by comparing terminal restriction fragment length polymorphisms of nosZ genes in the sediments, as the nosZ gene codes for nitrous oxide reductase, the last step in the denitrification pathway. We also determined the chemical and physical characteristics of the streams that were best correlated with denitrifying community composition. EI was strongly correlated with community composition and sediment physical and chemical properties, while septic tank density was not. Sites with high EI were sandier, with less fine sediment and lower organic carbon content, higher sediment cations (calcium, sodium and magnesium) and water filterable reactive phosphorus concentrations. These were also the best small-scale environmental variables that explained denitrifying community composition. Among our study streams, which differed in the degree of urban stormwater impact, sediment grain size and carbon content are the most likely drivers of change in community composition. Denitrifying community composition is another in a long list of ecological indicators that suggest the profound degradation of streams is caused by urban stormwater runoff. While the relationships between denitrifying community composition and denitrification rates are yet to be unequivocally established, landscape-scale indices of environmental impact such as EI may prove to be useful indicators of change in microbial communities.


Effect of luteinizing hormone-induced prohibitin and matrix metalloproteinases on ovarian epithelial tumor cell proliferation.
Recent studies have suggested that elevated gonadotropins contribute to ovarian epithelial tumor (OET) cell proliferation. However, the cellular effects of luteinizing hormone, a member of gonadotropins, on OET proliferation are controversial. Our previous work showed that luteinizing hormone has no effect on cell proliferation, but the molecular mechanism of such finding remains to be clarified. Considering that the cell growth in various types of tumors has been associated with regulations of prohibitin and matrix metalloproteinases, we aim to investigate a possible regulatory role of luteinizing hormone on prohibitin and matrix metalloproteinases to determine the roles of these molecules in OET proliferation. We found that LH stimulation resulted in a dose-dependent expression of prohibitin and MMPs and time-dependent phosphorylations of ERK and AKT. Blocking MAPK or PI3K/AKT signaling could attenuate LH-induced prohibitin and MMPs expression. Additionally, the depletion of prohibitin reduced the level of MMPs expression, and increased prohibitin expression abolished the positive effect of LH-induced MMP-9 on cellular growth. Therefore, we conclude that LH is able to up-regulate both prohibitin and MMP-9 in OET cells without the cellular growth effect due to opposing biologic functions for cell proliferation between these two molecules. The opposing cellular growth function between prohibitin and MMP-9 is a novel finding. Regulation of either molecule may be useful for future targeted therapy for ovarian epithelial cancers.


[Positive pressure ventilation in Cheyne-Stokes respiration].
Cheyne-Stokes respiration (CSR) is found in patients with chronic left ventricular failure and associated with a reduced prognosis. Continuous positive airway pressure (CPAP) improves the survival rate. In this retrospective study we report on the effect of different positive pressure ventilation modes in CSR. The observation period lasted from 1995 - 1999. Inclusion criteria was CSR with a respiratory disturbance index > 10/h whereas > 50 % of the events had to be central and/or mixed. In each patient a 4 week lasting intervention with each of CPAP, Bilevel CPAP in spontan mode (i.e. BiPAP S or BiPAP ST) and BiPAP in controlled mode (i.e. BiPAP T) was performed. Responder were defined by subjective and objective criteria. In total 41 males were included. Responder were distributed as follows: CPAP: n = 13 patients (31.7 %), BiPAP S/ST: n = 9 patients (22.0 %) and BiPAP T: n = 12 patients (29.3 %). In total 7 from 41 patients (17.1 %) rejected a long-term treatment with positive pressure ventilation. The majority of patients with CSR responded to CPAP and BiPAP S/ST mode. Compared to the other responder groups the best quality was reached with BiPAP T. However the latter was performed only by 29 % of the population.


Liver-directed treatment modalities for primary and secondary hepatic tumors.
Colorectal cancer liver metastases and hepatocellular carcinoma remain significant health problems in the United States and worldwide. Although surgical resection is often the treatment of choice, patient comorbidities or disease extent may preclude this option. Alternative approaches to primary and secondary hepatic malignancies have been developed, and their impact on disease control has been the subject of much recent study. These therapies can be administered alone but can also be effective when used in combination, or with other chemotherapeutic regimens. This article reviews the different techniques of liver-directed therapy and the available literature on short- and long-term outcomes.


Translatability of rat kidney mRNA after mercury administration.
Young male rats received an intraperitoneal injection of 0.5 mg HgCl2/kg body weight and 16 h later the kidneys were removed and homogenized to prepare the polysomal fraction from which the poly(A)+ RNA was obtained. The activity of this fraction was assessed by translating the poly(A)+ RNA in a mRNA-dependent rabbit reticulocyte lysate and the activity was markedly elevated relative to preparations from control rat kidneys. The incorporation of labelled leucine and cysteine, but not phenylalanine, into a low molecular weight protein (approximately 10 000 as judged by denaturing polyacrylamide gel electrophoresis) accounted for the increased mRNA activity. The mobility during electrophoresis of the denatured labelled product and carboxymethylated product, as well as their acidic isoelectric points, provided evidence that it is metallothionein mRNA which exhibits increased translatability in preparations derived from mercury-treated rats.


Role of immature myeloid Gr-1+ cells in the development of antitumor immunity.
One of the mechanisms by which tumor cells evade the immune system is the lack of proper antigen-presenting cells. Improvement in host immunity against tumor cells can be achieved by promoting the differentiation of dendritic cells (DCs) from immature myeloid cells (Gr-1(+)Ly-6C(+)F4/80(+)) that accumulate in the bone marrow and lymphoid organs of mice with large tumor burdens. The enriched immature myeloid cells inhibit T-cell proliferation and tumor-specific T-cell response, which can be reversed by the differentiation of immature myeloid cells or depletion of F4/80(+) cells. Sorted Gr-1(+)/F4/80(+) immature myeloid cells differentiated into CD11c(+) cells that express CD80 and I-A/I-E (MHC class II) in the presence of recombinant murine granulocyte macrophage colony-stimulating factor (GM-CSF). Furthermore, intratumoral gene delivery of GM-CSF not only promoted the differentiation of carboxyfluoroscein succinimidyl ester-labeled immature myeloid cells into CD11c(+) cells with the characteristics of mature DCs (CD80(+), I-A/I-E(+)) but also enhanced innate natural killer and adaptive cytolytic T-cell activities in mice treated with interleukin (IL)-12 and anti-4-1BB combination therapy. More importantly, intratumoral delivery of GM-CSF and IL-12 genes in combination with 4-1BB costimulation greatly improved the long-term survival rate of mice bearing large tumors and eradicated the untreated existing hepatic tumor. The results suggest that inducing the maturation of immature myeloid cells, thus preventing their inhibitory activity and enhancing their antigen-presenting capability, by GM-CSF gene therapy is a critically important step in the development of effective antitumor responses in hosts with advanced tumors.


Transfusion in the absence of inflammation induces antigen-specific tolerance to murine RBCs.
Most human transfusion recipients fail to make detectable alloantibodies to foreign RBC antigens ("nonresponders"). Herein, we use a murine model to test the hypothesis that nonresponders may be immunologically tolerant. FVB mice transfused with RBCs expressing transgenic human glycophorin A (hGPA) antigen in the absence of inflammation produced undetectable levels of anti-hGPA immunoglobulins, unlike those transfused in the presence of polyinosinic:polycytidylic acid-induced inflammation. Mice in the nonresponder group failed to produce anti-hGPA after subsequent transfusions in the presence of polyinosinic:polycytidylic acid, whereas anti-hGPA levels increased in the responder group. This tolerance was antigen specific, because nonresponders to hGPA produced alloantibodies to RBCs that expressed a different transgenic antigen. This tolerance was not an idiosyncrasy of the hGPA antigen nor of the recipient strain, because B10.BR mice transfused with membrane-bound hen egg lysozyme antigen-transgenic RBCs also demonstrated induced nonresponsiveness. These data demonstrate that RBCs transfused in the absence of inflammation can induce tolerance.


Enhancing the image quality of blue light cystoscopy through green-hue correction and fogginess removal.
Blue light cystoscopy (BLC) is a guideline-recommended endoscopic tool to detect bladder cancer with high sensitivity. Having clear, high-quality images during cystoscopy is crucial to the sensitive, efficient detection of bladder tumors; yet, important diagnostic information is often missed or poorly visualized in images containing illumination artifacts or impacted by impurities in the bladder. In this study, we introduce computational methods to remove two common artifacts in images from BLC videos: green hue and fogginess. We also evaluate the effect of artifact removal on the perceptual quality of the BLC images through a survey study and computation of Blind/Referenceless Image Spatial Quality Evaluator scores on the original and enhanced images. We show that corrections and enhancements made to cystoscopy images resulted in a better viewing experience for clinicians during BLC imaging and reliably restored lost tissue features that were important for diagnostics. Incorporating these enhancements during clinical and OR procedures may lead to more comprehensive tumor detection, fewer missed tumors during TURBT procedures, more complete tumor resection and shorter procedure time. When used in off-line review of cystoscopy videos, it may also better guide surgical planning and allow more accurate assessment and diagnosis.


Assesment of anogenital distance as a marker in diagnosis of prostate cancer.
Anogenital distance (AGD), the distance from the sexual organs to the anus, is a sexually dimorphic feature in mammals. In this study, we investigated the relationship between anogenital distance and prostate cancer (PCa). 52 patients diagnosed with PCa and 60 patients with benign prostate hyperplasia as a control group were included in the study. AGDAP (cephalad insertion of the penis to the center of the anus) and AGDAS (posterior base (first fold) of the scrotum to the center of the anus) measurements of patients were done and noted before biopsy. The mean ages of 52 patients diagnosed with PCa and 60 patients with benign prostatic hyperplasia (BPH) were 67.70 ± 7.74 and 67.03 ± 7.89, respectively. There was no statistically significant difference in terms of age and serum testosterone levels of the patients diagnosed with prostate cancer or BPH (p > 0.05). Mean PSA values of patients diagnosed with prostate cancer wto be statistically higher than patients with BPH (p = 0.000). The mean AGDAP measurements of patients diagnosed with prostate cancer were statistically higher than those diagnosed with BPH (p = 0.000) and there was no significant difference in AGDAS measurements.(p = 0.823; p > 0.05). Androgen exposure is thought to play a role in the development PCa. Also AGD may be an indicator of prenatal androgen activity. In our study, we found a direct correlation between AGDAP and PCa. In order to reach a definitive conclusion, randomized controlled trials with larger sample number are needed.


Low setting of feedback regulation of TSH secretion by thyroxine in pituitary dwarfism with TSH-releasing hormone deficiency.
Four patients with idiopathic pituitary dwarfism were shown to have growth hormone (GH), adrenocorticotropin (ACTH), and luteinizing hormone (LH) deficiencies. Basal levels of thyrotropin (TSH) were within normal range in three patients and slightly elevated in one. Exaggerated and delayed responses were obtained after TSH-releasing hormone (TRH) stimulation. Serum thyroxine (T4) values were low (2.3 +/- 0.4 mug/100 ml), while triiodothyronine (T3) levels were in the normal range (1.22 +/- 0.25 ng/ml), both rising substantially after exogenous TSH and consecutive TRH administration. Their hypothyroid state was, therefore, probably due to TRH deficiency. To examine the dose of L-T4 necessary to produce inhibition of the TSH response to TRH, 50 mug/m2/day of L-T4 was administered to these patients. At the end of 4 weeks of replacement, serum T4 rose to 5.2 +/- 0.5 mug/100 ml, whereas T3 was unchanged from the previous levels, after which TSH responses to TRH were completely suppressed in all patients. As a control group, six patients with primary hypothyroidism received gradually increasing doses of L-T4 for 4-week periods, and TSH response to TRH was tested at the end of each dosage of L-T4, until complete inhibition of TSH release was obtained. The primary hypothyroid patients required approximately 150 mug/m2/day of L-T4 for suppression of TSH response to TRH. At this dosage, serum T4 and T3 levels were 8.5 +/- 0.9 mug/100 ml and 2.34 +/- 0.5 ng/ml respectively, which were significantly higher than those levels in the pituitary dwarfs (P less than 0.001 for T4 and P less than 0.01 for T3). These observations indicate that the set point of TSH release in feedback inhibition by throxine is low in idiopathic hypopituitarism with TRH deficiency, and TRH seems to control the pituitary sensitivity to feedback regulation of thyroid hormones.


Synergism between soluble and dietary fiber bound antioxidants.
This study investigates the synergism between antioxidants bound to dietary fibers (DF) of grains and soluble antioxidants of highly consumed beverages or their pure antioxidants. The interaction between insoluble fractions of grains containing bound antioxidants and soluble antioxidants was investigated using (i) a liposome-based system by measuring the lag phase before the onset of oxidation and (ii) an ESR-based system by measuring the reduction percentage of Fremy's salt radical. In both procedures, antioxidant capacities of DF-bound and soluble antioxidants were measured as well as their combinations, which were prepared at different ratios. The simple addition effects of DF-bound and soluble antioxidants were compared with measured values. The results revealed a clear synergism for almost all combinations in both liposome- and ESR-based systems. The synergism observed in DF-bound-soluble antioxidant system paints a promising picture considering the role of fiber in human gastrointestinal (GI) tract health.


Virological and Serological Responses of Sheep and Cattle to Experimental Schmallenberg Virus Infection.
Schmallenberg virus (SBV) is an orthobunyavirus in the Simbu serogroup that emerged in Germany in late 2011 and was mostly associated with a mild transient disease of sheep and cattle. SBV is transmitted by biting midges (Culicoides species) and causes abortions, stillbirths, and congenital defects in naïve pregnant ruminants. Two separate studies were conducted with a primary objective of better understanding the virological and serological responses of sheep and cattle to different SBV isolates after experimental infection. The second objective was to produce immunoreagents and challenge materials for use in future vaccine and diagnostics research. These studies were carried out using the following infectious inocula: (i) infectious serum (IS) (ii) cell culture-grown virus, and (iii) infectious lamb brain homogenate. The responses were assessed in both species throughout the course of the experiment. SBV RNA in serum (RNAemia) was detected as early as 2 (in sheep) and 3 (in cattle) days postinfection (dpi) and peaked on 3 and 4 dpi in cattle and sheep, respectively. Cattle had higher levels of RNAemia compared with sheep. Experimental infection with IS resulted in the highest level of RNAemia in both species followed by cell culture-grown virus. A delayed, low level RNAemia was detected in cattle inoculated with infectious sheep brain. Isolation of SBV was only possible from 4 dpi sera from all cattle inoculated with IS and one sheep inoculated with cell culture-derived virus. SBV neutralizing antibodies were first detected on 14 dpi in both species. No specific gross and microscopic lesions were observed in either study. In conclusion, these studies highlight not only the difference in viremia and anti-SBV antibody level against the different SBV isolates, but also the extent of the response in the two host species.


Quality of life in systemic sclerosis: psychometric properties of the World Health Organization Disability Assessment Schedule II.
To determine the validity of the World Health Organization Disability Assessment Schedule II (WHODAS II) in systemic sclerosis (SSc). Patients enrolled in the Canadian Scleroderma Research Group registry participated in a standardized evaluation and completed the WHODAS II. Criterion validity was assessed by comparing the WHODAS II with the Medical Outcomes Study Short Form 36 (SF-36), construct validity was assessed by examining how it relates to common measures of outcome in SSc, and discriminative validity was assessed by examining how it distinguishes patients with more severe disease from those with less severe disease. A total of 402 patients with SSc were included (mean +/- SD age 55 +/- 13 years, 87% women, mean +/- SD disease duration 11 +/- 9 years). The mean +/- SD WHODAS II score was 24.6 +/- 17.4, and the greatest impairments were in life activities and mobility. There were moderate to good correlations between the WHODAS II and the SF-36 Physical Component Summary score (r = -0.44), the SF-36 Mental Component Summary score (r = -0.41), and measures of function (r = 0.54), depression (r = 0.44), pain (r = 0.40), and fatigue (r = -0.49, P < 0.0001 for all). The WHODAS II was able to consistently distinguish patients with milder disease from those with more severe disease. The WHODAS II had good psychometric properties in patients with SSc and should be considered a valid measure of health-related quality of life in SSc.


Can power-law scaling and neuronal avalanches arise from stochastic dynamics?
The presence of self-organized criticality in biology is often evidenced by a power-law scaling of event size distributions, which can be measured by linear regression on logarithmic axes. We show here that such a procedure does not necessarily mean that the system exhibits self-organized criticality. We first provide an analysis of multisite local field potential (LFP) recordings of brain activity and show that event size distributions defined as negative LFP peaks can be close to power-law distributions. However, this result is not robust to change in detection threshold, or when tested using more rigorous statistical analyses such as the Kolmogorov-Smirnov test. Similar power-law scaling is observed for surrogate signals, suggesting that power-law scaling may be a generic property of thresholded stochastic processes. We next investigate this problem analytically, and show that, indeed, stochastic processes can produce spurious power-law scaling without the presence of underlying self-organized criticality. However, this power-law is only apparent in logarithmic representations, and does not survive more rigorous analysis such as the Kolmogorov-Smirnov test. The same analysis was also performed on an artificial network known to display self-organized criticality. In this case, both the graphical representations and the rigorous statistical analysis reveal with no ambiguity that the avalanche size is distributed as a power-law. We conclude that logarithmic representations can lead to spurious power-law scaling induced by the stochastic nature of the phenomenon. This apparent power-law scaling does not constitute a proof of self-organized criticality, which should be demonstrated by more stringent statistical tests.


Nightmares in obstructive sleep apnoea.
Obstructive events in patients with obstructive sleep apnoea (OSA) cause recurrent sleep fragmentation and occasional desaturation, which can cause various parasomnias, including nightmares. Several lines of evidence suggest that OSA may be potentially associated with a higher frequency of nightmares. We searched for studies published from January 2000 until November 2020 in PubMed, the Cochrane Library, Web of Science and Google Scholar. The keywords Obstructive Sleep Apnoea / OSA / Nightmares / CPAP / PTSD / Sleep Quality / Dream / were used in various combinations. The literature search identified 1361 articles which were eligible to more careful examination. Secondary texts were also examined, evaluated for suitability, and added to the primary document list. Finally, a total of 168 articles were included in the review. According to current findings, OSA could affect emotional regulation via activation of limbic system during sympathetic activation and suppression of REM sleep essential to emotional regulation. The reviews also found an increased prevalence of nightmares in OSA patients. OSA is significantly associated with psychiatric morbidity, as was proved in several studies. There seems to be a strong link between nightmares, OSA, PTSD symptoms and other disorder such as unipolar depression. It is clear that therapy of OSA patients, especially those with psychiatric comorbidity, must be complex. In the case of nightmares, we should not forget to use psychotherapy as a first choice, particularly in patients with poor compliance to continuous positive airway pressure (CPAP) and poor sleep and overall life quality. In the same time, we should emphasise the healthy lifestyle and sleep hygiene.


The European Vulvovaginal Epidemiological Survey (EVES): impact on sexual function of vulvovaginal atrophy of menopause.
To estimate the impact of vulvovaginal atrophy (VVA) on sexual function in a clinical population of postmenopausal women. Women 45 to 75 years old and more than 12 months after the last menstruation, who attended menopausal/gynecological centers in Italy and Spain, were included. Women with at least one VVA symptom completed the following questionnaires: Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale revised (FSDS-R). A physical gynecological examination was performed to confirm the VVA diagnosis. Data were analyzed by chi-square and Student's t tests. In all, 2,160 evaluable women were included in the study. VVA was confirmed in 90% of the included participants. The negative impact on sexual function was significantly higher in women with than in women without confirmed VVA, as evaluated with the sexual function component (DIVA-C) of the DIVA questionnaire (P = 0.013). Statistically significant differences (P < 0.0005) were also detected in the scores of overall FSDS-R, the overall FSFI, and of all the FSFI subdomains (desire, arousal, lubrication, orgasm, satisfaction, and pain). For postmenopausal women with at least one VVA symptom, the presence of physician-confirmed VVA is associated with significant impaired sexual function, as shown by unadjusted analyses. Given the impact on quality of life and the prevalence of VVA, further research to improve and reduce VVA is warranted.


Multiple grafting to enzymatically synthesized polyesters.
Enzymatic polymerization is an environmentally benign process for the synthesis of biodegradable and biocompatible polymers. The regioselectivity of lipase B from Candida Antarctica (CAL-B) produces linear functional polyesters without protection-deprotection steps. In this work, two different methods for the enzymatic synthesis of functional polyesters based on renewable resources, as, e.g., glycerol, using CAL-B are outlined. Poly(glycerol adipate) was synthesized by enzymatic transesterification between glycerol and divinyl adipate or dimethyl adipate. Methods are also reported to graft poly(glycerol adipate) with different amounts of hydrophobic side chains (lauric, stearic, behenic, and oleic acids) and hydrophilic poly(ethylene glycol) side chains, respectively. The hydrophilicity or lipophilicity of grafted polyesters is well controlled by changing the degree of grafting of hydrophilic and hydrophobic side chains. The multiple grafted polyesters are characterized by NMR spectroscopy, differential scanning calorimetry, gel permeation chromatography, and X-ray diffraction. Furthermore, the self-assembly of the graft copolymers in water and their use as steric stabilizers for cubosomes are discussed. For this purpose mainly dynamic light scattering and small angle X-ray scattering have been employed.


Identification of a novel enzyme and the regulation of key enzymes in mammalian taurine synthesis.
Taurine has many pharmacological roles on various tissues. The maintenance of abundant taurine content in the mammalian body through endogenous synthesis, in addition to exogenous intake, is the essential factor for morphological and functional maintenances in most tissues. The synthesis of taurine from sulfur-containing amino acids is influenced by various factors. Previous literature findings indicate the influence of the intake of proteins and sulfur-containing amino acids on the activity of the rate-limiting enzymes cysteine dioxygenase and cysteine sulfinate decarboxylase. In addition, the regulation of the activity and expression of taurine-synthesis enzymes by hormones, bile acids, and inflammatory cytokines through nuclear receptors have been reported in liver and reproductive tissues. Furthermore, flavin-containing monooxygenase subtype 1 was recently identified as the taurine-synthesis enzyme that converts hypotaurine to taurine. This review introduces the novel taurine synthesis enzyme and the nuclear receptor-associated regulation of key enzymes in taurine synthesis.


Localization of glutaminase-like and aspartate aminotransferase-like immunoreactivity in neurons of cerebral neocortex.
The distribution of glutaminase (GLNase)- and aspartate aminotransferase (AATase)-immunoreactive cells was examined in the cerebral neocortex of rat and guinea pig and in the somatic sensorimotor and primary visual cortex of the Macaca fascicularis monkey. These enzymes are involved in the metabolism of glutamate and aspartate, two amino acids thought to be excitatory amino acid transmitters for cortical neurons. In each of the species examined a large percentage of layer V and VI pyramidal neurons have pronounced glutaminase-like immunoreactivity (GLNase IR). In contrast, neurons in layers I, II, and IV show little GLNase IR. Layer III in the rat and guinea pig contains only a few, densely labeled GLNase-like-immunoreactive (GLNase-Ir) pyramidal neurons, whereas in the monkey the number of GLNase-Ir cells in layer III varies between cytoarchitectonic fields. Area 3b of the primary somatic sensory cortex and area 17 (primary visual cortex) contain few GLNase-Ir cells in layer III. However, layer III contains moderate numbers of GLNase IR in cells in areas 3a, 1, 2, 5, and in the primary motor cortex. Within the motor cortex the largest pyramidal ("Betz") cells are not labeled. In marked contrast to the results with antibody to GLNase, antibody to AATase labels cells that appear nonpyramidal in form, and these cells are in all cortical layers in each of the species examined. This distribution is roughly similar throughout all areas of rodent neocortex, but in monkey visual cortex AATase-immunoreactive neurons are more numerous in layers II-III, IVc, and VI. When combined with the findings of other studies, our results suggest that GLNase IR marks pyramidal neurons that use an excitatory amino acid transmitter. Antibody to AATase appears to mark intrinsic cortical neurons. The AATase immunoreactivity of these cells could indicate that they use an excitatory amino acid transmitter. However, their form and distribution in cortex suggest that this antibody labels GABAergic neurons.


Biodegradable nitric oxide precursor-loaded micro- and nanoparticles for the treatment of Staphylococcus aureus biofilms.
Bacteria in biofilms are more difficult to eradicate than planktonic bacteria and result in treatment challenges for many chronic infectious diseases. Nitric oxide (NO) is an endogenous molecule that offers potential as an alternative to conventional antibiotics; however its sustained topical delivery to biofilms is not readily achieved. With this in mind, we report the development of biodegradable poly(lactide-co-glycolide) (PLGA) based microparticles (MP) and nanoparticles (NP) for encapsulation of the NO precursor isosorbide mononitrate (ISMN) and the controlled delivery to Staphylococcus aureus (S. aureus) biofilms. Firstly, water-in-oil-in-water (w/o/w) emulsification/solvent evaporation methods for PLGA NP and MP syntheses were experimentally optimised with respect to particle size and ISMN loading/encapsulation efficiency. The influence of various experiment parameters, such as the volume of inner aqueous phase, concentration of surfactants, mixing time on the particle size, drug loading and encapsulation efficiency were investigated systematically. Both PLGA MP and NP formulations enabled sustained ISMN release in physiological media over 3 to 5 days. PLGA MP with diameters of ∼3 μm and ISMN loading of 2.2% (w/w) were identified as the optimum delivery system and demonstrated significant antibacterial activity in S. aureus biofilms. This behaviour is considered to be due to targeted biofilm delivery through a combination of effective penetration and sustained release of ISMN.


[The effect of a different protein supply with regard to quality and quantity on growth and serum growth hormone in weaned rats].
A two-factorially experiment was done over a period of 42 days using 32 male, weaned Sprague-Dawley rats in order to study the effect of insufficient protein supplementation, with regard to quantity and quality (13% protein in comparison to 18%, and an essential amino acid index of 64 in comparison to 92%, resp.), on weight development and serum growth hormone concentration. Qualitative protein deficiency had a greater adverse effect on weight development and feed utilization than did quantitative protein deficiency. Both test factors combined brought about the lowest body weight and poorest feed utilization. A lowered hematocrit value occurred only after quantitative protein deficiency. The serum urea concentration was elevated after protein deficiency due to poor quality protein; the serum protein concentration tended toward reduction in both the case of qualitative as well as in the case of qualitative-quantitative protein deficiency. After providing the animals poor quality protein, growth hormone levels in serum were reduced, whereas the concurrence of both factors of protein deficiency caused the growth hormone concentration in serum to rise to a value 4.2-fold of the control value.


A teaching device for Furlow palatoplasty.
The Furlow double-opposing z-plasty technique of palate repair has become a common treatment for cleft palate. The procedure is more complicated than other methods of palate closure and is difficult for the trainee to visualize; It is even more difficult for the layperson without prior understanding of the concept of z-plasty to understand. A simple, inexpensive, portable model is described that shows the key elements of the repair and can be used for parent, patient, student, and resident teaching.


A Clinicopathological Correlation of International Federation of Gynecology and Obstetrics's PALM-COEIN Classification of Abnormal Uterine Bleeding: Indian Scenario.
Abnormal uterine bleeding (AUB) is a common problem affecting the women of reproductive age group and may also have a significant impact on their physical, social, and emotional aspects directly affecting their quality of life. The International Federation of Gynecology and Obstetrics (FIGO) devised a universally acceptable system of nomenclature and classification, namely PALM-COEIN classification of AUB in the year 2011. The objective of the present study was to analyze the structural (PALM) and functional (COEIN) component of FIGO system in the Indian scenario. Three hundred patients with complaints of AUB were taken. A clinical diagnosis according to PALM-COEIN system was made after thorough history and clinical examination. Additional investigations if required were done, and endometrial sampling or hysterectomy was done whichever indicated. A histological diagnosis was made, and each case was allocated a category according to PALM-COEIN classification. A clinicopathological correlation was done in the hysterectomy cases for structural causes (PALM). Leiomyoma (30%) was the most common cause of AUB closely followed by adenomyosis (29.66%) overall. The clinicopathological correlation in hysterectomy cases was good with concordance rate of 85.03%. The concordance between clinical and pathological diagnoses for AUB-L, AUB-A, AUB-M, and AUB-A, L was statistically significant with P < 05 in positive cases. However, additional finding of adenomyosis was diagnosed in 48.2% of the cases apart from primary clinical diagnosis. A good clinicopathological correlation was seen in the cases when classified according to PALM-COEIN classification. The system also provides for consideration of multiple etiologies contributing toward AUB both clinically and histopathologically. However, histopathology remains the cornerstone in establishing the accurate diagnosis as the cases without specific symptoms can be missed clinically.


Microwave-assisted extraction performed in low temperature and in vacuo for the extraction of labile compounds in food samples.
In this study, low temperature vacuum microwave-assisted extraction, which simultaneous performed microwave-assisted extraction (MAE) in low temperature and in vacuo environment, was proposed. The influencing parameters including solid/liquid ratio, extraction temperature, extraction time, degree of vacuum and microwave power were discussed. The predominance of low temperature vacuum microwave-assisted extraction was investigated by comparing the extraction yields of vitamin C, β-carotene, aloin A and astaxanthin in different foods with that in MAE and solvent extraction, and 5.2-243% increments were obtained. On the other hand, the chemical kinetics of vitamin C and aloin A, which composed two different steps including the extraction step of analyte transferred from matrix into solvent and the decomposition step of analyte degraded in the extraction solvent, were proposed. All of the decomposition rates (K(2)) for the selected analyte in low temperature, in vacuo and in nitrogen atmosphere decreased significantly comparing with that in conventional MAE, which are in agreement with that obtained from experiments. Consequently, the present method was successfully applied to extract labile compound from different food samples. These results showed that low temperature and/or in vacuo environment in microwave-assisted extraction system was especially important to prevent the degradation of labile components and have good potential on the extraction of labile compound in foods, pharmaceutical and natural products.


Retrotransposable elements and human disease.
Nearly 50% of the human genome is composed of fossils from the remains of past transposable element duplication. Mobilization continues in the genomes of extant humans but is now restricted to retrotransposons, a class of mobile elements that move via a copy and paste mechanism. Currently active retrotransposable elements include Long INterspersed Elements (LINEs), Short INterspersed Elements (SINEs) and SVA (SINE/VNTR/Alu) elements. Retrotransposons are responsible for creating genetic variation and on occasion, disease-causing mutations, within the human genome. Approximately 0.27% of all human disease mutations are attributable to retrotransposable elements. Different mechanisms of genome alteration created by retrotransposable elements include insertional mutagenesis, recombination, retrotransposition-mediated and gene conversion-mediated deletion, and 3' transduction. Although researchers in the field of human genetics have discovered many mutational mechanisms for retrotransposable elements, their contribution to genetic variation within humans is still being resolved.


Basal luteinizing hormone/follicle stimulating hormone ratio in diagnosis of central precocious puberty.
Precocious puberty is characterized by breast development in girls prior to 8 years old and may have acne, adult odor, growth spurt and menstruation. Conventionally, gonadotropin releasing hormone (GnRH) stimulation test is a gold standard for diagnosis of central precocious puberty but it is a time-comsuming procedure that is not practical on an out patient basis. To evaluate the basal luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in diagnosis of central precocious puberty in order to save time and cost. The GnRH stimulation tests were performed on 51 girls with breast development before 8 years old. The 51 girls were divided into 2 groups, 24 girls with central precocious puberty (CPP) and 27 girls with premature thelarche (PT), and the clinical data and GnRH stimulation tests data were compared between the 2 groups. The authors also compared the clinical data and GnRH stimulation tests data between 13 girls with PT and 12 girls with thelarche variants (TV) who developed puberty approximately 1 year later as confirmed by GnRH stimulation test. Girls with CPP had a large bone age and chronological age ratio and advancement of breast staging. Girls with TV had a greater level of basal luteinizing hormone (LH), peak LH and 120 min estradiol than girls with PT. Basal luteinizing hormone and follicle stimulating hormone (FSH) ratio greater than 0.2 can be used to diagnose CPP with 75 per cent sensitivity, 85 per cent specificity, 82 per cent positive predictive value (PPV) and 82 per cent negative predictive value (NPV). Girls with CPP have a basal LH/FSH ratio greater than 0.2 and this can be used as a cut-off point for the diagnosis CPP.


Finding minimum gene subsets with heuristic breadth-first search algorithm for robust tumor classification.
Previous studies on tumor classification based on gene expression profiles suggest that gene selection plays a key role in improving the classification performance. Moreover, finding important tumor-related genes with the highest accuracy is a very important task because these genes might serve as tumor biomarkers, which is of great benefit to not only tumor molecular diagnosis but also drug development. This paper proposes a novel gene selection method with rich biomedical meaning based on Heuristic Breadth-first Search Algorithm (HBSA) to find as many optimal gene subsets as possible. Due to the curse of dimensionality, this type of method could suffer from over-fitting and selection bias problems. To address these potential problems, a HBSA-based ensemble classifier is constructed using majority voting strategy from individual classifiers constructed by the selected gene subsets, and a novel HBSA-based gene ranking method is designed to find important tumor-related genes by measuring the significance of genes using their occurrence frequencies in the selected gene subsets. The experimental results on nine tumor datasets including three pairs of cross-platform datasets indicate that the proposed method can not only obtain better generalization performance but also find many important tumor-related genes. It is found that the frequencies of the selected genes follow a power-law distribution, indicating that only a few top-ranked genes can be used as potential diagnosis biomarkers. Moreover, the top-ranked genes leading to very high prediction accuracy are closely related to specific tumor subtype and even hub genes. Compared with other related methods, the proposed method can achieve higher prediction accuracy with fewer genes. Moreover, they are further justified by analyzing the top-ranked genes in the context of individual gene function, biological pathway, and protein-protein interaction network.


Simple agarose micro-confinement array and machine-learning-based classification for analyzing the patterned differentiation of mesenchymal stem cells.
The geometrical confinement of small cell colonies gives differential cues to cells sitting at the periphery versus the core. To utilize this effect, for example to create spatially graded differentiation patterns of human mesenchymal stem cells (hMSCs) in vitro or to investigate underpinning mechanisms, the confinement needs to be robust for extended time periods. To create highly repeatable micro-fabricated structures for cellular patterning and high-throughput data mining, we employed here a simple casting method to fabricate more than 800 adhesive patches confined by agarose micro-walls. In addition, a machine learning based image processing software was developed (open code) to detect the differentiation patterns of the population of hMSCs automatically. Utilizing the agarose walls, the circular patterns of hMSCs were successfully maintained throughout 15 days of cell culture. After staining lipid droplets and alkaline phosphatase as the markers of adipogenic and osteogenic differentiation, respectively, the mega-pixels of RGB color images of hMSCs were processed by the software on a laptop PC within several minutes. The image analysis successfully showed that hMSCs sitting on the more central versus peripheral sections of the adhesive circles showed adipogenic versus osteogenic differentiation as reported previously, indicating the compatibility of patterned agarose walls to conventional microcontact printing. In addition, we found a considerable fraction of undifferentiated cells which are preferentially located at the peripheral part of the adhesive circles, even in differentiation-inducing culture media. In this study, we thus successfully demonstrated a simple framework for analyzing the patterned differentiation of hMSCs in confined microenvironments, which has a range of applications in biology, including stem cell biology.


The role of food science and technology in humanitarian response.
In humanitarian contexts, ensuring access to safe, nutritious, good quality and culturally appropriate food in the right quantity at the right time and place during an emergency or a protracted crisis is an enormous challenge, which is likely to increase given uncertainties such as climate change, global political and economic instability and emerging pandemics like COVID-19. Several international organizations and non-government organizations have well established systems to respond to food security emergencies. However, the role of food science and technology in humanitarian response is not well understood and is seldom considered in humanitarian circles. The role of food science and technology in humanitarian response and the importance of addressing the requirements of the local consumers within the local food systems are discussed. Humanitarian food aid policies focus on immediate and short-term assistance to save lives. The implementation of emergency programs and projects tends to induce dependency on aid, rather than strengthening local food systems and ensuring resilience. Transformative change must embrace innovation across the whole food system with an increased emphasis on food science and technology that addresses local food security, generates employment and contributes to the local economy. There needs to be a move beyond rehabilitating and increasing agricultural production to addressing the whole food system with a view to link humanitarian assistance and longer-term support to sustainable livelihoods and resilience.


Molecular panel for detection of sepsis-related microorganisms.
Sepsis is a systemic inflammatory response related to high mortality rates in the hospital environment. Delayed etiological diagnosis and inadequate antimicrobial therapy are associated with treatment failures. Molecular tests based on polymerase chain reaction are regarded as faster and more accurate procedures than culture techniques for microbial identification, providing a higher rate of therapeutic success. To develop a panel of primers for DNA fragments of sepsis-related microorganisms. Primers for amplification of Enterobacter spp., Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida spp. were designed and tested for sensitivity and specificity on the basis of their respective standard strains. The intended specificity was obtained for P. aeruginosa, S. aureus and Candida spp primers. Sensitivity tests showed a threshold for detection from 5 ng to 500 fg in blood samples contaminated with microbial DNA. The molecular panel presented offers the advantage of a flexible 'open' system when compared to other multiplex detection methods.


IgA anti-tissue transglutaminase antibodies and IgG antibodies against deamidated gliadin peptides as predictors of celiac disease.
To compare the performance of IgA anti-tissue transglutaminase antibodies (IgA anti-tTG), IgA anti-endomysial antibodies (IgA EMA), and IgA/IgG antibodies against deamidated gliadin peptides (IgA/IgG anti-DGP) for the diagnosis of celiac disease. Descriptive study in patients with celiac disease. Anti-DGP (IgA/IgG), IgA EMA, IgA anti-tTG antibodies were measured and an intestinal biopsy was done. Sex: female (61 %). Median age: 78.4 months old. A total of 136 children were included; 108 had high IgA anti-DGP titers; 124, increased IgG anti-DGP titers; 128, positive IgA EMA titers; and 130, increased IgA anti-tTG titers. High IgG anti-DGP titers were observed in 4/6 patients with negative IgA anti-tTG antibodies. The combination of IgG anti-DGP + IgA anti-tTG antibodies showed a positive correlation in 134 patients and the IgG anti-DGP + EMA combination was positive in 133 children. IgA EMA, IgA anti-tTG, and IgG anti-DGP antibodies exhibited an adequate specificity and sensitivity. The IgG anti-DGP/anti-tTG combination showed a 98-99 % sensitivity and a 100 % specificity. The anti-tTG and IgG anti-DGP option yields excellent results, with a low cost and independence from the observer.


Factors contributing to the overuse of chemical pesticides in children with persistent head lice.
A growing number of head lice cases, for reasons that are not entirely clear, are repetitive or enduring. Despite the emerging phenomena, there has been little in the literature to guide school nurses in their day-to-day struggle with families experiencing head lice infestations that persist despite repeated treatment attempts. Children with persistent head lice are at increased risk of overexposure to chemical pesticides from multiple-treatment sources. In addition, school absences for persistent head lice infestations place children at risk educationally.


[Natural physical factors of the Kuban' Black Sea coastal area in the rehabilitative treatment of children with psoriasis and concomitant ophthalmoherpes].
The primary objective of this study was to optimize the process of remedial treatment at health reports of Sochi, Gelendzhik, and Anapa by introducing sun, air, and sea water baths in the system of sanatorium-and-spa treatment of the children with various nosologic forms of psoriasis and concomitant ophthalmoherpes that necessitated keratoplastic surgery. The study included children at the age of 7-13 years with plaque and nummular psoriasis vulgaris who received rehabilitative treatment after keratoplasty for ophthalmoherpes. The children were randomly allocated to two groups. One comprised patients based at the specialized children's sanatoria "Yunost", "Vulan", and "Bimlyuk" (Roszdrav) (group 1, n = 278). Patients of the control group were given conventional treatment in municipal outpatient settings in compliance with the existing standards (group 2, n = 278). The study showed a 2.39-fold decrease of the psoriasis area and severity index (PASI) in the children of group 1 compared with its 1.38-fold decrease in group 2. It is concluded that a combination of natural physical factors of the Kuban' Black Sea coastal area has highly beneficial effect on the outcome of postoperative treatment of children with plaque and nummular psoriasis vulgaris and concomitant ophthalmoherpes responsible for corneal ulceration that requires corrective keratoplastic surgery.


Talking to children about their HIV diagnosis: a discussion rooted in different global perspectives.
An online meeting was arranged with four professionals representing four countries to debate current practices and future steps in naming HIV to children (disclosing HIV status). This article considers the evidence and reports on the commentary and debate from the meeting. Naming HIV to children remains a challenge. Although studies identify some of the facilitators and barriers to informing children of their HIV diagnosis, further review of practice is required. This article presents a global perspective of naming practices from different settings. The article comprises commentary and a report of the online debate, along with supporting evidence. The four participating authors concluded that health professionals must work in collaboration with families to support early naming of HIV to children or having an open discussion about HIV in clinics. Naming when a child is younger reduces self-stigma and empowers children and young people to adhere to their medication, make informed decisions and share their own diagnosis appropriately. The authors concluded that health professionals play a key role in educating colleagues and the public to reduce stigma and discrimination. Professionals working with children and families living with HIV require support and resources to instil confidence in naming and facilitate naming of HIV status to a child.


Permissive hypofiltration.
Acute kidney injury (AKI) is a syndrome with a multitude of causes and is associated with high mortality and a permanent loss of renal function. Our current understanding of the most common causes of AKI is limited, and thus a silver bullet therapy remains elusive. A change in the approach to AKI that shifts away from the primary composite endpoint of death/dialysis, and instead focuses on improving survival and mitigating permanent renal damage, is likely to be more fruitful. We suggest that the current approach of augmenting renal function by increasing the renal blood flow or glomerular filtration rate during AKI may actually worsen outcomes. Analogous to the approach towards adult respiratory distress syndrome that limits ventilator-induced lung injury, we propose the concept of permissive hypofiltration. The primary goals of this approach are: resting the kidney by providing early renal replacement therapy, avoiding the potentially injurious adverse events that occur during AKI (for example, fluid overload, hypophosphatemia, hypothermia, and so forth), and initiating therapies focused on improving survival and mitigating permanent loss of kidney function.


Comparison of two hydrated forms of sodium inosine 5'-monophosphate.
The crystal and molecular structure of a decahydrated form of the sodium salt of inosine 5'-monophosphate (C10H12N4O8P-.Na+.10H2O) was solved to study the effect of hydration on the conformation of nucleic acids. Monoclinic, space group P2(1), a = 8.730 (3), b = 22.349 (7), c = 12.282 (4) A, beta = 109.68 (3) degrees, V = 2256.52 A3, Mr = 550.34, Z = 4, F(000) = 1196, Dx = 1.62 g cm-3, mu = 21.7 cm-1, lambda(Cu K alpha) = 1.54056 A, R = 0.070, wR = 0.102 for 3404 unique [Inet greater than 2 sigma (Inet)] observed reflections out of 3457 unique reflections. The two molecules (A and B) in the asymmetric unit differ in the arrangement of the first shell of hydration and in the torsion angles of the ribose and phosphate. The bond lengths and angles are similar to those of the structure of a less hydrated ('dry') form of the same nucleotide (C10H12N4O8P-.Na+.8H2O) determined previously in space group C222(1) [Rao & Sundaraligam (1969). J. Am. Chem. Soc. 91, 1210-1217]. The twofold symmetry in the 'dry' form is destroyed in the present crystal structure due to the relative displacement of the two independent molecules and reorganization of the hydration shell. Molecule A is different from (r.m.s. = 0.190 A) while molecule B is similar to (r.m.s. = 0.093 A) that of the 'dry' form. The conformation adopted is influenced mainly by the differences in the endocyclic torsion angles of the ribose.


Is central repair with coronary artery bypass grafting enough for multi-organ malperfusion in acute type A aortic dissection with coronary malperfusion?
Acute type A aortic dissection with coronary malperfusion syndrome is rare but associated with high mortality. Multi-organ malperfusion is an independent predictor of acute type A aortic dissection. Coronary malperfusion requires treatment, but it is not feasible to treat all malperfusions. The adequacy of "central repair and coronary artery bypass grafting" for patients with coronary and other organ malperfusion is unknown. Of the 299 patients who underwent surgery between 2008 and 2018, 21 patients with coronary malperfusion, who received cental repair with coronary artery graft bypass, were analyzed retrospectively. They were divided; into Group M (n = 13, coronary and other organ malperfusion) and Group O (n = 8, coronary malperfusion only). The patient background, surgical content, details of malperfusion, surgical mortality and morbidity, and long-term outcome were compared. There was no difference in operation time (205 ± 30 vs. 266 ± 88, p = 0.49), but the time from arrival to circulatory arrest tended to be shorter in Group M (81 vs. 134, p = 0.05). Among Group M, cerebral malperfusion was the most common at 92%. Two of the three cases with mesenteric malperfusion died. The mortality of Group M and Group O was 13% and 15% (P = 0.85), respectively. There was no difference in long-term mortality (p = 0.62). Central repair and coronary artery bypass grafting is a sufficiently acceptable treatment for patients with acute type A aortic dissection and multi-organ malperfusion, including coronary malperfusion.


Pure duplication of 19p13.3 in three members of a family with intellectual disability and literature review. Definition of a new microduplication syndrome.
This paper describes the presence of an interstitial pure duplication of 19p13.3 (4.95 Mb) in a patient with intellectual disability studied by array-CGH which was initially considered as a de novo alteration. The discovery of the same chromosomal alteration in a first-degree cousin of this patient led us to investigate the presence of insertional translocations, which were consequently found in three family generations. The same duplication was found in three intellectually disabled patients and among the translocation carrier family members a very high incidence of miscarriages are reported. A review of other published cases has allowed us to find three other patients with a similar pure duplication, all of them sharing some common clinical findings such as intrauterine growth retardation, microcephaly, motor and speech delay, moderate to severe intellectual disability, and dysmorphic features. These findings allow us to suggest the presence of a new microduplication syndrome in chromosomal region 19p13.3.


What came first: PKCtheta or the immune synapse?
Stimulation of T cells by peptide-presenting antigen-presenting cells (APCs) induces formation of a highly organized complex of receptors, signaling molecules and cytoskeleton components at the immune synapse (IS), the contact site between T cells and APCs. Conjugate formation between T cells and APCs initiates the formation of the IS. After this event, micrometer-scale molecular movements occur in the T cell plasma membrane and the actin cytoskeleton undergoes reorganization. Our current knowledge suggests that formation of the IS is an essential step during T cell activation. This is probably related to the proper localization of certain proteins in specific compartments. One of these proteins is protein kinase Ctheta (PKCtheta), which is absolutely required for T cell activation. During the last years we have made great advances in understanding the function and targets of this kinase, and recent reviews have summarized these findings. In contrast, we do not know the exact mechanism that activates PKCtheta after TCR engagement and the role of PKCtheta activation in the formation of the IS. In this review I analyze the mechanism of the translocation of PKCtheta and discuss the function of PKCtheta in the formation of the IS and, vice versa, the role of the IS in the translocation of PKCtheta.


The fourth dimension of tool use: temporally enduring artefacts aid primates learning to use tools.
All investigated cases of habitual tool use in wild chimpanzees and capuchin monkeys include youngsters encountering durable artefacts, most often in a supportive social context. We propose that enduring artefacts associated with tool use, such as previously used tools, partly processed food items and residual material from previous activity, aid non-human primates to learn to use tools, and to develop expertise in their use, thus contributing to traditional technologies in non-humans. Therefore, social contributions to tool use can be considered as situated in the three dimensions of Euclidean space, and in the fourth dimension of time. This notion expands the contribution of social context to learning a skill beyond the immediate presence of a model nearby. We provide examples supporting this hypothesis from wild bearded capuchin monkeys and chimpanzees, and suggest avenues for future research.


Antithrombotic therapy of acute stroke: thrombolytic agents.
Following the initial report of the clinical use of plasminogen activators (PAs) in cerebrovascular thrombosis in 1958, interest in the efficacy of this approach accelerated only when the need for acute intervention in stroke was recognized. The use of PAs in acute ischemic stroke is based on the observation that approximately 80-90% of focal cerebral ischemic events presenting as strokes within 8 hr of symptom onset are due to atherothrombotic and embolic occlusions.


An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions.
Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient's emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. #NCT00056524. A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions.


Evidence for a role of hemozoin in metabolism and gametocytogenesis.
Hemozoin is generally considered a waste deposit that is formed for the sole purpose of detoxification of free heme that results from the digestion of hemoglobin by Plasmodium parasites. However, several observations of parasite multiplication, both in vertebrate and invertebrate hosts are suggestive of a wider, but overlooked, metabolic role for this product. The presence of clinical peripheral blood samples of P. falciparum with high parasitemia containing only hemozoin-deficient (non-pigmented) asexual forms has been repeatedly confirmed. Such samples stand in contrast with other samples that contain mostly pigmented circulating trophozoites and gametocytes, indicating that pigment accumulation is a prominent feature of gametocytogenesis. The restricted size, i.e. below detection by light microscopy, of hemozoin in asexual merozoites and ringforms of P. falciparum implies its continuous turnover, supporting a role in metabolism. The prominent interaction of hemozoin with several antimalarial drugs, the involvement of proteins in hemozoin formation, and the finding of plasmodial genes coding for a heme-oxygenase-like protein argue for a wider and more active role for hemozoin in the parasite's metabolism. The observed association of hemozoin with crystalloids during ookinete development is consistent with a useful function to it during parasite multiplication in the invertebrate host. Finally, alternative mechanisms, other than hemozoin formation, provide substitute or additional routes for heme detoxification.


[Surface membrane proteins of endoplasmic reticulum in brain and liver cells].
A comparative study of proteins adsorbed on outer surface of microsomal membranes was carried out. Electrophoretic differences between endoplasmic reticulum proteins from liver and brain cells were revealed. These differences were not observed in the presence of sodium dodecyl sulphate. Proteins of brain microsomes are shown to bind in vitro with membranes of brain endoplasmic reticulum to a higher extent than with liver microsomal membranes.


Triterpenoids.
This review covers the isolation and structure determination of triterpenoids, including squalene derivatives, protostanes, lanostanes, holostanes, cycloartanes, dammaranes, euphanes, tirucallanes, tetranortriterpenoids, quassinoids, lupanes, oleananes, friedelanes, ursanes, hopanes, serratanes and saponins; 278 references are cited.


The monoclonal antibody 69A1 recognizes an epitope found on neurones with axons that fasciculate but not on those with non-fasciculating processes.
We have previously reported that the cell-type distribution and pattern of expression of the surface antigen recognized by the monoclonal antibody 69A1, suggests that it may be involved during the period of nerve fibre outgrowth and the formation of fibre bundles in the rat (Pigott & Kelly, 1986). In this current study, we have examined the expression of the epitope recognized by antibody 69A1 in regions of the rat central nervous system in which it is possible to distinguish between neurones with axons that fasciculate to form clearly defined fibre tracts and neurones with non-fasciculating processes. We have also examined antibody 69A1 labelling in several regions of the peripheral nervous system. We report that the 69A1 epitope is expressed on neurones with axons that fasciculate but is not found on neurones with short, non-fasciculating axons or on neurones without a morphologically identifiable axon. The antigen 69A1 has been purified and shown to be immunochemically closely related or identical to the L1 antigen.


CBP-93872 inhibits NBS1-mediated ATR activation, abrogating maintenance of the DNA double-strand break-specific G2 checkpoint.
CBP-93872 was previously identified as a G2 checkpoint inhibitor using a cell-based high-throughput screening system. However, its molecular actions as well as cellular targets are largely unknown. Here, we uncovered the molecular mechanisms underlying abrogation of the G2 checkpoint by CBP-93872. CBP-93872 specifically abrogates the DNA double-stranded break (DSB)-induced G2 checkpoint through inhibiting maintenance but not initiation of G2 arrest because of specific inhibition of DSB-dependent ATR activation. Hence, ATR-dependent phosphorylation of Nbs1 and replication protein A 2 upon DSB was strongly suppressed in the presence of CBP-93872. CBP-93872 did not seem to inhibit DNA-end resection, but did inhibit Nbs1-dependent and ssDNA-induced ATR activation in vitro in a dose-dependent manner. Taken together, our results suggest that CBP-93872 is an inhibitor of maintenance of the DSB-specific G2 checkpoint and thus might be a strong candidate as the basis for a drug that specifically sensitizes p53-mutated cancer cells to DSB-inducing DNA damage therapy.


["Dynamic" component of carotid artery stenosis in patients with cerebrovascular disorders].
Nifedipine is shown to abolish contraction of the vessel at the site of the internal carotid artery stenosis induced by a cold test. It can furthermore produce a direct 5-40% reduction of the stenosis, the effect being dependent both on the drug plasma level and the ability to rise such levels of prostacyclin. In some patients there is a possibility of nifedipine contrary action when it promotes stenosis (up to 5-30% increase) and leads to disturbances of cerebral circulation. Consequently, to make optimal therapeutic measures in relevant patients nifedipine should be tried for stenosis-directed action.


Association between recent herpes zoster but not herpes simplex infection and subsequent risk of malignancy in women: a retrospective cohort study.
The association between herpes zoster and subsequent cancer risk is still unclear. Consequently, doubts remain regarding the need for investigation of herpes patients for co-existing or subsequent malignancy. This is a retrospective cohort study comparing cancer risk in patients after herpes zoster and age-/sex-matched non-herpes zoster patients, in a primary care-based continuous morbidity database. We tested for interaction by gender, age, diabetes, HRT use or antiviral therapy. Analyses were repeated for patients with and without herpes simplex. The hazard ratio (HR) comparing cancer risk in herpes zoster vs. control patients was significant in all women, women aged > 65 years and subgroups of breast and colorectal cancer (HRs 1·60, 1·82, 2·14, 2·19, respectively). For men, a significant association was found for haematological cancers (HR 2·92). No associations were found with herpes simplex. No interaction was identified with antiviral therapy, diabetes or HRT treatment. We concluded that there was a moderate significant association between herpes zoster and subsequent cancer risk in women aged > 65 years, without any influence of antiviral therapy. No association was found with herpes simplex. There is insufficient reason for extensively testing older patients with herpes zoster or herpes simplex for the presence of occult cancer.


Redox-stat bioreactors for elucidating mobilisation mechanisms of trace elements: an example of As-contaminated mining soils.
The environmental fate of major (e.g. C, N, S, Fe and Mn) and trace (e.g. As, Cr, Sb, Se and U) elements is governed by microbially catalysed reduction-oxidation (redox) reactions. Mesocosms are routinely used to elucidate trace metal fate on the basis of correlations between biogeochemical proxies such as dissolved element concentrations, trace element speciation and dissolved organic matter. However, several redox processes may proceed simultaneously in natural soils and sediments (particularly, reductive Mn and Fe dissolution and metal/metalloid reduction), having a contrasting effect on element mobility. Here, a novel redox-stat (Rcont) bioreactor allowed precise control of the redox potential (159 ± 11 mV, ~ 2 months), suppressing redox reactions thermodynamically favoured at lower redox potential (i.e. reductive mobilisation of Fe and As). For a historically contaminated mining soil, As release could be attributed to desorption of arsenite [As(III)] and Mn reductive dissolution. By contrast, the control bioreactor (Rnat, with naturally developing redox potential) showed almost double As release (337 vs. 181 μg g-1) due to reductive dissolution of Fe (1363 μg g-1 Fe2+ released; no Fe2+ detected in Rcont) and microbial arsenate [As(V)] reduction (189 μg g-1 released vs. 46 μg g-1 As(III) in Rcont). A redox-stat bioreactor thus represents a versatile tool to study processes underlying mobilisation and sequestration of other trace elements as well.


Soyfoods, hyperuricemia and gout: a review of the epidemiologic and clinical data.
Soyfoods have long been a part of traditional Asian diets; they provide plentiful amounts of high-quality protein and have a favourable fatty acid profile. In addition, provocative research suggests soyfoods offer health benefits independent of the nutrients they provide. However, there is a widely-held belief among Asian health professionals and the public that soyfoods increase risk of gout and potentially precipitate acute attacks in patients with this disease. To examine the veracity of this belief, this review critically evaluated the relevant clinical and epidemiologic data. In addition, background information on the etiology and prevalence of hyperuricemia and gout in Asia is provided along with the results of a small survey of Asian healthcare professionals about their attitudes toward soyfoods. Among the healthcare professionals who responded to the survey, 95% considered soyfoods to be somewhat or very healthy and nutritious. In contrast, 48% expressed the view that soyfoods are likely to cause gout. However, none of the six epidemiologic studies identified provided any evidence that soy intake was associated with circulating uric acid levels, hyperuricemia or gout. Data from the five human intervention studies evaluated indicate soy protein does elevate serum uric levels, but in response to amounts comparable to Asian intake, the expected rise would almost certainly be clinically irrelevant. Although there is a need for long-term research, on the basis of the existing data there is no reason for individuals with gout or at risk of developing gout to avoid soyfoods.


In vitro investigation of the mutagenic potential of Aloe vera extracts.
A 2-year cancer bioassay in rodents with a preparation of Aloe vera whole leaf extract administered in drinking water showed clear evidence of carcinogenic activity. To provide insight into the identity and mechanisms associated with mutagenic components of the Aloe vera extracts, we used the mouse lymphoma assay to evaluate the mutagenicity of the Aloe vera whole leaf extract (WLE) and Aloe vera decolorized whole leaf extract (WLD). The WLD extract was obtained by subjecting WLE to activated carbon-adsorption. HPLC analysis indicated that the decolorization process removed many components from the WLE extract, including anthraquinones. Both WLE and WLD extracts showed cytotoxic and mutagenic effects in mouse lymphoma cells but in different concentration ranges, and WLD induced about 3-fold higher levels of intracellular reactive oxygen species than WLE. Molecular analysis of mutant colonies from cells treated with WLE and WLD revealed that the primary type of damage from both treatments was largely due to chromosome mutations (deletions and/or mitotic recombination). The fact that the samples were mutagenic at different concentrations suggests that while some mutagenic components of WLE were removed by activated carbon filtration, components with pro-oxidant activity and mutagenic activity remained. The results demonstrate the utility of the mouse lymphoma assay as a tool to characterize the mutagenic activity of fractionated complex botanical mixtures to identify bioactive components.


[GISE/AIAC position paper on percutaneous left atrial appendage occlusion in patients with nonvalvular atrial fibrillation: recommendations for patient selection, facilities, competences, organizing and training requirements].
Thromboembolism from the left atrial appendage is the most feared complication in patients with atrial fibrillation (AF). The cornerstone for the management of chronic nonvalvular AF is stroke reduction with oral anticoagulation (OAC). However, poor compliance, maintaining a narrow therapeutic window, and major side effects such as bleeding have severely limited its use, creating a therapeutic dilemma. About 20% of AF patients do not receive OAC due to contraindications and less than half of AF patients are not on OAC due to reluctance of the prescribing physician and/or patient non-compliance. Fortunately, over the past decade, the introduction of percutaneous approaches for left atrial appendage occlusion has offered a viable alternative to the management of nonvalvular AF in patients with OAC contraindication. Occlusion devices such as the Amplatzer Cardiac Plug and Watch man device have shown their noninferiority to OAC for stroke prophylaxis with less bleeding complications, while more recently some new devices have been introduced. The aim of this position paper is to review the most relevant clinical aspects of left atrial appendage occlusion from patient selection to periprocedural and follow-up management. In addition, the importance of a medical team and an organizational environment adequate to optimize all the steps of this procedure is discussed.


Rapid Screening of COVID-19 Directly from Clinical Nasopharyngeal Swabs Using the MasSpec Pen.
The outbreak of COVID-19 has created an unprecedent global crisis. While the polymerase chain reaction (PCR) is the gold standard method for detecting active SARS-CoV-2 infection, alternative high-throughput diagnostic tests are of a significant value to meet universal testing demands. Here, we describe a new design of the MasSpec Pen technology integrated to electrospray ionization (ESI) for direct analysis of clinical swabs and investigate its use for COVID-19 screening. The redesigned MasSpec Pen system incorporates a disposable sampling device refined for uniform and efficient analysis of swab tips via liquid extraction directly coupled to an ESI source. Using this system, we analyzed nasopharyngeal swabs from 244 individuals including symptomatic COVID-19 positive, symptomatic negative, and asymptomatic negative individuals, enabling rapid detection of rich lipid profiles. Two statistical classifiers were generated based on the lipid information acquired. Classifier 1 was built to distinguish symptomatic PCR-positive from asymptomatic PCR-negative individuals, yielding a cross-validation accuracy of 83.5%, sensitivity of 76.6%, and specificity of 86.6%, and validation set accuracy of 89.6%, sensitivity of 100%, and specificity of 85.3%. Classifier 2 was built to distinguish symptomatic PCR-positive patients from negative individuals including symptomatic PCR-negative patients with moderate to severe symptoms and asymptomatic individuals, yielding a cross-validation accuracy of 78.4%, specificity of 77.21%, and sensitivity of 81.8%. Collectively, this study suggests that the lipid profiles detected directly from nasopharyngeal swabs using MasSpec Pen-ESI mass spectrometry (MS) allow fast (under a minute) screening of the COVID-19 disease using minimal operating steps and no specialized reagents, thus representing a promising alternative high-throughput method for screening of COVID-19.


Adaptation of the membrane fatty acid composition by growth in the presence of n-alkanols influences glycosyltransferase expression in Streptococcus salivarius.
Growth of Streptococcus salivarius ATCC 25975 in the presence of n-alkanols in the series methanol to decan-1-ol led to a decrease in the unsaturated to saturated fatty acid ratio. Each member of the set of n-alkanols which was examined over a range of concentrations possessed a point at which extracellular glucosyltransferase (GTF) production was minimal; increasing the concentration of the n-alkanol past this point stimulated GTF production. This effect was greatest with hexan-1-ol although it was observed to a lesser extent with pentan-1-ol and heptan-1-ol. Reduced cell-associated fructosyltransferase activity was observed with increasing concentrations of each n-alkanol. Growth in the presence of 25 mM-propan-1-ol gave rise to a fatty acid profile in which 55% of the fatty acids were of an odd chain length. S. salivarius ATCC 25975 was shown to be able to utilize ethanol in a similar manner to propan-1-ol by growing it in the presence of 400 mM-[14C]ethanol. Analysis of the membrane lipids at the stationary phase of growth indicated that 17.6% of the carbon of the fatty acids was derived from ethanol. A leaky adh mutant, S. salivarius MJ 37501, was isolated. The leaky nature of the mutant enabled it to incorporate reduced levels of odd-chain-length fatty acids into its membrane lipids when grown in the presence of 100 mM-propan-1-ol, but not when grown in the presence of 25 mM-propan-1-ol. S. salivarius ATCC 25975 therefore metabolized propan-1-ol (and ethanol) via a constitutive alcohol dehydrogenase.


Pediatric choroid plexus neoplasms.
Choroid plexus tumors (CPT) are rare childhood neoplasms. The relatively small number of reported cases and the controversies surrounding the clinical and pathological classification of these tumors have made it difficult to define a standard of care for these patients. Our intention is to contribute to the body of knowledge of these tumors and further define the role of adjuvant therapy. We performed a retrospective review of 14 children with choroid plexus neoplasms referred to St. Jude Children's Research Hospital between October 1985 and December 1987. Ten patients had choroid plexus carcinoma (CPC) based on pathologic criteria and evidence of brain invasion at surgery or leptomeningeal disease (M+); 4 patients had choroid plexus papilloma (CPP). Patients with CPP were initially treated with surgery alone whereas patients with CPC were generally treated with postoperative therapy that included chemotherapy (CT) and/or craniospinal irradiation (CSI) with a focal boost to the primary site. For most patients CT consisted of combinations of cyclophosphamide, etoposide, vincristine, and a platinum agent. The median CSI dose was 35.2 Gy (range 24-46.2 Gy). The median primary site dose was 55.2 Gy (range 49.6-64 Gy). Seven of the 10 CPC cases presented with leptomeningeal dissemination; two of these patients have succumbed to disease. Of the 3 patients with M0 status, all are alive with no evidence of disease (NED). The medial time to relapse from the time of surgery was 5.3 mo (range 3-25 mo). Seven CPC patients were treated with gross total resection (GTR). Three of these patients (2 M0, 1 M+) received CT without CSI and are currently NED (27, 69, and 60 mo respectively). One M+ patient progressed on CT and has stable disease after CSI (6 mo), one (M0) received CT and CSI and is NED (120 mo), one (M+) is currently on CT with objective response (3 mo) and one (M+) died of progressive disease (24.5 mo) despite CT and CSI. Three patients with CPC had subtotal resection (STR). One of these patients (M+) received CT and CSI and is NED (23 mo), one (M0) had an elective second resection GTR alone and is currently NED (153 mo), and one (M+) developed progressive disease (13.5 mo) while on CT and died despite CSI. Among the 4 CPP patients, GTR was performed in two; both were NED at 54 and 81 mo. Two patients with CPP (one with focal atypia) were treated with STR initially; both transformed to CPC at 7 and 27 mo, respectively. Both were currently NED following salvage with (1) GTR and CSI alone (98 mo) or (2) STR, CT, and CSI (62 mo). Six of the 12 survivors in this series had significant neuropsychological sequelae. The prognosis of CPP is good for patients treated with GTR. Malignant transformation occurred in 2 CPP patients with less than GTR. Patients with localized CPC who undergo GTR have had a favorable outcome with the addition of chemotherapy or irradiation. CSI may not be routinely indicated in M0 children following GTR. There is evidence that salvage with radiation therapy may be successful following progression on chemotherapy. For patients treated with STR, the use of CT and CSI appears to be necessary.


Knockdown of Urothelial Carcinoma-Associated 1 Suppressed Cell Growth and Migration Through Regulating miR-301a and CXCR4 in Osteosarcoma MHCC97 Cells.
Liver cancer is one of the most common malignancies in the world and a leading cause of cancer-related mortality. Accumulating evidence has highlighted the critical role of long noncoding RNAs (lncRNAs) in various cancers. The present study aimed to explore the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in cell growth and migration in MHCC97 cells and its underlying mechanism. First, we assessed the expression of UCA1 in MHCC97 and three other cell lines by RT-qPCR. Then the expression of UCA1, miR-301a, and CXCR4 in MHCC97 cells was altered by transient transfection. The effects of UCA1 and miR-301 on cell viability, migration, invasion, and apoptosis were assessed. The results revealed that UCA1 expression was relatively higher in MHCC97 cells than in MG63, hFOB1.19, and OS-732 cells. Knockdown of UCA1 reduced cell viability, inhibited migration and invasion, and promoted cell apoptosis. However, the effect of UCA1 knockdown on cell growth and migration was blocked by miR-301a overexpression, whose expression was regulated by UCA1. We also found that miR-301a positively regulated CXCR4 expression. CXCR4 inhibition reversed the effect of miR-301a overexpression on cell growth and migration. Moreover, miR-301a activated the Wnt/β-catenin and NF-κB pathways via regulating CXCR4. The present study demonstrated that UCA1 inhibition exerted an antigrowth and antimigration role in MHCC97 cells through regulating miR-301a and CXCR4 expression.


Resistance to enfuvirtide, the first HIV fusion inhibitor.
Fusion inhibitors are a new class of antiretroviral drugs (ARVs) for the treatment of human immunodeficiency virus infection. Enfuvirtide is the first in this class to reach market approval. Fusion inhibitors block the last step in the three-step viral entry process consisting of attachment, co-receptor binding and fusion, thereby preventing viral capsid entry into the host cell. Enfuvirtide has a unique mechanism of action and high viral target specificity, and in clinical trials has been shown to exhibit both high efficacy and low toxicity. Enfuvirtide is a peptide mimetic of an essential region within viral envelope glycoprotein gp41 that functions by blocking gp41 structural rearrangements at a transitional pre-fusion conformation. Although different clinical isolates show variation in susceptibility to enfuvirtide, primary resistance has not been observed, and thus enfuvirtide-naive isolates remain clinically sensitive. Acquired resistance centres round a 10 amino acid motif between residues 36 and 45 in gp41 that forms part of the binding site of enfuvirtide. The 10 amino acid motif is critical for viral fusion, and enfuvirtide-resistant mutants show poor replicative capacity compared with wild type. Reversion to a wild-type, drug-sensitive state has been reported following enfuvirtide withdrawal.


Hypertrophic adenoid is a major infection site of human bocavirus 1.
Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide, mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can persist for long periods of time in humans, probably through maintaining concatemers of the virus single-stranded DNA genome in the nuclei of infected cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine tonsils samples from patients with chronic adenotonsillar diseases, but nothing is known about the virus replication levels in those tissues. A 3-year prospective hospital-based study was conducted to detect and quantify HBoV1 DNA and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal secretions (NPS), and peripheral blood (PB) from patients undergoing tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS, and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in this tissue. High viral loads and detectable mRNA in the AD were associated with HBoV1 detection in the other sample sites. The adenoids are an important site of HBoV1 replication and persistence in children with tonsillar hypertrophy. The adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and this is associated with the detection of HBoV1 in secretions.


Family and Social Context Contributes to the Interplay of Economic Insecurity, Food Insecurity, and Health.
In this study, we show how household health, economic instability, and food insecurity are inextricably linked; disruptions in individual health or income create cumulative and interdependent challenges faced by multiple household members. Drawing upon semi-structured focus groups with English- and Spanish-speaking clients of an urban food pantry, we demonstrate: (1) the impact of economic scarcity on health, (2) the impact of one household member's health on the health and food security of all household members, and (3) food sharing behaviors among family and social networks, including multi-generational families and non-kin individuals. We identify the gap between household-level assessments of food insecurity and individual-level health reports, which may obscure poor health among other household members. Understanding the social and family context of health and food insecurity may inform future interventions that address the interrelated challenges of diverse and disadvantaged households and communities.


An adoptive transfer method to detect low-dose radiation-induced bystander effects in vivo.
The potential for irradiated cells to induce biological effects in their unirradiated neighbors (known as the bystander effect) has been observed repeatedly in vitro. However, whether bystander effects occur in vivo under the specific conditions relevant to low-dose radiation protection is still unclear. To test this, the fate of bystander cells in the mouse spleen was examined using an adoptive transfer method designed to replicate the rare, irradiated cells in an organ that might be expected after a low-dose-rate, low-LET radiation exposure. Splenic lymphocytes radiolabeled with low activities of (3)H-thymidine were introduced into the spleens of unirradiated recipient mice. In this study, the apoptotic and proliferative response of the neighboring bystander spleen cells was compared to the response of spleen cells in parallel control recipients that received sham-irradiated cells. Neither the local area surrounding lodged radiolabeled cells nor the spleen as a whole showed a change in apoptosis or proliferation either 1 or 3 days after adoptive transfer. Increasing the irradiated cell numbers, increasing the mean (3)H-thymidine activity per cell, or exposing cells ex vivo to an acute X-ray dose also had no effect. Possible reasons for the absence of a bystander effect in the spleen under these conditions are discussed.


TCP BBR-n: Increased throughput for wireless-AC networks.
Google proposed a new TCP congestion control algorithm (CCA), Bottleneck Bandwidth and Round-trip propagation time (BBR) which has opened up new dimensions in congestion control. BBR tries to operate near Kleinrock's operating point to avoid excessive queue formation at the bottleneck and to use the link bandwidth optimally. BBR creates a model of the network path by measuring the bottleneck bandwidth and minimum round-trip time (RTT) to maximize the delivery rate and minimize latency. BBR v2 is an updated version of BBR which addresses many shortcomings of the original BBR (BBR v1) such as interprotocol fairness, RTT fairness, and excessive retransmissions. However, BBR v2 has certain limitations in its operation in IEEE 802.11ac (Wi-Fi 5) networks. The default BBR v2 limits the throughput of Wi-Fi 5 and an increased latency has been observed. This is because the Wi-Fi 5 frame aggregation logic is underutilized and fewer frames are being sent to the Wi-Fi 5 interface. In this paper, we have proposed BBR-n (BBR new) which provides better throughput than the generic BBR v2 in the Wi-Fi 5 networks. Real-time experiments were performed over a physical testbed using Flent to confirm that BBR-n achieves over double throughput as compared to generic BBR v2 and reduced latency in networks as compared to pure loss-based variants such as Cubic and Reno.


Acyclovir Sensitivity and Neurovirulence of Herpes Simplex Virus Type 1 with Amino Acid Substitutions in the Viral Thymidine Kinase Gene, Which Were Detected in the Patients with Intractable Herpes Simplex Encephalitis Previously Reported.
Several cases of herpes simplex encephalitis (HSE) caused by acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) have been reported. Amino acid substitutions of R41H, Q125H, and A156V in the viral thymidine kinase (vTK) gene have been reported to confer ACV resistance. Recombinant HSV-1 clones, containing each amino acid substitution in the vTK gene, were generated using the bacterial artificial chromosome system. A recombinant HSV-1 with the Q125H substitution showed ACV resistance while the R41H or A156V substitutions were ACV-sensitive. Furthermore, the Q125H recombinant HSV-1 was less virulent than the repaired virus, but it maintained neurovirulence in mice at relatively high levels. Substitution of Q125H, which was detected in the neonatal HSE patient, conferred ACV resistance, but the substitutions of R41H and A156V, which were detected in immunocompetent adult HSE patients, did not. This suggests that HSE caused by ACV-resistant HSV-1 might be a very rare event to occur during the course of ACV treatment in immunocompetent patients. Showing resistance to ACV treatment does not always indicate emergence of ACV-resistant HSV-1 in HSE patients.


Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background.
Sandy mice have a deletion mutation in the gene encoding dysbindin-1, Dtnbp1, with consequent reduction of the protein in heterozygotes and its loss in homozygotes. The sandy mouse thus serves as an animal model of dysbindin-1 function. As this protein is concentrated in synaptic tissue and affects transmitter release, it may affect neuronal processes that mediate behavior. To investigate the neurobehavioral effects of the Dtnbp1 mutation, we studied littermate sandy and wild-type controls on a C57BL/6J genetic background. The three animal groups were indistinguishable in their external physical characteristics, sensorimotor skills and indices of anxiety-like behaviors. In the open field, however, homozygous animals were hyperactive and appeared to show less habituation to the initially novel environment. In the Morris water maze, homozygous animals displayed clear deficits in spatial learning and memory with marginal deficits in visual association learning. Apart from the last mentioned deficits, these abnormalities are consistent with hippocampal dysfunction and in some cases with elevated dopaminergic transmission via D2 dopamine receptors. As similar deficits in spatial learning and memory have been found in schizophrenia, where decreased dysbindin-1 has been found in the hippocampus, the sandy mouse may also model certain aspects of cognition and behavior relevant to schizophrenia.


Development of multiplex real-time PCR for rapid identification and quantitative analysis of Aspergillus species.
The identification of Aspergillus species and azole resistance is highly important for the treatment of invasive aspergillosis (IA), which requires improvements in current fungal diagnostic methods. We aimed to develop multiplex real-time PCR to identify major Aspergillus section and azole resistance. BenA and cyp51A genes were used to design primers, probes, and control DNA for multiplex PCR. Qualitative and quantitative analysis was conducted for 71 Aspergillus and 47 non-Aspergillus isolates. Further, the limit of detection (LOD) and limit of quantitation (LOQ) from hyphae or conidia were determined according to the culture time. Newly developed real-time PCR showed 100% specificity to each Aspergillus section (Fumigati, Nigri, Flavi, and Terrei), without cross-reaction between different sections. In quantitative analysis of sensitivity measurements, LOD and LOQ were 40 fg and 400 fg, respectively. Melting temperature analysis of the cyp51A promoter to identify azole resistance showed temperatures of 83.0 ± 0.3°C and 85.6 ± 0.6°C for susceptible A. fumigatus and resistant isolates with TR34 mutation, respectively. The minimum culture time and fungal colony size required for successful detection were 24 h and 0.4 cm in diameter, respectively. The developed multiplex real-time PCR can identify common Aspergillus sections quantitatively and detect presence of the TR34 mutation. Further, this method shows high sensitivity and specificity, allowing successful detection of early-stage fungal colonies within a day of incubation. These results can provide a template for rapid and accurate diagnosis of IA.


Severely increased blood pressure in the emergency department.
Patients with severely increased blood pressure often present to the emergency department. Emergency physicians evaluate and treat hypertension in various contexts, ranging from the compliant patient with well-controlled blood pressure to the asymptomatic patient with increased blood pressure to the critically ill patient with increased blood pressure and acute target-organ deterioration. Despite extensive study and national guidelines for the assessment and treatment of chronically increased blood pressure, there is no clear consensus on the acute management of patients with severely increased blood pressure. In this article, we examine the broad spectrum of disease, from the asymptomatic to critically ill patient, and the dilemma it creates for the emergency physician in deciding how and when in the process to intervene.