Bacterial resistance to ultraviolet irradiation under anaerobiosis: implications for pre-phanerozoic evolution.
The concept that low concentrations of atmospheric oxygen and consequent unattenuated ultraviolet irradiation limited the emergence of Phanerozoic life, the Berkner-Marshall hypothesis, is no longer tenable. Anaerobic bacteria, which probably evolved far earlier than Metazoa, were irradiated in a special chamber under strictly anaerobic conditions. Both intrinsic resistance and photoreactivation by visible light were discovered in obligately and facultatively anaeroboc microbes. Atmospheric scientists have shown that small amounts of oxygen would have limied pre-Phanerozoic surface ultraviolet irradiation to fluxes well below those used in the anaerobic experiments described. Since adequate ultraviolet protection mechanisms evolved early, the late Proterozoic appearance of Metazoa probably was not related to high fluxes of solar ultraviolet radiation.


Associative memory retrieval modulates upcoming perceptual decisions.
Expectations can inform fast, accurate decisions. But what informs expectations? Here we test the hypothesis that expectations are set by dynamic inference from memory. Participants performed a cue-guided perceptual decision task with independently-varying memory and sensory evidence. Cues established expectations by reminding participants of past stimulus-stimulus pairings, which predicted the likely target in a subsequent noisy image stream. Participant's responses used both memory and sensory information, in accordance to their relative reliability. Formal model comparison showed that the sensory inference was best explained when its parameters were set dynamically at each trial by evidence sampled from memory. Supporting this model, neural pattern analysis revealed that responses to the probe were modulated by the specific content and fidelity of memory reinstatement that occurred before the probe appeared. Together, these results suggest that perceptual decisions arise from the continuous sampling of memory and sensory evidence.


Distressed and distracted by COVID-19 during high-stakes virtual interviews: The role of job interview anxiety on performance and reactions.
Employers have increasingly turned to virtual interviews to facilitate online, socially distanced selection processes in the face of the COVID-19 pandemic. However, there is little understanding about the experience of job candidates in these virtual interview contexts. We draw from Event System Theory (Morgeson et al., 2015) to advance and test a conceptual model that focuses on a high-stress, high-stakes setting and integrates literatures on workplace stress with literatures on applicant reactions. We predict that when applicants ruminate about COVID-19 during an interview and have higher levels of COVID-19 exhaustion, they will have higher levels of anxiety during virtual interviews, which in turn relates to reduced interview performance, lower perceptions of fairness, and reduced intentions to recommend the organization. Further, we predict that three factors capturing COVID-19 as an enduring and impactful event (COVID-19 duration, COVID-19 cases, COVID-19 deaths) will be positively related to COVID-19 exhaustion. We tested our propositions with 8,343 job applicants across 373 companies and 93 countries/regions. Consistent with predictions, we found a positive relationship between COVID-19 rumination and interview anxiety, and this relationship was stronger for applicants who experienced higher (vs. lower) levels of COVID-19 exhaustion. In turn, interview anxiety was negatively related to interview performance, fairness perceptions, and recommendation intentions. Moreover, using a relevant subset of the data (n = 6,136), we found that COVID-19 duration and deaths were positively related to COVID-19 exhaustion. This research offers several insights for understanding the virtual interview experience embedded in the pandemic and advances the literature on applicant reactions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Nanodisc Films for Membrane Protein Studies by Neutron Reflection: Effect of the Protein Scaffold Choice.
Nanodisc films are a promising approach to study the equilibrium conformation of membrane bound proteins in native-like environment. Here we compare nanodisc formation for NADPH-dependent cytochrome P450 oxidoreductase (POR) using two different scaffold proteins, MSP1D1 and MSP1E3D1. Despite the increased stability of POR loaded MSP1E3D1 based nanodiscs in comparison to MSP1D1 based nanodiscs, neutron reflection at the silicon-solution interface showed that POR loaded MSP1E3D1 based nanodisc films had poor surface coverage. This was the case, even when incubation was carried out under conditions that typically gave high coverage for empty nanodiscs. The low surface coverage affects the embedded POR coverage in the nanodisc film and limits the structural information that can be extracted from membrane bound proteins within them. Thus, nanodisc reconstitution on the smaller scaffold proteins is necessary for structural studies of membrane bound proteins in nanodisc films.


Economic shocks, resilience, and male suicides in the Great Recession: cross-national analysis of 20 EU countries.
During the 2007-11 recessions in Europe, suicide increases were concentrated in men. Substantial differences across countries and over time remain unexplained. We investigated whether increases in unaffordable housing, household indebtedness or job loss can account for these population differences, as well as potential mitigating effects of alternative forms of social protection. Multivariate statistical models were used to evaluate changes in suicide rates in 20 EU countries from 1981-2011. Models adjusted for pre-existing time trends and country-fixed effects. Interaction terms were used to evaluate modifying effects. Changes in levels of unaffordable housing had no effect on suicide rates (P = 0.32); in contrast, male suicide increases were significantly associated with each percentage point rise in male unemployment, by 0.94% (95% CI: 0.51-1.36%), and indebtedness, by 0.54% (95% CI: 0.02-1.06%). Spending on active labour market programmes (ALMP) (-0.26%, 95% CI: -0.08 to -0.45%) and high levels of social capital (-0.048%, 95% CI: -0.0096 to -0.087) moderated the unemployment-suicide association. There was no interaction of the volume of anti-depressant prescriptions (P = 0.51), monetary benefits to unemployed persons (P = 0.77) or total social protection spending per capita (P = 0.37). Active labour market programmes and social capital were estimated to have prevented ∼ 540 and ∼ 210 male suicides, respectively, arising from unemployment in the countries studied. Job losses were a critical determinant of variations in male suicide risks in Europe's recessions. Greater spending on ALMP and levels of social capital appeared to mitigate suicide risks.


[Toxigenic Bacillus cereus detection in lactic products with spices and dehydrated milk collected in Costa Rica].
Bacillus cereus is a Gram positive rod widely distributed in nature and associated to different types of food that, under some circumstances, may cause pathology to human beings. Diarrheic and emetic strains have been described based on the type of toxins produced. In order to determine the risk to health represented by this bacteria, the toxigenic potential of strains isolated from cheese with spices, spread cheese with spices and dehydrated milk, all sold in San José, Costa Rica, were determined using a multiplex PCR technique with oligonucleotides specific for the genes coding toxins HBL and Nhe. From 45 samples collected, 15 isolates of B cereus were obtained (60% coming from spread cheese with spices 7% from dehydrated milk and 13% from cheese with spices). All the strains analyzed presented at least one of the genes analyzed; six of them, coming from dehydrated milk and spread cheese, showed molecular evidence of the genes nheB, nheA, nheC, hblD, hblA y hblC, confirming the correlation described for the presence of operons codifying for HBL and Nhe. Nevertheless, the no detection of a gene cannot be considered as a definitive proof of its absence, given the existence of polymorphism in the sequences of the genes analyzed. The results obtained show that multiple of the B cereus strains found in lactic products from Costa Rica have the necessary genes for synthesizing toxins, so the correct handling of these products is very important since they can represent a risk for public health.


Concurrent 2018 Hot Extremes Across Northern Hemisphere Due to Human-Induced Climate Change.
Extremely high temperatures pose an immediate threat to humans and ecosystems. In recent years, many regions on land and in the ocean experienced heat waves with devastating impacts that would have been highly unlikely without human-induced climate change. Impacts are particularly severe when heat waves occur in regions with high exposure of people or crops. The recent 2018 spring-to-summer season was characterized by several major heat and dry extremes. On daily average between May and July 2018 about 22% of the populated and agricultural areas north of 30° latitude experienced concurrent hot temperature extremes. Events of this type were unprecedented prior to 2010, while similar conditions were experienced in the 2010 and 2012 boreal summers. Earth System Model simulations of present-day climate, that is, at around +1 °C global warming, also display an increase of concurrent heat extremes. Based on Earth System Model simulations, we show that it is virtually certain (using Intergovernmental Panel on Climate Change calibrated uncertainty language) that the 2018 north hemispheric concurrent heat events would not have occurred without human-induced climate change. Our results further reveal that the average high-exposure area projected to experience concurrent warm and hot spells in the Northern Hemisphere increases by about 16% per additional +1 °C of global warming. A strong reduction in fossil fuel emissions is paramount to reduce the risks of unprecedented global-scale heat wave impacts.


Controlling size, amount, and crystalline structure of nanoparticles deposited on graphenes for highly efficient energy conversion and storage.
A facilitated electrochemical reaction at the surface of electrodes is crucial for highly efficient energy conversion and storage. Herein, various nanoparticles (NPs) including Au, Pt, Pd, Ru, and RuO(2), were synthesized in situ and directly deposited on the ionic liquid (IL)-functionalized reduced graphene oxides (RGOs) in a controlled manner. The size, amount, and crystalline structures of discrete NPs were readily controlled, giving rise to enhanced methanol oxidation and pseudocapacitance. The well-defined nanostructure of decorated NPs and the favorable interaction between ILs and RGOs (or NPs) facilitated the electrochemical reaction, where NPs acted as electrocatalysts for energy conversion and played the role of redox-active electrodes for energy storage.


Risk of aspiration during anesthesia in patients with congenital insensitivity to pain with anhidrosis: case reports and review of the literature.
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease, characterized by episodes of unexplained fever, anhidrosis, pain insensitivity despite intact tactile perception, self-mutilating behavior, mental retardation, and autonomic nervous system (ANS) abnormalities. We present a case series of three patients with CIPA who underwent semielective orthopedic surgery under general anesthesia complicated by intraoperative regurgitation, and subsequent aspiration in two of the three cases. All three patients were nil per os (NPO) for at least 8 h prior to surgery. Two patients had their airways maintained with a laryngeal mask airway (LMA), and one patient had an endotracheal tube (ETT). The patients with an LMA suffered aspiration of gastric contents and subsequently developed hypoxic cardiac arrest. Although the patient with an ETT in situ regurgitated intraoperatively, the presence of the ETT prevented aspiration and any further potential complications. We review the perioperative complications typically observed in patients with CIPA and discuss the risks of using an LMA in these patients. We recommend that patients with CIPA always should be considered as having a "full stomach", regardless of the duration of their NPO status, due to their coexisting ANS abnormalities. Therefore, rapid-sequence induction with an ETT should be utilized for the anesthetic management in every patient with CIPA.


The Salmonella Effector SseK3 Targets Small Rab GTPases.
During infection, Salmonella species inject multiple type III secretion system (T3SS) effector proteins into host cells that mediate invasion and subsequent intracellular replication. At early stages of infection, Salmonella exploits key regulators of host intracellular vesicle transport, including the small GTPases Rab5 and Rab7, to subvert host endocytic vesicle trafficking and establish the Salmonella-containing vacuole (SCV). At later stages of intracellular replication, interactions of the SCV with Rab GTPases are less well defined. Here we report that Rab1, Rab5, and Rab11 are modified at later stages of Salmonella infection by SseK3, an arginine N-acetylglucosamine (GlcNAc) transferase effector translocated via the Salmonella pathogenicity island 2 (SPI-2) type III secretion system. SseK3 modified arginines at positions 74, 82, and 111 within Rab1 and this modification occurred independently of Rab1 nucleotide binding. SseK3 exhibited Golgi localization that was independent of its glycosyltransferase activity but Arg-GlcNAc transferase activity was required for inhibition of alkaline phosphatase secretion in transfected cells. While SseK3 had a modest effect on SEAP secretion during infection of HeLa229 cells, inhibition of IL-1 and GM-CSF cytokine secretion was only observed upon over-expression of SseK3 during infection of RAW264.7 cells. Our results suggest that, in addition to targeting death receptor signaling, SseK3 may contribute to Salmonella infection by interfering with the activity of key Rab GTPases.


Evidence of poorer survival in pregnancy-associated breast cancer.
To compare stage distribution, tumor characteristics, and survival outcome in pregnancy-associated and non-pregnancy-associated breast cancer, and to evaluate pregnancy as a risk factor for mortality in breast cancer. The California Cancer Registry (1991-1999) was linked with the California Patient Discharge Data Set to identify women with breast cancer occurring within 9 months before or 1 year after an obstetric delivery. Age-matched, non-pregnancy-associated breast cancer controls were also identified. Demographics, cancer stage, tumor size, histology, hormone receptor status, type of treatment, and survival were reviewed and compared. Predictive factors for death from breast cancer were identified using proportional hazards modeling. Seven hundred ninety-seven pregnancy-associated breast cancer cases were compared with 4,177 non-pregnancy-associated breast cancer controls. Pregnancy-associated breast cancer cases were significantly more likely to have more advanced stage, larger primary tumor, hormone receptor negative tumor, and mastectomy as a component of their treatment. In survival analysis, pregnancy-associated breast cancer had a higher death rate than non-pregnancy-associated breast cancer (39.2% compared with 33.4%, P=.002). In a multivariable analysis, advancing stage (2.22-10.76 times the risk of death for stages II-IV), race (African Americans had 68% increased risk of death over non-Hispanic whites), hormone receptor-negative tumors (20% increased risk of death over receptor-positive tumors), and pregnancy (14% increased risk of death over nonpregnant women) all were significant predictors of death. Pregnancy-associated breast cancer presented with more advanced disease, larger tumors, and increased percentage of hormone receptor-negative tumors. When controlled for stage, race, and hormone receptor status, pregnancy-associated breast cancer cases had a slightly higher risk of death, even when only localized-stage disease was considered. II.


Patterns and dynamics of rapid local adaptation and sex in varying habitat types in rotifers.
Local adaptation is an important principle in a world of environmental change and might be critical for species persistence. We tested the hypothesis that replicated populations can attain rapid local adaptation under two varying laboratory environments. Clonal subpopulations of the cyclically parthenogenetic rotifer Brachionus calyciflorus were allowed to adapt to two varying harsh and a benign environment: a high-salt, a food-limited environment and untreated culture medium (no salt addition, high food). In contrast to most previous studies, we re-adjusted rotifer density to a fixed value (two individuals per ml) every 3-4 days of unrestricted population growth, instead of exchanging a fixed proportion of the culture medium. Thus our dilution regime specifically selected for high population growth during the entire experiment and it allowed us to continuously track changes in fitness (i.e., maximum population growth under the prevailing conditions) in each population. After 56 days (43 asexual and eight sexual generations) of selection, the populations in the harsh environments showed a significant increase in fitness over time relative to the beginning compared to the population in untreated culture medium. Furthermore, the high-salt population exhibited a significantly elevated ratio of sexual offspring from the start of the experiment, which suggested that this environment either triggered higher rates of sex or that the untreated medium and the food-limited environment suppressed sex. In a following assay of local adaptation we measured population fitness under "local" versus "foreign" conditions (populations adapted to this environment compared to those of the other environment) for both harsh habitats. We found significantly higher fitness values for the local populations (on average, a 38% higher fitness) compared to the foreign populations. Overall, local adaptation was formed rapidly and it seemed to be more pronounced in the high-salt treatment.


Familial influence on offspring gambling: a cognitive mechanism for transmission of gambling behavior in families.
The problem-gambling literature has identified a range of individual, cognitive, behavioral and emotional factors as playing important roles in the development, maintenance and treatment of problem gambling. However, familial factors have often been neglected. The current study aims to investigate the possible influence of parental factors on offspring gambling behavior. A total of 189 families (546 individuals) completed several questionnaires including the South Oaks Gambling Screen (SOGS) and the Gambling Related Cognition Scale (GRCS). The relationships were examined using Pearson product-moment correlations and structural equation modeling (SEM) analyses. Results showed that generally parents' (especially fathers') gambling cognitions and gambling behaviors positively correlated with offspring gambling behaviors and cognitions. However, SEM analyses showed that although parental gambling behavior was directly related to offspring gambling behavior, parental cognitions were not related to offspring gambling behavior directly but indirectly via offspring cognitions. The findings show that the influence of parental gambling cognition on offspring gambling behavior is indirect and via offspring cognitions. The results suggest a possible cognitive mechanism of transmission of gambling behavior in the family from one generation to the next.


A flexible lab-on-a-chip for the synthesis and magnetic separation of magnetite decorated with gold nanoparticles.
Magnetite decorated with gold nanoparticles (Fe3O4-AuNPs) is a ferrimagnetic material with unprecedented applications in immunosensors, as a contrast agent for imaging diagnosis, and for the photothermal ablation of tumor cells. Here, we show the preparation of controlled amounts of Fe3O4-AuNPs without organic solvents, surfactants, or heat treatment. For this, we have developed a customized natural-rubber-based microfluidic device (NRMD) as a flexible lab-on-a-chip for the decoration of Fe3O4 with AuNPs. With a novel NRMD configuration, monodisperse Fe3O4-NPs (ϕ = 10 nm) decorated with AuNPs (ϕ = 4 nm) were readily obtained. The AuNPs were homogenous in terms of their size and their distribution on the Fe3O4-NP surfaces. Furthermore, the lab-on-a-chip was projected with an internal system for magnetic separation, an innovation in terms of aqueous/carrier phase separation. Finally, the nanomaterials produced with this NRMD are free of organic solvents and surfactants, allowing them to be used directly for medical applications.


m-Azido-phencyclidine covalently labels the rat brain PCP receptor, a putative K channel.
Phencyclidine (PCP) is a schizophrenomimetic drug of abuse. PCP binds with high affinity (apparent dissociation constant, KD less than 10(-6) M) to rat brain membranes and blocks, selectively, a voltage-gated, noninactivating K channel found in rat brain synaptosomes (presynaptic nerve terminals). Thus, it has been proposed that the high-affinity PCP receptor in brain is this K channel. Consistent with this hypothesis, we now show that several K channel blockers displace 3H-PCP from the rat brain receptor. Additionally, we have used a photolabile analog of PCP, m-azido-PCP (Az-PCP), to identify the brain PCP receptor/putative K channel. In the dark, Az-PCP bound reversibly to 2 classes of sites on rat brain synaptic membranes [KD = 0.14 +/- 0.01 microM (n = 5) for high-affinity binding, and KD = 255 +/- 55 microM for low-affinity binding]. Competitive binding studies between Az-3H-PCP and nonlabeled PCP analogs, and between Az-PCP and several tritiated PCP analogs, indicated that the high-affinity Az-PCP binding site is the high-affinity PCP receptor. Several amino-pyridines (APs) and tetraalkylamines (TAAs), which are known to block K channels in excitable cells, were also found to displace 3H-PCP from its high-affinity binding site on rat brain synaptic membranes. The rank order of potency for displacement of 3H-PCP from this site for the APs was 4-AP approximately equal to 3,4-diAP greater than 2-AP much greater than 3-AP; for the TAAs it was TBA greater than TEA much greater than TMA (the tetra-butyl, ethyl, and methyl amines, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Does formate reduce alpha-ketoglutarate and ammonia to glutamate?
The reported reduction of alpha-ketoglutarate and ammonia by formate is much slower than described (Morowitz et al., 1995). The formate reduction if any is small under these conditions. Glutamate is produced from a reduction by a second molecule of alpha-ketoglutarate involving an oxidative decarboxylation.


The legal and non-legal barriers to abortion access in Australia: a review of the evidence.
In Australia, about one in four pregnancies results in an induced abortion. The termination of a pregnancy is still, however, a criminal act in most jurisdictions, and access to abortion is not without barriers. This paper analyses existing access barriers and their implications. Databases and the grey literature were searched for publications that examined any legal and/or non-legal abortion access barrier applicable to Australia (2000-2016). Only those barriers that had been demonstrated to be the most restrictive were included and categorised. From the initial 410 studies, only 20 publications were identified that matched the inclusion criteria. They indicated that access barriers do indeed exist in Australia. In many parts of Australia, abortion is only legal under strict conditions. Relatively strong evidence was found on the limited abortion access of rural women and of an imminent shortage in the provision of late abortions. For other barriers only limited research evidence existed, or merely opinions were expressed. Very few studies were undertaken to link barriers to outcomes. Although this review can form a base for the national improvement of abortion access, the gap found in Australian research demonstrates a need for additional studies.


Dermatophytes and other fungi associated with skin mycoses in Tripoli, Libya.
This study sought to determine the prevalence of skin infections and their causative agents in the Libyan population. Samples were collected from 2224 patients attending the Dermatology Clinics of the Tripoli Medical Centre (TMC) between August 1997 and December 1999 and were submitted to a mycology laboratory for analysis. Diagnosis was confirmed by microscopic examination in 1180 cases (53.1%) and the causative agent was isolated and cultured in 1160 cases (52.2%). Dermatophytes, Malassezia furfur and Candida albicans were the most common etiological agents isolated. Tinea corporis accounted for 45.9% of cases (85% of cases occurred in children below 15 years of age). The frequency of the other clinical types in descending order was pityriasis versicolor 27.8% (322 cases), candidiosis 13.4% (156 cases), tinea pedis 8.1% (94 cases), tinea manuum 2.6% (30 cases) and tinea barbae 2.2% (26 cases). Trichophyton violaceum was the most common etiological agent, responsible for 44% (300 cases) of dermatophyte infections. Malassezia furfur was ranked the second most frequent causative agent being found in 27.8% of cases, followed by Trichophyton rubrum 13.8% (160 cases) and Candida albicans 10% (116 cases). Other species isolated included Microsporum canis 8.1% (94 cases), Epidermophyton floccosum 6.6% (76 cases) and Trichophyton mentagrophytes 3.1% (36 cases).


Infection and immunoglobulin concentrations in Chediak-Higashi mice.
The Chediak-Higashi syndrome (CHS) has been reported in man, cattle, mink, and mice. CHS humans and cattle have an increased incidence of pyogenic infections, whereas CHS mink are more susceptible to Aleutian disease. Age- and sex-matched groups of CHS mice (mutant strain) and C57 Bl/6N (parent strain) were challenged with Candida albicans, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus intravenously and Streptococcus pneumoniae intraperitoneally. A significant increase (P < 0.001) in mortality rate for the CHS mice was demonstrated with all five challenge organisms. Heterozygous mice challenged with C. albicans had a mortality rate essentially the same as C57 Bl/6N mice. The serum immunoglobulin concentrations of CHS mice were found to be the same or greater than the control or heterozygous mice. CHS mice have an increased susceptibility to pyogenic infections, which is not due to immunoglobulin deficiency. These mice may provide a useful laboratory model for the study of increased susceptibility to infection.


Induction of antisense Pax-3 expression leads to the rapid morphological differentiation of neuronal cells and an altered response to the mitogenic growth factor bFGF.
Mutations within the Pax-3 gene lead to a range of developmental abnormalities in both humans and mice. In this report, we have investigated the role that Pax-3 plays in neuronal cell development by specifically downregulating Pax-3 expression within a neuronal cell line. This was achieved by stably transfecting the neuronal cell line ND7 with an expression vector in which antisense Pax-3 RNA was produced under the control of the inducible MMTV promoter. In the stable transfectants, we found that the addition of dexamethasone led to the induction of antisense Pax-3 RNA and a rapid downregulation in endogenous Pax-3 protein expression. The decrease in endogenous Pax-3 protein expression corresponded with a dramatic change in the morphology of the cell: the normally rounded ND7 cells exhibited increased cell to substrate adhesion, extended long neurite processes and expressed genes such as snap-25 that are characteristic of a mature neuron. The morphological differentiation induced by a reduction in Pax-3 expression was followed 24-48 hours later by a cessation in cell proliferation. Interestingly the morphological differentiation and cessation in cell proliferation inducted in the cell lines lacking Pax-3 could be reversed by the addition of the mitogenic growth factor EGF but not by bFGF, whose receptor was downregulated in these cells. These results suggest that the expression of Pax-3 is essential to maintain the undifferentiated phenotype of these immature neuronal cells, and in its absence the cells acquire many of the characteristics of a mature neuronal cell. The slow onset of cell cycle arrest in the cells lacking Pax-3 argues against this transcription factor playing a direct role in the regulation of neuronal cell proliferation.


A possible role of prostaglandin F-2 alpha in the development of ovarian follicles in guinea-pigs.
Uterine PGF-2 alpha in the guinea-pig was eliminated by hysterectomy on Day 9 of the oestrous cycle and an increasing period of reduced PGF-2 alpha availability to the ovary was created by deferring replacement therapy with PGF-2 alpha from Day 9 to Day 11, 13 and 15. Ovulation, observed in 94% of the animals, was inevitably delayed. The treatment cycle length was progressively extended from the normal 15--16 days to 19--21 days. Similar results were obtained if endogenous PGF-2 alpha was suppressed by indomethacin injection instead of removing the uterus. That ovulation had been delayed and not occurred from more recently recruited follicles was evident from the total absence of atretic follicles of the expected size had they become atretic due to the lack of PGF-2 alpha at some critical time between Days 9 and 15. Pituitary homogenate and hCG injected on Day 16 shortened the PGF-2 alpha treatment cycle by 2 days, but stimulated ovulation in only 42% of the animals. When endogenous PGF-2 alpha was eliminated by hysterectomy and daily injections of indomethacin, follicular development ceased at approximately 0.8 mm instead of the 1.0 mm diameter found just before the preovulatory LH surge. It is suggested that (1) PGF-2 alpha has to act on developing follicles for a given period before they are capable of ovulation, and (2) that PGF-2 alpha is one of the factors required to stimulate the growth of the Graafian follicles at the end of the oestrous cycle.


Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-Tooth neuropathy.
Small heat shock proteins are molecular chaperones capable of maintaining denatured proteins in a folding-competent state. We have previously shown that missense mutations in the small heat shock protein HSPB1 (HSP27) cause distal hereditary motor neuropathy and axonal Charcot-Marie-Tooth disease. Here we investigated the biochemical consequences of HSPB1 mutations that are known to cause peripheral neuropathy. In contrast to other chaperonopathies, our results revealed that particular HSPB1 mutations presented higher chaperone activity compared with wild type. Hyperactivation of HSPB1 was accompanied by a change from its wild-type dimeric state to a monomer without dissociation of the 24-meric state. Purification of protein complexes from wild-type and HSPB1 mutants showed that the hyperactive isoforms also presented enhanced binding to client proteins. Furthermore, we show that the wild-type HSPB1 protein undergoes monomerization during heat-shock activation, strongly suggesting that the monomer is the active form of the HSPB1 protein.


A comparison between improvers and non-improvers among children with anemia enrolled in the WIC program.
To investigate differences between children ages one to five enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in the state of Texas whose anemia status improved and those whose anemia status did not improve. The study involved administration of a survey to a randomly selected stratified sample of parents and guardians of WIC children residing in the eleven public health regions in Texas. Subjects volunteered to complete the survey during a scheduled WIC appointment. A total of 459 usable surveys were completed. Fifty-one percent of the surveys were completed by parents/guardians of children classified as anemia improvers and 49% were completed by parents/guardians of children classified as anemia non-improvers. A majority of the respondents were the child's parent (97%). Most of the children were Hispanic/Latino (77%). More non-improvers than improvers were of young age (p < 0.01), had a parent/guardian who was 18-30 years of age (p < 0.01), lived in a household with four or more other children (p = 0.05) and were from households with a very low income (p = 0.03). Compared to improvers, non-improvers ate fewer snacks (p = 0.01) and a greater percentage never consumed dried fruits (p < 0.01). Knowledge level of the parents/guardians was similar for the two groups. A high percentage of parents/guardians of non-improvers incorrectly believed that their child's condition had improved. WIC staff and other public health educators can utilize these findings to identify those children with anemia who are at higher risk for non-improvement.


Gene expression profiles of cytosolic heat shock proteins Hsp70 and Hsp90 from symbiotic dinoflagellates in response to thermal stress: possible implications for coral bleaching.
Unicellular photosynthetic dinoflagellates of the genus Symbiodinium are the most common endosymbionts of reef-building scleractinian corals, living in a symbiotic partnership known to be highly susceptible to environmental changes such as hyperthermic stress. In this study, we identified members of two major heat shock proteins (HSPs) families, Hsp70 and Hsp90, in Symbiodinium sp. (clade C) with full-length sequences that showed the highest similarity and evolutionary relationship with other known HSPs from dinoflagellate protists. Regulation of HSPs gene expression was examined in samples of the scleractinian coral Acropora millepora subjected to elevated temperatures progressively over 18 h (fast) and 120 h (gradual thermal stress). Moderate to severe heat stress at 26°C and 29°C (+3°C and +6°C above average sea temperature) resulted in an increase in algal Hsp70 gene expression from 39% to 57%, while extreme heat stress (+9°C) reduced Hsp70 transcript abundance by 60% (after 18 h) and 70% (after 120 h). Elevated temperatures decreased an Hsp90 expression under both rapid and gradual heat stress scenarios. Comparable Hsp70 and Hsp90 gene expression patterns were observed in Symbiodinium cultures and in hospite, indicating their independent regulation from the host. Differential gene expression profiles observed for Hsp70 and Hsp90 suggests diverse roles of these molecular chaperones during heat stress response. Reduced expression of the Hsp90 gene under heat stress can indicate a reduced role in inhibiting the heat shock transcription factor which may lead to activation of heat-inducible genes and heat acclimation.


Characterization of cyclophilin D in freshwater pearl mussel (Hyriopsis schlegelii).
Cyclophilin D (referred to as HsCypD) was obtained from the freshwater pearl mussel (Hyriopsis schlegelii). The full-length cDNA was 2 671 bp, encoding a protein consisting of 367 amino acids. HsCypD was determined to be a hydrophilic intracellular protein with 10 phosphorylation sites and four tetratricopeptide repeat (TPR) domains, but no signal peptide. The core sequence region YKGCIFHRIIKDFMVQGG is highly conserved in vertebrates and invertebrates. Phylogenetic tree analysis indicated that CypD from all species had a common origin, and HsCypD had the closest phylogenetic relationship with CypD from Lottia gigantea. The constitutive mRNA expression levels of HsCypD exhibited tissue-specific patterns, with the highest level detected in the intestines, followed by the gonads, and the lowest expression found in the hemocytes.


Parachuting for charity: is it worth the money? A 5-year audit of parachute injuries in Tayside and the cost to the NHS.
All parachute injuries from two local parachute centres over a 5-year period were analysed. Of 174 patients with injuries of varying severity, 94% were first-time charity-parachutists. The injury rate in charity-parachutists was 11% at an average cost of 3751 Pounds per casualty. Sixty-three percent of casualties who were charity-parachutists required hospital admission, representing a serious injury rate of 7%, at an average cost of 5781 Pounds per patient. The amount raised per person for charity was 30 Pounds. Each pound raised for charity cost the NHS 13.75 Pounds in return. Parachuting for charity costs more money than it raises, carries a high risk of serious personal injury and places a significant burden on health resources.


Heme Oxygenase-1/Carbon Monoxide System and Embryonic Stem Cell Differentiation and Maturation into Cardiomyocytes.
The differentiation of embryonic stem (ES) cells into energetically efficient cardiomyocytes contributes to functional cardiac repair and is envisioned to ameliorate progressive degenerative cardiac diseases. Advanced cell maturation strategies are therefore needed to create abundant mature cardiomyocytes. In this study, we tested whether the redox-sensitive heme oxygenase-1/carbon monoxide (HO-1/CO) system, operating through mitochondrial biogenesis, acts as a mechanism for ES cell differentiation and cardiomyocyte maturation. Manipulation of HO-1/CO to enhance mitochondrial biogenesis demonstrates a direct pathway to ES cell differentiation and maturation into beating cardiomyocytes that express adult structural markers. Targeted HO-1/CO interventions up- and downregulate specific cardiogenic transcription factors, transcription factor Gata4, homeobox protein Nkx-2.5, heart- and neural crest derivatives-expressed protein 1, and MEF2C. HO-1/CO overexpression increases cardiac gene expression for myosin regulatory light chain 2, atrial isoform, MLC2v, ANP, MHC-β, and sarcomere α-actinin and the major mitochondrial fusion regulators, mitofusin 2 and MICOS complex subunit Mic60. This promotes structural mitochondrial network expansion and maturation, thereby supporting energy provision for beating embryoid bodies. These effects are prevented by silencing HO-1 and by mitochondrial reactive oxygen species scavenging, while disruption of mitochondrial biogenesis and mitochondrial DNA depletion by loss of mitochondrial transcription factor A compromise infrastructure. This leads to failure of cardiomyocyte differentiation and maturation and contractile dysfunction. The capacity to augment cardiomyogenesis via a defined mitochondrial pathway has unique therapeutic potential for targeting ES cell maturation in cardiac disease. Our findings establish the HO-1/CO system and redox regulation of mitochondrial biogenesis as essential factors in ES cell differentiation as well as in the subsequent maturation of these cells into functional cardiac cells.


Occipital to Angular Artery Bypass for Post-irradiation Ischemia: 3-Dimensional Operative Video.
The authors present a 3D surgical video of a direct occipital to angular artery bypass for cerebral revascularization in the setting of Post-irradiation middle cerebral artery stenosis and symptomatic hypoperfusion. The case refers to a 50-yr-old woman with a history of an unresectable residual skull base meningioma, previously approached through a left frontotemporal craniotomy, and treated with radiation 5 yr prior to presentation. She now presented with right-sided limb shaking transient ischemic attacks and aphasia, along with evidence of left middle cerebral artery territory ischemia. Her symptoms were progressive, despite extensive external carotid collateral blood supply through the prior craniotomy. The video analyzes the surgical steps of the procedure, emphasizing multiple surgical pearls. After positioning, an incision is designed to expose the full course of the occipital artery. After dissection of the donor vessel, a craniotomy is performed to expose the distal sylvian fissure. The donor and recipient vessels are prepared, and the anastomosis is performed with interrupted sutures given the sub-millimeter diameter of the recipient vessel (suture used: 10-0 Ethilon BV75-3 Taper, Ethicon, Johnson & Johnson). Every step of the closure is modified to avoid any constriction of the donor vessel. The patient tolerated the procedure well, and multiple modalities, both intra- and post operatively confirmed patency of, and robust flow within the bypass. No identifying patient information is included. However, the patient's consent was obtained for this publication.


Risk factors for first time incidence sciatica: a systematic review.
Characteristically, sciatica involves radiating leg pain that follows a dermatomal pattern along the distribution of the sciatic nerve. To our knowledge, there are no studies that have investigated risk factors associated with first time incidence sciatica. The purpose of the systematic review was to identify the longitudinal risk factors associated with first time incidence sciatica and to report incidence rates for the condition. For the purposes of this review, first time incidence sciatica was defined as either of the following: 1) no prior history of sciatica or 2) transition from a pain-free state to sciatica. Studies included subjects of any age from longitudinal, observational, cohort designs. The study was a systematic review. Eight of the 239 articles identified by electronic search strategies met the inclusion criteria. Risk factors and their respective effect estimates were reported using descriptive analysis and the preferred reporting items for systematic reviews and meta-analyses guidelines. Modifiable risk factors included smoking, obesity, occupational factors and health status. Non-modifiable factors included age, gender and social class. Incidence rates varied among the included studies, in part reflecting the variability in the operationalized definition of sciatica but ranged from <1% to 37%. A majority of the identified risk factors associated with first time sciatica are modifiable, suggesting the potential benefits of primary prevention. In addition, those risk factors are also associated with unhealthy lifestyles, which may function concomitantly toward the development of sciatica. Sciatica as a diagnosis is inconsistently defined among studies.


Avocado-soybean unsaponifiables (ASU) for osteoarthritis - a systematic review.
Patients suffering from osteoarthritis (OA) are often tempted to try 'alternative' treatment options. Avocado/soybean unsaponifiables (ASU) have shown some promise for OA. This systematic review is aimed at critically evaluating the data from rigorous clinical trials of ASU. Six databases were searched for randomised, placebo-controlled, double-blind trials of ASU. Four studies could be included. Key data were extracted according to predefined criteria and tabulated as well as discussed in narrative form. The methodological quality of the four studies was high. They included patients with OA of the knee and hip. The dose of ASU was 300 mg/day and one trial also included a group treated with 600 mg/day. Three of the four trials suggested efficacy of ASU for improving the symptoms of OA. The majority of rigorous trial data available to date suggest that ASU is effective for the symptomatic treatment of OA and more research seems warranted. However, the only real long-term trial yielded a largely negative result.


Soboliphyme baturini infection does not affect the nutritional condition of American marten (Martes americana) in Alaska.
Soboliphyme baturini, a stomach-dwelling nematode of American martens (Martes Americana), reaches high levels of infection; however, its effects on the nutritional condition of the host are unknown. To understand the effects of this parasite on American martens, we collected S. baturini and measured abdominal fat deposits from 155 marten carcasses on Prince of Wales Island, southeastern Alaska, in the winter 2006-2007. We analyzed how the dried mass of abdominal fat varied as a function of S. baturini intensity. Parasite intensity and nutritional condition were not correlated; these results suggest that American martens were able to withstand even very high levels of S. baturini infection (up to 178 parasites per host).


Screening for obsessive and compulsive symptoms: validation of the Clark-Beck Obsessive-Compulsive Inventory.
The 25-item Clark-Beck Obsessive-Compulsive Inventory (CBOCI) was developed to assess the frequency and severity of obsessive and compulsive symptoms. The measure uses a graded-response format to assess core symptom features of obsessive-compulsive disorder (OCD) based on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria and current cognitive-behavioral formulations. Revisions were made to the CBOCI on the basis of psychometric and item analyses of an initial pilot study of clinical and nonclinical participants. The construct validity of the revised CBOCI was supported in a subsequent validation study involving OCD, nonobsessional clinical, and nonclinical samples. A principal-factor analysis of the 25 items found 2 highly correlated factors of Obsessions and Compulsions. OCD patients scored significantly higher on the measure than nonobsessional anxious, depressed, and nonclinical samples. The questionnaire had strong convergent validity with other OCD symptom measures but more modest discriminant validity.


In Silico and In Vitro Approach for Evaluation of the Anti-Inflammatory and Antioxidant Potential of Mygalin.
There is a great interest in describing new molecules to be used as therapeutic targets in various diseases, particularly those that play a role in inflammatory responses and infection control. Mygalin is a synthetic analogue of spermidine, and previous studies have demonstrated its bactericidal effect against Escherichia coli, as well as its ability to modulate the inflammatory response of macrophages against lipopolysaccharide (LPS). However, the mechanisms through which mygalin regulates this inflammatory response remain poorly characterized. A set of platforms using molecular docking analysis was employed to analyze various properties of mygalin, including toxicity, biodistribution, absorption, and the prediction of its anti-inflammatory properties. In in vitro assays, we evaluated the potential of mygalin to interact with products of the inflammatory response, such as reactive oxygen species (ROS) and antioxidant activity, using the BMDM cell. The in silico analyses indicated that mygalin is not toxic, and can interact with proteins from the kinase group, and enzymes and receptors in eukaryotic cells. Molecular docking analysis showed interactions with key amino acid residues of COX-2, iNOS and 5-LOX enzymes. In vitro, assays demonstrated a significant reduction in the expression of iNOS and COX-2 induced by LPS, along with a decrease in the oxidative stress caused by the treatment with PMA, all without altering cell viability. Mygalin exhibited robust antioxidant activity in DPPH assays, regardless of the dose used, and inhibited heat-induced hemolysis. These studies suggest that mygalin holds promise for further investigation as a new molecule with anti-inflammatory and antioxidant properties.


Molecular data and ploidal levels indicate several putative allopolyploidization events in the genus Potentilla (Rosaceae).
Several naturally occurring hybrids in Potentilla (Rosaceae) have been reported, but no molecular evidence has so far been available to test these hypotheses of hybridization. We have compared a nuclear and a chloroplast gene tree to identify topological incongruences that may indicate hybridization events in the genus. Furthermore, the monophyly and phylogenetic position of the proposed segregated genera Argentina, Ivesia and Horkelia have been tested. The systematic signal from the two morphological characters, style- and anther shape, has also been investigated by ancestral state reconstruction, to elucidate how well these characters concur with the results of the molecular phylogenies. Six major clades, Anserina, Alba, Fragarioides, Reptans, ivesioid and Argentea, have been identified within genus Potentilla. Horkelia, Ivesia and Horkeliella (the ivesioid clade), form a monophyletic group nested within Potentilla. Furthermore, the origin of the proposed segregated genus Argentina (the Anserina clade) is uncertain but not in conflict with a new generic status of the group. We also found style morphology to be an informative character that reflects the phylogenetic relationships within Potentilla. Five well-supported incongruences were found between the nuclear and the chloroplast phylogenies, and three of these involved polyploid taxa. However, further investigations, using low copy molecular markers, are required to infer the phylogeny of these species and to test the hypothesis of hybrid origin.


Bronchoscopic microsampling is a useful complementary diagnostic tool for detecting lung cancer.
Bronchoscopic microsampling (BMS) is a novel and direct method with which to obtain epithelial lining fluid (ELF) from the lungs. Analysis of DNA hypermethylation of tumor suppressor genes (TSGs) is expected to be a sensitive tool for the early detection of lung cancer. It has been reported that the existence of EGFR mutations and EML4-ALK gene rearrangements are related to the sensitivity of corresponding kinase inhibitors. We aimed to evaluate the suitability of ELF as a sample for analyzing molecular changes specific for lung cancer. We collected ELF from 61 lung cancer patients by BMS from the airway close to the peripheral lung nodule and purified the nucleic acids. We performed methylation specific PCR in each ELF as well as matched serum and tumor tissue for TSGs for DNA methylation analysis. We also examined EGFR mutations and EML4-ALK rearrangement. The sensitivity for detecting DNA hypermethylation in ELF vs serum was 74.1% vs 18.5%. We found 60.1% of patients had at least one hypermethylation in ELF, while only 27.9% had it in serum. Of note, DNA hypermethylation was detected even in stage I patients (60.0%) and the detection rate was almost the same level in each stage. We also found the sensitivity for detecting EGFR mutation in ELF vs serum was 58.3% vs 8.3%. We detected an EML4-ALK fusion gene using ELF in one patient. BMS is an alternative method to detect cancer specific genetic and epigenetic alterations and will be a useful complementary diagnostic tool for lung cancer. Investigation of genetic and epigenetic changes associated with lung cancer has clinical importance for its diagnosis and management. The clinical usefulness of bronchoscopic microsampling (BMS) in lung cancer has not yet been evaluated. This study demonstrates that BMS could be useful for detecting lung cancer specific molecular changes and valuable for early diagnosis and determination of treatment options for lung cancer.


Activating AhR alleviates cognitive deficits of Alzheimer's disease model mice by upregulating endogenous Aβ catabolic enzyme Neprilysin.
Rationale: Neprilysin (NEP) is a major endogenous catabolic enzyme of amyloid β (Aβ). Previous studies have suggested that increasing NEP expression in animal models of Alzheimer's disease had an ameliorative effect. However, the underlying signaling pathway that regulates NEP expression remains unclear. The aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor. Recent studies have shown that AhR plays essential roles in the central nervous system (CNS), but its physiological and pathological roles in regulating NEP are not entirely known. Methods: Western blotting, immunofluorescence, quantitative RT-PCR and enzyme activity assay were used to verify the effects of AhR agonists on NEP in a cell model (N2a) and a mouse model (APP/PS1). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to investigate the roles of AhR in regulating NEP transcription. Object recognition test and the Morris water maze task were performed to assess the cognitive capacity of the mice. Results: Activating AhR by the endogenous ligand L-Kynurenine (L-KN) or FICZ, or by the exogenous ligand diosmin or indole-3-carbinol (I3C) significantly increases NEP expression and enzyme activity in N2a cells and APP/PS1 mice. We also found that AhR is a direct transcription factor of NEP. Diosmin treatment effectively ameliorated the cognitive disorder and memory deficit of APP/PS1 transgenic mice. By knocking down AhR or using a small molecular inhibitor targeting AhR or NEP, we found that diosmin enhanced Aβ degradation through activated AhR and increased NEP expression. Conclusions: These results indicate a novel pathway for regulating NEP expression in neurons and that AhR may be a potential therapeutic target for the treatment of Alzheimer's disease.


A comparison of hematopoiesis in normal and splenectomized mice treated with granulocyte colony-stimulating factor.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induces leukocytosis in vivo in both intact and splenectomized mice. Full dose response data showed a plateau in this effect at doses over 500 micrograms rhG-CSF/kg body weight/d in intact mice. The effect is magnified in splenectomized mice, where leukocyte numbers reach 100 x 10(6) mL after 4 days' treatment at 250 micrograms/kg/d. Further hematopoietic precursor populations are also affected in both marrow and the spleen; in general, marrow parameters were depressed, while splenic populations were enlarged. In splenectomized mice, both blood-borne stem cells were enhanced, and foci of extramedullary hematopoiesis were enlarged in addition to the effects seen in intact mice. In the marrow of splenectomized and intact mice treated with a high dose of G-CSF, erythroid suppression in the marrow was confirmed with radioactive iron. Our studies confirm and extend previous work on the mode of action of G-CSF, and indicate that side effects of high dose G-CSF therapy might include erythroid suppression in the bone marrow.


[A system of simple theoretically possible modes of transmission of genetic information].
A system of simple theoretically feasible methods of transfer of genetic information has been proposed. The system has been analyzed and the methods have been classified. The system allows to predict properties of organisms that use different ways of transfer of genetic information and estimate the pathways of evolution of these organisms. A scheme for verification of conclusions made on the basis of the system with viruses taken as an example.


Smart microneedle patches for rapid, and painless transdermal insulin delivery.
Insulin administration at mealtimes for the control of postprandial glucose is a major part of basal-bolus insulin therapy; however, painful subcutaneous (SC) injections lead to poor patient compliance. The microneedle (MN) patch, which allows painless transdermal drug delivery, is a promising substitute; however, it remains a big challenge to deliver insulin as rapidly as by SC injection. Here a novel MN patch is designed in which the MNs are coated with insulin/poly-l-glutamic acid (PGA) layer-by-layer (LBL) films at pH 3.0. This coating is pH-sensitive because the net charge of insulin turns from positive to negative when the pH increases from 3.0 to 7.4. As a result, when transferred to pH 7.4 media, e.g., when inserted into skin, the coating dissociates instantly and releases insulin rapidly. A brief epidermal application (<1 min) of the coated MNs is enough for complete film dissociation. More importantly, the coated MN patch exhibits a pharmacokinetic and a pharmacodynamic profile comparable to that of insulin administrated by SC injection, suggesting the coated MN patch can deliver insulin as rapidly as the SC injection. In addition, the patch exhibits excellent biocompatibility and storage stability. The new MN patch is expected to become a painless, convenient method for the control of postprandial glucose.


Formal auditory training in adult hearing aid users.
Individuals with sensorineural hearing loss are often able to regain some lost auditory function with the help of hearing aids. However, hearing aids are not able to overcome auditory distortions such as impaired frequency resolution and speech understanding in noisy environments. The coexistence of peripheral hearing loss and a central auditory deficit may contribute to patient dissatisfaction with amplification, even when audiological tests indicate nearly normal hearing thresholds. This study was designed to validate the effects of a formal auditory training program in adult hearing aid users with mild to moderate sensorineural hearing loss. FOURTEEN BILATERAL HEARING AID USERS WERE DIVIDED INTO TWO GROUPS: seven who received auditory training and seven who did not. The training program was designed to improve auditory closure, figure-to-ground for verbal and nonverbal sounds and temporal processing (frequency and duration of sounds). Pre- and post-training evaluations included measuring electrophysiological and behavioral auditory processing and administration of the Abbreviated Profile of Hearing Aid Benefit (APHAB) self-report scale. The post-training evaluation of the experimental group demonstrated a statistically significant reduction in P3 latency, improved performance in some of the behavioral auditory processing tests and higher hearing aid benefit in noisy situations (p-value < 0,05). No changes were noted for the control group (p-value <0,05). The results demonstrated that auditory training in adult hearing aid users can lead to a reduction in P3 latency, improvements in sound localization, memory for nonverbal sounds in sequence, auditory closure, figure-to-ground for verbal sounds and greater benefits in reverberant and noisy environments.


Mechanomyography and muscle function assessment: a review of current state and prospects.
Previous studies have explored to saturation the efficacy of the conventional signal (such as electromyogram) for muscle function assessment and found its clinical impact limited. Increasing demand for reliable muscle function assessment modalities continues to prompt further investigation into other complementary alternatives. Application of mechanomyographic signal to quantify muscle performance has been proposed due to its inherent mechanical nature and ability to assess muscle function non-invasively while preserving muscular neurophysiologic information. Mechanomyogram is gaining accelerated applications in evaluating the properties of muscle under voluntary and evoked muscle contraction with prospects in clinical practices. As a complementary modality and the mechanical counterpart to electromyogram; mechanomyogram has gained significant acceptance in analysis of isometric and dynamic muscle actions. Substantial studies have also documented the effectiveness of mechanomyographic signal to assess muscle performance but none involved comprehensive appraisal of the state of the art applications with highlights on the future prospect and potential integration into the clinical practices. Motivated by the dearth of such critical review, we assessed the literature to investigate its principle of acquisition, current applications, challenges and future directions. Based on our findings, the importance of rigorous scientific and clinical validation of the signal is highlighted. It is also evident that as a robust complement to electromyogram, mechanomyographic signal may possess unprecedented potentials and further investigation will be enlightening.


Ba(14)Cu(2)In(4)N(7), a new subnitride with isolated nitridocuprate groups and indium clusters.
Single crystals of Ba(14)Cu(2)In(4)N(7), tetradecabarium dicopper tetraindium heptanitride, were synthesized by slow cooling from 1023 K at 7 MPa of N(2) using an Na flux. The compound crystallizes in the monoclinic space group P2/m with Z = 2, and contains 0[CuN(2)] nitridocuprate units and distorted 0[In(4)] clusters. One Ba atom, not connected to any N atoms, is surrounded by 12 other Ba atoms in a barium cuboctahedron. The structural formula is expressed as (Ba)Ba(27)N(6)[CuN(2)](4)[In(4)](2).


Primary fascial closure during laparoscopic ventral hernia repair does not reduce 30-day wound complications.
Laparoscopic ventral hernia repair (LVHR) is associated with decreased wound morbidity compared to open repair. It remains unclear whether primary fascial closure (PFC) offers any benefit in reducing postoperative seroma compared to bridged repair. We hypothesized that PFC would have no effect on seroma formation following LVHR. A retrospective cohort study was performed using data from the prospectively maintained Americas Hernia Society Quality Collaborative. All patients undergoing LVHR from 2013 to 2016 were included. The primary outcome was seroma formation, diagnosed either clinically or radiographically. Secondary outcomes included surgical site infections (SSI), surgical site occurrences (SSO), and SSO requiring intervention. Patient characteristics and outcomes were compared between groups with univariate analysis using Pearson's chi-squared or Wilcoxon tests. Multivariable logistic regression controlling for patient and hernia characteristics was then performed to investigate the independent effect of PFC on seroma formation. 1280 patients were included in the study. 69% (n = 887) underwent PFC. Patients undergoing bridged repairs had slightly larger defects and were more likely to have a recurrent hernia. The overall rate of seroma formation was 10.4% (n = 133). There was no association on univariate analysis between PFC and wound complications. Similarly, on multivariable analysis, PFC had no significant effect on the risk of seroma formation (OR 0.87, 95% CI 0.58-1.31). PFC does not decrease the risk of short-term wound complications. Given that prior studies have also suggested no difference in hernia recurrence, PFC does not appear to improve postoperative outcomes for patients undergoing LVHR.


Examination of Duct Physiology in the Human Mammary Gland.
The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas.


Sensitization and exposure to pet allergens in asthmatics versus non-asthmatics with allergic rhinitis.
In sensitized subjects with allergic rhinitis (AR) or asthma, allergen exposure provokes symptoms. Among non-asthmatics with AR, an association between allergen sensitization, pollen season and lower airway inflammation has been demonstrated. Our aims were to compare AR and asthma with regard to patterns of allergen sensitization, the degree of airway hyperresponsiveness (AHR) and levels of exhaled nitric oxide (ENO). Finally, we wanted to relate our findings to previous or current exposure to household pets. Four hundred and thirty-one adolescents with different clinical phenotypes were randomly selected from a large-scale epidemiological survey. They were investigated with allergy screening, measurements of ENO and a methacholine bronchoprovocation test. Sensitization to pet allergens (cat, dog and horse) was associated with increased AHR and ENO both in asthmatics and non-asthmatics with AR. The risk of being sensitized to cat allergens was significantly reduced in those who had kept cats vs. those who had never kept them. Keeping dogs or horses did not influence the risk of being sensitized to the respective allergens. Only in steroid-naive, non-smoking asthmatics, a trend towards increased ENO in those sensitized and exposed to cat or dog allergens was seen. Although sensitization towards pet allergens was associated with inflammation in the lower airways irrespective of clinical phenotype, keeping pets did not increase the risk of being sensitized to pet allergens.


Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and meta-analysis.
To assess the long term effects of multidisciplinary biopsychosocial rehabilitation for patients with chronic low back pain. Systematic review and random effects meta-analysis of randomised controlled trials. Electronic searches of Cochrane Back Review Group Trials Register, CENTRAL, Medline, Embase, PsycINFO, and CINAHL databases up to February 2014, supplemented by hand searching of reference lists and forward citation tracking of included trials. Trials published in full; participants with low back pain for more than three months; multidisciplinary rehabilitation involved a physical component and one or both of a psychological component or a social or work targeted component; multidisciplinary rehabilitation was delivered by healthcare professionals from at least two different professional backgrounds; multidisciplinary rehabilitation was compared with a non- multidisciplinary intervention. Forty one trials included a total of 6858 participants with a mean duration of pain of more than one year who often had failed previous treatment. Sixteen trials provided moderate quality evidence that multidisciplinary rehabilitation decreased pain (standardised mean difference 0.21, 95% confidence interval 0.04 to 0.37; equivalent to 0.5 points in a 10 point pain scale) and disability (0.23, 0.06 to 0.40; equivalent to 1.5 points in a 24 point Roland-Morris index) compared with usual care. Nineteen trials provided low quality evidence that multidisciplinary rehabilitation decreased pain (standardised mean difference 0.51, -0.01 to 1.04) and disability (0.68, 0.16 to 1.19) compared with physical treatments, but significant statistical heterogeneity across trials was present. Eight trials provided moderate quality evidence that multidisciplinary rehabilitation improves the odds of being at work one year after intervention (odds ratio 1.87, 95% confidence interval 1.39 to 2.53) compared with physical treatments. Seven trials provided moderate quality evidence that multidisciplinary rehabilitation does not improve the odds of being at work (odds ratio 1.04, 0.73 to 1.47) compared with usual care. Two trials that compared multidisciplinary rehabilitation with surgery found little difference in outcomes and an increased risk of adverse events with surgery. Multidisciplinary biopsychosocial rehabilitation interventions were more effective than usual care (moderate quality evidence) and physical treatments (low quality evidence) in decreasing pain and disability in people with chronic low back pain. For work outcomes, multidisciplinary rehabilitation seems to be more effective than physical treatment but not more effective than usual care.


Modulation of BK channels contributes to activity-dependent increase of excitability through MTORC1 activity in CA1 pyramidal cells of mouse hippocampus.
Memory acquisition and synaptic plasticity are accompanied by changes in the intrinsic excitability of CA1 pyramidal neurons. These activity-dependent changes in excitability are mediated by modulation of intrinsic currents which alters the responsiveness of the cell to synaptic inputs. The afterhyperpolarization (AHP), a major contributor to the regulation of neuronal excitability, is reduced in animals that have acquired several types of hippocampus-dependent memory tasks and also following synaptic potentiation by high frequency stimulation. BK channels underlie the fast AHP and contribute to spike repolarization, and this AHP is reduced in animals that successfully acquired trace-eyeblink conditioning. This suggests that BK channel function is activity-dependent, but the mechanisms are unknown. In this study, we found that blockade of BK channels with paxilline (10 μM) decreased I AHP amplitude and increased spike half-width and instantaneous frequency in response to a +100 pA depolarization. In addition, induction of long term potentiation (LTP) by theta burst stimulation (TBS) in CA1 pyramidal neurons reduced BK channel's contribution to I AHP, spike repolarization, and instantaneous frequency. This result indicates that BK channel activity is decreased following synaptic potentiation. Interestingly, blockade of mammalian target of rapamycin (MTORC1) with rapamycin (400 nM) following synaptic potentiation restored BK channel function, suggesting a role for protein translation in signaling events which decreased postsynaptic BK channel activity following synaptic potentiation.


Sister Mary Joseph Nodules: A Case Report about a Rare Location of Skin Metastasis.
Umbilical skin metastases (or Sister Mary Joseph nodules) are rare. Their presence typically indicates the late manifestation of deep-seated abdominopelvic malignancy. They occur mainly in gynecological cancers, and gastrointestinal cancers in men. The most common histology is adenocarcinoma (∼75% of cases), but it can also rarely be squamous cell or undifferentiated carcinoma. These metastases can be present at diagnosis or appear at disease recurrence, and are associated with a very poor prognosis with an average survival of 11 months. We report the clinical case of a 58-year-old man with metastatic pancreatic adenocarcinoma and umbilical cutaneous metastasis after receiving first-line chemotherapy. The diagnosis was established upon liver biopsy in July 2019, after the patient presented with a complaint of transfixing abdominal pain. The first-line treatment consisted of six cycles of modified FOLFIRINOX chemotherapy. However, in November 2019, computed tomography (CT) scan showed disease progression. Second-line treatment with gemcitabine (Gemzar®) led to a 16% decrease in target lesions. During the fourth cycle, three periumbilical indurated nodules appeared. After six cycles, skin infiltration had increased, and the patient reported his abdominal pain had intensified. Reassessment by CT scan showed an increase in both hepatic and peritoneal disease progression. Third-line treatment with FOLFIRI, started on April 15, 2020, could not control the disease, leading to greater induration and subcutaneous infiltration, which were responsible for the increased pain and ultimate death. Umbilical skin metastases are rare, and they are associated with advanced metastatic disease and a very poor prognosis. Cases reporting Sister Mary Joseph nodules are needed to better understand the conditions and mechanisms of their appearance and dissemination.


Retinal Vessel Analysis as a Novel Screening Tool to Identify Childhood Acute Lymphoblastic Leukemia Survivors at Risk of Cardiovascular Disease.
Microvascular endothelial dysfunction is central to the pathogenesis of cardiovascular disease (CVD). The eye offers direct access for endothelial health assessment via the retinal microvasculature. The aim of the study was to investigate whether image-based retinal vessel analysis is a feasible method of assessing endothelial health in survivors of childhood acute lymphoblastic leukemia (cALL). Cardiovascular risk factors (CRFs) were estimated using the 30-year Framingham Risk Score in 73 childhood leukemia survivors (median age: 25; median years from diagnosis: 19) and 78 healthy controls (median age: 23). Radial arterial stiffness was measured using pulse wave analyzer, while endothelial activation markers were measured by soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). Retinal fundus images were analyzed for central retinal artery/vein equivalents (CRAE/CRVE) and arteriolar-venular ratio (AVR). cALL survivors had higher CRF (P<0.0001), arterial stiffness (P=0.001), and sVCAM-1 (P=0.007) compared with controls. Survivors also had significantly higher CRVE (P=0.021) while AVR was significantly lower (P=0.026) in survivors compared with controls, compatible with endothelial dysfunction. In cALL survivors with intermediate risk for CVD, CRAE, and AVR are significantly lower, while sVCAM-1 and sICAM-1 are significantly higher when compared with survivors with low CVD risk after adjusting with covariates (age, sex, and smoking status). cALL survivors have an increased risk of CVD compared with age-matched peers. The survivors demonstrated microvasculopathy, as measured by retinal vascular analysis, in addition to physical and biochemical evidence of endothelial dysfunction. These changes predate other measures of CVD. Retinal vessel analysis may be utilized as a robust screening tool for identifying survivors at increased risk for developing CVD.


Basal and pentagastrin-stimulated gastric secretion in young horses.
Equine gastric secretion was studied using a gastric cannula model after fasting (basal) and pentagastrin infusion. Gastric secretory rate, pH, osmolality, and electrolyte concentrations and outputs were determined over a 5-h period. Dose-response tests estimated that the maximally effective intravenous dose of pentagastrin was between 3 and 6 micrograms.kg-1.h-1. Basal secretory rate was 278 +/- 29 (SE) ml/15 min, and the pH was 2.00 +/- 0.31. Pentagastrin infusion at 6 micrograms.kg-1.h-1 increased secretory rate to 533 +/- 60 ml/15 min and decreased pH to 1.41 +/- 0.11. Basal gastric acid concentration and output were 38 +/- 5 meq/l and 211 +/- 36 mu eg.kg-1.h-1, respectively. Pentagastrin increased acid concentration to 60 +/- 5 meq/l and acid output to 474 +/- 61 mu eq.kg-1.h-1. Gastric fluid osmolality remained hypotonic during both basal and pentagastrin conditions. Sodium concentration remained high in comparison with hydrogen ion concentration, and sodium output increased during pentagastrin infusion. Equine gastric secretion did not attain maximal acid concentrations nor the marked drop in pH, which has been reported for other monogastric species. These data suggest that in the horse a large nonparietal component exists that modifies parietal secretions and is increased by pentagastrin stimulation.


Long-term outcomes of acute kidney injury.
Acute kidney injury (AKI) is common in the intensive care unit and is associated with significant morbidity and mortality. Based on the RIFLE criteria, AKI occurs in up to 67% of patients in the intensive care unit (ICU), with approximately 4% of critically ill patients requiring renal replacement therapy (RRT). It is well known that this subset of AKI patients who require RRT have an in-hospital mortality rate exceeding 50%. However, long-term outcomes of survivors of AKI requiring RRT remain poorly described. Long-term mortality is greater in those patients who survived AKI when compared with critically ill patients without AKI. Long-term morbidity, renal and extrarenal, is a frequent and underappreciated complication of AKI. Among survivors of AKI at long-term follow-up (1-10 years), approximately 12.5% are dialysis dependent (wide range of 1%-64%, depending on the patient population) and 19% to 31% have chronic kidney disease. According to the United States Renal Data System, "acute tubular necrosis without recovery" as a cause of end-stage kidney disease increased from 1.2% in 1994 to 1998 to 1.7% in 1999 to 2003. The incidence will likely continue to rise with the aging population, increase in comorbidities, and expansion of intensive care unit capabilities. AKI is an underrecognized cause of chronic kidney disease (CKD) and patients who survive should be followed closely for new CKD and/or progression of underlying CKD.


Ultraviolet photodetectors with high photosensitivity based on type-II ZnS/SnO2 core/shell heterostructured ribbons.
Semiconducting heterostructures with type-II band structure have attracted much attention due to their novel physical properties and wide applications in optoelectronics. Herein, we report, for the first time, a controlled synthesis of type-II ZnS/SnO2 heterostructured ribbon composed of SnO2 nanoparticles that uniformly cover the surface of ZnS ribbon via a simple and versatile thermal evaporation approach. Structural analysis indicated that the majority of SnO2 nanoparticles have an equivalent zone axis, i.e., <-313> of rutile SnO2, which is perpendicular to ±(2-1-10) facets (top/down surfaces) of ZnS ribbon. For those SnO2 nanoparticles decorated on ±(01-10) facets (side surfaces) of ZnS ribbon, an epitaxial relationship of (01-10)ZnO//(020)SnO2 and [2-1-10]ZnO//[001]SnO2 was identified. To explore their electronic and optoelectronic properties, we constructed field-effect transistors from as-prepared new heterostructures, which exhibited an n-type characteristic with an on/off ratio of ∼10(3) and a fast carrier mobility of ∼33.2 cm2 V(-1) s(-1). Owing to the spatial separation of photogenerated electron-hole pairs from type-II band alignment together with the good contacts between electrodes and ribbon, the resultant photodetector showed excellent photoresponse properties, including large photocurrent, high sensitivity (external quantum efficiency as high as ∼2.4×10(7)%), good stability and reproducibility, and relatively fast response speed. Our results suggest great potential of ZnS/SnO2 heterostructures for efficient UV light sensing, and, more importantly, signify the advantages of type-II semiconducting heterostructures for construction of high-performance nano-photodetectors.


[Premalignancies of colon].
The most common premalignant lesions of colorectal carcinoma include sporadic adenomas. Tubular and tubulovillous adenomas with mild dysplasia are considered benign lesions, while villous adenomas represent tumors with uncertain bio-logical behavior. In recent years, demonstrable growth of flat lesions in the proximal intestine has been seen. Precision and yield of colonoscopy depends to some extent on good preparation, careful screening of intestine and use of new instruments of better quality. As an indicator of screening colonoscopy quality, the so -called adenoma detection rate is used. The text briefly describes options of endoscopic and surgical resolving of premalignancies. In the Czech Republic, attendance in the screening program is low, which could be changed by prepared addressed invitations of clients. The population with a genetic or familiar risk is examined according to recommended procedures intended for increased- risk persons.


Cell senescence and human aging: where's the link?
Normal human cells will not divide forever in culture. After a defined number of passages, every culture enters a viable non-dividing state termed senescence. This led to the proposal that the progressive accumulation of senescent cells contributes to (but does not exclusively cause) the aging process. Data now suggest that cell senescence, like apoptosis, occurs as an anti-cancer mechanism. In vivo, extremely low rates of division occur over very long periods of time. Thus, by the end of its lifespan, an organism has performed a surprisingly large amount of cell turnover. In a normal culture the fraction of senescent cells increases smoothly with proliferation in vitro. This process can be accurately modelled by the progressive loss of telomeric sequence (proposed as a counting mechanism for senescence). Telomere length is usually maintained by the enzyme telomerase (repressed in many human tissues). Re-introduction of telomerase prevents the onset of senescence. However, data suggest that a separate telomere-independent pathway exists. Evidence that this pathway is present in humans is now emerging.


Preparation, physicochemical and biological evaluation of chitosan Pleurotus ostreatus polysaccharides active films for food packaging.
The aim of this study was to create CS-POP composite films by blending Pleurotus ostreatus stalk polysaccharides (POP) and chitosan (CS). The effects of adding different concentrations (0 %, 0.25 %, 0.5 %, 0.75 %, and 1 %) of POP on the mechanical, barrier, and optical properties of the CS films were investigated. When the POP content is at 0.5 %, the tensile strength of the composite film reaches its maximum value at 13.691 MPa, showing a significant improvement compared to the tensile strength of the pure CS film. The structure of the CS and CS-POP composite films was characterized by FT-IR spectroscopy, XRD, TGA and SEM. The results indicate that due to the interaction between the two types of CS and POP, the formation of Schiff base, and the intermolecular hydrogen bonds between CS and POP, the addition of POP to CS films can result in a smoother and more stable crystalline structure in the composite film. The CS-POP composite films exhibited enhanced antioxidant and antibacterial activity compared to the CS films alone, with the highest DPPH scavenging activity of 72.43 %. The composite films also showed significant inhibitory effects on the growth of E. coli.


Pathological Predictors for Defining a Therapeutic Strategy for Early Colon Cancer after Endoscopic Resection: Multicenter Retrospective Analysis from Surgically Resected Specimens.
For the possibility of regional lymph node metastasis (LNM), early colon cancer (ECC) is a boundary lesion between endoscopic resection and surgery. The aim of study is to clarify risk factors for LNM and to determine therapeutic strategy after endoscopic resection in patients with ECC. The histopathology of patients with ECC underwent surgery with LN dissection in 8 university hospitals were reviewed by experienced pathologist blinded to LN status. In total, 370 patients (107 with mucosal cancer, 263 with submucosal invasive colorectal carcinoma [SICC]) were enrolled. Excluding mucosal cancer, the LNM rate was 11.8% (31/263, including 15.4% [8/52] with pedunculated SICC [P-SICC] and 10.9% [23/211] with non-pedunculated SICC [NP-SICC]). Multivariate analysis showed that tumor sprouting (P < 0.001; odds ratio [OR], 8.83; 95% confidence interval [CI], 3.04-25.69), submucosal invasion depth (SM depth) > 2000 μm (P = 0.024; OR, 3.68; 95% CI, 1.19-11.37), and lymphatic invasion (P = 0.022; OR, 3.48; 95% CI, 1.19-10.13) were related to LNM. All LNMs with SM depth < 2000 μm showed tumor sprouting without lymphatic invasion. Significant risk factors for predicting LNM in patients with SICC were tumor sprouting, SM depth > 2000 μm, and lymphatic invasion.


Sleep, stress and compensatory behaviors in Australian nurses and midwives.
To describe sleep, stress and compensatory behaviors in nurses and midwives. The study included 41 midwives and 21 nurses working in Australian hospitals between 2005 and 2009. Participation was voluntary. All participants recorded on a daily basis their work and sleep hours, levels of stress and exhaustion, caffeine intake and use of sleep aids for a month (1,736 days, 1,002 work shifts). Participants reported moderate to high levels of stress and exhaustion on 20-40% of work days; experienced sleep disruption on more than 50% of work days; struggled to remain awake on 27% of work days; and suffered extreme drowsiness or experienced a near accident while travelling home on 9% of workdays. Age, perceived sleep duration and work hours were significant predictors of caffeine intake. About 60% of participants reported using sleep aids (about 20% reported taking prescription medications and 44% of nurses and 9% of midwives reported alcohol use as a sleep aid at least once during the study). Stress and workdays were significant predictors of sedative use. Overall, 22% reported being indifferent or mildly dissatisfied with their job. Sleep problems, high levels of stress and exhaustion and low job satisfaction are prevalent among nurses and midwives. The use of alcohol and sleeping pills as sleep aids, and the use of caffeine to help maintain alertness is also common. Nurses and midwives may use caffeine to compensate for reduced sleep, especially on workdays, and sleeping pills to cope with their daily work-related stress.


B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses.
Several recent studies have focused on the identification, functional analysis, and structural characterization of outer membrane proteins (OMPs) of Treponema pallidum (Tp). The Tp species encompasses the highly related pallidum, pertenue, and endemicum subspecies of this pathogen, known to be the causative agents of syphilis, yaws, and bejel, respectively. These studies highlighted the importance of identifying surface-exposed OMP regions and the identification of B-cell epitopes that could be protective and used in vaccine development efforts. We previously reported that the TprC and TprD OMPs of Tp are predicted to contain external loops scattered throughout the entire length of the proteins, several of which show a low degree of sequence variability among strains and subspecies. In this study, these models were corroborated using AlphaFold2, a state-of-the-art protein structure modeling software. Here, we identified B-cell epitopes across the full-length TprC and TprD variants using the Geysan pepscan mapping approach with antisera from rabbits infected with syphilis, yaws, and bejel strains and from animals immunized with refolded recombinant TprC proteins from three syphilis strains. Our results show that the humoral response is primarily directed to sequences predicted to be on surface-exposed loops of TprC and TprD proteins, and that the magnitude of the humoral response to individual epitopes differs among animals infected with various syphilis strains and Tp subspecies. Rather than exhibiting strain-specificity, antisera showed various degrees of cross-reactivity with variant sequences from other strains. The data support the further exploration of TprC and TprD as vaccine candidates.


Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors.
Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder's particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder's capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required.


Two novel sodium channel mutations associated with resistance to indoxacarb and metaflumizone in the diamondback moth, Plutella xylostella.
Indoxacarb and metaflumizone belong to a relatively new class of sodium channel blocker insecticides (SCBIs). Due to intensive use of indoxacarb, field-evolved indoxacarb resistance has been reported in several lepidopteran pests, including the diamondback moth Plutella xylostella, a serious pest of cruciferous crops. In particular, the BY12 population of P. xylostella, collected from Baiyun, Guangdong Province of China in 2012, was 750-fold more resistant to indoxacarb and 70-fold more resistant to metaflumizone compared with the susceptible Roth strain. Comparison of complementary DNA sequences encoding the sodium channel genes of Roth and BY12 revealed two point mutations (F1845Y and V1848I) in the sixth segment of domain IV of the PxNav protein in the BY population. Both mutations are located within a highly conserved sequence region that is predicted to be involved in the binding sites of local anesthetics and SCBIs based on mammalian sodium channels. A significant correlation was observed among 10 field-collected populations between the mutant allele (Y1845 or I1848) frequencies (1.7% to 52.5%) and resistance levels to both indoxacarb (34- to 870-fold) and metaflumizone (1- to 70-fold). The two mutations were never found to co-exist in the same allele of PxNav , suggesting that they arose independently. This is the first time that sodium channel mutations have been associated with high levels of resistance to SCBIs. F1845Y and V1848I are molecular markers for resistance monitoring in the diamondback moth and possibly other insect pest species.


Impact of non-alcoholic fatty liver disease and smoking on colorectal polyps.
Non-alcoholic fatty liver disease (NAFLD) and smoking have similar mechanisms of promoting colorectal polyps. The potential link between NAFLD and smoking in men and colorectal polyps has not been adequately evaluated. The aim is to investigate this association. A retrospective cross-sectional study was conducted on 2409 individuals undergoing a health check. Univariate and multivariate logistic regression were performed for analyzing the association between risk factors and colorectal polyps. Individuals were divided into four groups: Q1: NAFLD (-)/smoking (-); Q2: NAFLD (+)/smoking (-); Q3: NAFLD (-)/smoking (+); Q4: NAFLD (+)/smoking (+). Logistic analyses were used to explore associations for the whole study population and stratified groups. The prevalence of colorectal polyps was 38.8% in males, and that of colorectal polyps in smokers and individuals with NAFLD were 47.0% (428/911) and 42.9% (267/622), respectively. With Q1 as reference, subjects with NAFLD (+) and smoking habits (+) had the highest ORs for colorectal polyps (OR = 2.64, 95% CI: 1.91 - 3.64, P < 0.001), adenomatous polyps (OR = 2.06, 95% CI: 1.38 - 3.05, P < 0.05), non-adenomatous polyps (OR = 1.97, 95% CI: 1.39 - 2.80, P < 0.05), ≥ 3 polyps (OR = 2.05, 95% CI: 1.31 - 3.22, P < 0.05) and proximal polyps (OR = 1.58, 95% CI: 1.02 - 2.45, P < 0.05) after adjusting for confounding variables. Men with NAFLD and smoking habits have an increasing risk of colorectal polyps.


Does warmth moderate longitudinal associations between maternal spanking and child aggression in early childhood?
This study examines whether maternal warmth moderates the association between maternal use of spanking and increased child aggression between ages 1 and 5. Participants were 3,279 pairs of mothers and their children from a cohort study of urban families from 20 U.S. cities. Maternal spanking was assessed when the child was 1 year, 3 years, and 5 years of age. Maternal warmth and child aggressive behavior were measured at 3 years and 5 years of age. Models controlled for demographic characteristics (measured at the child's birth), child emotionality (measured at age 1), and maternal psychosocial risk factors (measured when children were 3 years old). Cross-lagged path models examined the within-time and longitudinal associations between spanking and child aggression. Results indicated that maternal spanking at age 1 was associated with higher levels of child aggression at age 3; similarly, maternal spanking at age 3 predicted increases in child aggression by age 5. Maternal warmth when children were 3 years old did not predict changes in child aggression between 3 and 5 years old. Furthermore, maternal warmth did not moderate the association between spanking and increased child aggression over time. Beginning as early as age 1, maternal spanking is predictive of child behavior problems, and maternal warmth does not counteract the negative consequences of the use of spanking.


Cross-presentation of human melanoma peptide antigen MART-1 to CTLs from in vitro reconstituted gp96/MART-1 complexes.
Heat shock proteins (HSPs) have two unique roles as constituents of tumor vaccines: (i) to shuttle associated tumor antigens into professional antigen-presenting cells (APCs) and (ii) to activate professional APCs. Here we investigated the shuttle function of the HSP gp96 (glycoprotein 96) for a human melanoma peptide antigen MART-1 that was noncovalently bound to gp96 in vitro. This in vitro complexing reaction was optimized using the radioiodinated MART-1 peptide and human gp96. Up to 20% of gp96 molecules could bind the peptide, assuming a 1:1 molar ratio. The binding was temperature-dependent and thus reversible. At -20 degrees C, 95% of the peptide remained complexed after 24 h, but 25% and 60% of the peptide dissociated at 37 degrees C within 6 and 24 h, respectively. This observation suggests that under the physiological conditions in APCs, spontaneous peptide dissociation from gp96 complexes may facilitate the delivery of peptide antigen into antigen presentation pathways. The gp96/MART-1 complexes stimulated an HLA A2-restricted MART-1-specific CTL clone dependent on the amount of complexed peptide and the presence of HLA-A2-positive APCs. The reaction was peptide-specific and could be blocked by an excess of untreated native gp96. These results show for the first time that peptide antigens from in vitro reconstituted gp96/peptide antigen complexes can be cross-presented by human APCs. These findings extend the scientific basis for further evaluating the use of either endogenous or in vitro reconstituted gp96/tumor-antigen complexes as tumor vaccines.


Lymphangiomatosis in a child: eight years' follow-up without treatment.
Lymphangiomatosis of the spleen with diffuse lymphangiomatosis of the bone is extremely rare and there is no consensus about management at present. Here, the authors report a child presenting initially with back pain and diagnosed as lymphangiomatosis on several sites throughout the bony structures and the spleen. The patient is in a stable state at the end of 8 years without any treatment. The authors also discuss the follow-up option that may be considered as a strategy for management.


Comparison of WIFi, University of Texas and Wagner Classification Systems as Major Amputation Predictors for Admitted Diabetic Foot Patients: A Prospective Cohort Study.
Classifications systems are powerful tools that could reduce the length of hospital stay and economic burden. The Would, Ischemia, and Foot Infection (WIFi) classification system was created as a comprehensive system for predicting major amputation but is yet to be compared with other systems. Thus, the objective of this study is to compare the predictive abilities for major lower limb amputation of WIFi, Wagner and the University of Texas Classification Systems among diabetic foot patients admitted in a tertiary hospital through a prospective cohort design. Sixty-three diabetic foot patients admitted from June 15, 2019 to February 15, 2020. Methods included one-on-one interview for clinico-demographic data, physical examination to determine the classification. Patients were followed-up and outcomes were determined. Pearson Chi-square or Fisher's Exact determined association between clinico-demographic data, the classifications, and outcomes. The receiver operating characteristic (ROC) curve determined predictive abilities of classification systems and paired analysis compared the curves. Area Under the Receiver Operating Characteristic Curve (AUC) values used to compare the prediction accuracy. Analysis was set at 95% CI. Results showed hypertension, duration of diabetes, and ambulation status were significantly associated with major amputation. WIFi showed the highest AUC of 0.899 (p = 0.000). However, paired analysis showed AUC differences between WIFi, Wagner, and University of Texas classifications by grade were not significantly different from each other. The WIFi, Wagner, and University of Texas classification systems are good predictors of major amputation with WIFi as the most predictive.