Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure.
Cardiotonic steroids (CTS) are implicated in pathophysiology of uremic cardiomyopathy. In the present study, we tested whether a monoclonal antibody (mAb) against the bufadienolide CTS, marinobufagenin (MBG), alleviates cardiac hypertrophy and fibrosis in partially nephrectomized (PNx) rats. In PNx rats, we compared the effects of 3E9 anti-MBG mAb and of Digibind, an affinity-purified digoxin antibody, on blood pressure and cardiac hypertrophy and fibrosis following 4 weeks after the surgery. In PNx rats, a fourfold elevation in plasma MBG levels was associated with hypertension, increased cardiac levels of carbonylated protein, cardiac hypertrophy, a reduction in cardiac expression of a nuclear transcription factor which is a negative regulator of collagen synthesis, Friend leukemia integration-1 (Fli-1), and an increase in the levels of collagen-1. A single intraperitoneal administration of 3E9 mAb to PNx rats reduced blood pressure by 59 mm Hg for 7 days and produced a significant reduction in cardiac weight and cardiac levels of oxidative stress, an increase in the expression of Fli-1, and a reduction in cardiac fibrosis. The effects of Digibind were similar to those of 3E9 mAb, but were less pronounced. In experimental chronic renal failure, elevated levels of MBG contribute to hypertension and induce cardiac fibrosis via suppression of Fli-1, representing a potential target for therapy.


Lactitol and β-cyclodextrin alleviate the intensity of goaty flavor.
Goat milk has balanced nutritional composition, is conducive to digestion and absorption, and does not easily lead to allergic reactions. However, the special goaty flavor in milk has seriously affected consumer acceptance. It is imperative to alleviate the goaty flavor in a safe and efficient way. This study indicated that the supplementation of 6 g kg-1 β-cyclodextrin or 8 g kg-1 lactitol in goat milk significantly alleviated goaty flavor and improved sensory characteristics. Furthermore, the supplementation of β-cyclodextrin and lactitol had a synergistic effect in reducing the content of free fatty acids that cause goaty flavor. The content of caproic acid (C6 H12 O2 ), octanoic acid (C8 H6 O2 ), and decanoic acid (C10 H20 O2 ) decreased by 42.46%, 39.45%, and 46.41%, respectively, after a combined group was supplemented with 6 g kg-1 β-cyclodextrin and 7 g kg-1 lactitol, which was significantly lower than in groups given β-cyclodextrin or lactitol individually. This study provides a novel and effective approach to alleviate goaty flavor and promote the competitiveness of goat milk products. © 2022 Society of Chemical Industry.


Positive virus detection in patients who recovered from COVID-19 during quarantine period between discharge and home: a two-center experience in Wuhan, China.
The incidence of re-positive virus detection in patients who recovered from COVID-19 during quarantine was 6.2% in two designated locations, in Wuhan, indicating that suggestions for patients after discharge to be quarantined before leaving for home might be necessary. This experience might be referred to by other countries with epidemic outbreak.


The transcriptional profile of keloidal Schwann cells.
Recently, a specific Schwann cell type with profibrotic and tissue regenerative properties that contributes to keloid formation has been identified. In the present study, we reanalyzed published single-cell RNA sequencing (scRNA-seq) studies of keloids, healthy skin, and normal scars to reliably determine the specific gene expression profile of keloid-specific Schwann cell types in more detail. We were able to confirm the presence of the repair-like, profibrotic Schwann cell type in the datasets of all three studies and identified a specific gene-set for these Schwann cells. In contrast to keloids, in normal scars, the number of Schwann cells was not increased, nor was their gene expression profile distinctly different from that of Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the AP1, STAT, and KLF families, and members of the IER genes in the dedifferentiation process of keloidal Schwann cells. Together, our analysis strengthens the role of the profibrotic Schwann cell type in the formation of keloids. Knowledge of the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.


Axillary temperature in transitional newborn infants before and after tub bath.
Twenty healthy newborn infants (mean 38.4 weeks gestation and 3,294 g) were studied to compare axillary temperatures before and after a deep-water tub bath. The bath was given in the mother's room in a plastic bassinet filled with 5 to 5 1/2 inches of warm water. Mean time was 4.4 hours postbirth. Mean infant temperature was 98.2 degrees F (36.8 degrees C) prebath and 98.0 degrees F (36.7 degrees C) postbath. Mean change was -0.2 degree F (-0.1 degree C) and was not significantly different. This significant absence of heat loss during tub baths suggests that infants need not be separated from their mothers and kept in nurseries under infrared warmers to prevent heat loss during their first bath.


Metabolic-based insecticide resistance mechanism and ecofriendly approaches for controlling of beet armyworm Spodoptera exigua: a review.
The beet army worm, Spodoptera exigua, is a widely distributed polyphagous pest of economically important crops worldwide. The management of this pest insect continues to face many challenges. Despite synthetic chemicals posing a serious threat to the environment, these remain the conventional approach for controlling S. exigua in the field. An over-reliance on chemical control has not only led to selection for resistance to insecticides and to a reduction of natural enemies, but has also polluted various components of ecosystem. Given these increasing pressures on the ecosystem, there is a need to implement integrated pest management (IPM) approaches exploiting a wider range of tools (biotechnological approaches, microbial control, biological control, cultural control, and use of host plant resistance) for an alternative to chemical control. The IPM approach can not only reduce the hazard of chemical residues in the environment and associated health problems, but may also provide best strategies to control insect pests. This review synthesizes published information on insecticide resistance of S. exigua and explores alternative IPM approaches to control S. exigua.


Thrombocytopenia and coagulation impairment after portacaval shunt in the rat.
A study has been performed to evaluate the effect of the portacaval shunt on some coagulation tests in the rats. Thrombocytopenia develops, accompanied by a decrease in the total protein and fibrinogen concentrations. Moreover, the Quick time is lengthened, whereas the partial thromboplastin time is not modified. The maximal amplitude and elasticity of the clot, recorded by thrombelastography, appear reduced, and k is lengthened. The results are discussed.


Effect of participation in a surgical site infection surveillance programme on hospital performance in Japan: a retrospective study.
The effect of hospital participation in the Japan Nosocomial Infection Surveillance (JANIS) programme on surgical site infection (SSI) prevention is unknown. To determine if participation in the JANIS programme improved hospital performance in SSI prevention. This retrospective before-after study analysed Japanese acute care hospitals that joined the SSI component of the JANIS programme in 2013 or 2014. The study participants comprised patients who had undergone surgeries targeted for SSI surveillance at JANIS hospitals between 2012 and 2017. Exposure was defined as the receipt of an annual feedback report 1 year after participation in the JANIS programme. The changes in standardized infection ratio (SIR) from 1 year before to 3 years after exposure were calculated for 12 operative procedures: appendectomy, liver resection, cardiac surgery, cholecystectomy, colon surgery, caesarean section, spinal fusion, open reduction of long bone fracture, distal gastrectomy, total gastrectomy, rectal surgery, and small bowel surgery. Logistic regression models were used to analyse the association of each post-exposure year with the occurrence of SSI. In total, 157,343 surgeries at 319 hospitals were analysed. SIR values declined after participation in the JANIS programme for procedures such as liver resection and cardiac surgery. Participation in the JANIS programme was significantly associated with reduced SIR for several procedures, especially after 3 years. The odds ratios in the third post-exposure year (reference: pre-exposure year) were 0.86 [95% confidence interval (CI) 0.79-0.84] for colon surgery, 0.72 (95% CI 0.56-0.92) for distal gastrectomy, and 0.77 (95% CI 0.59-0.99) for total gastrectomy. Participation in the JANIS programme was associated with improved SSI prevention performance in several procedures in Japanese hospitals after 3 years.


Work engagement in cancer care: The power of co-worker and supervisor support.
Co-worker and supervisor support can provide knowledge, advice and expertise which may improve motivation, confidence and skills. This exploratory study aimed to examine the association of co-worker and supervisor support, and other socio-demographic and practice variables with work engagement for cancer workers. The study surveyed 573 cancer workers in Queensland (response rate 56%). Study participants completed surveys containing demographics and psychosocial questionnaires measuring work engagement, co-worker and supervisor support. Of these respondents, a total of 553 responded to the items measuring work engagement and this forms the basis for the present analyses. Oncology nurses represented the largest professional group (37%) followed by radiation therapists (22%). About 54% of the workforce was aged >35 years and 81% were female. Multiple regression analysis was performed to identify explanatory variables independently associated with work engagement for cancer workers. After adjusting for the effects of other factors, co-worker and supervisor support were both significantly associated with work engagement. Having 16 years or more experience, being directly involved in patient care, having children and not being a shift worker were positively associated with work engagement. Annual absenteeism of six days or more was associated with low work engagement. The fitted model explained 23% of the total variability in work engagement. This study emphasises that health care managers need to promote co-worker and supervisor support in order to optimise work engagement with special attention to those who are not directly involved in patient care.


Great Ears: Low-Frequency Sensitivity Correlates in Land and Marine Leviathans.
Like elephants, baleen whales produce low-frequency (LF) and even infrasonic (IF) signals, suggesting they may be particularly susceptible to underwater anthropogenic sound impacts. Analyses of computerized tomography scans and histologies of the ears in five baleen whale and two elephant species revealed that LF thresholds correlate with basilar membrane thickness/width and cochlear radii ratios. These factors are consistent with high-mass, low-stiffness membranes and broad spiral curvatures, suggesting that Mysticeti and Proboscidea evolved common inner ear adaptations over similar time scales for processing IF/LF sounds despite operating in different media.


Advancing mycorrhizal trait-based ecology using both pure cultures and community-level traits.
Traits are the intermediate by which species respond to environmental filters and influence ecosystem functions. With the myriad of biogeochemical processes controlled by fungi, the past decade has witnessed a rising interest in applying trait-based approaches, core to the toolkit of plant and animal ecophysiologists, to fungi. One of the first challenges to tackle when working on fungal ecophysiology is to circumscribe the very definition of what we consider a fungal trait. Traits are characteristics/features possessed by an individual that can influence how it interacts with its environment. Here, the individual scale is both important, and problematic. Important because the very goal of comparative ecology is to measure traits on individuals belonging to known species. This allows us to populate trait databases, and syntheses of such databases can reveal key trade-offs and trait syndromes that govern species' life-histories. The scale of the individual is problematic, however, because it is hard to define for soil fungi, and because a rare minority of fungi can be sampled at the individual scale in the environment (e.g., macroscopic sporocarps, ectomycorrhizal root tips, lichen thalli). Beyond this minority, the individual organisms can only be accessed/sampled through establishing fungal cultures, which probably represents one of the main bottlenecks in the development of fungal trait databases. In this issue of Molecular Ecology, Zhang et al. (2022) show how interesting insights in fungal trait-based ecology can be gained by working at the community level.


Exposure assessment for a cohort of workers at a former uranium processing facility.
Exposure was assessed for a cohort of 6409 workers at a former uranium processing facility as part of a mortality study. Workers at the facility had potential for exposure to a wide variety of radiological and chemical agents including uranium, thorium, radon, external ionizing radiation, acid mists, asbestos, and various solvents. Organ dose from internal exposure to uranium was assessed, along with dose from external ionizing radiation and exposure to radon. Qualitative assessment of exposure to thorium, acid mists, asbestos, coal dust, welding fumes, and other chemicals was also performed. Mean cumulative organ dose from internal uranium exposure ranged from 1.1 mGy (lung) to 6.7 μGy (pancreas). Mean cumulative external ionizing radiation dose was 13.4 mGy. Mean cumulative radon exposure was 26 working level months (WLMs). The chemical agents to which the largest numbers of study subjects were exposed were acid mists, machining fluids, and a tributyl phosphate/kerosene mixture used in the refining process.


Tumour stimulation by anti-oestrogens.
Two women who developed tumour progression while taking anti-oestrogens are described and some of the possible mechanisms for this action are discussed.


Ion-exchange resins facilitate like-charged protein refolding: effects of porous solid phase properties.
We have previously found that addition of charged particles in a refolding solution can greatly increase the refolding yield of like-charged proteins. Herein, porous anion exchangers of different charged group densities, ligand chemistries, pore sizes and particle sizes were prepared with Sepharose FF gel for studying their effects on the oxidative refolding of like-charged lysozyme. We found that charge density had significant contribution to the enhancing effects on lysozyme refolding. At low resin concentration range (<0.04-0.1g/mL), the refolding yield increased with increasing charged group density and resin concentration. The yield then reached a plateau at a critical resin concentration; the higher the charge density, the lower the critical resin concentration. This implies that gel particles of higher charge density were favorable to offer higher refolding yield at lower added concentrations. In the gel concentration range in which refolding yield has reached plateau, there existed an optimum charge density that gave the highest refolding yield. It was attributed to the electrostatic repulsion effect of the charged groups on the like-charged protein, which reduced the accessible pore volume for the protein. At the same charge density, the refolding yield was independent of ligand chemistry, but a polyelectrolyte group of higher molecular weight was more suitable for grafting the gel to prepare matrices of high charge density. The resins of smaller size exhibited better facilitating effect, and the microporous resin was better than that with superpores. The research is expected to help design more effective charged materials for facilitating protein refolding.


Toxicity of thienopyridines on human neutrophil granulocytes and lymphocytes.
Thienopyridines can cause neutropenia and agranulocytosis. The aim of the current investigations was to compare cytotoxicity of ticlopidine, clopidogrel, clopidogrel carboxylate and prasugrel for human neutrophil granulocytes with the toxicity for lymphocytes and to investigate underlying mechanisms. For granulocytes, clopidogrel, ticlopidine, clopidogrel carboxylate and prasugrel were concentration-dependently toxic starting at 10μM. Cytotoxicity could be prevented by the myeloperoxidase inhibitor rutin, but not by the cytochrome P450 inhibitor ketoconazole. All compounds were also toxic for lymphocytes, but cytotoxicity started at 100μM and could not be prevented by rutin or ketoconazole. Granulocytes metabolized ticlopidine, clopidogrel, clopidogrel carboxylate and prasugrel, and metabolization was inhibited by rutin, but not by ketoconazole. Metabolism of these compounds by lymphocytes was much slower and could not be inhibited by ketoconazole or rutin. In neutrophils, all compounds investigated decreased the electrical potential across the inner mitochondrial membrane, were associated with cellular accumulation of ROS, mitochondrial loss of cytochrome c and induction of apoptosis starting at 10μM. All of these effects could be inhibited by rutin, but not by ketoconazole. Similar findings were obtained in lymphocytes; but compared to neutrophils, the effects were detectable only at higher concentrations and were not inhibited by rutin. In conclusion, ticlopidine, clopidogrel, clopidogrel carboxylate and prasugrel are toxic for both granulocytes and lymphocytes. In granulocytes, cytotoxicity is more accentuated than in lymphocytes and depends on metabolization by myeloperoxidase. These findings suggest a mitochondrial mechanism for cytotoxicity for both myeloperoxidase-associated metabolites and, at higher concentrations, also for the parent compounds.


[The role of medical imaging in paleoanthropology].
Study of the health status of ancient populations relies on the detection and analysis of bone or dental lesions from skeletons. In the absence of clinical or biological data, the identification of a pathology relies on anatomic and radiographic findings. Three paleopathological cases are presented and macroscopic and imaging findings are discussed. These include one case of eosinophilic granuloma, one case of Ewing sarcoma, and one case of secondary hypertrophic osteoarthropathy. Each case illustrates the value and limitations of retrospective diagnosis; an etiologic diagnosis can either be possible, suggested or unknown. Multiple biases, related to specimen preservation and the frequent non-specific nature of bony changes, make paleopathological diagnosis challenging. As such, the use of medical imaging seems valuable in the evaluation of such lesions. It allows non-invasive evaluation of the bone, underlying pathology, and lesion comparison to finally narrow the differential diagnosis.


Decay kinetics of HIV-1-RNA in seminal plasma with dolutegravir/lamivudine versus dolutegravir plus emtricitabine/tenofovir alafenamide in treatment-naive people living with HIV.
This was a substudy of a Phase IV, randomized clinical trial (ClinicalTrials.gov identifier: NCT04295460) aiming to compare the activity of dolutegravir/lamivudine versus dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) in the male genital tract. Participants were asymptomatic adults without sexually transmitted diseases, treatment-naive people living with HIV (PLWH), with CD4+ T cell counts >200 cells/mm3 and plasma HIV-1-RNA levels >5000 and <500 000 copies/mL, randomized (1:1) to DTG + TAF/FTC or dolutegravir/lamivudine. Blood plasma (BP) and seminal plasma (SP) were collected at baseline and Weeks 4, 8, 12 and 24. HIV-1-RNA was measured in BP and SP using the Cobas 6800 system (Roche Diagnostics) with a lower detection limit of 20 copies/mL. The primary efficacy endpoint was the proportion of subjects with undetectable SP HIV-1-RNA at Week 12 by intention-to-treat analysis. Fifteen participants in the DTG + TAF/FTC and 16 in the dolutegravir/lamivudine arms were analysed, with basal SP viral load of 4.81 (4.30-5.43) and 4.76 (4.09-5.23), P = 0.469, respectively. At Week 12, only one participant in each treatment arm had a detectable SP HIV-1-RNA (DTG + TAF/FTC, 141 copies/mL; dolutegravir/lamivudine, 61 copies/mL). Based on the estimated means, there was no significant difference in the decay of HIV-1-RNA in both BP and SP over time between the two arms of treatment (F = 0.452, P = 0.662, and F = 1.147, P = 0.185, respectively). After 12 weeks of treatment, there were no differences in the percentage of undetectable SP HIV-1-RNA in naive PLWH who started dolutegravir/lamivudine compared with DTG + TAF/FTC.


3,5,3'-triiodothyronine (T3) stimulates cell proliferation through the activation of the PI3K/Akt pathway and reactive oxygen species (ROS) production in chick embryo hepatocytes.
Thyroid hormones (THs) have a wide variety of essential roles in vertebrates, ranging from the regulation of key metabolic processes to cell proliferation and apoptosis. The classical mechanism of action of THs is genomic; 3,5,3'-triiodothyronine (T3) binds to specific nuclear receptors (TRs) and modifies the expression of specific genes. Recently, a new category of mechanisms, termed nongenomic, has been discovered for T3. These mechanisms include, among others, the rapid activation of signal transduction pathways, such as PI3K/Akt and MAPK, which eventually lead to cell proliferation. These effects are mediated in some cell types by a plasma membrane receptor, identified as integrin αvβ3, and in other cell types by cytoplasmic TRβ1. The aim of this work was to analyze the effect of T3 on the cell growth of chick embryo hepatocytes at two different stages of development, 14 and 19 days, and to determine the activation of the signal transduction pathways, focusing on the potential involvement of a plasma membrane receptor and the possible participation of PI3K/Akt and reactive oxygen species (ROS). Our results clearly show that T3 stimulates cell proliferation at both stages of development through the activation of the PI3K/Akt pathway and the production of small amounts of ROS, which operate as effective second messengers. Moreover, we prove that these effects are not initiated at the plasma membrane receptor for T3.


Optimization of Delivery of Pediatric Otolaryngology Surgical Antibiotic Prophylaxis.
There is limited evidence regarding use of routine perioperative antibiotics for pediatric otolaryngologic procedures. The objectives of this quality improvement study were (1) to characterize the otolaryngology case mix for which antibiotics were delivered and (2) determine the percentage of surgical encounters with appropriate timing of antibiotic administration. Pediatric otolaryngology procedures meeting criteria from 2015 to 2019 were evaluated as a component of an institution-wide pediatric surgical antibiotic prophylaxis study using A3 problem solving to identify and roll out interventions for appropriate antibiotic administration. Descriptive statistical analysis of the interrupted time-series data was used to describe the otolaryngology case mix for which antibiotics were delivered. The primary outcome measure was percentage of surgical encounters with appropriate timing of antibiotic administration in minutes relative to incision. In total, 1520 pediatric otolaryngology procedures with perioperative antibiotic delivery were performed from July 2015 to September 2019. While surgical site infection number (n = 2/year) was stable, administration of timely prophylactic antibiotics significantly improved: 27.5% of cases per month at baseline and 86.9% at the conclusion of the rollout of the sequential interventions (P < .001). Given the exceedingly low infection rate of clean otolaryngology surgery, there is limited evidence in favor of perioperative antibiotics for the majority of procedures. Prophylactic antibiotics were most commonly used in otologic surgery involving cochlear implantation or in the setting of draining ears or cholesteatoma and in clean-contaminated head and neck surgery cases. Iterative continuous performance improvement can optimize evidence-based delivery of preoperative prophylactic antibiotics. Additional interventions to ensure antimicrobial stewardship in pediatric otolaryngology are indicated.


Impact of early root competition on fitness components of four semiarid species.
Plant demographic and root exclusion approaches were used to examine the influence of roots of adult Artemisia tridentata, Agropyron desertorum, and Agropyron spicatum individuals on seedling survival of four C3 semiarid species, three perennials, Ar. tridentata, Ag. desertorum, Ag. spicatum, and an annual, Bromus tectorum. Furthermore, height of Ar. tridentata seedlings and seed production of B. tectorum were assessed. The probability of a seedling being alive significantly depended on the seedling species, the neighboring adult species, and on the depth to which root competition was excluded. As seedlings, survival of Agropyron species did not differ, whereas survival of Ar. tridentata seedlings was higher than Ag. desertorum and was similar to Ag. spicatum. Bromus tectorum maintained significantly higher survival rates than perennial seedlings. Established individuals of Ar. tridentata reduced seedling survival more than established individuals of either Agropyron species. Seedling survival significantly increased with greater depth of root exclusion for the perennials but did not significantly affect seedling survival of B. tectorum. Height of Ar. tridentata seedlings and seed production of B. tectorum significantly increased with depth of root exclusion. Seed production of B. tectorum was highest when competing with Ag. desertorum and was lowest with Ar. tridentata. Root competition decreased the seed population of B. tectorum in the next generation even though it had no impact on survival. Competition in the upper soil horizon occurs between seedlings and established adults early in the growing season and potentially restricts root growth of seedlings. In arid and semiarid ecosystems, soil moisture is depleted from the upper horizons first, resulting in the death of seedlings that do not have access to moisture.


Special topics in international adoption.
As international adoption has become more "mainstream," the issues recently addressed in domestic adoption have become more important in adoptions involving children originating in other countries. Certain groups of prospective adoptive parents, such as gay or lesbian couples, single parents, and parents with disabilities, have begun to apply to adopt in ever increasing numbers. Children who may have been considered unadoptable in the past are now routinely being offered to prospective adoptive parents. The numbers and ages of the children placed and the spacing between adoptions have come under scrutiny. The rates of adoption dissolutions and disruptions are being examined carefully by the receiving and sending countries. There is a pressing need for research into numerous social aspects of adoption.


Phthalates in plastic stationery in China and their exposure risks to school-aged children.
Phthalates have been strictly banned in children's products in many countries. However, as a product with a high frequency of daily contact with children, stationery is not strictly regulated for phthalates in many countries and the occurrences and risks of phthalates in stationery are rarely reported. In this study, the contents of sixteen types of common phthalates in stationery were determined and the exposure risk of these phthalates to children was also estimated. The total contents of phthalates in all stationery ranged from 5.56 to 3.46 × 105 μg/g, with a median value of 1.48 × 104 μg/g. Polyvinyl chloride (PVC) desk mats (DMs) contained the highest contents of phthalates among all types of stationery. Percutaneous absorption and hand-to-mouth ingestion levels of phthalates for school-age children from the DMs were 2.03 × 10-5 - 10.14 μg/kg-Bw/day and 2.14 × 10-5 - 10.67 μg/kg-Bw/day, respectively. Di-2-ethylhexyl phthalate (DEHP) had the highest proportion, detection rate, and exposure level among all measured phthalates. Our study revealed that phthalates in PVC stationery, especially classroom DMs, at both contents and exposure risks, were higher than those in many other children's plastic products. It was necessary to strengthen the management of plastic stationery from the perspective of materials and phthalates addition.


Ghrelin mitigates MPP+-induced cytotoxicity: Involvement of ERK1/2-mediated Nrf2/HO-1 and endoplasmic reticulum stress PERK signaling pathway.
Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease. Current pharmacological therapies for PD are inadequate and often accompanied by serious side effects. In search of neuroprotective agents being considered to be beneficial to PD therapy. Ghrelin confers neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned PD model, but the underlying mechanism remains not fully elucidated. Here, we utilized human neuroblastoma SH-SY5Y cells exposed to MPP+ as a PD model to investigate the underlying mechanism of Ghrelin. In our present work, cell viability, cell apoptosis, oxidative stress-related indicators, and the level of Nrf2, HO-1, PERK, eIF2α, ATF4, CHOP, and ERK1/2 were examined. The results showed that Ghrelin attenuated MPP+-induced change of cell viability, apoptosis, coupled with decreased Cytochrome c, caspase-9, and caspase-3 expressions. Consistently, Ghrelin suppressed MPP+-induced oxidative stress. Moreover, Ghrelin markedly enhanced Nrf2 expression and nuclear accumulation as well as HO-1 induction. Further investigations showed that Ghrelin significantly inhibited the endoplasmic reticulum stress PERK-eIF2α-ATF4-CHOP pathway. Interestingly, we then found that Ghrelin promoted phosphorylation of ERK1/2, and pharmacological inhibition of ERK signaling abolished the cytoprotective effect of Ghrelin. Furthermore, we also found promoting the activation of the Nrf2/ HO-1 pathway and suppressing of the PERK pathway were mediated by ERK1/2. These findings provided novel insights into the underlying mechanisms of Ghrelin exerted protective effect, suggesting its potential as a novel therapeutic strategy against PD.


Body image, physical activity, quality of life, and community reintegration of individuals with acquired mobility disability in a Nigerian population.
To assess the quality of life (QOL), physical activity (PA), community reintegration (CR), and body image (BI) among adults with acquired mobility disabilities. Relationships between the constructs were also assessed in order to ascertain how a change in one construct could influence the other. This cross-sectional survey involved 157 adults (mean age = 47.51 ± 21.08 years) consecutively recruited from conveniently selected centers in South-east Nigeria. The Short-Form 36-Item Health Survey, the Multidimensional Body Self Relations, the Reintegration to Normal Living Index, and the Short-Form 7-Day International Physical Activity questionnaires were used to assess participants' QOL, BI, CR, and PA respectively. Participants' scores and socio-demographic information were summarised using descriptive statistics while the Spearman test analysed the relationships between constructs. Participants' mean QOL (43.23 ± 13.07), CR (48.09 ± 22.84), and BI (2.91 ± 0.51) scores were poor while their mean PA score (4.39 ± 4.56 × 103 MET-min/week) was high. PA had significant positive relationships with CR (rho = 0.25; p < 0.01) and QOL (rho = 0.33; p < 0.01). BI had a significant positive relationship with CR (rho = 0.28; p = 0.01). PA was high for this sample of individuals with mobility disability receiving physiotherapy but QOL, CR, and BI were poor. Based on observed correlations, rehabilitation interventions for enhancing PA may help improve QOL and CR.IMPLICATIONS FOR REHABILITATIONMobility disabilities are very common and burdensome in Nigeria and other African countries.Quality of life, physical activity, community reintegration, and body image can be adversely affected among individuals with mobility disabilities.Understanding relationships between these constructs among individuals with mobility disabilities could help in enhancing rehabilitation planning and outcomes.Physical activity relates to both community reintegration and life quality, whereas body image relates to community integration.


Enabled interferon signaling evasion in an immune-competent transgenic mouse model of parainfluenza virus 5 infection.
Parainfluenza virus 5 (PIV5 or SV5) infects several mammalian species but is restricted from efficient replication in mice. In humans, PIV5 evades IFN signaling by targeting STAT1 for proteasomal degradation in a STAT2-dependent reaction. In contrast, cell culture experiments have demonstrated that the divergent murine STAT2 protein fails to support STAT1 targeting. Expression of human STAT2 in mouse cells can overcome the species restriction to enable PIV5-induced STAT1 degradation and subsequent IFN antagonism. Here, we describe a transgenic mouse that ubiquitously expresses human STAT2. PIV5 infection induces STAT1 degradation leading to enhanced virus replication and protein expression in the cells from the transgenic mouse but not from the non-transgenic littermates. Importantly, intranasal inoculation with PIV5 results in increased viral load in the lungs of the transgenic mice compared to wild-type littermates. These transgenic mice provide a small animal model to study the role of innate immune evasion in paramyxovirus pathogenesis.


Enhanced Th2 cell differentiation and function in the absence of Nox2.
Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models. Asthma phenotypes were analyzed in response to various allergen-induced experimental asthma using Nox2-deficient mice and recombinase gene-activating-1-deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T-cell activation, levels of activation-induced cell death (AICD), and regulatory T (Treg)-cell differentiation in Nox2-deficient T cells. Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2-null mice regardless of dose and route of various allergens. Nox2-deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg-cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production. Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T-cell-intrinsic manner.


Call for 24/7 end of life community nursing.
The government must ensure dying people have access to 24/7 community nursing, according to the End of Life Care Coalition.


Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.
Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing.


Synthesis of different sized and porous hydroxyapatite nanorods without organic modifiers and their 5-fluorouracil release performance.
Porous biocompatible hydroxyapatite (HAP) nanorods of various sizes were synthesized by the combination of chemical precipitation and hydrothermal method without the use of organic modifiers. The HAP nanorod samples were characterized by powder X-ray diffraction, transmission electron microscopy, and N2 adsorption/desorption techniques. HAP nanorods with average diameters and average lengths ranging from 8.5 to 26.6 nm and from 23.1 to 49.7 nm, respectively, could be controllably synthesized via these methods. Low autoclaving temperature and high pH value favored the formation of relatively small HAP nanorods. The TEM images showed that the nanorods possessed porous structures with average pore diameters ranging from 1.6 to 2.7 nm. These HAP nanoparticles effectively prolonged the release time of 5-fluorouracil up to 24h. The as-synthesized HAP nanorods displayed no cytotoxicity to bone marrow stem cells at low HAP concentration, indicating that these nanorod materials could serve as potential carriers for novel drug release systems.


A novel approach of prophylaxis to HBV recurrence after liver transplantation.
Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection is associated with a high rate of graft loss and poor survival, unless re-infection can be prevented. Human hepatitis B immune globulin (HBIG) and nucleoside analogues (NA) have long been utilized to prevent re-infection. Previously, we generated a human monoclonal antibody (mAb), HB that recognizes the surface antigen of hepatitis B virus (HBV). We have constructed a secreted version of HB and cloned its genes into recombinant adeno-associated virus (AAV). We compared the efficiency of AAV vector after a single injection via intramuscular or intravenous routes without additional intervention. Then, we evaluated the activity of antibody HB in tree shrews treated with rAAV-HB and in vitro experiments. So, intramuscular injection of rAAV-HB was a suitable method for the immunoprophylaxis of HBV infection. This human antibody will be useful for the immunoprophylaxis of HBV infection.


Outcome of 312 Japanese patients with carotid endarterectomy and factors associated with cardiovascular events--a single-center study in Japan.
There have only been a few reports regarding the outcomes and risk factors after CEA. To clarify the factors associated with outcome in patients with carotid stenosis who underwent carotid endarterectomy (CEA), we investigated cardiovascular events and mortality in the Kyushu Medical Center in Japan. We consecutively registered patients with significant carotid stenosis who had CEA performed over 10 years and compared the incidences of stroke, myocardial infarction, and death. On admission, we evaluated medical records for stroke risk factors, including hypertension, diabetes mellitus, hypercholesterolemia, atrial fibrillation, and current smoking habits. When performing CEA, blood pressure, heart rate, blood gases, and Doppler flow parameters in the carotid artery, and an electroencephalogram, were continuously monitored during the procedure. A shunt tube was inserted into both ends of the carotid artery, and a microscope was used. Although it was recommended that patients be evaluated by magnetic resonance imaging and ultrasound after the operation, we attempted to obtain information from the patient or a family member through a questionnaire or telephone survey if a patient did not come for assessment. We determined the factors associated with stroke, myocardial infarction, and death using Kaplan-Meier analyses. Of 312 CEA patients, 302 (96.8%) with confirmed outcomes were analyzed. We found that a factor associated with stroke was a history of ischemic stroke (P = .028). A history of myocardial infarction (P = .009) and the presence of peripheral arterial disease (PAD) (P = .001) were factors related to the future occurrence of myocardial infarction. Perioperative complications occurred in 6 patients (1.99%) including 1 death because of sepsis and 1 major ipsilateral stroke. Of the 302 patients who underwent CEA, 43 patients died in the follow-up period, and the 5-year survival rate was 83.9%. The number of patients who died because of myocardial infarction and cancer was 9 for each, and they were the leading causes of their death. Only 1 patient died because of stroke (2.3%). Patients with PAD had a significantly high mortality (P < .001). In patients who underwent CEA, a risk factor of future stroke was a history of stroke. A history of myocardial infarction or PAD was strongly associated with future occurrence of myocardial infarction or high mortality.


Severe ovarian hyperstimulation syndrome: a reevaluated therapeutic approach.
During the 10 years 1978 to 1987, 33 patients were hospitalized because of moderate and severe ovarian hyperstimulation syndrome (OHSS) in 39 treatment cycles. Twenty-five treatment cycles ended in moderate OHSS (group A), 7 had severe OHSS without a significant amount of ascites (group B1), and 7 had severe OHSS with ascites (group B2). Groups A and B1 received intravascular volume expander, electrolytes replacement, and indomethacin up to 300 mg/day. The patients in group B2 had significant clinical and biochemical improvement after abdominal paracentesis. Urinary output and creatinine clearance improved significantly, and a decrease in hematocrit, blood osmolarity, and weight reduction were achieved. A strategy for treatment of OHSS based on consecutive ultrasonographic examination, clinical and biochemical evaluation, and abdominal paracentesis in severe OHSS with clinically significant ascites is suggested.


Complete Genome Sequence of a New Member of the Marseilleviridae Recovered from the Brackish Submarine Spring in the Cassis Port-Miou Calanque, France.
Marseilleviridae is a rapidly expanding family of Acanthamoeba-infecting large DNA viruses distributed worldwide. We report here the complete 349-kbp genome sequence of Port-Miou virus, which is surprisingly close to that of Lausannevirus (isolated from the Seine River upstream from Paris, France), despite the strong dissimilarities of their sampling locations.


Priority setting: Consensus for Australia's infant safe sleeping public health promotion programme.
To develop focused priorities to inform the revision of Australia's Sudden Unexpected Death in Infancy (SUDI) risk reduction public health programme. A content expert consensus research activity was designed using two consensus techniques. The two-phase study employed a Delphi process (phase 1) and a Nominal Group workshop technique (phase 2). The Delphi invited 56 national and international content experts. The Nominal Group comprised 17 Australasian experts and stakeholders to ensure priority setting was relevant to the Australian context. Phase 1 established a ranked thematic list of 10 key SUDI risk reduction themes. Phase 2 addressed three nominal questions producing prioritised lists for: key-message wording; contextual information and strategies to support caregiver implementation of key messages; and considerations in redesigning and dissemination of a safe sleep campaign. The top four priority themes were: sleep position, sleep space, smoking and surface-sharing. This two-phase priority setting was successful in establishing clearly defined infant safe sleep priorities. International content expert participation in phase 1 strengthened priority setting outcomes while phase 2 ensured final outcomes provided a strong national focus reflective of identified needs of Australian families. Findings provide a foundation from which important components can be considered when revising and developing future SUDI risk reduction programmes.


A new species of Protozantaena Perkins, 1997 from the Great Escarpment of South Africa (Coleoptera, Hydraenidae).
Protozantaena birdi sp. nov. is described, based on specimens collected from the Compassberg and Winterberg ranges in the Eastern Cape Great Escarpment, South Africa; the seventh known species of the genus. Morphologically, the new species appears closely related to P. labrata Perkins, 1997, described from the Naukluft Range in the Central Namibian Great Escarpment. Both species live in the margins of small streams in open, semi-arid landscapes.


A clinical trial of a rehabilitation expert clinician versus usual care for providing manual wheelchairs.
To determine the effect of differing methods of dispensing wheelchairs. Quasi-experimental by day of week. Department of Veterans Affairs Medical Center. Eighty-four community-dwelling, cognitively intact patients prescribed a standard manual wheelchair. A multifactorial intervention consisting of an expert physical/occupational therapist who used a scripted evaluation that included an evaluation based on medical record review and self-reported and physical performance measures; individualization of the wheelchair and initiation of orders for additional occupational/physical therapy, equipment, or home modifications as needed; multimodal patient education; and telephone follow-up at 3 and 6 weeks. The primary outcome was amount of wheelchair use. Secondary outcomes were shoulder pain, wheelchair comfort and confidence, and home modifications. The intervention group had significantly greater wheelchair use than usual care at 2 weeks, 3 months, and 6 months (P=.01). Wheelchair use declined monotonically over time for the entire study sample (P<.001). There were no significant differences between the two groups in shoulder pain, wheelchair comfort or confidence, or home modifications. New wheelchair owners used the wheelchair more often if they received it from an expert therapist using a multifactorial intervention.


Economic evaluation of vaccination programme of 7-valent pneumococcal conjugate vaccine to the birth cohort in Japan.
Aiming to introduce 7-valent pneumococcal conjugate vaccine (PVC-7) into routine vaccination schedule, the government of Japan gives a temporary budget to encourage municipalities in launching public vaccination programme which started on November 26, 2010 and ends on March 31, 2012. This study aims to appraise the 'value for money' of PCV-7 vaccination programme from the societal perspective and the budget impact from the perspective of municipalities, which is responsible for providing routine vaccination. We conducted a cost-effectiveness analysis with Markov modelling and calculated incremental cost-effectiveness ratio (ICER) value of launching such programme with two levels of co-payment, ¥1000 (US$13) or ¥0, and two scenarios of the uptake of vaccine (vaccinated-alone or co-vaccinated with other vaccines). We found that when vaccinated-alone, ICERs in QALY were ¥7,441,000 (US$93,013) or ¥9,065,000 (US$113,313), and when co-vaccinated ¥7,441,000 (US$93,013) or ¥5,489,000 (US$68,613), without or with productivity loss, respectively, regardless of co-payment level of the programme. Co-vaccinated programmes had lower ICER than vaccinated-alone programmes due to the savings in productivity loss. By adopting WHO's classification that an intervention is 'cost-effective' if ICER (in QALY) is between 1 and 3 times of GDP as a criterion, PCV-7 vaccination programme in Japan is concluded as "cost-effective" from the perspective of society. The introduction of either no co-payment or ¥1000 (US$13) co-payment vaccination programme appears to be not budget saving for the first 6 years, whereas the level of budget impact are less than ¥11,000,000 (US$137,500) or ¥8,500,000 (US$106,250), respectively, for a municipality with 1000 birth cohort in the 1st year and 2nd to 5th year birth cohort proportional to the birth cohort population of estimated future population.


The course of psychiatric co-morbidity in patients with breast cancer--results from the prospective multi-centre BRENDA II study.
This study examined the frequency of psychiatric co-morbidity in patients with breast cancer, its changes over time and predictors for these changes. In a prospective study with measurements before surgery (t1, baseline), 1 month (t2) and 8 months thereafter (t3) using the Patient Health Questionnaire, we examined the course of psychiatric co-morbidity in breast cancer patients. The co-morbidity courses were grouped into healthy (no co-morbidity during the study), acute (co-morbidity at t1 and/or t2, but not at t3), emerging (no co-morbidity at t1, but at t3) and chronic (co-morbidity at t1 and t3). Of the 598 participants, 19% had acute, 10% emerging and 9% chronic psychiatric co-morbidity. Acute co-morbidity was more common in patients with poor quality of life (odds ratio (OR) 9.6, 95% confidence interval (CI) 4.4-20.8) and somatic co-morbidity (OR 3.8, CI 1.1-12.4). Patients who perceived support from their doctors had acute co-morbidity less frequently (OR 0.7, CI 0.5-1.0). Emerging co-morbidity occurred more often in younger patients (OR 2.4, CI 1.2-4.7) and in patients with another cancer in their own (OR 2.0, CI 1.1-3.9) or family (OR 2.1, CI 1.1-4.3) histories, less often in patients with support from doctors (OR 0.6, CI 0.4-1.0). Chronic co-morbidity was related to poor quality of life (OR 12.1, CI 3.6-39.9). We found acute and emerging psychiatric co-morbidities less often in patients who reported having a supportive doctor-patient relationship. Patients that require psycho-oncological support often have poor quality of life and have experienced cancer before. Copyright © 2015 John Wiley & Sons, Ltd.


Host-microbiome interactions: Gut-Liver axis and its connection with other organs.
An understanding of connections between gut microbiome and liver has provided important insights into the pathophysiology of liver diseases. Since gut microbial dysbiosis increases gut permeability, the metabolites biosynthesized by them can reach the liver through portal circulation and affect hepatic immunity and inflammation. The immune cells activated by these metabolites can also reach liver through lymphatic circulation. Liver influences immunity and metabolism in multiple organs in the body, including gut. It releases bile acids and other metabolites into biliary tract from where they enter the systemic circulation. In this review, the bidirectional communication between the gut and the liver and the molecular cross talk between the host and the microbiome has been discussed. This review also provides details into the intricate level of communication and the role of microbiome in Gut-Liver-Brain, Gut-Liver-Kidney, Gut-Liver-Lung, and Gut-Liver-Heart axes. These observations indicate a complex network of interactions between host organs influenced by gut microbiome.


Estimation of the capacity for self-purification of transformed rivers of Khanty-Mansi Autonomous Okrug-Yugra (Russia).
This article presents an estimation of the self-purification capacity of rivers flowing through an area of the Ob River basin at Khanty-Mansi Autonomous Okrug-Yugra, which has been significantly transformed by the oil and gas industry. The research was done on the rivers of the Ob River basin in oil fields in 2003-2006 and 2018-2019. The coefficient of mineralization of organic matter has been used as a criterion of the rivers' water self-purification levels. The mineralization coefficient was based on the ratio of numbers of bacteria consuming ammonium nitrogen and polymer substances as well as saprophytic heterotrophic bacteria. According to the results obtained, most rivers draining the oil field area (75% in 2003-2006 and 79% in 2018-2019) were characterized by a low potential for self-purification. The highest level of self-purification criteria was obtained for two rivers: the Ai-Pim River in the Surgut region and the Ovyn'yegan River in the Oktyabrsky region. The high level of self-purification detected with the coeficient of mineralization ensures the maintenance of a certain trophical level and environmental balance of the aquatic ecosystem. Complicated technological processes applied in the oil and gas industry, as well as outdated equipment and poor environmental management, often lead to pipeline accidents and other infrastructure failures. Hazardous pollutants flow into rivers from the watershed area and further into the Gulf of Ob of the Kara Sea. Continuous monitoring of water quality and water resource management based on the results obtained will constitute serious measures to prevent deterioration of aquatic ecosystems. It is necessary to include microbiological parameters in monitoring programs, as this helps to identify the processes of transformation of chemicals found in the river. The use of self-purification assessment methodology for rivers in oil field areas yields effective results in the decision-making process in the sphere of water resource management, significantly reducing ecological risks in the Ob River basin and, as a consequence, in the Arctic region. Integr Environ Assess Manag 2023;19:988-993. © 2022 SETAC.


A glutathione S-transferase inducer from papaya: rapid screening, identification and structure-activity relationship of isothiocyanates.
We have developed a simple system for rapid detection and measurement of glutathione S-transferase placental form (GSTP1) that detoxify polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, (RL34) cells. Survey of fruit extracts for GST inducing ability identified both papaya and avocado as significant sources. Benzyl isothiocyanate (BITC) was isolated from papaya methanol extract as a principal inducer of GST activity. Further, the GST inducing ability of a total of 20 isothiocyanates (ITCs) and their derivatives was investigated. Some ITCs showed significant induction, and BITC was one of the most potent inducers among all compounds tested in the present study. The modification of isothiocyanate group (-NCS) or introduction of substituent group to the alpha-carbon modifies GST induction. Moreover, a significant correlation (P<0.01, r=0.913) between the GST activity enrichment and GSTP1 protein induction by ITCs was observed. We also indicated that phenethyl ITC and nitrophenyl ITC, potently inducing GST activity, but not inactive benzyl isocyanate, are potential inducers of intracellular reactive oxygen intermediates (ROIs). Our system of GSTP1 induction is appropriate for the chemical research such as screening and identification of novel type of inducers as well as the structure-activity relationship studies, providing mechanistic insight into essential structural elements for GSTP1 induction.


The Effects of Very Low Energy Diets and Low Energy Diets with Exercise Training on Skeletal Muscle Mass: A Narrative Review.
In recent years, very-low-energy diets (VLEDs) have been recognised as a viable strategy for improving the extent of weight loss and cardio-metabolic outcomes in people who are either overweight or obese. However, concerns exist regarding the reductions in lean body mass (LBM) during VLEDs, particularly in vulnerable demographic groups, such as middle-aged and older adults already prone to developing sarcopenia. Sarcopenia is itself associated with multiple adverse outcomes, including frailty, cardio-metabolic deterioration and increased mortality. Therefore, a number of studies investigating strategies to ameliorate this detrimental effect of VLEDs have attempted to address this concern. This narrative review explores the potential benefits and limitations of exercise and/or protein supplementation for LBM retention during VLEDs based on the available evidence. Current studies suggest that both protein supplementation and exercise training may result in improved LBM retention (and skeletal muscle function) during VLEDs. However, uncertainty remains concerning the interactions between intervention types, based on discordant outcomes reported in the literature and the heterogeneity of exercise modalities in achieving this particular outcome.


[Copying and free drawing by patients with Alzheimer disease of different dementia stages].
In this study we assessed the drawing abilities in 37 patients with probable Alzheimer's disease according to NINCDS-ADRDA criteria. Drawing abilities (drawing: house, flower, clock; Rey-Osterrieth figure; copying: MMST-figure; Rey-Osterrieth figure) were quantified with different rating schemes and related to other neuropsychological assessments. All patients underwent a positron emission tomography with 18-FDG. Drawing performance was highly correlated with severity of dementia--expressed in MMST scores (r = 0.78; p < 0.0001)--with visuo-spatial short-term memory (r = -0.69; p = 0.001), and writing abilities (r = -0.77; p < 0.0001). The summarized drawing score showed a statistically significant correlation with the rate of temporoparietal glucose metabolism measured with positron emission tomography and 18-FDG (r = 0.39; p = 0.017). In the drawings of AD patients omittings and simplifications were typical, whereas perseverations rarely occurred. In severely demented patients closing-in phenomenons could be described, too. A subgroup of AD patients with visuo-constructive impairment as the leading symptom could not be identified.


Translocation of acylated pardaxin into cells.
Acylated pardaxin is translocated through the cytoplasmic membrane and is accumulated in the nucleoli of NG108-15 and chromaffin cells. The uptake is time- and dose-dependent and temperature-sensitive. However, the binding of acylated 125I-pardaxin cannot be reduced by competition with pardaxin acylated with Rudinger's reagent. In this respect, acylated pardaxin resembles the Tat protein 37-71 fragment. Metabolic inhibitors do not significantly reduce the uptake of acylated 125I-pardaxin. Acylated pardaxin might be useful as a vector to translocate other molecules.


Combination of vitamin D metabolites with selective inhibitors of vitamin D metabolism.
1alpha,25(OH)2D3 exerts antiproliferative, differentiating effects on many cell types, including cancer tissues. In most of its target cells, levels of 1alpha,25(OH)2D3 are regulated by local synthesis via CYP27B and metabolism via CYP24. Rapidly induced by vitamin D, CYP24 repeatedly hydroxylates the vitamin D side chain and ultimately terminates hormonal activity. Aiming at increased hormone levels, lifetime and function, numerous vitamin D analogs have been synthesized with structural modifications, which impede oxidation of the vitamin D side chain. Our group followed a different strategy, namely, blocking 1,25(OH)2D3 metabolism with inhibitors of CYP24. As appropriate inhibitors, we exploited compounds termed azoles, which directly bind to the heme iron of the CYPs via an azole nitrogen and to other parts of the substrate site. We synthesized some 400 azoles and tested their potential to selectively inhibit CYP24, but not hormone synthesis by the related CYP27B. Using primary human keratinocyte cultures as the source of CYP24 and CYP27, we discovered some 50 inhibitors of CYP24 with IC50 values in the nanomole range and selectivities up to 60-fold. As the first representative of selective CYP24 inhibitors, VID400 underwent preclinical development. In human keratinocytes, VID400 stabilized levels of endogenously produced 1alpha,25(OH)2D3, and thereby strongly amplified and prolonged expression of CYP24, a surrogate marker of hormonal function. In parallel, antiproliferative activity showed up at 100-fold or more lower concentrations of 1alpha,25(OH)2D3. This data suggests that CYP24 inhibitors could become attractive drugs in antiproliferative therapy, used as single entities to increase or extend endogenous hormone function or in combination with low doses of potent analogs. Moreover, we used selective inhibitors as valuable tools to (a) elucidate regulatory mechanisms of vitamin D synthesis and metabolism, (b) determine intrinsic activities of the otherwise highly transient vitamin D metabolites and (c) model the active sites of CYP24 and CYP27B.


Fabrication and finite element simulation of antibacterial 3D printed Poly L-lactic acid scaffolds coated with alginate/magnesium oxide for bone tissue regeneration.
This study proposes 3D-printed Poly L-lactic acid (PLA) scaffolds coated with alginate/MgO, and includes three different cellular topologies. Three unique scaffold models were considered: Perovskite type 1 (P1), Perovskite type 2 (P2), and IWP. Each scaffold was coated with alginate/MgO at the concentrations of 0 wt%, 5 wt%, 10 wt%, 15 wt%, and 20 wt%. For morphological and phase study, the microstructure of fabricated scaffolds was characterized using a Field Emission Scanning Electron Microscope (FESEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD) analysis. Besides, the biological characteristics of scaffolds, such as biocompatibility, antibacterial activity, and cell survival were studied after 21 days of soaking in the simulated body fluid (SBF). The results of biological studies indicate that the apatite layer covered the majority of composite scaffold's surface and sealed the pores' surface. The material properties of Alginate/MgO RVEs were evaluated under PBC, and it described that the elastic modulus enhanced from 100 (pure Alginate) to 130 MPA by adding 20 wt% MgO nanoparticles. The presented findings were compared to the results obtained by the experimental procedure and revealed satisfactory agreement. RVE-achieved material properties were used in the additional studies on the scaffolds to find the best candidate due to the material properties and architectures. Furthermore, experiment and finite element simulation were used to evaluate the mechanical properties of scaffolds under the compressive deformation. According to the results, the compressive strength of structures follows the order σPerovskite type 1>σPerovskite type 2 >σIWP. The results indicate that increasing MgO content from 0 wt% to 20 wt% enhances each structure's compressive strength and elastic modulus. In conclusion, based on the biological findings and simulation results, PLA scaffold with Perovskite type 1 (P1) architecture coated with Alginate/ 20 wt% MgO had the best response which is the final research candidate.


Rarely tested or treated but highly prevalent: Hypercholesterolemia in ED observation unit patients with chest pain.
Hypercholesterolemia (HCL) is common among Emergency Department (ED) patients with chest pain but is typically not addressed in this setting. This study aims to determine whether a missed opportunity for Emergency Department Observation Unit (EDOU) HCL testing and treatment exists. We conducted a retrospective observational cohort study of patients ≥18 years old evaluated for chest pain in an EDOU from 3/1/2019-2/28/2020. The electronic health record was used to determine demographics and if HCL testing or treatment occurred. HCL was defined by self-report or clinician diagnosis. Proportions of patients receiving HCL testing or treatment at 1-year following their ED visit were calculated. HCL testing and treatment rates at 1-year were compared between white vs. non-white and male vs. female patients using multivariable logistic regression models including age, sex, and race. Among 649 EDOU patients with chest pain, 55.8% (362/649) had known HCL. Among patients without known HCL, 5.9% (17/287, 95% CI 3.5-9.3%) had a lipid panel during their index ED/EDOU visit and 26.5% (76/287, 95% CI 21.5-32.0%) had a lipid panel within 1-year of their initial ED/EDOU visit. Among patients with known or newly diagnosed HCL, 54.0% (229/424, 95% CI 49.1-58.8%) were on treatment within 1-year. After adjustment, testing rates were similar among white vs. non-white patients (aOR 0.71, 95% CI 0.37-1.38) and men vs. women (aOR 1.32, 95% CI 0.69-2.57). Treatment rates were similar among white vs. non-white (aOR 0.74, 95% CI 0.53-1.03) and male vs. female (aOR 1.08, 95% CI 0.77-1.51) patients. Few patients were evaluated for HCL in the ED/EDOU or outpatient setting after their ED/EDOU encounter and only 54% of patients with HCL were on treatment during the 1-year follow-up period after the index ED/EDOU visit. These findings suggest a missed opportunity to reduce cardiovascular disease risk exists by evaluating and treating HCL in the ED or EDOU.


Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging.
Tributyltin (TBT) is known as an endocrine-disrupting chemical. This study investigated the effects and possible mechanisms of TBT exposure on inducing human articular chondrocyte senescence in vitro at the human-relevant concentrations of 0.01-0.5 μM and mouse articular cartilage aging in vivo at the doses of 5 and 25 μg/kg/day, which were 5 times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively. TBT significantly increased the senescence-associated β-galactosidase activity and the protein expression levels of senescence markers p16, p53, and p21 in chondrocytes. TBT induced the protein phosphorylation of both p38 and JNK mitogen-activated protein kinases in which the JNK signaling was a main pathway to be involved in TBT-induced chondrocyte senescence. The phosphorylation of both ataxia-telangiectasia mutated (ATM) and histone protein H2AX (termed γH2AX) was also significantly increased in TBT-treated chondrocytes. ATM inhibitor significantly inhibited the protein expression levels of γH2AX, phosphorylated p38, phosphorylated JNK, p16, p53, and p21. TBT significantly stimulated the mRNA expression of senescence-associated secretory phenotype (SASP)-related factors, including IL-1β, TGF-β, TNF-α, ICAM-1, CCL2, and MMP13, and the protein expression of GATA4 and phosphorylated NF-κB-p65 in chondrocytes. Furthermore, TBT by oral gavage for 4 weeks in mice significantly enhanced the articular cartilage aging and abrasion. The protein expression of phosphorylated p38, phosphorylated JNK, GATA4, and phosphorylated NF-κB-p65, and the mRNA expression of SASP-related factors were enhanced in the mouse cartilages. These results suggest that TBT exposure can trigger human chondrocyte senescence in vitro and accelerating mouse articular cartilage aging in vivo.


Factors associated with depression among young female migrants in Ethiopia.
Mental health disorders represent a significant share of disease burden for adolescents and young people and depression is among the leading causes of morbidity within this age group. With rural-urban migration increasing in many settings, and young females being among the main migrants, few studies have examined the impact of such major transitions on mental health. This paper measures levels of depression among young women who are rural-urban migrants in Ethiopia, as well as factors associated with depression. This was part of a largescale study of urban migrant females aged 15-24 in Ethiopia, which took place in seven cities. Multiple categories of migrants were interviewed. We used modified PHQ-9 questions to measure depression and logistic regression models to examine its association with various characteristics including patterns of migration and violence. In all, 4,495 migrant females were interviewed. Twenty-one percent of migrant young women displayed symptoms of moderate or severe depression. Symptoms of depression were more common among commercial sex workers (37%) than among other categories of migrants. Factors significantly associated with depression were being in commercial sex work (OR 1.70), migrating before age 15 (OR 1.37), using a broker to find a job (OR 1.53), experiencing forced first sex (OR 2.16) and experiencing beating in the last three months (OR 2.16). This study reveals significant levels of depression among young women in Ethiopia who are rural-urban migrants. The study highlights the need to expand measurement of mental health conditions in health surveys and underscores the need for additional investments in mental health infrastructure, programs and services for marginalized groups in sub-Saharan Africa.


Let the question determine the methods: descriptive epidemiology done right.
What does it mean to control for confounding, and when do we actually need to do it? To answer this, we need a well-defined research question, driven by the goal of the study. For descriptive goals, we explain that confounding adjustment is often not just unnecessary but can be harmful.


Canadian Society of Clinical Chemists Harmonized Clinical Laboratory Lipid Reporting Recommendations on the Basis of the 2021 Canadian Cardiovascular Society Lipid Guidelines.
There is limited guidance on laboratory reporting and interpretation of lipids and lipoproteins used in cardiovascular risk stratification. This contributes to inconsistencies in lipid reporting across clinical laboratories. Recently, the Canadian Cardiovascular Society (CCS) published the 2021 CCS guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. A subcommittee of the Working Group on Reference Interval Harmonization of the Canadian Society of Clinical Chemists has developed harmonized lipid reporting recommendations that are aligned with the 2021 CCS guidelines, to improve the standardization of lipid assessment and clinical decision-making. The proposed harmonized lipid reporting recommendations were critically reviewed by a broad range of laboratory and clinical experts across Canada. Feedback from approximately 30 expert reviewers was reviewed by the Working Group on Reference Interval Harmonization lipid subcommittee, and consensus decisions were incorporated into the 2021 harmonized lipid reporting recommendations. In this position statement, we provide 6 recommendations for laboratory reporting of lipid parameters. These recommendations include implementing the new National Institutes of Health equation to replace the Friedewald equation for calculating low-density lipoprotein cholesterol, offering lipoprotein (a), either as an in-house or send-out test, and using assays that report lipoprotein (a) in molar units (nmol/L). We also developed a harmonized lipid reporting format with interpretive comments that includes flagging results based on screening patients using treatment decision thresholds in a primary prevention setting. Overall, harmonized lipid reporting will help bridge the gap between clinical guideline recommendations and clinical laboratory reporting and interpretation, and will improve cardiovascular risk assessment across Canada.


Lower nitric oxide susceptibility of trivalent antimony-resistant amastigotes of Leishmania infantum.
We previously documented the induction of Leishmania amastigote apoptosis by trivalent antimony (SbIII) and nitric oxide (NO). We demonstrate here that SbIII-resistant amastigotes were resistant to NO toxicity when delivered extracellularly by NO donors or intracellularly via macrophage activation. Shared biochemical targets for SbIII and NO resistance in Leishmania are discussed.


Completion pneumonectomy for lung cancer treatment: early and long term outcomes.
To analyze the experience of completion pneumonectomy for lung cancer at a single institution in China. From January 1988 to December 2007, 92 patients underwent completion pneumonectomy for the treatment of lung cancer. The indications were second primary lung cancer (n=51), Local metastasis (n=37) and Lung metastasis (n=4). The median interval between the primary operation and CP was 24.4 months (1.5-145 m). There was no intraoperative deaths. The CP procedure lasted 4.3 h (1.5-8 h). Blood loss in the CP performance was 1854.5 ml (200-9100 ml) 9 (9.78%) patients died in the postoperative period: pulmonary embolism (n = 2), disseminated intravascular coagulation (DIC) after the multisystem failure (n = 1), respiratory failure after contralateral pneumonia (n = 5), bronchopleural fistula (BPF) with acute respiratory distress syndrome (ARDS) (n = 1) 31(33.7%) patients had at least one major nonfatal complication. The 1, 3 and 5 year survival rates were 81%, 26% and 14% respectively. Completion pneumonectomy for lung cancer is a safe surgical procedure for the skilled surgeon though it has a relatively higher complications and the long-term survival is acceptable.


Ectopic hormone-secreting pheochromocytoma: a francophone observational study.
Ectopic hormone-secreting pheochromocytomas are rare; only case reports exist in the literature. This condition has been linked with increased malignancy, familial syndromes, and ACTH secretion. We wanted to test these hypotheses and shed light on the nature of ectopic hormone-secreting pheochromocytomas. This is a multicenter (francophone) observational study. Inclusion was based upon abnormal preoperative hormone tests in patients with pheochromocytoma that normalized after removal of the tumor. Where possible, immunohistochemistry was performed to confirm that ectopic secretion came from the tumor. Sixteen cases were found: nine female and seven male patients. Median age was 50.5 (range 31-89) years. Most presented with hypertension, diabetes, or cushingoid features. Ten patients had specific symptoms from the ectopic hormone secretion. Two had a familial syndrome. Of eight patients with excess cortisol secretion, three died as a result of the tumor resection: two had pheochromocytomas >15 cm and their associated cortisol hypersecretion complicated their postoperative course. The other died from a torn subhepatic vein. The 13 survivors did not develop any evidence of malignancy during follow-up (median 50 months). Symptoms from the ectopic secretion resolved after removal of the tumor. Immunohistochemistry was performed and was positive in eight tumors: five ACTH, three calcitonins, and one VIP. Most pheochromocytomas with ectopic secretion are neither malignant nor familial. Most ectopic hormone-secreting pheochromocytoma cause hypercortisolemia. Patients with a pheochromocytoma should be worked up for ectopic hormones, because removal of the pheochromocytoma resolves those symptoms. Associated cortisol secretion needs careful attention.


A solidification procedure to facilitate kinematic analyses based on video system data.
When video-based motion analysis systems are used to measure segmental kinematics, the major source of error is the displacement of skin-fixed markers relative to the underlying skeletal structure. Such displacements cause the marker representation of the segment to deform, thereby decreasing the accuracy of subsequent three-dimensional kinematic calculations. We have developed a two-step solidification procedure to address this problem. First, the mean rigid shape is computed which best represents the time-varying marker configuration of each segment. Second, a least-squares minimization is used to replace the measured marker coordinates with those corresponding to the best-fit mean rigid shape. Rigid body theory can then be applied unambiguously to perform kinematic analyses. To evaluate this approach, we defined an unperturbed three-dimensional reference movement using kinematic data from the swing phase of gait. After perturbing the marker coordinates with artificial noise, the rotation matrix and translation vector (absolute and relative movement) between each pair of successive images were computed using (1) reference frames fixed directly to the perturbed marker coordinates, (2) a least-squares minimization procedure found in the literature, and (3) the proposed solidification procedure. The least-squares and solidification procedures produced extremely similar results which, relative to the direct calculation, reduced kinematic errors on average by 20-25% when the maximum distance between markers was small (e.g. < 15 cm). The solidification methodology therefore combines the numerical benefits of the least-squares method with the conceptual benefits of a rigid body method.


Investigation of the retinal biocompatibility of acid violet for chromovitrectomy.
The primary objective was to investigate the retinal biocompatibility of acid violet (AV) as a vital dye for chromovitrectomy. The secondary objective was to evaluate the capacity of AV to stain the anterior capsule of the lens. An amount of 0.05 ml of 0.25 g/l and 0.5 g/l AV was injected intravitreally in the OD, while balanced salt solution (BSS) was applied in the OS for control. Clinical examination and histology with light microscopy (LM) were performed after 7 days. Retinal cell layers were evaluated for morphologic alterations and number of cells. The electroretinographic (ERG) changes were assessed at baseline and 7 days. In another part of the study, 0.1 ml of 0.25 g/l AV was injected into the anterior chamber of ex-vivo porcine eyes, and its capacity to stain the anterior capsule was determined. Cadaveric eyes were used to test the capacity of AV to stain the internal limitant membrane (ILM) during vitrectomy. The gross histopathologic appearance of the retina, choroids, sclera, and optic nerve was within normal limits, without any signs of severe retinal necrosis or cystic degeneration. AV caused no substantial retinal alterations in retinal layers by LM at either the lower or higher dose when compared with the control eye. The injection of AV did not induce considerable ERG alterations. The violet dye stained the anterior capsule after anterior chamber injection and the ILM, allowing a safer capsulorrhexis and vitrectomy. Acid violet may be safe for the retina at concentrations of 0.25 and 0.50 g/l after intravitreous injection, and may be used as a vital dye for staining the anterior capsule and the ILM.


Reductive activation of carbon-fluorine bonds in perfluoroalkyl ligands: an unexpected route to the only known tetrafluorobutatriene transition metal complex: Ir(eta 5-C5Me5)(PMe3)(2,3-eta 2 -CF2[double bond]C[double bond]C[double bond]CF2).
Six-electron reduction of the perfluoro-sec-butyl ligand in Cp*Ir(PMe3)I(C4F9) with sodium naphthalenide affords the first known example of a transition metal complex of tetrafluorobutatriene, Cp*Ir(PMe3)(C4F4). The free ligand is a highly unstable compound. The compound has been completely characterized by a single-crystal X-ray diffraction study; the center coordinated double bond shows significant elongation, and the flanking fluoroalkenes show significant shortening, as compared to the dimensions in the free ligand.


Improving educational preparation for transcultural health care.
There is increasing evidence that the health care needs of people from black and ethnic minority groups in England are not being met. A growing number of initiatives are being undertaken to remedy the situation. Many of them are focused on health care delivery at local and national levels. However, unless the preparation of health care professionals in the area of multi-cultural health care is appropriate and effective, a great deal of corrective action will continue to have to be taken. Despite 1997 having been the European Year Against Racism, it is still necessary to consider what educational preparation should be like. The article draws on identified inadequacies in health care provision as well as examples of initiatives taken to improve care provision. The author identifies deficiencies in educational preparation and proposes a range of actions to be taken. The article is focused on nursing, midwifery and health visiting education in England, but is deemed to be relevant to all health care professionals not only in Europe but other continents, as they become increasingly international and multi-ethnic.


Sleep patterns in pregnancy: a longitudinal study of polysomnography recordings during pregnancy.
To evaluate the differences in sleep of women throughout pregnancy compared with those of nonpregnant control subjects. Four pregnant women were studied longitudinally during their pregnancy using inpatient polysomnography. Measurements included electroencephalography, electrocardiography, and continuous-pulse oximetry. Four healthy nonpregnant women matched for age and weight were used as control subjects. The total sleep time was recorded, and percentages of each sleep stage were generated. Qualitative differences in sleep between pregnancy patients and control subjects were evident. Control subjects displayed a normal appearance of slow-wave sleep in stages 3 and 4 (delta sleep). When pregnant patients did display delta sleep, it appeared abnormal secondary to extensive alpha-wave intrusion. Even when including this abnormal delta sleep in a quantitative comparison, the pregnant patients had a significantly shorter percentage of total sleep time in delta sleep (4.9+/-1.9% vs 21.9+/-6.0%, p=0.03). Sleep in pregnancy is characterized by loss of normal slow-wave sleep. Thus, sleep stages 3 and 4 are shortened during pregnancy. This sleep alteration is persistent when followed longitudinally during pregnancy.


Stimuli-responsive cancer nanomedicines inhibit glycolysis and impair redox homeostasis.
The solid tumors are characterized with oxidative stress and metabolic reprogramming, which has been independently used for targeted tumor monotherapy. However, the potential of targeting metabolism-redox circuit in tumor therapy has long been neglected. Herein, we report a hybrid nanocarrier for concurrent targeting of glycolysis and redox balance in the current work. The nanocarriers are made of pH- and ATP-responsive zeolitic imidazolate framework (ZIF-8) as the porous core that was further coated with poloxamer 407 as the steric stabilizer. Two active cargos, glucose oxidase (GOx) and 3-bromopyruvate (3-BrPA) were co-loaded in the core of nanocarrier. GOx is well-known for its ability of producing hydrogen peroxide at the expense of glucose and oxygen. 3-BrPA can reduce oxygen and glucose consumption through glycolysis, which sensitized cancer cells to GOx-induced apoptosis. At the cellular level, the hybrid nanocarrier significantly impaired the redox balance in the liver hepatocellular carcinoma cell line (HepG2), as evidenced by the depletion of glutathione and boost of reactive oxygen species. The potency of hybrid nanocarrier in terms of suppressing HepG2 cell energy metabolism was proven by the exhaustion of ATP. As a consequence, cell viability was greatly reduced. The in vivo efficacy of hybrid nanocarriers was demonstrated in HepG2 tumor-bearing mice. The current work presents an approach of targeting metabolism-redox circuit for tumor treatment, which may enrich the available anti-tumor strategies. STATEMENT OF SIGNIFICANCE: Metabolic alterations and elevated reactive oxygen species (ROS) are two characteristics of cancer. The metabolic patterns of cancer cells are elaborately reprogrammed to enable the rapid propagation of cancer cells. However, the potential of targeting the metabolism-redox circuit in anti-tumor therapy has long been neglected. As a proof-of-concept, we report an engineered stimuli-responsive nanomedicine that can eradicate cancer cells via cooperative glycolysis inhibition and redox impairment. The current work presents an approach of targeting the metabolism-redox circuit for tumor treatment, which may enrich the available anti-tumor strategies.


Cholecystokinin-octapeptide-induced hypothermia in rats: dose-effect and structure-effect relationships, effect of ambient temperature, pharmacological interactions and tolerance.
Subcutaneous injection of cholecystokinin octapeptide (CCK-8) (0.005-1.25 mg/kg) elicited dose-dependent hypothermia in rats. The threshold of the response was between 0.01 and 0.05 mg/kg and the dose-response curve levelled off at doses larger than 0.2-0.5 mg/kg. Warm and cold ambient temperatures decreased and increased the response, respectively. Pretreatment with capsaicin, morphine, naloxone, atropine, haloperidol or propranolol did not affect the response to CCK-8, whereas pretreatment with phenoxybenzamine and a large dose of proglumide, an antagonist for CCK-receptors, attenuated the hypothermia. It seems that neither capsaicin-sensitive thermal and non-thermal afferents, nor opiate mechanisms are involved in the response, but alpha-adrenoceptors might be of some importance in the hypothermia. Non-sulphated-CCK-8, the C-terminal tetrapeptide and hexapeptide, [D-Ala4]-CCK-8 and [D-Met6]-CCK-8 were ineffective. Chronic treatment with CCK-8 resulted in the development of tolerance to the thermoregulatory effect, while the hypothermic responses to apomorphine and capsaicin were not affected. It seems that the tolerance cannot be attributed to conditioned homeostatic reactions.


Remission of pseudo-spondylitis with treatment of Whipple's disease.
An HLA-B27 negative case of Whipple's Disease with 'spondylitis' is reported in which antibiotic therapy gave sustained remission of spondylitis as well as intestinal disease.


Application of weighted gene co-expression network analysis to reveal key modules and hub genes in generalized aggressive periodontitis.
The aim of this study was to construct a gene co-expression network to identify key modules and genes in people with generalized aggressive periodontitis. We used database GSE79705 to construct a co-expression network by weighted gene co-expression network analysis (WGCNA). In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. A total of 51 co-expression modules were conducted, darkseagreen1 and blue1 modules were the most significantly related to generalized aggressive periodontitis. Genes in the darkseagreen1 module enriched in affecting cellular response to tumor necrosis factor and vascular endothelial growth factor production, and the blue1 module enriched in the regulation of ion transport, proteinaceous extracellular matrix and neuropeptide binding. Besides, we found that 4 hub genes (SNRPG, MRPL22, MRPS18C and CEP290) played an important role in the occurrence of generalized aggressive periodontitis. Through this study, we identified two modules and four hub genes associated with generalized aggressive periodontitis. Besides, 4 hub genes (SNRPG, MRPL22, MRPS18C and CEP290) can be expected to trigger new therapeutic drug development for generalized aggressive periodontitis.


Neurotrophin effects on survival and expression of cholinergic properties in cultured rat septal neurons under normal and stress conditions.
These studies tested the hypothesis that survival-promoting effects of neurotrophins on basal forebrain cholinergic neurons are enhanced under stress. Septal neurons from embryonic day 14-15 rats exposed for 10-14 d to neurotrophin [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4 (NT-4), each at 100 ng/ml] showed a two- to threefold increase in choline acetyltransferase (ChAT) activity, with little evidence of synergistic interactions. Neurotrophins produced no significant increase in the survival of total or acetylcholinesterase (AChE)-positive neurons at moderate plating density (1200-1600 cells/mm2). However, with very low plating densities (2-28 cells/mm2) BDNF, NT-3, and NT-4 (but not NGF) increased total neuronal survival, and BDNF increased survival of AChE-positive neurons. NGF and BDNF enhanced ChAT activity and survival of cholinergic neurons after a 24 hr hypoglycemic stress, even when added 1 hr after stress onset. All four tested neurotrophins increased total neuronal survival after hypoglycemic stress. These results suggest that neurotrophins are important for preservation of central cholinergic function under stress conditions, with different neurotrophins protecting against different stresses. The stress-associated survival-promoting effects of neurotrophins were not limited to the cholinergic subpopulation.


CLCA1 suppresses colorectal cancer aggressiveness via inhibition of the Wnt/beta-catenin signaling pathway.
Chloride channel accessory 1 (CLCA1) belongs to the calcium-sensitive chloride conductance protein family, which is mainly expressed in the colon, small intestine and appendix. This study was conducted to investigate the functions and mechanisms of CLCA1 in colorectal cancer (CRC). The CLCA1 protein expression level in CRC patients was evaluated by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and western blotting analysis. Using CRISPR/Cas9 technology, CLCA1-upregulated (CLCA1-ACT) and CLCA1-knockout cells (CLCA1-KO), as well as their respective negative controls (CLCA1-ACT-NC and CLCA1-KO-NC), were constructed from the SW620 cell line. Cell growth and metastatic ability were assessed both in vitro and in vivo. The association of CLCA1 with epithelial-mesenchymal transition (EMT) and other signaling pathways was determined by western blotting assays. The expression level of CLCA1 in CRC tissues was significantly decreased compared with that in adjacent normal tissue (P< 0.05). Meanwhile, the serum concentration of CLCA1 in CRC patients was also significantly lower when compared with that of healthy controls (1.48 ± 1.06 ng/mL vs 1.06 ± 0.73 ng/mL, P = 0.0018). In addition, CLCA1 serum concentration and mRNA expression level in CRC tissues were inversely correlated with CRC metastasis and tumor stage. Upregulated CLCA1 suppressed CRC growth and metastasis in vitro and in vivo, whereas inhibition of CLCA1 led to the opposite results. Increased expression levels of CLCA1 could repress Wnt signaling and the EMT process in CRC cells. Our findings suggest that increased expression levels of CLCA1 can suppress CRC aggressiveness. CLCA1 functions as a tumor suppressor possibly via inhibition of the Wnt/beta-catenin signaling pathway and the EMT process.


Human apolipoprotein E allele-specific brain expressing transgenic mice.
Transgenic mice were created using human apolipoprotein E2, E3, and E4 gene fragments driven by the human glial acidic fibrillary protein (GFAP) promoter. Founders were obtained and progeny were assayed for transgene expression in the brain by RNase protection, immunohistochemistry, and Western blotting, demonstrating robust apolipoprotein E (apoE) brain expression, with human apoE representing up to approximately 0.2% of total brain protein. Selected lines were bred to apoE-deficient mice yielding mice which expressed the human transgenic apoE isoforms in the absence of endogenous apoE. Immunohistochemistry revealed accumulation of the transgene encoded human apoE throughout the brain. Double immunofluorescence showed co-expression of the apoE transgene with endogenous glial acidic fibrillary protein. Primary astrocyte cultures from the transgenic mice secreted human apoE into the medium. Aged apoE4 transgenic mouse brain failed to demonstrate any evidence of senile plaques. These mice may be useful for elucidation of the mechanism by which apoE4 is associated with Alzheimer's disease.


Fat Grafting for Facial Rejuvenation with Cryopreserved Fat Grafts.
Fat grafting to the face for volume augmentation, and skin rejuvenation have become a popular procedure. However, the main obstacles to fat grafting include the unpredictable volume maintenance rate and the unpredictable number of treatments needed to obtain a satisfactory rejuvenate effect. Therefore, many patients need repeat sessions. However, serial fat grafting with fresh fat imposes a burden on the patient not only because of the pain but also because of the downtime of harvesting. Therefore, if the fat can be cryopreserved, and used many times in 1 harvesting, those burdens can be reduced.


One-year change in sarcopenia was associated with cognitive impairment among haemodialysis patients.
Our study aimed to evaluate change in sarcopenia, its defining components over 1 year follow-up and investigate associations with subsequent cognitive decline, incident mild cognitive impairment (MCI) and dementia among patients undergoing haemodialysis (HD). In the multicentre, longitudinal study, 1117 HD patients aged 56.8 ± 14.3 years (654 men; and 463 women) from 17 dialysis centres in Guizhou Province, China, were recruited in 2019 and followed up for 1 year in 2020. Sarcopenia was diagnosed with Asian Working Group for Sarcopenia criteria using appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Body composition was measured using body composition monitor; body water, weight, and height were corrected to calculate ASMI. HGS was measured by mechanical handgrip dynamometer. Cognitive function was measured with Mini Mental State Examination. Multivariate linear, logistic regression models and subgroup analyses were employed to examine the associations of changes in sarcopenia, ASMI, and HGS with Mini Mental State Examination score change, and incident MCI, dementia. Four hundred fourteen (37.1%) patients had sarcopenia at baseline; during 1 year follow-up, 257 (23.0%) developed MCI and 143 (12.8%) developed dementia. According to changes in sarcopenia, patients were stratified into four groups: non-sarcopenia; non-sarcopenia to sarcopenia; sarcopenia; and sarcopenia to non-sarcopenia. HD patients in sarcopenia and non-sarcopenia to sarcopenia groups had higher risk of MCI (34.8%, 32.0%, vs. 17.4%) and dementia (20.6%, 19.8%, vs. 8.7%), compared non-sarcopenia group (P < 0.001). Multivariate linear regression analyses showed that sarcopenia [regression coefficients (β) -1.098, 95% confidence interval (CI) -1.872, -0.324, P = 0.005] and non-sarcopenia to sarcopenia (β -1.826, -2.441, -1.212, P < 0.001) were associated with faster cognitive decline compared to non-sarcopenia. HGS decline (β 0.046, 0.027-0.064, P < 0.001) and ASMI decline (β 0.236, 0.109-0.362, P < 0.001) were both positively associated with cognitive decline. Multivariate logistic regression analyses demonstrated that patients with sarcopenia and non-sarcopenia to sarcopenia were both at increased risk of developing MCI [odds ratio (OR) 1.788, 95% CI 1.115-2.870, P = 0.016 and OR 1.589, 95% CI 1.087-2.324, P = 0.017, respectively], but only non-sarcopenia to sarcopenia was at increased risk of dementia (OR 1.792, 95% CI 1.108-2.879, P = 0.017). Both greater change of ASMI and HGS had lower risk of MCI with adjusted ORs of 0.857 (0.778-0.945, P = 0.002) and 0.976 (0.963-0.989, P < 0.001). Robust associations were found among female individuals, aged >60 years, and with low educational level. Longitudinal associations were observed between new-onset, persistent sarcopenia, and cognitive impairment. Early detection and intervention should be implemented to delay the onset of sarcopenia and improve cognitive health among HD patients.


Biomechanical properties of human pelvic organs.
To comparatively define the biomechanical characteristics of the pelvic organs (the vagina, bladder, and rectum), which are crucial for the maintenance of pelvic support. Despite minimal fundamental studies, meshes are increasingly implanted into the vesicovaginal and rectovaginal spaces to replace disrupted native tissues and to treat pelvic organ prolapse. However, the mechanical characteristics of these materials have not yet been compared with those of the "functional unit," the vagina, bladder, and rectum. Samples from 5 fresh female cadavers without prolapse were collected. Uniaxial tension tests under monotonic and cyclic loading were performed and the stress-strain curves obtained. The biomechanical properties of the vaginal, bladder, and rectal tissues differed significantly. We were able to demonstrate a nonlinear relationship between the stress and strain and a visco-hyperelastic behavior with a Mullins effect of damage of the tissues examined. Comparable rigidity was found between the investigated tissues at low strains; however, at large strain levels, marked differences could be observed. The vagina was much more rigid and less extendible than the rectal tissue, which, in turn, was more rigid than the bladder tissue. The anterior and posterior vagina revealed a different stiffness, and the bladder tissue was anisotropic at large strain levels. Our results underline the pivotal role of the vaginal tissue for the maintenance of pelvic support. The observed differences with respect to tissue rigidity should have pronounced effects on the physiologic organ function, pointing to the necessity of a differentiated view on using the same prosthetic material for different anatomic locations.