Diurnal rhythms in cholinergic modulation of rapid dopamine signals and associative learning in the striatum.
Dysregulation of biological rhythms plays a role in a wide range of psychiatric disorders. We report mechanistic insights into the rhythms of rapid dopamine signals and cholinergic interneurons (CINs) working in concert in the rodent striatum. These rhythms mediate diurnal variation in conditioned responses to reward-associated cues. We report that the dopamine signal-to-noise ratio varies according to the time of day and that phasic signals are magnified during the middle of the dark cycle in rats. We show that CINs provide the mechanism for diurnal variation in rapid dopamine signals by serving as a gain of function to the dopamine signal-to-noise ratio that adjusts across time of day. We also show that conditioned responses to reward-associated cues exhibit diurnal rhythms, with cue-directed behaviors observed exclusively midway through the dark cycle. We conclude that the rapid dopamine signaling rhythm is mediated by a diurnal rhythm in CIN activity, which influences learning and motivated behaviors across the time of day.


Intranasal oxytocin decreases cross-frequency coupling of neural oscillations at rest.
Recent research has suggested a role for the hormone oxytocin in social cognition and behavior. Administration of intranasal oxytocin modulates multiple brain regions during experimental tasks; however, the neural mechanisms that underscore the changes associated with oxytocin administration are yet to be fully elucidated. In a double-blind placebo controlled design using electroencephalography, the effects of intranasal oxytocin on neural oscillations (delta, theta, alpha, beta) and their coupling during the resting state were examined. Prior work suggested that coupling of slow and fast waves are indicative of the integration of motivational and cognitive processes. While neural oscillations were unaffected by oxytocin relative to placebo administration; oxytocin decreased delta-beta, delta-alpha, theta-alpha, and theta-beta coupling. These findings suggest that one mechanism through which intranasal oxytocin may modulate brain and behavior is through affecting the cross-frequency coupling of neural oscillations, a phenomenon that has been associated with specific cognitive and motivational states.


Building quantitative relationship between changed sequence and changed oxygen affinity in human hemoglobin beta-chain.
244 point mutations have been recorded in human hemoglobin beta-chain, of which some change the oxygen affinity of human hemoglobin beta-chain. We use the amino-acid distribution probability to quantify these mutations, and use the cross-impact analysis with Bayes' law to determine the probability that changes the oxygen affinity of human hemoglobin beta-chain under mutations.


Adherence to a healthy diet and odds of metabolic syndrome: A cross-sectional study.
Metabolic syndrome (MetS) is a major health concern around the world. Dietary factors, including diet quality, play a significant role in its pathophysiology. Healthy Eating Index (HEI) is a tool used as a valid measurement of the individual's diet quality. We aimed at investigating the relationship between diet quality as assessed by HEI-2015 and the risk of MetS and its components in a cross-sectional sample of suburban individuals from PERSIAN Kavar cohort study (PKCS), Fars province, Iran. 2225 individuals meeting the eligibility criteria participated in the study. The relevant data were obtained from the baseline phase of PKCS. MetS was defined according to cut-offs presented by the National Cholesterol Education Program Adult Treatment Panel III (ATP III). HEI-2015 was calculated for the included individuals. Odds ratios were estimated. P-values <0.05 were considered as significant. The overall prevalence of MetS was 27.3%. Individuals with lower HEI-2015 scores had higher odds for MetS and its components. We observed that those who were categorized as the top HEI-2015 tertile had 42% (OR: 0.58; 95% CI: 0.38-0.90) lower odds of high blood pressure in the overall population. Also, the odds of high serum triacylglycerol was lower (OR: 0.72; 95% CI: 0.57-0.90) in those with the highest HEI-2015 scores. We found that higher dietary quality measured by HEI will decrease the risk of developing MetS, hypertension, and hypertriglyceridemia among Iranian adults. However, future interventional studies are required to further elucidate the issue.


Location of nicotinic and muscarinic cholinergic and mu-opiate receptors in rat cerebral neocortex: evidence from thalamic and cortical lesions.
In vitro receptor binding techniques were used to identify the cellular location of nicotinic and muscarinic cholinergic and mu-opiate receptors in the fronto-parietal region of rat cerebral neocortex. Changes in the normal pattern of receptor binding of ligands for these 3 receptors were examined in a series of adjacent sections after unilateral thalamic fiber or cortical cell lesions. Thalamocortical fibers were destroyed by making either electrolytic lesions or kainic acid injections centered in the region of the thalamic ventrobasal complex. These lesions reduced cortical labeling of nicotinic ([3H]nicotine) and mu-opiate ([3H]DAGO) receptors while they did not affect cortical muscarinic ([3H]quinuclidinyl benzilate ([3H]QNB)) labeling. Intracortical injections of quinolinic acid (QA) were used to destroy cortical neurons and spare extrinsic fibers. Cortical QA lesions markedly reduced muscarinic and mu-opiate labeling, but had no significant effect on nicotinic binding at short survivals. Our results suggest that a subset of nicotinic receptors is located presynaptically on the specific thalamo-cortical fibers, while muscarinic receptors are located primarily on cortical neurons. Receptors of the mu-opiate type appear to be located both presynaptically on thalamo-cortical terminals and on intrinsic cortical neurons. The differences in the location of these receptor types suggest that each one modulates discrete aspects of cortical processing.


Extracellular application of cobalt: a fast and simple method for delineating invertebrate neurosecretory pathways.
The extracellular cobalt backfilling technique was shown to be an excellent method to obtain cobalt backfills of invertebrate neurosecretory cells (NSCs). Aqueous cobalt was placed in an extracellular suction electrode into which a portion of a neurohaemal (NH) region containing the axons and/or terminals of NSCs was drawn. Spontaneously discharging extracellular action potentials were recorded as the cobalt was applied to the NH region, and the greater the electrical activity, the more extensive the cobalt backfilling. The greatest success occurred with 0.5 M cobalt chloride dissolved in physiological saline. No backfills were obtained in the absence of electrical activity. This technique was shown to backfill NSCs terminating in NH regions of the insect, Rhodnius prolixus, the isopod crustacean, Oniscus asellus, and the freshwater pulmonate snail, Helisoma. Combined with a light insensitive silver intensification method, this paper describes a relatively fast and simple method for delineating invertebrate neurosecretory pathways.


Culture duration alters the glutathione content and sensitivity to ethacrynic acid of rat hepatocyte monolayer cultures.
Many of the differentiated functions of hepatocytes are lost in culture, yet addition of certain medium supplements can aid in the retention of differentiated character. Therefore, the effect of time in monolayer culture on rat hepatocyte glutathione (GSH) synthesis and sensitivity to the GSH detoxicated xenobiotic ethacrynic acid was examined in cultures with and without medium supplementation by transferrin and sodium selenite. GSH content was found to be about 12 nmol/micrograms DNA at 4 hr in culture and to approximately triple by 24 hr. Intracellular GSH levels continued to increase in transferrin/sodium selenite-supplemented cultures, from 32 to 41.6 nmol/micrograms DNA, while GSH levels in unsupplemented cultures declined to 18 nmol/micrograms DNA. However, the rate of GSH synthesis after diethylmaleate depletion was found to decrease from 4.2 to 2.8 nmol/hr/micrograms DNA at 4 and 24 hr after inoculation, respectively. GSH repletion rate increased to 3.9 nmol/hr/micrograms DNA at 48 hr. The GSH accumulation rate after depletion in supplemented cultures did not vary significantly over the initial 48 hr. Incubation for 3 hr with 100 microM ethacrynic acid (EA) did not elicit an increase in LDH leakage in hepatocyte monolayers after 4 or 48 hr in culture or in cultures with supplemented medium at any time point tested. Cultures 24 hr in medium without transferrin/sodium selenite supplementation exhibited significant LDH leakage after 3 hr of EA treatment. Over the 3 hr EA treatment, intracellular GSH content was decreased in all cultures. Only in the 24 hr unsupplemented cultures did GSH depletion exceed the 90% level previously associated with depletion of the mitochondrial pool of GSH and EA toxicity in hepatocytes. The experiments show that during the redifferentiation of hepatocytes in culture, a transient period occurs when apparent GSH synthesis is depressed and enhanced sensitivity to GSH-detoxicated compounds is observed. This period of increased sensitivity is prevented or at least delayed by inclusion of supplemental transferrin and sodium selenite, suggesting that redifferentiation can be regulated by extracellular influences.


Natural course of acute and chronic monophasic inflammatory demyelinating polyneuropathies (IDP). A retrospective analysis of 266 cases.
The present study analyses one of the largest IDP series published as yet: 266 cases, hospitalised between 1950 and 1983, conventionally treated and uniformly supervised. There was GBS in 84%, chronic IDP in 13%, polyneuritis cranialis in 1.5%, Miller Fisher and predominantly sensory neuropathy in 0.8% each. Numerous features including preceding events, course and outcome have been investigated. Latencies between onset and maximal deficit lacked (expected) bimodality. Sensory involvement was severe, mortality (18%) and maximal disability (20% requiring ventilation) high, autonomic dysfunction (71%) prominent. Statistical comparison of various features confirmed old age, rapid onset and need for ventilation as unfavorable predicting factors. However, preceding infection, bulbar paralysis and onset of paresis in proximal muscles evolved as unfavorable prognostic features as well.


Functional Diversity and Evolution of the Drosophila Sperm Proteome.
Spermatozoa are central to fertilization and the evolutionary fitness of sexually reproducing organisms. As such, a deeper understanding of sperm proteomes (and associated reproductive tissues) has proven critical to the advancement of the fields of sexual selection and reproductive biology. Due to their extraordinary complexity, proteome depth-of-coverage is dependent on advancements in technology and related bioinformatics, both of which have made significant advancements in the decade since the last Drosophila sperm proteome was published. Here, we provide an updated version of the Drosophila melanogaster sperm proteome (DmSP3) using improved separation and detection methods and an updated genome annotation. Combined with previous versions of the sperm proteome, the DmSP3 contains a total of 3176 proteins, and we provide the first label-free quantitation of the sperm proteome for 2125 proteins. The top 20 most abundant proteins included the structural elements α- and β-tubulins and sperm leucyl-aminopeptidases. Both gene content and protein abundance were significantly reduced on the X chromosome, consistent with prior genomic studies of X chromosome evolution. We identified 9 of the 16 Y-linked proteins, including known testis-specific male fertility factors. We also identified almost one-half of known Drosophila ribosomal proteins in the DmSP3. The role of this subset of ribosomal proteins in sperm is unknown. Surprisingly, our expanded sperm proteome also identified 122 seminal fluid proteins (Sfps), proteins originally identified in the accessory glands. We show that a significant fraction of 'sperm-associated Sfps' are recalcitrant to concentrated salt and detergent treatments, suggesting this subclass of Sfps are expressed in testes and may have additional functions in sperm, per se. Overall, our results add to a growing landscape of both sperm and seminal fluid protein biology and in particular provides quantitative evidence at the protein level for prior findings supporting the meiotic sex-chromosome inactivation model for male-specific gene and X chromosome evolution.


Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression.
The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.


Another "double bubble" sign or "double bladder" sign: fetal intra-abdominal umbilical vein varix.
Fetal intra-abdominal umbilical vein varix increases the incidence of fetal/neonatal morbidity and mortality. Its early diagnosis may be clinically important. For a case of this disorder, we have proposed the new name of "double bladder" sign; "another double bubble" sign may also illustrate this disorder.


Program evaluation in graduate nursing education: hardiness as a predictor of success among nursing administration students.
In an effort to develop meaningful program evaluation data, this exploratory study examined hardiness and stress among a select group of graduate nursing administration students at The University of Texas at Arlington in Arlington, TX. Students completed a questionnaire, which included the Hardiness Scale and Perceived Stress Scale, at both beginning and end of their program. Six to 12 months after graduation, each participant completed a telephone survey with items related to hardiness and American Association of Colleges of Nursing and American Organization of Nurse Executives core competencies. Mean scores for both hardiness and stress did improve from beginning to end of program; however, alpha coefficient reliabilities were disappointing, so no further quantitative analyses were completed. Most enlightening were the telephone interviews, which revealed that graduates were engaged in behaviors indicative of high hardiness. Use of hardiness as a guiding construct may prove useful to nursing administration program faculty in developing and refining a quality program; use of both quantitative and qualitative methods are recommended for obtaining meaningful program evaluation data.


A functional decaisoleucine-containing signal sequence. Construction by cassette mutagenesis.
An alkaline phosphatase signal sequence optimized for formation of a hydrophobic alpha-helix functions very efficiently in the transport process. This mutant contained a core region comprised of 9 consecutive leucine residues (Kendall, D. A., Bock, S. C., and Kaiser, E. T. (1986) Nature 321, 706-708). We have now constructed a second mutant containing a decaisoleucine core region. Isoleucine was chosen because it is an isomer of leucine with comparable hydrophobicity but in synthetic peptides isoleucine favors beta-sheet formation. Surprisingly, this mutant precursor was also processed efficiently, and mature alkaline phosphatase was correctly targeted to the Escherichia coli periplasm. Since the effective length of a beta-strand is extended relative to an alpha-helix, conformational differences should be mirrored by the relative effectiveness of shortened polyisoleucine and polyleucine core regions. However, analysis of two additional mutants containing truncated segments of either polyleucine or polyisoleucine did not reveal any differences and both accumulate as precursors. We conclude that these mutants do not adopt critically different structures. This comparative analysis was facilitated by construction of a new plasmid, CASS3. This plasmid contains unique restriction sites flanking the DNA region coding for the signal sequence hydrophobic core segment. Consequently, the wild type core-encoding region can be readily replaced with synthetic oligonucleotides coding for new structural units and multiple amino acid substitutions can be made without the need for step-wise mutagenesis.


Cellulose nanocrystals from acacia bark-Influence of solvent extraction.
The isolation of cellulose nanocrystals from different lignocellulosic materials has shown increased interest in academic and technological research. These materials have excellent mechanical properties and can be used as nanofillers for polymer composites as well as transparent films for various applications. In this work, cellulose isolation was performed following an environmental friendly procedure without chlorine. Cellulose nanocrystals were isolated from the exhausted acacia bark (after the industrial process of extracting tannin) with the objective of evaluating the effect of the solvent extraction steps on the characteristics of cellulose and cellulose nanocrystals. It was also assessed the effect of acid hydrolysis time on the thermal stability, morphology and size of the nanocrystals, through TGA, TEM and light scattering analyses. It was concluded that the extraction step with solvents was important in the isolation of cellulose, but irrelevant in the isolation of cellulose nanocrystals. Light scattering experiments indicated that 30min of hydrolysis was long enough for the isolation of cellulose nanocrystals.


Bacterial virulence and inflammatory response in infants with febrile urinary tract infection or screening bacteriuria.
Two populations were analyzed prospectively after a first episode of urinary tract infection. Asymptomatic infants were screened at 2 weeks and at 3 and 10 months of age, and bacteriuria was confirmed by bladder puncture. Infants with febrile urinary tract infection were enrolled during the same study period. The inflammatory response was characterized by the presence of fever, serum C-reactive protein, microsedimentation rate, urinary leukocyte excretion, and width of the ureters. The bacteria were defined for O:K:H serotype, hemolysin production, resistance to the bactericidal effect of serum, attachment to uroepithelial cells, and specificity for the globoseries of glycolipid receptors. In agreement with previous studies, the frequency of increased inflammatory signs and of attaching Escherichia coli was significantly higher in infants with febrile urinary tract infection than in the screening group. Within both patient groups, however, children infected with attaching E. coli strains had significantly more inflammatory signs. The results suggest that adherence facilitates the presentation of bacterial components capable of causing inflammation in the tissues in the urinary tract.


Effect of Variable Doses of Zinc Oxide Nanoparticles on Male Albino Mice Behavior.
Zinc oxide nanoparticles (ZnO NPs) have diverse utility these days ranging from being part of nanosensors to be ingredient of cosmetics. Present study was designed to report the effect of variable doses of ZnO NPs on selected aspects of male albino mice behavior. Nano particles were synthesized by sol-gel auto-combustion method (Data not shown here). 10 week old male albino mice were divided into four experimental groups; group A, B and C were orally supplemented with 50 (low dose), 300 (medium dose) and 600 mg/ml solvent/kg body weight (high dose) of ZnO NPs for 4 days. Group D (control) orally received 0.2 M sodium phosphate buffer (solvent for ZnO NPs) for the same duration. A series of neurological tests (Rota rod, open field, novel object and light-dark box test) were conducted in all groups and performance was compared between ZnO NPs treated and control group. Muscular functioning during rota rod test was significantly improved in all ZnO NPs treated mice as compared to control group. While no significant differences in open field, novel object and light-dark box test performance were observed when data from studied parameters of specific ZnO NPs treatment were compared with the control group indicating that applied doses of ZnO NPs did not affect the exploratory, anxiolytic behavior and object recognition capability of adult male albino mice.


New function of polysaccharide from Rubus chingii Hu: protective effect against ethyl carbamate induced cytotoxicity.
Rubus chingii Hu is a widely cultivated fruit in China and has declared multiple bioactivities including antioxidative activity. Ethyl carbamate (EC), mostly found in fermented food and alcoholic beverages, is a recognized human carcinogen, and researchers have proposed the correlation between oxidative stress and its toxicity. This study acquired the polysaccharide from R. chingii (RP) and explored its effect on EC-induced cytotoxicity using Caco-2 cells as the cell model. Results showed that RP exhibited protection against EC-induced toxicity by repairing redox imbalance as indicative of mitigated mitochondrial membrane potential collapse, attenuated reactive oxygen species overproduction, and impeded glutathione depletion. Moreover, the structural features of RP were characterized and revealed that it was mainly constituted by galacturonic acid and arabinose, with an average molecular weight of 7.039 × 105 g mol-1 . Overall, our results provided a new approach dealing with the toxicity caused by EC from the perspective of oxidative stress and described a new potential healthy value of R. chingii Hu, which could contribute to the development of a promising dietary supplement and functional food. © 2020 Society of Chemical Industry.


Use of an EK-2 vector for the cloning of DNA from higher organisms.
A certified EK2 bacteriophage lambda vector, which is useful for cloning fragments of DNA from higher organisms, is described.


Sudden death in a dog with aortic coarctation.
A previously healthy, one-year-old, intact female Vizsla dog collapsed and experienced cardiopulmonary arrest after a stressful event. Postmortem examination identified juxtaductal aortic coarctation (AoCo) with complex morphology. Located in the isthmus aorta adjacent to the ligamentum arteriosum, the AoCo comprised a shelf-like structure caused by invagination of the aortic wall into the lumen. Just distally, a second region of aortic occlusion resulted from an obstructing aortic membrane that restricted blood flow into the descending aorta through a small, eccentric ostium. Plausibly, the AoCo contributed to high afterload which led to reduction of coronary blood flow, myocardial hypoxia, and sudden death during physical stress. Although AoCo is a well-recognized congenital defect in humans, it has been reported only rarely in animals. The present case details the gross and histologic features of a complex, juxtaductal AoCo in a dog who died suddenly after stress. These morphologic findings may be informative when contemplating diagnosis of this anomaly.


An overview of FSH-FSHR biology and explaining the existing conundrums.
FSH was first identified in 1930 and is central to mammalian reproduction. It is indeed intriguing that despite being researched upon for about 90 years, there is still so much more to learn about FSH-FSHR biology. The purpose of this review is to provide an overview of current understanding of FSH-FSHR biology, to review published data on biological and clinical relevance of reported mutations, polymorphisms and alternately spliced isoforms of FSHR. Tissue-resident stem/progenitor cells in multiple adult tissues including ovaries, testes and uterus express FSHR and this observation results in a paradigm shift in the field. The results suggest a direct action of FSH on the stem cells in addition to their well-studied action on Granulosa and Sertoli cells in the ovaries and testes respectively. Present review further addresses various concerns raised in recent times by the scientific community regarding extragonadal expression of FSHR, especially in cancers affecting multiple organs. Similar population of primitive and pluripotent tissue-resident stem cells expressing FSHR exist in multiple adult tissues including bone marrow and reproductive tissues and help maintain homeostasis throughout life. Any dysfunction of these stem cells results in various pathologies and they also most likely get transformed into cancer stem cells and initiate cancer. This explains why multiple solid as well as liquid tumors express OCT-4 and FSHR. More research efforts need to be focused on alternately spliced FSHR isoforms.


An evaluation of indexes as support tools in the diagnosis of sleep apnea.
This article evaluates several indexes as support tools to diagnose patients with Sleep Apnea-Hypopnea Syndrome (SAHS). Some of these indexes, such as the Apnea-Hypopnea Index, have been standardized and studied in depth in the literature. Other indexes are used extensively in the reports that commercial polysomnographs generate. However, they have not been studied in detail and clinicians have no standardized guidelines for interpreting them. Examples are the mean and maximum duration of apneas and hypopneas. Finally, several novel indexes proposed by the authors are also evaluated. To evaluate the indexes, we have used a database of 274 patients who have undergone a polysomnographic test. Several feature selection techniques were used to assess the capability of each index to discriminate between healthy and SAHS patients. The capability of the indexes for diagnosing the patients was analyzed by using decision trees which were trained using each index individually, and all the indexes together. Our results suggest that some indexes which are often present in the reports of commercial polysomnographs provide little or no information. On the other hand, other indexes that are usually not considered have a great capability to discern between SAHS and control patients.


Treatment of intracranial meningiomas in patients over 70 years old.
The neurosurgeon often finds himself in the position to having to decide whether or not to operate on an elderly patient suffering from intracranial meningioma. The decision is rarely easy and the results often disappointing. We studied 46 cases of intracranial meningioma in patients over 70 years of age, 34 patients were operated on while 12 patients were not, although both groups were subjected to long term follow-up. The operative mortality rate was 12%, a rate which increased to 20% at 3 months follow-up. Various unfavourable prognostic factors were taken into consideration, the most significant of which were: poor overall clinical condition, peritumoral oedema, the presence of diabetes mellitus and the duration of surgery. A scored grading system was created to standardize surgical indications in elderly patients with cerebral meningioma. An analysis of the grading system, when applied to patients submitted to surgery, showed that the decreased patients within 3 months of surgery had a score which varied from 7 to 12, with a mean score of 10. The surviving patients had a score averaging from 10 to 16 with a mean of 13. The patients with the lowest scores (7-9) had a 100% mortality rate while those in the upper ranges (13-16) demonstrated a mortality rate of 0%. Among the conservatively treated patients the worst outcome was seen in patients with a grading equal to or less than 12.


An artificial LAMA2-GelMA hydrogel microenvironment for the development of pancreatic endocrine progenitors.
The biomimetic pancreatic microenvironment improves the differentiation efficiency and function of human embryonic stem cell-derived β-cells (SC-β cells). Thus, a laminin subunit alpha 2-gelatin methacrylate (LAMA2-GelMA) hybrid hydrogel as a bionics carrier for the formation and maturation of endocrine lineage was developed in our research, based on pancreas proteomics analysis of postnatal mice. Pancreatic endocrine cells cultured on the hybrid hydrogel in vitro, which was composed of 0.5 μg/mL LAMA2 protein and 4% GelMA, the expression of transcription factors (TFs), including NKX6.1, NKX6.2, and NEUROD1 were upregulated. Single-cell transcriptomics was performed after LAMA2 knockdown during the early differentiation of pancreatic progenitor (PP) cells, a marked decrease in the forkhead box protein A2 (FOXA2+)/GATA-binding factor 6 (GATA6+) cluster was detected. Also, we clarified that as a receptor of LAMA2, integrin subunit alpha 7 (ITGA7) participated in Integrin-AKT signaling transduction and influenced the protein levels of FOXA2 and PDX1. In vivo experiments showed that, PP cells encapsulated in the LAMA2-GelMA hydrogel exhibited higher serum C-peptide levels compared to the GelMA and Matrigel groups in nude mice and reversed hyperglycemia more quickly in STZ-induced diabetic nude mice. Taken together, our findings highlighted the feasibility of constructing a pancreas-specific microenvironment based on proteomics and tissue engineering for the treatment of diabetes.


Social activity as mediator between social support and psychological quality of life among people with rare diseases: A national repetitive cross-sectional study.
Considerable proportion of people with rare diseases (RDs) have suffered from severe mental health problems. However, specific attention on the psychological quality of life (QoL) of people with RDs is sparse. Evidence documented the benefits of social support and social activity on recipients' mental health and overall QoL, but no corresponding study answered how both social support and social activity work on the psychological QoL among people with RDs. This study aims to report the psychological QoL and evaluate the mediating role of social activity between social support and psychological QoL among people with RDs. Data were from two national repetitive cross-sectional surveys, conducted in China in February 2016 and February 2018. In this study, eligible people were those aged 18 or above and had clinical-diagnosed RDs. Psychological QoL was measured by the subdomain of World Health Organization Quality of Life: Brief Version. Social support was measured by the Medical Outcomes Study Social Support Survey. Social activity was measured with seven items selected from the measurement on leisure activities used by the Chinese General Social Survey. Using the mediation model, we assessed the direct and indirect (via social activity) association between social support and psychological QoL, both on overall and subtypes of RDs. We controlled for a variety of potential socioeconomic and demographic confounding factors. Of the 2403 adults studied, their average score of psychological QoL was 42.49 out of 100. The psychological QoL was directly associated with received emotional/information support (coefficient = 0.159, 95% CI = [0.093, 0.231], p < 0.0001) and positive social interaction (coefficient = 0.159, 95% CI = [0.097, 0.221], p < 0.0001). The psychological QoL was indirectly (via social activity) associated with received tangible support (coefficient = -0.035, 95% CI = [-0.046, -0.025], p < 0.0001) and positive social interaction (coefficient = 0.056, 95% CI = [0.040, 0.074], p < 0.0001). Above results by subtypes of RDs were also reported. The causal inference was not able to be investigated due to the cross-sectional study design. People with RDs suffered from a low psychological QoL. Social activity mediated the association between social support and psychological QoL, but its mediating role depended on the subscales of social support as well as the subtypes of RDs. Customized measures based on the type of RDs and support that will be provided could perhaps improve the psychological QoL of people with RDs directly and indirectly.


Fluid-responsiveness, blood volume and perfusion in preoperative haemodynamic optimisation of hip fracture patients; a prospective observational study.
Preoperative resuscitation strategies in patients with hip fracture (HF) are lacking. We aimed to investigate fluid-responsiveness, peripheral perfusion index (PPI) and blood volume (BV)-status in patients with HF undergoing resuscitation in the preoperative phase. In a prospective observational study, we evaluated preoperative fluid-responsiveness, indices of perfusion and BV before and after lumbar epidural analgesia in 50 patients with HF shortly after admittance. Initially, 18 (36%) patients were fluid-responsive (≥10% increased SV in response to 250 ml fluid bolus) and 13 (26%) presented hypovolaemia (deviation of measured BV from estimated BV ≤ 0.9). According to fluid-responsiveness, no difference in absolute values of cardiac index (CI) (2.7 L [2.1-3.3] vs. 2.8 L [2.3-3.4], p = .5) was seen, but cardiac output (CO) rose significantly in the hypovolaemic patients: 9% [5-18] vs. 1% [-3-7], p = .004. After epidural analgesia, 26 (52%) patients were again fluid-responsive and 15 (30%) were hypovolaemic. CI was now significantly lower in fluid-responsive patients (2.2 L [1.7-2.7] vs. 2.9 L [2.3-3.5], p = .001). Prior to epidural analgesia, no significant trend towards hypovolaemic patients having lower indices of perfusion was seen. After epidural analgesia, more patients with hypovolaemia presented with PPI≤1.5 (8 (53%) vs. 3 (9%), p = .001) and absolute values of PPI were also significantly lower if IBV was low (1.4 [0.9-3.2] vs. 3.2 [2.4-4.8], p = .01). PPI correlated with hypovolaemia after epidural analgesia (rho 0.4 [0.1-0.7], p = .007). Preoperative fluid-responsivity in HF patients might be attributable to elements of hypovolaemia and sympathetic compensatory ability conjointly, confounding the use of SV-guided resuscitation. PPI could be associated with BV, which may support clinicians during perioperative haemodynamic optimisation.


Functional analysis of inhibitor of apoptosis 1 of the silkworm Bombyx mori.
Recent advances in genome-wide surveys have revealed a number of lepidopteran insect homologs of mammalian and Drosophila genes that are responsible for apoptosis regulation. However, the underlying molecular mechanisms for apoptosis regulation in lepidopteran insect cells remain poorly understood. In the present study, we demonstrated that the transfection of Bombyx mori BM-N cells with dsRNA against the B. mori cellular iap1 gene (cbm-iap1) induces severe apoptosis that is accompanied by an increase of caspase-3-like protease activity. In these apoptotic cells, the cleaved form of the endogenous initiator caspase Dronc (Bm-Dronc) was detected, indicating that cBm-IAP1 protein depletion by RNAi silencing resulted in the activation of Bm-Dronc. In transient expression assays in BM-N cells, cBm-IAP1 suppressed the apoptosis triggered by Bm-Dronc overexpression and depressed the elevation of caspase-3-like protease activity, but also increased the cleaved form of Bm-Dronc protein. cBm-IAP1 also suppressed the caspase-3-like protease activity stimulated by Bm-caspase-1 overexpression. Co-immunoprecipitation experiments demonstrated that cBm-IAP1 strongly interacts with Bm-Dronc, but only has weak affinity for Bm-caspase-1. Transient expression analyses showed that truncated cBm-IAP1 proteins defective in the BIR1, BIR2 or RING domain were unable to suppress Bm-Dronc-induced apoptosis. In addition, BM-N cells expressing truncated cBm-IAP1 proteins underwent apoptosis, suggesting that intact cBm-IAP1, which has anti-apoptotic activity, was replaced or displaced by the overexpressed truncated cBm-IAP1 proteins, which are incapable of interfering with the apoptotic caspase cascade. Taken together, the present results demonstrate that cBm-IAP1 is a vital negative regulator of apoptosis in BM-N cells and functions by preventing the activation and/or activity of Bm-Dronc and Bm-caspase-1.


Synthetic relaxometry combined with MUSE DWI and 3D-pCASL improves detection of hippocampal sclerosis.
To investigate the diagnostic value of synthetic MRI combined MUSE DWI and 3D-pCASL in hippocampal sclerosis (HS). A total of 30 HS patients participated in the study. At the same time, 51 healthy volunteers were collected as the control group. All patients and healthy volunteers underwent epilepsy MR scanning protocol (including oblique coronal MAGiC, MUSE DWI, and axial 3D-pCASL) at 3.0 T MR scanner.The independent samples T test and Mann-Whitney U test were used to compare the differences of the apparent dispersion coefficient(ADC), cerebral blood flow(CBF) and quantitative parameters, including T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) values, in the hippocampus of the affected side of HS and the contralateral and control groups, respectively. The diagnostic performance was evaluated using binary logistic regression analysis and area under the receiver operating characteristic (ROC) curves (AUC). Significant statistical differences in T1, T2, CBF, and ADC values were observed between the affected hippocampus of HS patients and contralateral and control hippocampus (all P < 0.005). The T2 has higher discrimination abilities compared with other univariable parameters, with the AUC of 0.899. The combined T2, ADC and CBF model had the best diagnostic performance of HS in MTLE patients with AUC, sensitivity and specificity of 0.946, 86.67 %, 93.33 %, respectively. Relaxometry parameters derived from synthetic MRI contributed to diagnosis of HS. The proposed approach combining T2, ADC and CBF showed a strong diagnostic capability.


Preclinical safety evaluation.
Before pharmaceutical products are evaluated in humans, it is essential that they undergo a rigorous safety assessment using in vitro models and studies in preclinical species. Once products progress into the clinic, additional preclinical studies are needed to support further clinical testing. Although regulatory guidelines provide a good framework for the types of studies that should be performed, there are some areas where it is unclear how these should be applied to microbicides, what study designs should be used, whether certain tests are relevant or if additional assays are appropriate. In this chapter we provide an overview of the key issues for the preclinical development of microbicides, and describe the purpose of each of the tests along with the key considerations to be taken into account when designing the individual safety studies as well as the overall preclinical program.


Prognostic value of neutrophil-to-lymphocyte ratio in advanced cancer patients receiving immunotherapy.
The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in cancer patients. However, the performance of NLR as an early marker of efficacy of immune checkpoint inhibitors (ICI) is still understudied. We studied the utility of NLR at baseline (bNLR), before the second dose of immunotherapy (NLR2) and the NLR trend for predicting efficacy outcomes. We included all patients with advanced cancer treated with ICI from June 2013 to April 2019 at La Paz University Hospital, Madrid (Spain). We examined bNLR, NLR2 and NLR trend and explored the association with progression-free survival (PFS) at 6 months, median PFS and overall survival (OS). We included 211 patients. PFS and OS were significantly longer in the low bNLR group than in the high bNLR group [HR 0.71 (95% CI 0.60-0.84) and HR: 0.66 (95% CI 0.55-0.79), respectively]. Regarding NLR2, patients with low NLR2 had significantly longer PFS and OS than patients with high NLR2 [HR 0.67 (95% CI 0.57-0.79) and HR: 0.60 (95% CI 0.50-0.72), respectively]. Finally, for NLR trend, PFS and OS for patients with NLR trend < 1 were significantly longer than those patients with NLR trend ≥ 1 [HR 0.59 (95% CI 0.43-0.82) and HR 0.63 (95% CI 0.44-0.90), respectively]. At the multivariate analysis for PFS and OS, bNLR, NLR2 and NLR trend were all independent prognostic factors for PFS and OS. bNLR, NLR2 and NLR trends are independent prognostic factors for survival in patients on immunotherapy. The dynamics of NLR in patients on immunotherapy is a promising marker that needs further investigation.


Transdisciplinarity in Research: Perspectives of Early Career Faculty.
Early career faculty experiences and perspectives on transdisciplinary research are important yet understudied. Assistant professors at 50 top-ranked social work programs completed an online survey assessing perspectives on the salience of transdisciplinary training in their field, obstacles to or negative impacts of transdisciplinary training, and current environments. Content analysis and descriptive statistics were used. A large majority of all participants (N ¼ 118) believed that transdisciplinary research is important, that greater training is needed, and that they are relatively well prepared in related skill sets. They are expected to build cross-disciplinary collaborations, yet only a small minority believed that social work researchers are nationally recognized as important collaborators, or that they are prepared to navigate tensions on research teams. We offer a multilevel framework of structural and training supports needed to realize transdisciplinary research in social work with relevance to other disciplines.


In vivo studies in male mice on the mutagenic effects of inorganic arsenic.
The ability of sodium meta-arsenite (NaAsO2) to produce genetic damage in vivo has been evaluated in mice by the micronucleus test on bone marrow cells and the dominant lethality and sperm abnormality assays on male germ cells. The dose-related linear increase of micronuclei observed in somatic cells together with the negative results obtained in reproductive cells suggest that NaAsO2, under the conditions of the present experiments, displays clastogenic properties in vivo in laboratory animals, but is unable to produce heritable damage.


Failure to Obtain Baseline Signals of Transcranial Motor-Evoked Potentials in Spine Surgery: Analysis of the Reasons.
Among the various intraoperative neurophysiologic monitoring (IONM) techniques, transcranial motor-evoked potential (Tc-MEP) has recently become the most widely used method to monitor motor function. However, we often find that Tc-MEP is not sufficiently detected at the start of surgery. Therefore, we aimed to analyze the reasons and risk factors for not detecting sufficient baseline signal of Tc-MEP from the beginning of spinal surgery. We categorized IONM data from 1058 patients who underwent spine surgeries at a single institution from 2014 to 2020 and categorized them into 2 groups: 1) "poor MEP" if Tc-MEP could not be sufficiently obtained and 2) "normal MEP" if Tc-MEP could be sufficiently obtained from the surgery. We analyzed the patient's age, gender, underlying disease, operation type, level numbers, baseline motor function, existence of pathologic reflex, myelopathy, and duration from the onset and clinical diagnosis. The rate of failure to obtain sufficient baseline Tc-MEP signals in spine surgery was 21.8% (231/1058). Multivariate analysis showed significant associations of existence of diabetes mellitus, myelopathy, thoracic spine surgery, baseline motor deficit and tumor, and trauma disease with loss of meaningful and interpretable signals in baseline Tc-MEP (P < 0.05). Only 15 of 231 patients (6.4%) showed a trend of signal recovery after decompression procedures. Various factors (myelopathy, diabetes mellitus, thoracic surgery, baseline motor deficit, tumor, and trauma) were closely related to not obtaining sufficient baseline signals for Tc-MEP. When operating on patients with these considerations, we need to consider the efficacy and usefulness of Tc- MEP.


Immunohistochemical localization of acetaminophen-bound liver proteins.
A sensitive immunofluorescence assay was developed for localizing acetaminophen (APAP) protein adducts in liver sections from treated mice. Affinity-purified anti-APAP antibodies, when applied to liver sections from mice given 600 mg APAP/kg, po, were preferentially localized in cells of the centrilobular region. At 30 min after dosing, covalently bound APAP was detected only in those cells most proximal to the central vein. Thereafter, binding spread throughout the centrilobular zone. However, by 8 hr the overall intensity of staining decreased and binding appeared more diffuse. Western blot analysis of electrophoretically resolved proteins from similarly treated mice revealed a corresponding temporal arylation of cytosolic proteins by APAP and indicated that the fluorescence detected at 30 min was associated with arylation of protein(s) of 44 kDa. The findings demonstrate the sensitivity and utility of immunohistochemical techniques in the study of covalently bound toxicants and emphasizes the temporal link between selective protein arylation in individually targetted cells to the development of APAP hepatotoxicity.


Financial Coaching Offers New Paths To A Healthy Future.
With tax assistance, financial literacy education, and other programs, Boston Medical Center helps families rise out of poverty.


The use of off pump surgery for management of penetrating coronary artery injury.
Penetrating trauma to the chest leading to coronary artery injury is associated with a high mortality rate, especially in the case of injury to the left anterior descending (LAD) coronary artery. The mortality rate remains high whether they are managed with primary ligation or with coronary artery bypass grafting using conventional cardiopulmonary bypass techniques. We report a case of proximal LAD coronary artery injury successfully treated with off pump coronary revascularisation.


Retinal nerve fiber layer thickness in optic tract syndrome.
Optic tract syndrome (OTS) is characterized by incongruous homonymous hemianopia and a perpendicular pattern of bilateral optic atrophy due to the optic tract lesion. However, loss of retinal nerve fiber layer thickness (RNFLT) associated with OTS has not been quantitatively assessed. A 20-year-old woman with blunt head trauma showed normal visual acuity, color vision, ocular motility, and intraocular pressure. Because of a relative afferent pupillary defect in her left eye and left-sided homonymous hemianopia, we suspected right-sided optic tract damage, although magnetic resonance imaging detected no intracranial lesion. Using optical coherence tomography (OCT), the RNFLT of this case was measured at 31 months after the trauma and compared with age-matched normal controls (n = 41). Nasal, temporal, superior, and inferior quadrant RNFLT was reduced by 22%, 21%, 5%, and 46% in the right eye and 76%, 64%, 25%, and 27% in the left eye, respectively. The reduction was > 3 x the standard deviation of the normal mean values in the nasal and temporal quadrants of the left eye and in the inferior quadrant of the right eye. OCT can determine the RNFLT reduction corresponding to the characteristic patterns of optic atrophy of OTS.


Synthesis of 6-deoxymaltooligosaccharides and a study of their lipid-binding properties.
Amylose reacted in N,N-dimethylformamide with crystalline bromomethylenedimethylammonium bromide (Vilsmeier bromide) to give 6-bromo-6-deoxyamylose with a high degree of substitution. Reduction of the bromoamylose with sodium borohydride yielded 6-deoxyamylose that, following controlled acetolysis, gave 6-deoxymaltooligosaccharides. Such oligosaccharides, of appropriate chain-length, formed stable complexes with long-chain fatty acids that have a dissociation constant of about 2 microM in their interaction with parinaric acid (trans-9,11,13,15-octadecatetraenoic acid). Treatment of 6-bromoamylose with sodium methoxide in dimethyl sulfoxide produced a 3,6-anhydroamylose that contains few unaltered D-glucose units. This anhydroamylose also bound to a palmitoyl-resin column, suggesting that the polymer may be partially helical and somewhat lipophylic. Finally, reaction of 6-bromoamylose with methylvinyl ether led to the 2,3-di(methoxyethyl) ether that, on reaction with sodium methoxide, gave the 6-methyl ether from which 6-O-methylamylose was obtained by mild acid hydrolysis.


Proteome profile of bovine ruminal epithelial tissue based on GeLC-MS/MS.
The proteome of rumen epithelial tissue was analysed by SDS-PAGE coupled with LC-MS/MS. 813 non-redundant proteins were identified of which 7.4 % featured membrane-spanning domains and 15.4 % harboured a signal peptide. According to the gene ontology annotation, the most abundant proteins exhibited binding activities related to their molecular functions, were proteins of cellular components or belonged to various metabolic processes. A predominant group of canonical pathways in the rumen epithelial tissue was identified using the IPA software. The GeLC-MS/MS approach was used to characterise the entire protein expression repertoire in rumen tissue, providing a more detailed understanding of the important biological processes in the rumen.


Real-world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis.
Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA-NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA-NPC patients. Patients with LA-NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan-Meier method, and compared by the log-rank test. A p-value of <0.05 was considered statistically significant. A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p < 0.001), smoking (p = 0.003), more comorbidity (p = 0.014), kidney disease (p = 0.016), and lower baseline creatinine clearance (p < 0.001). Intensity-modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p < 0.001). Patients who received carboplatin were associated with delay (p = 0.049) and hospitalization (p = 0.006), whereas cisplatin CCRT had more dose reduction (p = 0.001). Patients treated with cisplatin had CCRT interruption from grade 3-4 mucositis (p = 0.019) more than carboplatin, whereas carboplatin had more grade 3-4 thrombocytopenia (p < 0.001). The 5-year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p = 0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence-free survival in multivariate analysis. Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real-world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin-ineligible patients with LA-NPC treated with CCRT.


Precise measurement of the activity of 186Re, 188Re radiopharmaceuticals.
The paper presents the results obtained in the assurance of traceability along the whole chain: production, distribution, use in hospitals, for the activity measurement of radiopharmaceuticals containing 186Re, 188Re and 186Re + 188Re mixtures. Standardization of the solutions, 4piPC-beta-efficiency relations and responses of a Centronic IG 12/20A ionization chamber and other radioisotope calibrators are presented. Gamma-ray and bremsstrahlung radiation contributions in the total response were evaluated. Some of the relevant results were compared with literature data.


Fulminant, CMV-associated, haemophagocytic syndrome following unrelated bone marrow transplantation.
We report a case of haemophagocytic syndrome (HPS) occurring after allogeneic bone marrow transplantation (BMT) for acute promyelocytic leukaemia (APL) in a patient in fourth complete remission (CR). Anti-cytomegalovirus (CMV) antibody (Ab) was negative in this patient before BMT. BMT was performed from an HLA-identical unrelated donor who was positive for CMV Ab. After bone marrow engraftment and haematological recovery, severe acute graft-versus-host disease (GVHD) developed. This patient was treated with methylprednisolone in addition to cyclosporin A (CsA). Acute GVHD showed partial improvement, but CMV antigenaemia was observed. Despite administration of gancyclovir and immunoglobulin, CMV antigenaemia showed no improvement and HPS developed. As no other infections or malignancies were observed, we suspect that CMV infection was the trigger for development of HPS.


pH, K+, and PO2 of the extracellular space during ischaemia of primate cerebral cortex.
pH and K+ from the extracellular space, PO2, and CBF have been measured in the same region during progressive ischaemia of primate cerebral cortex. As blood flow was reduced, the other changes had the following sequence. PO2 fell rapidly to 30% of control levels at regional CBF (rCBF) of 30 ml 100 g-1 min-1. As CBF was further reduced, PO2 continued to fall. pH remained stable until around 20 ml 100 g-1 min-1, below which pH fell rapidly, with an exponential increase in H+ concentration. K+ showed the well-known relationship to CBF, remaining normal until around 10 ml 100 g-1 min-1, below which K+ rose rapidly. pHe and log K+ were lin-early related and confirmed that pH fell by 0.3 U before K+ rose significantly, and fell by 0.6 U before the massive rise in K+. The mechanisms involved in this sequence of events and the role of pH changes in the development of the so-called "ischaemic penumbra" are discussed.


Radiation Therapy for Benign Disease: Arteriovenous Malformations, Desmoid Tumor, Dupuytren Contracture, Graves Ophthalmopathy, Gynecomastia, Heterotopic Ossification, Histiocytosis.
Although the use of ionizing radiation in malignant conditions has been well established, its application in benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, in instances where the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the current use of radiation therapy in some of the more common benign conditions.


Electrochemical determination of cocaine using screen-printed cytochrome P450 2B4 based biosensors.
This paper describes the development of screen-printed cytochrome P450 2B4 based biosensors, from the fabrication of the device using a single screen-printing technology to its characterization and application in the determination of cocaine street samples. Voltammetric measurements were first performed in order to study the electrochemical behavior of the enzyme trapped in the structure of the working electrode, as well as its interaction with one of its substrates, cocaine. Then, chronoamperometric measurements were carried out for the characterization of the biosensors. Calibration curves under optimum conditions of the experimental variables have been used for establishing the reproducibility (5.91%, n=5), the repeatability (10.45%, n=3) and the capability of detection (0.2mM, α=β=0.05) of the described method in the calibration range from 0.2 to 1.2mM. Finally, the performance of the developed biosensors has been successfully probed by the analysis of the purity of cocaine street samples.


Enhanced sensitivity for pulse dipolar EPR spectroscopy using variable-time RIDME.
Pulse dipolar EPR spectroscopy (PDS) measurements are an important complementary tool in structural biology and are increasingly applied to macromolecular assemblies implicated in human health and disease at physiological concentrations. This requires ever higher sensitivity, and recent advances have driven PDS measurements into the mid-nanomolar concentration regime, though optimization and acquisition of such measurements remains experimentally demanding and time expensive. One important consideration is that constant-time acquisition represents a hard limit for measurement sensitivity, depending on the maximum measured distance. Determining this distance a priori has been facilitated by machine-learning structure prediction (AlphaFold2 and RoseTTAFold) but is often confounded by non-representative behaviour in frozen solution that may mandate multiple rounds of optimization and acquisition. Herein, we endeavour to simultaneously enhance sensitivity and streamline PDS measurement optimization to one-step by benchmarking a variable-time acquisition RIDME experiment applied to CuII-nitroxide and CuII-CuII model systems. Results demonstrate marked sensitivity improvements of both 5- and 6-pulse variable-time RIDME of between 2- and 5-fold over the constant-time analogues.


Changes in the Microbiome Profile in Different Parts of the Intestine in Piglets with Diarrhea.
Determining the taxonomic composition of microbial consortia of the piglet intestine is of great importance for pig production. However, knowledge on the variety of the intestinal microbiome in newborn piglets is limited. Piglet diarrhea is a serious gastrointestinal disease with a high morbidity and mortality that causes great economic damage to the pig industry. In this study, we investigated the microbiome of various sections of the piglet intestine and compared the microbiome composition of healthy and diarrheal piglets using high-throughput sequencing of the 16S rRNA gene. The results showed that bacteria of the Lactobacillus genus were the most common in the ileum, while Fusobacterium and Bacteroides dominated in the rectum. Comparing the microbiome composition of healthy and diarrheal piglets revealed a reduced number of Lactobacillus bacteria as a hallmark of diarrhea, as did an increased content of representatives of the Escherichia-Shigella genus and a reduced number of Bacteroides, which indicates the contribution of these bacteria to the development of diarrhea in piglets. The relative abundance of Enterococcus bacteria was higher in the diarrhea group. Although some bacteria of this genus are commensals, a small number of species may be associated with the development of diarrhea in piglets. Therefore, our results indicate that the gut microbiome may be an important factor in the development of diarrhea in piglets.


Prevalence of mental disorders among middle school students in Shaoxing, China.
In China, adolescents account for about a quarter of those treated for mental disorders each year, and adolescent mental health issues have become a social hotspot. Although several epidemiological surveys of mental disorders have been conducted in China, no study has yet focused on the prevalence of mental disorders among adolescents in a certain region of Zhejiang. In the first stage, 8219 middle school students aged 12-18 years in a city of Zhejiang Province (Shaoxing) were screened with the mental health screening checklist. In the second stage, participants who screened positive were tested with the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Then, the prevalence of mental disorders were calculated. The overall prevalence in this population was 12.4%, with prevalence rates exceeding 20% in both the 17- and 18-year-old age groups. The most common mental disorders were obsessive-compulsive disorder (OCD) (9.1%) and major depressive disorder (MDD) (8.9%). Mental disorders are common among middle school students, and girls are at higher risk than boys. As the most prevalent mental disorders, OCD and MDD should receive timely attention, especially for upper grade students.


Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.
Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX.


Plant and microorganisms support media for electricity generation in biological fuel cells with living hydrophytes.
Plant support media may impact power output in a biological fuel cell with living plants, due to the physical and biochemical processes that take place in it. A material for support medium should provide the suitable conditions for the robust microbial growth and its metabolic activity, degrading organic matter and other substances; and, transferring electrons to the anode. To consider the implementation of this type of bio-electrochemical systems in constructed wetlands, this study analyzes the electrochemical behavior of biological fuel cells with the vegetal species Phragmites australis, by using two different support media: graphite granules and a volcanic slag, commonly known as tezontle (stone as light as hair, from the Aztec or Nahuatl language). Derived from the results, both, graphite and tezontle have the potential to be used as support medium for plants and microorganisms supporting a maximum power of 26.78mW/m(2) in graphite reactors. These reactors worked under mixed control: with ohmic and kinetic resistances of the same order of magnitude. Tezontle reactors operated under kinetic control with a high activation resistance supplying 9.73mW/m(2). These performances could be improved with stronger bacterial populations in the reactor, to ensure the rapid depletion of substrate.


Beta-receptor downregulation in congenital heart disease: a risk factor for complications after surgical repair?
Neurohormonal activation in children with heart failure due to congenital heart disease leads to downregulation of myocardial beta-receptors that may influence the postoperative course after cardiothoracic surgery. Myocardial biopsies of 26 children (aged 14+/-4 months) were obtained from the right atrium during cardiac surgery. Patients were allocated to either of two groups based on the duration of their intensive care unit stay: group 1 comprised those who stayed less than 7 days (n = 17), whereas group 2 comprised those who stayed more than 7 days, plus 3 infants who died during the early postoperative course (n = 9). For beta1- and beta2-mRNA quantitation, real-time polymerase chain reaction with fluorescence-labeled products was used. Values for myocardial beta1-receptor gene expression were twice as high in group 1 children compared with group 2 (beta1-receptor 0.12+/-0.07 versus 0.06+/-0.03, p = 0.0016; beta2-receptor 0.12+/-0.07 versus 0.06+/-0.03, p = 0.0071). Beta-receptor gene expression in 16 children who received standard treatment for heart failure averaged lower than in the 10 children who received additional propranolol. Beta-receptor downregulation due to congestive heart failure has an impact on the postoperative course in children with congenital disease and depends on heart failure therapy.


Time dependence of mortality risk and defibrillator benefit after myocardial infarction.
Prophylactic implantable defibrillators (ICDs) improve survival in patients with impaired ventricular function after myocardial infarction (MI), but it is uncertain whether mortality risk and survival benefit depend on the elapsed time from MI. The Multicenter Automatic Defibrillator Implantation Trial II examined the impact of ICDs on survival in post-MI patients with ejection fractions < or =30%. In 1159 patients, mean time from most recent MI to enrollment was 81+/-78 months. Patients were randomized to an ICD (n=699) or conventional care (n=460) in a 3:2 ratio. Mortality rates (deaths per 100 person-years of follow-up) in both treatment groups were analyzed by time from MI divided into quartiles (<18, 18 to 59, 60 to 119, and > or =120 months). In conventional care patients, these rates increased as time from MI increased (7.8%, 8.4%, 11.6%, 14.0%; P=0.03). Mortality rates in ICD patients were consistently lower in each quartile and showed minimal increase over time (7.2%, 4.9%, 8.2%, 9.0%; P=0.19). Covariate-adjusted hazard ratios for risk of death associated with ICD therapy were 0.97 (95% CI, 0.51 to 1.81; P=0.92) for recent MI (<18 months) and 0.55 (95% CI, 0.39 to 0.78; P=0.001) for remote MI (> or =18 months). Mortality risk in patients with ejection fractions < or =30% increases as a function of time from MI. The survival benefit associated with ICDs appears to be greater for remote MI and remains substantial for up to > or =15 years after MI.


Differences in happiness between smokers, ex-smokers and never smokers: cross-sectional findings from a national household survey.
Happiness has become established as an important psychological dimension and not merely the obverse of depression and anxiety. Ex-smokers report that they are happier than when they were smoking but this could reflect biased recall. To date, no studies have examined happiness as a function of smoking status in ex-smokers of varying length of abstinence compared with current and never smokers. A cross-sectional household study of a nationally representative sample of adults examined the association between smoking status (never smoker, smoker, ex-smoker<1 year, ex-smoker ≥ 1 year) and two standard measures of happiness adjusting for sociodemographic characteristics (N=6923). After adjusting for age, gender and social grade, ex-smokers of ≥ 1 year reported higher levels of happiness than smokers (p<0.001) and similar levels to never smokers. Ex-smokers of <1 year had similar levels to smokers. Smoking to feel less depressed (p<0.001) or anxious (p<0.044) were the only smoking characteristics associated with lower happiness among current smokers. Ex-smokers who have stopped for a year or more are happier than current smokers and similar to never smokers. Whilst these results are cross-sectional and have to be interpreted with caution, this adds to the evidence that smoking may decrease happiness and stopping may increase it.


NT-pro BNP in AECOPD-PH: old biomarker, new insights-based on a large retrospective case-controlled study.
Pulmonary hypertension (PH) is one of the common complications in chronic obstructive pulmonary disease (COPD). The study aimed to evaluate the predicting ability of N-terminal pro brain natriuretic peptide (NT-pro BNP) in patients with AECOPD-PH and its relationship with the severity of PH. A large retrospective case-controlled study (n = 1072) was performed in the First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2020, and patients were divided into stable COPD (n = 178), AECOPD (n = 688) and AECOPD-PH group (n = 206). Different statistical models were used to screen for reliable and stable biomarkers. In unadjusted analysis and PSM (model 1, 2, 3), red cell distribution width (RDW), total bilirubin (TBIL), and NT-pro BNP were higher in patients with AECOPD-PH than those in AECOPD group. Logistic regression analysis showed, when the range of NT-proBNP was 271-1165 pg/mL (OR: 0.293; 95%CI: 0.184-0.467; P < 0.001) and NT-proBNP > 1165 pg/mL (OR: 0.559; 95%CI: 0.338-0.926; P = 0.024), the morbidity risk of PH in AECOPD patients was increased, so did TBIL. In receiver operating characteristic (ROC) curves, at the cut-off value of NT-proBNP was 175.14 pg/mL, AUC was 0.651 (P < 0.001), which was better than TBIL (AUC: 0.590, P < 0.001). As for the results of rank correlation analysis, NT-proBNP had a weak correlation with severity of PH with AECOPD (rs = 0.299, P = 0.001) and its relative relevance with other biomarkers (RDW was 0.359 and TBIL was 0.238, P < 0.001). Our findings suggest that NT-proBNP has a diagnostic efficacy in AECOPD-PH and NT-proBNP has a weak correlation with severity of PH with AECOPD.


Segmentation-guided Denoising Network for Low-dose CT Imaging.
To reduce radiation exposure and improve diagnosis in low-dose computed tomography, several deep learning (DL)-based image denoising methods have been proposed to suppress noise and artifacts over the past few years. However, most of them seek an objective data distribution approximating the gold standard and neglect structural semantic preservation. Moreover, the numerical response in CT images presents substantial regional anatomical differences among tissues in terms of X-ray absorbency. In this paper, we introduce structural semantic information for low-dose CT imaging. First, the regional segmentation prior to low-dose CT can guide the denoising process. Second the structural semantical results can be considered as evaluation metrics on the estimated normal-dose CT images. Then, a semantic feature transform is engaged to combine the semantic and image features on a semantic fusion module. In addition, the structural semantic loss function is introduced to measure the segmentation difference. Experiments are conducted on clinical abdomen data obtained from a clinical hospital, and the semantic labels consist of subcutaneous fat, muscle and visceral fat associated with body physical evaluation. Compared with other DL-based methods, the proposed method achieves better performance on quantitative metrics and better semantic evaluation. The quantitative experimental results demonstrate the promising performance of the proposed methods in noise reduction and structural semantic preservation. While, the proposed method may suffer from several limitations on abnormalities, unknown noise and different manufacturers. In the future, the proposed method will be further explored, and wider applications in PET/CT and PET/MR will be sought.


NO2 inhalation enhances asthma susceptibility in a rat model.
Nitrogen dioxide (NO2) is a major air pollutant. Epidemiologic studies have found that NO2 exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO2 inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m3 NO2 (28 days, 5 h/day). The results showed that NO2 exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m3 NO2 (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO2 exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO2 exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1β, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO2 exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-κB (NF-κB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-γ, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO2-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO2-associated respiratory diseases.


Pneumonectomy for unilateral destroyed lung with pulmonary hypertension due to systemic blood flow through broncho-pulmonary shunts.
Three decades ago, a few patients with pulmonary hypertension and respiratory failure associated with a unilateral destroyed lung were reported to have been treated by a pneumonectomy. In the present study, we investigated the clinical features, operative indications, and results of four cases with pulmonary hypertension that underwent a pneumonectomy for a unilateral destroyed lung. Four patients (three males, one female) with a destroyed lung and pulmonary hypertension (mean pulmonary arterial pressure >25 mmHg) were treated by a pneumonectomy between 1999 and 2002 at our institution. Their mean age was 59 years old (range 42-68 years). The underlying lung disease, Medical Research Council (MRC) dyspnea scale, respiratory function, arterial blood gas analysis, pulmonary arterial pressure, preoperative management, operative procedure, and postoperative course for each were reviewed retrospectively. The underlying lung disease that caused the destroyed lung was bronchiectasis in two patients, chronic empyema with bronchopleural fistula in one, and necrotizing pneumonia in one. The average mean pulmonary artery pressure was 33 mmHg (range 25-42 mmHg), which decreased to 27 mmHg (range 19-36 mmHg) after occlusion of the pulmonary artery in the affected lung. Following the pneumonectomy, the average mean pulmonary artery pressure was decreased to 17 mmHg (range 11-25 mmHg). Chronic inflammatory symptoms and functional impairments (showed by blood gas analysis, pulmonary arterial pressure, or MRC dyspnea scale) improved post-pneumonectomy. There was no operative death, though postoperative cardiorespiratory failure occurred in one patient. All patients were discharged from the hospital. We concluded that a pneumonectomy procedure may be indicated for selected patients with a unilateral destroyed lung and pulmonary hypertension due to systemic blood flow though broncho-pulmonary shunts.


Filtration extraction method using a microfluidic channel for measuring environmental DNA.
The environmental DNA (eDNA) method, which is widely applied in biomonitoring, is limited to laboratory analysis and processing. In this study, we developed a filtration/extraction component using a microfluidic channel, the Biryu-Chip (BC), and a filtration/extraction method, the BC method, to minimize the volume of the sample necessary for DNA extraction and subsequent PCR amplification. We tested the performance of the BC method and compared it with that of the Sterivex filtration/extraction method using aquarium and river water samples. We observed that using the BC method, the same concentration of extracted DNA was obtained with 1/20-1/40 of the filtration volume of the Sterivex method, suggesting that the BC method can be widely used for eDNA measurement. In addition, we performed on-site measurements of eDNA within 30 min using a mobile PCR device, demonstrating that filtration and extraction can be performed easily and quickly using the BC method. The PCR results obtained using the BC method were similar to those obtained using the Sterivex method. The BC method requires fewer steps; therefore, the risk of DNA contamination can be reduced. When combined with mobile PCR, the BC method can be applied to easily detect eDNA within 30 min from the collection of water sample, even on-site.


Morphological Variability of the Mandible Shape of the Common Vole Microtus arvalis (Rodentia, Arvicolidae) Semi-species from the Hybrid Zone.
The mandible shape of the common vole semi-species from the hybrid zone was studied for the first time using the methods of geometric morphometry. The hybrid specimens were found to display high morphological variability being closer to the parental Microtus obscurus than to M. arvalis form. The main trends of changes in the mandible shape were primarily observed in the horizontal plane.


Comparison of hemagglutination-inhibition, complement-fixation and enzyme-linked immunosorbent assay for quantitation of human rotavirus antibodies.
The hemagglutination-inhibition test for detecting rotavirus antibody was evaluated by using simian rotavirus SA-11 as hemagglutinating antigen. Results show that the test is as sensitive as either complement fixation or the enzyme-linked immunosorbent assay for detecting antibody to rotavirus in human sera.


Oral micronized progesterone for prevention of preterm birth.
To evaluate oral micronized progesterone (OMP) to prevent preterm birth (PTB). A randomized, double-blind, placebo-controlled trial of 150 women with at least one PTB who received 100 mg of OMP or placebo twice a day from recruitment (18-24 weeks) until 36 weeks or delivery. PTB occurred in 29 (39.2%) women in the OMP group (n=74) compared with 44 (59.5%) in the control group (n=74, P=0.002). Mean gestational age at delivery was higher in the OMP group (36.1 vs 34.0 weeks, P<0.001). Fewer preterm births occurred between 28 and 31 weeks plus 6 days in the OMP group (RR 0.20; 95% CI, 0.05-0.73, P<0.001). Neonatal age at delivery (34 vs 32 weeks, P<0.001), birth weight (2400 vs 1890 g, P<0.001), NICU stay (>24 h, P<0.001), and Apgar scores (P<0.001) were more favorable in the OMP group, and fewer neonatal deaths occurred (3 vs 7, P=0.190). OMP reduced the risk of PTB between 28 and 31 weeks plus 6 days, NICU admissions, and neonatal morbidity and mortality in high risk patients.


Applying a biopsychosocial model to inner city asthma: Recent approaches to address pediatric asthma health disparities.
Pediatric asthma in inner cities is often severe and children living in these urban locations with socioeconomic disadvantage experience greater asthma morbidity. There are many interconnected risk factors that individually, and in combination, enhance asthma morbidity. These include biologic factors innate to the child, such as genetics and allergen susceptibility, as well as factors related to the family and neighborhood context. The biopsychosocial model can be used to frame these risk factors and develop interventions specific to the inner city. Successful inner city asthma interventions exist and key characteristics include multi-tiered components that operate within the community to coordinate disease management resources between patients, families and health care systems.


Monoamine neurotransmitters in the evolution of infarction in ischemic striatum: morphologic correlation.
Evolution of infarction following cerebral ischemia is a delayed process, with spongiform degeneration of the neuropil occurring 6 to 8 hours after onset of ischemia. The brains of gerbils with stroke following unilateral carotid artery ligation were examined for catecholamine-derived fluorescence (CADF) by the Falck-Hillarp technique to study the relationship of catecholamine (CA) metabolism with damage to the neuropil. CADF could still be identified in the striatum for up to 16 hours after stroke and there appeared to be spongiform degeneration of the neuropil in relation to accumulations of CADF at 7 and 16 hours after stroke. Pretreatment of gerbils with a-methyl-p-tyrosine 400 mg/kg 6 hours prior to carotid ligation depleted the striatum of CADF until 16 hours after stroke and appeared to reduce the spongiform degeneration of the neuropil, though it did not affect ischemic degeneration of neuronal cell bodies. The continued presence of CADF in the striatum for up to 16 hours after stroke supports the previously reported findings that CA nerve terminals are still functional for 8 hours after stroke and that CA metabolism continues even though levels of CA are reduced immediately after onset of ischemia due to carotid artery ligation.


Anaesthetic complications of mediastinal masses and superior vena caval obstruction.
Two patients with mediastinal tumour and superior vena caval obstruction who, after general anaesthesia, experienced respiratory difficulties requiring intubation or reintubation are presented. Possible aetiological mechanisms are discussed in relation to these cases.


Retrograde intrarenal surgery by flexible ureteroscope in patients with spinal deformities.
To present our experience with retrograde intrarenal surgery (RIRS) for managing renal stones in patients with spinal deformities. We retrospectively reviewed the records of patients. We retrospectively reviewed the records of seven patients with congenital scoliosis (n = 5), spina bifida (n = 2) who had undergone RIRS for renal stones. Stone-free status was determined by CT 30 days after the procedure and was defined as the absence of stones in the kidney or residual fragments ≤1 mm. Mean patient age was 27 years (18-45 years), and mean stone size was 176 mm (143-340 mm). The average operative time was 38 minutes (25-53 minutes), and postoperative hospital stay was 1 day (1-2 days). A stone-free status was obtained in six (85.7 %) patients, and one patient was considered to have treatment failure. This patient was managed by a repeat RIRS. A Double-J stent was placed at the end of the procedure in all (100 %) patients. No severe complications, either from anesthesia or the surgical procedure, were observed, and no blood transfusion was reported. The good clearance rate with a low incidence of complications shown by the present study has demonstrated that RIRS is a safe and effective procedure for renal stones in patients with spinal deformities.


Correlation between VEGFR2 rs2071559 polymorphism and glioma risk among Chinese population.
We investigated the correlation between vascular endothelial growth factor 2 (VEGFR2) polymorphism and glioma risk among Chinese population. Case-control study design was adopted, and blood samples and clinical data of 250 glioma cases and 260 control subjects were collected. Epidemiological questionnaire survey was performed, and DNA extraction, concentration normalization and packaging were carried out using Qiagen Blood Kit. TaqMan method was performed for VEGFR2 rs2071559 genotyping. C allele of VEGFR2 rs2071559 genotype was the susceptibility allele contributing to the risk of glioma (OR=1.813, 95% CI: 1.393-2.359, P=0.014). CC genotypes of VEGFR2 rs2071559 were associated with increased risk of glioma (OR=2.068, 95% CI: 1.164-3.674, P=0.014; Adjusted OR=1.883, 95% CI: 1.430~3.013, P=0.018). CC genotypes of VEGFR2 rs2071559 were associated with glioma risk among Chinese population. However, the role of VEGFR2 rs2071559 polymorphism in glioma susceptibility remains to be further clarified.


An immobilized hybridoma culture perfusion system for production of monoclonal antibodies.
A fixed bed perfusion system for hybridoma cell immobilization is presented. The system consists of a culturing vessel (300 ml total volume) in which polyurethane (PU) sponges in the form of small cubes of about 5 mm sides are packed. Cells are immobilized by physical entrapment in the foam matrix. By entrapment of the cells in the pores of the matrix high cell concentration can be maintained in a mechanically protected environment. Medium is continuously circulated by an airlift pump mounted in the cell-free chamber (700 ml total volume).Medium flow rate, feeding rate, dissolved oxygen, pH, nutrient uptake and waste product formation can be easily monitored and controlled. Steady state conditions are established with medium dilution rates of 1.0-1.5 reactor volume per day. The steady state is characterized by a constant cell density, constant culture volume and constant glucose and lactate levels. Cell-free supernatant is collected continuously in a cold room adjacent to the 37°C culture room. Monoclonal antibodies (MAb) are produced at a concentration of 150-200 μg/ml for several weeks. An important feature of the system is the capacity to maintain a population of cells after the growth phase in a non-proliferating state for extended time periods expressing high titers of MAb.


Risk Perception and Disaster Preparedness in Immigrants and Canadian-Born Adults: Analysis of a National Survey on Similarities and Differences.
Research has documented that immigrants tend to experience more negative consequences from natural disasters compared to native-born individuals, although research on how immigrants perceive and respond to natural disaster risks is sparse. We investigated how risk perception and disaster preparedness for natural disasters in immigrants compared to Canadian-born individuals as justifications for culturally-adapted risk communication and management. To this end, we analyzed the ratings on natural disaster risk perception beliefs and preparedness behaviors from a nationally representative survey (N = 1,089). Factor analyses revealed three underlying psychological dimensions of risk perception: external responsibility for disaster management, self-preparedness responsibility, and illusiveness of preparedness. Although immigrants and Canadian-born individuals shared the three-factor structure, there were differences in the salience of five risk perception beliefs. Despite these differences, immigrants and Canadian-born individuals were similar in the level of risk perception dimensions and disaster preparedness. Regression analyses revealed self-preparedness responsibility and external responsibility for disaster management positively predicted disaster preparedness whereas illusiveness of preparedness negatively predicted disaster preparedness in both groups. Our results showed that immigrants' risk perception and disaster preparedness were comparable to their Canadian-born counterparts. That is, immigrant status did not necessarily yield differences in risk perception and disaster preparedness. These social groups may benefit from a risk communication and management strategy that addresses these risk perception dimensions to increase disaster preparedness. Given the diversity of the immigrant population, the model remains to be tested by further population segmentation.


SPINK1 Gene is Significantly Associated With Pancreatitis: A Comprehensive Meta-Analysis.
This research was applied to case-control studies of the association between pancreatitis and SPINK1 gene to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. MEDLINE and Embase were searched to identify longitudinal studies evaluating pancreatitis and SPINK1. Odds ratios (ORs) and 95% confidence interval (CI) were pooled using random-effect models and calculated using Carlin method. Publication bias was assessed using Egger et al's approach (A famous statistic method by Egger et al). Sensitivity, heterogeneity, and trim and fill analyses were conducted. Based on the results, we found that (1) the results support for the association between pancreatitis and SPINK1, when analyzed totally and by subdivision (total [OR, 7.771; 95% CI, 5.232-11.543; P < 0.000]; European [OR,6.400; 95% CI, 4.346-9.426; P < 0.000]; Asian [OR, 11.823; 95% CI, 4.612-30.310; P < 0.000]; American [OR, 3.777; 95% CI, 1.596-8.939; P = 0.002]; mixed: [OR, 13.566; 95% CI, 2.322-79.252, P = 0.004]); (2) no evidence indicates that this association is accounted for by any one study, and no evidence indicates any publication bias exists. The results indicated that SPINK1 gene, particularly the N34S mutation, has a genetic association with the development of pancreatitis.


Impact of elevated body mass index on cumulative live birth rate and obstetric safety in women undergoing assisted reproductive technology.
This study evaluated the impact of elevated body mass index (BMI) on short- and long-term outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. A total of 7229 patients undergoing IVF/ICSI fresh cycles and subsequent frozen embryo transfer cycles from 2014 to 2020 were divided into normal (18.5-24.9 kg/m2) and high BMI (≥ 25 kg/m2) groups. Ovarian response, pregnancy outcomes, and safety of both mother and fetus were the main outcome measures. Furthermore, multivariate analysis was used to determine whether BMI was associated with cumulative live birth rate (CLBR). Results showed that for younger women (< 38 year), CLBR was significantly reduced in the high BMI group compared with the normal BMI control and was accompanied by fewer retrieved oocytes and available embryos. Additionally, the incidence of hypertensive disorders of pregnancy, fetal macrosomia, and cleft lip and palate birth defects resulting from cumulative live births was significantly higher compared with the normal BMI group. No differences were observed among older women (≥ 38 year). Multivariate analysis revealed that high BMI was a risk factor for CLBR. Our study suggested that elevated BMI has a greater adverse impact on younger women.


Injecting drug use is associated with HIV risk perception among Mexican Americans in the Rio Grande Valley of South Texas, USA.
Injecting drug use (IDU) remains an actual risk variable in human immunodeficiency virus (HIV) infection in most ethnic populations, and the association between actual risk and individual perception of HIV risk varies across studies and samples. This study aimed to examine the relationship between IDU and HIV risk perception among Mexican Americans residing in Rio Grande Valley, South Texas. A cross-sectional study of IDU as a predictor of HIV risk perception. Two hundred and seventy-five participants [IDUs 11.9%, non-IDUs 88.1%] were assessed for an association between IDU and individual risk perception for HIV infection, as well as history of drug use and HIV risk perception, using Chi-squared statistic for independence and a logistic regression model for the prevalence odds ratio (POR). There was no statistically significant difference between IDUs and non-IDUs with respect to the sociodemographic variables, except for income and gender (P<0.05). The results indicated a statistically significant decrease in HIV risk perception among IDUs compared with non-IDUs, after adjustment for age, gender, sexual preference, history of drug use and marital status [POR 0.26, 95% confidence intervals (CI) 0.11-0.65]. Likewise, history of drug use was associated with decreased HIV risk perception (POR 0.44, 95% CI 0.22-0.98). These results suggest an inverse correlation between actual risk of HIV infection, such as IDU, and HIV risk perception. Therefore, assessment of HIV risk perception, which is a significant determinant of behaviour change, is essential to reduce the prevalence of HIV infection in the targeted population.


Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs.
We recorded impulses from afferent vagal C-fibres (conduction velocities 0.8-2.4 m/sec) arising from endings in the lungs of anesthetized dogs with open chest. Endings were of two types ('pulmonary' and 'bronchial') distinguished by their response and accessibility to capsaicin and phenyl diguanide injected into the right or left atrium. 'Pulmonary' endings, stimulated only by capsaicin and accessible through the pulmonary circulation, have been described previously. 'Bronchial' endings were stimulated by both capsicin and phenyl diguanide and were accessible through the bronchial circulation. Eight of 28 'bronchial' endings were located in large airways within 4 cm of the hilum, and two were in small airways near the edge of the lung. The precise location of the remaining 'bronchial' endings was not determined but we think that many were in the airways. 'Bronchial' endings had a sparse and irregular spontaneous discharge. They were stimulated by the inhalation of 5% histamine aerosol, the evoked discharge having no obvious relation to the phase of ventilation. A few were weakly stimulated by hyperinflating the lungs; deflation was without effect. The function of these endings is unknown.


Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study.
Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment. To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years). A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates. We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment. Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.


Ecological studies of Eastern Australian fruit flies (Diptera: Tephritidae) in their endemic habitat : II. The spatial pattern of abundance.
11 fruit fly species captured at 47 sites in a natural forest area at Cooloola (south-east Queensland) revealed specific patterns of spatial abundance. Although all species were collected throughout the study area, D. bryoniae, D. mayi, D. neohumeralis and D. tryoni were more prevalent (average number caught per trap) in the open Eucalypt forest than the rainforest, whereas C. aequalis, D. absonifacies and D. endiandrae were more prevalent in the rainforest. D. cacuminatus, D. choristus, D. quadratus and D. signatifrons were equally prevalent throughout both forest types. Fly numbers were not distributed randomly throughout the trap sites. The clumped dispersion patterns seemed to be species specific as assessed and summarised by Taylor's Power Law. The exponent (b) relating mean spatial abundance to its variance ranged from 1.6-5.11 for the 11 species captured. Changing patterns of trap catches from one sampling period to another were analysed using correlograms for the 6 most abundant species (D. tryoni, D. neohumeralis, D. endiandrae, C. aequalis, D. cacuminatus and D. mayi). These revealed changing patterns of relative spatial abundance which can be related, in part, to changing population abundance levels. The various spatial patterns recognised are related to each species movement, breeding and feeding behaviour. It is proposed that flies migrate into the rainforest area from distant locations and that the rainforest habitat is an important adult feeding site.


Fungal infection in patients with end-stage liver disease: low frequency or low index of suspicion.
End-stage liver disease (ESLD) is associated with dysregulation of the immune system and increased susceptibility to infections. Although invasive fungal infection (IFI) is a growing public health problem, studies of IFI in ESLD are lacking. The aims of this study were to screen for IFI in ESLD and to assess risk factors and serum interleukin 17 (IL-17) as a marker of the cellular immune response. Both blood and ascitic fluid samples were collected from 46 patients with ESLD for fungal culture and PCR. Serum IL-17 levels were determined. Seven patients had isolated IFI (four had spontaneous fungal peritonitis, two had fungemia, and one had a disseminated fungal infection) and five cases had combined fungal and bacterial infections. Spontaneous fungal peritonitis was attributed to Candida species, while fungemia was caused by Aspergillus species. Patients with IFI had higher serum IL-17 levels and increased mortality compared to patients without IFI. A history of antibiotic use (p = 0.002), higher model for end-stage liver disease (MELD) scores (p = 0.04), and hepatorenal syndrome (p = 0.006) were risk factors for IFI. Patients with ESLD had a low frequency of IFI; however, in patients with these infections, delayed diagnosis and treatment may contribute to a high fatality rate. Thus, clinicians should have a high index of suspicion for this unusual but lethal entity, as prompt detection and appropriate treatment can improve the outcome.