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The outbreak of Covid-19 negatively affected mental health and increased loneliness. The subjective feeling of loneliness is influenced by genetic and social factors and has a negative impact on mental health. From March 2020 to June 2021 loneliness was investigated in N = 517 individuals using monthly acquired questionnaire data and Latent Growth Curve Analysis. Associations of social factors and polygenic risk scores (PRSs, n = 361) with class membership were investigated. Three classes ("average", 40%; "not lonely", 38%; "elevated loneliness", 22%) were identified, that differ significantly regarding loneliness, mental dysfunction, and response to the lockdown phases. Individuals with a high PRS for neuroticism are more likely to belong to the "elevated loneliness" class, living with another person is a protective factor. As the "elevated loneliness" class was at the highest risk of mental dysfunction, our findings underscore the importance of identifying those individuals to implement counteractive measures. [ABSTRACT FROM AUTHOR]

Background: Early pregnancy loss (unintended pregnancy loss before 20 completed weeks of gestation) is a common adverse pregnancy outcome, with previous evidence reporting incidence ranging from 10 to 30% of detected pregnancies. The objective of this systematic review and meta-analysis is to determine the incidence and range of early pregnancy loss in contemporary pregnant populations based on studies with good internal and external validity. Findings may be useful for clinical counseling in pre-conception and family planning settings and for people who experience early pregnancy loss. Methods: We will search MEDLINE, EMBASE, and CINAHL databases using combinations of medical subject headings and keywords. Peer-reviewed, full-text original research articles that meet the following criteria will be included: (1) human study; (2) study designs: controlled clinical trials or observational studies with at least 100 pregnancies in the denominator, or systematic reviews of studies using these designs; (3) conducted in high-income countries; (4) reporting early pregnancy loss incidence, defined as unintended early pregnancy loss occurring prior to 20 weeks' gestation expressed as the number of losses among all pregnancies in the study period; (5) among a contemporary (1990 or later) general population of pregnancies; and (6) published between January 1, 1990, and August 31, 2021. We will assess the quality of included studies according to the United States Preventive Services Task Force Criteria for Assessing Internal and External Validity of Individual Studies. If appropriate, based on methodological comparability across included studies, we will conduct meta-analyses using random effects models to estimate the pooled incidence of early pregnancy loss among all studies with both good internal and external validity, with meta-analyses stratified by study design type (survey-based or self-reported and medical record-based), by induced abortion restrictions (restricted vs. unrestricted), and by gestational age (first trimester only vs. all gestational ages before 20 weeks). Discussion: This systematic review will synthesize existing evidence to calculate a current estimate of early pregnancy loss incidence and variability in reported incidence estimates in high-income settings. The findings of this review may inform updates to clinical counseling in pre-conception and family planning settings, as well as for patients experiencing early pregnancy loss. Systematic review registration: We have registered this review with the International Prospective Register of Systematic Reviews (PROSPERO #226267). [ABSTRACT FROM AUTHOR]

The endocannabinoid system is important for skin homeostasis and alterations are linked to inflammatory diseases like atopic dermatitis (AD). Importantly, activation of cannabinoid receptor CB2 decreases pruritus and inflammation in mouse models. Reduction of inactivation of endogenous cannabinoids could, therefore, be a therapeutic option for AD. Dogs spontaneously develop AD, which closely mimics the human disease making them suitable to test new therapies. Our study aimed to test the effects of a topical endocannabinoid membrane transporter inhibitor (WOL067-531, 1% gel) on pruritus and dermatitis in a canine model of AD. Nineteen Beagles allergic to dust mites (DM) were randomized to receive either active ingredient or vehicle on inguinal area while challenged epicutaneously with DM twice weekly for 28 days. Treatment was administered twice daily and started after three challenges (day 8). Dermatitis and pruritus were scored weekly by personnel blinded to treatment allocation. Dermatitis was scored using a validated scoring system and pruritus was scored using camera recordings. After a 4-week washout, dogs were crossed over and the study was repeated. On days 15 and 22, dermatitis scores were significantly increased after DM challenge in the vehicle group (16.34, p = 0.0089 and 7.42, p = 0.04845, respectively) but not in the active ingredient group (p = 0.3177 and p = 0.3190, respectively). Significant decrease on pruritus both on inguinal area and overall (p = 0.048 and p = 0.032, respectively) occurred in the active ingredient group. No adverse effects were noted. In conclusion, the newly developed topical endocannabinoid membrane transporter inhibitor (WOL067-531) minimized allergic flares and pruritus in a canine model of AD. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women? SUMMARY ANSWER: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders. WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear. STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. participants, setting, methods: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo. MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, 2 1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH. limitations, reasons for caution: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. WIDER IMPLICATIONS OF THE FINDINGS: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose. [ABSTRACT FROM AUTHOR]

This paper proves that the ratios of consecutive terms of the m-bonacci sequence converge to a limit φm < 2 and, as m → ∞, these φm converge to 2. Further, it is shown that the generating functions for the m-bonacci sequences converge pointwise to the geometric series. [ABSTRACT FROM AUTHOR]

This study investigated the effects of a skin protectant solution (dimethicone 2%) on clinical signs and skin barrier function in canine atopic dermatitis (AD). Eighteen dogs with AD were randomly divided into two groups, one received dimethicone and the other received the vehicle (cyclomethicone) on selected areas (pinnae, groin, and axillae) daily for 4 weeks. Owners and investigators were blinded regarding group allocation. Clinical efficacy was evaluated using a scoring system and skin barrier by measuring the transepidermal water loss. Twelve dogs completed the study (50% drop rate in the vehicle and 20% in the dimethicone). For clinical signs, analysis of variance showed an effect of time (P < 0.005; day 0 > day 28) and region (axillae < groin < pinnae) but no effect of group or group × time interaction. For transepidermal water loss, analysis of variance showed only a main effect of region (axillae > pinnae > groin). Pearson found no correlation between transepidermal water loss and clinical scores. In this pilot study dimethicone had no significant effect on clinical signs and transepidermal water loss in canine atopic dermatitis. [ABSTRACT FROM AUTHOR]

Information on the pathophysiology of glucocorticoid-induced osteoporosis (010) is limited, since its clinical picture often reflects a combined effect of glucocorticoids (GC) and the treated systemic disease (i.e., inflammation and immobility). In 50 healthy adult (30-mo-old) primiparous Göttingen minipigs, we studied the short-term (8 mo, n = 30) and long-term (15 mo, n = 10) effect of GC on bone and mineral metabolism longitudinally and cross-sectionally compared with a control group (n = 10). All animals on GC treatment received prednisolone orally at a dose of 1.0 mg·kg body wt-1·day-1 for 8 wk and thereafter at 0.5 mg/kg body wt day-1. In the short term, GC reduced bone mineral density (BMD) at the lumbar spine by -47.5 ± 5.1 mg/cm³ from baseline (P < 0.001), which was greater (P < 0.05) than the loss [not significant (NS)] in the control group of -11.8 ± 12.6 mg/cm³. Calcium absorption decreased from baseline by -2,488 ± 688 mg/7 days (P < 0.001) compared with -1,380 ± 1,297 mg/7 days (NS) in the control group. Plasma bone alkaline phosphatase (BAP) decreased from baseline by -17.8 ± 2.2 U/l (P < 0.000), which was significantly different (P < 0.05) from the value of the control group of -1.43 ± 4.8 U/l. In the long term, the loss of BMD became more pronounced and bone mineral content (BMC), trabecular thickness, mechanical stability, calcium absorption, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and parathyroid hormone tended to be lower compared with the control group. There was a negative association between the cumulative dose of GC and BMD, which was associated with impaired osteoblastogenesis. In conclusion, the main outcomes after GC treatment are comparable to symptoms of GC-induced osteoporosis in human subjects. Thus the adult Göttingen miniature pig appears to be a valuable animal model for GC-induced osteoporosis. [ABSTRACT FROM AUTHOR]

A lengthened response time when a distractor becomes a target, called negative priming, is an undisputed phenomenon in selective attention, yet just what the underlying mechanism responsible for negative priming is has not been resolved. In this study, the proportion of attended repetition trials was manipulated in order to test the predictions of three theories that have been proposed for explaining spatial negative priming: distractor suppression (e.g., Tipper, 1985), episodic memory retrieval (e.g., Neill, Valdes, & Terry, 1995), and novelty bias (e.g., Milliken, Tipper, Houghton, & Lupiáñez, 2000). The results supported the proposal that a novelty bias, which is flexible and can be overridden, is the primary mechanism responsible for priming in spatial tasks. Memory retrieval obscured the novelty bias for target processing, was more selective in older adults, and did not affect distractor processing. Novelty bias and distractor suppression may share the same inhibitory attentional mechanism. [ABSTRACT FROM AUTHOR]

Background and objective: The augmentation of the effect of neuromuscular blocking drugs with volatile anaesthetics is well documented, but the mechanism remains unclear. The pharmacological interaction and relative plasma concentrations of mivacurium isomers were investigated during either propofol- or isoflurane-maintained anaesthesia. Methods: Forty-four patients were randomly assigned to one of two groups: isoflurane or propofol- All patients received an initial dose of mivacurium 0.1 mg kg[sup-1]. After recovery of the first twitch (T1) response measured by acceleromyography to 5%, a T1 depression of 90-99% was maintained by infusion. After a steady state was reached, blood samples were taken after 10 and 30 min for analysis of mivacurium isomers. Recovery times for T1 to 25/50/75/90% (TW25-90), train-of-four ratio 25/70% and recovery index (time TW25-75) were recorded after stop of infusion. Results: In the isoflurane group, lower infusion rates were needed (3.0 ± 1.6 versus 3.6 ± 1.6 μg kg[sup-1] min[sup-1]) and there was a slower recovery (significant for train-of-four ratio 70%: 21.9 versus 17.9 min). The plasma concentrations of mivacurium and its trans—trans isomer (in percentage of the total) were significantly higher in the isoflurane group (10 min: 52.6 versus 25.8%; 30 min: 49.6 versus 23.2%). Conclusions: For mivacurium, the phenomenon of 'potentiation' of the effect of muscle relaxants by volatile anaesthetics could be clue to an increase in the plasma concentration of the potent trans—trans-isomer. [ABSTRACT FROM AUTHOR]

Overexpression and/or mutations of oncogenes, tumour suppressor genes and tumour rejection genes have been observed in several human malignancies. Their analyses might be of diagnostic importance. Therefore, malignant hepatocytes derived from hepatocellular carcinoma (HCC) tissue as well as non-malignant hepatocytes derived from focal nodular hyperplasia (FNH) were studied. Samples containing normal human hepatocytes (HC) served as controls. Cellular material was obtained by fine-needle aspiration biopsy guided by ultrasound. Cells were analysed for expression and mutation of the oncogene MDM2, the genes GAGE-1,-2 coding for tumour-associated antigens and the candidate tumour suppressor geneFHIT. Different patterns of non-mutant FHIT transcripts including precise deletion of exons were found in 7/10 HCC, 2/10 FNH and 2/10 HC. However, expression of non-mutant GAGE-1,-2 RNA was demonstrated exclusively in 6/10 HCC samples. Further genetic features specific of HCC were point mutations in a zinc-finger motif of MDM2 (3/10 HCC samples). Neither GAGE-1,-2 expression nor MDM2 mutations were observed in the FNH samples, or in normal hepatocytes. Our findings suggest that occurrence of variable FHIT transcripts is not restricted to hepatic malignant tumours. In contrast, MDM2 mutations and GAGE-1,-2 expression were associated with HCC specimens. Therefore, the RT-PCR assays for GAGE-1,-2 and MDM2 might be useful adjuncts in cytodiagnosis of liver neoplasms. [ABSTRACT FROM AUTHOR]

Bradyrhizobium japonicum mutant 132 was obtained by random TnphoA mutagenesis of strain 110spc4. A 6.5 kb BamHI kanamycin-resistance-coding DNA fragment of mutant 132 was used as a hybridization probe to clone the corresponding wild-type fragment. DNA sequence analysis of a 3213 bp BamHI-CIal fragment revealed that three open reading frames (ORFs) were encoded in the same orientation. Based on sequence similarities to other proteins in the database, the second ORF was called sipS (signal peptidase). The TnphoA insertion in mutant 132 was found to be in frame near the 3' end of sipS. The resulting SipS-PhoA hybrid polypeptide was shown to be expressed in free-living B. japonicum and in Escherichia coli cultures. An immunoblot analysis with a polyclonal antibody directed against the alkaline phosphatase revealed the appearance of a weak signal of a 70 kDa polypeptide both in B. japonicum and in E. coli, in agreement with the calculated size of the hybrid polypeptide. A much stronger 52 kDa band was also detected. Mutant 132 was specifically disturbed in the interaction with soybean (Glycine max) when the bacteria were released from the infection threads. The bacteroids were not stably maintained within the symbiosome. Numerous vesicles were found in the plant cytosol, which finally resulted in the formation of large vacuoles within the infected nodule cells. Immunohistochemical analyses with antibodies directed against nodulins of the peribacteroid membrane indicated a lower expression of these proteins. The mutant phenotype was genetically complemented by a 4.4 kb BamHI fragment including sipS. Subfragments thereof also complemented a temperature-sensitive E. coli lepB mutant, demonstrating that the B. japonicum fragment was functionally replacing Lepts in E. coli. Genetic studies suggested that the three genes are organized in one common operon which is expressed from a promoter upstream of the sequenced region. Inactivation of the gene downstream of sipS did not result in a detectable phenotype. [ABSTRACT FROM AUTHOR]