Efficacy of cognitive behavioural therapy for insomnia or sleep disturbance in pregnant women: A systematic review ad meta-analysis

During pregnancy many women may experience negative emotions and sleep disturbances. This systematic review and meta-analysis was conducted to assess the efficacy of cognitive behavioural therapy for insomnia (CBT-I) or sleep disturbance in pregnant women. From the earliest available publications to 15 April 2022, seven electronic literature databases were searched: PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Database for Chinese Science and Technology Journal. Randomised controlled trials of CBT-I in pregnant women with insomnia or sleep disorders were included. The methodological bias of the included studies was assessed using the Cochrane risk of bias tool. The meta-analysis was performed using RevMan 5.4 software. Stata Statistical Software: Release 15 was used for sensitivity analysis and publication bias. We included eight randomised controlled trials involving 743 pregnant women. Meta-analysis showed that, compared with the control group, CBT-I significantly improved the Insomnia Severity Index (mean difference [MD] = −4.25, 95% confidence interval [CI, −6.32, −2.19], p < 0.001), The Pittsburgh Sleep Quality Index (MD = −3.30, 95% CI [−4.81, −1.79], p < 0.001), sleep onset latency (standardised mean difference [SMD] = −1.25, 95% CI [−2.01, −0.50], p = 0.001), anxiety (SMD = −0.99, 95% CI [−1.32, −0.67], p < 0.001), and depression (SMD = −0.40, 95% CI [−0.72, −0.07], p = 0.02). No significant differences were found in total sleep time (SMD = 0.31, 95% CI [−0.54, 1.17], p = 0.47) and sleep efficiency (SMD = 0.80, 95% CI [−0.53, 2.13], p = 0.24). CBT-I significantly improved pregnant women's sleep quality, insomnia severity, depression, and anxiety. This meta-analysis provides evidence that CBT-I is valid for insomnia or sleep disturbances during pregnancy.     

Association of copy number variation across the genome with neuropsychiatric traits in the general population

Copy number variants (CNVs) are associated with psychiatric conditions in clinical populations. The relationship between rare CNV burden and neuropsychiatric traits in young, general populations is underexplored. A total of 6,807 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were studied. CNVs were inferred from single nucleotide polymorphism‐array data using PennCNV. After excluding children with known candidate CNVs for schizophrenia (SCZ), rare (<1%) CNV burden (total number of genes affected by CNVs, total length of CNVs, and largest CNV carried) was analyzed in relation to: psychotic experiences (PEs) and anxiety/depression in adolescence; autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD), ASD and ADHD traits, and cognitive measures during childhood. Outcomes were also assessed in relation to known SCZ CNVs. The number of genes affected by rare CNVs was associated with a continuous measure of ASD: the standardized mean difference [SMD] per gene affected was increased by 0.018 [95%CI 0.011,0.025], p = 3e‐07 for duplications and by 0.021 [95%CI 0.010, 0.032], p = 1e‐04 for deletions. In line with our published results on educational attainment in ALSPAC, intelligence quotient (IQ) was associated with CNV burden: the SMD per gene affected was −0.017 [95%CI −0.025, −0.008] p = 1e‐04 for duplications and −0.023 [95%CI −0.037, −0.009], p = .002 for deletions. Associations were also observed for measures of coherence, attention, memory, and social cognition. SCZ‐associated deletions were associated with IQ (SMD: −0.617 [95%CI −0.936, −0.298], p = 2e‐04), but not with PEs or other traits. We found that rare CNV burden and known SCZ candidate CNVs are associated with neuropsychiatric phenotypes in a nonclinically ascertained sample of young people.     

Perceived social support mediates the association between attachment and cardiovascular reactivity in young adults

To understand the influence of social relationships on cardiovascular responses to stress, the present study investigated perceived affectionate support as a mediating variable explaining the association between specific attachment bonds (i.e., mother, father, partner, best friend) and cardiovascular reactivity (CVR). Utilizing a standardized stress testing protocol, 138 young adults completed measures of attachment and social support, with continuous cardiovascular measurements obtained using the Finometer Pro hemodynamic monitor. Results showed that the association between anxious and avoidant attachment and reactivity were mediated by perceived affectionate support; insecure attachment was linked to lower levels of perceived social support, which in turn was associated with lower CVR. For anxious attachment, this was noted only for mothers (SBP: B = −0.94, 95% CI [−1.94, −0.20]; DBP: B = −0.57, [−1.27, −0.10]), fathers (SBP: B = −0.72, [−1.42, −0.17]; DBP: B = −0.48, [−1.01, −0.13]), and best friends (SBP: B = −0.64, [−1.23, −0.18]; DBP: B = −0.40, [−0.81, −0.12]). For avoidant attachment, it was evident only for fathers (SBP: B = −0.70, [−1.33, −0.17]; DBP: B = −0.48, [−0.92, −0.15]) and partners (SBP: B = −0.78, [−1.64, −0.09]; DBP: B = −0.53, [−1.10, −0.11]). These findings suggest that insecure attachment is associated with lower levels of reactivity, which have been linked to negative health outcomes such as poor self-reported health, depression, and obesity. Overall, this research expands on the support and relationship science literature by incorporating under-researched aspects of social relationships (i.e., specific attachment styles) and focusing on the mechanisms by which they are associated with physiological stress responses.     

Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis

Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (−3.7 g/L, 95% CI, −5.3 to −2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.     

Changes in total lower limb support moment in middle-aged patients undergoing arthroscopic partial meniscectomy — A longitudinal observational cohort study

BackgroundPatients with a meniscal tear are frequently treated with arthroscopic partial meniscectomy (APM) which may alter the net extension moment across the entire lower limb – known as the total support moment (TSM).PurposeTo investigate changes in TSM during walking in patients undergoing APM.MethodsThree-dimensional motion analysis of walking was performed in individuals with meniscal tear prior to APM and 12 months after. Peak TSM, positive ankle (ASM), knee (KSM), and hip (HSM) moments at the time of peak TSM were calculated together with corresponding angular impulses.ResultsPatients (n = 20) were middle aged (45.9 ± 6.3 years) and the majority male (70%). At baseline a lower KSM (mean [95%CI]; 0.59 Nm/BM · HT% [− 1.93; 3.11], P = 0.048) and a trend towards lower peak TSM (0.46 Nm/BM · HT% [− 1.82; 2.78], P = 0.099) were observed for the APM leg compared with the contralateral. Pre- versus post-APM change scores indicated a relative decrease in loading of the contralateral leg for peak TSM (− 0.49 Nm/BM · HT% [− 0.96; − 0.01], P = 0.047) and a trend towards a relative increase in loading of the APM leg for peak KSM (− 0.41 Nm/BM · HT% [− 0.92; 0.09], P = 0.105). No differences were observed in angular impulse variables.ConclusionsPrior to APM a strategy to unload the injured knee was manifested by reduced KSM and a tendency to a reduced peak TSM. A more equal distribution of joint moments between injured and contralateral legs was observed 12 months following APM.     

Prevalence and risk factors for Chlamydia trachomatis infection in adolescent females and young women in central Brazil

In order to determine the prevalence and risk factors for Chlamydia trachomatis infection in adolescent females and young women in central Brazil, 296 subjects attending two public health services were evaluated. The overall prevalence of C. trachomatis infection, as determined using polymerase chain reaction, was 19.6% (95% confidence interval [CI], 15.3–24.7). In multivariate analysis, young age (odds ratio [OR]_adjusted 2.32, 95%CI 1.1–4.8, p<0.05) and having 2–3 (OR_adjusted 3.41, 95%CI 1.6–6.3, p<0.05) or ≥4 sexual partners in life (OR_adjusted 3.10, 95%CI 1.1–6.3, p<0.05) were factors significantly associated with chlamydial infection. In conclusion, the prevalence of C. trachomatis infection was high in the studied population and risk factors were related to age and sexual behavior.     

Widowhood and cognitive decline in adults aged 50 and over: A systematic review and meta-analysis

While widowhood is known to be associated with poorer physical and mental health outcomes, studies examining the association of widowhood with cognition have yielded mixed results. This review aimed to elucidate the link between widowhood and cognitive decline.A systematic search of Medline, Embase, PsycInfo, CINAHL and Scopus (until December 2020) was conducted to identify studies on the association between widowhood (vs. being married) and cognition in cognitively healthy adults aged 50 +.A cross-sectional meta-analysis (of 10 studies; n = 24,668) found a significant association of widowhood with cognition (g = − 0.36, 95% CI [− 0.47, − 0.25], p = < 0.001). Meta-regressions suggested that study design, cognitive domain measured, sample age, difference in mean age between widowed and married groups, and study continent did not account for observed heterogeneity. A longitudinal meta-analysis (of 3 studies; n = 10,378) found that the “continually widowed” group (from baseline to follow-up) showed significantly steeper declines in cognition compared to the “continually married” group (g = − 0.15, 95%CI [− 0.19, − 0.10], p = < 0.001).Findings indicate that widowhood may be a risk factor for cognitive decline. As there are no effective treatments for cognitive impairment, studying mechanisms by which widowhood might be associated with poorer cognition could inform prevention programs for those who have experienced spousal bereavement.     

The effects of recruitment of renal functional reserve on renal cortical and medullary oxygenation in non-anesthetized sheep

Aim

Recruitment of renal functional reserve (RFR) with amino acid loading increases renal blood flow and glomerular filtration rate. However, its effects on renal cortical and medullary oxygenation have not been determined. Accordingly, we tested the effects of recruitment of RFR on renal cortical and medullary oxygenation in non-anesthetized sheep.

Methods

Under general anesthesia, we instrumented 10 sheep to enable subsequent continuous measurements of systemic and renal hemodynamics, renal oxygen delivery and consumption, and cortical and medullary tissue oxygen tension (PO₂). We then measured the effects of recruitment of RFR with an intravenous infusion of 500 ml of a clinically used amino acid solution (10% Synthamin® 17) in the non-anesthetized state.

Results

Compared with baseline, Synthamin® 17 infusion significantly increased renal oxygen delivery mean ± SD maximum increase: (from 0.79 ± 0.17 to 1.06 ± 0.16 ml/kg/min, p < 0.001), renal oxygen consumption (from 0.08 ± 0.01 to 0.15 ± 0.02 ml/kg/min, p < 0.001), and glomerular filtration rate (+45.2 ± 2.7%, p < 0.001). Renal cortical tissue PO₂ increased by a maximum of 26.4 ± 1.1% (p = 0.001) and medullary tissue PO₂ increased by a maximum of 23.9 ± 2.8% (p = 0. 001).

Conclusions

In non-anesthetized healthy sheep, recruitment of RFR improved renal cortical and medullary oxygenation. These observations might have implications for the use of recruitment of RFR for diagnostic and therapeutic purposes.     

Effects of the COVID-19 pandemic on sleep quality in children and adolescents: A systematic review and meta-analysis

We synthesise the literature on the potential influence of the COVID-19 pandemic on sleep quality in children and adolescents. The search identified studies that examined the relationship between sleep quality and disorders during the COVID-19 pandemic. It began in May 2021 and has had two updates with the last in January 2022. The databases used were LILACS, PubMed, and EMBASE. Random effects models were performed to explore heterogeneity between studies. Data were presented as continuous variables (mean value and standard deviation) to perform a meta-analysis. Twenty-nine studies from 16 countries were identified: Nine had children and eight had adolescents. The overall quality of the studies ranged from high (27.6%) to medium (65.5%) and low (6.9%). Eight studies were eligible for meta-analysis. There was an increase in sleep duration during the pandemic when compared with the previous period 0.33 (95%CI −0.07; 0.60) (p < 0.001) and late bedtime 0.78 (95%CI −0.33; 1.22) (p < 0.001). A trend toward reduced sleep efficiency was also detected 0.54 (95%CI −0.75; −0.33) p = 0.20. Parents’ reports of increased use of screen media/electronic devices were associated with worse sleep quality. The results suggest an influence of the pandemic on sleep characteristics such as increased sleep duration, late bedtimes, and poor sleep quality. These alterations were related to changes in family routines during this period.     

Cognitive impairment no dementia and associations with health literacy,self-management skills,and functional health status

ObjectivesTo determine the prevalence of cognitive impairment no dementia (CIND) among a diverse, community-based population, and establish associations between CIND and health literacy, chronic disease self-management and functional health status.Methods863 primary care adults without dementia aged 55–74. Adjusted logistic and linear regressions were used to assess associations between CIND (None, Mild, Moderate/Severe) and outcomes.Results36 % participants exhibited CIND. It was strongly associated with limited health literacy (Newest Vital Signs: Mild [OR 3.25; 95 % CI 1.93, 5.49], Moderate/Severe [OR 6.45; 95 % CI 3.16, 13.2]; Test of Functional Health Literacy in Adults: Mild [OR 3.46; 95 % CI 2.08, 5.75], Moderate/Severe [OR 8.82; 95 % CI 4.87, 16.0]; all p’s < 0.001) and poor chronic disease self-management (Mild [B = −11.2; 95 % CI −13.5, -8.90], Moderate/Severe CI [B = −21.0; 95 % CI −23.6, −18.4]; both p’s < 0.001). Associations between CIND and functional health status were non-significant.ConclusionsCIND was prevalent in this cohort, and strongly associated with requisite skills for managing everyday health needs.Practice ImplicationsAttention to subtle declines in chronic disease self-care may assist with CIND identification and care management within this population. When CIND is observed, clinicians should also expect and address difficulties with self-management.     

A predictive model of vitamin D insufficiency in older community people: From the São Paulo Aging & Health Study (SPAH)

Objective

To evaluate the prevalence of 25-hydroxyvitamin D insufficiency (25OHD < 20 ng/mL) and to develop a predictive model for this status.

Methods

This is a cross-sectional study including 908 community-dwelling older subjects, 18% (158) of which were randomly selected to be a “test” sample, with the remaining (750) composing a “development” sample. A radioimmunoassay technique was used to measure 25OHD levels. Anthropometrical data, information about lifestyle habits and co-morbidities were obtained. Multiple logistic regression models were created. An Index Risk of Vitamin D Insufficiency (IRVDI) was designed and subsequently validated. The performance of this tool was assessed through ROC analysis.

Results

The prevalence of 25OHD < 20 ng/mL was of 58.0% (CI 95% 51.6–64.6). The clinical independent factors for 25OHD < 20 ng/mL were female gender (OR = 2.16; 95%CI 1.13–4.13; p = 0.020), diabetes (OR = 1.84; 95%CI 1.23–2.74; p = 0.003) and season (winter/spring) (OR = 3.63, 95%CI 2.62–4.88; p < 0.001). After statistical adjustments, the IRVDI was able to identify older people at risk for vitamin D insufficiency with a sensitivity of 55.9%, specificity 72.3% and ROC area of 0.685 (p < 0.001).

Conclusions

Our results suggest that vitamin D insufficiency is common among Brazilian community-dwelling elderly. Female gender, diabetes and the season (winter/spring) were the important parameters that predicted this status. The clinical use of these parameters can be help to design and target appropriate public health interventions. The IRVDI is a convenient tool for the selection of older people at risk for vitamin D insufficiency.     

βA globin gene haplotypes in Mexican Huichols: Genetic relatedness to other populations

The haplotypes of 97 β^A independent chromosomes from a Mexican Huichol Native American group were analyzed. The analysis also included 87 β^A chromosomes from a Mexican Mestizo population previously studied. Among Huichols, eight different 5′ β haplotypes (5Hps) were observed, with types 1(+ − − − −), 13(+ + + − +) and 2(− + + − +) at frequencies of 0.794, 0.093, and 0.041, respectively. In Mestizos, 17 5Hps were found, types 1, 3(− + − + +), 2, 5(− + − − +) and 9(− − − − −) being the most common at frequencies of 0.391, 0.172, 0.092, 0.069, and 0.046, respectively. 3′ haplotype (3Hps) frequency distributions were 0.443(+ +), 0.083(+ −), and 0.474(− +) in Huichols and 0.563(+ +), 0.149(+ −), and 0.287(− +) in Mestizos. Pairwise comparison for both haplotype distributions between the two populations showed significant differences. Pairwise distributions of 3Hps for Huichols were compared with nine worldwide populations, three African, two Asian, two Melanesian, one Caucasian, and one United States Native American. The distributions of the Huichol were different (P < 0.05) from all populations except the Native American. Nei's genetic distances showed the Huichols to be closer to the Native Americans, followed by Melanesians from Vanuatu and Asians; Africans were the farthest. The 5Hp distributions in Mexicans were also compared with 23 worldwide populations (including African, Native American, Asian, Caucasian, and Pacific Islanders). Huichol distributions were different (P < 0.05) from all other populations except Koreans. The Mestizo distribution was also different from the others, except three Caucasian groups. Nei's genetic distance between the same populations disclosed that the Huichols are in relatively close proximity to five out of six Asian populations considered. The same analysis with grouped worldwide populations showed Native Americans as population closest to the Huichols, followed by Pacific Islanders and Asians. Present observations are consistent with an important Asian contribution to the Huichol genome in this chromosomal region. Am. J. Hum. Biol. 12:201–206, 2000. © 2000 Wiley-Liss, Inc.     

Midregional pro-adrenomedullin and copeptin: exercise kinetics and association with the cardiopulmonary exercise response in comparison to B-type natriuretic peptide

Purpose

Midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-vasopressin (copeptin) are novel biomarkers providing prognostic information in various settings. We aimed to (1) assess the kinetics of MR-proADM and copeptin during cardiopulmonary exercise testing (CPET); (2) assess the relationship of MR-proADM and copeptin measured at rest with peak oxygen consumption (peak VO₂) and other key CPET parameters; (3) compare this relationship to that of B-type natriuretic peptide (BNP).

Methods

In 162 patients undergoing symptom-limited CPET for evaluation of exercise intolerance, MR-proADM, copeptin, and BNP were measured at rest and peak exercise.

Results

There was a significant rise in copeptin and BNP (p < 0.001) but not in MR-proADM (p = 0.60) from rest to peak exercise. MR-proADM (r = ?0.57; p < 0.001) and BNP (r = ?0.49; p < 0.001) but not copeptin were significantly and inversely related to peak VO₂. MR-proADM was inversely correlated to the percentage of predicted heart rate achieved and peak oxygen pulse and directly related to the peak ventilation/carbon dioxide production relationship, the physiological dead space-to-tidal volume ratio, and the alveolo-arterial oxygen gradient (p ≤ 0.01 for all), and these associations were at least as strong as for BNP. In contrast, copeptin was not significantly related to any of these parameters (p > 0.05 for all).

Conclusion

In contrast to BNP and copeptin, MR-proADM is not immediately affected by a maximal exercise test. MR-proADM but not copeptin is at least as good an indicator of low peak VO₂ and CPET parameters reflecting an impaired cardiac output reserve, ventilatory efficiency and diffusion capacity as BNP, and thereby a global cardiopulmonary stress marker.     

Fit-Fat Index is better associated with heart rate variability compared to fitness and fatness alone as indicators of cardiometabolic human health

Objectives

Cardiorespiratory fitness and fatness indicators have been related to heart rate variability (HRV) parameters. The Fit-Fat Index (FFI) is a single index combining cardiorespiratory fitness and fatness indicators. To the best of our knowledge, no studies have previously analyzed whether FFI are related to cardiac autonomic nervous system activity assessed through HRV parameters. This study aimed (i) to examine the association of cardiorespiratory fitness, fatness indicators, and FFI with HRV parameters; and (ii) to report what of the different fatness indicators included in FFI is better associated with HRV parameters in sedentary adults.

Methods

One hundred and fifty healthy adults (74 women; 76 men), aged between 18 and 65 years old, participated in this cross-sectional study. We measured cardiorespiratory fitness (maximal oxygen consumption) and fatness indicators (waist-to-height ratio [WHR], fat mass percentage [FM%] and visceral adipose tissue [VAT]). Three FFIs were calculated as the quotient between cardiorespiratory fitness and one out of three possible fatness indicators: Fit-Fat Index calculated waist-to-height ratio (FFI_WHR), Fit-Fat Index calculated with FM% (FFI_FM%), and Fit-Fat Index calculated with VAT (FFI_VAT). HRV parameters were measured in resting conditions using a Polar RS800CX.

Results

FFI_WTHR, FFI_FM% and FFI_VAT were related to different HRV parameters (β ranges between −0.507 and 0.529; R² ranges between 0.096 and 0.275; all p < .001) and the association was stronger with HRV parameters than the isolated fitness or fatness indicators (β ranges between −0.483 and 0.518; R² ranges between 0.071 and 0.263; all p < .001). FFI_VAT was the index more consistently associated with HRV parameters (β ranges between −0.507 and 0.529; R² ranges between 0.235 and 0.275; all p < .001).

Conclusion

Our study suggests that compound FFIs are better predictors of HRV parameters than either cardiorespiratory fitness or fatness indicators alone. The FFI_VAT was the best index in terms of its association to HRV.     

IL6 and FAS/FASL gene polymorphisms may be associated with disease progression in HIV-1-positive ethnically mixed patients

The progression of AIDS depends on the complex host and virus interactions. The most important disease progression hallmarks are immune activation and apoptosis. In this study, we address the prevalence of polymorphisms related to proinflammatory and apoptotic genes, such as IFNG (+874T/A), TNF (308G/A), IL6 (−174G/C), IL8 (−251A/T), FAS (−670A/G), and FASL (−124A/G) in 160 ethnically mixed HIV-1-infected patients from multicentre cohorts with different clinical outcomes (13 elite controllers [EC], 66 slow long-term non-progressors [LTNPs], and 81 progressors [P]). The genotyping was accomplished by TaqMan-qPCR. Among all the polymorphisms analyzed in the cytokines, the IL6 −174G/C polymorphism showed a higher frequency of GG genotype in the LTNP and LTNP+EC groups as compared to the P group. Moreover, there was a significantly higher frequency of the G allele in the LTNP and LTNP+EC groups as compared to the P group. On the other hand, the levels of CD4⁺ T lymphocytes were higher among individuals showing the AA and AG genotypes for the FASL −124A/G polymorphism as compared to the GG genotype. Furthermore, the AG and AA genotypes were more frequent, as compared to the GG genotype, in individuals showing a lower viral load. In contrast, for the FAS −670A/G polymorphism, a significantly higher viral load was observed in individuals with the AG genotype as compared to the GG genotype. In conclusion, we found three genetic allelic variants of the IL6 −174G/C, FASL −124A/G, and FAS −670A/G polymorphisms that were related to disease progression and immunological and virological markers in cohorts of HIV-1-positive ethnically mixed patients.     

Assessment of functional roles and therapeutic potential of integrin receptors in osteoarthritis: A systematic review and meta-analysis of preclinical studies

BackgroundIntegrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the roles of integrins in different stages of OA remain elusive.ObjectivesThis study aimed to synthesize all published preclinical evidence on the roles of integrin receptors in different stages of OA to identify the potential target for drug development in alleviating OA pathogenesis.MethodsMajor electronic databases were used to identify related original articles. The methodological quality of all included studies was appraised using the SYRCLE risk of bias tool. We used the generic inverse variance with random effects model to calculate standardized mean differences (SMDs) and 95% confidence interval (CI).ResultsSeventeen studies were included in this systematic review. Integrin α5β1 activation increases the histopathological score both in early [SMD, 6.39; 95%CI (2.90, 9.87); p = 0.0003] and late [SMD, 3.41; 95%CI (2.44, 4.38); p < 0.00001] stage of OA. Integrin α5β1 also increased the core catabolic factors like MMP-3, IL-1β, and TNF-α. Interestingly, the inactivation of α5β1 integrin did not change the histopathological score (p = 0.84). Similarly, β1 integrin notably increased histopathological score at both stages of OA [early; SMD, 7.13; 95%CI (2.01, 12.24); p = 0.006]; [late; SMD, 10.25; 95%CI (5.11, 15.39); p < 0.0001], and increased the MMP-13 levels. However, integrin β1 was upregulated at the early stage and downregulated at the late stage of OA. Furthermore, α2β1 integrin significantly increased histopathological score [SMD, 3.14; 95%CI (2.18, 4.10); p < 0.00001] and MMP-13 [SMD, 2.24; 95%CI (0.07, 4.41); p = 0.04]. Deactivating integrin α1β1 increased histopathological score in late [SMD, 1.53; 95%CI (0.80, 2.26); p < 0.0001], but not in early [SMD, 0.90; 95%CI (−1.65, 3.45); p = 0.49] stage of OA.ConclusionThis study provides evidence that α5β1, α2β1, and α1β1 integrin might be the potential target for future drug development in alleviating OA pathogenesis. Further work is required to establish our findings through activating/deactivating these receptors in different stages of OA.     

Iron status in HIV-1 infection: implications in disease pathology

Background

There had been conflicting reports with levels of markers of iron metabolism in HIV infection. This study was therefore aimed at investigating iron status and its possible mediation of severity of HIV- 1 infection and pathogenesis.

Method

Eighty (80) anti-retroviral naive HIV-1 positive and 50 sero-negative controls were recruited for the study. Concentrations of serum total iron, transferrin, total iron binding capacity (TIBC), CD₄⁺ T -lymphocytes, vitamin C, zinc, selenium and transferrin saturation were estimated.

Results

The mean CD₄⁺ T-lymphocyte cell counts, serum iron, TIBC, transferrin saturation for the tests and controls were 319 ± 22, 952 ± 57 cells/μl (P < 0.001), 35 ± 0.8, 11.8 ± 0.9?μmol/l (P < 0.001), 58.5 ± 2.2, 45.2 ± 2.4?μmol/l (P < 0.005) and 68.8 ± 3.3, 27.7 ± 2.2%, (P <0.001), respectively, while mean concentrations of vitamin C, zinc and selenium were 0.03 ± 0.01, 0.3 ± 0.04 (P < 0.001), 0.6 ± 0.05, 11.9 ± 0.26?μmol/l (P < 0.001) and 0.1 ± 0.01, 1.2 ± 0.12?μmol/l (P < 0.001) respectively. Furthermore, CD₄⁺ T-lymphocyte cell count had a positive correlation with levels of vitamin C (r = 0.497, P < 0.001), zinc (r = 0.737, P < 0.001), selenium (r = 0.639, P < 0.001) and a negative correlation with serum iron levels (r = ?0.572, P < 0.001).

Conclusion

It could be inferred that derangement in iron metabolism, in addition to oxidative stress, might have contributed to the depletion of CD₄⁺ T cell population in our subjects and this may result in poor prognosis of the disease.

     

The effects of high intensity training upon respiratory gas exchanges during fixed term maximal incremental exercise in man

Summary The response of respiratory gas exchanges to a 6 week high intensity training program was examined in 5 healthy males during fixed term maximal incremental treadmill exercise. Training was performed 3 d·wk^–1 and consisted of a progressive series of repeated 15 sec and 30 sec maximal runs, and weight training exercises for the leg extensor muscles. Respiratory gases during the tests were continuously monitored using an on-line system. Muscle biopsy samples were obtained from the m. vastus lateralis before and after training for histochemical determination of fibre distribution based on myosin ATP-ase activity, and fibre cross-sectional area based on NADH-Tetrazolium Reductase activity. Training significantly increased the proportion of type IIa fibres (+5.9±2.0%,p<0.001) and decreased type I fibres (–6.3±2.0%,p<0.001), the distribution of type IIb fibres remained unchanged (+0.4±0.9%). Muscle cross-sectional area also showed a significant increase after training in type I (+ 318±215 m²,p<0.05), IIa (+652±207 m²,p<0.001) and IIb (+773±196 m²,p< 0.001) fibres. During fixed term maximal incremental exercise the mean carbon dioxide output ( ) and mean respiratory exchange ratio ( ) were significantly increased (p<0.01) after training. The R-time relationship was at all times shifted to the left after training, being significantly (p<0.01) so over the final five min of exercise. No changes in mean exercise oxygen uptake ( ), maximum oxygen uptake ( ) and maximum heart rate (FHR_max) were observed between tests. These results indicate that high intensity training can significantly affect respiratory exchange during fixed term progressive exercise.     

Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer

Objective

Whether moderate to severe obesity (body mass index (BMI) ≥ 30 to <40 kg/m²) contributes to breast cancer recurrence and mortality remains uncertain.

Subjects and methods

1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis.

Results

Of the 1155 included women, mean age, 58.4 ± 11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR = 1.71, 95%CI, 1.12–2.62, p = 0.014), disease beyond Stage 1 (HR = 2.87, 95% CI 1.73–4.75, p < 0.001), OAET (HR = 0.26, 95%CI 0.14–0.46, p < 0.001), mastectomy (HR = 3.28, 95%CI 1.98–5.44, p < 0.001) and radiotherapy (HR = 2.12, 95%CI 1.24–3.63, p = 0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48–7.03, p = 0.003) and OAET use (HR 0.41, 95%CI 0.17–0.98, p = 0.046) were significantly associated with an event.

Conclusion

Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment.