Risk Factor For Later Development Research Articles

A Systematic Review and Meta-analysis to Identify Risk Factors for Developing Long COVID-19.

This systematic review and meta-analysis was undertaken to identify the risk factors of long coronavirus disease 2019 (COVID-19) to provide insight for selecting cases for more aggressive monitoring and treatment after COVID-19 infection and reduce morbidity due to long COVID-19. All relevant studies published till July 2022 were searched for in PubMed, Trip database, and the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library). Reference lists of the studies selected for appraisal were also considered. The National Institute of Health Clinical Database and Google Scholar were searched for unpublished studies. All cohort studies which studied risk factors for long COVID-19 in adults (>18 years age-group) were included. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were used for data extraction and bias assessment were. The outcomes were risk factors identified as being related with persistent symptoms 3 months after recovery from COVID-19. Random-effects model (RevMan 5.3) was used to pool the data. Total nine studies were included with overall quality scores ranging from 16 to 19 out of the maximum 22. Pooled results demonstrated statistically significant association of long COVID-19 with female gender [odds ratio (OR) -1.67; 95% confidence interval (CI) 1.33-2.09], need of hospitalization (OR -1.80; 95% CI 1.22-2.64), and hospital stay (OR 2.41; 95% CI 0.75-4.07). Female gender, need for hospitalization and duration of hospitalization during acute COVID-19 infection are the risk factors for later development of long COVID-19. There should be specific guidelines for monitoring and treatment of this population after acute COVID-19 infection.

Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress

BackgroundEarly life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels. MethodsMale Wistar rats exposed to these stress paradigms were subjected to a comprehensive behavioral analysis. In hippocampal synaptosomes we investigated neurotransmitter release and glutamate concentration. The expression of CaMKII and the content of monoamines were determined in selected brain regions. Brain-derived neurotrophic factor (BDNF) mRNA was quantified by radioactive in situ hybridization. ResultsWe report a distinct behavioral phenotype in the double-hit group. Double-hit and SPS groups had decreased hippocampal presynaptic glutamatergic function. In hippocampus, double-hit stress caused a decrease in autophosphorylation of CaMKII. In prefrontal cortex, both SPS and double-hit stress had a similar effect on CaMKII autophosphorylation. Double-hit stress, rather than SPS, affected the norepinephrine and serotonin levels in prefrontal cortex, and suppressed BDNF gene expression in prefrontal cortex and hippocampus. LimitationsThe study was conducted in male rats only. The affected brain regions cannot be restricted to hippocampus, prefrontal cortex and amygdala. ConclusionDouble-hit stress caused more pronounced and distinct behavioral, molecular and functional changes, compared to MD or SPS alone.

Baseline cerebrovascular reactivity predicts longitudinal enlarged perivascular space burden in the basal ganglia among cognitively normal older adults

AbstractBackgroundIncreasing evidence suggests that enlarged perivascular spaces (ePVS) on magnetic resonance images (MRIs) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that cerebrovascular dysfunction, as assessed by an MRI measure of cerebrovascular reactivity (CVR), may contribute to ePVS development.Method79 cognitively normal, older adults (46 women, age range 60‐84) were recruited to undergo baseline MRI scanning and follow‐up scanning approximately 2.5 years later. Of the 79 participants scanned at baseline, 50 returned for follow‐up. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. All scanning methods were identical across time points and included collection of T1‐weighted, T2‐weighted FLAIR, and quantitative susceptibility mapping (QSM) images. Cerebrovascular dysfunction was assessed using CVR, a measure of the ability of cerebrovasculature to dilate in response to vasoactive stimuli. Participants underwent blocked administration of breathing either room air or hypercapnic gas, while blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was performed. CVR values were computed for baseline scans in specific regions by dividing change in BOLD signal by change in end‐tidal CO2. Baseline and follow‐up ePVS counts were performed by a single rater who was blinded to participant demographics. ePVS were individually and manually counted using STRIVE criteria in a representative, axial slice of the basal ganglia (BGePVS) and centrum semiovale (CSePVS).ResultBGePVS and CSePVS significantly increased during the follow‐up period. Mixed effects models indicated that baseline basal ganglia CVR values significantly predicted increased BGePVS counts after controlling for age, sex, education, and time point (p = <0.001). Furthermore, this effect was present bilaterally: Baseline CVR in the left hemisphere predicted increased BGePVS in the left hemisphere (p = <0.001) and baseline CVR in the right hemisphere predicted increased BGePVS in the right hemisphere (p = <0.001). Conversely, there was no longitudinal relationship between baseline CVR and increased CSePVS (p = 0.449).ConclusionThese results demonstrate that low baseline CVR is a risk factor for later development of ePVS. Localization of these findings to the basal ganglia suggests that it is particularly vulnerable to cerebrovascular dysfunction.

Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia.

Increasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the pathogenesis of ePVS remains unknown. Here, we tested the possibility that baseline cerebrovascular dysfunction, as measured by a magnetic resonance imaging measure of cerebrovascular reactivity, contributes to the later development of ePVS. Fifty cognitively unimpaired, older adults (31 women; age range, 60-84 years) underwent magnetic resonance imaging scanning at baseline and follow-up separated by ≈2.5 years. ePVS were counted in the basal ganglia, centrum semiovale, midbrain, and hippocampus. Cerebrovascular reactivity, an index of the vasodilatory capacity of cerebral small vessels, was assessed using carbon dioxide inhalation while acquiring blood oxygen level-dependent magnetic resonance images. Low baseline cerebrovascular reactivity values in the basal ganglia were associated with increased follow-up ePVS counts in the basal ganglia after controlling for age, sex, and baseline ePVS values (estimate [SE]=-3.18 [0.96]; P=0.002; [95% CI, -5.11 to -1.24]). This effect remained significant after accounting for self-reported risk factors of cerebral small vessel disease (estimate [SE]=-3.10 [1.00]; P=0.003; [CI, -5.11 to -1.09]) and neuroimaging markers of cerebral small vessel disease (estimate [SE]=-2.72 [0.99]; P=0.009; [CI, -4.71 to -0.73]). Our results demonstrate that low baseline cerebrovascular reactivity is a risk factor for later development of ePVS.

Comparison of disease severity in glaucoma patients identified byscreening in the 1990s and in routine clinical care in the 2010s in Sweden.

In a previous study comparing the amount of visual field damage at presentation in patients having open-angle glaucoma (OAG) identified through screening and in patients diagnosed in routine clinical practice in the 1990s, the damage was considerably worse in the clinically diagnosed patients. In the present study we compare visual field damage at presentation in the same 402 screened patients with that seen in 281 newly detected previously untreated patients clinically diagnosed in the 2010s. The perimetric visual field index mean deviation (MD) was compared in the two groups of patients. In the clinical patients diagnosed with bilateral visual field damage the median MD was -5.1 dB in the better eye and -13.0 dB in the worse eye. In the screened patients the median MD in the better eye was -6.5 dB and -11.5 dB in the worse eye. The differences between the clinical and screened patients were non-significant, p = 0.28 and p = 0.67 respectively. More clinical patients had severe visual field loss, defined as MD less than -20 dB, in the worse eye than in the screened patients, 18.5% versus 12.7% respectively, p = 0.037. The visual field damage at presentation in clinically diagnosed OAG patients has improved in the past 20 years, but the proportion of patients with severe visual field loss in at least one eye, almost 20%, is still unacceptably high considering that severe visual field damage at presentation is the most important risk factor for later development of glaucoma blindness.

Four reasons why we should screen for dissociation in competitive sports

Four reasons why we should screen for dissociation in competitive sports

Association Between Hypertensive Disorders of Pregnancy and Dementia: a Systematic Review and Meta-Analysis.

Prior meta-analyses report a 2- to 4-fold increased risk of later cardiovascular disease among women with a history of hypertensive disorders of pregnancy (HDP). Given HDP's vascular underpinnings, it is hypothesized to also be a risk factor for later dementia. We aim to summarize the evidence for the impact of HDP on dementia and consider unique associations between HDP and dementia subtypes. Observational studies on the relationship between HDP and dementia were identified from online electronic databases to July 1, 2021 (PROSPERO identifier: CRD42020185630). We included observational studies published in English. Exposure among women was any HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other/unspecified HDP. Outcome was any dementia and dementia subtypes: Alzheimer's disease, vascular dementia, or other/unspecified dementias. For our primary analyses, we included 5 cohort studies with a total of 183 874 women with and 2 309 705 women without HDP. Pooled analysis found a 38% higher risk of all-cause dementia among women with, versus without, any type of HDP (adjusted hazard ratio, 1.38 [95% CI, 1.18-1.61]; P<0.01). When examining association by HDP and dementia subtypes, we found that women with, versus without, any type of HDP had over a 3-fold higher risk of vascular dementia (adjusted hazard ratio, 3.14 [95% CI, 2.32-4.24]; P<0.01). Our findings indicate that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia. Further research among more racially/ethnically diverse populations quantifying HDP's effect on all-cause dementia, and specifically vascular dementia, is warranted.

Early-life associations between per- and polyfluoroalkyl substances and serum lipids in a longitudinal birth cohort

BACKGROUND AND AIM: Exposures to per- and polyfluoroalkyl substances (PFASs) may affect metabolic outcomes, including serum lipid concentrations. However, few studies have evaluated potential associations between PFASs and lipids longitudinally. In this study we estimated associations between PFAS and lipid concentrations at birth and at several points in childhood and identified sensitive periods of exposure. METHODS: This study included 490 children from a prospective cohort in the Faroe Islands. Concentrations of five PFASs were measured in serum collected at birth and ages 18 months, 5 years and 9 years. Serum lipid concentrations were measured at birth, 18 months and 9 years. We estimated associations between PFAS and lipid concentrations and evaluated possible effect modification by sex. We further tested whether PFAS associations with age-9 lipids varied by exposure period using multiple informant models of repeated PFAS exposures. RESULTS:Childhood PFAS exposures were positively associated with lipids at age 9. Increases in age-9 concentrations of perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA) and perfluorooctanesulfonic acid (PFOS) were positively associated with total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). For example, a doubling of PFDA at age nine was associated with a 0.19 mmol/L increase in TC (95% CI: 0.07, 0.32), a 0.10 mmol/L increase in HDL-C (95% CI: 0.05, 0.15) and a 0.12 mmol/L increase in LDL-C (95% CI: 0.02, 0.22). We found significant differences in estimated effects by sex, with stronger positive associations between PFASs and TC and LDL-C in girls, and stronger positive associations with HDL-C in boys. Exposure period was a significant modifier of PFAS effects in multiple informant models. CONCLUSIONS:These findings suggest that childhood PFAS exposures may be associated with elevated serum lipid concentrations. This is a public health concern, as a detrimental lipid profile in childhood is a risk factor for later development of hyperlipidemia and cardiovascular disease. KEYWORDS: Chemical exposures, Children's environmental health, Endocrine disrupting chemicals, Obesity and metabolic disorders, PFAS

Communication skills predict social-emotional competencies

IntroductionStudies have shown that many children with early language difficulties also have delays in social-emotional competencies as well as social-emotional and behavioral problems. It is unclear if these conditions are causally related, if they share a common underlying etiology, or if there are bidirectional effects. Studies investigating these associations have mostly involved children who are already using words to communicate, but it is important to know whether delays in preverbal communication and language development have any effects on these associations. The aim of the present study was to examine associations between preverbal communication and early verbal skills in infancy and subsequent social-emotional competencies and ensuing social-emotional and behavioral problems in early toddlerhood. The role of background factors known to influence early language development was also examined. MethodsThe sample consisted of 395 children (51.6% boys) from the Finnish Steps Study cohort. Language was assessed at age 13 months (+ 1 month) with the MacArthur Communicative Development Inventory for Infants (CDI-I), and the social-emotional domain was assessed at age < 17 months with the Brief Infant–Toddler Social and Emotional Assessment (BITSEA). ResultsInfants with lower preverbal gestural communication and receptive language skills had a higher risk of delays in social-emotional competencies in toddlerhood than children with better communication skills, but not of elevated social-emotional and behavioral problems. ConclusionsThe results indicate that lower early communication skills can predict delays in the development of social-emotional competencies, which has been found to be a risk factor for later development of social-emotional and behavioral problems. It is important to monitor early communication skills to provide guidance to parents in supporting early pragmatic communication and language development in infancy, if needed.

Early-life associations between per- and polyfluoroalkyl substances and serum lipids in a longitudinal birth cohort

BackgroundExposures to per- and polyfluoroalkyl substances (PFASs) may affect metabolic outcomes, including lipid concentrations in the blood. However, few studies have evaluated potential associations between PFASs and lipids longitudinally. ObjectivesWe estimated associations between PFAS and lipid concentrations at birth and at several points in childhood. MethodsWe measured concentrations of five major PFASs in cord serum and in serum collected at 18 months, five years and nine years in 490 children from a prospective cohort in the Faroe Islands. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations were measured at birth, 18 months and nine years. We estimated associations between PFAS and lipid concentrations and evaluated possible effect modification by sex. We also tested whether PFAS associations with age-nine lipids varied by exposure period. ResultsSerum PFAS concentrations at ages five and nine were positively associated with lipid concentrations at age nine. Cross-sectional associations between PFASs and lipids at age nine were the strongest, with increases in serum concentrations of perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA) and perfluorooctanesulfonic acid (PFOS) associated with increases in TC, HDL-C and LDL-C. We found statistically significant differences in estimated PFAS effects by sex, where girls had stronger positive associations between PFASs and TC and LDL-C and boys had stronger positive associations with HDL-C. In repeated measure models, exposure period was a significant modifier of PFAS effects. ConclusionsOur findings suggest that childhood PFAS exposures may be associated with elevated serum lipid concentrations. This is a public health concern, as a detrimental lipid profile in childhood is a risk factor for later development of hyperlipidemia and cardiovascular disease.

Progressive Cognitive and Post-Traumatic Stress Disorder-Related Behavioral Traits in Rats Exposed to Repetitive Low-Level Blast.

Many military veterans who experienced blast-related traumatic brain injuries (TBI) in the conflicts in Iraq and Afghanistan currently have chronic cognitive and mental health problems including post-traumatic stress disorder (PTSD). Besides static symptoms, new symptoms may emerge or existing symptoms may worsen. TBI is also a risk factor for later development of neurodegenerative diseases. In rats exposed to repetitive low-level blast overpressure (BOP), robust and enduring cognitive and PTSD-related behavioral traits develop that are present for at least one year after blast exposure. Here we determined the time-course of the appearance of these traits by testing rats in the immediate post-blast period. Three cohorts of rats examined within the first eight weeks exhibited no behavioral phenotype or, in one cohort, features of anxiety. None showed the altered cued fear responses or impaired novel object recognition characteristic of the fully developed phenotype. Two cohorts retested 36 to 42 weeks after blast exposure exhibited the expanded behavioral phenotype including anxiety as well as altered cued fear learning and impaired novel object recognition. Combined with previous work, the chronic behavioral phenotype has been observed in six cohorts of blast-exposed rats studied at 3-4 months or longer after blast injury, and the three cohorts studied here document the progressive nature of the cognitive/behavioral phenotype. These studies suggest the existence of a latent, delayed emerging and progressive blast-induced cognitive and behavioral phenotype. The delayed onset has implications for the evolution of post-blast neurobehavioral syndromes in military veterans and its modeling in experimental animals.

Race-based differences in drug use prior to onset of opioid use disorder

Rates of opioid use disorder (OUD) have increased dramatically over the past two decades, a rise that has been accompanied by changing demographics of those affected. Early exposure to drugs is a known risk factor for later development of opioid use disorder; but how and whether this risk factor may differ between racial groups is unknown. Our study seeks to identify race differences in self-report of current and past substance use in OUD-diagnosed treatment-seeking individuals. Patients (n = 157) presenting for methadone maintenance treatment at a racially diverse urban opioid treatment program were approached and consented for study involvement. Participants were administered substance use history questionnaires and urine drug screening at intake. Chi-square, t-tests, and rank-sum were used to assess race differences in demographic variables. Logistic and linear regressions assessed the relationship between race and substance use for binary and continuous variables, respectively. 61% of the population identified as Black and 39% as White. Black participants were significantly older; age was thus included as a covariate. Logistic regressions demonstrated that despite similar urine toxicology at intake, White participants were significantly more likely to report having used prescription opioids and psychedelic, stimulant, and sedative substance classes prior to their first use of non-pharmaceutical opioids. Compared to Black participants, White treatment-seeking OUD-diagnosed individuals reported using a wider range of substances ever and prior to first use of non-pharmaceutical opioids. There were no differences, however, in presentation for OUD treatment, suggesting different pathways to OUD, which may carry important clinical implications.

Aβ42 mediated activation of the NLRP3 inflammasome predicts cognitive and gait performance in midlife type 2 diabetes mellitus (T2DM)

AbstractBackgroundMidlife Type 2 Diabetes Mellitus (T2DM) is a potent risk factor for later development of dementia. However, putative mechanisms mediating this risk are poorly understood. The NLRP3 inflammasome receptor, which drives strong pro‐inflammatory responses, has been implicated in both T2DM and Alzheimer’s disease (AD) pathogenesis, and can be activated by Amyloid β1‐42 (Aβ42).MethodPeripheral Blood Mononuclear Cells (PBMCs) were isolated from participants with T2DM (N = 39; 52.04 ± 8.01 years) and matched controls (N = 21; 52.16 ± 7.82 years) without any evidence of cognitive impairment. PBMCs were incubated for 18 hours under the following conditions: (i) Lipopolysaccharide (LPS), (ii) Aβ42, (iii) LPS &amp; Aβ42 and (iv) LPS &amp; Nigericin (potent NLRP3 activator). Cytokine production was measured using ELISA and gene expression using qPCR. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Gait speed was measured under normal and dual‐task conditions (reciting alternate letters of the alphabet). Wilcoxon rank‐sum tests were used for univariate analysis and Poisson and linear regression models used for multivariate analyses, adjusting for important covariates.ResultsTreatment of PBMCs under all four conditions resulted in a significant production of the pro‐inflammatory cytokines IL‐1β and IL‐6, which did not differ between T2DM and healthy controls. Greater IL‐1β production (an NLRP3‐dependent cytokine) under both Aβ‐42 (ii) and LPS &amp; Nigericin (iv) conditions was associated with greater likelihood of error on the MoCA (aIRR 1.01, p = 0.010; aIRR 1.01, p = 0.004). Further, greater IL‐1β production under both LPS &amp; Aβ42 (iii) and LPS &amp; Nigericin (iv) conditions was associated with a greater slowing effect (cost) on the dual‐task (adjusted: β = 0.31, 0.04‐0.58, p = 0.023; 0.029, 0.05 – 0.54, p = 0.019). Effects were seen in the cohort overall, regardless of T2DM status, but were stronger in those with T2DM.ConclusionsGreater activation of the NLRP3 inflamamsome by Aβ42 was associated with poorer cognitive and gait performance in midlife T2DM. Further work will follow this cohort longitudinally and assess the ability of innate immune NLRP3 activity to predict later cognitive trajectories in those with midlife T2DM.

Characteristics of graft-versus-host disease occurring after alemtuzumab-containing allogeneic stem cell transplants: incidence, organ involvement, risk factors and survival.

T-cell depletion with alemtuzumab represents an effective form of graft-versus-host disease (GVHD) prophylaxis after allogeneic haematopoietic stem cell transplantation (allo-HSCT); however, little is known regarding the impact of in vivo alemtuzumab on either the incidence or clinical characteristics of acute and chronic GVHD. We therefore studied 201 consecutive adult patients who received an alemtuzumab-based, reduced-intensity conditioned (RIC) allograft. With a median follow-up of 24months, the cumulative incidence of classic acute and late acute (persistent, recurrent and late onset) GVHD grades II-IV (grades III-IV) was 34% (13%) and 20% (8%) respectively; the cumulative incidence of classic chronic GVHD and overlap syndrome were 4% and 7% respectively. A previous diagnosis of classic acute GVHD is a risk factor for chronic GVHD (hazard ratio 10·91, 95% confidence interval 2·35-50·63, P=0·0023) while late onset acute GVHD is not a risk factor for later development of chronic GVHD. Unrelated donor transplant is a risk factor for the development of classic acute GVHD but not for late onset or chronic GVHD. In conclusion, this study describes a distinctive pattern of GVHD following alemtuzumab-RIC allografts, identifies the risk factors for GVHD development and provides prognostic information of patients with GVHD.

Metachronous Neoplasias Arise in a Higher Proportion of Colon Segments From Which Large Polyps Were Previously Removed, and Can be Used to Estimate Incomplete Resection of 10–20 mm Colorectal Polyps

Incomplete resection of polyps could be an important cause of post-colonoscopy colorectal cancer. However, it is difficult to study progression of incompletely removed polyps or their clinical importance. We aimed to estimate incomplete polyp resection using risk of metachronous neoplasia per colon segment. We performed a retrospective study of 1031 patients (6186 colon segments) who initially underwent resection of a large (10-20 mm) neoplastic polyp at 2 academic medical centers (from 2000 through 2012) and then underwent a subsequent colonoscopy within 0.5 to 5 years. We determined the proportions of metachronous neoplasia in colon segments from which a single large neoplastic polyp was removed and in segments without prior neoplasia. We then used the absolute difference in proportions between these groups to estimate the rate of incomplete resection. Our analysis assumed that development of metachronous neoplasia in each colon segment was the consequence of a newly grown polyp, a previously missed polyp, or an incompletely removed polyp. Metachronous neoplasia was detected in 177 of 757 segments (23.4%) with a single large polyp, and in 438 of 4232 segments (10.3%) without any neoplasia at baseline colonoscopy (P < .001). Resections were therefore estimated to be incomplete in 13.0% of segments (95% CI, 9.8-16.2). This proportion was greater for sections with non-pedunculated polyps (18.3%; 95% CI, 14.2-22.5) than pedunculated polyps (3.5%; 95% CI, -0.7 to -11.3; P < .001). A higher proportion of piecemeal resections appeared to be incomplete (28.0%; 95% CI, 20.2-35.7) than of en bloc resections (9.2%; 95% CI, 5.9-12.5) (P < .001). No differences in incomplete resection were associated with polyp histology. Metachronous neoplasia arises in a significantly higher proportion of colon segments from which a polyp was previously removed. Based on these data, we estimate that 13% of all large polyps are incompletely resected and 18% of large non-pedunculated polyps are incompletely resected. These findings indicate that incomplete resection could be a risk factor for later development of neoplasia. Segment metachronous neoplasia might be used as a marker of resection quality.

An Animal Model of Alcohol Binge Drinking: Chronic-Intermittent Ethanol Administration in Rodents.

Binge drinking (BD), characterized by intermittent consumption of large quantities of alcohol in short periods of time, is the main alcohol consumption pattern in adolescents and young adults. BD has serious biomedical consequences, and it is a prominent risk factor for later development of alcohol use disorders. Rodent models offer exceptional power to study these negative consequences of BD. This chapter focuses on one of these BD models: the chronic-intermittent ethanol administration (CIEA) paradigm. Essentially, CIEA consists of the administration in rats or mice of i.p. injections of ethanol (doses: 3-4g/kg) for several consecutive days each week, in alternation with several days without injections, during several weeks. Due to our interest in the neurobehavioral effects of BD, a combination of the CIEA model with a battery of behavioral tests is described, with emphasis on the effects of alcohol BD on different kinds of memory. The CIEA model, in combination with behavioral tasks, seems to be a useful tool for studying the neurobehavioral effects of BD as well as for developing potential prevention and treatment strategies.

No evidence of the role of early chemical exposure in the development of \u03b2-cell autoimmunity

Exposure to environmental chemicals can modulate the developing immune system, but its role in the pathogenesis of type 1 diabetes is largely unexplored. Our objective was to study the levels of circulating concentrations of environmental pollutants during the first years of life and their associations with the later risk of diabetes-predictive autoantibodies. From two birth-cohort studies including newborn infants with HLA-conferred susceptibility to type 1 diabetes (FINDIA and DIABIMMUNE), we identified case children with at least one biochemical diabetes-associated autoantibody (n = 30–40) and from one to four autoantibody-negative controls per each case child matched for age, gender, diabetes-related HLA-risk, delivery hospital, and, in FINDIA, also dietary intervention group. Plasma levels of 13 persistent organic pollutants and 14 per- and polyfluorinated substances were analyzed in cord blood and plasma samples taken at the age of 12 and 48 months. Both breastfeeding and the geographical living environment showed association with circulating concentrations of some of the chemicals. Breastfeeding-adjusted conditional logistic regression model showed association between decreased plasma HBC concentration at 12-month-old children and the appearance of diabetes-associated autoantibodies (HR, 0.989; 95% Cl, 0.978–1.000; P = 0.048). No association was found between the plasma chemical levels and the development of clinical type 1 diabetes. Our results do not support the view that exposure to the studied environmental chemicals during fetal life or early childhood is a significant risk factor for later development of β-cell autoimmunity and type 1 diabetes.

Peter H. Venables (1923–2017)

Peter H. Venables (1923–2017)

Influence of evolution on cam deformity and its impact on biomechanics of the human hip joint.

Anatomy and biomechanics of the human hip joint are a consequence of the evolution of permanent bipedal gait. Habitat and behaviour have an impact on hip morphology and significant differences are present even within the same biological family. The forces acting upon the hip joint are mainly a function of gravitation and strength of the muscles. Acetabular and femoral anatomy ensure an inherently stable hip with a wide range of motion. The femoral head in first human ancestors with upright gait was spherical (coxa rotunda). Coxa rotunda is also seen in close human relatives (great apes) and remains the predominant anatomy of present-day humans. High impact sport during adolescence with open physis however can activate an underlying genetic predisposition for reinforcement of the femoral neck, causing an epiphyseal extension and the formation of an osseous asphericity at the antero-superior femoral neck (cam deformity). The morphology of cam deformity is similar to the aspherical hips of quadrupeds (coxa recta), with the difference that in quadrupeds the asphericity is posterior. It has been postulated that this is due to the fact that humans bear weight on the extended leg, while quadrupeds bear weight at 90-100° flexion. The asphericity alters the biomechanical properties of the joint and as it is forced into the acetabulum leading to secondary cartilage damage. It is considered a risk factor for later development of osteoarthritis of the hip. Clinically this presents as reduced range of motion, which can be an indicator for the structural deformity of the hip. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:XX-XX, 2018.

Endometriosis-associated Ovarian Cancers.

Endometriosis-associated cancers include clear cell and endometrioid ovarian carcinoma. A history of endometriosis has long been considered to be a risk factor for later development of these malignancies; however, recent molecular genetic evidence has provided unequivocal evidence that these lesions are in fact the precursors for endometriosis-associated cancers. Herein, we will explore the relationship between endometriosis and ovarian carcinomas, similarities between the premalignant lesions and their cancerous counterparts, and the potential role of mutations and the ovarian microenvironment that may contribute to malignant transformation.