Objective
To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association.
Design
A pooled ...analysis of six cohort studies.
Setting
The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE).
Population
18 555 women from the UK, USA and Australia.
Methods
VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects.
Main outcome measures
Hot flushes and night sweats.
Results
Frequency data showed that early menarche ≤11 years was associated with an increased risk of ‘often’ hot flushes (RRR 1.48, 95% CI 1.24–1.76) and night sweats (RRR 1.59, 95% CI 1.49–1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94–1.42) and 1.27 (95% CI 1.01–1.58) for ‘severe’ hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and ‘often’ VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of ‘severe’ VMS.
Conclusions
Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk.
Tweetable
Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.
Tweetable
Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.
Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed.
To determine the rate ...of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day.
Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks’ gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA.
Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg Bayesian posterior probability (pp) = 0.93 and 0.92, respectively. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg.
Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. ClinicalTrials.gov (NCT02626299).
In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and vitreous. Here, ...an inhibitor responsible for the avascularity of these ocular compartments is identified as pigment epithelium-derived factor (PEDF), a protein previously shown to have neurotrophic activity. The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization. These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness.
•The human PAG displays a crude somatotopic map with a rostro-caudal organisation of the face and body.•Cutaneous noxious stimulation predominantly activates the lateral column of the contralateral ...PAG.•Deep muscular pain predominantly activates the ventrolateral column of the contralateral PAG.
The midbrain periaqueductal grey (PAG) is a critical region for the mediation of pain-related behavioural responses. Neuronal tract tracing techniques in experimental animal studies have demonstrated that the lateral column of the PAG (lPAG) displays a crude somatotopy, which is thought to be critical for the selection of contextually appropriate behavioural responses, without the need for higher brain input. In addition to the different behavioural responses to cutaneous and muscle pain – active withdrawal versus passive coping – there is evidence that cutaneous pain is processed in the region of the lPAG and muscle pain in the adjacent ventrolateral PAG (vlPAG). Given the fundamental nature of these behavioural responses to cutaneous and muscle pain, these PAG circuits are assumed to have been preserved, though yet to be definitively documented in humans. Using ultra-high field (7-Tesla) functional magnetic resonance imaging we determined the locations of signal intensity changes in the PAG during noxious cutaneous heat stimuli and muscle pain in healthy control participants. Images were processed and blood oxygen level dependant (BOLD) signal changes within the PAG determined. It was observed that noxious cutaneous stimulation of the lip, cheek, and ear evoked maximal increases in BOLD activation in the rostral contralateral PAG, whereas noxious cutaneous stimulation of the thumb and toe evoked increases in the caudal contralateral PAG. Analysis of individual participants demonstrated that these activations were located in the lPAG. Furthermore, we found that deep muscular pain evoked the greatest increases in signal intensity in the vlPAG. These data suggest that the crude somatotopic organization of the PAG may be phyletically preserved between experimental animals and humans, with a body-face delineation capable of producing an appropriate behavioural response based on the location and tissue origin of a noxious stimulus.
Nitrogen oxides (NOx) have fallen steadily across the US over the last 15 years. At the same time, NOx concentrations decrease on weekends relative to weekdays, largely without co-occurring changes ...in other gas-phase emissions, due to patterns of diesel truck activities. These trends taken together provide two independent constraints on the role of NOx in the nonlinear chemistry of atmospheric oxidation. In this context, we interpret interannual trends in wintertime ammonium nitrate (NH4NO3) in the San Joaquin Valley of California, a location with the worst aerosol pollution in the US and where a large portion of aerosol mass is NH4NO3. Here, we show that NOx reductions have simultaneously decreased nighttime and increased daytime NH4NO3 production over the last decade. We find a substantial decrease in NH4NO3 since 2000 and conclude that this decrease is due to reduced nitrate radical-initiated production at night in residual layers that are decoupled from fresh emissions at the surface. Further reductions in NOx are imminent in California, and nationwide, and we make a quantitative prediction of the response of NH4NO3. We show that the combination of rapid chemical production and efficient NH4NO3 loss via deposition of gas-phase nitric acid implies that high aerosol days in cities in the San Joaquin Valley air basin are responsive to local changes in NOx within those individual cities. Our calculations indicate that large decreases in NOx in the future will not only lower wintertime NH4NO3 concentrations but also cause a transition in the dominant NH4NO3 source from nighttime to daytime chemistry.
Saksenaea species (spp.) are uncommon causes of mucormycosis but are emerging pathogens mostly associated with trauma and soil contamination often in immunocompetent hosts. Due to lack of sporulation ...in the laboratory, diagnosis and susceptibility testing is difficult so optimal treatment regimens are unknown. We describe an unusual case of disseminated infection with a favourable outcome to date.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Disc displacement without reduction (DDwoR) can cause pain and limitations in mouth opening, with a significant impact on function. The optimal management strategy for DDwoR is unclear. Treatments ...include conservative management such as mandibular manipulation, occlusal splints, and patient education/self-management, as well as arthrocentesis, which is a minimally invasive procedure. The aim of this systematic review and meta-analysis was to ascertain whether there is a role for arthrocentesis in the management of DDwoR. Studies analysing the outcomes pain and maximum mouth opening (MMO) in patients with DDwoR treated by arthrocentesis or occlusal coverage devices were eligible for inclusion. Following a database search, six studies with a total of 343 participants were found to be eligible for analysis (three prospective observational studies, one retrospective observational study, one non-randomized single-blind clinical trial, and one unblinded randomized clinical trial). When compared to occlusal coverage splints, arthrocentesis demonstrated a slight improvement in pain, although this was statistically non-significant (standardized mean difference (SMD) −0.50, 95% confidence interval (CI) −1.04 to 0.05, P = 0.07; I2 = 81%), and a significant improvement in MMO (SMD 0.79 mm, 95% CI 0.24–1.35 mm, P = 0.005; I2 = 79%). However, due to the significant heterogeneity between studies and the high risk of bias, along with the paucity of double-blind randomized controlled clinical trials, definitive conclusions cannot be drawn for this clinical question.
•We asked pregnant women to complete an online version of a 7-question food frequency questionnaire that estimates DHA intake without assistance.•A trained nutritionist then readministered the ...questionnaire.•The results demonstrated that the online version had good sensitivity and specificity for detecting low and high DHA intakes.
The secondary analyses of two large, recently completed randomized clinical trials of DHA supplementation in pregnancy found that women with a low baseline DHA status benefited from randomization to a higher dose (800 vs 0 and 1000 vs 200 mg/day DHA). To obtain DHA status, it is necessary to obtain a blood sample and conduct an analysis using gas chromatography (GC) or GC-mass spectrometry (GCMS), both barriers to clinics where pregnant women receive advice on nutrition. Participants consuming less than 150 mg/day of DHA at baseline in our recent trial had a lower risk of early preterm birth and preterm birth when assigned to 1000 vs 200 m/day DHA. DHA intake was determined using a 7-question food frequency questionnaire administered by a trained nutritionist. Because the need for trained personnel to administer the questionnaire would be a barrier to implementing this finding in clinical management of pregnancy, the goal of this study was to determine if an online version of the questionnaire could be validly completed without assistance.
Herpes zoster and postherpetic neuralgia occur more often with increasing age. In this controlled trial among 38,546 adults 60 years of age or older, vaccination with a live attenuated ...varicella–zoster vaccine reduced the incidence of postherpetic neuralgia by 66.5 percent (as compared with placebo) and the incidence of herpes zoster by 51.3 percent.
In adults 60 years of age or older, vaccination with a live attenuated varicella–zoster vaccine reduced the incidence of postherpetic neuralgia by 66.5 percent (as compared with placebo) and the incidence of herpes zoster by 51.3 percent.
Herpes zoster, or shingles, is characterized by unilateral radicular pain and a vesicular rash that is generally limited to a single dermatome.
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Herpes zoster results from reactivation of latent varicella–zoster virus (VZV) within the sensory ganglia.
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The incidence and severity of herpes zoster increase with advancing age; more than half of all persons in whom herpes zoster develops are older than 60 years. Complications occur in almost 50 percent of older persons with herpes zoster.
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The most frequent debilitating complication is postherpetic neuralgia, a neuropathic pain syndrome that persists or develops after the dermatomal rash has healed. . . .
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