Acrolein depletes the neuropeptides CGRP and substance P in sensory nerves in rat respiratory tract.

The mammalian respiratory tract is densely innervated by autonomic and sensory nerves around airways and blood vessels. Subsets of these nerves contain a number of putative neurotransmitter peptides, such as substance P and calcitonin gene-related peptide (CGRP) in sensory nerves and vasoactive intestinal polypeptide (VIP), possibly serving autonomic functions. CGRP is also found in endocrine cells in rat airway epithelium. These peptides are all pharmacologically potent effectors of bronchial and vascular smooth muscle and bronchial secretion. Their functions in vivo are less well established. We have therefore examined the effects of inhaled acrolein, a sensory irritant, on three pulmonary neuropeptides: CGRP, substance P, and VIP. Groups of rats (n = 3 each) were exposed for 10 min to acrolein in air (Ct = 510, 1858, and 5693 mg.min/m3) or to air alone. Fifteen minutes later they were killed (pentabarbitone IP) and their respiratory tracts were dissected and fixed in 0.4% p-benzoquinone solution. Cryostat sections were stained by indirect immunofluorescence for a general nerve marker (PGP 9.5) and neuropeptides. The acrolein-treated animals had a dose-related decrease in tracheal substance P- and CGRP-immunoreactive nerve fibers compared with controls. No change was seen in total nerve fiber distribution and number (PGP 9.5) or VIP immunoreactivity, nor in CGRP-immunoreactive epithelial endocrine cells. It is concluded that the rat tracheal peptidergic nerves are a sensitive indicator of inhaled irritant substances. Their reduced immunoreactivity may be because of a release of sensory neuropeptides that could play a role in the physiological response to irritant or toxic compounds

Mother–infant interactions with infants with congenital visual impairment and associations with longitudinal outcomes in cognition and language

Background: This study investigated mother–infant interactions, including maternal maintaining of infant attentional focus and sensitivity, with infants with congenital severe and profound visual impairment (VI) and the association with developmental trajectories from one to three years. Method: Fifty‐five infants and mothers were video‐recorded playing together with a standard set of toys at Time 1 (T1) mean age 12.95 months (8.13–17.05 months). Maintain was categorized as the mother following and maintaining the child’s focus, and Sensitivity, the mother’s responsiveness and contingency to infant behaviour. Vision level was measured using the Near Detection Scale. Cognition and language were measured at T1, 12 months later (T2) and 24 months later (T3) using the Reynell‐Zinkin Scales. Results: Cross‐sectional analyses showed that mothers of infants with severe VI (basic form vision) produced higher rates of Maintain compared to those with children with profound VI (light perception at best). Linear mixed‐effects models examining developmental progression from T1 to T3 (controlling for vision level) showed an average increase of 5 DQ points (CI 95%: 1.03–9.08) in verbal comprehension for higher Sensitivity. No significant findings were found for Maintain. Conclusions: The findings suggest that mother–infant interactions (maternal Maintain) are associated with level of vision at infancy, but only maternal Sensitivity has a long‐term positive association with advances in verbal comprehension from infancy to about three years. They highlight the need for incorporating strategies related to parent–infant interactions, including increased sensitivity, into early intervention for children with visual impairment

Fetal alcohol spectrum disorder and youth justice: a prevalence study among young people sentenced to detention in Western Australia

Objectives: To estimate the prevalence of fetal alcohol spectrum disorder (FASD) among young people in youth detention in Australia. Neurodevelopmental impairments due to FASD can predispose young people to engagement with the law. Canadian studies identified FASD in 11%–23% of young people in corrective services, but there are no data for Australia. Design: Multidisciplinary assessment of all young people aged 10–17 years 11 months and sentenced to detention in the only youth detention centre in Western Australia, from May 2015 to December 2016. FASD was diagnosed according to the Australian Guide to the Diagnosis of FASD. Participants: 99 young people completed a full assessment (88% of those consented; 60% of the 166 approached to participate); 93% were male and 74% were Aboriginal. Findings: 88 young people (89%) had at least one domain of severe neurodevelopmental impairment, and 36 were diagnosed with FASD, a prevalence of 36% (95% CI 27% to 46%). Conclusions: This study, in a representative sample of young people in detention in Western Australia, has documented a high prevalence of FASD and severe neurodevelopmental impairment, the majority of which had not been previously identified. These findings highlight the vulnerability of young people, particularly Aboriginal youth, within the justice system and their significant need for improved diagnosis to identify their strengths and difficulties, and to guide and improve their rehabilitation

Attitudes About COVID-19 and Health (ATTACH): Online Survey and Mixed Methods Study

Background: Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden. / Objective: In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020. / Methods: The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll questions related to COVID-19 2 times daily and a monthly survey assessing mental health, social isolation, physical health, and quality of life. Poll question responses were graphed using 95% Clopper–Pearson (exact) tests with 95% CIs. Pearson correlations, hierarchical linear regression analyses, and generalized linear models assessed relationships, predictors of self-reported outcomes, and group differences, respectively. / Results: By October 31, 2020, 1405, 80, and 90 participants had consented to participate in the UK, United States, and Mexico, respectively. Descriptive data for the UK daily poll questions indicated that participants generally followed social distancing measures, but worry and negative impacts on families increased as the pandemic progressed. Although participants generally reported feeling that the reasons for current measures had been made clear, there was low trust that the government was doing everything in its power to meet public needs. In the UK, 1282 participants also completed a monthly survey (94.99% [1326/1396] White, 72.22% [1014/1404] female, and 20.12% [277/1377] key or essential workers); 18.88% (242/1282) of UK participants reported a preexisting mental health disorder, 31.36% (402/1282) reported a preexisting chronic medical illness, and 35.11% (493/1404) were aged over 65; 57.72% (740/1282) of participants reported being more sedentary since the pandemic began, and 41.89% (537/1282) reported reduced access to medical care. Those with poorer mental health outcomes lived in more deprived neighborhoods, in larger households (Ps<.05), had more preexisting mental health disorders and medical conditions, and were younger than 65 years (all Ps<.001). / Conclusions: Communities who have been exposed to additional harm during the COVID-19 pandemic were experiencing worse mental outcomes. Factors including having a medical condition, or living in a deprived neighborhood or larger household were associated with heightened risk. Future longitudinal studies should investigate the link between COVID-19 exposure, mental health, and sociodemographic and residential characteristics

S-100 protein positive cells in nasopharyngeal carcinoma (NPC): absence of prognostic significance. A clinicopathological and immunohistochemical study of 40 cases

An immunohistochemical study of S-100 protein in 43 nasopharyngeal carcinomas (NPC) of known clinical evolution (33 primary and 10 metastatic) is presented. Sixty per cent of primary site cases as well as all metastatic forms showed S-100 protein positive cells intermingled with tumour cells. These S-100 positive elements were identified as Langerhans cells. No significant differences were found when correlating S-100 protein positivity and histological NPC variants, neither in age nor in sex of patients. Statistical analysis failed to demonstrate any positive correlation between S-100 protein reactivity and clinical survival

Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

<p>Abstract</p> <p>Background</p> <p>Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients.</p> <p>Methods</p> <p>The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1) in exhaled breath condensate (EBC) during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed.</p> <p>Results</p> <p>In asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline F_ENOand the increase in F_ENOor BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed.</p> <p>Conclusion</p> <p>The release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients.</p

Imperfect Forward Secrecy: How Diffie-Hellman Fails in Practice

International audienceWe investigate the security of Diffie-Hellman key exchange as used in popular Internet protocols and find it to be less secure than widely believed. First, we present Logjam, a novel flaw in TLS that lets a man-in-the-middle downgrade connections to " export-grade " Diffie-Hellman. To carry out this attack, we implement the number field sieve discrete log algorithm. After a week-long precomputation for a specified 512-bit group, we can compute arbitrary discrete logs in that group in about a minute. We find that 82% of vulnerable servers use a single 512-bit group, allowing us to compromise connections to 7% of Alexa Top Million HTTPS sites. In response, major browsers are being changed to reject short groups. We go on to consider Diffie-Hellman with 768-and 1024-bit groups. A small number of fixed or standardized groups are in use by millions of servers. Performing precomputations for just ten of these groups would allow a passive eavesdropper to decrypt traffic to up to 66% of IPsec VPN servers, 26% of SSH servers, 24% of popular HTTPS sites, or 16% of SMTP servers. In the 1024-bit case, we estimate that such computations are plausible given nation-state resources, and a close reading of published NSA leaks shows that the agency's attacks on VPNs are consistent with having achieved such a break. We conclude that moving to stronger key exchange methods should be a priority for the Internet community

Imperfect forward secrecy: How Diffie-Hellman fails in practice

International audienceWe investigate the security of Diffie-Hellman key exchange as used in popular Internet protocols and find it to be less secure than widely believed. First, we present Logjam, a novel flaw in TLS that lets a man-in-the-middle downgrade connections to "export-grade" Diffie-Hellman. To carry out this attack, we implement the number field sieve discrete logarithm algorithm. After a week-long precomputation for a specified 512-bit group, we can compute arbitrary discrete logarithms in that group in about a minute. We find that 82% of vulnerable servers use a single 512-bit group, and that 8.4% of Alexa Top Million HTTPS sites are vulnerable to the attack. a In response, major browsers have changed to reject short groups. We go on to consider Diffie-Hellman with 768-and 1024-bit groups. We estimate that even in the 1024-bit case, the computations are plausible given nation-state resources. A small number of fixed or standardized groups are used by millions of servers; performing precomputation for a single 1024-bit group would allow passive eavesdropping on 18% of popular HTTPS sites, and a second group would allow decryption of traffic to 66% of IPsec VPNs and 26% of SSH servers. A close reading of published NSA leaks shows that the agency's attacks on VPNs are consistent with having achieved such a break. We conclude that moving to stronger key exchange methods should be a priority for the Internet community