Exposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent.
To ...investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters.
Men living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman’s correlation.
We found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25–80); whereas lead (OR = 4.51, 95%CI 0.86–23) and cadmium (OR = 3.45, 95%CI 0.77–16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility.
Our findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements
•Cd may impact negatively on Total sperm count.•Pb and Cd may impact negatively on Progressive sperm motility.•Se may have beneficial effects on detrimental ones of Cd and Pb.•These results may be useful for therapeutic and preventive intervention.
Effects of violence on transgender people Testa, Rylan J; Sciacca, Laura M; Wang, Florence ...
Professional psychology, research and practice,
10/2012, Letnik:
43, Številka:
5
Journal Article
Recenzirano
While recent research on transgender populations has demonstrated high rates of experiencing violence, there has been little research attention to the mental health implications of these experiences. ...This study utilized data collected from the Virginia Transgender Health Initiative Survey (THIS) of transgender people (individuals who described their gender identity as different from their sex assigned at birth) collected from 2005–2006. Current study analyses were limited to two subgroups: trans women (n = 179) and trans men (n = 92). We hypothesized that, as in the general population, exposure to physical and sexual violence would be related to suicidal ideation, suicide attempts, and substance abuse. Both trans women and trans men in this sample were at high risk for physical and sexual violence, as well as suicidal ideation and suicide attempt. Logistic regression analyses indicated that among both trans women and trans men, those who had endured physical and/or sexual violence were significantly more likely than those who had not had such experiences to report a history of suicide attempt and multiple suicide attempts. In addition, among trans men, history of physical and sexual violence were each related to alcohol abuse. Among trans women, history of sexual violence was related to alcohol abuse and illicit substance use. Patterns of violence against transgender people were identified and are discussed, including frequent gender-related motivation for violence, low prevalence of reporting violence to police, and variety of perpetrators of violence. Clinical implications and recommendations are provided. (PsycINFO Database Record (c) 2016 APA, all rights reserved) (Source: journal abstract)
Throughout much of the suicide literature, statistical methods for predicting suicide risk have employed techniques that are oftentimes insensitive for generating meaningful conclusions or ...inappropriate due to varying amounts of follow-up in longitudinal studies. Previous studies investigating risk factors for suicide among transgender individuals have also suffered from similar methodological and statistical limitations. With use of survival analytic techniques, the present study aimed to establish the temporal relationship between risk factors and suicide attempts for this population. This study constituted a secondary analysis of retrospective data gathered from 2005 to 2006 through the Virginia Transgender Health Initiative Survey and was limited to two subgroups within the overall sample of 350 participants: trans women (n = 179) and trans men (n = 92). Utilizing Cox proportional hazards models with time-dependent covariates, the effect of physical violence, sexual violence, illicit substance use, and problematic drinking behavior on risk of first suicide attempt was examined. It was found that past physical violence, sexual violence, and illicit drug use more than doubled the risk of first suicide attempt. Further, both past physical violence and illicit drug use were found to be independent risk factors in the multivariable Cox proportional hazards model, corresponding to a substantial increase in risk when both factors were present. The effect of identified risk factors on subsequent suicide attempts was assessed using logistic regression analysis. Only exposure to past sexual violence significantly affected risk of subsequent suicide attempts. Differences between trans women and trans men subgroups were also investigated in relation to suicide risk but did not yield significant findings. Post-hoc analyses explored the potential protective effect of living full-time in their gender identity of choice as well as the impact of prior physical violence, sexual violence, and/or illicit drug use on first suicide attempt among transgender youth. By quantifying the magnitude of the effect of various risk factors on suicide attempts, a rationale is provided for developing programs aimed at risk prevention and early intervention. Further, recommendations are proposed to promote culturally competent suicide risk assessment and management strategies among clinicians assisting transgender individuals.
Alzheimer’s disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and ...phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu2+ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu2+ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of Aβ:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu2+ complexes.
Alzheimer’s disease (AD) is linked to the abnormal accumulation of amyloid β peptide (Aβ) aggregates in the brain. Silybin B, a natural compound extracted from milk thistle (Silybum marianum), has ...been shown to significantly inhibit Aβ aggregation in vitro and to exert neuroprotective properties in vivo. However, further explorations of silybin B’s clinical potential are currently limited by three main factors: (a) poor solubility, (b) instability in blood serum, and (c) only partial knowledge of silybin’s mechanism of action. Here, we address these three limitations. We demonstrate that conjugation of a trehalose moiety to silybin significantly increases both water solubility and stability in blood serum without significantly compromising its antiaggregation properties. Furthermore, using a combination of biophysical techniques with different spatial resolution, that is, TEM, ThT fluorescence, CD, and NMR spectroscopy, we profile the interactions of the trehalose conjugate with both Aβ monomers and oligomers and evidence that silybin may shield the “toxic” surfaces formed by the N-terminal and central hydrophobic regions of Aβ. Finally, comparative analysis with silybin A, a less active diastereoisomer of silybin B, revealed how even subtle differences in chemical structure may entail different effects on amyloid inhibition. The resulting insight on the mechanism of action of silybins as aggregation inhibitors is anticipated to facilitate the future investigation of silybin’s therapeutic potential.
Alzheimer’s disease (AD) is the most common cause of dementia, characterized by a spectrum of symptoms associated with memory loss and cognitive decline with deleterious consequences in everyday ...life. The lack of specific drugs for the treatment and/or prevention of this pathology makes AD an ever-increasing economic and social emergency. Oligomeric species of amyloid-beta (Aβ) are recognized as the primary cause responsible for synaptic dysfunction and neuronal degeneration, playing a crucial role in the onset of the pathology. Several studies have been focusing on the use of small molecules and peptides targeting oligomeric species to prevent Aβ aggregation and toxicity. Among them, peptide fragments derived from the primary sequence of Aβ have also been used to exploit any eventual recognition abilities toward the full-length Aβ parent peptide. Here, we test the Aβ8‑20 fragment which contains the self-recognizing Lys-Leu-Val-Phe-Phe sequence and lacks Arg 5 and Asp 7 and the main part of the C-terminus, key points involved in the aggregation pathway and stabilization of the fibrillary structure of Aβ. In particular, by combining chemical and biological techniques, we show that Aβ8‑20 does not undergo random coil to β sheet conformational transition, does not form amyloid fibrils by itself, and is not toxic for neuronal cells. Moreover, we demonstrate that Aβ8‑20 mainly interacts with the 4–11 region of Aβ1‑42 and inhibits the formation of toxic oligomeric species and Aβ fibrils. Finally, our data show that Aβ8‑20 protects neuron-like cells from Aβ1‑42 oligomer toxicity. We propose Aβ8‑20 as a promising drug candidate for the treatment of AD.
Omicron spike (S) encoding vaccines as boosters, are a potential strategy to improve COVID-19 vaccine efficacy against Omicron. Here, macaques (mostly females) previously immunized with Ad26.COV2.S, ...are boosted with Ad26.COV2.S, Ad26.COV2.S.529 (encoding Omicron BA.1 S) or a 1:1 combination of both vaccines. All booster vaccinations elicit a rapid antibody titers increase against WA1/2020 and Omicron S. Omicron BA.1 and BA.2 antibody responses are most effectively boosted by vaccines including Ad26.COV2.S.529. Independent of vaccine used, mostly WA1/2020-reactive or WA1/2020-Omicron BA.1 cross-reactive B cells are detected. Ad26.COV2.S.529 containing boosters provide only slightly higher protection of the lower respiratory tract against Omicron BA.1 challenge compared with Ad26.COV2.S-only booster. Antibodies and cellular immune responses are identified as complementary correlates of protection. Overall, a booster with an Omicron-spike based vaccine provide only moderately improved immune responses and protection compared with the original Wuhan-Hu-1-spike based vaccine, which still provide robust immune responses and protection against Omicron.
Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Approximately 40% of patients do not ...respond to individual biologic therapies and 5-20% are refractory to all. In a biopsy-based, precision-medicine, randomized clinical trial in RA (R4RA; n = 164), patients with low/absent synovial B cell molecular signature had a lower response to rituximab (anti-CD20 monoclonal antibody) compared with that to tocilizumab (anti-IL6R monoclonal antibody) although the exact mechanisms of response/nonresponse remain to be established. Here, in-depth histological/molecular analyses of R4RA synovial biopsies identify humoral immune response gene signatures associated with response to rituximab and tocilizumab, and a stromal/fibroblast signature in patients refractory to all medications. Post-treatment changes in synovial gene expression and cell infiltration highlighted divergent effects of rituximab and tocilizumab relating to differing response/nonresponse mechanisms. Using ten-by-tenfold nested cross-validation, we developed machine learning algorithms predictive of response to rituximab (area under the curve (AUC) = 0.74), tocilizumab (AUC = 0.68) and, notably, multidrug resistance (AUC = 0.69). This study supports the notion that disease endotypes, driven by diverse molecular pathology pathways in the diseased tissue, determine diverse clinical and treatment-response phenotypes. It also highlights the importance of integration of molecular pathology signatures into clinical algorithms to optimize the future use of existing medications and inform the development of new drugs for refractory patients.
Maternal high blood glucose during pregnancy increases the risk for both maternal and fetal adverse outcomes. The mechanisms underlying the regulator effects of hyperglycemia on placental development ...and growth have not been fully illustrated yet. The placenta expresses high amounts of both insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R). It has been reported that the placenta of diabetic women has structural and functional alterations and the insulin/IGF system is likely to play a role in these changes. The aim of the present study was to measure the content of IR and IGF-1R and their phosphorylation in the placenta of women with type 1 diabetes mellitus (T1D) or with gestational diabetes mellitus (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy.
Placental tissues were obtained from 80 Caucasian women with a singleton pregnancy. In particular, we collected placenta samples from 20 T1D patients, 20 GDM patients and 40 NGT women during pregnancy. Clinical characteristics and anthropometric measures of all women as well as delivery and newborn characteristics were recorded. Patients were also subdivided on the basis of peripartum glycemia either ≥90 mg/dl or <90 mg/dl, regardless of the diagnosis.
In T1D patients, a higher rate of adverse outcomes was observed. Compared to the GDM women, the T1D group showed significantly higher average capillary blood glucose levels at the third trimester of pregnancy and at peripartum, and higher third-trimester HbA1c values. In both T1D and GDM women, HbA1c values during pregnancy correlated with glucose values in the peripartum period (R-squared 0.14, p=0.02). A positive correlation was observed between phosphorylation of placental IR and the glucose levels during the third trimester of GDM and T1D pregnancy (R-squared 0.21, p=0.003). In the placenta of T1D patients, IGF-1R phosphorylation and IR isoform A (IR-A) expression were significantly increased (p=0.006 and p=0.040, respectively), compared to the NGT women. Moreover, IGF-1R phosphorylation was significantly increased (p<0.0001) in the placenta of patients with peripartum glucose >90 mg/dl, while IR-A expression was increased in those with peripartum blood glucose higher than 120 mg/dl (p=0.046).
To the best of our knowledge, our study represents the first one in which an increased maternal blood glucose level during pregnancy is associated with an increased IGF-1R phosphorylation and IR-A expression in the placenta. Both these mechanisms can promote an excessive fetal growth.
Alzheimer's disease (AD) is the most common cause of dementia, characterized by a spectrum of symptoms associated with memory loss and cognitive decline with deleterious consequences in everyday ...life. The lack of specific drugs for the treatment and/or prevention of this pathology makes AD an ever-increasing economic and social emergency. Oligomeric species of amyloid-beta (Aβ) are recognized as the primary cause responsible for synaptic dysfunction and neuronal degeneration, playing a crucial role in the onset of the pathology. Several studies have been focusing on the use of small molecules and peptides targeting oligomeric species to prevent Aβ aggregation and toxicity. Among them, peptide fragments derived from the primary sequence of Aβ have also been used to exploit any eventual recognition abilities toward the full-length Aβ parent peptide. Here, we test the Aβ
fragment which contains the self-recognizing Lys-Leu-Val-Phe-Phe sequence and lacks Arg 5 and Asp 7 and the main part of the C-terminus, key points involved in the aggregation pathway and stabilization of the fibrillary structure of Aβ. In particular, by combining chemical and biological techniques, we show that Aβ
does not undergo random coil to β sheet conformational transition, does not form amyloid fibrils by itself, and is not toxic for neuronal cells. Moreover, we demonstrate that Aβ
mainly interacts with the 4-11 region of Aβ
and inhibits the formation of toxic oligomeric species and Aβ fibrils. Finally, our data show that Aβ
protects neuron-like cells from Aβ
oligomer toxicity. We propose Aβ
as a promising drug candidate for the treatment of AD.
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