Genital chronic graft-versus-host disease: an unmet need that requires trained gynecologists.

OBJECTIVE: Menopause and chronic graft-versus-host disease (cGvHD) are the leading causes of morbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT). Genitalia are one of the target organs of cGvHD causing sexual dysfunction and local symptoms, which may impair women's quality of life. The aim of this study is to describe the prevalence and clinical characteristics of genital cGvHD. METHODS: A retrospective cross-sectional observational study was performed including 85 women with alloHSCT. All women were diagnosed and counseled by a trained gynecologist. Health-related quality of life was assessed by the Cervantes Short-Form Scale and sexual function was evaluated by the Female Sexual Function Index. RESULTS: Seventeen women (20%) included in the study were diagnosed with genital cGvHD. The main complaints were vulvovaginal dryness (42.2%) and dyspareunia (29.4%), the presence of erythema/erythematous plaques (52.9%) being the most frequent sign. Median time from transplant to diagnosis of genital cGvHD was 17 months among those with mild involvement, 25 months for moderate and 42 months for severe forms. Mortality was 29.4% in patients who developed cGvHD with genital involvement versus 8.8% among those without (p = 0.012). CONCLUSION: Early gynecological evaluation might allow to identify patients with mild forms of genital cGvHD, potentially enabling better management and improved outcomes.

Efficacy and Safety of Up-dosing Antihistamines in Chronic Spontaneous Urticaria: A Systematic Review of the Literature.

BACKGROUND AND OBJECTIVES: According to current guidelines, oral antihistamines are the first-line treatment for chronic spontaneous urticaria (CSU). Up-dosing antihistamines to 4-fold the licensed dose is recommended if control is not achieved. Such indications are based mainly on expert opinion. Objectives: To critically review and analyze clinical evidence on the efficacy and safety of higher-than-licensed dosage of second-generation oral antihistamines in the treatment of CSU. MATERIAL AND METHODS: A systematic literature review was performed following a sensitive search strategy. All articles published in PubMed, EMBASE, and the Cochrane Library between 1961 and October 2018 were examined. Publications with CSU patients prescribed secondgeneration antihistamines in monotherapy compared with placebo, licensed dosages, and/or higher dosages were included. Articles were evaluated by peer reviewers. Quality was evaluated using the Jadad and Oxford scores. RESULTS: We identified 337 articles, of which 14 were included in the final evaluation (fexofenadine, 6; cetirizine, 2; levocetirizine and desloratadine, 1; levocetirizine, 1; rupatadine, 2; ebastine, 1; and bilastine, 1). Only 5 studies were placebo-controlled. The number of patients included ranged from 20 to 439. The observation lapse was ≤16 weeks. High fexofenadine doses produced a significant dosedependent response and controlled urticaria in most patients. Cetirizine, levocetirizine, rupatadine, and bilastine were more effective in up-dosing. The most frequent adverse events were headache and drowsiness. CONCLUSION: The low quality and heterogeneity of the articles reviewed made it impossible to reach robust conclusions and reveal the need for large-scale randomized clinical trials.

The dominant limb preferentially stabilizes posture in a bimanual task with physical coupling.

Humans are endowed with an ability to skillfully handle objects, like when holding a jar with the nondominant hand while opening the lid with the dominant hand. Dynamic dominance, a prevailing theory in handedness research, proposes that the nondominant hand is specialized for postural stability, which would explain why right-handed people hold the jar steady using the left hand. However, the underlying specialization of the nondominant hand has only been tested unimanually, or in a bimanual task where the two hands had different functions. Using a dedicated dual-wrist robotic interface, we tested the dynamic dominance hypothesis in a bimanual task where both hands carry out the same function. We examined how left- and right-handed subjects held onto a vibrating virtual object using their wrists, which were physically coupled by the object. Muscular activity of the wrist flexors and extensors revealed a preference for cocontracting the dominant hand during both holding and transport of the object, which suggests proficiency in the dominant hand for stabilization, contradicting the dynamic dominance hypothesis. While the reliance on the dominant hand was partially explained by its greater strength, the Edinburgh inventory was a better predictor of the difference in the cocontraction between the dominant and nondominant hands. When provided with redundancy to stabilize the task, the dominant hand preferentially cocontracts to absorb perturbing forces.NEW & NOTEWORTHY We found that subjects prefer to stabilize a bimanually held object by cocontracting their dominant limb, contradicting the established view that the nondominant limb is specialized toward stabilization.

Histological findings after non-ablative Er:YAG laser therapy in women with severe vaginal atrophy.

Objective: The aim of this study was to evaluate the effect of non-ablative erbium vaginal laser treatment on vaginal mucosa tissue affected by severe atrophy.Methods: Ten patients with severe genitourinary syndrome of menopause were treated with two sessions of the non-ablative erbium-doped yttrium aluminium garnet laser (Er:YAG laser) separated by 4 weeks. Vaginal biopsies were performed before and 3 months after the second treatment. The improvement in vaginal atrophy was assessed using multiple measuring tools before and 6 months after the treatment. The degree of patients' satisfaction was also assessed.Results: Microscopic examination showed significant changes in the main structural components of the vaginal wall mucosa after two non-ablative Er:YAG laser sessions. The epithelial thickness increased from 45 µm (10-106 µm) to 153 µm (97-244 µm) measured 3 months after the final laser treatment. Vaginal atrophy improved in all patients by all measured outcomes. The degree of patient satisfaction was very high (3.6 on the Likert four-point scale). No adverse events or complications were observed in any of the sessions. Conclusion: The non-ablative Er:YAG laser seems to be a safe and effective method to increase epithelial thickness of the vaginal mucosa in patients with severe vaginal atrophy.

Relationships of body surface thermography with core temperature, birth weight and climatic variables in neonatal lambs born during early spring in an arid region.

The main cause of death in newborn lambs is hypothermia, so is necessary to identify the factors affecting variations in body surface temperatures of sheep neonates because approximately 60% of their body heat losses occur through the skin. This study aimed to establish relationships among body surface thermography from different regions with rectal temperature (RT), birth weight (BW) and climatic variables in hair breed newborn lambs during early spring in an arid region. Data of body surface temperatures measured by infrared thermography (entire head, eye, muzzle, ear, entire body, shoulder, rump, loin, right flank, belly and leg), RT and BW were collected at 0, 12 and 24 h post-lambing in 85 lambs born in early spring. Relative humidity [RH], temperature [Te] and temperature-humidity index [THI] were also recorded. RT was not correlated with surface temperatures at 0 and 24 h, but it was at 12 h with all of them (0.36 ≤ r ≤ 0.44). BW and some surface temperatures were negatively correlated at 0 and 24 h (-0.24 ≤ r ≤ -0.30), but positively at 12 h (0.25 ≤ r ≤ 0.27). All surface temperatures were positively correlated (0.51 ≤ r ≤ 0.85) with Te and THI in the three sampling times. Principal component (PC) analysis showed that PC1 explained the majority of the variance (71-72%), followed by PC2 (8-9%) at 0, 12 and 24 h. Body surface temperatures increased as Te and THI also increased, but decreased with the increase in HR. In conclusion, under early spring environment (predominantly cold), the variations in body surface temperatures of hair sheep neonates were more closely related to climatic variables than to RT and BW. Thermography proved to be an effective tool to determine body heat loss by radiation in skin of neonate lambs.

Application of thermal lens microscopy (TLM) for measurement of Cr(VI) traces in wastewater.

In this work, we demonstrate for the first time that Thermal Lens Microscopy technique (TLM) can be applied to monitor the dynamics of a photocatalytic process in-situ. The photocatalytic reduction of hexavalent chromium -Cr(VI)- in aqueous solution using CdS and irradiated with visible light is monitored by TLM. Since the values of Cr(VI) concentration obtained after the photocatalytic process were close to those imposed by the international regulations for drinking water, the use of TLM allowed its measurement with a better reliability than with UV spectroscopy, usually used in this kind of analysis.

The coexistence temperature of hydrogen clathrates: A molecular dynamics study.

Extensive molecular dynamics simulations in the equilibrium isobaric-isothermal (NPT) ensemble were developed to determine the coexistence temperatures of the water hydrogen mixture using the direct coexistence method. The water molecules were modeled using the four-site TIP4P/Ice analytical potential, and the hydrogen molecules were described using a three-site potential. The simulations were performed at different pressures (p = 900, 1500, 3000, and 4000 bars). At each pressure, a series of simulations were developed at different temperatures (from 230 to 270 K). Our results followed a line parallel to the experimental coexistence temperatures and underestimated these temperatures by approximately 25 K in the investigated range. The final configurations could or could not contain a fluid phase depending on the pressure, in accordance with the phase diagram. In addition, we explored the dynamics of the H2 molecules through clathrate hydrate cages and observed different behaviors of the H2 molecules in the small cages and the large cages of the sII structure.

Thermoregulatory response to outdoor heat stress of hair sheep females at different physiological state.

Forty Dorper × Pelibuey sheep females were used to evaluate the effects of physiological state on physiological variables and serum concentrations of metabolites, thyroid hormones, and electrolytes under outdoor heat stress conditions. Females were selected as follows (n = 10 per group): weaning ewe lambs (WEL; 3 months old), replacement nulliparous ewes (RNE; 8 months old), non-pregnant and non-lactating multiparous ewes (NME; 3-4 years old) and lactating multiparous ewes (LME; 3-4 years old). While physiological variables were measured both morning and afternoon, blood samples were collected before feeding in the morning to determine all blood components. Three contrasts were constructed: (1) WEL vs. older ewes, (2) RNE vs. multiparous ewes, and (3) NME vs. LME. Compared with older ewes, WEL had higher (P < 0.01) rectal temperature (RT) and hair coat temperatures through the day, and also higher (P < 0.01) respiratory rate (RR) only in the afternoon. Serum levels of glucose and cholesterol were lower (P ≤ 0.02) in WEL than in older ewes. Nulliparous ewes compared with multiparous had always similar RT but higher (P ≤ 0.05) hair coat temperatures in most of the body regions by the morning and higher (P < 0.01) RR, without difference for hair coat temperatures in the afternoon. Only serum glucose (P = 0.07) and urea nitrogen (P < 0.01) levels were affected by parturition number, being lower in multiparous ewes. Regarding the effect of lactation, while RR was unaffected, afternoon RT and hair coat temperatures in most of the body regions through the day were higher (P ≤ 0.03) in lactating ewes. In addition, LME had lower (P < 0.01) serum levels of glucose, cholesterol, and urea nitrogen, but higher (P = 0.02) triiodothyronine levels than NME. In conclusion, ewe lambs and lactating ewes were less tolerant to heat stress, while nulliparous and multiparous ewes showed similar thermoregulatory ability.

Effects of an Educational Intervention on Breast Self-Examination, Breast Cancer Prevention-Related Knowledge, and Healthy Lifestyles in Scholars from a Low-Income Area in Bogota, Colombia.

The aim of this study was to evaluate the effects of an educational intervention on breast self-examination, cancer prevention-related knowledge, practices, and behavior change in scholars from a low-income area in Bogota, Colombia. Uncontrolled trial was conducted in 155 scholars. Two educational sessions, 90 min each, were carried out in March 2015 according to the Colombian guidelines for educational communication in the framework of cancer control. All participants completed a self-reported questionnaire at pre- and post-intervention, as well as 1, 3, and 6 months after the intervention. Breast self-examination was practiced by 78.1% of the scholars, and the overall knowledge of breast cancer risk factors was poor. The educational intervention resulted in significant improvements on breast self-examination practice, the knowledge of the technique, and the knowledge of the main risk factors for breast cancer as well as the practice of physical activity and vegetable intake at 6 months follow-up. An educational intervention according to the Colombian guidelines for educational communication in the framework of cancer control improved the practice of breast self-examination, cancer prevention-related knowledge, as well as the practice of physical activity and vegetable consumption in scholars from a low-income area in Bogota, Colombia. Further randomized controlled studies are warranted.

The psychometric properties of the Ages & Stages Questionnaires for ages 2-2.5: a systematic review.

BACKGROUND: Early identification of children with potential development delay is essential to ensure access to care. The Ages & Stages Questionnaires (ASQ) is used as population outcome indicators in England as part of the 2.5-year review. METHOD: The aim of this article was to systematically review the worldwide evidence for the psychometric properties of the ASQ third edition (ASQ-3TM ) and the Ages & Stages Questionnaires®: Social-Emotional (ASQ:SE). Eight electronic databases and grey literature were searched for original research studies available in English language, which reported reliability, validity or responsiveness of the ASQ-3TM or ASQ:SE for children aged between 2 and 2.5 years. Twenty studies were included. Eligible studies used either the ASQ-3TM or the ASQ:SE and reported at least one measurement property of the ASQ-3TM and/or ASQ:SE. Data were extracted from all papers identified for final inclusion, drawing on Cochrane guidelines. RESULTS: Using 'positive', 'intermediate' and 'negative' criteria for evaluating psychometric properties, results showed 'positive' reliability values in 11/18 instances reported, 'positive' sensitivity values in 13/18 instances reported and 'positive' specificity values in 19/19 instances reported. CONCLUSIONS: Variations in age or language versions used, quality of psychometric properties and quality of papers resulted in heterogeneous evidence. It is important to consider differences in cultural and contextual factors when measuring child development using these indicators. Further research is very likely to have an important impact on the interpretation of the ASQ-3TM and ASQ:SE psychometric evidence.

Rotavirus activates dendritic cells derived from umbilical cord blood monocytes.

Rotavirus is the most common cause of acute infectious diarrhea in human neonates and infants. However, the studies aimed at dissecting the anti-virus immune response have been mainly performed in adults. Dendritic cells (DCs) play a crucial role in innate and acquired immune responses. Therefore, it is very important to determine the response of neonatal and infant DCs to rotavirus and to compare it to the response of adult DCs. Thus, we determined the response of monocyte-derived DCs from umbilical cord blood (UCB) and adult peripheral blood (PB) to rotavirus in vitro. It was found that the rotavirus and its genome, composed of segmented doubled stranded RNA (dsRNA), induced the activation of neonatal DCs, as these cells up-regulated the levels of CD40, CD86, MHC II, TLR-3 and TLR-4, the production of cytokines IL-6, IL-12/23p40, IL-10, TGF-ß (but not of IL-12p70), and the message for TNF-α and IFN-ß. This activation enabled the neonatal DCs to induce a strong proliferation of allogeneic CD4+ T cells and the production of IFN-γ. Moreover, neonatal DCs could be infected by rotavirus and sustain its replication. Neonatal DCs had a similar response as adult DCs towards rotavirus and its genome. However, adult DCs had a biased pro-inflammatory response compared to neonatal DCs, which showed a biased regulatory profile, as they produced higher levels of IL-10 and TGF-ß, and were less efficient in inducing a Th1 type response. So it can be concluded that rotavirus and its genome can induce the activation of neonatal DCs in spite of their tolerogenic bias.

Effects of seasonal ambient heat stress (spring vs. summer) on physiological and metabolic variables in hair sheep located in an arid region.

Twenty Dorper × Pelibuey primiparous ewes were used to evaluate effects of seasonal ambient heat stress (i.e., spring vs. summer) on physiological and metabolic responses under production conditions in an arid region. Ten ewes experiencing summer heat stress (i.e., temperature = 34.8 ± 4.6 °C; THI = 81.6 ± 3.2 units) and 10 under spring thermoneutral conditions (temperature = 24.2 ± 5.4 °C; THI = 68.0 ± 4.8 units) were corralled together to measure rectal temperature, respiratory frequency, and skin temperatures at 0600, 1200, 1800, and 2400 h on four occasions over 40 days. Blood metabolite and electrolyte concentrations were also measured at 0600 and 1800 hours. Data were analyzed with a completely randomized design using repeated measurements in time. Rectal and skin temperatures, as well as respiratory frequency, were higher (P < 0.01) in summer than spring at all measured days. Blood serum glucose, cholesterol, triglycerides, and chlorine concentrations were lower (P < 0.01) in summer than spring at 0800 and 1800 hours. In contrast, summer heat stress increased (P < 0.01) blood urea and potassium concentrations at 0800 and 1800 hours. Compared with spring thermoneutral conditions, summer heat stress affected the physiological and metabolic status of hair breed ewes in an arid region, which included blood metabolite and electrolyte adjustments to efficiently cope with summer heat stress.

The thioredoxin/peroxiredoxin/sulfiredoxin system: current overview on its redox function in plants and regulation by reactive oxygen and nitrogen species.

In plants, the presence of thioredoxin (Trx), peroxiredoxin (Prx), and sulfiredoxin (Srx) has been reported as a component of a redox system involved in the control of dithiol-disulfide exchanges of target proteins, which modulate redox signalling during development and stress adaptation. Plant thiols, and specifically redox state and regulation of thiol groups of cysteinyl residues in proteins and transcription factors, are emerging as key components in the plant response to almost all stress conditions. They function in both redox sensing and signal transduction pathways. Scarce information exists on the transcriptional regulation of genes encoding Trx/Prx and on the transcriptional and post-transcriptional control exercised by these proteins on their putative targets. As another point of control, post-translational regulation of the proteins, such as S-nitrosylation and S-oxidation, is of increasing interest for its effect on protein structure and function. Special attention is given to the involvement of the Trx/Prx/Srx system and its redox state in plant signalling under stress, more specifically under abiotic stress conditions, as an important cue that influences plant yield and growth. This review focuses on the regulation of Trx and Prx through cysteine S-oxidation and/or S-nitrosylation, which affects their functionality. Some examples of redox regulation of transcription factors and Trx- and Prx-related genes are also presented.

Ultrasound-guided intermediate cervical plexus block for carotid endarterectomy using a new anterior approach: a two-centre prospective observational study.

The aim of this prospective, double-centre, observational study performed in 116 patients was to describe a new anterior approach of ultrasound-guided intermediate cervical plexus block for carotid endarterectomy. The median (IQR [range]) volume of ropivacaine 0.5% administered was 30 (25-30 [20-45]) ml. Supplemental local anaesthesia (infiltration and topical) was needed in 66 (57%) patients. Overall, 41 (35%) patients needed additional sedation (18 midazolam; 23 remifentanil). There was no intra-operative complication or systemic toxicity of ropivacaine. One regional anaesthesia procedure was converted to general anaesthesia because of patient agitation. Adverse effects were of short duration and did not affect surgery. Satisfaction scores were high for 92 (79%) patients (63 satisfied; 29 very satisfied) and 104 (90%) surgeons (51 satisfied; 53 very satisfied). This study shows that the ultrasound-guided intermediate cervical plexus block using an anterior approach is feasible and provides similar results to other regional techniques during carotid endarterectomy.

Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors.

The Y155H amino acid substitution in the neuraminidase gene (NA) has previously been associated with highly reduced inhibition by neuraminidase inhibitors in the seasonal H1N1 influenza A virus which circulated in humans before the 2009 pandemic. During the 2012/13 epidemic season in Spain, two A(H1N1) pdm09 viruses bearing the specific Y155H substitution in the NA were detected and isolated from two patients diagnosed with severe respiratory syndrome and pneumonia requiring admission to the intensive care unit. Contrary to what was observed in the seasonal A(H1N1) viruses, neither of the Y155H A(H1N1) pdm09 viruses described here showed a phenotype of reduced inhibition by NAIs as determined by the neuraminidase enzyme inhibition assay (MUNANA). High-throughput sequencing of the NA of both Y155H viruses showed that they were composed to >99% of H155 variants. We believe that this report can contribute to a better understanding of the biological significance of amino acid substitutions in the neuraminidase protein with regard to susceptibility of influenza viruses to neuraminidase inhibitors. This is of critical importance for optimal management of influenza disease patients.

Proteasome-dependent degradation of histone H1 subtypes is mediated by its C-terminal domain.

Histone H1 is involved in chromatin compaction and dynamics. In human cells, the H1 complement is formed by different amounts of somatic H1 subtypes, H1.0-H1.5 and H1X. The amount of each variant depends on the cell type, the cell cycle phase, and the time of development and can be altered in disease. However, the mechanisms regulating H1 protein levels have not been described. We have analyzed the contribution of the proteasome to the degradation of H1 subtypes in human cells using two different inhibitors: MG132 and bortezomib. H1 subtypes accumulate upon treatment with both drugs, indicating that the proteasome is involved in the regulation of H1 protein levels. Proteasome inhibition caused a global increase in cytoplasmatic H1, with slight changes in the composition of H1 bound to chromatin and chromatin accessibility and no alterations in the nucleosome repeat length. The analysis of the proteasome degradation pathway showed that H1 degradation is ubiquitin-independent. The whole protein and its C-terminal domain can be degraded directly by the 20S proteasome in vitro. Partial depletion of PA28γ revealed that this regulatory subunit contributes to H1 degradation within the cell. Our study shows that histone H1 protein levels are under tight regulation to prevent its accumulation in the nucleus. We revealed a new regulatory mechanism for histone H1 degradation, where the C-terminal disordered domain is responsible for its targeting and degradation by the 20S proteasome, a process enhanced by the regulatory subunit PA28γ.