Gene expression analysis reveals diabetes-related gene signatures.

BACKGROUND: Diabetes is a spectrum of metabolic diseases affecting millions of people worldwide. The loss of pancreatic ß-cell mass by either autoimmune destruction or apoptosis, in type 1-diabetes (T1D) and type 2-diabetes (T2D), respectively, represents a pathophysiological process leading to insulin deficiency. Therefore, therapeutic strategies focusing on restoring ß-cell mass and ß-cell insulin secretory capacity may impact disease management. This study took advantage of powerful integrative bioinformatic tools to scrutinize publicly available diabetes-associated gene expression data to unveil novel potential molecular targets associated with ß-cell dysfunction. METHODS: A comprehensive literature search for human studies on gene expression alterations in the pancreas associated with T1D and T2D was performed. A total of 6 studies were selected for data extraction and for bioinformatic analysis. Pathway enrichment analyses of differentially expressed genes (DEGs) were conducted, together with protein-protein interaction networks and the identification of potential transcription factors (TFs). For noncoding differentially expressed RNAs, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which exert regulatory activities associated with diabetes, identifying target genes and pathways regulated by these RNAs is fundamental for establishing a robust regulatory network. RESULTS: Comparisons of DEGs among the 6 studies showed 59 genes in common among 4 or more studies. Besides alterations in mRNA, it was possible to identify differentially expressed miRNA and lncRNA. Among the top transcription factors (TFs), HIPK2, KLF5, STAT1 and STAT3 emerged as potential regulators of the altered gene expression. Integrated analysis of protein-coding genes, miRNAs, and lncRNAs pointed out several pathways involved in metabolism, cell signaling, the immune system, cell adhesion, and interactions. Interestingly, the GABAergic synapse pathway emerged as the only common pathway to all datasets. CONCLUSIONS: This study demonstrated the power of bioinformatics tools in scrutinizing publicly available gene expression data, thereby revealing potential therapeutic targets like the GABAergic synapse pathway, which holds promise in modulating α-cells transdifferentiation into ß-cells.

Motor Reaction Time, Sarcopenia and Functional Skills in Elderly Women: A Cross-Sectional Study.

IMPORTANCE: Aging generates changes over the years. Because of this, the musculoskeletal system is directly degraded and suffer deficits in its performance in elderly patients with Sarcopenia, as this condition is characterized by a decrease in muscle mass and function. OBJECTIVE: Correlate the motor reaction time and functional skills of non-sarcopenic, pre-sarcopenic and sarcopenic elderly women, and analyze influence on the risk of falls. DESIGN: Cross-sectional observational analytical study, following the methodological strategies of STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), carried out under the approval of the Research Ethics Committee of the Unievangélica University, no. 3.694.235/2019. SETTING: Participants were evaluated regarding: cognitive status, level of physical activity, fear of falling, body composition, motor reaction time, static and dynamic balance, gait kinetics, strength and endurance of the lower limbs and finally handgrip strength. PARTICIPANTS: A total of 59 volunteer elderly women were assessed following the diagnostic criteria for sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). RESULTS: The results show that there was a greater difference in motor reaction time between the non-sarcopenic and sarcopenic elderly women due to the executing organ being damaged by the presence of sarcopenia, causing motor response to slowdown. Functional deficit, fear of falling and greater risk of falls were observed in the sarcopenic group, under the harmful influence of increased motor reaction time. CONCLUSION: Sarcopenic elderly women present increased motor reaction time, that is, slowed motor responses due to decreased muscle mass, strength and impaired musculature, which generate functional deficits that contribute to an increased risk of falls.

Microbial Indicators of Dental Health, Dysbiosis, and Early Childhood Caries.

Dental caries lesions are a clinical manifestation of disease, preceded by microbial dysbiosis, which is poorly characterized and thought to be associated with saccharolytic taxa. Here, we assessed the associations between the oral microbiome of children and various caries risk factors such as demographics and behavioral and clinical data across early childhood and characterized over time the salivary and dental plaque microbiome of children before clinical diagnosis of caries lesions. Children (N = 266) were examined clinically at ~1, 2.5, 4, and 6.5 y of age. The microbiome samples were collected at 1, 2.5, and 4 y. Caries groups consisted of children who remained caries free (International Caries Detection and Assessment System [ICDAS] = 0) at all time points (CFAT) (n = 50); children diagnosed with caries (ICDAS ≥ 1) at 6.5 y (C6.5), 4 y (C4), or 2.5 y of age (C2.5); and children with early caries or advanced caries lesions at specific time points. Microbial community analyses were performed on zero-radius operational taxonomic units (zOTUs) obtained from V4 of 16S ribosomal RNA gene amplicon sequences. The oral microbiome of the children was affected by various factors, including antibiotic use, demographics, and dietary habits of the children and their caregivers. At all time points, various risk factors explained more of the variation in the dental plaque microbiome than in saliva. At 1 y, composition of saliva of the C4 group differed from that of the CFAT group, while at 2.5 y, this difference was observed only in plaque. At 4 y, multiple salivary and plaque zOTUs of genera Prevotella and Leptotrichia were significantly higher in samples of the C6.5 group than those of the CFAT group. In conclusion, up to 3 y prior to clinical caries detection, the oral microbial communities were already in a state of dysbiosis that was dominated by proteolytic taxa. Plaque discriminated dysbiotic oral ecosystems from healthy ones better than saliva.

Abdominal TRPV1 channel desensitization enhances stress-induced hyperthermia during social stress in rats.

AIMS: In rats, stress-induced hyperthermia caused by social interaction depends on brown adipose tissue (BAT) thermogenesis and peripheral vasoconstriction. However, the peripheral mechanisms responsible for regulating the level of hyperthermia during social stress are still unknown. The transient receptor potential vanilloid 1 (TRPV1) subfamily, expressed in sensory and visceral neurons, can serve as a thermoreceptor. Here, we tested the hypothesis that the abdominal TRPV1 is essential in regulating stress-induced hyperthermia during social stress. MAIN METHODS: Male Wistar rats received an intraperitoneal injection of Resiniferatoxin (RTX) - an ultra-potent capsaicin analog, (i.e., to desensitize the TRPV1 channels) or vehicle. Seven days later, we evaluated the effects of abdominal TRPV1 channels desensitization on core body temperature (CBT), brown adipose tissue (BAT) temperature, tail skin temperature, and heart rate (HR) of rats subjected to a social stress protocol. KEY FINDINGS: We found abdominal TRPV1 desensitization increased CBT and BAT temperature but did not change tail skin temperature and HR during rest. However, under social stress, we found that abdominal TRPV1 desensitization heightened the increase in CBT and BAT caused by stress. Also, it abolished the increase in tail skin temperature that occurs during and after social stress. TRPV1 desensitization also delayed the HR recovery after the exposure to the social stress. SIGNIFICANCE: These results show that abdominal TRPV1 channels desensitization heightens stress-induced hyperthermia, causing heat dissipation during and after social stress, enabling optimal thermal control during social encounters.

The Current Regulations in Handling Autopsy of COVID-19 Corpses: A Narrative Review.

The COVID-19 pandemic has affected millions of people around the world either directly or indirectly. Deaths have been attributed to COVID-19 as the underlying cause of death or as a contributing cause of death. It is estimated that millions of excess deaths were associated with the COVID-19 pandemic in 2020 and 2021. The importance of a clinical autopsy on COVID-19 corpses lies in understanding the pathogenesis of the disease better. Moreover, a forensic autopsy may be performed on a COVID-19-infected corpse when indicated for medico-legal purposes. From the autopsy perspective, handling COVID-19-infected corpses requires specific guidelines and safety measures to be followed to limit the transmission of SARS-CoV-2, the causative virus. This is essential as COVID-19 is an emerging infectious disease caused by a newly discovered virus. This review narrates the safety measures that should be followed at different stages of handling COVID-19 corpses, starting from the death scene to burial and funeral. Ethical issues in handling COVID-19 corpses are also briefed in this review. As COVID-19 can be transmitted through infected bodies, it is crucial to wear recommended personal protective equipment, specifically for aerosol-generating procedures. There are specific safety measures to be considered before transporting the body to the mortuary, with particular requirements to be implemented there, such as specific engineering controls, staff training, and autopsy room precautions. After conducting the autopsy, disinfection of the tools and equipment, body bags, transport vehicles, and the autopsy room should be considered.

Predictability of Sex from Frontal Sinus in Nepalese Population.

Background Various methods had been used for personal identification. Scientific basis of identification was initiated and progressed after 19th century which may be attributed to various scientists. With the invention of X-ray the field of identification further progressed. Modern radiological diagnostic equipments have greatly assisted in the field of forensic. Frontal sinuses are paired lobulated air cavities located posterior to superciliary arches in the frontal bone. Computed Tomography is best used to study frontal sinuses. Objective To evaluate bilateral Frontal sinus for sexual dimorphism using Computed Tomography. Method Anterior posterior length, transverse width and height of the bilateral Frontal sinus were directly measured on CT DICOM image, using Electronic Caliper in DICOM viewer software. A total 100 CT scans, 50 of each sex were collected was analysed using SPSS-20 in present study. Result The mean age distribution for male is 34.74±8.66, and for females 35.34±8.88. The mean of all the measurements take was larger in males in comparison to females with p < 0.00. The paired t test showed left side is larger than right. The discriminant function showed high significance for each measurement and also when all the measurements were combined. Conclusion Though the study being unique for Nepalese population, caution should be taken when frontal sinus is used as the only parameter. However in combination with other morphometric data is advised.

Skyrmion-(Anti)Vortex Coupling in a Chiral Magnet-Superconductor Heterostructure.

We report experimental coupling of chiral magnetism and superconductivity in [IrFeCoPt]/Nb heterostructures. The stray field of skyrmions with radius ≈50 nm is sufficient to nucleate antivortices in a 25 nm Nb film, with unique signatures in the magnetization, critical current, and flux dynamics, corroborated via simulations. We also detect a thermally tunable Rashba-Edelstein exchange coupling in the isolated skyrmion phase. This realization of a strongly interacting skyrmion-(anti)vortex system opens a path toward controllable topological hybrid materials, unattainable to date.

Rapid detection of biofilm-producing Candida species via MALDI-TOF mass spectrometry.

AIMS: The aim of this study was to evaluate the formation of biofilm by Candida spp. isolated from the bloodstream, using traditional spectrophotometric methodologies. In addition, the goal was to compare the results with those obtained through MALDI-TOF/MS, as well as to verify its use as a potential tool for the detection of biofilm-forming strains. METHODS AND RESULTS: Hundred and thirteen isolates of Candida spp. were studied: 41 were Candida albicans, 27 C. tropicalis, 18 C. glabrata, 17 C. parapsilosis and 10 C. krusei. Metabolic activity was determined through the tetrazolium salt (XTT) reduction assay and biomass by staining with Crystal Violet. All isolates were able to form biofilm, 94% of which were strong producers, with high biomass quantification (95%; 107/113) and high metabolic activity (99%; 112/113). Mass spectra of the biofilm-producing isolates showed differences in the intensity of mass peaks when compared with the spectra of the nonproducing strains. CONCLUSIONS: It was demonstrated that MALDI-TOF/MS was able to detect specific biofilm proteins, as the mass spectra of the isolates presented differences when compared with nonproducing strains. SIGNIFICANCE AND IMPACT OF THE STUDY: MALDI-TOF/MS can become a valuable tool for biofilm detection at the moment of the identification of the microorganism, thus contributing greatly to the management of patients with Candidemia.

Homicidal Pesticide Poisoning - An Overview.

Pesticides are chemical or biological agents used to repel or kill pests. Pesticides are potent and lethal toxic substances that are also being infamously used for homicidal purposes due to their easy availability and rapid action. In this review, we look at 21 articles related to homicidal pesticide poisoning in the literature with an emphasis on fatal doses, routes of administration, and profiles of victims and perpetrators. Organophosphates and rodenticides were the most commonly used classes of pesticides, and ingestion was the most common route of administration; however, other modes of administration, such as through intraperitoneal injection, were also reported. Interestingly, we have noticed that victims involved in homicidal poisoning were mostly in close relationships with perpetrators. Most perpetrators were either spouses or other immediate family members. Abiding by the regulations that govern the production, sale, and use of pesticides and proper documentation of the related trail can help control the prevalence of homicidal pesticide poisoning. Recognition of the distinct morbid anatomy of the poisoning cases, alongside a high index of suspicion in cases that fit the profile, is essential for forensic analysis.

Landmark publications on Sudden Infant Death Syndrome: A bibliometrics analysis.

Sudden infant death syndrome (SIDS) is a poorly understood disorder, and its pathophysiology and risk factors remain unclear. Research in the area is the key to combating the pervasive prevalence of this fatal disorder. We sought to identify the top 50 articles concerning SIDS and study their bibliometric characteristics to gain an insight into the research trends in this area. Using the Scopus database, two independent reviewers conducted a literature search using a prespecified search string. Results were arranged according to the citation count, and the top 50 relevant articles were selected. No time restrictions were set, and all types of articles were included. A detailed analysis was carried out to identify the trends and characteristics of the top 50 articles. The top 50 articles were published between 1972 and 2011, with the most productive 5-year interval being 1991-1995. These 50 papers accumulated a total of 13,703 citations (median = 236 citations per paper). Among these, about 9% were self-citations. The citations received by these core papers seemed to decline post-2009. The top 50 articles were published in 21 different journals, with Pediatrics contributing the most (n = 15). US authors were listed for 60% of the articles (n = 30). None of the articles originated from Asian authors. Our manuscript highlights the characteristics of impactful articles on SIDS - and this can act as a directive for researchers aiming to publish on this topic. Bibliometric parameters suggest a decreasing research interest in the fi eld of SIDS, which is concerning, and efforts should be made to promote research. Furthermore, the lack of influential research from Asian authors is also troubling. Funding should preferably be directed toward Asian researchers to bridge the gap in knowledge.

Mixed-effects modelling for crossed and nested data: an analysis of dengue fever in the state of Goiás, Brazil.

Dengue fever is a viral disease transmitted by the mosquito Aedes aegypti. In order to avoid epidemics and deaths, this transmitting vector must be controlled. This work assembles, for the first time, data from multiple governmental bodies describing the number of dengue cases reported, and meteorological conditions in 20 cities in the Goiás state, Brazil, from 2008 to 2015. We then apply generalised linear mixed modelling to this novel data set to model dengue occurrences in this state, where the tropical climate favours the proliferation of the main transmitting vector of this disease. The number of reported dengue cases is estimated using meteorological variables as fixed effects, and city and year data are included in the model as random effects. The proposed models can cope with complex data structures, such as nested data, while taking into account the particularities of each year dependent on the city under analysis. The results confirm that precipitation, minimum temperature, and relative air humidity contribute to the increase of dengue cases number, while year and city location are determining factors. Public policies, based on these new results, together with joint actions involving local populations, are essential to combat the vector transmitting dengue and avoid epidemics.

Cutaneous Leishmaniosis caused by Leishmania martiniquensis in a Horse in Florida.

We report a new case of cutaneous leishmaniosis caused by Leishmania (Mundinia) martiniquensis in a horse in Florida, USA. A 10-year-old neutered male Quarter horse was presented with multifocal to coalescing, raised, ulcerated and oozing, non-healing wounds on both pinnae of several weeks' duration. After a few months, the lesions regressed spontaneously. Biopsies of the lesions were performed with microscopical findings of epidermal hyperplasia with multifocal ulceration and focally extensive, dermal pyogranulomatous inflammation with numerous intact and degenerate neutrophils being surrounded by epithelioid macrophages, lymphocytes and plasma cells, as well as rare eosinophils. Within the macrophages, and freely within the inflammatory infiltrate, were small (2-4 µm) round, basophilic protozoal organisms. Immunohistochemistry and colourimetric in-situ hybridization were positive for amastigote forms of Leishmania spp. The species L. martiniquensis was identified by polymerase chain reaction targeting the ITS-1 gene performed with extracts from formalin-fixed and paraffin wax-embedded samples of skin lesions. L. martiniquensis causes an ulcerative pyogranulomatous dermatitis in horses with spontaneous healing. This second autochthonous case in Florida, 5 years after the first case, suggests that this parasite may have become endemic in this state.

Antichagasic effect of violacein from Chromobacterium violaceum.

AIMS: Violacein (VIO), a bacterial pigment produced by Chromobacterium violaceum, was examined to evaluate the antichagasic activity and its action mechanism against Trypanosoma cruzi Y strain. METHODS AND RESULTS: Violacein was tested against the epimastigote, trypomastigote and amastigote forms of T. cruzi Y strain (benznidazole-resistant strain). VIO inhibited all T. cruzi developmental forms, including amastigotes, which is implicated in the burden of infection in the chronic phase of Chagas disease (CD). VIO induced cell death in T. cruzi through apoptosis, as determined by flow cytometry analyses with specific molecular probes and morphological alterations, such as involvement of reactive oxygen species and changes in mitochondrial membrane potential and cell shrinkage. CONCLUSION: The results suggest antichagasic activity of VIO against T. cruzi Y strain with apoptotic involvement. SIGNIFICANCE AND IMPACT OF THE STUDY: The treatment of CD has limited efficacy and side effects that restrict patient tolerability and compliance. The VIO molecule could be used as a model for therapeutic alternatives for this disease.

Analysis of risk factors for maxillary denture-related oral mucosal lesions: A cross-sectional study.

BACKGROUND: To evaluate the frequency of maxillary dentures-related lesions and the possible associated risk factors. MATERIAL AND METHODS: Ninety-seven participants were selected, and a complete anamnesis, physical examination and tests of occlusion vertical dimension (OVD), retention and stability of the denture, biofilm quantification, cytopathology, sialometry, pH analysis and buffer capacity of the saliva were performed. Statistical analyses were performed with the Pearson's chi-square, Mann-Whitney tests, and Pearson's coefficient (p<0.05). RESULTS: In 78% of the participants at least one denture-related lesion was found. Denture-associated stomatitis (63%), inflammatory fibrous hyperplasia (19%) and traumatic ulceration (11%) were the 3 most frequent lesions. The habit of night use of the denture was considered an independent risk factor for the development of oral lesions [OR=3.0 (95% CI 1.09-8.56); p<0.05]. Furthermore, the longest period of use of the same denture and biofilm also had statistically significant relation to oral lesions. The biofilm seems to be more related to the prevalence of oral lesions according to the multiple logistic regression [OR=1.3 (95% CI: 1.01-1.83) p<0.05]. The lack of a dentures' cleaning solution and detrition of the prothesis were independent risk factors for denture-associated stomatitis. Male gender, loss of OVD and bad buffer capacity were risk factors for angular cheilitis. Fractures of the base and repair of broken dentures were risk factors for traumatic ulcers. CONCLUSIONS: These results show a high frequency of denture-related lesions. Besides, participants hygiene habits and poor quality of the dentures were the main factors for the development of these lesions.

Association of high-fat diet with neuroinflammation, anxiety-like defensive behavioral responses, and altered thermoregulatory responses in male rats.

Overweight and obesity are a worldwide pandemic affecting billions of people. These conditions have been associated with a chronic low-grade inflammatory state that is recognized as a risk factor for a range of somatic diseases as well as neurodevelopmental disorders, anxiety disorders, trauma- and stressor-related disorders, and affective disorders. We previously reported that the ingestion of a high-fat diet (HFD; 45% fat kcal/g) for nine weeks was capable of inducing obesity in rats in association with increased reactivity to stress and increased anxiety-related defensive behavior. In this study, we conducted a nine-week diet protocol to induce obesity in rats, followed by investigation of anxiety-related defensive behavioral responses using the elevated T-maze (ETM), numbers of FOS-immunoreactive cells after exposure of rats to the avoidance or escape task of the ETM, and neuroinflammatory cytokine expression in hypothalamic and amygdaloid nuclei. In addition, we investigated stress-induced cutaneous thermoregulatory responses during exposure to an open-field (OF). Here we demonstrated that nine weeks of HFD intake induced obesity, in association with increased abdominal fat pad weight, increased anxiety-related defensive behavioral responses, and increased proinflammatory cytokines in hypothalamic and amygdaloid nuclei. In addition, HFD exposure altered avoidance- or escape task-induced FOS-immunoreactivity within brain structures involved in control of neuroendocrine, autonomic, and behavioral responses to aversive stimuli, including the basolateral amygdala (BLA) and dorsomedial (DMH), paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. Furthermore, rats exposed to HFD, relative to control diet-fed rats, responded with increased tail skin temperature at baseline and throughout exposure to an open-field apparatus. These data are consistent with the hypothesis that HFD induces neuroinflammation, alters excitability of brain nuclei controlling neuroendocrine, autonomic, and behavioral responses to stressful stimuli, and enhances stress reactivity and anxiety-like defensive behavioral responses.

Urban blue: A global analysis of the factors shaping people's perceptions of the marine environment and ecological engineering in harbours.

Marine harbours are the focus of a diverse range of activities and subject to multiple anthropogenically induced pressures. Support for environmental management options aimed at improving degraded harbours depends on understanding the factors which influence people's perceptions of harbour environments. We used an online survey, across 12 harbours, to assess sources of variation people's perceptions of harbour health and ecological engineering. We tested the hypotheses: 1) people living near impacted harbours would consider their environment to be more unhealthy and degraded, be more concerned about the environment and supportive of and willing to pay for ecological engineering relative to those living by less impacted harbours, and 2) people with greater connectedness to the harbour would be more concerned about and have greater perceived knowledge of the environment, and be more supportive of, knowledgeable about and willing to pay for ecological engineering, than those with less connectedness. Across twelve locations, the levels of degradation and modification by artificial structures were lower and the concern and knowledge about the environment and ecological engineering were greater in the six Australasian and American than the six European and Asian harbours surveyed. We found that people's perception of harbours as healthy or degraded, but not their concern for the environment, reflected the degree to which harbours were impacted. There was a positive relationship between the percentage of shoreline modified and the extent of support for and people's willingness to pay indirect costs for ecological engineering. At the individual level, measures of connectedness to the harbour environment were good predictors of concern for and perceived knowledge about the environment but not support for and perceived knowledge about ecological engineering. To make informed decisions, it is important that people are empowered with sufficient knowledge of the environmental issues facing their harbour and ecological engineering options.

Comparison of the Sensitivity of Three Methods for the Early Diagnosis of Sporotrichosis in Cats.

Sporotrichosis is caused by species of fungi within the Sporothrix schenckii complex that infect man and animals. In Rio de Janeiro, Brazil, an epidemic has been observed since 1998, with most of the cases being related to transmission from infected cats. Although the definitive diagnosis of feline sporotrichosis is made by fungal culture, cytopathological and histopathological examinations are used routinely, because the long culture period may delay treatment onset. However, alternative methods are desirable in cases of low fungal burden. Immunohistochemistry (IHC) has been described as a sensitive method for diagnosing human and canine sporotrichosis, but there are no reports of its application to cats. The aim of this study was to analyse the sensitivity of cytopathological examination (Quick Panoptic method), histopathology (Grocott silver stain) and anti-Sporothrix IHC by blinded comparisons, using fungal culture as the reference standard. Samples were collected from 184 cats with sporotrichosis that exhibited skin ulcers. The sensitivities of Grocott silver stain, cytopathological examination and IHC were 91.3%, 87.0% and 88.6%, respectively. Grocott silver stain showed the best performance. IHC showed high sensitivity, as did cytopathological examination and these may be considered as alternative methodologies. When the three methods were combined, the diagnosis was established in 180 (97.8%) out of 184 cases. Taken together, these findings indicate the need to implement these methods as routine tools for the early diagnosis of sporotrichosis in cats, notably when fungal culture is not available.

Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: High BMI is key.

OBJECTIVE: Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder. STUDY DESIGN: Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients. RESULTS: Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002). CONCLUSION: Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.

Philometra saltatrix (Nematoda: Philometridae) in the ovary of the bluefish, Pomatomus saltatrix (Linnaeus, 1766), off the coast of the state of Rio de Janeiro, Brazil.

The aims of the present study were to identify and describe the occurrence of nematode parasites in the gonads of bluefish Pomatomus saltatrix from off the coast of the state of Rio de Janeiro, Brazil. Only females were found to be parasitized by the nematodes, which were identified as P. saltatrix using morphological, morphometric and molecular data. Infection of female bluefish by this nematode had the following values: prevalence, 48.7%; mean intensity, 2.6; mean abundance, 1.3; and range of infection, 1-10 specimens. Histopathological examination of transverse and longitudinal sections of the parasitized ovaries showed nematodes at different stages of development among oocytes, but no indication of any associated inflammatory reaction. The presence of nematodes in the ovaries of bluefish is an important indication of fish hygiene, and parasitized fish are usually rejected by consumers because of their repugnant appearance.

A CDC42-centered signaling unit is a dominant positive regulator of endothelial integrity.

Endothelial barrier function is carefully controlled to protect tissues from edema and damage inflicted by extravasated leukocytes. RhoGTPases, in conjunction with myriad regulatory proteins, exert both positive and negative effects on the endothelial barrier integrity. Precise knowledge about the relevant mechanisms is currently fragmented and we therefore performed a comprehensive analysis of endothelial barrier regulation by RhoGTPases and their regulators. Combining RNAi with electrical impedance measurements we quantified the relevance of 270 Rho-associated genes for endothelial barrier function. Statistical analysis identified 10 targets of which six promoted- and four reduced endothelial barrier function upon downregulation. We analyzed in more detail two of these which were not previously identified as regulators of endothelial integrity. We found that the Rac1-GEF (Guanine nucleotide Exchange Factor) TIAM2 is a positive regulator and the Cdc42(Rac1)-GAP (GTPase-Activating Protein) SYDE1 is a negative regulator of the endothelial barrier function. Finally, we found that the GAP SYDE1 is part of a Cdc42-centered signaling unit, also comprising the Cdc42-GEF FARP1 and the Cdc42 effector PAK7 which controls the integrity of the endothelial barrier. In conclusion, using a siRNA-based screen, we identified new regulators of barrier function and found that Cdc42 is a dominant positive regulator of endothelial integrity.