Abnormal salivary total and oligomeric alpha-synuclein in Parkinson's disease

In Parkinson’s disease (PD), alpha-synuclein (a-syn) can be detected in biological fluids including saliva. Although previous studies found reduced a-syn total (a-syntotal) concentration in saliva of PD patients, no studies have previously examined salivary a-syn oligomers (a-synolig) concentrations or assessed the correlation between salivary a-syntotal, a-synolig and clinical features in a large cohort of PD patients. Is well known that a-synolig exerts a crucial neurotoxic effect in PD. We collected salivary samples from 60 PD patients and 40 age- and sex-comparable healthy subjects. PD was diagnosed according to the United Kingdom Brain Bank Criteria. Samples of saliva were analyzed by specific anti-a-syn and anti-oligomeric a-syn ELISA kits. A complete clinical evaluation of each patient was performed using MDS-Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, Montreal Cognitive Assessment and Frontal Assessment Battery. Salivary a-syntotal was lower, whereas a-synolig was higher in PD patients than healthy subjects. The a-synolig/a-syntotal ratio was also higher in patients than in healthy subjects. Salivary a-syntotal concentration negatively correlated with that of a-synolig and correlated with several patients’ clinical features. In PD, decreased salivary concentration of a-syntotal may reflect the reduction of a-syn monomers (a-synmon), as well as the formation of insoluble intracellular inclusions and soluble oligomers. The combined detection of a-syntotal and a-synolig in the saliva might help the early diagnosis of P

Differential redox state contributes to sex disparities in the response to influenza virus infection in male and female mice

Influenza virus replicates intracellularly exploiting several pathways involved in the regulation of host responses. The outcome and the severity of the infection are thus strongly conditioned by multiple host factors, including age, sex, metabolic, and redox conditions of the target cells. Hormones are also important determinants of host immune responses to influenza and are recently proposed in the prophylaxis and treatment. This study shows that female mice are less susceptible than males to mouse-adapted influenza virus (A/PR8/H1N1). Compared with males, PR8-infected females display higher survival rate (+36%), milder clinical disease, and less weight loss. They also have milder histopathological signs, especially free alveolar area is higher than that in males, even if pro-inflammatory cytokine production shows slight differences between sexes; hormone levels, moreover, do not vary significantly with infection in our model. Importantly, viral loads (both in terms of viral M1 RNA copies and tissue culture infectious dose 50%) are lower in PR8-infected females. An analysis of the mechanisms contributing to sex disparities observed during infection reveals that the female animals have higher total antioxidant power in serum and their lungs are characterized by increase in (i) the content and biosynthesis of glutathione, (ii) the expression and activity of antioxidant enzymes (peroxiredoxin 1, catalase, and glutathione peroxidase), and (iii) the expression of the anti-apoptotic protein Bcl-2. By contrast, infected males are characterized by high expression of NADPH oxidase 4 oxidase and phosphorylation of p38 MAPK, both enzymes promoting viral replication. All these factors are critical for cell homeostasis and susceptibility to infection. Reappraisal of the importance of the host cell redox state and sex-related effects may be useful in the attempt to develop more tailored therapeutic interventions in the fight against influenza

HAART as a Strategy for Reduction of HIV-1 Transmission in Sub-Saharan Africa: Survival and Virus Load Parameters from the Drug Resource Enhancement against AIDS and Malnutrition Program

Background: The concept of universal antiretroviral use as a strategy for reduction of new cases of HIV infection has been evaluated in mathematical models as a potential approach to curtailing the Sub-Saharan African epidemic. In order to further substantiate such models, additional strategic parameters based on robust patient data should be considered, including survival of HIV-infected populations under HAART and subject infectivity as determined by HIV RNA levels. Methods: A retrospective cohort study was conducted in a population of patients enrolled in DREAMcenters throughout sub-Saharan Africa in order to determine survival under HAART. Cox regression analysis was performed evaluating parameters associated with survival such as CD4 cell count, viral load, body mass index (BMI) and hemoglobin (HB) levels. DREAM criteria for HAART initiation included (1) WHO stage 3-4 regardless of CD4 cell value (2) 100,000 copies in any subject. Virus load response to HAART was assessed in a subset of patients. Results: Adult non-pregnant patients who accessed DREAM centers from 1/2002 to 7/2009 were evaluated. A total of 34,295 patients (22,249 females/12,041 males) were included. Median age was 34 years (IQR:29-42) and median observation time 476 days (IQR:206 –950). Baseline median viral load, CD4 cell counts, HB and BMI values were 4.4 (IQR:3.6-5.0), 243 (IQR:109-416), 10.8 (IQR:9.2-12.4), and 20.3 (IQR:18.3-22.7).Over time 23,795 patients initiated HAART. Cox survival analysis (adjusted for Viral Load and HB) according to CD4 cell strata was performed. The relative risk of death in the lowest CD4 stratum (500) was 3.3 [2.7 –4.1]. Survival estimates at >7 years of HAART ranged from 50% to 95% according to baseline CD4 cell count and HB levels. In a subset of 13,405 subjects who received HAART for >6 months with at least 2 virus load measures available, 55.9% achieved < 50 copies/ml and an additional 19.7% achieved levels < 400 copies/ml (75.6% total). Final median virus load value was 58 (IQ: 0 –2000). Conclusions: Contrary to more conservative estimates used in mathematical modeling studies, patients in our cohort demonstrated a significant survival benefit even within the lowest CD4 cell stratum. Patients on HAART had low potential infectivity as measured by plasma virus load. Cohort data from African patients can contribute to the further refinement of predictive models

Peribiliary gland damage due to liver transplantation involves peribiliary vascular plexus and vascular endothelial growth factor

Extrahepatic bile ducts are characterized by the presence of peribiliary glands (PBGs), which represent stem cell niches implicated in biliary regeneration. Orthotopic liver transplantation may be complicated by non-anastomotic strictures (NAS) of the bile ducts, which have been associated with ischemic injury of PBGs and occur more frequently in livers obtained from donors after circulatory death than in those from brain-dead donors. The aims of the present study were to investigate the PBG phenotype in bile ducts after transplantation, the integrity of the peribiliary vascular plexus (PVP) around PBGs, and the expression of vascular endothelial growth factor-A (VEGF-A) by PBGs. Transplanted ducts obtained from patients who underwent liver transplantation were studied (N=62). Controls included explanted bile duct samples not used for transplantation (N=10) with normal histology. Samples were processed for histology, immunohistochemistry and immunofluorescence. Surface epithelium is severely injured in transplanted ducts; PBGs are diffusely damaged, particularly in ducts obtained from circulatory-dead compared to brain-dead donors. PVP is reduced in transplanted compared to controls. PBGs in transplanted ducts contain more numerous progenitor and proliferating cells compared to controls, show higher positivity for VEGF-A compared to controls, and express VEGF receptor-2. In conclusion, PBGs and associated PVP are damaged in transplanted extrahepatic bile ducts; however, an activation of the PBG niche takes place and is characterized by proliferation and VEGF-A expression. This response could have a relevant role in reconstituting biliary epithelium and vascular plexus and could be implicated in the genesis of non-anastomotic strictures

An assessment of option B implementation for the prevention of mother to child transmission in Dschang, Cameroon: results from the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) cohort

Introduction: Scaling up of antiretroviral therapy (ART) to HIV+ pregnant women is crucial for the elimination of HIV infection in children. The aim of this study was to evaluate the feasibility and effectiveness of triple ART for Prevention of Mother-to Child Transmission (PMTCT) in Cameroon. Methods: HIV-positive pregnant women attending the DREAM Centre of Dschang, Cameroon for prenatal care were enrolled in a prospective cohort study, and received ART until the end of breastfeeding or indefinitely if their CD4 count was &lt;350mm3. Infants were evaluated for HIV infection at 1, 6 and 12 months of age. Results: A total of 298 women were enrolled. Among them, 152 were already on established ART. Women were followed until 6 months after delivery with a retention rate of 92.6%. Eight women died. Those with a CD4 count &lt;350 cells/mm3 during pregnancy had the highest mortality risk (RR 2.53; 95% CL= 1.86-3.44). The HIV  transmission rate was 1.2% at 12 months with an HIV free survival of 91%. In the proportional Cox regression analysis, the following factors were positively associated with infant mortality: maternal CD4&lt; 350 cells/mm3, no breastfeeding in the first 6 months of life, weight-for-age z score &lt; -2. Conclusion: Results confirm the feasibility and effectiveness of the implementation of Option B, with very low rates of HIV MTC  transmission, and potential benefits to the health of mothers and infants with earlier initiation of ART. Breastfeeding again demonstrates to be highly beneficial for the growth and survival of HIV exposed children.Pan African Medical Journal 2016; 2

The Third International Symposium on Fungal Stress – ISFUS

Stress is a normal part of life for fungi, which can survive in environments considered inhospitable or hostile for other organisms. Due to the ability of fungi to respond to, survive in, and transform the environment, even under severe stresses, many researchers are exploring the mechanisms that enable fungi to adapt to stress. The International Symposium on Fungal Stress (ISFUS) brings together leading scientists from around the world who research fungal stress. This article discusses presentations given at the third ISFUS, held in São José dos Campos, São Paulo, Brazil in 2019, thereby summarizing the state-of-the-art knowledge on fungal stress, a field that includes microbiology, agriculture, environmental science, ecology, biotechnology, medicine, and astrobiology

Rationale for BepiColombo Studies of Mercury's Surface and Composition

BepiColombo has a larger and in many ways more capable suite of instruments relevant for determination of the topographic, physical, chemical and mineralogical properties of Mercury's surface than the suite carried by NASA's MESSENGER spacecraft. Moreover, BepiColombo's data rate is substantially higher. This equips it to confirm, elaborate upon, and go beyond many of MESSENGER's remarkable achievements. Furthermore, the geometry of BepiColombo's orbital science campaign, beginning in 2026, will enable it to make uniformly resolved observations of both northern and southern hemispheres. This will offer more detailed and complete imaging and topographic mapping, element mapping with better sensitivity and improved spatial resolution, and totally new mineralogical mapping. We discuss MESSENGER data in the context of preparing for BepiColombo, and describe the contributions that we expect BepiColombo to make towards increased knowledge and understanding of Mercury's surface and its composition. Much current work, including analysis of analogue materials, is directed towards better preparing ourselves to understand what BepiColombo might reveal. Some of MESSENGER's more remarkable observations were obtained under unique or extreme conditions. BepiColombo should be able to confirm the validity of these observations and reveal the extent to which they are representative of the planet as a whole. It will also make new observations to clarify geological processes governing and reflecting crustal origin and evolution. We anticipate that the insights gained into Mercury's geological history and its current space weathering environment will enable us to better understand the relationships of surface chemistry, morphologies and structures with the composition of crustal types, including the nature and mobility of volatile species. This will enable estimation of the composition of the mantle from which the crust was derived, and lead to tighter constraints on models for Mercury's origin including the nature and original heliocentric distance of the material from which it formed.Peer reviewe

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon