Infectious Diseases

To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.

Although silicon nanoparticles dispersed in liquids are used in various applications ranging from bio-labeling to hydrogen production, their reactivities with their solvents and their catalytic properties remain still unexplored. Here, we discovered that, because of their surface structures and mechanical strain, silicon nanoparticles react strongly with their solvents and may act as catalysts for the dehydrogenation, at room temperature, of secondary alcohols (e.g. isopropanol) into ketones and hydrogen. This catalytic reaction was monitored by gas chromatography, pH measurements, mass spectroscopy and solid-state NMR. This discovery provides new understanding of the role played by silicon nanoparticles, and nanosilicon in general, in their reactivity in solvents in general as well as being candidates in catalysis.

Materials. Aq 1 and PDI 2 chromophores were synthesized, purified, and characterized as previously described. Oligonucleotide synthesis was carried out using phosphoramidite chemistry on an Expedite 8909 synthesizer. For Aq and PDI monomers the coupling time was extending to 15 minutes. For PDI an additional wash cycle using dichloromethane was added to the protocol. The oligonucleotides were deprotected by incubating in 30% ammonium hydroxide at room temperature for 24 h, purified by RP-HPLC and characterized using MALDI-TOF spectroscopy. Thermal dissociation profiles were recorded on a Perkin Elmer Lambda 2 UV/VIS spectrometer with a Peltier Temperature Programmer. Circular dichroism (CD) spectra were recorded on a Jasco-J-815 CD spectrometer.

Aedes aegypti is the main vector for yellow fever, dengue, chikungunya and Zika viruses. Recent outbreaks of dengue and chikungunya have been reported in Kenya. Presence and abundance of this vector is associated with the risk for the occurrence and transmission of these diseases. This study aimed to characterize the presence and abundance of Ae. aegypti adult mosquitoes from rural and urban sites in western and coastal regions of Kenya. Presence and abundance of Ae. aegypti adult mosquitoes were determined indoors and outdoors in two western (urban Kisumu and rural Chulaimbo) and two coastal (urban Ukunda and rural Msambweni) sites in Kenya. Sampling was performed using quarterly human landing catches, monthly Prokopack automated aspirators and monthly Biogents-sentinel traps. A total of 2,229 adult Ae. aegypti mosquitoes were collected: 785 (35.2%) by human landing catches, 459 (20.6%) by Prokopack aspiration and 985 (44.2%) by Biogents-sentinel traps. About three times as many Ae. aegypti mosquitoes were collected in urban than rural sites (1,650 versus 579). Comparable numbers were collected in western (1,196) and coastal (1,033) sites. Over 80% were collected outdoors through human landing catches and Prokopack aspiration. The probability of collecting Ae. aegypti mosquitoes by human landing catches was significantly higher in the afternoon than morning hours (P<0.001), outdoors than indoors (P<0.001) and in urban than rural sites (P = 0.008). Significantly more Ae. aegypti mosquitoes were collected using Prokopack aspiration outdoors than indoors (P<0.001) and in urban than rural areas (P<0.001). Significantly more mosquitoes were collected using Biogents-sentinel traps in urban than rural areas (P = 0.008) and in western than coastal sites (P = 0.006). The probability of exposure to Ae. aegypti bites was highest in urban areas, outdoors and in the afternoon hours. These characteristics have major implications for the possible transmission of arboviral diseases and for the planning of surveillance and control programs.

Background: Combined antiretroviral therapy (cART) has been associated with significant decrease in the mortality and morbidity in patients with HIV/AIDS. However, there has been increased recognition of immune dysregulation syndromes related to recovery of immunity on cART. HIV-mediated CD8 encephalitis is a rare neurological syndrome due to perivascular inflammation caused by infiltration of CD8+ cells. Methods & Materials: We report the clinical and pathological features of three cases of CD8 encephalitis which will sensitise the clinicians to have high index of suspicion to recognize this entity early. Results: All three patients were men with a mean age of 42.3 years. The mean duration of HIV was 10 years. The patient's mean CD4 at presentation was 392 cells/microL and blood HIV viral load was 11,588.3 copies/ml. All patients presented with an average duration of 4 months with cognitive decline, especially memory disturbances and tremors. The mean cerebrospinal fluid (CSF) cell count was 65 cells/ml, lymphocyte predominant (mean -97%), and protein was 171.3 mg/dl. The CSF lymphocyte subset analysis showed a median CD8 cell proportion of 54.7%. CSF was tested negative for viral infections (HSV1, HSV2, CMV, JC virus and VZV) and VDRL. The CSF cultures were sterile and GeneXpert was negative. MRI brain revealed diffuse hyper intensities involving the deep grey and white matter and typical perivascular hyperintensities were present in one patient. All patients were started on steroids after excluding other etiologies. Two patients made a complete recovery while one patient in whom the diagnosis was delayed succumbed to the illness. Postmortom brain biopsy of the patient who had a fatal outcome demonstrated perivascular cuffing with lymphocytes positive for CD8 and negative for CD4 and CD20 markers on immunohistochemistry, consistent with CD8 encephalitis. Conclusion: CD8 encephalitis is a rare but potentially treatable cause of cognitive decline in patients with HIV on cART. The typical presentation includes memory impairment with extrapyramidal symptoms like tremors with lymphocytosis in CSF and predominant CD8 cells in CSF. MRI may show the typical perivascular hyperintensities in the deep brain tissue. Aggressive early steroid treatment after excluding opportunistic infections is likely to result in complete recovery.

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC 50 = 4.5 nM) compared with vorinostat (VOR; EC 50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC 50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 mM VOR resulted in 2-to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART.

Background. Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation. Methods. Wild-type (WT), COX-1 and COX-2 heterozygous (COX-1 +/Ϫ and COX-2 +/Ϫ ), and homozygous COX-deficient (COX-1 Ϫ/Ϫ and COX-2 Ϫ/Ϫ ) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX-deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined. Results. COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX-deficient mice, whereas cell proliferation was increased in WT and COX-1deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-a and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-a mRNA expression was further increased by COX deficiency. Prostaglandin E 2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B 4 and LTC 4 levels were increased to a similar extent in infected WT and COX-deficient mice. Conclusions. COX deficiency enhances H. pylori-induced gastritis, probably via TNF-a expression. COX-2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation. Cyclooxygenases (COXs) are the rate-limiting enzymes in the production of prostanoids and are also the pharmacological target of nonsteroidal anti-inflammatory drugs (NSAIDs) . There are 2 isoforms of COX:

Prescribing individualized moderate exercise intensity is a useful method to reach positive effects on health status in obese adults. This study aimed to establish a practical reference equation to estimate the heart rate (HR) at individual ventilatory threshold (IVT) (HR IVT ). One hundred sixty-one obese subjects were clinically evaluated and characterized by anthropometric and body composition. Participants performed the six-minute walking test (6-MWT) and the cardiopulmonary exercise test to assess IVT. Multiple regression analysis for HR IVT , including 6-MWT, anthropometric, and body composition parameters, as independent variables, was performed for both gender separately. A cross-validation study was also performed to determine the accuracy of the prediction equation. Whereas HR IVT was not significantly different between males (121.5±18.3 bpm) and females (117.6±17.1 bpm), it differently correlated with physical and performance parameters. Therefore, two sex-specific equations were developed including 6-MWT HR and HR rest (R 2 = 0.69 and 0.65 and root mean square errors of 8.8 and 10.1 bpm for females and males, respectively). In conclusion, in female and male obese adults, the 6-MWT might be used to predict HR at IVT. These outcomes are useful to prescribe optimal physical activity intensity when gold standard methods (e.g. gas exchange analysis) are unavailable.

The use of the Individual Ventilatory Threshold (IVT), as parameter to prescribe exercise intensity in individuals with obesity, has become more frequent during the last years. This study aimed to evaluate the relationship between IVT and Maximal Fat Oxidation (MFO) in women with obesity. Fifty-two obese female adults (age = 43.6±10.9 years; BMI = 38.5±5.2 kg/m 2 ) were included in this study. According to the BMI classification, subjects were divided into three groups: Obese Class I (OBI, n = 16); Obese Class II (OBII, n = 20) and Obese Class III (OBIII, n = 16). All subjects performed an incremental graded exercise test to evaluate peak oxygen uptake (VO 2peak ), IVT and MFO. MFO was evaluated using a stoichiometric equation. Fat max zone was determined for each subject within 10% of fat oxidation rates at MFO. For each HR, %HR max , VO 2 and %VO 2peak variable, Pearson's correlation test was done between IVT and MFO exercise intensity. When statistical correlation was found we used a comparative statistical analysis to assess differences between IVT and MFO. Statistical significance was set at P � 0.05. For each HR, %HR max , VO 2 and %VO 2peak variable there was a positive significant correlation (P<0.01) between IVT and MFO. No significant differences were found for HR, % HR max , and VO 2 between IVT and MFO. %VO 2peak was significantly higher at IVT than at MFO (P = 0.03).

Prescribing individualized moderate exercise intensity is a useful method to reach positive effects on health status in obese adults. This study aimed to establish a practical reference equation to estimate the heart rate (HR) at individual ventilatory threshold (IVT) (HRIVT). One hundred sixty-one obese subjects were clinically evaluated and characterized by anthropometric and body composition. Participants performed the six-minute walking test (6-MWT) and the cardiopulmonary exercise test to assess IVT. Multiple regression analysis for HRIVT, including 6-MWT, anthropometric, and body composition parameters, as independent variables, was performed for both gender separately. A cross-validation study was also performed to determine the accuracy of the prediction equation. Whereas HRIVT was not significantly different between males (121.5±18.3 bpm) and females (117.6±17.1 bpm), it differently correlated with physical and performance parameters. Therefore, two sex-specific equations w...

SummaryInvasive fungal infections (IFI) of the Central Nervous System (IFI‐CNS) and Paranasal Sinuses (IFI‐PS) are rare, life‐threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI‐CNS (71/89) and IFI‐PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5‐79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI‐...

Apd1, a cytosolic yeast protein, and Aim32, its counterpart in the mitochondrial matrix, have a C-terminal thioredoxinlike ferredoxin domain and a widely divergent N-terminal domain. These proteins are found in bacteria, plants, fungi and unicellular pathogenic eukaryotes, but not in Metazoa. Our chemogenetic experiments demonstrate that the highly conserved cysteine and histidine residues within the C-X8-C-X24-75-H-X-G-G-H motif of the TLF domain of Apd1 and Aim32 proteins are essential for viability upon treatment of yeast cells with the redox potentiators gallobenzophenone or pyrogallol, respectively. UV-Vis, EPR and Mössbauer spectroscopy of purified wild type Apd1 and three His to Cys variants demonstrated that Cys207 and Cys216 are the ligands of the ferric ion and His255 and His259 are the ligands of the reducible iron ion of the [2Fe-2S]2+/1+ cluster. The [2Fe-2S] center of Apd1 (Em,7 = -164±5 mV, pKox1,2=7.9±0.1 and 9.7±0.1) differs from both dioxygenase (Em,7 ≈ -150 mV, pK...

Accurate diagnosis of tuberculosis, especially by using rapid molecular assays, can reduce transmission of drug resistant tuberculosis in communities. However, the frequency of resistance conferring mutations varies with geographic location of Mycobacterium tuberculosis, and this affects the efficiency of rapid molecular assays in detecting resistance. This has created need for characterizing drug resistant isolates from different settings to investigate frequencies of resistance conferring mutations. Here, we describe the prevalence and patterns of rifampicin-and isoniazid-resistance conferring mutations in isolates from Uganda, which could be useful in the management of MDR-TB patients in Uganda and other countries in sub-Saharan Africa. Ninety seven M. tuberculosis isolates were characterized, of which 38 were MDR, seven rifampicin-resistant, 12 isoniazid-mono-resistant, and 40 susceptible to rifampicin and isoniazid. Sequence analysis of the rpoB rifampicin-resistance determining region (rpoB/RRDR) revealed mutations in six codons: 588, 531, 526, 516, 513, and 511, of which Ser531Leu was the most frequent (40%, 18/45). Overall, the three mutations (Ser531Leu, His526Tyr, Asp516Tyr) frequently associated with rifampicin-resistance occurred in 76% of the rifampicin resistant isolates while 18% (8/45) of the rifampicin-resistant isolates lacked mutations in rpoB/RRDR. Furthermore, sequence analysis of katG and inhA gene promoter revealed mainly the Ser315Thr (76%, 38/50) and C(-15)T (8%, 4/50) mutations, respectively. These two mutations combined, which are frequently associated with isoniazid-resistance,

Influenza is a major cause of respiratory infections worldwide, resulting in considerable morbidity and mortality. Children aged <5 years and those with underlying medical conditions are at particular risk. 1 Much of the data on pediatric influenza comes from developed countries in temperate climates, which have distinct seasonal peaks in winter. 2 Reported hospitalization rates have ranged from 0.9 to 3.2 per 1000 children aged <2 years. Vaccination of children against seasonal influenza is therefore widely recommended in temperate countries. In contrast, much less is known about the clinical impact of childhood seasonal influenza in tropical countries, mainly due to a perception that influenza is not a significant health problem 9 and to a lack of diagnostic virology facilities. However, studies from tropical Singapore 10 and subtropical Hong Kong 11 have indicated that the burden of influenza equals or even exceeds rates seen in temperate countries. With avian influenza (H5N1) and pandemic influenza A (H1N1) originating from developing countries, a detailed understanding of influenza becomes increasingly critical in these less well-studied areas. This study aimed to describe the clinical features of children hospitalized with laboratory-confirmed seasonal influenza in tropical Malaysia. In particular, we focused on clinical presentations, complications, and predictors of severe disease. Influenza cases over a 25-year period were also examined for seasonal patterns. The University Malaya Medical Centre (UMMC) is a 900-bed teaching hospital in Kuala Lumpur, Malaysia. It has 130 pediatric beds and approximately 6000 pediatric admissions annually. All pediatric patients <15 years of age who were admitted with laboratory-confirmed influenza from 2002 to 2007, were identified International Journal of Infectious Diseases 14S (2010) e36-e40

To assess knowledge, pregnancy attitudes and contraceptive practices in relation to the Zika virus outbreak in Brazil. We interviewed 526 women 18 to 49 years old in primary health services in a Northeastern capital of Brazil, in 2016. They provided information about their knowledge of Zika transmission and health consequences, their receipt of counseling related to sexual and perinatal transmission of Zika, their pregnancy intentions and reassessment of contraceptive options in the context of the Zika virus outbreak. Awareness about Zika congenital syndrome was high, but knowledge about sexual transmission was low. Few women had changed pregnancy intentions or contraceptive practices in response to Zika. Pregnant women were more likely to access counseling about family planning, condom use and pregnancy postponement due to Zika virus than non-pregnant women, which may suggest that health system responses followed pregnancy occurrence. We observed missed opportunities for prevention...

The period of European maritime expansion that started in the 15 th century had a great impact on trading, on human migrations and consequently in the dispersion of infectious diseases. Portugal was at the core of this expansion, however studies about parasitic infections, especially helminths, are lacking. This study aims to help reduce this gap presenting the results of microscopic analysis of soil sediments collected from the São Jorge churchyard of Sarilhos Grandes (Montijo). Consecrated in the 14 th century AD, it remained as a burial ground until the 19 th century. Soil samples collected from the pelvic girdle of five adult individuals and samples taken as control were analysed under the microscope after current conventional methodological procedures were undertaken. Eggs from Ascaris lumbricoides were identified. Also eggs of trichostrongyle type species were identified in two individuals and may represent the first report in archaeological European samples. Food remains include potato and rice starches, muscle fibres, bivalves, pollen grains and fungi spores. The stratigraphy interpretation together with potato findings put the oldest skeletons to a chronology around the 16 th century AD. These results are consistent with historical sources that documented the prominence of Tagus River nearby villages in maritime expansion.

Background: Soil-transmitted helminths and intestinal protozoa infection are widespread in developing countries, yet an accurate diagnosis is rarely performed. The aim of this study was to evaluate the recently developed mini-FLOTAC method and to compare with currently more widely used techniques for the diagnosis of intestinal parasitic infections in different settings. Methodology/Principal Findings: The study was carried out in Dharamsala, Himachal Pradesh, India, and in Bukumbi, Tanzania. A total of 180 pupils from two primary schools had their stool analyzed (n = 80 in Dharamsala and n = 100 in Bukumbi) for intestinal parasitic infections with three diagnostic methods: direct fecal smear, formol-ether concentration method (FECM) and mini-FLOTAC. Overall, 72% of the pupils were positive for any intestinal parasitic infection, 24% carried dual infections and 11% three infections or more. The most frequently encountered intestinal parasites were Entamoeba coli, Entamoeba histolytica/dispar, Giardia intestinalis, hookworm, (and Schistosoma mansoni, in Tanzania). Statistically significant differences were found in the detection of parasitic infections among the three methods: mini-FLOTAC was the most sensitive method for helminth infections (90% mini-FLOTAC, 60% FECM, and 30% direct fecal smear), whereas FECM was most sensitive for intestinal protozoa infections (88% FECM, 70% direct fecal smear, and 68% mini-FLOTAC). We present the first experiences with the mini-FLOTAC for the diagnosis of intestinal helminths and protozoa. Our results suggest that it is a valid, sensitive and potentially low-cost alternative technique that could be used in resource-limited settings -particularly for helminth diagnosis.

Background: Soil-transmitted helminths and intestinal protozoa infection are widespread in developing countries, yet an accurate diagnosis is rarely performed. The aim of this study was to evaluate the recently developed mini-FLOTAC method and to compare with currently more widely used techniques for the diagnosis of intestinal parasitic infections in different settings. Methodology/Principal Findings: The study was carried out in Dharamsala, Himachal Pradesh, India, and in Bukumbi, Tanzania. A total of 180 pupils from two primary schools had their stool analyzed (n = 80 in Dharamsala and n = 100 in Bukumbi) for intestinal parasitic infections with three diagnostic methods: direct fecal smear, formol-ether concentration method (FECM) and mini-FLOTAC. Overall, 72% of the pupils were positive for any intestinal parasitic infection, 24% carried dual infections and 11% three infections or more. The most frequently encountered intestinal parasites were Entamoeba coli, Entamoeba histolytica/dispar, Giardia intestinalis, hookworm, (and Schistosoma mansoni, in Tanzania). Statistically significant differences were found in the detection of parasitic infections among the three methods: mini-FLOTAC was the most sensitive method for helminth infections (90% mini-FLOTAC, 60% FECM, and 30% direct fecal smear), whereas FECM was most sensitive for intestinal protozoa infections (88% FECM, 70% direct fecal smear, and 68% mini-FLOTAC). We present the first experiences with the mini-FLOTAC for the diagnosis of intestinal helminths and protozoa. Our results suggest that it is a valid, sensitive and potentially low-cost alternative technique that could be used in resource-limited settings -particularly for helminth diagnosis.

Peri-and postoperative complications diminish the outcome of lung transplantation (LTx) in patients with cystic fibrosis (CF). We hypothesized that the degree of pathological findings on pre-LTx high resolution computed tomography (HRCT) is associated with higher morbidity and mortality in CF. All our CF patients undergoing LTx between 2001 and 2011 were included. HRCT examinations were evaluated according to a scoring system for pulmonary disease in CF patients, the Severe Advanced Lung Disease (SALD) score and for pleural involvement. Fifty-three patients were included. Dominant infectious/inflammatory disease according to the SALD score was observed in 10 patients (19%). Five (50%) of those patients died within one week after LTx, compared to 2 (5%) patients without dominant infectious/inflammatory disease (p<0.001). This difference in survival percentage remained also significant in multivariate analysis. Patients with infectious/inflammatory disease received more packed red blood cells; 26 versus 8 in the first week (p<0.001). Pleural thickening was associated with higher requirement (10 units) for blood transfusion during LTx, compared to patients with normal pleura (4 units). The analysis of HRCT in CF patients according to the SALD score showed that dominant infectious/inflammatory disease is associated with a higher mortality after LTx. If confirmed in other studies, HRCT might aid estimation of surgical risk in some adult CF patients.

Peri- and postoperative complications diminish the outcome of lung transplantation (LTx) in patients with cystic fibrosis (CF). We hypothesized that the degree of pathological findings on pre-LTx high resolution computed tomography (HRCT) is associated with higher morbidity and mortality in CF. All our CF patients undergoing LTx between 2001 and 2011 were included. HRCT examinations were evaluated according to a scoring system for pulmonary disease in CF patients, the Severe Advanced Lung Disease (SALD) score and for pleural involvement. Fifty-three patients were included. Dominant infectious/inflammatory disease according to the SALD score was observed in 10 patients (19%). Five (50%) of those patients died within one week after LTx, compared to 2 (5%) patients without dominant infectious/inflammatory disease (p&lt;0.001). This difference in survival percentage remained also significant in multivariate analysis. Patients with infectious/inflammatory disease received more packed red...

The Authors present the new EU Regulation n. 429/2016 on Animal Health in the hippiatric field, with the aim of highlighting the appropriate guidelines for the SSN veterinarian on communicable infectious diseases of equidae subjected to reporting obligations. The work is articulated in macro-chapters, including the detailed description of the new Animal Health Law, emerging diseases and the concept of disease notification. In this way, we want to provide support to the Official veterinarian, and to increase the level of knowledge of the application the new regulation and the compliance with it

Photoluminescence of CH 3 NH 3 PbI 3 perovskite depends strongly on sample preparation, atmosphere, crystal size, etc. However, the origin of these dependencies is always misunderstood due to the co-works of many different factors. Herein, we prepared hexagonal-shaped single crystals with tens of micrometers in size and observed a red-shifted PL emission (800 -830 nm) mainly from the crystal edges besides the usual band-to-band transition (760 nm) from the central regions. Also, significantly different time-resolved dynamics and excitation power dependencies were observed. To summary, we conclude that the red-shifted component comes from the depth of the crystal where monomolecular recombination occurs involving photogenerated charges and unintentional doped charges, while the normal PL is emitted by bimolecular recombination from the surface layers. These results showed the significance of pure optical effects in perovskite crystals and would promote detailed understanding of the charge dynamics and recombination in perovskite crystalline materials of different geometries and sizes.

HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population. We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4&gt;350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. 12 HIV-infected and 45-uninfected participants were included in the final a...

Background The coronavirus disease 2019 (COVID-19) has emerged as a global health and economic security threat with staggering cumulative incidence worldwide. Given the severity of projections, hospitals across the globe are creating additional critical care surge capacity and limiting patient routine access to care for other diseases like tuberculosis (TB). The outbreak fuels panic in sub-Saharan Africa where the healthcare system is fragile in withstanding the disease. Here, we looked over the COVID-19 containment measures in Ethiopia in context from reliable sources and put forth recommendations that leverage the health system response to COVID-19 and TB. Main text Ethiopia shares a major proportion of the global burden of infectious diseases, while the patterns of COVID-19 are still at an earlier stage of the epidemiology curve. The Ethiopian government exerted tremendous efforts to curb the disease. It limited public gatherings, ordered school closures, directed high-risk civil...

Changes during the puerperium are still unclear, particularly in women with hypertension. The choice of antihypertensives, both to control very high blood pressure episodes and to keep blood pressure stable, also requires further elucidation. Currently, there are no clear data to guide the decision for the choice of postpartum antihypertensives. Captopril plays an important role in the treatment of very high blood pressure episodes and may be used postpartum. Clonidine has been used as an alternative in pregnant or postpartum women with contraindications to captopril, with satisfactory effect. The objective of the present study was to evaluate the effectiveness and safety of clonidine compared to captopril for treating severe postpartum hypertension. A randomized, drug-controlled, triple-blind clinical trial evaluating postpartum women receiving captopril or clonidine. Inclusion criteria consisted of: women with hypertensive disorders of pregnancy systolic blood pressure (SBP) ≥180 ...

Objective: To evaluate the presence of flu-like syndrome suggestive of COVID-19 in men who have sex with men (MSM) and engaged in casual sex during a period of social isolation. Method: National epidemiological survey, applied in April and May 2020, by adaptation of Respondent Drive Sampling. Results: 1,337 MSM participated in the survey, of which 514 (38.4%) had fever associated with another sign or symptom of flu-like syndrome. Social, demographic characteristics, sexual practices and activities during the period of social isolation were statistically associated with the presence of flu-like syndrome. There was a statistical difference (p < 0.001) in the average of partners between those who had signs and symptoms of flu-like syndrome (3.5) and those who did not (1.7). Conclusion: Evidence of signs and symptoms indicative of flu-like syndrome suggestive of COVID 19 in Brazilian MSM who were involved in casual sex during the period of social isolation.

The difficulties in making an exact diagnosis of pulmonary tuberculosis in children have led to the development of different approaches for diagnosis. The aim of this study was to compare the validity of Edwards' score and a new modified Edwards' score in the diagnosis of childhood pulmonary tuberculosis. A cross sectional study was carried out at Al Azher University hospitals. One hundred twenty children were enrolled in the study and were divided to two groups. Tuberculosis group included 60 children with positive pathozyme TB complex test and respiratory symptoms and/or chest-X-ray (CXR) findings that improved using exclusively anti-tuberculosis drugs. Control group included 60 children with significant respiratory symptoms in the form of cough and or difficult breathing or tachypnea of duration not less than 7 days with or without CXR findings and who recovered from their symptoms and/or CXR findings using treatment other than anti-tuberculosis drugs and demonstrated negative pathozyme TB complex test. At enrolment the following investigations were performed: tuberculin skin test (TST), CXR postro-anterior view, complete blood count, ESR and pathozyme TB comp1ex plus test. Edwards' score and a new modified score were applied separately to all enrolled children. Sensitivity and specificity for diagnosis of pulmonary tuberculosis were higher for new modified Edwards' score than Edwards' score (93.3%, 95% versus 86.7%, 88.30% respectively). Also, positive and negative predictive values were higher for new modified Edwards' score compared with Edwards' score (95.9%, 93.4% versus 88.1%, 86.9% respectively). The mean score for diagnosis of pulmonary tuberculosis was higher in new modified Edwards' score than Edwards' score (11.4 ± 0.5 versus 10.3 ± 0.4 respectively). There was agreement between Edward score and new modified Edwards' score in diagnosis of 52 cases as pulmonary tuberculosis. It was concluded that new modified Edwards' score is better than Edwards' score in the diagnosis of childhood pulmonary tuberculosis. It was recommended to conduct a community based study with large sample size to evaluate the validity of new modified score when used on the large scale.

The immune response after early exposure to or infection with Onchocerca volvulus was investigated in an autochthonous focus caused by the migration of infected persons to a previously unaffected area in Ecuador. Peripheral blood mononuclear cell (PBMC) proliferative and cytokine responses (interferon [IFN]-g and interleukin [IL]-5) to filarial antigens were measured in 14 subjects with serologic evidence of exposure and in 7 subjects with evidence of dermal microfilarial DNA and were compared with responses in 43 subjects with chronic O. volvulus infections. PBMC proliferative and cytokine responses (IFN-g and IL-5) to parasite antigens were elevated in the early exposure/infection group, compared with those in the chronic infection group. Addition of an IL-10-neutralizing antibody to filaria antigen-stimulated cultures resulted in significantly elevated proliferative responses in the chronic infection group. The findings suggest that early exposure and early parasite patency are associated with a vigorous cellular response, but, as infections become chronic, the cellular response becomes down-regulated, partly through an IL-10-dependent mechanism. Immunoepidemiologic studies of Onchocerca volvulus infection have identified differences in cellular immune responsiveness in persons living in endemic regions that depend on parasitologic status. Subjects with patent infection (e.g., microfilariae in the skin) tend to have a parasite-specific cellular immune response characterized by poor lymphocyte proliferation, impaired production of Th1 cytokines (interleukin [IL]-2 and interferon [IFN]-g), and prominent production of Th2 cytokines (IL-4, IL-5, and IL-10), whereas those without clinical or parasitologic evidence of infection, despite evidence of exposure to the parasite (e.g., O. volvulus-specific antibody response), have enhanced lymphocyte proliferation and production of both Th1 cytokines (IL-2 and IFN-g) [1-8] and Th2 cytokines (IL-5) . The latter group has been termed putative immune (PI) or endemic normal (EN), and subjects in this group are assumed to have protective immunity to O. volvulus infection. These relatively distinct immune and parasitologic phenotypes are characteristic of adults in endemic regions and are

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta-and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats. To examine the apparent contradiction of unstable, interruption-positive SCA10 expansion alleles and to determine whether the instability originates outside of the interrupted region, we sequenced approximately 1 kb of the 5'-end of SCA10 expansions using the ATCCT-PCR product in individuals across multiple generations from four SCA10 families. We found that the greatest instability within this region occurred in paternal transmissions of the allele in stretches of pure ATTCT motifs while the intervening interrupted sequences were stable. Overall, the ATCCT interruption changes by only one to three repeat units and therefore cannot account for the instability across the length of the disease allele. We conclude that the AT-rich interruptions locally stabilize the SCA10 expansion at the 5'-end but do not completely abolish instability across the entire span of the expansion. In addition, analysis of the interruption alleles across these families support a parsimonious single origin of the mutation with a shared distant ancestor.

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta-and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats. To examine the apparent contradiction of unstable, interruption-positive SCA10 expansion alleles and to determine whether the instability originates outside of the interrupted region, we sequenced approximately 1 kb of the 5'-end of SCA10 expansions using the ATCCT-PCR product in individuals across multiple generations from four SCA10 families. We found that the greatest instability within this region occurred in paternal transmissions of the allele in stretches of pure ATTCT motifs while the intervening interrupted sequences were stable. Overall, the ATCCT interruption changes by only one to three repeat units and therefore cannot account for the instability across the length of the disease allele. We conclude that the AT-rich interruptions locally stabilize the SCA10 expansion at the 5'-end but do not completely abolish instability across the entire span of the expansion. In addition, analysis of the interruption alleles across these families support a parsimonious single origin of the mutation with a shared distant ancestor.

Gastroenteritic salmonellosis is still the second cause diagnosed of infectious diarrhea, most of these clinical pictures are mild and self-limited and therefore the use of antibiotics is limited to few cases. The aim of the study was to describe the episodes of diarrhea caused by Salmonella enterica subsp. enterica, assessing the suitability of the request and the use of antibiotics according to the criteria included in the methodology. A retrospective, descriptive, observational study was conducted, collecting data from the clinical history. A total of 122 episodes were included. The reason for consultation was diarrhea, which generated a greater demand in the Hospital Emergency Services (42.6%). The most frequent serotypes isolated were Enteritidis (53.3%), and Typhimurium (40.2%). The adequate request of the stool was 90.2%. Antibiotic was prescribed in 64.6% (79) of the episodes, most patients under 65 years (58 episodes), the average age was 48.43 years. They were treated main...

BackgroundLittle is known about the long-term course of symptoms for mild coronavirus disease 2019 (COVID-19) when accounting for symptoms due to other causes. We aimed to compare symptoms day by day for non-hospitalised individuals who tested positive and negative with polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsWe followed 210 test-positive and 630 individually matched test-negative health-care workers of the Central Denmark Region up to 90 days after the test, April-June 2020. They daily reported seven COVID-19 related symptoms. Symptom courses were compared graphically and by conditional multivariable logistic regression.ResultsThirty % of test-positive and close to zero of test-negative participants reported a reduced sense of taste and smell during all 90 days of follow-up (adjusted odds ratio [aOR] 86.07, 95% CI 22.86-323). Dyspnoea was reported by an initial 20% of test-positive with a gradual decline to about 5% after 30...

Iron is an important nutrient for the survival and growth of many organisms. In order to survive, iron uptake from the environment must be strictly regulated and maintained to avoid iron toxicity. The ferric uptake regulator protein (Fur) regulates genes involved in iron homeostasis in many bacteria, including phytopathogens. However, to date, the role played by Fur in the biology of Pectobacterium carotovorum subsp. brasiliense (Pcb1692), an important pathogen of potatoes, has not yet been studied. To this end, we used the lambda recombineering method to generate a fur mutant strain of Pcb1692 and assessed the virulence and fitness of the mutant strain. The results showed that production of siderophores in Pcb1692Δfur increased compared to the Pcb1692 wild-type and the complemented strain Pcb1692Δfur-pfur. However, production of N-acyl homoserine lactone (AHLs), biofilm formation, exopolysaccharide (EPS) production, virulence on potato tubers and swimming motility, were all significantly decreased in Pcb1692Δfur compared to the wild-type and complemented Pcb1692Δfur-pfur strains. The Pcb1692Δfur mutant also demonstrated significant sensitivity to oxidative stress when exposed to H 2 O 2 . Consistent with phenotypic results, qRT-PCR results demonstrated that Fur down-regulates genes which encode proteins associated with: iron uptake (HasA-extracellular heme-binding protein and Ferrodoxin-AED-0004132), stress response (SodC-superoxide dismutase), plant cell wall degrading enzymes (PrtA and CelV) and motility (FlhC and MotA). We conclude that the ferric uptake regulator protein (Fur) of Pcb1692 regulates traits that are important to host-pathogens interactions.

Iron is an important nutrient for the survival and growth of many organisms. In order to survive, iron uptake from the environment must be strictly regulated and maintained to avoid iron toxicity. The ferric uptake regulator protein (Fur) regulates genes involved in iron homeostasis in many bacteria, including phytopathogens. However, to date, the role played by Fur in the biology of Pectobacterium carotovorum subsp. brasiliense (Pcb1692), an important pathogen of potatoes, has not yet been studied. To this end, we used the lambda recombineering method to generate a fur mutant strain of Pcb1692 and assessed the virulence and fitness of the mutant strain. The results showed that production of siderophores in Pcb1692Δfur increased compared to the Pcb1692 wild-type and the complemented strain Pcb1692Δfur-pfur. However, production of N-acyl homoserine lactone (AHLs), biofilm formation, exopolysaccharide (EPS) production, virulence on potato tubers and swimming motility, were all significantly decreased in Pcb1692Δfur compared to the wild-type and complemented Pcb1692Δfur-pfur strains. The Pcb1692Δfur mutant also demonstrated significant sensitivity to oxidative stress when exposed to H 2 O 2 . Consistent with phenotypic results, qRT-PCR results demonstrated that Fur down-regulates genes which encode proteins associated with: iron uptake (HasA-extracellular heme-binding protein and Ferrodoxin-AED-0004132), stress response (SodC-superoxide dismutase), plant cell wall degrading enzymes (PrtA and CelV) and motility (FlhC and MotA). We conclude that the ferric uptake regulator protein (Fur) of Pcb1692 regulates traits that are important to host-pathogens interactions.

The ability to adapt to adverse conditions permits many bacterial species to be virtually ubiquitous and survive in a variety of ecological niches. This ability is of particular importance for many plant pathogenic bacteria that should be able to exist, except for their host plants, in different environments e.g. soil, water, insect-vectors etc. Under some of these conditions, bacteria encounter absence of nutrients and persist, acquiring new properties related to resistance to a variety of stress factors (cross-protection). Although many studies describe the phenomenon of cross-protection and several regulatory components that induce the formation of resistant cells were elucidated, the global comparison of the physiology of cross-protected phenotype and growing cells has not been performed. In our study, we took advantage of RNA-Seq technology to gain better insights into the physiology of cross-protected cells on the example of a harmful phytopathogen, Pectobacterium atrosepticum (Pba) that causes crop losses all over the world. The success of this bacterium in plant colonization is related to both its virulence potential and ability to persist effectively under various stress conditions (including nutrient deprivation) retaining the ability to infect plants afterwards. In our previous studies, we showed Pba to be advanced in applying different adaptive strategies that led to manifestation of cell resistance to multiple stress factors. In the present study, we determined the period necessary for the formation of cross-protected Pba phenotype under starvation conditions, and compare the transcriptome profiles of non-adapted growing cells and of adapted cells after the cross-protective effect has reached the maximal level. The obtained data were verified using qRT-PCR. Genes that were expressed differentially (DEGs) in two cell types were classified into functional groups and categories using different approaches. As a result, we portrayed physiological features that distinguish cross-protected phenotype from the growing cells.

1 Profesor, Departamento de Cirugía General, Universidad de Antioquia, Hospital Universitario San Vicente de Paúl, Medellín, Colombia. 2 Residente, Departamento de Cirugía Plástica, Maxilofacial y de la Mano, Universidad de Antioquia, Medellín, Colombia. 3 Residente, Departamento ...

Chagas disease is a parasitic disease, endemic in South America. As of today, there is no effective treatment in its chronic stage. We have recently identified 134 FDA approved drugs with potential antitrypanosomal activity. In this paper, we propose a novel method for selecting combinations of drugs (drug cocktails), to provide a more effective treatment against Chagas disease. We define three measures to evaluate the predicted performance of a cocktail, establishing in this way a mathematical foundation for its analysis. This allows us to model the drug cocktail selection as a multi-objective optimisation problem, that we show can be solved efficiently with state-of-the-art evolutionary algorithms. Our analysis retrieves 57 drug cocktails containing between 2 and 6 drugs. We discuss the improvement of the cocktail selection given by our method, and the application of this approach to the identification of cocktails against other parasitic diseases.

About 2.5% of the world population, corresponding to about 177 million individuals, are infected by hepatitis C virus (HCV), a small, single-stranded RNA virus. The prevalence of HCV infection among dialysis patients in Japan, Europe, and North America during the 2012 to 2015 period was found to be 8.7% in the DOPPS study. Nosocomial HCV spread in hemodialysis facilities still occurs. Increased hepatic tissue iron has been shown to play a deleterious role in the course of hepatitis C, favor development of fibrosis and cirrhosis and possibly increase the risk of liver cancer in the general population. Regular loss of blood in the hemodialysis circuit, in routine blood sampling for laboratory tests (for uremia monitoring), and in gut due to uremic enteropathy, invariably results in iron deficiency for which patients are commonly treated with intravenous (IV) iron preparations. Data on the effects of IV iron in hemodialysis patients with hepatitis C are limited (2 studies) and strongly suggest that parenteral iron may contribute to hepatocellular injury. Iatrogenic iron overload is extremely prevalent among hemodialysis population worldwide. Iron overload and toxicity has emerged as one of the most controversial topic in the management of anemia in dialysis patients. Given the known impact of iron in promoting growth and virulence of HCV and the associated liver disease, it is necessary to use iron therapy cautiously and closely monitor plasma markers of iron metabolism and liver iron stores non-invasively by means of MRI to avoid iron overload in this vulnerable population.

The term "sign" has been used to describe various phenomena observed in patients with coronavirus disease 2019 . Discrepancies in the use of this term have been identified when it is used in context with COVID-19. The goals of this review are to provide an overview, describe signs, and clarify misconceptions regarding the use of these terms in COVID-19 patients. PubMed and Medline databases were searched using individual and Medical Subject Headings (MeSH) terms, including coronavirus, COVID-19, and sign, in human studies within the English literature published from inception to December 31, 2020. Studies where the word "sign" was used in a context different from that for COVID-19 (e.g., sentinel sign) were excluded. Three hundred fifty-seven studies were potentially identified and after applying the exclusion criteria and further adjudication, 92 studies constituted the final data set. The majority of signs found in the COVID-19 literature have been applied and aptly described primarily in radiologic diseases of the chest. The term "sign," in other situations, is often misappropriated as it actually represents a physical finding rather than a sign. A total of 27 radiologic signs have been identified on chest computed tomography (CT) or high-resolution CT (HRCT), and 18 cutaneous signs (or findings) have been observed during the physical examination in COVID-19. Signs lack sufficient sensitivity or specificity by themselves; however, in the appropriate clinical setting, they should raise clinical suspicion for this infectious disease.

Seventy-two stocks of Trypanosoma rruZi isolated from both sides of the West Andes highland (Bolivia, Chile and Peru) were analysed by isoenzyme electrophoresis at 12 loci. The data, which were interpreted in terms of population and evolutionary genetics, corroborated the hypothesis of T. rrun' clonal population structure previously proposed, and indicated extensive genetic variability within the taxon T . cruzi. Fifteen different clones (or zymodemes) were identified, which could be grouped into 3 different clusters. Several clones from 2 of these clusters were isolated both in Chile and Bolivia, suggesting a significant circulation of invertebrate and/or vertebrate hosts of T. m" between these 2 countries. Low clonal variability in Peru suggested the occurrence of a 'founder effect' in this country. The potential usefulness of a cladistic approach in epidemiology is discussed.

Ferroelectrics (FEs) are materials of paramount importance with a wide diversity of applications. Herein, we propose a postsynthetic methodology for the smart implementation of ferroelectricity in chiral metal-organic frameworks (MOFs): following a single-crystal to single-crystal cation metathesis, the Ca(2+) counterions of a preformed chiral MOF of formula Ca6(II){Cu(II)24[(S,S)-hismox]12(OH2)3}·212H2O (1), where hismox is a chiral ligand derived from the natural amino acid l-histidine, are replaced by CH3NH3(+). The resulting compound, (CH3NH3)12{Cu(II)24[(S,S)-hismox]12(OH2)3}·178H2O (2), retains the polar space group of 1 and is ferroelectric below 260 K. These results open a new synthetic avenue to enlarge the limited number of FE MOFs.