Resolving the relaxation complexity of vitrimers: time-temperature superpositions of a time-temperature non-equivalent system

Vitrimers are polymer networks that, thanks to covalent bond exchange, combine desirable properties of thermoplastic and thermosets, such as flowability and insolubility. For this reason, vitrimers are considered to be good candidates for a number of innovative applications from self-healing soft robots to hard reprocessable materials. All these applications are related to the unusual thermomechanical behavior of vitrimers, consequence of the non-trivial interplay between the polymer network dynamics and the thermally activated chemical link exchange. Here we use solid-state rheology to investigate the properties of a recently developed epoxy-based vitrimer. The rheological analysis demonstrates that the mechanical spectrum is composed of two relaxation processes with distinct activation energies which are associated with glass dynamics and covalent bond exchange, respectively. This makes the material thermo-rheologically complex and time temperature equivalence does not apply. Nonetheless, thanks to mechanical spectral analysis in a wide range of stiffness, time and temperature, we are able to depict the time-temperature-relaxation landscape in an enough precise way to account for the two dynamical processes and recombine them to predict the mechanical moduli in a wide (virtually unlimited) interval of frequencies, from low temperatures (close to room temperature) to high temperatures (above the Tg)

Human African trypanosomiasis

Human African trypanosomiasis (sleeping sickness) occurs in sub-Saharan Africa. It is caused by the protozoan parasite Trypanosoma brucei, transmitted by tsetse flies. Almost all cases are due to Trypanosoma brucei gambiense, which is indigenous to west and central Africa. Prevalence is strongly dependent on control measures, which are often neglected during periods of political instability, thus leading to resurgence. With fewer than 12 000 cases of this disabling and fatal disease reported per year, trypanosomiasis belongs to the most neglected tropical diseases. The clinical presentation is complex, and diagnosis and treatment difficult. The available drugs are old, complicated to administer, and can cause severe adverse reactions. New diagnostic methods and safe and effective drugs are urgently needed. Vector control, to reduce the number of flies in existing foci, needs to be organised on a pan-African basis. WHO has stated that if national control programmes, international organisations, research institutes, and philanthropic partners engage in concerted action, elimination of this disease might even be possible

Prevalence and risk factors of Strongyloides stercoralis in haemodialysis in Cochabamba, Bolivia: a cross-sectional study.

BACKGROUND Strongyloidiasis is an infectious disease that can be fatal in immunocompromised patients. Patients with end-stage renal failure who are on dialysis have a considerably weakened immune system, and organ transplantation is a major risk factor for severe strongyloidiasis. Knowledge of the local epidemiology in tropical and subtropical areas is an essential prerequisite for designing an appropriate strategy to prevent this potentially lethal complication. In this study, we aimed to estimate the prevalence and associated risk factors of S. stercoralis infection in patients on dialysis in Cochabamba, Bolivia. METHODS A cross-sectional study was carried out among patients undergoing haemodialysis in Cochabamba (elevation 2,500 m, temperate climate), collecting information on socio-demographic, lifestyle, and clinical variables, and using one coproparasitological technique (the modified Baermann technique) and one serological (ELISA) test for S.stercoralis diagnosis. RESULTS In total, 149 patients participated in the study (mean age = 51.4 years, 48.3% male). End-stage renal disease was predominantly (59%) of hypertensive and/or diabetic origin. The positive serological prevalence was 18.8% (95% CI: 13.3%-25.9%). Based on the sensitivity and specificity of the ELISA test, the estimate of the actual prevalence was 15.1% (95% CI: 9.4%-20.7%). Stool samples of 105 patients (70.5%) showed a coproparasitological prevalence of 1.9% (95% CI: 0.52%-6.68%). No potential risk factors were significantly associated with S. stercoralis infection. CONCLUSIONS We found a high seroprevalence of S. stercoralis in Bolivian patients undergoing haemodialysis in Cochabamba. We recommend presumptive antiparasitic treatment at regular intervals to avoid the potentially fatal complications of severe strongyloidiasis

Effectiveness of a 10-Day Melarsoprol Schedule for the Treatment of Late-Stage Human African Trypanosomiasis: Confirmation from a Multinational Study (Impamel II)

BackgroundTreatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study MethodsA total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up ResultsThe cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively ConclusionsThe 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiens

Influence of Leishmania (Viannia) Species on the Response to Antimonial Treatment in Patients with American Tegumentary Leishmaniasis

Background. Pentavalent antimonials (SbV) are the first-line chemotherapy for American tegumentary leishmaniasis (ATL). There are, however, reports of the occurrence of treatment failure with these drugs. Few studies in Latin America have compared the response to SbV treatment in ATL caused by different Leishmania species. Methods. Clinical parameters and response to SbV chemotherapy were studied in 103 patients with cutaneous leishmaniasis (CL) in Peru. Leishmania isolates were collected before treatment and typed by multilocus polymerasechain-reaction restriction fragment—length polymorphism analysis. Results. The 103 isolates were identified as L. (Viannia) peruviana (47.6%), L. (V.) guyanensis (23.3%), L. (V.) braziliensis (22.3%), L. (V.) lainsoni (4.9%), L. (Leishmania) mexicana (1%), and a putative hybrid, L. (V.) braziliensis/L. (V.) peruviana (1%). L. (V.) guyanensis was most abundant in central Peru. Of patients infected with the 3 former species, 21 (21.9%) did not respond to SbV chemotherapy. The proportions of treatment failure (after 12 months of follow-up) were 30.4%, 24.5%, and 8.3% in patients infected with L. (V.) braziliensis, L. (V.) peruviana, and L. (V.) guyanensis, respectively. Infection with L. (V.) guyanensis was associated with significantly less treatment failure than L. (V.) braziliensis, as determined by multiple logistic regression analysis (odds ratio, 0.07 [95% confidence interval, 0.007-0.8]; P = .03). Conclusions. Leishmania species can influence SbV treatment outcome in patients with CL. Therefore, parasite identification is of utmost clinical importance, because it should lead to a species-oriented treatmen

Clinical and Parasite Species Risk Factors for Pentavalent Antimonial Treatment Failure in Cutaneous Leishmaniasis in Peru

Background. Treatment for cutaneous leishmaniasis (CL) with standard pentavalent antimonial therapy is hampered by cumbersome administration, toxicity, and potential failure. Knowledge of factors influencing treatment outcome is essential for successful management. Methods. A case-control study of incident cases was performed with patients experiencing their first CL episode. The standard treatment for CL for these patients was 20 mg/kg/day of sodium stibogluconate for 20 days. Clinical and epidemiological data were recorded, and parasite isolates were species typed. Patients were followed up for 6 months to assess treatment outcome. Clinical cure was defined as complete wound closure and re-epithelization without inflammation or infiltration; new lesions, wound reopening, or signs of activity were classified as treatment failure. Descriptive, bivariate, and logistic regression analyses were performed. Results. One hundred twenty-seven patients were recruited; 63 (49.6%) were infected with Leishmania (Viannia) peruviana, 29 (22.8%) were infected with Leishmania (Viannia) braziliensis, 27 (21.3%) were infected with Leishmania (Viannia) guyanensis, and 8 (6.3%) were infected with other species. Only patients infected with the 3 most common species were selected for risk-factor analysis (n=119). Final failure rate at 6 months was 24.4% (95% confidence interval [CI], 16.5%-32.1%), with 96% of failures occurring within the first 3 months of follow-up assessment. Risk factors for treatment failure identified in the final multivariate model were age (per year, odds ratio [OR], 0.95; 95% CI, 0.92-0.99; P=.017), stay of <72 months in area of disease acquisition (OR, 30.45; 95% CI, 2.38-389.25; P=.009), duration of disease <5 weeks (OR, 4.39; 95% CI, 1.12-17.23; P=.034), additional lesion (per lesion, OR, 2.06; 95% CI, 1.3-3.28; P=.002), infection with L. (V.) peruviana (OR, 9.85; 95% CI, 1.01-95.65; P=.049), and infection with L. (V.) braziliensis (OR, 22.36; 95% CI, 1.89-263.96; P=.014). Conclusions. The identification of parasite species and clinical risk factors for antimonial treatment failure should lead to an improved management of CL in patients in Per

Vulnerability to snakebite envenoming: a global mapping of hotspots.

BACKGROUND Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. METHODS We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. FINDINGS We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. INTERPRETATION Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease

Multisystem diseases and infections

Differential diagnosis of fevers?, Fever without localizing features?, Sepsis?, Cancer?, General rules of cancer management?, Rheumatoid arthritis?, Osteoarthritis?, Systemic lupus erythematosus?, Typhoid and paratyphoid fevers?, Rickettsioses?, Bartonella?, Ehrlichia?, Coxiella?, Relapsing fevers?, Leptospirosis?, Brucellosis?, Plague?, Melioidosis?, Anthrax?, African trypanosomiasis?, American trypanosomiasis?, Visceral leishmaniasis (kala-azar)?, Infectious mononucleosis?, Measles?, Arboviruses and zoonotic haemorrhagic fever viruses , Ebola and Marburg virus diseases, Crimean-Congo haemorrhagic fever, Rift Valley fever, Lassa fever, Hantavirus infections, Severe fever and thrombocytopenia, Zika virus, Japanese encephalitis , Dengue virus, Yellow fever, West Nile virus , Kyasanur Forest Disease, Chikungunya, Ross River fever, O'nyong nyon