Low Plasma Lipids Are Associated with Relapsing and Lethal Visceral Leishmaniasis in HIV-Infected Patients.

Visceral leishmaniasis (VL) results from protozoa Leishmania infantum and L. donovani infection. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both groups of patients in the first episode and with relapsing VL. Still, the strongest blood cell indicator associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and twenty-three with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low low-density lipoprotein. After CD4+ decreases, lymphocyte CD8+ reduction is the final stage of immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia and fat exhaustion provoked by the co-occurrence of both diseases, which can finally lead to death.

Redefining the simplicity of the craniomandibular complex of nightjars: The case of Systellura longirostris (Aves: Caprimulgidae) by means of anatomical network analysis.

To study morphological evolution, it is necessary to combine information from multiple intersecting research fields. Here, we report on the structure of the bony and muscular elements of the craniomandibular complex of birds, highlighting its morphological architecture and complexity (or simplification) in the context of anatomical networks of the Band-winged Nightjar Systellura longirostris (Caprimulgiformes, Caprimulgidae). This species has skull osteology and jaw myology that departs from the general structural plan of the craniomandibular complex of Neornithes and is considered morphologically simple. Our goal is to test if its simplification is also reflected in its anatomical network, particularly in those parameters that measure complexity and to explore if the distribution of the networks in a phylomorphospace is conditioned by their evolutionary history or by convergence. Our results show that S. longirostris clusters with other Strisores and momotids and is segregated from the other bird species analyzed when plotted in the phylomorphospace, as a consequence of convergence in the network parameters. Systellura has a craniomandibular complex consisting of fewer muscles connecting more bones than the model species (e.g., the rock pigeon or the guira cuckoo). In this sense, Systellura is actually more complex regarding the number of integrative bony parts, while its craniomandibular complex is simpler. According to its anatomical network, Systellura also can be interpreted as less complex, particularly compared with other Strisores and taxa that reflect the general structure of the craniomandibular complex in Neornithes.

Emergent Crisis of COVID-19 Pandemic: Mental Health Challenges and Opportunities.

Mental health is a fundamental human right and is part of the well-being of society. The public health burden of mental health disorders affects people's social and economic status around the world. Coronavirus's (COVID-19) negative impact on the economy and mental health worldwide is concerning. This is a worldwide emergency, and there is an urgent need for research about this topic to prevent long-lasting adverse effects on the population. Unpreparedness and inconsistencies in guidelines, lockdowns, containment strategies, unemployment, financial losses, physical distancing, isolation, chaos, and uncertainty are among factors that lead to a rise in emotional distress, anxiety, and depression. Governments' decisions affect the socioeconomic status of a country and the psychological well-being of the people. COVID-19 pandemic exposed disparities in multiple mental health care systems by having adverse mental health effects in people with pre-existing mental health disorders and previously healthy individuals. Aggregation of concurrent or cumulative comorbid risk factors for COVID-19 disease and its psychosocial sequelae could provide invaluable information for the public health stakeholders. This review aims to address the burden and the psychosocial impact of the COVID-19 pandemic, the challenges and opportunities facing mental health systems, and proposes new strategies to improve the mental health outcomes in the post-COVID era.

The cranio-mandibular complex of the nightjar Systellura longirostris (Aves, Caprimulgiformes): functional relationship between osteology, myology and feeding.

Here we address the morphology of the cranial musculoskeletal in the South American Band-winged nightjar (Systellura longirostris, Caprimulgiformes, Aves) with the focus upon in how the mouth closure and opening mechanism is. Bony characters such as the thinness of the interorbital septum and the reduction of the postorbital process co-assist the location of large eyes, although correlations between eye size brain mass and body mass revealed that the Band-winged nightjar's eye is bigger than expected. The reduction of the processus orbitalis of the os quadratum would allow the great mouth opening given by a large maxillary protraction. Systellura longirostris shows a zona flexoria intramandibularis with marked reduction in bone ossification that helps to the lateral opening of the jaws. In Systellura longirostris, the m. pseudotemporalis profundus, m. adductor mandibulae externus superficialis, and m. adductor mandibulae externus medialis are absent. The adductor muscles represent 66.614% of the total mandibular muscle mass. Physiological Cross Sectional Area (PCSA) values of the adductor muscles are high and the fibers are relatively long compared to other zoophagous birds, another condition that favors adduction. The m. adductor mandibulae externus profundus is the largest jaw muscle regarding its mass but its osteological correlate on the neurocranium, the fossa temporalis, is absent. In the absence of some muscles in charge of the bill closing, an elastic instability model for jaw closing is proposed.

Comparison of the Pharmacokinetics and Pharmacodynamics of LY2963016 Insulin Glargine and EU- and US-Approved Versions of Lantus Insulin Glargine in Healthy Subjects: Three Randomized Euglycemic Clamp Studies.

OBJECTIVE: LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products manufactured by distinct processes but with identical amino acid sequences. Three studies evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) similarity of LY IGlar and the European Union- and US-approved versions of IGlar. RESEARCH DESIGN AND METHODS: These were three single-site, randomized, double-blind, two-treatment, four-period, crossover, euglycemic clamp studies. In each study, fasted healthy subjects received 0.5 units/kg s.c. doses of two different insulin glargine products on two occasions each, following a randomized sequence. A ≥7-day washout period separated the doses. Blood samples were collected predose and up to 24 h postdose to assess PK; PD was assessed by a euglycemic clamp lasting up to 24 h. RESULTS: A total of 211 subjects participated in the three studies. The PK (area under the curve [AUC]; maximum observed concentration [Cmax]) and PD (maximum glucose infusion rate [Rmax]; total glucose infusion during the clamp [Gtot]) were similar between LY IGlar and IGlar, with the ratios of geometric means ranging from 0.90 to 0.95 for PK parameters and from 0.91 to 0.99 for PD parameters across studies. In all cases, the 90% CIs for the ratios of geometric means were completely contained in the prespecified acceptance limits of 0.80-1.25. Adverse events were similar between treatments. CONCLUSIONS: These studies demonstrated that the PK and PD properties of LY IGlar and IGlar were similar after single 0.5 units/kg s.c. doses in healthy subjects, contributing to the totality of evidence supporting similarity of these products.

Comparative pharmacokinetics of a once-daily tramadol extended-release tablet and an immediate-release reference product following single-dose and multiple-dose administration.

The pharmacokinetics of a once-daily formulation of tramadol (Tramadol Contramid OAD 200-mg tablets) following single-dose and multiple-dose administration was compared with that of an immediate-release product (tramadol IR 50-mg tablets) in 2 separate studies. In both studies, AUC parameters met bioequivalence criteria, whereas C(max) of Tramadol Contramid OAD was lower than that of tramadol IR following a 200-mg daily dosage. After single-dose administration, the mean tramadol concentration at 1 hour postdose was within the range associated with analgesic efficacy (>100 ng/mL), and the mean concentration remained above this level for the remainder of the dosing interval. Steady state was attained within 48 hours following multiple-dose administration. Tramadol Contramid OAD provides a rapid rise in plasma concentrations and an equivalent daily systemic exposure as tramadol IR, with a reduction in peak plasma concentrations.

Quantification of free circulating tumor DNA as a diagnostic marker for breast cancer.

AIM: To determine whether the amounts of circulating DNA could discriminate between breast cancer patients and healthy individuals by using real-time PCR quantification methodology. METHODS: Our standard protocol for quantification of cell-free plasma DNA involved 175 consecutive patients with breast cancer and 80 healthy controls. RESULTS: We found increased levels of circulating DNA in breast cancer patients compared to control individuals (105.2 vs. 77.06 ng/mL, p < 0.001). We also found statistically significant differences in circulating DNA amounts in patients before and after breast surgery (105.2 vs. 59.0 ng/mL, p = 0.001). Increased plasma cell-free DNA concentration was a strong risk factor for breast cancer, conferring an increased risk for the presence of this disease (OR, 12.32; 95% CI, 2.09-52.28; p < 0.001). CONCLUSIONS: Quantification of circulating DNA by real-time PCR may be a good and simple tool for detection of breast cancer with a potential to clinical applicability together with other current methods used for monitoring the disease.