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Severe acute respiratory syndrome coronavirus 2 is a recently discovered pathogen responsible of coronavirus disease 2019 (COVID-19). The immunological changes associated with this infection are largely unknown. We evaluated the peripheral blood mononuclear cells profile of 63 patients with COVID-19 at diagnosis. We also assessed the presence of association with inflammatory biomarkers and the 28-day mortality. Lymphocytopenia was present in 51 of 63 (80.9%) patients, with a median value of 720 lymphocytes/µl (IQR 520-1,135). This reduction was mirrored also on CD8+ (128 cells/µl, IQR 55-215), natural killer (67 cells/µl, IQR 35-158) and natural killer T (31 cells/µl, IQR 11-78) cells. Monocytes were preserved in total number but displayed among them a subpopulation with a higher forward and side scatter properties, composed mainly of cells with a reduced expression of both CD14 and HLA-DR. Patients who died in the 28 days from admission (N=10, 15.9%), when compared to those who did not, displayed lower mean values of CD3+ (337.4 cells/µl vs 585.9 cells/µl; p=0.028) and CD4+ cells (232.2 cells/µl vs 381.1 cells/µl; p=0.042) and an higher percentage of CD8+/CD38+/HLA-DR+ lymphocytes (13.5% vs 7.6%; p=0.026). The early phases of COVID-19 are characterized by lymphocytopenia, predominance of Th2-like lymphocytes and monocytes with altered immune profile, which include atypical mononuclear cells.

Polypharmacy represents a major clinical and public health issue in older persons. We aimed to measure the prevalence of polypharmacy, and the main predictors of drug prescription in nursing home residents. Post hoc analyses of the “Incidence of pNeumonia and related ConseqUences in nursing home Residents” (INCUR) study were conducted. Polypharmacy was defined as the prescription of 5 or more drugs. A frailty index (FI) was computed according to the model proposed by Rockwood and Mitnitski using 36 health deficits, including diseases, signs, symptoms, and disabilities. Linear regression models were performed to identify the main predictors of the number of prescribed drugs. The INCUR study enrolled 800 patients (mean [SD] age 86.2 [4.1] years, 74.1% women). The mean number of medications prescribed at the baseline was 8.5 (SD 4.1). Prevalence of polypharmacy was found 86.4%. The mean FI was 0.38 (SD 0.10). A fully adjusted linear multivariate regression model found an inverse and independent association between age and number of prescribed drugs (beta − 0.07, 95% CI − 0.13, − 0.02; p = 0.005). Conversely, the FI was independently and positively associated with the number of medications (beta 4.73, 95% CI 1.17, 8.29; p = 0.009). The prevalence of polypharmacy is high among older persons living in nursing home. Age and FI are significantly associated with the number of drugs. The number of prescribed drugs tends to decrease with age, whereas a direct association with frailty is reported.

The main motivations of growth hormone (GH) treatment of Prader-Willi syndrome (PWS) are the stimulation of growth and lean muscle mass. Furthermore GH therapy in Prader-Willi children seems to favorably affect their behavior and mental performances. It is still a matter of discussion whether GH therapy in PWS should be considered responsible for specific adverse events. The most significant of them are scoliosis and breathing disorders, the latter considered being responsible for some deaths, reported in children with PWS, mainly at the beginning of GH therapy. Obstructive sleep apnea was occasionally reported also in patients treated with GH for several years. The review reports and discusses the latest data related to side effects of long-term GH treatment in children with PWS.

Background Social insects are among the most serious invasive pests in the world, particularly successful at monopolizing environmental resources to outcompete native species and achieve ecological dominance. The invasive success of some social insects is enhanced by their unicolonial structure, under which the presence of numerous queens and the lack of aggression against non-nestmates allow high worker densities, colony growth, and survival while eliminating intra-specific competition. In this study, we investigated the population genetics, colony structure and levels of aggression in the tawny crazy ant, Nylanderia fulva , which was recently introduced into the United States from South America. Results We found that this species experienced a genetic bottleneck during its invasion lowering its genetic diversity by 60%. Our results show that the introduction of N. fulva is associated with a shift in colony structure. This species exhibits a multicolonial organization in its native range, with colonies clearly separated from one another, whereas it displays a unicolonial system with no clear boundaries among nests in its invasive range. We uncovered an absence of genetic differentiation among populations across the entire invasive range, and a lack of aggressive behaviors towards conspecifics from different nests, even ones separated by several hundreds of kilometers. Conclusions Overall, these results suggest that across its entire invasive range in the U.S.A., this species forms a single supercolony spreading more than 2000 km. In each invasive nest, we found several, up to hundreds, of reproductive queens, each being mated with a single male. The many reproductive queens per nests, together with the free movement of individuals between nests, leads to a relatedness coefficient among nestmate workers close to zero in introduced populations, calling into question the stability of this unicolonial system in which indirect fitness benefits to workers is apparently absent.

Abstract Objective Given the risks of long-term opioid therapy, patients may benefit from tapering these medications. There is little evidence to guide providers’ approach to this process. We explored primary care providers’ experiences discussing and implementing opioid tapering with patients on long-term opioid therapy. Design Qualitative study using six semistructured, in-person focus groups. Subject Primary care providers (N = 40). Setting Six academically affiliated primary care clinics in university, urban safety net, and Veterans Health Administration medical centers in Colorado. Methods Focus groups were audio-recorded, transcribed, and analyzed using a mixed inductive-deductive approach in ATLAS.ti. Emergent themes were identified through an iterative, multidisciplinary team-based process. Results We identified 1) strategies for identifying candidates for opioid tapering, 2) barriers to opioid tapering, and 3) facilitators of opioid tapering. Strategies for identifying candidates for opioid tapering included evidence of high-risk behavior, serious adverse events, opioid-related side effects, and patient preference. Barriers included the providers’ emotional burden, inadequate resources, and a lack of trust between patient and provider. Facilitators of opioid tapering included empathizing with the patient’s experience, preparing patients for opioid tapering, individualizing implementation of opioid tapering, and supportive guidelines and policies. Conclusions While discussing and implementing opioid tapering present significant challenges, primary care providers described key facilitators. These findings suggest a need to develop and test the effectiveness of resources to support patient-centered opioid tapering and locally developed policies to support and standardize providers’ approaches to opioid prescribing.

Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants. In this review, we have collected data obtained from various research groups on the antimicrobial activities of these alkaloids against conventional antibiotic-resistant strains. In addition, the structure–function relationship was described and commented on, highlighting the high potential of alkaloids as antimicrobials.

The Pictet-Spengler reaction (P-S) is one of the most direct, efficient, and variable synthetic method for the construction of privileged pharmacophores such as tetrahydro-isoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), and polyheterocyclic frameworks. In the lustro (five-year period) following its centenary birthday, the P-S reaction did not exit the stage but it came up again on limelight with new features. This review focuses on the interesting results achieved in this period (2011–2015), analyzing the versatility of this reaction. Classic P-S was reported in the total synthesis of complex alkaloids, in combination with chiral catalysts as well as for the generation of libraries of compounds in medicinal chemistry. The P-S has been used also in tandem reactions, with the sequences including ring closing metathesis, isomerization, Michael addition, and Gold- or Brønsted acid-catalyzed N-acyliminium cyclization. Moreover, the combination of P-S reaction with Ugi multicomponent reaction has been exploited for the construction of highly complex polycyclic architectures in few steps and high yields. The P-S reaction has also been successfully employed in solid-phase synthesis, affording products with different structures, including peptidomimetics, synthetic heterocycles, and natural compounds. Finally, the enzymatic version of P-S has been reported for biosynthesis, biotransformations, and bioconjugations.