Uruguay has one of the highest per capita milk intakes worldwide, even with a limited supply of lactose‐free products; furthermore, the admixed nature of its population is well known, and various ...frequencies of lactase persistence (LP) are observed in the source populations. We aimed to contribute to the understanding of the relation between allelic variants associated with LP, milk consumption, digestive symptoms, and genetic ancestry in the Uruguayan population. Samples of saliva or peripheral blood were collected from 190 unrelated individuals from two regions of Uruguay, genotypes for polymorphic sites in a fragment within the LCT enhancer were determined and allelic frequencies calculated in all of them. Data were collected on frequency of milk and dairy consumption and self‐reported symptoms in a subsample of 153 individuals. Biparental and maternal ancestry was determined by analyzing individual ancestry markers and mitochondrial DNA. Twenty‐nine percentage of individuals reported symptoms attributed to the ingestion of fresh milk, with abdominal pain, bloating and flatulence being the most frequent. European LP‐associated allele T‐13910 showed a frequency of 33%, while other LP‐associated alleles like G‐13915 and T‐14011 were observed in very low frequencies. Associations between self‐reported symptoms, fresh milk intake, and C/T‐13910 genotype were statistically significant. No evidence of association between genetic ancestry and C/T‐13910 was found, although individuals carrying one T‐13910 allele appeared to have more European ancestry. In conclusion, the main polymorphism capable of predicting lactose intolerance in Uruguayans is C/T‐13910, although more studies are required to unravel the relation between genotype and lactase activity, especially in heterozygotes.
Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid ...and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections.
Background
Knowledge of chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys is limited as few studies have explored this disorder. This study aimed to identify the usefulness ...of assessing hormonal parameters in male adolescents with CKD and their correlation with PD in a 12‐month follow‐up period.
Methods
A prospective cohort study was conducted among male adolescents with CKD (stages IV and V). Data regarding the age at puberty onset were collected from the patients’ clinical records and through interview. The patients were followed up for 12 months during their pubertal development. At the beginning, routine hormonal profile tests were performed to examine the patients’ thyroid profile, prolactin levels, luteinizing hormone, follicle‐stimulating hormone, testosterone, leptin, and receptor leptin. The hormonal profiles of patients with and without PD were compared. Comparisons between the groups were performed using the Student t‐test and Fisher's exact tests. Logistic regression analysis was also performed.
Results
Data of 64 patients (26/64 with PD) were analyzed. The median age was 15 years and the median time for CKD evolution was 11 months. No differences between groups were noted in the general or biochemical characteristics of the patients. The hormonal parameters, prolactin levels were higher and the free leptin and free thyroxine levels were lower in patients with PD. Leptin receptor levels of >0.90 ng/mL (risk ratio RR, 8.6; P = 0.004) and hyperprolactinemia (RR, 21.3; P = 0.049) were the risk factors for PD.
Conclusions
Leptin receptor levels of >0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.
Crimean–Congo haemorrhagic fever (CCHF) is an emerging tick‐borne human disease in Spain. Understanding the spatiotemporal dynamics and exposure risk determinants of CCHF virus (CCHFV) in animal ...models is essential to predict the time and areas of highest transmission risk. With this goal, we designed a longitudinal survey of two wild ungulate species, the red deer (Cervus elaphus) and the Eurasian wild boar (Sus scrofa), in Doñana National Park, a protected Mediterranean biodiversity hotspot with high ungulate and CCHFV vector abundance, and which is also one of the main stopover sites for migratory birds between Africa and western Europe. Both ungulates are hosts to the principal CCHFV vector in Spain, Hyalomma lusitanicum. We sampled wild ungulates annually from 2005 to 2020 and analysed the frequency of exposure to CCHFV by a double‐antigen ELISA. The annual exposure risk was modelled as a function of environmental traits in an approach to understanding exposure risk determinants that allow us to predict the most likely places and years for CCHFV transmission. The main findings show that H. lusitanicum abundance is a fundamental driver of the fine‐scale spatial CCHFV transmission risk, while inter‐annual risk variation is conditioned by virus/vector hosts, host community structure and weather variations. The most relevant conclusion of the study is that the emergence of CCHF in Spain might be associated with recent wild ungulate population changes promoting higher vector abundance. This work provides relevant insights into the transmission dynamics of CCHFV in enzootic scenarios that would allow deepening the understanding of the ecology of CCHFV and its major determinants.
Adolescent access to quality healthcare is key to prevention and early intervention for health risk behaviors. This paper provides a healthcare provider perspective on barriers and facilitators to ...youth accessing care.
Five focus groups were conducted from November to December 2020 with providers from a variety of healthcare settings. Participants were asked to describe their respective adolescent patient populations, adolescent-specific health concerns, and organizational accommodations specific for youth services. Transcripts were analyzed using Inductive Thematic Analysis and themes were grouped using a social-ecological framework.
At an individual level, providers noted that an adolescent's knowledge and ability to navigate services varied greatly across settings. Providers identified provider trust and parent/guardian support as key interpersonal factors that support adolescents' access to services. Organizational factors included bureaucratic barriers and the clinic's reputation among youth. Community factors centered on mistrust within healthcare systems and stigmatization of seeking certain types of services. Participants also described how state-level policies influence parent/guardian consent requirements, which can limit adolescents' access to care.
Adolescent access to and utilization of healthcare in the United States is a complex problem requiring systems-level change. Healthcare organizations and providers have the opportunity and capacity to positively influence adolescents' healthcare access and experiences, however a lack of standardized, clinic-level priorities and guidelines can limit adolescent-centered care.
Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized S(3P) protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4
+
and cytotoxic CD8
+
T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.
Purpose
The purpose of this study was to develop and characterize the relevance and potential utility of an electronically delivered acceptance- and mindfulness-based approaches to physical activity ...promotion for insufficiently active breast cancer survivors.
Methods
The acceptance- and mindfulness-based physical activity intervention was delivered to participants electronically over the course of 4–8 weeks. It consisted of didactic videos, experiential exercises, and workbook-type activities that targeted principles from acceptance and commitment therapy (ACT). We conducted semi-structured, in-depth interviews with participants after they completed the intervention. Three coders conducted qualitative data analysis on interview transcripts to identify overarching themes and subthemes.
Results
We recruited 30 participants. Of those, 16 engaged in an individual interview. The mean age of the sample was 58.4 years (SD = 13.8). The sample was relatively well educated (50.0% college graduates) and mostly overweight or obese (58.8%). We identified two overarching themes from interviews. They were centered on (1) internal and external barriers to physical activity adherence and (2) the utility of targeting core ACT processes (acceptance and defusion, mindfulness, and values clarification) for physical activity promotion.
Conclusion
Intervention content was perceived to be acceptable, relevant, and to fulfill important needs related to healthy living. Findings suggest that this approach to physical activity promotion can be delivered effectively online. Electronically delivered acceptance- and mindfulness-based approaches hold promise for helping insufficiently active breast cancer survivors increase physical activity.
As responsible providers, we always obtain “informed consent” from patients and families prior to initiating a new medication. Informed consent refers to discussing the indications, benefits, risks, ...contraindications, and side effect profiles of medications. It can be uncomfortable for patients to hear a long list of adverse effects for medications that we, as their providers, are actually recommending to alleviate, not add to, the patient's symptoms. Much like other pharmaco‐active compounds, psychiatric medications have a long list of side effects grouped by organ system, some of which seem to cause more apprehension than others. One of the side effects that is most concerning to patients and their families is weight gain. Why this side effect seems to “weigh more heavily” on patients' minds is likely a reflection of current beauty standards, and the association among millennials/boomers between weight and other values including morality, inner strength, discipline, and overall health.
Chronic lymphocytic leukemia (CLL) is a disease of the elderly, but chronological age does not accurately discriminate frailty status at the inter-individual level. Frailty describes a person’s ...overall resilience. Since CLL is a stressful situation, it is relevant to assess the patient´s degree of frailty, especially before starting antineoplastic treatment. We are in the era of targeted therapies, which have helped to control the disease more effectively and avoid the toxicity of chemo (immuno) therapy. However, these drugs are not free of side effects and other aspects arise that should not be neglected, such as interactions, previous comorbidities, or adherence to treatment, since most of these medications are taken continuously. The challenge we face is to balance the risk of toxicity and efficacy in a personalized way and without forgetting that the most frequent cause of death in CLL is related to the disease. For this purpose, comprehensive geriatric assessment (GA) provides us with the opportunity to evaluate multiple domains that may affect tolerance to treatment and that could be improved with appropriate interventions. In this review, we will analyze the state of the art of GA in CLL through the five Ws.