Searching for Digenic Inheritance in Deaf Brazilian Individuals Using the Multiplex Ligation-Dependent Probe Amplification Technique

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Mutations in the genes coding for connexin 26 (Cx26), connexin 30 (Cx30), and connexin 31 (Cx31) are the main cause of autosomal recessive nonsyndromic sensorineural hearing loss (AR-NSNHL). The 35delG mutation is the most frequent in the majority of Caucasian populations and may account for up to 70% of all GJB2 mutations. As a large number of affected individuals (10%-40%) with GJB2 mutations carry only one mutant allele, it has been postulated that the presence of additional mutations in the GJB6 gene (Cx30) explains the deafness condition found in these patients. In the present study, we screened the c. 35delG mutation in similar to 600 unrelated Brazilian patients, with moderate to profound AR-NSNHL. Other point mutations in the coding region of the GJB2 gene were screened by sequencing analysis as well as the IVS 1 + 1 G> A splice site mutation in the same gene. Digenic mutations including large deletions and duplications were investigated in the Cx26, 30, and 31 genes in monoallelic individuals for mutations in the GJB2 gene. Large deletions and duplications were assessed by multiplex ligation-dependent probe amplification. We found 46 patients with mutations in only one GJB2 allele. Different pathogenic mutations associated with c. 35delG were found in 13 patients. Two patients were identified with digenic heterozygous mutations. Our findings contributed to more accurate diagnosis and more appropriate genetic counseling in 28% of patients studied (13/46).1512849853Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Photosynthetic quantum efficiency in south‐eastern Amazonian trees may be already affected by climate change

Tropical forests are experiencing unprecedented high‐temperature conditions due to climate change that could limit their photosynthetic functions. We studied the high‐temperature sensitivity of photosynthesis in a rainforest site in southern Amazonia, where some of the highest temperatures and most rapid warming in the Tropics have been recorded. The quantum yield (F v /F m ) of photosystem II was measured in seven dominant tree species using leaf discs exposed to varying levels of heat stress. T 50 was calculated as the temperature at which F v /F m was half the maximum value. T 5 is defined as the breakpoint temperature, at which F v /F m decline was initiated. Leaf thermotolerance in the rapidly warming southern Amazonia was the highest recorded for forest tree species globally. T 50 and T 5 varied between species, with one mid‐storey species, Amaioua guianensis , exhibiting particularly high T 50 and T 5 values. While the T 50 values of the species sampled were several degrees above the maximum air temperatures experienced in southern Amazonia, the T 5 values of several species are now exceeded under present‐day maximum air temperatures

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans

Seroprevalence of Protective Antibodies Against Influenza and the Reduction of the Influenza Incidence Rate: An Annual Repeated Cross-Sectional Study From 2014 to 2019

Background: Seroepidemiological studies provide estimates of population-level immunity, prevalence/incidence of infections, and evaluation of vaccination programs. We assessed the seroprevalence of protective antibodies against influenza and evaluated the correlation of seroprevalence with the cumulative annual influenza incidence rate. Methods: We conducted an annual repeated cross-sectional seroepidemiological survey, during June-August, from 2014 to 2019, in Portugal. A total of 4326 sera from all age groups, sex, and regions was tested by hemagglutination inhibition assay. Seroprevalence and geometric mean titers (GMT) of protective antibodies against influenza were assessed by age group, sex, and vaccine status (65+ years old). The association between summer annual seroprevalence and the difference of influenza incidence rates between one season and the previous one was measured by Pearson correlation coefficient (r). Results: Significant differences in seroprevalence of protective antibodies against influenza were observed in the population. Higher seroprevalence and GMT for A(H1N1)pdm09 and A(H3N2) were observed in children (5-14); influenza B seroprevalence in adults 65+ was 1.6-4.4 times than in children (0-4). Vaccinated participants (65+) showed significant higher seroprevalence/GMT for influenza. A strong negative and significant correlation was found between seroprevalence and ILI incidence rate for A(H1N1)pdm09 in children between 5 and 14 (r = -0.84; 95% CI, -0.98 to -0.07); a weak negative correlation was observed for A(H3N2) and B/Yamagata (r ≤ -0.1). Conclusions: The study provides new insight into the anti-influenza antibodies seroprevalence measured in summer on the ILI incidence rate in the next season and the need for adjusted preventive health care measures to prevent influenza infection and transmission.Luís Ribeiro and Ana Sofia Marinho from Centro Hospitalar Universitário de São João, E. P. E.; Lídia Santos, Patrícia Miguel, Paula Branquinho, and Paula Soares from Centro Hospitalar Universitário de Lisboa Central, E. P. E.; Margarida Figueiredo and Daniela Cochicho from Instituto Português de Oncologia de Lisboa, Francisco Gentil, E.P. E.; Diana Barros from Centro Hospitalar de Setúbal, E. P. E.; Ivo Rosa, Ana Mira, and José Brito from Hospital do Espírito Santo de Évora, E. P. E., are acknowledged for their work at hospital laboratories as members of the Portuguese Laboratory Network for Influenza and Other Respiratory Viruses Diagnosis. The authors acknowledge the coordinators of WHO Collaborating Centre for Reference and Research on Influenza at Francis Crick Institute, London, for supporting the Portuguese National Influenza Reference Laboratory, with technical advice and reference reagents

Hospitalization of older adults due to ambulatory care sensitive conditions

OBJECTIVE To analyze the temporal evolution of the hospitalization of older adults due to ambulatory care sensitive conditions according to their structure, magnitude and causes. METHODS Cross-sectional study based on data from the Hospital Information System of the Brazilian Unified Health System and from the Primary Care Information System, referring to people aged 60 to 74 years living in the state of Rio de Janeiro, Souhteastern Brazil. The proportion and rate of hospitalizations due to ambulatory care sensitive conditions were calculated, both the global rate and, according to diagnoses, the most prevalent ones. The coverage of the Family Health Strategy and the number of medical consultations attended by older adults in primary care were estimated. To analyze the indicators’ impact on hospitalizations, a linear correlation test was used. RESULTS We found an intense reduction in hospitalizations due to ambulatory care sensitive conditions for all causes and age groups. Heart failure, cerebrovascular diseases and chronic obstructive pulmonary diseases concentrated 50.0% of the hospitalizations. Adults older than 69 years had a higher risk of hospitalization due to one of these causes. We observed a higher risk of hospitalization among men. A negative correlation was found between the hospitalizations and the indicators of access to primary care. CONCLUSIONS Primary healthcare in the state of Rio de Janeiro has been significantly impacting the hospital morbidity of the older population. Studies of hospitalizations due to ambulatory care sensitive conditions can aid the identification of the main causes that are sensitive to the intervention of the health services, in order to indicate which actions are more effective to reduce hospitalizations and to increase the population’s quality of life