Determinación de maderas carbonizadas procedentes de contextos arqueológicos de la Tradición Guaraní

En este trabajo se presentan la metodología y los resultados de un estudio exploratorio de identificación taxonómica de maderas carbonizadas recuperadas en contextos arqueológicos. Las muestras analizadas proceden de dos sitios arqueológicos localizados en la margen izquierda del alto río Uruguay (municipio de Porto Mauá, Rio Grande do Sul, Brasil). Los sitios Barra do Santo Cristo 1 y Três Bocas 2, con dataciones radiocarbónicas de ca. 410 y 500 años AP, corresponden a asentamientos residenciales asignados a la ocupación guaraní meridional. Si bien estos contextos presentan baja preservación de restos orgánicos, es común encontrar carbones dispersos en la capa de ocupación y concentrados en estructuras interpretadas como fogones. Para la realización de este estudio se llevaron a cabo observaciones macroscópicas en las muestras seleccionadas de cada sitio y posteriormente se las complementó con análisis de microscopía electrónica de barrido. En base a las características morfológicas de las tres secciones diagnósticas, a la comparación con maderas actuales y a la consulta bibliográfica específica fue posible determinar taxonómicamente los macrorrestos vegetales. Un porcentaje mayoritario de ellos fue asignado a la familia Lauraceae. Por último, y de acuerdo a la información aportada por este análisis, se plantean interpretaciones acerca de la vegetación disponible en el ambiente y la selección de maderas como combustible.This paper presents the methodology and results of an exploratory study of taxonomic identification of charcoals sampled in archaeological contexts. The analyzed samples come from two archaeological sites located on the left bank of the upper Uruguay River (municipality of Porto Mauá, Rio Grande do Sul, Brazil). The sites Barra do Santo Cristo 1 and Três Bocas 2, with radiocarbon dates between ca. 410 and 500 years BP, were residential settlements attributed to the southern Guaraní occupation. While these contexts present low preservation of organic remains, it is common to find scattered charcoals in occupation layer and concentrated in structures interpreted as hearths. For this study, macroscopic observations were conducted on selected charcoal samples from each site and then supplemented with scanning electron microscopy analysis. Based on the anatomical characteristics of the three diagnostic sections, comparison with present types of wood and specific literature, it was possible to determine the taxonomic class of plant macroremains. So far, most of them were assigned to Lauraceae. Finally and according to information provided by this analysis, we propose interpretations about wood availability in the environment, environmental characteristics at the time of the occupations and the selection of wood for fuel.Fil: Costa Angrizani, Rodrigo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento Cientifico de Arqueologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mange, Emiliano. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento Cientifico de Arqueologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romero Alves, M.. Universidad Nacional de la Plata. Facultad de Ciencias Agrarias y Forestales; Argentin

Reducing microscopy-based malaria misdiagnosis in a low-resource area of Tanzania

Misdiagnosis of malaria is a major problem in Africa leading not only to incorrect individual level treatment, but potentially the acceleration of the spread of drug resistance in low-transmission areas. In this paper we report on the outcomes of a simple intervention that utilized a social entrepreneurship approach (SEA) to reduce misdiagnosis associated with hospital-based microscopy of malaria in a low-transmission area of rural Tanzania. A pre-post assessment was conducted on patients presenting to the hospital outpatient department with malaria and non-malaria like symptoms in January 2009 (pre-intervention) and June 2009 (post-intervention). All participants were asked a health seeking behavior questionnaire and blood samples were taken for local and quality control microscopy. Multivariate logistic regression was conducted to determine magnitude of misdiagnosis with local microscopy pre- versus- post intervention. Local microscopy pre-intervention specificity was 29.5% (95% CI = 21.6% – 38.4%) whereas the post intervention specificity was 68.6% (95% CI = 60.2% - 76.2%). Both pre and post intervention sensitivity were difficult to determine due to an unexpected low number of true positive cases. The proportion of participants misdiagnosed pre-intervention was 70.2% (95%CI = 61.3%-78.0%) as compared to 30.6% (95%CI = 23.2%–38.8%) post-intervention. This resulted in a 39.6% reduction in misdiagnosis of malaria at the local hospital. The magnitude of misdiagnosis for the pre-intervention participants was 5.3 (95%CI = 3.1–9.3) that of the post-intervention participants. In conclusion, this study provides evidence that a simple intervention can meaningfully reduce the magnitude of microscopy-based misdiagnosis of malaria for those individuals seeking treatment for uncomplicated malaria. We anticipate that this intervention will facilitate a valuable and sustainable change in malaria diagnosis at the local hospital

Experiences with surgical management of undescended testis at a tertiary care hospital in north-western Tanzania

Background: Undescended testes (UDT) are prone to a lot of complications but early detection and correction give good results. There is paucity of published data on UDT in our setting. This study describes the clinical presentation, management and outcome of this condition at Bugando Medical Centre (BMC) in northwestern TanzaniaMethods: This was a retrospective study of patients who were admitted and operated for undescended testis at BMC between July 2006 and June 2014. Results: A total of 84 patients with 102 UDT were studied. Forty-six (54.9%) patients were aged above 5 years. Majority (72.5%) UDT were non-palpable. The right side was involved in 54.8%; left side in 23.8% while 21.4% were bilateral.  Associated inguinal hernia was reported in 48 (77.4%) patients. Ultrasonography was performed in 34 (45.9%) patients with non-palpable testes and was used to locate 12(35.3%) testes.  Laparoscopy was not used in any patient. At surgery, 54 (52.9%) testes were found in the inguinal canal, 28 (27.5%) in the superficial inguinal pouch, 10 (9.8%) in the abdomen and 10 (9.8%) testes were not found. Out of the 92 (90.2%) visible testes, 69 (75.0%) underwent orchidopexy (single stage in 54 (78.3%) testes and multistage in 15 (21.7%) testes) and 23 (25.0%) orchidectomy. Single stage procedures were more likely in patients less than 5 years, with palpable testes and those with testes located at the superficial inguinal pouch (p < 0.001). Postoperative complications were recorded in 8(9.5%) patients. The overall success rate of treatment was 95.7%. In this study, only 12 (14.3%) patients were available for follow up at 12 months after discharge.Conclusion: Patients with UDT presented late in our hospital because diagnosis by birth attendants was rarely made even though the anomaly was obvious at birth. The parents, patients themselves and development of complications drew attention to undescended testis. Health awareness campaign, thorough genital examination after birth and regular screening of toddlers for UDT may result in early presentatio

Large, Prospective Analysis of the Reasons Patients Do Not Pursue BRCA Genetic Testing Following Genetic Counseling

Genetic counseling (GC) and genetic testing (GT) identifies high‐risk individuals who benefit from enhanced medical management. Not all individuals undergo GT following GC and understanding the reasons why can impact clinical efficiency, reduce GT costs through appropriate identification of high‐risk individuals, and demonstrate the value of pre‐GT GC. A collaborative project sponsored by the Michigan Department of Health and Human Services prospectively collects anonymous data on BRCA‐related GC visits performed by providers in Michigan, including demographics, patient/family cancer history, GT results, and reasons for declining GT. From 2008 to 2012, 10,726 patients underwent GC; 3476 (32.4%) did not pursue GT. Primary reasons included: not the best test candidate (28.1%), not clinically indicated (23.3%), and insurance/out of pocket cost concerns (13.6%). Patient disinterest was the primary reason for declining in 17.1%. Insurance/out of pocket cost concerns were the primary reason for not testing in 13.4% of untested individuals with private insurance. Among untested individuals with breast and/or ovarian cancer, 22.5% reported insurance/out of pocket cost concerns as the primary reason for not testing and 6.6% failed to meet Medicare criteria. In a five‐year time period, nearly one‐third of patients who underwent BRCA GC did not pursue GT. GT was not indicated in almost half of patients. Insurance/out of pocket cost concerns continue to be barriers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146968/1/jgc40859.pd

Reducing malaria misdiagnosis: the importance of correctly interpreting Paracheck Pf® "faint test bands" in a low transmission area of Tanzania

Although malaria rapid diagnostic tests (RDTs) have been extensively evaluated since their introduction in the early 1990's, sensitivity and specificity vary widely limiting successful integration into clinical practice. This paper reviews specific issues surrounding RDT use in field settings and presents results of research investigating how to interpret "faint test bands" on ParaCheck Pf® in areas of low transmission in order to reduce malaria misdiagnosis.\ud A multi-phase cross-sectional study was conducted at a remote hospital in the northern Tanzanian highlands. Capillary blood samples were taken from consenting participants (n = 319) for blood smear and ParaCheck Pf® testing. Primary outcome variables were sensitivity, specificity and proportion misdiagnosed by ParaCheck Pf® and local microscopy. ParaCheck Pf® "faint bands" were classified as both true positives or true negatives during evaluation to determine appropriate clinical interpretation. Multivariate logistic regression adjusted for age and gender was conducted to determine odds of misdiagnosis for local microscopy and ParaCheck Pf®. Overall, 23.71% of all ParaCheck Pf® tests resulted in a "faint band" and 94.20% corresponded with true negatives. When ParaCheck Pf® "faint bands" were classified as positive, specificity was 75.5% (95% CI = 70.3%-80.6%) as compared to 98.9% (95% CI = 97.0%-99.8%) when classified as negative. The odds of misdiagnosis by local microscopy for those > 5 years as compared to those ≤ 5 years are 0.370 (95% CI = 0.1733-0.7915, p = 0.010). In contrast, even when ParaCheck Pf® faint bands are considered positive, the odds of misdiagnosis by ParaCheck Pf® for those > 5 years as compared to those ≤ 5 years are 0.837 (95% CI = 0.459-1.547, p = 0.5383). We provide compelling evidence that in areas of low transmission, "faint bands" should be considered a negative test when used to inform clinical decision-making. Correct interpretation of RDT test bands in a clinical setting plays a central role in successful malaria surveillance, appropriate patient management and most importantly reducing misdiagnosis

Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding-fasting response and the circadian clock.

RNA polymerase III (Pol III) synthesizes short noncoding RNAs, many of which are essential for translation. Accordingly, Pol III activity is tightly regulated with cell growth and proliferation by factors such as MYC, RB1, TRP53, and MAF1. MAF1 is a repressor of Pol III transcription whose activity is controlled by phosphorylation; in particular, it is inactivated through phosphorylation by the TORC1 kinase complex, a sensor of nutrient availability. Pol III regulation is thus sensitive to environmental cues, yet a diurnal profile of Pol III transcription activity is so far lacking. Here, we first use gene expression arrays to measure mRNA accumulation during the diurnal cycle in the livers of (1) wild-type mice, (2) arrhythmic javax.xml.bind.JAXBElement@59c2c50e knockout mice, (3) mice fed at regular intervals during both night and day, and (4) mice lacking the javax.xml.bind.JAXBElement@160cb27a gene, and so provide a comprehensive view of the changes in cyclic mRNA accumulation occurring in these different systems. We then show that Pol III occupancy of its target genes rises before the onset of the night, stays high during the night, when mice normally ingest food and when translation is known to be increased, and decreases in daytime. Whereas higher Pol III occupancy during the night reflects a MAF1-dependent response to feeding, the rise of Pol III occupancy before the onset of the night reflects a circadian clock-dependent response. Thus, Pol III transcription during the diurnal cycle is regulated both in response to nutrients and by the circadian clock, which allows anticipatory Pol III transcription

NiO Nanofibers as a Candidate for a Nanophotocathode

p-type NiO nanofibers have been synthesized from a simple electrospinning and sintering procedure. For the first time, p-type nanofibers have been electrospun onto a conductive fluorine doped tin oxide (FTO) surface. The properties of the NiO nanofibers have been directly compared to that of bulk NiO nanopowder. We have observed a p-type photocurrent for a NiO photocathode fabricated on an FTO substrate

Pharmacokinetic/Pharmacodynamic Evaluation of the Dipeptidyl Peptidase 1 Inhibitor Brensocatib for Non-cystic Fibrosis Bronchiectasis

BACKGROUND AND OBJECTIVE: Brensocatib is an investigational, first-in-class, selective, and reversible dipeptidyl peptidase 1 inhibitor that blocks activation of neutrophil serine proteases (NSPs). The NSPs neutrophil elastase, cathepsin G, and proteinase 3 are believed to be central to the pathogenesis of several chronic inflammatory diseases, including bronchiectasis. In a phase II study, oral brensocatib 10 mg and 25 mg reduced sputum neutrophil elastase activity and prolonged the time to pulmonary exacerbation in patients with non-cystic fibrosis bronchiectasis (NCFBE). A population pharmacokinetic (PPK) model was developed to characterize brensocatib exposure, determine potential relationships between brensocatib exposure and efficacy and safety measures, and inform dose selection in clinical studies. METHODS: Pharmacokinetic (PK) data pooled from a phase I study of once-daily brensocatib (10, 25, and 40 mg) in healthy adults and a phase II study of once-daily brensocatib (10 mg and 25 mg) in adults with NCFBE were used to develop a PPK model and to evaluate potential covariate effects on brensocatib pharmacokinetics. PK–efficacy relationships for sputum neutrophil elastase below the level of quantification (BLQ) and reduction in pulmonary exacerbation and PK–safety relationships for adverse events of special interest (AESIs; periodontal disease, hyperkeratosis, and infections other than pulmonary infections) were evaluated based on model-predicted brensocatib exposure. A total of 1284 steady-state brensocatib concentrations from 225 individuals were included in the PPK data set; 241 patients with NCFBE from the phase II study were included in the pharmacodynamic (PD) population for the PK/PD analyses. RESULTS: The PPK model that best described the observed data consisted of two distributional compartments and linear clearance. Two significant covariates were found: age on volume of distribution and renal function on apparent oral clearance. PK–efficacy analysis revealed a threshold brensocatib exposure (area under the concentration–time curve) effect for attaining sputum neutrophil elastase BLQ and a strong relationship between sputum neutrophil elastase BLQ and reduction in pulmonary exacerbations. A PK–safety evaluation showed no noticeable trends between brensocatib exposure and the incidence of AESIs. Based on the predicted likelihood of clinical outcomes for sputum neutrophil elastase BLQ and pulmonary exacerbations, brensocatib doses of 10 mg and 25 mg once daily were selected for a phase III clinical trial in patients with NCFBE (ClinicalTrials.gov identifier: NCT04594369). CONCLUSIONS: PPK results revealed that age and renal function have a moderate effect on brensocatib exposure. However, this finding does not warrant dose adjustments based on age or in those with mild or moderate renal impairment. The PK/PD evaluation demonstrated the clinically meaningful relationship between suppression of neutrophil elastase activity and reduction in exacerbations in brensocatib-treated patients with NCFBE, supporting further development of brensocatib for bronchiectasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40262-022-01147-w

Pathological Features of Breast Cancer seen in Northwestern Tanzania: A Nine Years Retrospective Study.

Breast cancer is more common in Western Countries compared to African populations. However in African population, it appears that the disease tends to be more aggressive and occurring at a relatively young age at the time of presentation. The aim of this study was to describe the trend of Breast Cancer in Northwestern Tanzania. This was a retrospective study which involved all cases of breast cancer diagnosed histologically at Bugando Medical Center from 2002 to 2010. Histological results and slides were retrieved from the records in the Pathology department, clinical information and demographic data for patients were retrieved from surgical wards and department of medical records. Histology slides were re-evaluated for the histological type, grade (By modified Bloom-Richardson score), and presence of necrosis and skin involvement. Data was entered and analyzed by SPSS computer software version 15. There were 328 patients histologically confirmed to have breast cancer, the mean age at diagnosis was 48.7 years (+/- 13.1). About half of the patients (52.4%) were below 46 years of age, and this group of patients had significantly higher tendency for lymph node metastasis (p = 0.012). The tumor size ranged from 1 cm to 18 cm in diameter with average (mean) of 5.5 cm (+/- 2.5), and median size of 6 cm. Size of the tumor (above 6 cm in diameter) and presence of necrosis within the tumor was significantly associated with high rate of lymph node metastasis (p = 0.000). Of all patients, 64% were at clinical stage III (specifically IIIB) and 70.4% had lymph node metastasis at the time of diagnosis. Only 4.3% of the patients were in clinical stage I at the time of diagnosis. Majority of the patients had invasive ductal carcinoma (91.5%) followed by mucinous carcinoma (5.2%), Invasive lobular carcinoma (3%) and in situ ductal carcinoma (0.3%). In all patients, 185 (56.4%) had tumor with histological grade 3. Breast cancer in this region show a trend towards relative young age at diagnosis with advanced stage at diagnosis and high rate of lymph node metastasis. Poor Referral system, lack of screening programs and natural aggressive biological behavior of tumor may contribute to advanced disease at the time of diagnosis