Genome-wide association studies (GWAS) have identified several risk
variants for late-onset Alzheimer's disease (LOAD)
1
,
2
. These
common variants have replicable but small effects on LOAD risk and ...generally do
not have obvious functional effects. Low-frequency coding variants, not detected
by GWAS, are predicted to include functional variants with larger effects on
risk. To identify low frequency coding variants with large effects on LOAD risk,
we performed whole exome-sequencing (WES) in 14 large LOAD families and
follow-up analyses of the candidate variants in several large case-control
datasets. A rare variant in
PLD3
(phospholipase-D family,
member 3, rs145999145; V232M) segregated with disease status in two independent
families and doubled risk for AD in seven independent case-control series (V232M
meta-analysis; OR= 2.10, CI=1.47-2.99; p= 2.93×10
-5
, 11,354
cases and controls of European-descent). Gene-based burden analyses in 4,387
cases and controls of European-descent and 302 African American cases and
controls, with complete sequence data for
PLD3,
indicate that
several variants in this gene increase risk for AD in both populations (EA: OR=
2.75, CI=2.05-3.68; p=1.44×10
-11
, AA: OR= 5.48, CI=1.77-16.92;
p=1.40×10
-3
).
PLD3
is highly expressed in
brain regions vulnerable to AD pathology, including hippocampus and cortex, and
is expressed at lower levels in neurons from AD brains compared to control
brains (p=8.10×10
-10
). Over-expression of PLD3 leads to a
significant decrease in intracellular APP and extracellular Aβ42 and
Aβ40, while knock-down of PLD3 leads to a significant increase in
extracellular Aβ42 and Aβ40. Together, our genetic and functional
data indicate that carriers of
PLD3
coding variants have a
two-fold increased risk for LOAD and that
PLD3
influences APP
processing. This study provides an example of how densely affected families may
be used to identify rare variants with large effects on risk for disease or
other complex traits.
This study was carried out of the region of Monastir in Central Tunisia, between July and August 2010. Larvae were collected using a floatation technique with magnesium sulfate in mud samples. The ...fourth instar larva of Culicoides cataneii Clastrier, 1957 and Culicoides sahariensis Callot, Kremer, Bailly-Choumara, 1970 are described, illustrated and drawn. Measurements of instars IV are also presented. This is the first record of Culicoides cataneii and Culicoides sahariensis (Diptera: Ceratopogonidae) to Tunisia.
To evaluate the prognosis of HIV-infected patients admitted to ICUs and to identify factors predictive of short- and long-term survival.
A prospective study from January 1, 1990, to December 31, ...1992, including all consecutive HIV-infected patients admitted to our ICU for the first time. ICU survivors were followed up until January 1, 1994.
An 18-bed infectious diseases ICU in a 1,300-bed university hospital in Paris.
Four hundred twenty-one HIV-related admissions were recorded during the study period (33.5% of 1,258 admissions to ICU); 354 HIV-infected patients were first ICU admissions and were analyzed.
Predictive factors on univariate and multivariate analyses (logistic regression and Cox model) for short- and long-term mortality were performed. Respiratory failure was the main cause of admission (49.2%), followed by neurologic disorders (26.8%), sepsis (10.2%), heart failure (4.5%), and miscellaneous disorders (9.3%). For these groups, in-ICU and in-hospital mortality rates were as follows: 16.7% and 33.9%; 23.2% and 41.1%; 38.9% and 58.3%; 25% and 68.8%; and 12.1% and 24.2%, respectively. In-ICU and in-hospital mortality rates were significantly different across the groups (p=0.026 and 0.002, respectively). Multivariate analysis showed that the in-hospital outcome was significantly associated with functional status (p=0.05), time since AIDS diagnosis (p=0.04), HIV disease stage (0.016), simplified acute physiology score (SAPS I) (p=0.06), need for mechanical ventilation (p<0.000001), and its duration (p=0.0001). In the 281 patients who were discharged alive from the ICU, cumulative survival rates were 51%±38% at 6 months, 28%±38% at 12 months, and 18%±30% at 24 months. Median and crude mean±SD survival times were 199 days and 316±343 days. Multivariate analysis showed that the long-term outcome was significantly associated with functional status (p=0.000001), weight loss (p=0.00001), the CD4 count (p=0.00001), the HIV disease stage (p=0.01), the duration of AIDS (p=0.001), the admission cause group (p=0.03), and the SAPS I at admission (p=0.00001).
The short-term (in-ICU and in-hospital) outcome of HIV-infected patients was mainly related to the severity of the acute illness (SAPS I, cause of admission, need for and duration of mechanical ventilation), and to the preadmission health status, based on functional status and weight loss. Some of these parameters, in particular the SAPS I and preadmission health status, also influenced the long-term outcome. Whereas HIV-related variables had little impact on the in-ICU outcome, they were closely related with the in-hospital outcome and even more strikingly with the long-term outcome. Thus, the life expectancy of HIV-infected patients, which depends primarily on the natural history of the HIV infection, is the most powerful determinant of the long-term prognosis. Our results confirm that ICU support for HIV-infected patients should not be considered futile.
Este estudo do tipo intervenção comunitária controlada unicega não randomizada teve por objetivo avaliar o impacto das visitas realizadas pelos agentes comunitários de saúde e líderes voluntários da ...Pastoral da Criança sobre o pré-natal de gestantes pobres em Rio Grande, Rio Grande do Sul, Brasil. Aplicaram-se questionários padronizados antes e depois do parto buscando conhecer suas características demográficas, reprodutivas, assistência recebida durante o pré-natal e nível sócio-econômico e condição de moradia. Estas gestantes foram divididas em três grupos, sendo dois grupos-intervenção e um controle. Dentre as 339 gestantes estudadas, 115 pertenciam ao grupo cuja intervenção foi realizada pelos agentes comunitários de saúde, 116 pelos líderes voluntários da pastoral e 108 pertenciam ao grupo controle. Gestantes visitadas pelos agentes comunitários iniciaram o pré-natal mais precocemente, realizaram maior número de consultas, exames clínicos e testes laboratoriais, foram mais comumente orientadas sobre amamentação e suplementadas com sulfato ferroso. A participação de familiares nas consultas de pré-natal foi maior entre gestantes visitadas pelos líderes voluntários. Visitas domiciliares podem melhorar a qualidade do pré-natal entre gestantes pobres e aumentar a participação de familiares, sobretudo do marido, na gestação.
The aim of this study is to consider the parietal complications of the hydatid cyst of the liver: the subcutaneous rupture of the cyst and spontaneous cutaneous fistula of liver hydatid cyst. 1(st) ...case: A 24-year-old woman, who underwent surgery 10 years ago for hydatid cyst of the liver, was admitted for a right hypochondrium mass and a fistula draining clear liquid containing cystic elements. Computed tomography (CT) showed a large cystic lesion in the subcutaneous tissue communicating with another cystic mass in the liver. The diagnosis of a cyst-cutaneous fistula due to a peritoneal hydatid cyst was established. The patient underwent surgical treatment and recovered uneventfully. 2(nd) case: A 40-year-old woman presented with a mass in her right hypochondrium. The diagnosis of subcutaneous rupture of a hydatid cyst of liver was established by ultrasonography and CT-scan. The patient underwent surgical treatment and recovered uneventfully. Parietal complications of hydatid cyst of the liver are extremely rare, clinical presentation can be derailing. The diagnosis is usually established by ultrasonography and CT-scan.
The aim of this study was to assess knowledge on prenatal care and pregnancy risk among women in poor neighborhoods in the city of Rio Grande, Rio Grande do Sul State, Brazil. Data were collected ...using a cross-sectional design. A standard questionnaire was applied to all pregnant women from poor neighborhoods. Trained interviewers visited these women at home, covering demographic, socioeconomic, and reproductive data and knowledge concerning prenatal care and pregnancy risk factors. A total of 367 pregnant women were interviewed using non-random sampling. Except for urine tests and HIV testing, spontaneously reported as necessary, other procedures were reported by no more than 30% of the women. Digital vaginal examination, clinical breast examination, and Pap smear were reported by a maximum of 7% of the women. Only two-thirds felt that vaginal bleeding and abdominal pain were serious signs during gestation. Other signs and symptoms were reported by a maximum of one-third of the women. In conclusion, knowledge of prenatal tests and situations indicating serious risk fell far short of the desired levels. Improving this level of information in pregnant women could help reduce maternal and child morbidity and mortality.
Les mycétomes sont des pseudotumeurs inflammatoires des tissus mous sous-cutanés et éventuellement osseux. Ils sont le plus souvent polyfistulisés et évoluent sur un mode chronique. Ils peuvent être ...endémiques ou sporadiques selon les régions. Le but de notre étude est de déterminer les particularités cliniques et thérapeutiques des mycétomes dans notre pays.
C’est une étude multicentrique rétrospective sur une période de 127 ans (1892–2019), incluant tous les cas de mycétome diagnostiqués.
Soixante-dix-huit patients ont été inclus avec une prédominance masculine (sex-ratio=1,88). L’âge moyen était de 43 ans (12–78 ans). Les patients étaient d’origine rurale dans 63 % des cas, principalement des agriculteurs. Les atteintes du pied sont les plus retrouvées (80,7 %), suivies de la jambe (11,5 %), du genou (2 cas), de la main (2 cas), une seule atteinte du dos et de la nuque et une seule atteinte cervicale. Dans 42 cas (53,84 %) une atteinte osseuse était présente. La durée d’évolution moyenne était de 10,25 ans (3 mois–15 ans). Les mycétomes actinomycosiques étaient retrouvés dans 75,64 % des cas contre 24,36 % des mycétomes d’origine fongique. L’examen direct a montré des grains dans 77 % des cas. Le traitement était médical dans tous les cas (antibiotiques pour l’actinomycétome et antifongiques pour l’eumycétome), associé dans 21 cas à un geste chirurgical. La guérison a été obtenu dans 42 cas.
Les mycétomes sont rares dans notre pays. Les actinomycétomes sont les plus fréquents. Le traitement est long et mal codifié avec de mauvais résultats en cas d’eumycétomes, d’où l’intérêt de la prévention au sein des populations à risques.
Low molecular weight peptides were isolated from the chromatin of wheat sprouts. Following gel filtration the peptide fraction shows a sharp inhibiting activity on the growth of HeLa cancer cells. ...Infrared (IR) spectroscopy and mass spectrometry have been utilized to characterize the wheat sprout peptides in an attempt to recognize the peptide sequence involved in the control of cell growth. The quantitative presence of a peptide with MH+=572 appears proportional to the cell growth inhibition activity. This compound has been subjected to extensive mass spectrometry analysis. The automatic computational analysis of the ions of second, third and fourth generations indicate a peptide sequence, AcHis-Asp-Ser-Glu-, that binds at the C-terminal a molecule of ethanolamine. Moreover, the results show that some sequences of the wheat sprout peptide family are present in the peptide fractions isolated from several other tissues, thus supporting the hypothesis of ubiquitous regulatory peptides.
The seasonal dynamics of cell density and photosynthetic pigment contents of the zooxanthellae hosted by Montastrea cavernosa were investigated on coastal reefs off Picãozinho (06º42'05"/07º07'30"S ...and 34º48'37"/34º50'00" W), Northeast Brazil between September 1999 and 2000. A distinct pattern of these parameters was found: cell numbers were greater during the rainy season (autumn/winter) while photosynthetic pigments were greater during the dry season (summer). Both parameters showed drastic reductions during heavy rains (June and July 1999). We speculate that this pattern is largely influenced by the rain cycles which, owing to their magnitude and frequency, affect the water clarity and the seasonal physiological condition of the cells.
A dinâmica sazonal na densidade de células e na concentração de pigmentos fotossintetizantes das zooxantelas de Montastrea cavernosa foram analisados no período setembro/1999 a setembro/2000 nos Recifes do Picãozinho (06º42'05"/07º07'30" S e 34º48'37"/34º50'00" W), Nordeste do Brasil. Verificou-se que existe um padrão distinto entre estes parâmetros, com maior quantidade de células no período chuvoso e maior concentração de pigmentos fotossintetizantes na época de estiagem. Ambos os parâmetros apresentaram, no entanto, uma nítida redução em seus valores nos meses de maiores índices pluviométricos (junho e julho /1999). Especulamos que tal fato deve estar relacionado com o regime de chuvas que pode variar em magnitude e freqüência, afetando a qualidade ótica da água e o estado fisiológico das células.
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