Lower limb alignment in healthy Japanese adults.

BACKGROUND: Knowledge regarding the normal alignment of the lower limb is important when considering alignment for total knee arthroplasty. However, few studies have explored the lower limb alignment of healthy Japanese subjects. METHODS: Between July and October 2020, we performed whole leg standing radiography of 120 legs of 60 healthy adult Japanese volunteers aged <50 years in the closed-leg stance. The measurement parameters were hip knee ankle angle (positive for varus), percentage of constitutional varus (hip knee ankle angle ≥ 3°), mechanical axis deviation ratio, mechanical lateral distal femoral angle, medial proximal tibial angle, joint line convergence angle (positive for lateral opening), and tibial joint line angle (positive for medial inclination). RESULTS: The mean measured values for all volunteers, men and women, were as follows: hip knee ankle angle (°), 2.3, 2.6, and 2.0; mechanical axis deviation ratio, 35.8, 35.6, and 36.9; mechanical lateral distal femoral angle (°), 86.7, 87.0, and 86.7; medial proximal tibial angle (°), 85.6, 85.0, and 86.2; joint line convergence angle (°), 0.6, 0.3, and 0.8; and tibial joint line angle (°), -1.0, -0.7, -1.4, respectively. The percentage of constitutional varus was 35.8% overall, 35.8% in men and 35.3% in women. Only the medial proximal tibial angle was smaller in men than that in women (p = 0.003). CONCLUSIONS: The mechanical lateral distal femoral and medial proximal tibial angles were smaller, hip knee ankle angle was larger, and percentage of constitutional varus was higher in Japanese subjects than those reported for subjects in other countries. Our findings improve the understanding of Japanese-specific alignments when considering alignment for lower limb surgery, especially, total knee arthroplasty.

Evaluation of hindfoot and knee alignment by the hip-to-calcaneus view in patients with knee osteoarthritis and healthy individuals.

BACKGROUND: Hip-to-calcaneus (HC) view is a whole-leg standing view that can visualize the hindfoot in detail. The aim of this study was to investigate the reliability and validity of tibiocalcaneal angle in HC view (H-TCA) by comparing it with that in long axial view (L-TCA). We also verified whether periarticular knee alignment parameters, measured conventionally in whole-leg standing radiography, could be measured in HC view. METHOD: Sixty healthy volunteers and 61 patients with medial knee osteoarthritis were included. H-TCA was measured by two examiners in the healthy group, and intra-class correlation coefficients (ICCs) were evaluated. H-TCA and L-TCA were then measured in the healthy and osteoarthritis groups and correlated. Finally, we measured hip-knee-ankle angle, mechanical axis deviation ratio, mechanical lateral distal femoral angle, medial proximal tibial angle, and joint-line convergence angle in HC view and conventional whole-leg standing radiography to evaluate statistical differences and correlations. RESULTS: The intra-observer and inter-observer ICCs were 0.86 and 0.76, respectively. Correlation coefficients (r) between H-TCA and L-TCA were r = 0.87 in healthy group and r = 0.81 in osteoarthritis group, indicating a strong positive correlation in both groups. There was no significant difference in periarticular knee alignment parameters between HC view and conventional whole-leg radiography. CONCLUSIONS: Hindfoot evaluation in HC view showed high intra-observer and inter-observer reliabilities and strong positive correlation with TCA in long axial view. By using HC view before knee surgery, such as total knee arthroplasty, other necessary alignments can be evaluated simultaneously.

Effectiveness of Bone Marrow-Derived Platelet-Rich Fibrin on Rotator Cuff Healing in a Rabbit Degenerative Model.

BACKGROUND: Platelet-rich fibrin (PRF) is a second-generation platelet concentrate. Although peripheral blood-derived PRF (P-PRF) is commonly applied in biological augmentation, there is no report about the therapeutic effect of bone marrow-derived PRF (BM-PRF) for degenerative rotator cuff tears (RCTs). PURPOSE/HYPOTHESIS: To examine the effects of platelet-rich plasma (PRP), P-PRF, and BM-PRF during rotator cuff repair (RCR) in degenerative RCTs in rabbits. We hypothesized that BM-PRF would accelerate the bone-tendon healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: Degenerative RCT models were created 2 weeks before beginning the study, and 68 juvenile rabbits were divided into 4 groups: the control, PRP, P-PRF, and BM-PRF groups. RCR without augmentation was done in the control group. PRP was prepared by centrifuging peripheral blood twice using a plastic tube. P-PRF and BM-PRF were prepared by centrifuging peripheral blood and bone marrow, respectively, using a glass tube. Rabbits from PRP, P-PRF, and BM-PRF groups were administered the augmentation in a similar fashion for RCR, between the rotator cuff and the footprint of the humerus. At 4, 8, and 12 weeks, rabbits were euthanized and histologically assessed using hematoxylin and eosin staining, Alcian blue staining, and immunohistochemical staining for type I and III collagen. The sections were also evaluated with immunofluorescence staining of vascular endothelial growth factor (VEGF) at 4 weeks. RESULTS: The continuity was significantly better in the BM-PRF group at 4 weeks (P < .05). Immunofluorescence staining demonstrated that VEGF-positive stained cells were significantly greater in the BM-PRF group than in the control group (P < .01). The modified tendon maturing score was significantly greater in the BM-PRF group than in the control and PRP groups at 12 weeks (P < .05). There was no significant difference in the modified tendon maturing score of the P-PRF group compared with the control group. CONCLUSION: The rabbit model of degenerative RCTs demonstrated that RCR combined with BM-PRF enhanced tendon-bone continuity and increased the VEGF-positive cells at 4 weeks and obtained preferable tendon-bone maturation at 12 weeks. CLINICAL RELEVANCE: RCR augmented with BM-PRF has the potential to improve clinical outcomes for RCTs.

Assessment of the severity of curly toe.

BACKGROUND: Curly/underlapping toe involves flexion, adduction, and varus deformity of the interphalangeal joints. There are no previous reports showing the relationship between physical examination and X-ray findings among patients with curly toe deformity. METHODS: We investigated the clinical findings of 116 consecutive patients associated with 239 underlapping toes. We compared the age and affected toes between patients whose deformities were pointed out at a pediatric medical examination (group 1) and those referred for medical treatment (group 2). The degree of curly toe deformity was graded by a physical examination and X-ray. RESULTS: The average age at presentation was 2.7 years. The affected toes were significantly different between groups 1 and 2 (p < .001). The morbidity of each toe differed significantly in group 2 (p < .005) but not in group 1. The correlation between the appearance grading and classification by X-ray was very strong using Spearman's rank correlation coefficient. The severity of curly toe was divided into mild in 104 toes, moderate in 105 toes, and severe in 17 toes. The methods of conservative treatment were observation only in 15 cases, manipulations in 30 cases, taping in 67 cases, and a brace in 9 cases. Surgery was performed in 8% of cases. CONCLUSION: Curly toe deformity of the third or fourth toes tend to be referred for medical treatment because of the abnormality. Our grading system using a physical examination and classification by X-ray was useful for assessing the severity of curly toe.

Forefoot Deformities in Patients with Rheumatoid Arthritis: Mid- to Long-Term Result of Joint-Preserving Surgery in Comparison with Resection Arthroplasty.

BACKGROUND: Joint-preserving surgery for the forefoot has been increasingly performed for rheumatoid arthritis (RA). We compared joint-preserving surgeries with resection arthroplasty for RA in the forefoot. METHODS: Forefoot surgeries were performed on 62 toes in 42 patients with RA (men: 2; women: 40) between 2002 and 2018. Three groups were compared: PP-31 toes treated with joint-preserving surgery involving the modified Mann method for the big toe and offset osteotomy for lesser toes, PR-15 toes treated with joint-preserving surgery for the big toe and resection arthroplasty for lesser toes, and RR-16 toes treated with resection arthroplasty for all the toes. RESULTS: The PP group had significantly higher mean scores on a scale for RA in the foot and ankle at the latest follow-up than the RR group (86 vs. 75 points; p < 0.05). Hallux valgus (angle > 20°) of the big toe at the latest follow-up recurred in 10 (32%), 9 (60%), and 16 (100%) patients in the PP, PR, and RR groups, respectively. A revision surgery was performed in one patient each in the PP and PR groups. CONCLUSIONS: Joint-preserving surgery is superior to resection arthroplasty in preventing function loss and the recurrence of hallux valgus.

Characterization of a novel glycolipid with a difucosylated H-antigen in human blood group O erythrocytes with monoclonal antibody HMMC-1 and its detection in human uterine cervical carcinoma tissues.

Humanized monoclonal antibody HMMC-1 established by immunizing transchromosomal mice with a human uterine endometrial cancer cell line has been found to react with the H-antigen carried on core l O-glycans through cotransfection of glycosyltransferases for O-glycans and inhibition of antibody-binding with synthetic oligosaccharides. However, direct binding analysis of an antibody against glycosphingolipids from human erythrocytes with different ABO blood groups revealed that it was able to bind selectively with polar glycolipids in blood group O, but not blood group A, B and AB erythrocytes. Unexpectedly, typical monofucosylated H-glycolipids, IV2Fucα-nLc4Cer and VI2Fucα-nLc6Cer, which are the precursors for A and B-glycolipids, and were present not only in blood group O, but also A, B and AB-erythrocytes, were not the antigens for the HMMC-1 antibody. The antigen comprised less than 0.001% of the total glycolipids in blood group O-erythrocytes, and was purified by conventional silica gel column chromatography. Structural determination by permethylation, GC-MS, and ESI-TOFMS demonstrated that the structure was a novel glycolipid with a difucosylated H-antigen, Fucα1-2Galß1-4GlcNAcß1-3Gal(2-1αFuc)ß1-4GlcNAcß1-3Galß1-4GlcNAcß1-3Galß1-4Glcß1-1'Cer, VI2,VIII2(Fucα)2-nLc8Cer, whose terminal difucosylated structure was the epitope of the HMMC-1 antibody. The HMMC-1 glycolipid was detected in five out of 29 tissues from patients suffering from uterine cervical carcinomas, irrespective of their ABO-blood groups.

Overexpression of HexCer and LacCer containing 2-hydroxylated fatty acids in cholangiocarcinoma and the association of the increase of LacCer (d18:1-h23:0) with shorter survival of the patients.

Alteration of glycosphingolipid (GSL) synthesis is observed in many types of cancer. In this study, we have analyzed the expression of sphingolipids and GSLs in cholangiocarcinoma (CCA) tissues and adjacent normal liver tissues. Neutral lipids were extracted from tissue samples using mild-alkaline treatment method followed by TLC and LC-MS analysis. The expression of ceramides, hexosylceramides (HexCer), and lactosylceramides (LacCer) was altered in CCA tissues, 61.1% (11/18) of them showing an increase whereas 38.9% (7/18) showing a decrease, compared with the adjacent normal tissue. Cers and GSLs containing 2-hydroxylated fatty acids except one LacCer molecular species were overexpressed in CCA tissues, and the increase of LacCer (d18:1-h23:0) was correlated with shorter survival of CCA patients, suggesting the involvement of GSL synthesis and fatty acid hydroxylation in progression of CCA. Taken together, we have demonstrated in this study the increase of GSL synthesis and fatty hydroxylation in CCA, which probably be used as a target for CCA treatment.

Globo-series glycosphingolipids enhance Toll-like receptor 4-mediated inflammation and play a pathophysiological role in diabetic nephropathy.

Alteration of glycosphingolipid (GSL) expression plays key roles in the pathogenesis and pathophysiology of many important human diseases, including cancer, diabetes and glycosphingolipidosis. Inflammatory processes are involved in development and progression of diabetic nephropathy, a major complication of type 2 diabetes mellitus. GSLs are known to play roles in inflammatory responses in various diseases, and levels of renal GSLs are elevated in mouse models of diabetic nephropathy; however, little is known regarding the pathophysiological role of these GSLs in this disease process. We studied proinflammatory activity of GSLs in diabetic nephropathy using spontaneously diabetic mouse strain KK. Mice were fed a high-fat diet (HFD) (60% kcal from fat) or normal diet (ND) (4.6% kcal from fat) for a period of 8 wk. HFD-feeding resulted in quantitative and qualitative changes of renal globo-series GSLs (particularly Gb3Cer), upregulation of TNF-α, and induction of renal inflammation. Gb3Cer/Gb4Cer treatment enhanced inflammatory responses via TLR4 in TLR4/MD-2 complex expressing cells, including HEK293T, mouse bone marrow-derived macrophages (BMDMs) and human monocytes. Our findings suggest that HFD-induced increase of Gb3Cer/Gb4Cer positively modulate TLR4-mediated inflammatory response, and that such GSLs play an important pathophysiological role in diabetic nephropathy.

Abnormal immunolabelling of SMAD4 in cell block specimens to distinguish malignant and benign pancreatic cells.

BACKGROUND: Accurate diagnosis of malignant and benign pancreatic lesions can be challenging, especially with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples that are small and/or degraded. In the present study, we determined how to best evaluate abnormal SMAD4 expression by immunohistochemical staining on cell block specimens from EUS-FNA samples. RESULTS: In surgically resected pancreas, when abnormal SMAD4 immunolabelling was evaluated as negative SMAD4 expression, the sensitivity was low (33%), but when it was evaluated as decreased SMAD4 expression, the sensitivity improved (53%). Specificity and positive predictive value were high for both evaluations. There were no false-positive cases. In cell block specimens, decreased SMAD4 expression showed 47% sensitivity and 72% specificity, while negative SMAD4 expression showed lower sensitivity (20%) and higher specificity (100%). Both evaluations in cell block specimens showed lower sensitivity and specificity compared to resected specimens. False-positive and -negative rates were higher for cell blocks than for resected specimens. CONCLUSIONS: Decreased SMAD4 immunolabelling provided improved sensitivity as compared to negative SMAD4 immunolabelling; therefore, it is important to compare SMAD4 expression in a sample to its expression in normal cells. Abnormal SMAD4 labelling showed low sensitivity and high specificity; therefore, SMAD4 staining using EUS-FNA samples might be helpful to detect malignancies that possess SMAD4 gene abnormalities.

Probable transfusion-transmitted Zika virus in Brazil.

BACKGROUND: Zika virus (ZIKV) is an emerging arthropod-borne flavivirus transmitted by Aedes mosquitoes. Recent commentaries regarding ZIKV routes of transmission describe a potential transmission by transfusion. Herein, we report a probable case of transfusion-transmitted ZIKV infection through a platelet transfusion that was detected from postdonation information. CASE REPORT: A blood donor made a voluntary telephone report to the blood donor facility 3 days after donation and informed the facility of a febrile illness (fever, malaise, and headaches). Due to the ongoing dengue epidemic, the initial clinical investigation included dengue among other possible diagnoses. The serology and molecular laboratory results excluded dengue infection. However, stored samples from the donation were positive for ZIKV on reverse transcription-polymerase chain reaction (RT-PCR) analysis. A retrospective investigation demonstrated that the platelet concentrate, which was part of a pool, had been transfused after a liver transplantation. A physician had evaluated the patient 4 days after surgery. Laboratory investigation showed enzyme-linked immunosorbent assay results that were negative for dengue immunoglobulin M antibodies; however, the results were positive for hemagglutination inhibition antibodies against flavivirus. ZIKV RT-PCR and virus isolation analyses in cell cultures from recipient serum were both positive. The sequencing confirmed ZIKV in the donor and patient samples. Ten partial nucleotide sequences from the ZIKV strain that were detected in the donor were aligned and compared with the ZIKV genome detected in the recipient, revealing a 99.8% homology between the two strains. CONCLUSIONS: This is a case of probable transmission of ZIKV through blood transfusion. The patient had been transfused with the blood product from an infected donor, most likely in the incubation period after ZIKV infection but prior to clinical disease onset. This report emphasizes the importance of postdonation information and recipient investigations during outbreaks of potentially blood-borne infections.

Immunization of A4galt-deficient mice with glycosphingolipids from renal cell cancers resulted in the generation of anti-sulfoglycolipid monoclonal antibodies.

In this study, we immunized Gb3/CD77 synthase gene (A4galt) knockout (KO) mice with glycosphingolipids (GSLs) extracted from 3 renal cell cancer (RCC) cell lines to raise monoclonal antibodies (mAbs) reactive with globo-series GSLs specifically expressed in RCCs. Although a number of mAbs reactive with globo-series GSLs were generated, they reacted with both RCC cell lines and normal kidney cells. When we analyzed recognized antigens by mAbs that were specifically reactive with RCC, but not with normal kidney cells at least on the cell surface, many of them turned out to be reactive with sulfoglycolipids. Eight out of 11 RCC-specific mAbs were reactive with SM2 alone, and the other 3 mAbs were more broadly reactive with sulfated glycolipids, i.e. SM3 and SM4 as well as SM2. In the immunohistochemistry, these anti-sulfoglycolipids mAbs showed RCC-specific reaction, with no or minimal reaction with adjacent normal tissues. Thus, immunization of A4galt KO mice with RCC-derived GSLs resulted in the generation of anti sulfated GSL mAbs, and these mAbs may be applicable for the therapeutics for RCC patients.

Clinicopathological Features of 15 Occult and 178 Clinical Pancreatic Ductal Adenocarcinomas in 8339 Autopsied Elderly Patients.

OBJECTIVE: The aim of the study was to investigate the clinicopathological features of pancreatic cancer at different stages using autopsy results. METHODS: We retrospectively evaluated 8399 consecutive cases of autopsy performed between 1972 and 2013 at our geriatric hospital. RESULTS: Macroscopic pancreatic lesions were detected in 6.13% of the cases. Primary and secondary pancreatic tumors were observed in 2.88% and 2.10% of the cases, respectively. Most primary tumors were invasive ductal adenocarcinomas (193 cases [2.31%]; mean patient age, 78.09 years) with a peak incidence at 50 to 59 years. Occult invasive ductal adenocarcinoma was discovered incidentally in 15 cases, with distant metastasis present in 26.67% of those. Microscopically, occult and advanced tumors exhibited similar characteristics such as hyalinized fibrous stroma, necrosis, invasion into vessels, peripancreatic fat tissues, and extrapancreatic nerve plexus. Mucin 1 and 2 immunohistochemical expression levels were also similar. Occult cancer incidence increased with age. Patients aged 85 years or older had shorter survival, a small tumor size, and a low incidence of lymph node metastasis. Approximately 8% of pancreatic invasive ductal adenocarcinomas progressed asymptomatically and were discovered incidentally at autopsy. CONCLUSIONS: Pancreatic cancers in elderly patients tend to progress asymptomatically, but once symptoms develop, they are more often fatal than those in younger patients.

Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes.

Nutritional recommendations have promoted the increased need to consume n-3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n-3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high-fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high-fat group (HG); flaxseed oil group (FOG); and control group (CG) (non-diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and ß-cell mass in female offspring.

Maternal exposure to diets containing flaxseed flour or flaxseed oil during pregnancy and lactation protects the aortic remodeling in adult male offspring of diabetic rat dams.

BACKGROUND: Diabetes during pregnancy is associated with cardiovascular complications in the fetus and extends into adulthood. Therapeutic applications of flaxseed have been studied in cardiovascular disorders, because its oilseed is the best plant source of omega-3 fatty acid, which is currently considered by researchers to be an essential protective against cardiovascular disease. The aim of this study was to evaluate the influence of flaxseed flour and oil on cardiovascular biochemical parameters and the histoarchitecture of the aorta in adult rats which were offspring of diabetic mothers. RESULTS: At 100 days of age in offspring it was observed that maternal consumption of a high-fat diet containing flaxseed oil (FOG) and flaxseed flour (FFG) did not affect the serum concentration of monocyte chemoattractant protein-1, vascular endothelial growth factor, cholesterol, triglycerides, high-density-, low-density- or very-low-density-lipoprotein cholesterol. However, the thickness of the intima media layer of the aorta was significantly smaller in FOG and FFG groups; the lumen area was similar among the groups; and a higher percentage of elastic fiber was found in FOG and FFG groups. CONCLUSION: These data suggest that the use of both flaxseed flour and its oil reduces the remodeling of the aorta; however; it has not been possible to modify the cardiovascular biochemical parameters.

Effect of maternal use of flaxseed oil during pregnancy and lactation on glucose metabolism and pancreas histomorphometry of male offspring from diabetic rats.

AIM: Investigate if the maternal use of flaxseed oil prevents pancreatic alterations in the offspring of diabetic mothers. METHODS: Diabetes was induced in female wistar rats (n=12) by a high-fat diet and low-dose of streptozotocin. After the confirmation of the diabetes (glucose >300 mg/dL), rats were mated and once pregnancy was confirmed, they were allocated into three groups (n=6): high-fat group (HFG); flaxseed oil group (FOG); and control group (CG) (nondiabetic rats). At weaning, male offspring (n=12/group) received a standard chow diet. The animals were euthanized in two phases: at 100 and at 180 days, (n=6/group). The pancreas was collected for histomorphometric and immunohistochemistry analysis. RESULTS: HFG showed hypertrophy of pancreatic islets at 100 and at 180 days (p<0.0001), while the FOG offspring had islets with smaller diameters compared to HFG at both phases of sacrifice (p<0.0001). HFG had a lower percentage of small islets when compared to CG and FOG, which had a higher percentage when compared to HFG (p=0.0053) at 100 days. At 180 days HFG showed higher percentage of larger islets (p=0.00137) and lower percentage of smaller islets (p=0.00112), when compared to FOG. HFG showed lower islet insulin immunodensity at 100 days (p<0.0001) and 180 days (p<0.0001), whereas FOG was similar to CG (p<0.0001) at 100 days and higher at 180 days (p<0.0001). CONCLUSIONS: Flaxseed oil reduced the damage caused by maternal hyperglycemia, promoting normal pancreas histomorphometry and ß cell mass.

Febre amarela silvestre: reemergencia de transmissao no estado de Sao Paulo, Brasil, 2009 / Fiebre amarilla silvestre: re emergencia de transmision en el estado de Sao Paulo, Brasil, 2009 / Yellow fever: reemerging in the state of Sao Paulo, Brazil, 2009

OBJETIVO Descrever a investigação do surto de febre amarela silvestre e as principais medidas de controle realizadas no estado de São Paulo. MÉTODOS Estudo descritivo do surto de febre amarela silvestre na região sudoeste do estado, entre fevereiro e abril de 2009. Foram avaliados casos suspeitos e confirmados em humanos e primatas não humanos. A investigação entomológica, em ambiente silvestre, envolveu captura em solo e copa de árvore para identificação das espécies e detecção de infecção natural. Foram realizadas ações de controle de Aedes aegypti em áreas urbanas. A vacinação foi direcionada para residentes dos municípios com confirmação de circulação viral e nos municípios contíguos, conforme recomendação nacional. RESULTADOS Foram confirmados 28 casos humanos (letalidade 39,3%) em áreas rurais de Sarutaiá, Piraju, Tejupá, Avaré e Buri. Foram notificadas 56 mortes de primatas não humanos, 91,4% do gênero Alouatta sp . A epizootia foi confirmada laboratorialmente em dois primatas não humanos, sendo um em Buri e outro em Itapetininga. Foram coletados 1.782 mosquitos, entre eles Haemagogus leucocelaenus , Hg. janthinomys/capricornii , Sabethes chloropterus , Sa. purpureus e Sa. undosus . O vírus da febre amarela foi isolado de um lote de Hg. leucocelaenus procedente de Buri. A vacinação foi realizada em 49 municípios, com 1.018.705 doses aplicadas e o registro de nove eventos adversos graves pós-vacinação. CONCLUSÕES Os casos humanos ocorreram entre fevereiro e abril de 2009 em áreas sem registro de circulação do vírus da febre amarela há mais de 60 anos. A região encontrava-se fora da área com recomendação de vacinação, com alto percentual da p...

OBJETIVO Describir la investigación de brote de fiebre amarilla silvestre y las principales medidas de control realizadas en el estado de Sao Paulo. MÉTODOS Estudio descriptivo del brote de fiebre amarilla silvestre en la región suroeste del Estado, entre febrero y abril de 2009. Se evaluaron casos sospechosos y confirmados en humanos y primates no humanos. La investigación entomológica, en ambiente silvestre, involucró capturo en suelo y copa de árboles para identificación de las especies y detección de infección natural. Se realizaron acciones de control de Aedes aegypti en áreas urbanas. La vacunación fue direccionada a residentes de los municipios con confirmación de circulación viral y en los municipios contiguos, siguiendo recomendación nacional. RESULTADOS Se confirmaron 28 casos en humanos (letalidad 39,3%) en áreas rurales de Sarutaiá, Pirajú, Tejupá, Avaré y Buri. Se notificaron 56 muertes de primates no humanos, 91,4% del género Allouatta sp. La epizootia fue confirmada laboratorialmente en dos primates no humanos siendo uno de Buri y el otro de Itapetininga. Se colectaron 1.782 mosquitos, entre ellos Haemagogus leucocelaenus, Hg. janthinomys/capricornii, y Sabethes chloropterus, Sa. purpureus y Sa. undosus. El virus de la fiebre amarilla fue aislado de un lote de Hg. leucocelaenus procedente de Buri. La vacunación fue realizada en 49 municipios, con 1.018.705 dosis aplicadas y el registro de nueve eventos adversos graves post-vacunación. CONCLUSIONES Los casos humanos ocurrieron entre febrero a abril de 2009 en áreas sin registro de circulación del virus de la fiebre amarilla por más de 60 años. La región se encontraba fuera del área de recomendación de vacunación, con alto porcentaje de población susceptible. La adopción oportuna de medidas de control permitió ...

OBJECTIVE To describe the investigation of a sylvatic yellow fever outbreak in the state of Sao Paulo and the main control measures undertaken. METHODS This is a descriptive study of a sylvatic yellow fever outbreak in the Southwestern region of the state from February to April 2009. Suspected and confirmed cases in humans and in non-human primates were evaluated. Entomological investigation in sylvatic environment involved capture at ground level and in the tree canopy to identify species and detect natural infections. Control measures were performed in urban areas to control Aedes aegypti . Vaccination was directed at residents living in areas with confirmed viral circulation and also at nearby cities according to national recommendation. RESULTS Twenty-eight human cases were confirmed (39.3% case fatality rate) in rural areas of Sarutaiá, Piraju, Tejupá, Avaré and Buri. The deaths of 56 non-human primates were also reported, 91.4% were Allouatta sp. Epizootics was confirmed in two non-human primates in the cities of Itapetininga and Buri. A total of 1,782 mosquitoes were collected, including Haemagogus leucocelaenus , Hg. janthinomys/capricornii , and Sabethes chloropterus, Sa. purpureus and Sa. undosus . Yellow fever virus was isolated from a group of Hg. Leucocelaenus from Buri. Vaccination was carried out in 49 cities, with a total of 1,018,705 doses. Nine serious post-vaccination adverse events were reported. CONCLUSIONS The cases occurred between February and April 2009 in areas with no recorded yellow fever virus circulation in over 60 years. The outbreak region occurred outside the original recommended vaccination area with a high percentage of susceptible population. The fast adoption of control measures interrupted the human transmission within a month and the confirmation of viral circulation in humans, monkeys and mosquitoes. The results allowed the identification of new areas of viral circulation but ...

Fast preparation of an N-acetylglucosaminylated peptide segment for the chemoenzymatic synthesis of a glycoprotein.

A novel GlcNAc-Asn unit carrying trifluoroacetic acid (TFA)-sensitive O-protecting groups was prepared. The unit was used for the solid-phase peptide synthesis (SPPS) of the N-acetylglucosaminylated emmprin (35-69) thioester via one-step deprotection by TFA combined with the N-alkylcysteine thioesterification method. This segment was used for the synthesis of the first Ig domain (22-104) of emmprin carrying GlcNAc by one-pot ligation with other segments using the thioester method. Finally, the sugar chain was elongated by transglycosylation using glycosynthase to give the Ig domain carrying the disialo- and asialo-complex-type sugar chain.

Serological survey of hantavirus in rodents in Uberlândia, Minas Gerais, Brazil / Inquérito sorológico de hantavírus em roedores, Uberlândia, Minas Gerais, Brasil

We conducted a serological survey to determine the presence of hantavirus infection in rodents in Uberlândia, Minas Gerais as well as to identify and characterize associated factors. Rodents were captured using Sherman live-capture traps set in rural and peri-urban environments. A total of 611 rodents were captured. There was a higher trap success in peri-urban areas (26.3%) and a higher prevalence of antibodies among rodents captured in rural areas (2.9%). Necromys lasiurus was the most common species (42.2%) and the more frequently infected (4.6%). One Calomys tener (1/141; 0.7%) and one Calomys sp. (1/14; 7.1%) were also positive for the hantavirus infection. In N. lasiurus, antibody prevalence correlated with population density (p < 0.01), age class (p = 0.003) and presence of scars (p = 0.02). The data confirm that horizontal transmission is the main mechanism that maintains the virus in nature. The higher seropositivity in N. lasiurus is consistent with genetic studies that associate this species with an Araraquara virus reservoir; the seropositivity of C. tener and Calomys sp. may indicate the occurrence of spillover infection or the presence of other circulating hantaviruses.

Realizamos um estudo transversal para identificar a presença de infecção por hantavírus em roedores em Uberlândia, Minas Gerais, e também para identificar e caracterizar fatores associados. Roedores foram capturados usando armadilhas do tipo Sherman em ambientes rural e periurbano. Um total de 611 roedores foi capturado. Houve maior sucesso de captura na área periurbana (26,3%) e maior prevalência de anticorpos entre os roedores capturados na área rural (2,9%). Necromys lasiurus foi a espécie mais encontrada (42,2%) e a mais frequentemente infectada (4,6%). Um Calomys tener (1/141; 0.7%) e um Calomys sp. (1/14; 7.1%) foram também positivos. Os dados obtidos mostram que em N. lasiurus, a prevalência de anticorpos está relacionada à densidade populacional (p < 0.01), a classe de idade (p = 0.003) e a presença de cicatrizes (p = 0.02), confirmando que a transmissão horizontal é o principal mecanismo que mantém o vírus na natureza. A maior positividade em N. lasiurus é consistente com estudos genéticos que permitem associar esta espécie como reservatório do vírus Araraquara; a soropositividade de C. tener e Calomys sp. pode indicar a ocorrência de "spillover infection" ou a presença de outros hantavírus circulantes.

Yellow fever epizootics in non-human primates, São Paulo state, Brazil, 2008-2009 / Epizootias de febre amarela em primatas não humanos no estado de São Paulo, Brasil, 2008-2009

Since 2000, the expansion of Sylvatic Yellow Fever (YF) has been observed in the southeast of Brazil, being detected in areas considered silent for decades. Epizootics in non-human primates (NHPs) are considered sentinel events for the detection of human cases. It is important to report epizootic events that could have impact on the conservation status of susceptible species. We describe the epizootics in NHPs, notified in state of São Paulo, Brazil, between September 2008 to August 2009. Ninety-one epizootic events, involving 147 animals, were reported in 36 counties. Samples were obtained from 65 animals (44.2%). Most of the epizootics (46.6%) were reported between March and April, the same period during which human cases of YF occurred in the state. Biological samples were collected from animals found dead and were sent to Instituto Adolfo Lutz, in São Paulo. Two samples, collected in two counties without an indication for YF vaccination, were positive for the virus. Another 48 animals were associated with YF by clinical-epidemiological linkage with laboratory confirmed cases. Because the disease in human and NHPs occurred in the same period, the detection of the virus in NHPs did not work as sentinel, but aided in the delineation of new areas of risk.

Desde 2000, vem sendo observada a expansão da febre amarela (FA) no Sudeste do Brasil, sendo detectados casos em áreas consideradas silenciosas por décadas. Epizootias em primatas não humanos (NHPs) são considerados eventos sentinela para a detecção de casos humanos. É importante relatar eventos epizoóticos que podem ter impacto sobre o estado de conservação de espécies sensíveis. Descrevemos as epizootias, notificadas em NHPs no estado de São Paulo, Brasil, entre setembro de 2008 a agosto de 2009. Noventa e um eventos epizoóticos, envolvendo 147 animais, foram notificados em 36 municípios. As amostras foram obtidas a partir de 65 animais (44,2%). A maioria das epizootias (46,6%) foram registradas entre março e abril, no mesmo período no qual YF em que casos humanos ocorreram no estado. As amostras biológicas foram coletadas de animais encontrados mortos e enviadas ao Instituto Adolfo Lutz, em São Paulo. Duas amostras, coletadas em dois municípios, sem indicação para a vacinação de febre amarela, foram positivos para o vírus. Outros 48 animais foram associados com FA por vínculo clínico-epidemiológico com casos confirmados laboratorialmente. Devido a doença em humanos e NHPs terem ocorrido no mesmo período, a detecção do vírus em NHPs não funcionou como sentinela, mas ajudou no processo de delimitação de novas áreas de risco.

Improved high-fat diet-induced glucose intolerance by an oral administration of phytosphingosine.

We have previously reported that phytoceramide and phytosphingosine (PHS) stimulated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ) in cells. PPARγ is a therapeutic target for type 2 diabetes. We found in this study that an oral administration of PHS improved diet-induced glucose intolerance in mice. Since PHS is highly expressed in yeast, PHS in fermented foods may improve diabetes.