Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis.

INTRODUCTION: Aim of this analysis was to report toxicity and clinical outcomes in oligorecurrent prostate cancer (PCa) patients treated with single fraction stereotactic radiosurgery (SRS) for bone metastases. METHODS: We separately analyzed clinical data of PCa patients with bone oligometastases enrolled in a prospective phase I trial (DESTROY-2). DESTROY-2 was based on SRS delivered using volumetric modulated arc therapy in patients with primary or metastatic tumors in several extra-cranial body sites. Acute and late toxicity, biochemical tumor response, local control (LC), distant metastases-free (DPFS), progression-free (PFS), time to next-line systemic treatment-free (NEST-FS), and overall survival (OS) were calculated. RESULTS: Data on 37 PCa patients, carrying out 50 bone metastases, candidates for curative-intent treatment and treated with SRS at our Institution were collected. SRS dose ranged between 12 and 24 Gy. One grade 1 acute skin toxicity in one patient treated on the hip (24 Gy) and one grade 1 late skin toxicity in a patient with a scapular lesion (24 Gy) were recorded. No cases of bone fracture were registered in the treated population. With a median follow-up of 25 months (range 3-72 months) 2-year actuarial LC, DPFS, PFS, and OS were 96.7%, 58.1%, 58.1%, and 95.8%, respectively. Median and 2-year NEST-FS were 30 months (range 1-69 months) and 51.2%, respectively. CONCLUSIONS: Data analysis showed few toxicity events, high local control rate and prolonged NEST-FS after linear accelerator-based radiosurgery of bone oligometastases from PCa. The possibility of postponing systemic treatments in patients with oligometastatic PCa by means of SRS should be taken into account. Further prospective studies on larger series are needed to confirm the reported results.

Lactobacillus plantarum Lp62 exerts probiotic effects against Gardnerella vaginalis ATCC 49154 in bacterial vaginosis.

The severe side-effects elicited by conventional antibiotic therapy and the recurrence of Bacterial vaginosis-associated bacteria and bacterial resistance have led to the development of novel alternative therapies, among which genital probiotics are widely used. In this study, we aimed to evaluate the antimicrobial activities of Lactobacillus plantarum Lp62 and its supernatant against Gardnerella vaginalis, using both in vitro and in vivo approaches. In vitro assays were used to evaluate the viability of the strain and the antimicrobial activities of the supernatant in different pH ranges. An in vivo assay was performed on female BALB/c mice, wherein the animals were divided into eight groups: four control groups and four treated groups (for curative and preventive therapies). After infecting and treating the mice, the animals were killed to quantify the bacterial load using qPCR, evaluate leucocyte cellular response, determine vaginal cytokine levels and perform cytokine tissue gene expression. Our analyses revealed significant activity of the strain and its supernatant against G. vaginalis. Preliminary in vitro tests showed that the strain grew with equal efficiency in different pH ranges. Meanwhile, the presence of halo and inhibition of pathogen growth established the significant activity of the supernatant against G. vaginalis. We observed that both micro-organisms are resident bacteria of mouse microbiota and that the lactobacilli population growth was affected by G. vaginalis and vice versa. We also observed that the treated groups, with their low bacterial load, absence of leucocyte recruitment, reduced cytokine levels in the vaginal lavage and normalized cytokine gene expression, successfully controlled the infection.

Past, present, and future of COVID-19: a review.

SARS-CoV-2 has recently emerged, becoming a global threat, affecting directly all human beings owing to its morbidity and mortality and indirectly, due to the enormous economic and psychological impact produced by social isolation, the most effective measure so far, but unsustainable for a long period. The scientific effort to understand and control SARS-CoV-2 transmission and clinical impact has been huge, and important achievements are highlighted in this review. Diagnosis is central and is the first step in recognizing and fighting any infectious agent. Instrumental to that is the quality of the data, relying on serological and molecular surveys in addition to trustworthy clinical records. However, the fast spread of a virus adapted for human-to-human respiratory transmission raised a demand for millions of molecular tests that are simply not available. Several candidate drugs are under evaluation in clinical trials. Those with an already recognized safety profile are more auspicious, since, if proven effective, can cut several steps of production and phase 2 and 3 trials. More than one hundred vaccine prototypes are in different stages of development, however, safety and efficacy evaluations cannot be obviated, implicating, most optimistically, in at least months for us to have an effective immunization, the definite measure to allow a safe return to the pre-pandemic lifestyle. Science has never been more necessary and present in daily life. Relying on the best of human wit is the only way out to this pandemic, saving as many lives as possible.

Past, present, and future of COVID-19: a review

SARS-CoV-2 has recently emerged, becoming a global threat, affecting directly all human beings owing to its morbidity and mortality and indirectly, due to the enormous economic and psychological impact produced by social isolation, the most effective measure so far, but unsustainable for a long period. The scientific effort to understand and control SARS-CoV-2 transmission and clinical impact has been huge, and important achievements are highlighted in this review. Diagnosis is central and is the first step in recognizing and fighting any infectious agent. Instrumental to that is the quality of the data, relying on serological and molecular surveys in addition to trustworthy clinical records. However, the fast spread of a virus adapted for human-to-human respiratory transmission raised a demand for millions of molecular tests that are simply not available. Several candidate drugs are under evaluation in clinical trials. Those with an already recognized safety profile are more auspicious, since, if proven effective, can cut several steps of production and phase 2 and 3 trials. More than one hundred vaccine prototypes are in different stages of development, however, safety and efficacy evaluations cannot be obviated, implicating, most optimistically, in at least months for us to have an effective immunization, the definite measure to allow a safe return to the pre-pandemic lifestyle. Science has never been more necessary and present in daily life. Relying on the best of human wit is the only way out to this pandemic, saving as many lives as possible.

Evolución de artralgias posterior a cirugía bariátrica / Evolution of arthralgia subsequent to bariatric surgery

Resumen Objetivo: En este estudio, se propuso establecer la relación entre la pérdida de peso y la evolución de las artropatías en un grupo de pacientes obesos sometidos a cirugía bariátrica. Materiales y Método: Investigación correlacional y de corte longitudinal, retrospectivo, donde se revisaron 33 historias de pacientes obesos mórbidos con artralgia en cualquier articulación, sometidos a cirugía bariátrica. Se realizó el análisis descriptivo de las variables numéricas según la distribución de los datos. Como prueba de relación se utilizó la Prueba T de Student para comparación de proporciones, asumiendo un valor p < 0,05. Resultados: 63,3% fueron femeninas, siendo la rodilla la principal articulación afectada (51,5%), con reducción considerable de su índice de masa corporal poscirugía. Al compararse los promedios del IMC inicial, a los 3, 6 y 12 meses, se encontraron diferencias estadísticamente significativas (p < 0,01). La desaparición de la artralgia en la mayoría de los pacientes ocurrió durante los primeros 3 meses, principalmente pacientes con obesidad grado I y II, en contraste con aquellos pacientes con obesidad grado III y IV, quienes requirieron un mayor lapso, para lograr la desaparición total de la artralgia. Conclusiones: La disminución gradual del dolor articular estuvo en relación directa a la reducción de las cifras de peso del paciente ya operado, mejorando la calidad de vida de los pacientes de la muestra.

Aim: In this study it was proposed to establish the relationship between weight loss and the evolution of the joint diseases in a group of obese patients undergoing bariatric surgery. Materials and Method: Cutting longitudinal, retrospective, and correlational research where studied 33 morbidly obese patients histories and arthralgia, in any joint they was undergoing bariatric surgery. It was the descriptive analysis of the numerical variables according to the distribution of the data. As proof of relationship the Student T test was used for comparison of proportions, assuming a P-value < 0.05. Results: 63.3% were female, being the main affected joint (51.5%), with significant reduction in their rate of body mass post surgery knee. To compare the averages of initial IMC, 3, 6 and 12 months statistically significant differences were found (p < 0.01). The disappearance of arthralgia in patients most occurred during the first 3 months, mainly patients with obesity grade I and II, in contrast to those patients with obesity grade III and IV, who required a greater period, to achieve the total disappearance of arthralgia. Conclusion: The gradual decrease in the pain joint was in direct relation to the reduction of the numbers of weight of the patient already operated, improving the quality of life of the patients of the indicated.

First phylogenetic analysis of dengue virus serotype 4 circulating in Espírito Santo state, Brazil, in 2013 and 2014.

The purpose of the present study was to reconstruct the phylogeny of dengue virus serotype 4 (DENV-4) that was circulating in Espírito Santo state, Brazil, in 2013 and 2014, and to discuss the epidemiological implications associated with this evolutionary hypothesis. Partial envelope gene of eight DENV-4 samples from Espírito Santo state were sequenced and aligned with 72 worldwide DENV-4 reference sequences from GenBank. A phylogenetic tree was reconstructed through Bayesian Inference and the Time of the Most Recent Common Ancestor was estimated. The study detected the circulation of DENV-4 genotype II in Espírito Santo state, which was closely related to strains from the states of Mato Grosso collected in 2012 and of São Paulo sampled in 2015. This cluster emerged around 2011, approximately 4 years after the entry of the genotype II in Brazil through its northern states, possibly imported from Venezuela and Colombia. This is so far the first phylogenetic study of the DENV-4 circulating in Espírito Santo state and shows the importance of an internal route of dengue viral circulation in Brazil to the introduction of the virus into this state.

Influence of demographics on clinical outcome of dengue: a cross-sectional study of 6703 confirmed cases in Vitória, Espírito Santo State, Brazil.

Dengue presents a wide clinical spectrum of signs and symptoms, with characteristics of the host potentially influencing the disease evolution. Therefore, the purpose of this study was to evaluate the influence of gender and age on dengue clinical outcomes in a recent outbreak situation in Brazil, applying a cross-sectional design and including 6703 dengue cases with laboratory confirmation, occurring in Vitória, Espírito Santo State, Brazil, between 2007 and 2013. Data were obtained from the Information System for Notifiable Diseases. Overall, 11·3% of the sample presented with severe dengue, which affected 13·0% of males, 10·0% of females, 8·8% of children, 12·5% of adolescents, 10·5% of adults and 15·5% of the elderly. Age was higher in the severe dengue group (P = 0·03). Severe dengue was associated with males and the elderly (P < 0·01); however, considering only severe cases, children presented haemorrhage and plasma leakage more frequently than older age groups. The results emphasize the importance of a differentiated protocol for management of dengue cases, taking into consideration host factors like age. These findings also suggest the elderly and children as priority groups for immunization in a future implementation of a vaccine.

Efficacy of oral administration of lactic acid bacteria isolated from cocoa in a fermented milk preparation: reduction of colitis in an experimental rat model.

We investigated the probiotic potential of lactic acid bacteria (LAB) obtained from cocoa fermentation using an experimental rat model of colitis. Cocoa beans were collected from fermentation boxes every 12 h for 5 days to isolate the microorganisms. Strains were isolated by serial dilution and plating on MRS agar. Gram-positive and catalase-negative rods were subjected to DNA extraction, polymerase chain reaction, and sequencing. Ten strains were randomly pooled and used to prepare a fermented milk drink that was used to treat the experimental colitis. A parallel group was treated with a single strain drink. Serum concentrations of cytokines and IgA, total and differential counts of blood leukocytes, and histological appearance were compared with the untreated control colitis group. Eighty strains of LAB were identified as Lactobacillus fermentum (68) and Lactobacillus plantarum (12). The multi-strain LAB pool significantly reduced the total number of leukocytes. There was a significant reduction in the percentage of neutrophils and monocytes compared with the control colitis group. IFN-γ concentration was downregulated in animals treated with the LAB pool. IL-10 and IgA increased significantly in the group treated with the strains. Histological analysis showed that the LAB pool reduced the inflammatory infiltrate and restored tissue architecture. The group treated with the single strain LAB drink (L. fermentum) showed no signs of inflammation remission. The results confirm the probiotic action of cocoa-derived LAB in the treatment of experimental colitis. Studies using isogenic models and humans will clarify the mechanisms of immune response modulation in inflammatory bowel disease.

Pre-transplant shedding of BK virus in urine is unrelated to post-transplant viruria and viremia in kidney transplant recipients.

BK virus-(BKV) associated nephropathy (BKVN) is a major cause of allograft injury in kidney transplant recipients. In such patients, subclinical reactivation of latent BKV infection can occur in the pre-transplant period. The purpose of this study was to determine whether urinary BKV shedding in the immediate pre-transplant period is associated with a higher incidence of viruria and viremia during the first year after kidney transplantation. We examined urine samples from 34 kidney transplant recipients, using real-time quantitative polymerase chain reaction to detect BKV. Urine samples were obtained in the immediate pre-transplant period and during the first year after transplant on a monthly basis. If BKV viruria was detected, blood samples were collected and screened for BKV viremia. In the immediate pre-transplant period, we detected BKV viruria in 11 (32.3%) of the 34 recipients. During the first year after transplantation, we detected BKV viruria in all 34 patients and viremia in eight (23.5%). We found no correlation between pre-transplant viruria and post-transplant viruria or viremia (p = 0.2). Although reactivation of latent BKV infection in the pre-transplant period is fairly common among kidney transplant recipients, it is not a risk factor for post-transplant BKV viruria or viremia.

Serum profile of cytokines interferon gamma and interleukin-10 in ewes subjected to artificial insemination by cervical retraction.

This study evaluated the influence of artificial insemination (AI) by cervical retraction (CRI) on serum levels of interferon gamma (IFNγ) and interleukin-10 (IL-10) in ewes. Synchronized pluriparous Santa Inês ewes were subjected to natural mating (NM, n = 8) and AI, which was performed for a fixed time (55 ± 1 hour) by CRI (n = 8) or laparoscopy (n = 8). Ewes were classified as pregnant, with return to estrus (RE) or with embryonic loss (EL). Blood samples were collected on Day 0, Day 3, Day 5, Day 12, and Day 17 (Day 0 = AI/NM) for progesterone dosage and cytokines were quantified from Day 0 to Day 12. Progesterone levels were constant, except for a decrease in ewes with RE at Day 17 (P < 0.05). Regardless of the reproductive method used, there was no difference in the IFNγ and IL-10 levels at any time, with averages of 642.1, 713.2, and 741.2 pg/mL for IFNγ and 667.1, 616.8, and 721.1 pg/mL for IL-10 when using CRI, laproscopy, and NM, respectively. Regarding the physiological status, ewes with EL had lower serum levels of IFNγ and IL-10 than pregnant ewes and ewes with RE, regardless of the reproductive method used, with averages of 769.1, 714.9, and 555.7 pg/mL for IFNγ and 713.8, 699.3, and 578.7 pg/mL for IL-10 in pregnant ewes, ewes with RE and EL, respectively (P < 0.01). In conclusion, AI by CRI in Santa Inês ewes does not alter the profile of serum cytokines IFNγ and IL-10 and does not induce an inflammatory reaction that can compromise pregnancy.

Absence of nonprimate hepacivirus-related genomes in blood donors seroreactive for hepatitis C virus displaying indeterminate blot patterns.

Despite intensive search, no primate homologue to the Hepatitis C Virus (HCV) has ever been found. The search for a zoonotic origin for HCV has been renewed recently when a virus, now known as non-primate hepacivirus (NPHV), with a high homology to HCV was found in dogs. A variable proportion of anti-HCV reactive blood donors submitted to the immunoblot (IB) to confirm their HCV status, present indeterminate results. The degree of homology between HCV and NPHV suggests that humans may be infected by NPHV or NPHV-like viruses. Maximum similarity between NHPV and HCV is observed in the nonstructural regions 3 and 5. Peptides representing both domains are present in IB assays, so it is reasonable to suppose that blood donors harboring such viruses may display cross-reactivity to the HCV antigenic fractions. Fifty-nine plasma samples from blood donors found reactive for anti-HCV and presenting IB indeterminate results were submitted to five distinct PCR reactions under low-stringency conditions, employing primers targeting GBV-C 5'UTR and NS3, Flavivirus-genus NS5 and NPHV 5'UTR and NS3. No amplification was obtained with all primer pairs tested except for five samples that amplified both 5'UTR and NS3 fragments from GBV-C. Unbiased next-generation sequencing may prove or rule out the existence of HCV-related viruses in IB indeterminate samples.

Viability and resistance of lactobacilli isolated from cocoa fermentation to simulated gastrointestinal digestive steps in soy yogurt.

To study the potential probiotic characteristics such as decrease of pH, microbial viability, and tolerance to simulated digestive steps of fermented soy beverage ("soy yogurt") produced with lactobacilli isolated from cocoa fermentation (Lactobacillus fermentum TcUESC01 and Lactobacillus plantarum TcUESC02) during fermentation and refrigerated storage. The sensory acceptance of the yogurts was also tested. Samples of soy yogurt produced with L. fermentum TcUESC01 or L. plantarum TcUESC02 were collected during fermentation (0, 4, 8, and 12 h) and refrigerated storage (1, 9, 18, and 27 d), and submitted to pH and bacterial viability determinations. Tolerance to simulated digestion steps was done with refrigerated storage samples at 9 °C. Simulated digestion was performed in 3 successive steps: exposure to pepsin-HCl solution, bile shock, and simulated small intestinal juice. During storage, a decrease in pH and lactobacillus viability was observed. L. fermentum TcUESC01 showed to be more resistant than L. plantarum TcUESC02 to simulated gastrointestinal digestion. All soy yogurts showed acceptable hedonic scores (greater than 5 in a 9-point hedonic scale ranging from "like extremely" to "dislike extremely") in sensory evaluation for flavor, aroma, color, consistency, and overall impression. L. plantarum TcUESC02 and, especially, L. fermentum TcUESC01 showed potential probiotic characteristics when considering pH, cell viability, and tolerance to simulated digestive steps and did not affect the sensory characteristics when supplemented to soy yogurt during storage.

Denaturing gradient gel electrophoresis analysis of 16S ribosomal DNA to monitor changes in mouse gut bacterial communities during Salmonella enterica serovar Enteritidis latent infection.

Changes in intestinal microbial flora during a 4-week period of Salmonella enterica serovar Enteritidis colonization in resistant mice (latent carrier animals) were evaluated using a culture independent method involving denaturing gradient gel electrophoresis. The contents of the ileocecal portion of the intestines produced 26 bands. Fifty-seven percent of the bands were expressed in more than 80% of the samples. Forty percent of the bands present in the negative control were common to all samples, and 60% differed from those obtained 12 h and 1, 5, 10, and 28 days post-inoculation (PI). A dendrogram distinguished the negative control as the external group, and 2 clusters were formed with 76% similarity, separating the 12-h PI and 3-day PI time points from the others. These groupings were also revealed through multivariate analysis in a principal component analysis and the Venn diagram. The production of interferon γ 12 h and 3 days PI may explain this brief imbalance in microbiota that was quickly reversed in the subsequent days. These findings demonstrate that S. enterica serovar Enteritidis can colonize the gut and persist in balance with the microbiota of resistant hosts.

Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome is a rare autosomal dominant congenital disorder characterized by postnatal growth retardation, psychomotor developmental delay, skeletal anomalies, peculiar facial morphology, and tumorigenesis. Mutations in the gene encoding the cAMP response element-binding protein (CREB, also known as CREBBP or CBP) on chromosome 16p13.3 have been identified. In addition, some patients with low intelligence quotients and autistic features bear large deletions. Based on these observations, we used multiplex ligation-dependent probe amplification to search for large deletions affecting the CREBBP gene in a Rubinstein-Taybi syndrome patient. We identified a novel heterozygote deletion removing five exons (exons 17-21), encoding the histone acetyltransferase domain. We propose the use of multiplex ligation-dependent probe amplification as a fast, accurate and cheap test for detecting large deletions in the CREBBP gene in the sub-group of Rubinstein-Taybi syndrome patients with low intelligence quotients and autistic features.

Lactic acid bacteria dynamics during spontaneous fermentation of cocoa beans verified by culture-independent denaturing gradient gel electrophoresis.

Cocoa is naturally fermented in the field before the cocoa seeds are removed for processing. We assessed the dynamics of lactic acid bacteria during cocoa fermentation in Bahia, Brazil. During five days of fermentation, temperature and pH were measured and beans were collected for genomic DNA extraction every 12 h. The DNA was used as a template for amplification with Lac1-Lac2 and Lac3-Lac2 for denaturing gradient gel electrophoresis analyses. pH values ranged from 3.34 to 4.98, while the temperature varied from 23° to 50°C. Lac1-Lac2 primers permitted detection of 11 operational taxonomic units. Twenty-eight operational taxonomic units were obtained with the primer pair Lac3-Lac2. It was observed that there were variations between the numbers of operational taxonomic units throughout the process, probably because of changes in pH and temperature. The greatest similarity in amplified samples was obtained with the primers Lac3-Lac2.

Detection of Salmonella Enteritidis in asymptomatic carrier animals: comparison of quantitative real-time PCR and bacteriological culture methods.

Quantification of Salmonella in asymptomatic carrier animals can be used to assess microbial risk and monitor the level of contamination in domestic animals used for food production. We examined the sensitivity, specificity and accuracy of real-time qPCR, without pre-enrichment or selective enrichment stages, for the quantification of S. enterica serovar Enteritidis in resistant mice, as a model of asymptomatic carrier animal. The results were compared with those obtained by traditional bacteriological culture methods, the gold standard test. Two hundred and forty-three samples, including spleen, liver, mesenteric lymph nodes, portions of intestine, intestinal content of the ileocecal portion, and feces, were collected from a group of 27 C57BL/6 mice, that had been intragastrically inoculated with high doses of S. enterica serovar Enteritidis. The real-time qPCR assay presented a consistent linearity of the standard curve (r(2) = 0.999), with very low differences between melting temperatures, and low coefficients of variation in intra- (< 1%) and interassay (< 2%) comparisons. The primers were highly specific; there was no amplification with other Salmonella serovars or with DNA from uninfected tissues and feces from mice. The detection limit of the technique was defined as 32 copies of S. enterica serovar Enteritidis. A sensitivity of 90%, a specificity of 77% and an accuracy of 79% were obtained. The higher sensitivity of PCR was reflected in a kappa coefficient of 0.41, showing moderate agreement between tests. We conclude that real-time qPCR is a good alternative for diagnostic scanning in asymptomatic carrier animals, due to its high sensitivity and rapidity.

Tissue and serum immune response in chronic hepatitis C with mild histological lesions.

The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-alpha, TGF-beta and CD4(+) and acinar IFN-gamma, TNF-alpha, IL-1beta and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-beta. Significant positive correlations were found between portal CD4+ and TNF-alpha, portal CD8(+) and TGF-beta, portal CD45(+)RO and TNF-alpha, acinar CD45(+)RO and IFN-gamma and acinar CD57(+) and TGF-beta. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4(+) T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.

Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury.

Herein, we describe a confirmed case of Loxosceles spider bite that illustrates the critical complications seen in loxoscelism, including skin necrosis, rhabdomyolysis, hemolysis, coagulopathy, acute kidney failure, and electrolyte disorders. Upon initial assessment, laboratory studies revealed the following: the white blood cell count was 29,400 WBCs/mm(3), hemoglobin was 9.2g/dL, and the platelet count was 218,000 cells/mm(3). Coagulation studies revealed the following: international normalized ratio, 1.83; activated partial-thromboplastin time, 62 s; D-dimer, 600 ng/mL (normal range <500 ng/mL); free protein S, 37% (normal range=64-114%); protein C, negative; and antithrombin III, negative. Various serum levels were abnormal: urea, 110 mg/dL; creatinine, 3.1mg/dL; indirect bilirubin, 3.8 mg/dL; creatine kinase, 1631 U/L; lactate dehydrogenase, 6591 U/L; potassium 6.2 mmol/L. Urine tests were positive for hemoglobin and bilirubin. In addition, concentrations of interleukin-6 and tumor necrosis factor-alpha were notably elevated in the serum. In conclusion, physicians must be alert to the possibility of loxoscelism when a patient presents with the clinical and laboratory findings described above, especially if the patient resides in an endemic area. Advances in our understanding of multiple pathways and mediators that orchestrate the response to Loxosceles venom might reveal new possibilities for the management of loxoscelism.

Tempo and mode of ERV-K evolution in human and chimpanzee genomes.

Several families of endogenous retrovirus (ERV) exist in copious numbers in the genomes of primate species. Therefore, we undertook a systematic search for endogenous retrovirus sequences from the ERV-K family, comparing across both human (Homo sapiens) and chimpanzee (Pan troglodytes) genomes. Using conserved motifs of the ERV-K as query we identified and characterized 76 complete ERV-K elements, 54 in human (HERV-K), 34 of which were described previously, and 21 in the chimpanzee (CERV-K). Phylogenetic analysis using coding regions and LTRs showed the existence of two main branches. Group I was the most heterogeneous and had an average integration time of 18.3 MYBP (million years before present), using rates ranging from 1.5 to 4.0 x 10(-9) s/s/y (substitution per site per year). Group O/N integrated around 19.4 MYBP and nested Group N integrated about 14 MYBP. We found evidence for strong positive selection on the gag, pol and env coding regions and for A/T hypermutation. Our data suggest that the endogenous elements were possibly involved in chromosomal rearrangements and retained a great deal of information from their active stage, most likely as a consequence of host interactions. This study also contributes to the annotation effort of both human and chimpanzee genomes.