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Understanding how populations diverge is one of the oldest and most compelling questions in evolutionary biology. An in depth understanding of how this process operates in planktonic marine animals, where barriers for gene flow are seemingly absent, is critical to understanding the past, present, and future of ocean life. Mnemiopsis plays an important ecological role in its native habitat along the Atlantic coast of the Americas and is highly destructive in its non-native habitats in European waters. Although historical literature described three species of Mnemiopsis , the lack of stable morphological characters has led to the collapse of this group into a single species, Mnemiopsis leidyi . We generate high-quality reference genomes and use a whole-genome sequencing approach to reveal that there are two species of Mnemiopsis along its native range and show that historical divergence between the two species coincides with historical glacial melting. We define a hybridization zone between species and highlight that environmental sensing genes likely contribute to the invasive success of Mnemiopsis . Overall, this study provides insights into the fundamental question of how holopelagic species arise without clear barriers to gene flow and sheds light on the genomic mechanisms important for invasion success in a highly invasive species.

Failure to thrive (FTT) refers to a condition where a child does not gain weight or grow at the expected rate for their age and gender. An accepted definition includes a weight less than the lowest acceptable range on standardized growth charts. FTT is often a diagnostic challenge for providers treating children with mixed etiologies. This report discusses the case of an 11-year-old female with a diagnosis of Crohn's disease and avoidant and restrictive food intake disorder (ARFID). Management by an interprofessional healthcare team has been difficult, given the multifactorial nature of the patient's weight loss. This report suggests that behavioral and psychological aspects, such as aversion to eating and reluctance to experiment with different foods, may align with symptoms of Crohn's disease in children. It also emphasizes the importance of timely diagnosis and appropriate interventions, as they can mitigate psychological and developmental setbacks., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Valencia et al.)

Ehlers-Danlos syndrome (EDS) is a collection of genetic disorders caused by abnormalities in collagen and typified by hyperflexible joints, hyperextensible skin, and a tendency for easy bruising and tissue injuries. Hypermobile Ehlers-Danlos syndrome (hEDS), the most common subtype, presents a diagnostic challenge due to the lack of specific genetic markers. This case report describes a 13-year-old girl with hEDS, presenting with hypermobility, thoracolumbar scoliosis, constipation, glucosuria, microscopic hematuria, urticaria, and intermittent episodes of bilateral hand and feet swelling. Genetic testing revealed a variant of uncertain significance in the COL9A2 gene. An echocardiogram showed a mildly dilated aortic root. The complexity of her presentation underscores the challenges in diagnosing and managing hEDS with multisystem involvement., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Cosare et al.)

This study underscores the persistent underrepresentation of women in academic dermatology leadership positions by examining the gender composition of editorial boards across top dermatology journals, emphasizing the urgent need for proactive strategies to promote diversity, equity, and inclusion., (©Mindy D Szeto, Torunn E Sivesind, Lori S Kim, Katie A O’Connell, Kathryn A Sprague, Yvonne Nong, Daniel M Strock, Annie L Cao, Jieying Wu, Lauren M Toledo, Sophia M Wolfe, Wyatt Boothby-Shoemaker, Robert P Dellavalle. Originally published in JMIR Dermatology (http://derma.jmir.org), 21.05.2024.)

Objective: To determine the implication of the new AJCC staging system for pT classification in a cohort of patients with SCC of the lip mucosa and compare it to other oral cavity sites., Methods: Retrospective cohort of 744 patients treated between 2002 and 2017, by the Head and Neck Surgery Department of the University of Sao Paulo., Results: Of 95 lip patients, 42 had pT upstage (58.1% of pT1 to pT2-3 and 50% of pT2 to pT3). Similar DFS/OS observed for those pT1 maintained or upstaged to pT2-3, pT2 patients upstaged to pT3 presented worse OS (49.4% versus 92.3%, P = .032). The comparison between lip and other mouth topographies, denoted better prognosis for pT1-2, but not for pT3-4a. Lip tumors had lower DOI, rates of perineural/angiolymphatic invasion, nodal metastasis, recurrence, and death., Conclusion: The inclusion of DOI to the new pT classification better stratifies patients with SCC of the lip mucosa upstaged to pT3 by assessing inferior OS., Level of Evidence: 3 Laryngoscope, 131:E2770-E2776, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Given the difficulties of controlling the tick Rhipicephalus microplus due to acaricide resistance, this study aimed to ascertain whether shearing could reduce infestation in cattle. 17 taurine cattle were sheared on the anterior third of one randomly selected side. Shearing was undertaken using a machine with a blade, leaving coats with a thickness of 1 mm. Subsequently, eight evaluations were performed once a week, counting adult females of R. microplus with a diameter > 4.5 mm on the anterior third of both sides (shorn and unshorn). The coat length was also monitored by taking five hair samples from each animal fortnightly (1, 15, 29, 43 and 57 days post shorn) from a central area of both shoulders (shorn and unshorn). The tick counts and hair length data were transformed for normalisation and were analysed using mixed models. The tick and hair length means were significantly higher for the unshorn side. Tick counts were significantly lower on the sheared side until the fifth evaluation, with the final three presenting no differences between the sides. The hair length was significantly lower for the sheared side during the five evaluations. We conclude that as the hair length increased, there was also an increase in the number of ticks on the sheared side. Although this method is not practical for large herds, it can be deemed an option in extreme conditions of tick infestation. In addition, the study reinforces the suggestion that the selection and/or use of cattle with shorter hairs may contribute to reduced tick infestation.

Imported malaria is a malaria infection diagnosed outside the area where it was acquired and is induced by human migration and mobility. This retrospective study was performed based on secondary data from 2007 to 2015. In total, 736 cases of imported malaria (79.7% of 923 cases) were recorded in Rio de Janeiro state. Of the imported cases, 55.3% came from abroad, while 44.7% came from other regions of Brazil. Most cases of imported malaria in Brazil (85.5%) originated in Amazônia Legal, and Burundi (Africa) accounted for 59% of the cases from abroad. Analyses of the determinants of imported malaria in Rio de Janeiro state must be continued to understand the relationship between the origin and destination of cases.

Background: Extra-Amazonian malaria mortality is 60 times higher than the Amazon malaria mortality. Imported cases correspond to approximately 90% of extra-Amazonian cases. Imported malaria could be a major problem if it occurs in areas with receptivity, because it can favor the occurrence of outbreaks or reintroductions of malaria in those areas. This study aimed to model territorial receptivity for malaria to serve as an entomological surveillance tool in the State of Rio de Janeiro, Brazil. Geomorphology, rainfall, temperature, and vegetation layers were used in the AHP process for the receptivity stratification of Rio de Janeiro State territory., Results: The model predicted five receptivity classes: very low, low, medium, high and very high. The 'very high' class is the most important in the receptivity model, corresponding to areas with optimal environmental and climatological conditions to provide suitable larval habitats for Anopheles (Nyssorhynchus) vectors. This receptivity class covered 497.14 km 2 or 1.18% of the state's area. The 'high' class covered the largest area, 17,557.98 km 2 , or 41.62% of the area of Rio de Janeiro State., Conclusions: We used freely available databases for modeling the distribution of receptive areas for malaria transmission in the State of Rio de Janeiro. This was a new and low-cost approach to support entomological surveillance efforts. Health workers in 'very high' and 'high' receptivity areas should be prepared to diagnose all febrile individuals and determine the cause of the fever, including malaria. Each malaria case must be treated and epidemiological studies must be conducted to prevent the reintroduction of the disease.

Introduction: Tuberculosis remains as a global public health problem and its occurrence and distribution is associated with social inequalities. Itaboraí is among the priority Brazilian municipalities for tuberculosis control. The study aimed to combine social indicators into a composite indicator to measure differences in living conditions of the population in Itaboraí, as well as evidence of health inequalities related to tuberculosis., Methods: An ecological study, with spatial analysis of tuberculosis and its relation to socioeconomic and demographic status of households. Data were obtained from individuals declared in the Mortality Information System (SIM), notified in the Notification of Injury Information System - SINAN or Tuberculosis Special Treatment Information System - SITETB from 2007 to 2013., Results: Evidence indicates association between sociodemographic inequalities and occurrence of tuberculosis in the population. Findings point to a lower percentage of healing and a higher percentage of abandonment and death in areas with high social vulnerability, with a relative risk over twice as high than that found in areas of lower vulnerability., Conclusion: The study showed strong evidence that the influence of unequal sociodemographic conditions have a negative impact on health conditions of the population in Itaboraí.

Objective: To analyze the determinants for the occurrence of human visceral leishmaniasis linked to the conditions of vulnerability., Methods: This is an ecological study, whose spatial analysis unit was the Territorial Analysis Unit in Araguaína, State of Tocantins, Brazil, from 2007 to 2012. We have carried out an analysis of the sociodemographic and urban infrastructure situation of the municipality. Normalized primary indicators were calculated and used to construct the indicators of vulnerability of the social structure, household structure, and urban infrastructure. From them, we have composed a vulnerability index. Kernel density estimation was used to evaluate the density of cases of human visceral leishmaniasis, based on the coordinates of the cases. Bivariate global Moran's I was used to verify the existence of spatial autocorrelation between the incidence of human visceral leishmaniasis and the indicators and index of vulnerability. Bivariate local Moran's I was used to identify spatial clusters., Results: We have observed a pattern of centrifugal spread of human visceral leishmaniasis in the municipality, where outbreaks of the disease have progressively reached central and peri-urban areas. There has been no correlation between higher incidences of human visceral leishmaniasis and worse living conditions. Statistically significant clusters have been observed between the incidences of human visceral leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012) and the indicators and index of vulnerability., Conclusions: The environment in circumscribed areas helps as protection factor or increases the local vulnerability to the occurrence of human visceral leishmaniasis. The use of methodology that analyzes the conditions of life of the population and the spatial distribution of human visceral leishmaniasis is essential to identify the most vulnerable areas to the spread/maintenance of the disease., Objetivo: Analisar determinantes para a ocorrência da leishmaniose visceral humana vinculados às condições de vulnerabilidade., Métodos: Estudo ecológico, cuja unidade de análise espacial foi a Unidade de Análise Territorial em Araguaína, TO, de 2007 a 2012. Foi realizada análise da situação sociodemográfica e de infraestrutura urbana no município. Indicadores primários normalizados foram calculados e utilizados na construção de indicadores de vulnerabilidade de estrutura social, de estrutura domiciliar e de infraestrutura urbana. A partir deles, foi composto um índice de vulnerabilidade. A estimativa de Kernel foi utilizada para avaliar a densidade de casos de leishmaniose visceral humana, com base nas coordenadas dos casos. O I-Moran Global Bivariado foi empregado para verificar a existência de autocorrelação espacial entre a incidência de leishmaniose visceral humana e os indicadores e índice de vulnerabilidade. I-Moran Local Bivariado foi utilizado para identificar clusters espaciais., Resultados: Foi observado um padrão de disseminação centrífuga da leishmaniose visceral humana no município, em que surtos da doença atingiram progressivamente áreas centrais e periurbanas. Houve correlação entre maiores incidências de leishmaniose visceral humana e piores condições de vida. Foram observados clusters estatisticamente significativos entre as incidências de leishmaniose visceral humana nos dois períodos analisados (2007 a 2009 e 2010 a 2012) e os indicadores e índice de vulnerabilidade., Conclusões: O ambiente em áreas circunscritas contribui como fator de proteção ou aumenta a vulnerabilidade local à ocorrência de leishmaniose visceral humana. O uso de metodologia que analisa as condições de vida da população e distribuição espacial da leishmaniose visceral humana é essencial na identificação de áreas mais vulneráveis à disseminação/manutenção da doença.

Objective: This study aims to analyze the association between the incidence of tuberculosis and different socioeconomic indicators in a territory of intense transformation of the urban space., Methods: This is an ecological study, whose analysis units were the neighborhoods of the city of Itaboraí, state of Rio de Janeiro, Brazil. The data have been analyzed by generalized linear models. The response variable was incidence of tuberculosis from 2006 to 2011. The independent variables were the socio-demographic indicators. The spatial distribution of tuberculosis was analyzed with the elaboration of thematic maps., Results: The results have shown a significant association between the incidence of tuberculosis and variables that reflect different dimensions of living conditions, such as consumer goods, housing conditions and its surroundings, agglomeration of population, and income distribution., Conclusions: The disproportionate incidence of tuberculosis in populations with worse living conditions highlights the persistence of socioeconomic determinants in the reproduction of the disease. Different municipal public sectors need to better articulate with local tuberculosis control programs to reduce the social burden of the disease., Objetivo: Analisar a associação entre incidência de tuberculose e diferentes indicadores socioeconômicos em território em intensa transformação do espaço urbano., Métodos: Estudo ecológico, cujas unidades de análise foram os bairros do município de Itaboraí, RJ. Os dados foram analisados por modelos lineares generalizados. A variável resposta foi incidência de tuberculose de 2006 a 2011. As variáveis independentes foram os indicadores sociodemográficos. A distribuição espacial da tuberculose foi analisada por meio da elaboração de mapas temáticos., Resultados: Os resultados apontaram associação significativa entre a incidência de tuberculose e variáveis que refletem diferentes dimensões de condições de vida, como bens de consumo, condições de moradia e seu entorno, aglomeração populacional e distribuição de renda., Conclusões: O acometimento desproporcional da tuberculose em grupos populacionais com piores condições de vida ressalta a persistência dos determinantes socioeconômicos na reprodução da doença. Faz-se necessária a melhor articulação de diferentes setores públicos municipais com o programa local de controle da tuberculose visando à redução da carga social da doença.

Background: Indicine breeds of bovines are highly resistant and taurine breeds are susceptible to the cattle tick, Rhipicephalus microplus, a species which causes great damage to livestock. Animals use their tongues for self-grooming, an important behavior for ridding themselves of ectoparasites. However, the role of tongue morphology, notably the filiform papillae, in this process is not known., Findings: This study compared features of the filiform papillae of tongues in eight Nelores (indicine breed) and eight Holsteins and two Brown Swiss (taurine breeds) and verified how they associate with tick loads. Biopsies were taken from identical positions of tongues and measured by scanning electron microscopy. One-way analysis of variance detected significant differences between morphological features of tongues from indicine and taurine breeds: Nelores had longer papillae (mean of 2.3 mm ± 0.029 SD; P < 0.001), and more papillae per cm(2) (mean of 25.2 papillae ± 1.92 SD; P < 0.05) than European bovines (means of, respectively, 1.8 mm ± 0.027 SD and 20.9 ± 0.74 SD papillae per cm(2)). After infestations with equal numbers of larvae, loads of adult ticks were inversely correlated with length of papillae and directly correlated with distances between the apices of papillae (P = 0.014; r = -0.566 and P = 0.018; r = 0.567, Pearson product momentum correlation, respectively)., Conclusions: Spacing between papillae is smaller in Nelores, thus their tongues may be rougher and, consequently, more effective in removing tick larvae during self-grooming, explaining the greater resistance to ticks among Zebu breeds of cattle.

Every child had an average of three episodes of diarrhea per year in developing countries in the twentieth century. The decrease of the number of deaths due to diarrhea in Brazil was more closely related to the use of control techniques than to changes in lifestyle conditions. This article seeks to analyze the spatial distribution of morbidity due to diarrhea among children and its relation with lifestyle conditions. This was an ecological study, with the suburbs of the city of Itaborai as units of analysis. The population studied was the number of hospitalizations of children < 5 years for diarrhea between 2006 and 2009, available in Hospital Information Systems. The Diarrhea Hospitalization Ratio (DHR) indicator and Composite Lifestyle Quality (CLQ) indicator were established. Diarrhea still accounts for a large number of hospitalizations of children (15.5% between 2006 and 2009). The DHR was high in this period (69.7 hospitalizations/ 1.000 NV). The spatial analysis identified that the suburbs with the highest DHR were, in most cases, those with the highest population agglomerations and better lifestyle conditions.

Black vultures (Coragyps atratus) are often present near calving sites, and under this situation they may play a positive role by removing animal carcasses and afterbirth or a negative role by attacking neonate calves or disturbing cow-calf behaviours following parturition. Cow-calf behaviour was recorded over a 4-year study period from a total of 300 births involving 200 Nellore, 54 Guzerat, 20 Gyr and 26 Caracu cows. The calving site in relation to the location of the herd, considering cow-calf pairs within, close or distant to the herd, the presence of vultures and the behaviour of cows and calves were recorded instantaneously, at 5-min interval. On average, vultures were present at 80% of the calving sites. The frequency of vultures present at calving sites was dependent on the years for the Nellore herd, increasing from 1998 to 2003. When vultures were present, the time that the cow was in contact with its calf decreased, and the percentage of time that the cow was standing still increased. Vultures were observed pecking cows and their neonates during 34.1% of all recordings. However, in only two cases pecking injuries were actually observed on calves that were noted to be very weak. The preliminary results suggest that although black vultures cannot be characterized as a predator of neonate calves, they sometimes attack neonate calves and their presence near the calving sites alter the behaviours of cows and calves.

The knowledge of the interaction between mother and offspring might contribute to enhance the welfare of the offspring and to improve the reproductive efficiency of the cow. However, there is still little information available about such interaction in some cattle breeds. A series of observational studies were set up, addressing the mother-offspring relationships of Nelore, Guzerat and Gyr cattle breeds. Firstly, the behaviour of cows and calves around the time of parturition was described, and then, the underlying factors that affect the calves' survival and development were studied. Special attention was given to the failure or delay in the first suckling. The results together are indicative of genetic variability for some studied variables, indicating the possibility of selection for calf vigour (using latency to stand up and latency to suckle as its indicators) and maternal ability (using percentage of time in contact with the calves), in spite of the estimates of heritability were low and presented high standard deviation for all variables. The individual variability in their suckling behaviour and the efficiency in first suckling cannot be explained by a single isolated underlying factor. By now, there are some results available, although there are many questions without answers. The field is still open for the development of future research.

Aedes aegypti and Ae. albopictus are vectors of dengue viruses, which cause endemic disease in the city of Manaus, capital of the state of Amazonas, Brazil. More than 53 thousand cases have been registered in this city since the first epidemic in 1998. We evaluated the hypothesis that different ecological conditions result in different patterns of vector infestation in Manaus, by measuring the infestation level in four neighborhoods with different urbanization patterns, during the rainy (April), dry (August), and transitional (November) seasons. Ae. aegypti predominated throughout the study areas and sampling periods, representing 86% of all specimens collected in oviposition traps. High frequencies of houses positive for both species were observed in all studied sites, with Ae. aegypti present in more than 84% of the houses in all seasons. Ae. albopictus, on the other hand, showed more spatial and temporal variation in abundance. We found no association between infestation level and house traits. This study highlights the homogeneity of dengue vector distribution in Manaus.

The aim of our investigation was to evaluate, with a prevalence study, the modes of transmission of Hepatitis B virus (HBV), within infected subjects and their household contacts in the State of Amazon, western Brazilian Amazon. We studied 97 index cases and 258 household contacts. Out of the 258 household contacts of HBV, 51.6% had serological markers of a past infection, 12.0% signs of active infection, suggesting that the virus circulates within household members. The high prevalence among siblings (23.6%) demonstrates the importance of personal contact in the transmission of this virus. Another indirect indicator of intra-familial transmission was the high prevalence of HBV markers within contacts of a fulminant hepatitis. The vertical transmission of HBV in our region may or may not occur, but if it does it as a rare event. Our results demonstrate the importance of the presence of HBV, and demand other investigations to clarify the inter-familial transmission of these viruses in our region.

This study analyzes the Rio de Janeiro Municipal AIDS Information System, specifically the system's strengths and limitations in the epidemic's current context, from a broader perspective of epidemiological surveillance. The objective was to provide a brief description of the system, considering its different components. The authors further analyzed records pertaining to the reporting and investigation of AIDS cases from 1985 to 1995 and an update of the database as a contribution to the system's quality. The results showed improvement in the consistency of the AIDS database, particularly for the following variables: occupation, neighborhood, school, and exposure category, although the study found concrete limitations in the system's design and structure for dealing with the complexity and heterogeneity of AIDS surveillance. The study thus identified the need to construct an efficient HIV/AIDS surveillance system, based on epidemiological indicators aimed at monitoring and evaluating changes in the epidemiological pattern and analysis of the impact on morbidity and mortality resulting from access to more efficient forms of prevention and new treatments.

The protein kinase family represents both a huge opportunity and a challenge for drug development. The conservation of structural features within the ATP binding cleft initially led to the belief that specificity would be difficult to achieve. This dogma has now been clearly dispelled with the discovery and clinical testing of a group of first generation compounds, which are characterized by a high degree of selectivity towards a variety of oncology targets. The structural basis for selectivity and potency has now been clarified with the crystallization of a number of such targets in complex with inhibitors. The protein kinase inhibitor field is now ripe for the structure based exploitation of additional highly validated targets from a variety of therapeutic areas.

Background: The lymphocyte-specific kinase Lck is a member of the Src family of non-receptor tyrosine kinases. Lck catalyzes the initial phosphorylation of T-cell receptor components that is necessary for signal transduction and T-cell activation. On the basis of both biochemical and genetic studies, Lck is considered an attractive cell-specific target for the design of novel T-cell immunosuppressants. To date, the lack of detailed structural information on the mode of inhibitor binding to Lck has limited the discovery of novel Lck inhibitors., Results: We report here the high-resolution crystal structures of an activated Lck kinase domain in complex with three structurally distinct ATP-competitive inhibitors: AMP-PNP (a non-selective, non-hydrolyzable ATP analog); staurosporine (a potent but non-selective protein kinase inhibitor); and PP2 (a potent Src family selective protein tyrosine kinase inhibitor). Comparison of these structures reveals subtle but important structural changes at the ATP-binding site. Furthermore, PP2 is found to access a deep, hydrophobic pocket near the ATP-binding cleft of the enzyme; this binding pocket is not occupied by either AMP-PNP or staurosporine., Conclusions: The potency of staurosporine against Lck derives in part from an induced movement of the glycine-rich loop of the enzyme upon binding of this ligand, which maximizes the van der Waals interactions present in the complex. In contrast, PP2 binds tightly and selectively to Lck and other Src family kinases by making additional contacts in a deep, hydrophobic pocket adjacent to the ATP-binding site; the amino acid composition of this pocket is unique to Src family kinases. The structures of these Lck complexes offer useful structural insights as they demonstrate that kinase selectivity can be achieved with small-molecule inhibitors that exploit subtle topological differences among protein kinases.

Protein kinases are involved in a wide variety of signal transduction processes; their deregulation has been implicated in a number of human diseases, including cancer and disorders of the immune system. The recently determined structures of two protein kinases, cAPK and CDK2, in complex with an inhibitor, staurosporine, provide a detailed account of inhibitor-kinase interactions and inhibitor selectivity.

N-Hydroxyureas based on the 1,4-benzodioxan template were prepared from appropriately substituted 1,4-benzodioxan-2-methanols as the key intermediates and evaluated in the in vitro guinea pig polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay for their 5-LO inhibitory activity. Placement of a 7-phenoxy or 7-p-fluorophenoxy substituent resulted in a dramatic increase in in vitro potency. Selected compounds were subsequently assayed in an ex vivo dog model of LTB4 synthesis at a dose of 1.0 mg/kg. The 7-phenoxy derivatives 16 and 17 showed modest duration of action (DA) in this dog model. The 6-regioisomers 21 and 22 were less potent. Replacement of the 7-phenoxy group of 16 with the p-fluorophenoxy moiety enhanced the DA dramatically. Compound 18 (CGS 25667), which had an IC50 value of 100 nM in the in vitro guinea pig 5-LO assay, had a DA of 8.5 h (zileuton, DA = 8.5 h) at the oral dose of 1.0 mg/kg. Optical antipodes (24, 26) of 18 were independently synthesized in high (> 95%) enantiomeric purity from commercially available optically active glycidyl tosylates and evaluated. In the in vitro assay, the 2S-(-)-enantiomer (24, CGS 25997, IC50 = 85 nM) was found to be twice as active as the 2R-(+)-counterpart (26, CGS 25998, IC50 = 180 nM). In the ex vivo experiment, 24, which dose dependently inhibited plasma 5-LO activity, was shown to be significantly longer acting than 26, with a DA of 8.4 h when dosed orally at 1.0 mg/kg.

Persistent Mg2+ deficiency may interfere with restoration of normal tissue K+ levels. This study examined: a) the effects of chronic furosemide treatment on K+ of sartorius, aorta and ventricle of rats fed Mg2(+)-deficient (100 ppm) or Mg2(+)-sufficient (400 ppm) diet and deionized water; b) whether normal tissue K+ is restored by oral K+ or K+/Mg2+ supplementation with continued furosemide therapy. Levels of Mg2+ were also measured. Furosemide (20 mg/kg i.p.) decreased K+ in sartorius, aorta and ventricle by 5.5, 4.3 and 19.9 microEq/gm (p less than .05), respectively, in rats fed 100 ppm Mg2+ diet. Furosemide did not alter K+ levels in rats fed 400 ppm Mg2+ diet. K+ supplementation (1 mEq/kg for 7 days) restored K+ to normal in sartorius but the addition of Mg2+ supplementation was necessary to restore K+ levels to normal in ventricle and aorta. These data indicate that furosemide can decrease tissue K+ in rats on a Mg2(+)-deficient diet. This decrease can be reversed during diuretic administration by K+ supplementation in sartorius, or K+ plus Mg2+ supplementation in ventricle and aorta.

In the suburban district of Campo Grande, Municipality of Rio de Janeiro (Brazil) cases of both Leishmania domovani and L. b. braziliensis infections occur. In March 1982 we examined a white male child, five years old, with fever, weight loss and distended abdomen, symptoms said to have started three months before. After the first month a papular lesion appeared on his forehead, rapidly increasing in size and becoming ulcerated: Parasites were isolated from both the ulcer and the bone marrow by culturing in BHI-agar with rabbit blood and a liquid overlay of modified LIT medium. Using the techniques of zymodeme analysis, schizodeme analysis and serodeme analysis using monoclonal antibodies, the parasite from the ulcer was identified as L. b. braziliensis and that from the bone marrow as L. donovani. This seems to be the first described case of concurrent infection of man with a visceral and cutaneous Leishmania. It indicates that, at least in humans, a previous infection with L. donovani does not protect against L. b. braziliensis. This result has important implications for the development of vaccines against leishmaniases.

Forty dogs from the periphery of the city of Rio de Janeiro were studied. All dogs where diagnosed as positive for leishmaniasis either parasitologically and/or serologically. Among them, 19 came from areas where only Visceral Leishmaniasis (VL) occurs (Realengo, Bangu, Senador Camará). Clinical signs of the disease were seen in 36.8% of the cases, including emaciation - 100%, lymphadenopathy and depilation - 85.7%. The other 21 dogs came from an area (Campo Grande) where both diseases (VL, and American Cutaneous Leishmaniasis - ACL) occur. Clinical signs of the disease, mainly cutaneous or mucocutaneous ulcers were seen in 76.2% of the cases. Leishmania parasites were found in 39 cases: 22% in viscera, 42.5% in viscera and normal skin and 35% in cutaneous or mucocutaneous ulcers. All the Leishmania stocks isolated from dogs which came from Realengo, Bangu, Senador Camará (VL area), and from Campo Grande (VL + ACL area) were characterized as L. donovani (except in one case) according to their schizodeme, zymodeme and serodeme. The only stock characterized as L. b. braziliensis, was isolated from the lymph node of a dog from Campo Grande with visceral disease and without skin lesions. Antimony therapy attempted in eight Leishmania donovani positive dogs was unsuccessful.