Transient neonatal diabetes due to a missense mutation (E227K) in the gene encoding the ATP‐sensitive potassium channel (KCNJ11)

Neonatal diabetes is a monogenic form of diabetes. Herein, we report on a newborn presenting diabetic ketoacidosis at 17 days of life . A KCNJ11 mutation was identified. In such cases, insulin can be replaced by sulfonylurea with a successful metabolic control, as an example of how molecular diagnosis may influence the clinical management of the disorder.     

Pulmonary adenocarcinoma T1N0M0 and its classification

Over the last decade, use of the term bronchioloalveolar carcinoma (BAC) has come under constant scrutiny as some consider it an anachronism or a term that provides incorrect information about this neoplasm. To that extent, it has recently been suggested to replace the term BAC with that of in situ adenocarcinoma (AIS) or minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure bronchioloalveolar growth (AIS) or predominant bronchioloalveolar growth and ≤5-mm invasion (MIA). However, as of today, there is no comprehensive study of these tumors, and most of what has been published in this context is based on a review of the literature that focused on scattered short series of cases describing either small adenocarcinomas or BAC. More recently, a large series of cases of a more comprehensive nature that included all early-stage adenocarcinomas (T1N0M0) has cast some doubt regarding the need for the proposed change in nomenclature. At the same time, it was suggested that if indeed that notion is maintained, a more serious and comprehensive study of actual cases must be undertaken. The details of the issues surrounding this subject are presented in this review.     

Description and molecular characterization of Haemoproteus macrovacuolatus n. sp. (Haemosporida,Haemoproteidae), a morphologically unique blood parasite of black-bellied whistling duck (Dendrocygna autumnalis) from South America

During a surveillance programme on avian influenza in wild birds in the east of Colombia, 42 % of examined wild black-bellied whistling ducks (Dendrocygna autumnalis) were infected with undescribed Haemoproteus sp., which macrogametocytes possess one or several huge (2.5 μm in largest diameter) conspicuous roundish vacuoles, a unique character of avian haemoproteids. This parasite is named Haemoproteus (Parahaemoproteus) macrovacuolatus and described here using data on the morphology of its gametocytes, host cells and sequences of the complete mitochondrial genome and cytochrome b fragments. Illustrations of blood stages of the new species and DNA sequence information are provided. The phylogenetic analysis identified a closely related lineage C033, reported in South Asian ducks belonging to Dendrocygna. We also found that all Haemoproteus lineages from Passeriformes conformed a monophyletic group. Whereas we cannot exclude that this pattern could be an artefact of the limited taxonomic sampling in non-passeriform birds, thus this finding is worthy of attention. This study adds to our knowledge of the phylogenetic relationships among species of avian haemoproteids and describes a new haemoparasite in a non-passerine host.     

Fatty acid profiles in Leishmania spp. isolates with natural resistance to nitric oxide and trivalent antimony

Fatty acids, especially those from phospholipids (PLFA), are essential membrane components that are present in relatively constant proportions in biological membranes under natural conditions. However, under harmful growth conditions, such as diseases, environmental changes, and chemical exposure, the fatty acid proportions might vary. If such changes could be identified and revealed to be specific for adverse situations, they could be used as biomarkers. Such biomarkers could facilitate the identification of virulence and resistance mechanisms to particular chemotherapeutic agents. Therefore, specific biomarkers could lead to better therapeutic decisions that would, in turn, enhance treatment effectiveness. The objective of this study was to compare the fatty acid profiles of trivalent antimony and nitric oxide (NO)-resistant and -sensitive Leishmania chagasi and Leishmania amazonensis isolates. Fatty acid methyl esters (FAMEs) were obtained from total lipids (MIDI), ester-linked lipids (ELFA), and ester-linked phospholipids (PLFA). FAMEs were analyzed by chromatography and mass spectrometry. Species- or resistance-associated differences in FAME profiles were assessed by nonmetric multidimensional scaling, multiresponse permutation procedures, and indicator species analyses. The isolate groups had different MIDI-FAME profiles. However, neither the ELFA nor PLFA profiles differed between the sensitive and resistant isolates. Levels of the fatty acid 18:1 Δ9c were increased in sensitive isolates (p?<?0,001), whereas the fatty acid 20:4 Δ5,8,11,14 showed the opposite trend (p?<?0.01). We conclude that these two fatty acids are potential biomarkers for NO and antimony resistance in L. chagasi and L. amazonensis and that they could be helpful in therapeutic diagnoses.     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.     

Conserved features of intermediates in amyloid assembly determine their benign or toxic states

Some amyloid-forming polypeptides are associated with devastating human diseases and others provide important biological functions. For both, oligomeric intermediates appear during amyloid assembly. Currently we have few tools for characterizing these conformationally labile intermediates and discerning what governs their benign versus toxic states. Here, we examine intermediates in the assembly of a normal, functional amyloid, the prion-determining region of yeast Sup35 (NM). During assembly, NM formed a variety of oligomers with different sizes and conformation-specific antibody reactivities. Earlier oligomers were less compact and reacted with the conformational antibody A11. More mature oligomers were more compact and reacted with conformational antibody OC. We found we could arrest NM in either of these two distinct oligomeric states with small molecules or crosslinking. The A11-reactive oligomers were more hydrophobic (as measured by Nile Red binding) and were highly toxic to neuronal cells, while OC-reactive oligomers were less hydrophobic and were not toxic. The A11 and OC antibodies were originally raised against oligomers of Aβ, an amyloidogenic peptide implicated in Alzheimer's disease (AD) that is completely unrelated to NM in sequence. Thus, this natural yeast prion samples two conformational states similar to those sampled by Aβ, and when assembly stalls at one of these two states, but not the other, it becomes extremely toxic. Our results have implications for selective pressures operating on the evolution of amyloid folds across a billion years of evolution. Understanding the features that govern such conformational transitions will shed light on human disease and evolution alike.     

Genetic Characterization of Atypical Mansonella (Mansonella) ozzardi Microfilariae in Human Blood Samples from Northeastern Peru

Abstract. DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical microfilariae were clustered into the Mansonella group and indistinguishable from M. ozzardi based on these DNA markers.     

Oral lesions in renal transplant

To prevent rejection of kidney transplants, patients must be kept in immunosuppressive therapy for a long time, which includes the use of drugs such as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of these drugs reduces the general immune response of transplant patients and thus increases their susceptibility to infections. Moreover, these drugs increase the potential of developing lesions. Therefore, oral hygiene in kidney transplant recipients contributes to maintenance of the transplanted organ and its function. Thus, an investigation of oral lesions could be counted as a notable work. The aim of this study was to investigate oral lesions in a group of 21 kidney transplant patients under immunosuppressive therapy attended during a 1-year period in the Nephrology Department of the Federal University of Sergipe, Brazil. Data related to sex, age, etiology of renal disease, types of renal transplant, time elapsed after transplantation, immunosuppressive treatment, use of concomitant agents, and presence of oral lesions were obtained. All patients received a kidney transplant from a living donor, and the mean posttransplantation follow-up time was 31.6 months; 71.5% used triple immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten patients were also treated with calcium-channel blockers. Of the 21 transplant patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most common alteration, followed by candidiasis and superficial ulcers. One case of spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a variety of manifestations related to renal transplantation under immunosuppressive therapy.     

Craniomaxillofacial features in hereditary multiple exostosis

Hereditary multiple exostosis is the most common form of bone dysplasia. This entity is also known as diaphyseal aclasis, hereditary deforming chondrodysplasia, multiple hereditary exostoses, multiple osteochondromatosis, multiple cartilaginous exostosis, dyschondroplasia, and Ehrenfried disease. It is an inherited autosomal dominant disease with predominance in males and a benign condition characterized by the presence of multiple exostosis or osteochondromas arising from long and flat bones.Osteochondroma is the most common benign tumor in persons between 10 and 30 years of age. It accounts for 20% to 50% of all benign tumors and 10% to 15% of all bone tumors. It is more commonly located at the level of the metaphysis of long bones. However, osteochondroma is rare at the level of the facial bones and skull base. It has been reported in the maxillary sinus and in different parts of the mandible, such as the condyle, ramus, body, and symphyseal region. It is very uncommon in the coronoid process and occipital bone.Jacob disease, or osteochondroma of the mandibular coronoid process, is a benign skeletal tumor that is rare in the oral and maxillofacial skeleton. A review of the literature revealed only 41 histologically proven cases of 52 reported cases. To the best of the authors' knowledge this is the first clinical report of bilateral coronoid osteochondroma and associated occipital exostosis in a patient with hereditary multiple exostosis.     

Quality of Life in 833 outpatients with major depression treated with open-label venlafaxine extended release: An observational 24-week study

BACKGROUND Quality of Life (QoL) assessments are common in medicine and, recently, in psychiatry, mostly in patients with chronic mental illness. We evaluated QoL in depressed outpatients treated with venlafaxine-XR over a period of 24 weeks. METHOD We evaluated 833 patients with DSM-IV major depression using the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), the Montgomery-Åsberg Depression Rating Scale (MÅDRS), and the QoL in Depression Scale (QLDS). The patients received venlafaxine-XR and we evaluated them after 4, 8, and 24 weeks of treatment. RESULTS HAM-D scores decreased from a baseline of 24.6 &#45 6.3 to 6.0 &#45 5.5 (mean &#45 SD; P <0.0001) after 24 weeks. HAM-A scores decreased from a baseline of 32.3 &#45 7.9 to 6.8 &#45 6.8 ( P <0.0001) after 24 weeks. QLDS scores decreased from a baseline of 25.8 &#45 5.8 to 6.6 &#45 7.5 ( P <0.0001) after 24 weeks, indicating improvement in QoL. The response after 4 weeks was also significant and continued improving during the study. Venlafaxine-XR was shown to be safe and well tolerated. DISCUSSION Open-label venlafaxine-XR was safe, effective, well tolerated, and improved not only depression and anxiety symptoms, but also QoL, in outpatients with major depression. This study has the limitations of any non-randomized, non-blinded multiple-site clinical trial.