Resolution and Resurgence of Schistosoma haematobium—induced Pathology After Community-based Chemotherapy in Ghana, as Detected by Ultrasound

Community-based treatment is recommended for endemic populations with urinary schistosomiasis; however, the optimal target group for treatment and retreatment interval have not been established. Using ultrasound, this study identified subpopulations whose lesions were most likely to respond to treatment and characterized resurgence of pathology. Ultrasound examination of 1202 infected patients was followed by chemotherapy with praziquantel. A sample of 698 patients was followed for 18 months after treatment. Nearly all types of bladder pathologies resolved after treatment, regardless of patient's age or intensity of initial infection. However, many patients' upper urinary tract pathologies (62.5%) did not resolve. During the 18-month follow-up period, reappearance of severe bladder pathologies was rare, and < 10% of persons had resurgence of mild bladder pathologies. For this population, re-treatment is not needed annually but might be cost effective if given several years later. Confirmation from other areas is required before general policies can be forme

Nutritional status and childhood wheezing in rural Bangladesh.

OBJECTIVE: To investigate the association between current childhood nutritional status and current wheezing among pre-school children in rural Bangladesh. DESIGN: Cross-sectional study. SETTING: Matlab region, rural Bangladesh. SUBJECTS: Children (n 912) aged 4·5 years. Anthropometric measurements of the mothers and their children were taken during a 1-year period from December 2007 to November 2008. Current wheezing was identified using the International Study of Asthma and Allergies in Childhood questionnaire. Serum total IgE was measured by human IgE quantitative ELISA. IgE specific antibody to dust mites (Dermatophagoides pteronyssinus) was measured by the CAP-FEIA system (Phadia AB, Uppsala, Sweden). RESULTS: Wheezing at 4·5 years old was significantly associated with stunting (OR = 1·58; 95 % CI 1·13, 2·22) and underweight (OR = 1·39; 95 % CI 1·00, 1·94). The association with stunting remained significant after adjustment for sex, birth weight, birth length, gestational age at birth, mother's parity, maternal BMI, family history of asthma, socio-economic status, season of birth and intervention trial arm (OR = 1·74; 95 % CI 1·19, 2·56). CONCLUSIONS: Stunting was a significant risk factor for wheezing among rural Bangladeshi children. Further studies will be required to confirm the relationship between nutritional status and allergic illnesses in developing countries

Toxic Systemic Reaction after Bee Stings in a Bitch

Background: Bee sting poisonings are common in dogs, and toxic systemic presentation may represent a life-threatening condition. Apis mellifera venom is a complex mixture of melitin, apamine, phospholipase, hyaluronidase and degranulating peptides, that causes local injury at the site of inoculation and multiple organ complications, including hemolysis, kidney injury, muscular damage, cardiovascular and respiratory complications. The present work reports a complete and detailed description of a dog’s systemic toxic reaction to bee stings, including history, clinical signs, laboratory findings, emergency care and development, as well as possible association with later immunomediated arthritis. Case: A 6-year-old female German Shepperd suffered multiple bee stings. First care was conducted by a veterinary at the site, where he only received promethazine, meloxicam and dexamethasone. After 24 h and significant progression of symptoms, the animal was forwarded to a specialized veterinary hospital. The patient was evaluated throughout 9 days, and presented intense edema, respiratory distress, tongue necrosis and grade II of acute kidney injury. Extensive laboratory exams were conducted throughout the hospitalization. Main laboratory findings included polycythemia, leukocytosis by neutrophilia and monocytosis, thrombocytopenia and azotemia. Urinalysis evidenced turbid aspect, dark yellow color and intense proteinuria, reinforcing kidney damage. Abdominal ultrasound examination identified blood clots in the bladder, and liver with reduced echogenicity and echotexture, suggesting acute inflammation. Therapy aimed to stabilize the patient, control kidney damage and avoid anaphylaxis. Treatment included intensive care support, promethazine, hydrocortisone, dexamethasone, dipyrone, methadone, metronidazole, ampicillin, clindamycin and tramadol. Following successful treatment, the animal presented immunomediated polyarthritis, possibly associated to both the poisoning and later diagnosed hemoparasitosis (both Erlichia and Babesia). Discussion: Massive bee attacks can cause severe complications, however, data regarding emergency care records are scarce. Based on clinical signs and laboratory findings, the patient presented toxic systemic reaction, including grade II of acute kidney injury and significant cardiorespiratory distress. Another important complication was tongue necrosis, that demanded attention and special supportive care, including feeding tube and specific feed. Treatment also focused in reducing edema and control possible anaphylaxis, providing analgesia and antibiotic therapy. Laboratory findings have been previously described, with evidence of immune-mediated reaction. Follow-up consultations revealed normal parameters, and an unusual presentation of claudication. Investigation concluded that polyarthritis could be responsible for such finding and may be a result of the deposition of immunomediated complexes in the joints, due in this case to the bee poisoning and later positive diagnosis for both Erlichia and Babesia. Systemic reactions to bee stings are complex, and full clinical and laboratory profile aid in both the prognosis and treatment options. Special attention must be given to tongue damage and supportive care is essential for maintaining feeding conditions. Arthritis should be considered as possible complication, reinforcing the importance of follow-up consultations. Keywords: bee attack, dog, envenomation, melittin; poisoning, phospholipase A2

Risk Factors for Kala-Azar in Bangladesh

Since 1990, South Asia has experienced a resurgence of kala-azar (visceral leishmaniasis). To determine risk factors for kala-azar, we performed cross-sectional surveys over a 3-year period in a Bangladeshi community. By history, active case detection, and serologic screening, 155 of 2,356 residents had kala-azar with onset from 2000 to 2003. Risk was highest for persons 3–45 years of age, and no significant difference by sex was seen. In age-adjusted multivariable models, 3 factors were identified: proximity to a previous kala-azar patient (odds ratio [OR] 25.4, 95% confidence interval [CI] 15–44 within household; OR 3.2 95% CI 1.7–6.1 within 50 m), bed net use in summer (OR 0.7, 95% CI 0.53–0.93), and cattle per 1,000 m2 (OR 0.8, 95% CI 0.70–0.94]). No difference was seen by income, education, or occupation; land ownership or other assets; housing materials and condition; or keeping goats or chickens inside bedrooms. Our data confirm strong clustering and suggest that insecticide-treated nets could be effective in preventing kala-azar

The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34+ samples. however, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. we observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34+ samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. the EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients

Analysis of Hypoxia and Hypoxia-Like States through Metabolite Profiling

In diverse organisms, adaptation to low oxygen (hypoxia) is mediated through complex gene expression changes that can, in part, be mimicked by exposure to metals such as cobalt. Although much is known about the transcriptional response to hypoxia and cobalt, little is known about the all-important cell metabolism effects that trigger these responses.Herein we use a low molecular weight metabolome profiling approach to identify classes of metabolites in yeast cells that are altered as a consequence of hypoxia or cobalt exposures. Key findings on metabolites were followed-up by measuring expression of relevant proteins and enzyme activities. We find that both hypoxia and cobalt result in a loss of essential sterols and unsaturated fatty acids, but the basis for these changes are disparate. While hypoxia can affect a variety of enzymatic steps requiring oxygen and heme, cobalt specifically interferes with diiron-oxo enzymatic steps for sterol synthesis and fatty acid desaturation. In addition to diiron-oxo enzymes, cobalt but not hypoxia results in loss of labile 4Fe-4S dehydratases in the mitochondria, but has no effect on homologous 4Fe-4S dehydratases in the cytosol. Most striking, hypoxia but not cobalt affected cellular pools of amino acids. Amino acids such as aromatics were elevated whereas leucine and methionine, essential to the strain used here, dramatically decreased due to hypoxia induced down-regulation of amino acid permeases.These studies underscore the notion that cobalt targets a specific class of iron proteins and provide the first evidence for hypoxia effects on amino acid regulation. This research illustrates the power of metabolite profiling for uncovering new adaptations to environmental stress

Feedback Enhances Feedforward Figure-Ground Segmentation by Changing Firing Mode

In the visual cortex, feedback projections are conjectured to be crucial in figure-ground segregation. However, the precise function of feedback herein is unclear. Here we tested a hypothetical model of reentrant feedback. We used a previous developed 2-layered feedforwardspiking network that is able to segregate figure from ground and included feedback connections. Our computer model data show that without feedback, neurons respond with regular low-frequency (∼9 Hz) bursting to a figure-ground stimulus. After including feedback the firing pattern changed into a regular (tonic) spiking pattern. In this state, we found an extra enhancement of figure responses and a further suppression of background responses resulting in a stronger figure-ground signal. Such push-pull effect was confirmed by comparing the figure-ground responses withthe responses to a homogenous texture. We propose that feedback controlsfigure-ground segregation by influencing the neural firing patterns of feedforward projecting neurons

Feed-Forward Segmentation of Figure-Ground and Assignment of Border-Ownership

Figure-ground is the segmentation of visual information into objects and their surrounding backgrounds. Two main processes herein are boundary assignment and surface segregation, which rely on the integration of global scene information. Recurrent processing either by intrinsic horizontal connections that connect surrounding neurons or by feedback projections from higher visual areas provide such information, and are considered to be the neural substrate for figure-ground segmentation. On the contrary, a role of feedforward projections in figure-ground segmentation is unknown. To have a better understanding of a role of feedforward connections in figure-ground organization, we constructed a feedforward spiking model using a biologically plausible neuron model. By means of surround inhibition our simple 3-layered model performs figure-ground segmentation and one-sided border-ownership coding. We propose that the visual system uses feed forward suppression for figure-ground segmentation and border-ownership assignment