Novel quinoxaline compound against extended-spectrum beta-lactamases producing bacteria.

OBJECTIVE: Extended-spectrum beta-lactamases (ESBLs) targeting beta-lactam antibiotics pose a major healthcare challenge. Carbapenems are known to be less impacted. However, the emergence of carbapenem-resistant strains can add further complexity to this existing challenge. With slow drug discovery and rapid resistance, repurposing existing drugs is crucial. This research study aims to provide insight into the antimicrobial effectiveness of 3-hydrazinoquinoxaline-2-thiol against diverse clinical ESBL-producing isolates. MATERIALS AND METHODS: The broth microdilution assay was conducted on a total of sixty-nine clinical ESBL-producing isolates to assess the minimum inhibitory concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol. The assay was conducted in triplicate, and the average MIC values were calculated. RESULTS: The most repeatedly observed MIC was 64 µg/ml (37.7%), followed by 256 µg/ml (23.2%) and 128 µg/ml (17.4%). Other MICs: 32 µg/ml (11.6%), 16 µg/ml (7.2%), 4-8 µg/ml (1.4%). CONCLUSIONS: This study demonstrated an effect of 3-hydrazinoquinoxaline-2-thiol on various ESBL-producing strains in vitro, indicating its promising therapeutic potential. To comprehensively understand the drug, rigorous testing, including pharmacokinetics, resistance assays, safety assessments, and exploration of potential synergies with other antibiotics against ESBL-producing organisms, is crucial.

Heparin-Induced Thrombocytopenia in Infants after Heart Surgery.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) in infants is a rare disorder, and the diagnosis and management of HIT still remains challenging. Argatroban is a synthetic direct thrombin inhibitor (DTI) that is widely used for treating HIT. However, little is known about the efficacy of the activated clotting time (ACT) test in monitoring DTI treatment as an alternative to the routinely used activated partial thromboplastin time (aPTT). METHODS: Between July 2013 and January 2015, four infants were diagnosed with HIT after surgical correction of congenital anomalies. In all cases, heparin was used during cardiopulmonary bypass (CPB). Diagnosis of HIT was based on the "4 Ts" pretest clinical scoring system, and platelet factor 4 (PF4) antibody was detected using enzyme-linked immunosorbent assay. Argatroban was used in treating HIT. When argatroban was infused, anticoagulation tests (aPTT, prothrombin time [PT], thrombin time [TT], and fibrinogen) were performed every 4 to 12 hours. ACT was used in addition to monitor the anticoagulation effect of argatroban. The target ACT was 1.5 to 3.0 times the baseline. ACT was measured every 2 to 4 hours and remeasured 1 hour after each dosage adjustment. RESULTS: Thrombocytopenia (defined as a 50% decrease in platelet count) occurred during the 3rd to 6th day postoperatively. After the diagnosis of HIT, argatroban was started immediately, and platelet counts stabilized and gradually increased. Anticoagulation effect of argatroban was successful monitored by ACT and aPTT. Poor correlation between the ACT test and aPTT test (R = 0.270, p = 0.092) was noted in one patient. ACT values increased rapidly after 3 to 7 days on argatroban treatment. In most cases, low dosage of argatroban was given ranging from 0.04 to 5.00 µg/kg/min. CONCLUSION: Argatroban may be an effective medicine in treating HIT in infants, in a reduced dosage. The great fluctuation in argatroban dosage during the course of HIT treatment necessitates close monitoring. ACT test may be reliable and convenient for monitoring HIT treatment and may contribute to positive clinical outcomes in infants. The efficacy of argatroban and the use of ACT monitoring in the management of HIT infants needs further study.

How do low-birthweight neonates fare 2 years after discharge from a low-technology neonatal care unit in a rural district hospital in Burundi?

OBJECTIVES: As neonatal care is being scaled up in economically poor settings, there is a need to know more on post-hospital discharge and longer-term outcomes. Of particular interest are mortality, prevalence of developmental impairments and malnutrition, all known to be worse in low-birthweight neonates (LBW, <2500 g). Getting a better handle on these parameters might justify and guide support interventions. Two years after hospital discharge, we thus assessed: mortality, developmental impairments and nutritional status of LBW children. METHODS: Household survey of LBW neonates discharged from a neonatal special care unit in Rural Burundi between January and December 2012. RESULTS: Of 146 LBW neonates, 23% could not be traced and 4% had died. Of the remaining 107 children (median age = 27 months), at least one developmental impairment was found in 27%, with 8% having at least five impairments. Main impairments included delays in motor development (17%) and in learning and speech (12%). Compared to LBW children (n = 100), very-low-birthweight (VLBW, <1500 g, n = 7) children had a significantly higher risk of impairments (intellectual - P = 0.001), needing constant supervision and creating a household burden (P = 0.009). Of all children (n-107), 18% were acutely malnourished, with a 3½ times higher risk in VLBWs (P = 0.02). CONCLUSIONS: Reassuringly, most children were thriving 2 years after discharge. However, malnutrition was prevalent and one in three manifested developmental impairments (particularly VLBWs) echoing the need for support programmes. A considerable proportion of children could not be traced, and this emphasises the need for follow-up systems post-discharge.

Caesarean sections in rural Burundi: how well are mothers doing two years on?

SETTING: A caesarean section (C-section) is a life-saving emergency intervention. Avoiding pregnancies for at least 24 months after a C-section is important to prevent uterine rupture and maternal death. OBJECTIVES: Two years following an emergency C-section, in rural Burundi, we assessed complications and maternal death during the post-natal period, uptake and compliance with family planning, subsequent pregnancies and their maternal and neonatal outcomes. METHODS: A household survey among women who underwent C-sections. RESULTS: Of 156 women who underwent a C-section, 116 (74%) were traced; 1 had died of cholera, 8 had migrated and 31 were untraceable. Of the 116 traced, there were no post-operative complications and no deaths. At hospital discharge, 83 (72%) women accepted family planning. At 24 months after hospital discharge (n = 116), 23 (20%) had delivered and 17 (15%) were pregnant. Of the remaining 76 women, 48 (63%) were not on family planning. The main reasons for this were religion or husband's non-agreement. Of the 23 women who delivered, there was one uterine rupture, no maternal deaths and three stillbirths. CONCLUSIONS: Despite encouraging maternal outcomes, this study raises concerns around the effectiveness of current approaches to promote and sustain family planning for a minimum of 24 months following a C-section. Innovative ways of promoting family planning in this vulnerable group are urgently needed.

Contexte : Une césarienne est une intervention d'urgence destinée à sauver une vie. Eviter une nouvelle grossesse pendant au moins 24 mois après une césarienne est important afin de prévenir une rupture utérine et un décès maternel.Objectifs : Deux ans après une césarienne en urgence, dans le Burundi rural, nous avons évalué : les complications et les décès maternels pendant la période post-natale ; la couverture de la planification familiale et son adhérence ; les grossesses suivantes et leur devenir pour la mère et le nouveau-né.Méthodes : Enquête à domicile auprès de femmes qui ont bénéficié d'une césarienne.Résultat : Sur 156 femmes qui ont bénéficié d'une césarienne, 116 (74%) ont pu être retrouvées ; 1 était décédée du choléra, 8 avaient déménagé et 31 n'ont pas pu être localisées. Sur les 116 femmes retrouvées, il n'y a eu aucune complication post-opératoire et aucun décès. Lors de leur sortie de l'hôpital, 83 (72%) femmes ont accepté une contraception. A 24 mois après leur sortie (n = 116), 23 (20%) avaient accouché et 17 (15%) étaient enceintes. Sur les 76 femmes restantes, 48 (63%) n'avaient pas de contraception. Les motifs principaux étaient la religion ou le désaccord du mari. Parmi les 23 qui avaient accouché, il y a eu une rupture utérine, aucun décès maternel, mais il y a eu trois mort-nés.Conclusion : En dépit de résultats encourageants pour les mères, cette étude pose la question de l'efficacité des approches actuelles de la promotion et de la pérennité de la planification familiale pendant un minimum de 24 mois. Il est urgent de trouver des manières innovantes de promouvoir la planification familiale dans ce groupe vulnérable.

Marco de referencia: La cesárea es una intervención de urgencia que salva vidas. Es importante evitar un embarazo por lo menos durante los 24 meses que siguen a la operación, con el fin de evitar la ruptura uterina y la mortalidad materna.Objetivos: El seguimiento durante 2 años después de una cesárea de urgencia en una zona rural de Burundi tuvo por objeto evaluar las complicaciones y la mortalidad materna durante el período posnatal, la aceptación y el cumplimiento del método de anticoncepción y examinar los siguientes embarazos con su desenlace materno y neonatal.Método: Se llevó a cabo una encuesta domiciliaria de las mujeres en quienes se había practicado una cesárea.Resultados: Se evaluaron 116 de las 156 mujeres (74%) que se sometieron a una cesárea; una paciente falleció por cólera, 8 migraron y fue imposible localizar 31 mujeres. Durante el seguimiento de las 116 mujeres no se observaron complicaciones postoperatorias ni defunciones. En el momento del alta hospitalaria, 83 mujeres aceptaron practicar un método anticonceptivo (72%). Veinticuatro meses después del alta hospitalaria, 23 mujeres habían tenido un parto (20%) y 17 estaban embarazadas (15%). De las 76 mujeres restantes, 48 no seguían ningún método de planificación familiar (63%); las principales razones aducidas fueron religiosas o el desacuerdo del cónyuge. En los 23 casos de mujeres que tuvieron un parto, ocurrió una ruptura uterina sin mortalidad materna, pero hubo tres mortinatos.Conclusión: Pese a la buena perspectiva de los desenlaces maternos favorables, el estudio pone de manifiesto inquietudes con respecto a la eficacia de las estrategias vigentes de promoción y mantenimiento de los métodos anticonceptivos durante un mínimo de 24 meses. Se precisan con urgencia estrategias innovadoras que estimulen la planificación familiar en este grupo vulnerable de mujeres.

Crystal structure of a molybdopterin synthase-precursor Z complex: insight into its sulfur transfer mechanism and its role in molybdenum cofactor deficiency.

In almost all biological life forms, molybdenum and tungsten are coordinated by molybdopterin (MPT), a tricyclic pyranopterin containing a cis-dithiolene group. Together, the metal and the pterin moiety form the redox reactive molybdenum cofactor (Moco). Mutations in patients with deficiencies in Moco biosynthesis usually occur in the enzymes catalyzing the first and second steps of biosynthesis, leading to the formation of precursor Z and MPT, respectively. The second step is catalyzed by the heterotetrameric MPT synthase protein consisting of two large (MoaE) and two small (MoaD) subunits with the MoaD subunits located at opposite ends of a central MoaE dimer. Previous studies have determined that the conversion of the sulfur- and metal-free precursor Z to MPT by MPT synthase involves the transfer of sulfur atoms from a C-terminal MoaD thiocarboxylate to the C-1' and C-2' positions of precursor Z. Here, we present the crystal structures of non-thiocarboxylated MPT synthase from Staphylococcus aureus in its apo form and in complex with precursor Z. A comparison of the two structures reveals conformational changes in a loop that participates in interactions with precursor Z. In the complex, precursor Z is bound by strictly conserved residues in a pocket at the MoaE dimer interface in close proximity of the C-terminal glycine of MoaD. Biochemical evidence indicates that the first dithiolene sulfur is added at the C-2' position.

Comparison as a lymphoscintigraphic agent between 99Tcm dextran and 99Tcm antimony sulphide colloid.

To determine its suitability as a lymph node imaging agent, 99Tcm dextran (99TcmDx) was compared with 99Tcm antimony sulphide colloid (99TcmSb2S3) in rabbits and dogs. In two groups of five rabbits each, absorption from the interstitial injection site, popliteal lymph node sequestration and total body uptake and distribution of both agents were determined. In three dogs, both agents were studied simultaneously, 99TcmDx and 99TcmSb2S3 being injected into the left and right hind feet respectively; therefore, only popliteal lymph node sequestration and image qualities were evaluated. Uptake curves in the rabbits indicated that total body uptake of 99TcmDx is faster and greater than that of 99TcmSb2S3. In spite of rapid lymph node uptake rates, total popliteal lymph node sequestration of 99TcmDx is significantly lower than that observed for 99TcmSb2S3. While lymph node uptake of 99TcmDx in dogs is higher than in rabbits, disparity between the two agents persists and is demonstrable in the image in both species. Reduced lymph node sequestration of 99TcmDx may result from its non-colloidal nature as well as its instability, both of which render this agent unsuitable for imaging pathological features of lymph nodes although its rapid absorption and distribution may be ideal characteristics for the study of lymphatic kinetics.

A field trial of suppression of Aedes aegypti population by releasing sterile males into a domestic population.

After release of an average of 1260 sterile male each day for a period of sixty two days, the average fertility of Aedas aegypti population remained above 50% in Ererwani village. It is concluded that the irradiated sterile males may not be suitable as a control measure, despite the fact that irradiation was carried out in nitrogen atmosphere.