Modeling the impact of novel diagnostic tests on pediatric and extrapulmonary tuberculosis

BACKGROUND: Extrapulmonary tuberculosis (EPTB) and most pediatric TB cannot be diagnosed using sputum-based assays. The epidemiological impact of different strategies to diagnose EPTB and pediatric TB is unclear. METHODS: We developed a dynamic epidemic model of TB in a hypothetical population with epidemiological characteristics similar to India. We evaluated the impact of four alternative diagnostic test platforms on adult EPTB and pediatric TB mortality over 10 years: (1) Nucleic acid amplification test optimized for diagnosis of EPTB (“NAAT-EPTB”); (2) NAAT optimized for pediatric TB (“NAAT-Peds”); (3) more deployable NAAT for sputum-based diagnosis of adult pulmonary TB (“point-of-care (POC) sputum NAAT”); and (4) more deployable NAAT capable of diagnosing all forms of TB using non-invasive, non-sputum specimens (“POC non-sputum NAAT”). RESULTS: NAAT-EPTB lowered adult EPTB mortality by a projected 7.6% (95% uncertainty range [UR]: 6.5-8.8%). NAAT-Peds lowered pediatric TB mortality by 6.8% (UR: 4.9-8.4%). POC sputum NAAT, though only able to diagnose pulmonary TB, reduced projected pediatric TB deaths by 13.3% (UR: 4.6-15.7%) and adult EPTB deaths by 8.4% (UR 2.0-9.3%) simply by averting transmission of disease. POC non-sputum NAAT had the greatest effect, lowering pediatric TB mortality by 34.7% (UR: 26.8-38.7), and adult EPTB mortality by 38.5% (UR: 30.7-41.2). The relative impact of a POC sputum NAAT (i.e., enhanced deployability) versus NAAT-EPTB (i.e., enhanced ability to specifically diagnose TB-NSP) on adult EPTB mortality depends most strongly on factors that influence transmission, with settings of higher transmission (e.g., higher per-person transmission rate, lower diagnostic rate) favoring POC sputum NAAT. CONCLUSION: Although novel tests for pediatric TB and EPTB are likely to reduce TB mortality, major reductions in pediatric and EPTB incidence and mortality also require better diagnostic tests for adult pulmonary TB that reach a larger population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-477) contains supplementary material, which is available to authorized users

Attitudes of Emergency Department Staff towards the Role of Clinical Pharmacists in a Region of Saudi Arabia - A Pilot Study

Purpose: To evaluate the attitudes and perceptions of medical doctors and nurses in the Emergency Department ED towards the role of clinical pharmacists.Methods: A pilot study was conducted among the medical and paramedical staff of the ED of Public Hospital, Eastern Region, Saudi Arabia, Al-Ahsa, using a 24-item questionnaire on Doctor of Pharmacy (Pharm-D) program as well as clinical pharmacist and medical staff attitudes toward the availability and possible role of clinical pharmacist in EDs. The data analysed statistically.Results: Sixteen of the 20 respondents expressed a willingness to participate in the study. Six (37.5 %) of the respondents were doctors while the rest were nursing staff. Ten (62.5 %) of the ED staff were aware of the professional degree held by clinical pharmacists (i.e., Pharm-D), and a majority, 12 (75.0 %) had heard of a health care professional called a clinical pharmacist. While exploring medical staff attitude toward the availability of a full-time pharmacist in EDs, 13 (81.3 %) of the respondents viewed this favorably while that regarding the role of pharmacists in drug adherence and patient care was viewed less favorably. Fourteen (87.5%) disagreed with giving prescription rights to clinical pharmacists for minor ailments.Conclusion: These findings highlight the need to enhance the interaction between the medical and paramedical staff on the one hand, and the clinical pharmacist on the other. Clinical pharmacists need to be given an opportunity to prove their capabilities in direct patient care in order to facilitate the full participation of future Pharm-D graduates in direct patient care in the Saudi health care system

Contribution à l’évaluation de la contamination par les métaux lourds de trois espèces de poissons, des sédiments et des eaux du Lac Tchad

Les fleuves Logone et Chari qui se jettent dans le Lac Tchad, sont exposés à toute forme de pollution. Le but de ce travail est d’évaluer la  contamination par les métaux lourds des eaux, des sédiments et des poissons du Lac Tchad. Trois espèces de poissons: Tilapia nilotica, Lates niloticus et Arius latiscutatus ont été obtenues au Lac Tchad et  transportées sous glace au laboratoire. Le Cd, le Pb et le Cr ont été dosés dans la tête, le foie, la chair et les os de ces poissons, dans les sédiments et l’eau au spectrophotomètre d’absorption atomique. Le Cd et le Pb n’étaient pas détectés dans les eaux et les sédiments. En comparant nos résultats obtenus dans la chair des poissons, à la grille de qualité de Mersch, la pollution des eaux du Lac Tchad va d’une situation intermédiaire (Cd) à une pollution importante (Cr). Les sédiments étaient plus  contaminés que les eaux. Toutes ces valeurs sont au-delà des normes existantes. L’analyse des variances (ANOVA) inter espèces, au seuil de 95% entre les organes, montre qu’il y a une corrélation positive (r = 0,74) et très significative (p = 0,02) entre la chair et les os des différentes espèces.Mots clés : Lac Tchad, métaux lourds, poissons, bioaccumulation

Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from Apoptosis after serum withdrawal

Sciatic nerve (SN) transection-induced apoptosis of dorsal root ganglion neurons (DRGN) is one factor determining the efficacy of peripheral axonal regeneration and the return of sensation. Here, we tested the hypothesis that caspase-2(CASP2) orchestrates apoptosis of axotomised DRGN both in vivo and in vitro by disrupting the local neurotrophic supply to DRGN. We observed significantly elevated levels of cleaved CASP2 (C-CASP2), compared to cleaved caspase-3 (C-CASP3), within TUNEL+DRGN and DRG glia (satellite and Schwann cells) after SN transection. A serum withdrawal cell culture model, which induced 40% apoptotic death in DRGN and 60% in glia, was used to model DRGN loss after neurotrophic factor withdrawal. Elevated C-CASP2 and TUNEL were observed in both DRGN and DRG glia, with C-CASP2 localisation shifting from the cytosol to the nucleus, a required step for induction of direct CASP2-mediated apoptosis. Furthermore, siRNAmediated downregulation of CASP2 protected 50% of DRGN from apoptosis after serum withdrawal, while downregulation of CASP3 had no effect on DRGN or DRG glia survival. We conclude that CASP2 orchestrates the death of SN-axotomised DRGN directly and also indirectly through loss of DRG glia and their local neurotrophic factor support. Accordingly, inhibiting CASP2 expression is a potential therapy for improving both the SN regeneration response and peripheral sensory recovery

Comparing pregnancy outcomes in patients with criteria and non-criteria autoimmune disease: A systematic review

Background: Not all patients fulfil criteria for specific autoimmune rheumatic diseases (ARDs) and are then defined as having non-criteria (nc)ARD. It is uncertain whether well-recognised associations with adverse pregnancy outcomes in patients with criteria ARD also exist in patients with ncARD or undifferentiated connective tissue disease (UCTD). Therefore, we undertook a systematic review of the prevalence of adverse pregnancy outcomes in various ncARD and UCTD compared with criteria ARD to identify whether there are increased risks and to examine for any benefits of treatment. // Methods: This study was conducted in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using online databases including Medline and PubMed from inception to the beginning of April 2021 using appropriate keywords for various ARD and pregnancy outcomes. // Results: After screening 665 articles, 36 articles were chosen for full text review and 15 selected for final analysis. There were eight studies of nc antiphospholipid syndrome (APS) of more than 7000 pregnancies and seven studies of UCTD of more than 1000 pregnancies. No studies of any other ncARD in pregnancy were identified. We found that patients with either ncAPS or UCTD seem to have an increased burden of poor pregnancy outcomes compared with the general population. Despite the heterogeneity and poor quality of the studies, we also noted that ncAPS and criteria APS patients may have similar rates of obstetric complications with standard and/or non-standard APS treatment regimens. // Conclusion: Our findings of increased risks of poor pregnancy outcomes in patients with ncAPS or UCTD will be helpful for pre-pregnancy counselling and management of these patients in pregnancy and support their referral to specialist obstetric-rheumatology and obstetric-haematology clinics

Dosimetric Evaluation of a New Rotating Gamma System for Stereotactic Radiosurgery

Purpose: A novel rotating gamma stereotactic radiosurgery (SRS) system (Galaxy RTi) with real-time image guidance technology has been developed for high-precision SRS and frameless fractionated stereotactic radiotherapy (SRT). This work investigated the dosimetric quality of Galaxy by comparing both the machine treatment parameters and plan dosimetry parameters with those of the widely used Leksell Gamma Knife (LGK) systems for SRS. Methods: The Galaxy RTi system uses 30 cobalt-60 sources on a rotating gantry to deliver non-coplanar, non-overlapping arcs simultaneously while the LGK 4C uses 201 static cobalt-60 sources to deliver noncoplanar beams. Ten brain cancer patients were unarchived from our clinical database, which were previously treated on the LGK 4C. The lesion volume for these cases varied from 0.1 cm3 to 15.4 cm3. Galaxy plans were generated using the Prowess TPS (Prowess, Concord, CA) with the same dose constraints and optimization parameters. Treatment quality metrics such as target coverage (%volume receiving the prescription dose), conformity index (CI), cone size, shots number, beam-on time were compared together with DVH curves and dose distributions. Results: Superior treatment plans were generated for the Galaxy system that met our clinical acceptance criteria. For the 10 patients investigated, the mean CI and dose coverage for Galaxy was 1.77 and 99.24 compared to 1.94 and 99.19 for LGK, respectively. The beam-on time for Galaxy was 17.42 minutes compared to 21.34 minutes for LGK (both assuming dose rates at the initial installation). The dose fall-off is much faster for Galaxy, compared with LGK. Conclusion: The Galaxy RTi system can provide dose distributions with similar quality to that of LGK with less beam-on time and faster dose fall-off. The system is also capable of real-time image guidance at treatment position to ensure accurate dose delivery for SRS.Comment: 14 pages, 7 figure

Enzymatic and biochemical characterization of Bungarus sindanus snake venom acetylcholinesterase

This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high level of acetylcholinesterase (AChE) activity. The enzyme showed optimum activity at alkaline pH (8.5) and 45ºC. Krait venom AChE was inhibited by substrate. Inhibition was significantly reduced by using a high ionic strength buffer; low ionic strength buffer (10 mM PO4 pH 7.5) inhibited the enzyme by 1. 5mM AcSCh, while high ionic strength buffer (62 mM PO4 pH 7.5) inhibited it by 1 mM AcSCh. Venom acetylcholinesterase was also found to be thermally stable at 45ºC; it only lost 5% of its activity after incubation at 45ºC for 40 minutes. The Michaelis-Menten constant (Km) for acetylthiocholine iodide hydrolysis was found to be 0.068 mM. Krait venom acetylcholinesterase was also inhibited by ZnCl2, CdCl2, and HgCl2 in a concentrationdependent manner. Due to the elevated levels of AChE with high catalytic activity and because it is more stable than any other sources, Bungarus sindanus venom is highly valuable for biochemical studies of this enzyme

Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells

Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction

Primary cutaneous melanoma of the breast: A case report

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Primary cutaneous melanoma of the breast is a very rare tumour, accounting for < 5 % of all malignant melanomas. Case presentation: A young lady was seen in the breast clinic for a skin lesion in the right breast. Clinical examination and investigations confirmed a diagnosis of a primary cutaneous melanoma of the breast. The lesion was excised and the patient made good recovery. She has shown no signs of local recurrence and is under regular follow-up in the dermatology clinic. Conclusion: This case is educational as it shows that the treatment of breast cutaneous melanoma is similar to that for any skin parts with surgery remaining the main therapeutic option. It also shows that mastectomy is unnecessary as it does not improve the results obtained by wide local excision of melanoma. Background Primary cutaneous melanoma rarely affects the breast, accounting for less than 5 % of all malignant melanomas