A Decision Rule for Predicting Bacterial Meningitis in Children with Cerebrospinal Fluid Pleocytosis When Gram Stain Is Negative or Unavailable

Objectives:  Among children with cerebrospinal fluid (CSF) pleocytosis, the task of separating aseptic from bacterial meningitis is hampered when the CSF Gram stain result is unavailable, delayed, or negative. In this study, the authors derive and validate a clinical decision rule for use in this setting.
Methods:  This was a review of peripheral blood and CSF test results from 78 children (<19 years) presenting to Children's Hospital Columbus from 1998 to 2002. For those with a CSF leukocyte count of >7/μL, a rule was created for separating bacterial from viral meningitis that was based on routine laboratory tests, but excluded Gram stain. The rule was validated in 158 subjects seen at the same site (Columbus, 2002–2004) and in 871 subjects selected from a separate site (Boston, 1993–1999).
Results:  One point each (maximum, 6 points) was assigned for leukocytes >597/μL, neutrophils >74%, glucose <38 mg/dL, and protein >97 mg/dL in CSF and for leukocytes >17,000/mL and bands to neutrophils >11% in peripheral blood. Areas under receiver-operator-characteristic curves (AROCs) for the resultant score were 0.98 for the derivation set and 0.90 and 0.97, respectively, for validation sets from Columbus and Boston. Sensitivity and specificity pairs for the Boston data set were 100 and 44%, respectively, at a score of 0 and 97 and 81% at a score of 1. Likelihood ratios (LRs) increased from 0 at a score of 0 to 40 at a score of ≥4.
Conclusions:  Among children with CSF pleocytosis, a prediction score based on common tests of CSF and peripheral blood and intended for children with unavailable, negative, or delayed CSF Gram stain results has value for diagnosing bacterial meningitis.     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

Turnaround time and barriers to treatment of newly diagnosed cancer in Uganda: a mixed-methods longitudinal study

IntroductionCancer represents a growing public health concern. Late-stage at diagnosis, limited access to effective treatment, and loss to follow-up are responsible for dismal outcomes.ObjectiveTo describe care pathways, turnaround times, and identify barriers to timely initiation of cancer treatmentMethodsUsing a sequential mixed-methods design involving focus group discussions, we followed up 50 participants between January, and June 2018. We computed the median observed turnaround time to treatment (TTT) at each care step and reported delay as deviations from the proposed ideal turnaround times.ResultsThe ideal TTT with either chemotherapy, or radiotherapy, or surgery was 8, 14, and 21 days respectively. At a median follow-up time of 35.5 days (IQR 17–66), only 29 of the 50 study participants had completed all steps between registration and initiation of treatment, and the observed median TTT was 16 days (9 – 22 days) for chemotherapy, and 30 days (17 – 49 days) for radiotherapy, reflecting a significant delay (p-value = 0.017). Reported barriers were; shortage of specialists, patients required visits to outside facilities for staging investigations, prohibitive costs, poor navigation system and time wastage.ConclusionsWhen compared to the recommended ideal turnaround time, there was significant institutional delay in access to chemotherapy and radiotherapy attributed to multiple external and internal healthcare system barriers.     

Discovery of novel protein tyrosine phosphatase sigma inhibitors through the virtual screening with modified scoring function

Protein tyrosine phosphatase sigma (PTPσ) is a promising target for the development of therapeutics for the neurological diseases caused by the impaired recovery from neural injury. Based on the virtual screening with the scoring function involving a new accurate solvation energy term and in vitro enzyme assay, we identified seven competitive PTPσ inhibitors with the associated IC₅₀ values ranging from 5 to 11 μM. These inhibitors are structurally diverse and expected to have desirable physicochemical properties as a drug candidate. Therefore, they deserve consideration for further development by structure–activity relationship studies to optimize the inhibitory activities against the neurological diseases. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of PTPσ are discussed in detail.     

Situation analysis of TB microscopy centres in Ghana.

SETTING: Public health laboratories in Ghana performing tuberculosis (TB) microscopy. OBJECTIVE: To assess the situation of the laboratories in terms of staff strength, technical skills, documentation, biosafety practices, equipment, supplies and disposal systems. DESIGN: Methods used for data collection were interviews using a structured questionnaire, informal observation of laboratory registers, disposal systems and safety measures for sputum handling. RESULTS: Of 114 laboratories visited between 2000 and 2001, 102 (89.5%) were performing TB microscopy. Of the staff working in the laboratories, 9% were medical technologists, 24% laboratory technicians, 37% laboratory assistants and 30% orderlies. Average false-negative and -positive rates were respectively 13% and 14%. Although most of the centres (85.3%) were using the recommended TB laboratory register for recording, in most cases they were not filled in accurately or completely. The majority of the available microscopes had mechanical or optical faults. Availability of other materials for smear preparation and staining ranged from 44% to 82%. The main methods employed for disposal of laboratory waste were burning and burying, but conditions were poor in most of the facilities visited. CONCLUSION: Training of laboratory personnel in TB microscopy and establishment of a quality assurance system are needed in Ghana.