Background and objectives A kidney disease of unknown cause is common in Sri Lanka's lowland (dry) region. Detailed clinical characterizations of patients with biopsy-proven disease are limited, and there is no current consensus on criteria for a noninvasive diagnosis. Design, setting, participants, & measurements We designed a prospective study in a major Sri Lankan hospital servicing endemic areas to ascertain pathologic and clinical characteristics of and assess risk factors for primary tubulointerstitial kidney disease. We used logistic regression to determine whether common clinical characteristics could be used to predict the presence of primary tubulointerstitial kidney disease on kidney biopsy. Results From 600 new patients presenting to a tertiary nephrology clinic over the course of 1 year, 87 underwent kidney biopsy, and 43 (49%) had a biopsy diagnosis of primary tubulointerstitial kidney disease. On detailed biopsy review, 13 (30%) had evidence of moderate to severe active kidney disease, and six (15%) had evidence of moderate to severe chronic tubulointerstitial kidney disease. Patients with tubulointerstitial kidney disease were exclusively born in endemic provinces; 91% spent a majority of their lifespan there. They were more likely men and farmers (risk ratio, 2.0; 95% confidence interval, 1.2 to 2.9), and they were more likely to have used tobacco (risk ratio, 1.7; 95% confidence interval, 1.0 to 2.3) and well water (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). Three clinical characteristics-age, urine dipstick for protein, and serum albumin-could predict likelihood of tubulointerstitial kidney disease on biopsy (model sensitivity of 79% and specificity of 84%). Patients referred for kidney biopsy despite comorbid diabetes or hypertension did not experience lower odds of tubulointerstitial kidney disease. Conclusions A primary tubulointerstitial kidney disease occurs commonly in specific regions of Sri Lanka with characteristic environmental and lifestyle exposures.

Crown shapes in mammalian teeth vary considerably from species to species, and morphological characters in crown shape have been used to identify species. Cusp pattern is one of the characters in crown shape. In the processes governing the formation of cusp pattern, the Shh pathway has been implicated as an important player. Suppression of Shh signaling activity in vitro in explant assays appears to induce supernumerary cusp formation in wild-type tooth germs. However, the in vivo role of Shh signaling in cusp pattern formation and the molecular mechanisms by which Shh regulates cusp patterning are not clear. Here, through in vivo phenotypic analyses of mice in which Shh activity was suppressed and compared with wild-type mice, we characterized differences in the location, number, incidence, and shape of supernumerary cusps in molars at embryonic day 15.5. We found that the distances between cusps were reduced in molars of Shh activity–suppressed mice in vivo. These findings confirm and extend the previous idea that Shh acts as an inhibitor in the reaction-diffusion model for cusp pattern formation by negatively regulating the intercuspal distance. We uncovered a significant reduction of expression level of Sostdc1, which encodes a secreted modulator of Wnt signaling, after suppression of Shh activity. The supernumerary cusp formation in Sostdc1−/− mice and compound Sostdc1 and Lrp mutant mice indicates a strong association between Wnt and Shh signaling pathways in cusp patterning. In further support of this idea, there is a high degree of similarity in the supernumerary cusp patterns of mice lacking Sostdc1 or Shh at embryonic day 15.5. These results suggest that Shh plays an inhibitory role in cusp pattern formation by modulating Wnt signaling through the positive regulation of Sostdc1.

BackgroundMaternal vaginal colonization with antibiotic resistant organisms is a growing concern in countries with high antibiotic resistance rates.MethodsA low vaginal swab was collected from mothers on admission, on discharge and a peri-rectal swab was collected from the neonates born to these mothers on discharge. Routine microbiological methods were used to identify the colonization rates for Escherichia coli, Klebsiella spp. and Streptococcus agalactiae.ResultsThe pre-delivery colonization rate among the 250 participants for total Enterobacteriaceae was 18.8%. The colonization rates for Klebsiella spp., E. coli and S. agalactiae were, 12.4, 5.6 and 14.8% respectively. Two Klebsiella spp. and two E. coli isolates were confirmed to be exentend spectrum β lactamase (ESBL) producers with the commonest resistant determinant being blaCTX-M. Post-delivery swabs were collected from 130 participants and the colonization rates were 41.5% for Enterobacteriaceae, 25.4% for Klebsiella spp., 10.8% for E. coli, and 10.8% for S. agalacteiae. Three Klebsiella isolates and one E. coli isolate were confirmed to be ESBL producers with the commonest resistant determinant being blaCTX-M. Considering the 130 participants with both samples, there was a significant increase in the colonization with any Enterobacteriaceae and Klebsiella spp. (p < 0.05). Peri-rectal swabs were collected from neonates in 159 instances. The isolation rates for Enterobacteriaceae was 34%. The genus specific isolation rate for Klebsiella was 21.4% while the rates for E. coli and S.agalactiae were 10.1 and 5.7% respectively. Two of the E. coli were confirmed to be ESBL producers while none of the klebsiellae were identified to be so. Considering these 159 instances where both the mother and baby were sampled, random amplification of polymorphic DNA (RAPD) analysis revealed that Enterbacteriaceae with same strain type was present in 6.9% of the instances, indicating possible transfer between the mother and neonate. The transfer rate for ESBL producers were 0.6%.ConclusionsThe lower level of antimicrobial resistance among these potentially community acquired isolates is encouraging. However, in view of the increasing level of resistance reported elsewhere in the region, regular monitoring is warranted.

BackgroundInfections with multi drug resistant (MDR) organisms are a major problem in intensive care units (ICUs). Proper infection control procedures are mandatory to combat the spread of resistant organisms within ICUs. Well stablished surveillance programmes will enhance the adherence of the staff to infection control protocols. The study was conducted to assess the feasibility of using basic molecular typing methods and routine hospital data for laboratory surveillance of resistance organisms in resource limited settings.MethodsA retrospective study was conducted using consecutive Gram negative isolates obtained from an ICU over a six month period. Antibiotic sensitivity patterns and random amplified polymorphic DNA (RAPD) based typing was performed on the given isolates.ResultsOf the seventy isolates included in the study, seven were E.coli. All E.coli were MDRs and Extended Spectrum β lactamse (ESBL) producers carrying bla CTX-M. Fourteen isolates were K.pneumoniae, and all were MDRs and ESBL producers. All K.pneumoniae harboured bla SHV while 13 harboured bla CTX-M. The MDR rate among P.aeruginosa was 13% (n=15) while all acinetobacters (n=30) were MDRs. Predominant clusters were identified within all four types of Gram negatives using RAPD and the ICU stay of patients overlapped temporally.ConclusionWe propose that simple surveillance methods like RAPD based typing and basic hospital data can be used to convince hospital staff to adhere to infection control protocols more effectively, in low and middle income countries.

No abstract

Background: The skull is a complex structure formed by the craniofacial bones’ elaborate organization. The growth pattern in each craniofacial bone of the postnatal skull has been presented in wild-type mice. However, the skull’s growth pattern, determined by the craniofacial bones’ coordinated growth, is unfamiliar. This study aimed to examine the overall morphological change in the mid-sagittal plane of the postnatal mice’s skulls and interaction between the craniofacial bones.Methods: Geometric morphometric principal component analysis was performed in the mid-sagittal plane of 31 wild-type mice’s skulls from postnatal days 28 to 98. The relationship between the cranial base and cranial vault was investigated by comparing skulls with early fusion and non-fusion of intersphenoid synchondrosis (ISS).Results: The cranial vault flattening and sphenoid bone length increased with age. The cranial vault curvature and sphenoid base length showed a positive correlation that was confirmed by comparing the skulls with early fusion and non-fusion of ISS. The sphenoid bone length and cranial vault angle significantly decreased in the skulls with early fusion of ISS compared to non-fusion skulls.Conclusions: It is suggested that the cranial vault flattening is sphenoid bone length-induced but cranial vault length-independent during postnatal mice skull development.