Spectrum of Skin Lesions of Post-Kala-Azar Dermal Leishmaniasis in Kala-azar Endemic Areas of Bangladesh

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL) and serves as a potential reservoir for Leishmania parasite. The study was aimed to evaluate the spectrum of skin lesions of PKDL in kala-azar endemic areas in Bangladesh. This cross sectional study was carried out to observe the characteristics of skin lesions among 250 PKDL cases. The suspected PKDL patients in highly endemic villages of Fulbaria Upazilla of Mymensingh district.were subjected to a dipstick test (rK39) for kala azar. The median time interval between diagnosing kala-azar and PKDL was 23 month (m-21, r- 0-60 months). The most common skin lesions were multiple symmetrical hypopigmented macules with irregular margins in 179(71.6%) cases followed by erythematous facial induration in 74(29.6%), papular in 33(13.2%), nodular in 28(11.2%) cases, combination of macules, papules, nodules and plaques in 88(35.2%) cases, annular in 7(2.8%) cases and Papillomatous mucosal growth in 2(0.8%) cases. Sites of involvement were mostly in face (92.4%), Trunk (84.8%), extremities (33.2%), oral mucosa and tongue (0.8%) and Genitalia (1.2%). Suspicion of PKDL on the basis of skin lesions will lead to early diagnosis and prompt treatment will impart an important role in prevention and eradication of Leishmaniasis in Bangladesh.     

Design and Validation of Additively Manufactured Metallic Cellular Scaffold Structures for Bone Tissue Engineering

Bone-related defects that cannot heal without significant surgical intervention represent a significant challenge in the orthopedic field. The use of implants for these critical-sized bone defects is being explored to address the limitations of autograft and allograft options. Three-dimensional cellular structures, or bone scaffolds, provide mechanical support and promote bone tissue formation by acting as a template for bone growth. Stress shielding in bones is the reduction in bone density caused by the difference in stiffness between the scaffold and the surrounding bone tissue. This study aimed to reduce the stress shielding and introduce a cellular metal structure to replace defected bone by designing and producing a numerically optimized bone scaffold with an elastic modulus of 15 GPa, which matches the human’s cortical bone modulus. Cubic cell and diagonal cell designs were explored. Strut and cell dimensions were numerically optimized to achieve the desired structural modulus. The resulting scaffold designs were produced from stainless steel using laser powder bed fusion (LPBF). Finite element analysis (FEA) models were validated through compression testing of the printed scaffold designs. The structural configuration of the scaffolds was characterized with scanning electron microscopy (SEM). Cellular struts were found to have minimal internal porosity and rough surfaces. Strut dimensions of the printed scaffolds were found to have variations with the optimized computer-aided design (CAD) models. The experimental results, as expected, were slightly less than FEA results due to structural relative density variations in the scaffolds. Failure of the structures was stretch-dominated for the cubic scaffold and bending-dominated for the diagonal scaffold. The torsional and bending stiffnesses were numerically evaluated and showed higher bending and torsional moduli for the diagonal scaffold. The study successfully contributed to minimizing stress shielding in bone tissue engineering. The study also produced an innovative metal cellular structure that can replace large bone segments anywhere in the human body.     

Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival

Introduction: The presence of positive nodal disease (LND) and the number of lymph nodes involved (LNB) are known to be significant prognostic markers for resected adenocarcinoma of the pancreas. In addition, the ratio of the number of involved nodes to the number of nodes resected known as the lymph node ratio (LNR) is emerging as an important prognostic marker. The role of the resection margin (RM) as presently defined (R1 ≤ 1 mm) is unclear as results differ based on the dataset. The aim of this study was to assess the impact of nodal disease and a redefined RM on outcome.Material and methods: Retrospective analysis of pancreatic head resections for adenocarcinomas from 2003–2009. The RM was re-analysed based on tumour clearance and categorized into: histopathological evidence of a tumour; ≤0.5 mm, ≤1 mm, ≤1.5 mm, or ≤2.0 mm of the actual surgical resection margin. The impact of histopathological variables on cancer-specific survival (CSS) and disease-free survival (DFS) was analysed.Results: LND, LNB and LNR were independent prognostic markers for CSS (P = 0.048, 0.003, 0.016) but, did not influence DFS. A LNR < 0.143 was associated with a higher CSS [38.16 ± 4.69 versus 20.59 ± 2.20 months, P = 0.0042, hazard ratio (HR) 3.74 (95% confidence interval (CI) 1.52–9.23)]. An R1 RM was not associated with CSS or DFS on multivariate analysis, irrespective of the distance. LNB and LNR maintained independent significance irrespective of the size of the RM.Conclusion: LNB and LNR are the only prognostic factors for CSS in patients with pancreatic head adenocarcinoma, but do not predict recurrence. Microscopic RMs does not seem to influence the outcome even when redefined. Further prospective studies are indicated to substantiate these findings.     

Chemometric Evaluation of Near Infrared,Fourier Transform Infrared,and Raman Spectroscopic Models for the Prediction of Nimodipine Polymorphs

The objective of this study was to assess the performance of the chemometric model to predict the proportion of the recrystallized polymorphs of nimodipine from the cosolvent formulations. Ranging from 100% to 0% (w/w) of polymorph I, the two polymorphs mixtures were prepared and characterized spectroscopically using Fourier transformed infrared spectroscopy (FTIR), near-infrared spectroscopy (NIR), and Raman spectroscopy. Instrumental responses were treated to construct multivariate calibration model using principal component regression (PCR) and partial least square regression approaches. Treated data showed better model fitting than without treatment, which demonstrated higher correlation coefficient (R²) and lower root mean square of standard error (RMSE) and standard error (SE). Multiple scattering correction and standard normal variate exhibited higher R² and lower RMSE and SE values than second derivative. Goodness of fit for FTIR and NIR (R² ~ 0.99) data was better than Raman (R² ~ 0.95). Furthermore, the models were applied on the recrystallized polymorphs obtained by storing nimodipine-cosolvent formulations at selected stability conditions. The relative composition of the polymorphs differed with storage conditions. NIR-chemical imaging on recrystallized sample of nimodipine at 15°C qualitatively corroborated the model-based prediction of the two polymorphs. Therefore, these studies strongly suggest the importance of the potential utility of the chemometric model in predicting nimodipine polymorphs.     

Evidence for a role for Galphai1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Galphai1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder

We have examined platelet functional responses and characterized a novel signaling defect in the platelets of a patient suffering from a chronic bleeding disorder. Platelet aggregation responses stimulated by weak agonists such as adenosine diphosphate (ADP) and adrenaline were severely impaired. In comparison, both aggregation and dense granule secretion were normal following activation with high doses of collagen, thrombin, or phorbol-12 myristate-13 acetate (PMA). ADP, thrombin, or thromboxane A2 (TxA2) signaling through their respective Gq-coupled receptors was normal as assessed by measuring either mobilization of intracellular calcium, diacylglycerol (DAG) generation, or pleckstrin phosphorylation. In comparison, Gi-mediated signaling induced by either thrombin, ADP, or adrenaline, examined by suppression of forskolin-stimulated rise in cyclic AMP (cAMP) was impaired, indicating dysfunctional Galphai signaling. Immunoblot analysis of platelet membranes with specific antiserum against different Galpha subunits indicated normal levels of Galphai2,Galphai3,Galphaz, and Galphaq in patient platelets. However, the Galphai1level was reduced to 25% of that found in normal platelets. Analysis of platelet cDNA and gDNA revealed no abnormality in either the Galphai1 or Galphai2 gene sequences. Our studies implicate the minor expressed Galphai subtype Galphai1 as having an important role in regulating signaling pathways associated with the activation of alphaIIbbeta3 and subsequent platelet aggregation by weak agonists.     

Prophylactic Peritoneal Dialysis After the Arterial Switch Operation: A Retrospective Cohort Study

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