ISPAD ANNUAL CONFERENCE HIGHLIGHTS 2023.

The 49th Annual Conference of the International Society of Pediatric and Adolescent Diabetes (ISPAD), held from October 18 to 21, 2023, in Rotterdam, Netherlands, showcased significant advancements and diversity in paediatric and adolescent diabetes research and clinical innovations. The conference, renowned for its global impact, brought together experts to discuss cutting-edge developments in the field. Highlights from the plenary sessions included ground-breaking research on immunotherapies and diabetes technologies and offering new insights into personalised treatment approaches. Keynote speakers emphasised the importance of early diagnosis, prevention and the potential of novel biomarkers in predicting disease progression. The symposia covered a broad spectrum of topics, from advancements in continuous glucose monitoring technologies to the latest in hybrid closed loop systems which promise to revolutionise diabetes management for young patients.

Bowel Endometriosis Management by Colorectal Resection: Laparoscopic Surgical Technique & Outcome.

Background and Objectives: Bowel deep infiltrating endometriosis (DIE) management by colorectal resection is a complex procedure. The purpose of the present study is to delineate a meticulous approach to the assessment of the patient, step-wise surgical technique, pre, and postoperative care, and its short-term and long-term outcomes. Methods: This is a single-center retrospective study done on patients of bowel DIE managed by colorectal resection between January 1, 2019 to June 30, 2021. Results: There was a significant improvement in the symptomatology of patients post-surgery. Our surgical technique is feasible with acceptable short-term and long-term outcomes. Conclusion: Bowel DIE management can be proficiently executed with a proper diagnostic approach, appropriate surgical expertise with exhaustive pelvic anatomy knowledge especially concerning autonomic nerve plexus.

Fine-scale population genetic structure of the Bengal tiger (Panthera tigris tigris) in a human-dominated western Terai Arc Landscape, India.

Despite massive global conservation strategies, tiger populations continued to decline until recently, mainly due to habitat loss, human-animal conflicts, and poaching. These factors are known to affect the genetic characteristics of tiger populations and decrease local effective population sizes. The Terai Arc Landscape (TAL) at the foothills of the Himalaya is one of the 42 source sites of tigers around the globe. Therefore, information on how landscape features and anthropogenic factors affect the fine-scale spatial genetic structure and variation of tigers in TAL is needed to develop proper management strategies for achieving long-term conservation goals. We document, for the first time, the genetic characteristics of this tiger population by genotyping 71 tiger samples using 13 microsatellite markers from the western region of TAL (WTAL) of 1800 km2. Specifically, we aimed to estimate the genetic variability, population structure, and gene flow. The microsatellite markers indicated that the levels of allelic diversity (MNA = 6.6) and genetic variation (Ho = 0.50, HE = 0.64) were slightly lower than those reported previously in other Bengal tiger populations. We observed moderate gene flow and significant genetic differentiation (FST= 0.060) and identified the presence of cryptic genetic structure using Bayesian and non-Bayesian approaches. There was low and significantly asymmetric migration between the two main subpopulations of the Rajaji Tiger Reserve and the Corbett Tiger Reserve in WTAL. Sibship relationships indicated that the functionality of the corridor between these subpopulations may be retained if the quality of the habitat does not deteriorate. However, we found that gene flow is not adequate in view of changing land use matrices. We discuss the need to maintain connectivity by implementing the measures that have been suggested previously to minimize the level of human disturbance, including relocation of villages and industries, prevention of encroachment, and banning sand and boulder mining in the corridors.

Ectopic teeth in ovarian teratoma: a rare appearance.

Teratoma consists of tissues derived from all the three germ layers, and there may be presence of appendages as a representation of these germ layers as well. Teratomas of the ovary are known to occur in a fairly large number of women. These may be present clinically at a much later stage, permitting a limited treatment plan. Newer diagnostic techniques are always welcome in identifying these lesions. This case report discusses the case of a 40-year-old woman with a large teratoma in the right ovary and its diagnostic and surgical modalities.

Granulocytic Sarcoma of Parotid Gland in a 4-Year-Old Child with Subleukemic AML: A Diagnostic Challenge!

A 4-year-old male child presented to our outpatient department with large swelling in the parotid region. Routine investigations were all within normal limits, and evaluation of complete blood count was normal except for anaemia. Excisional biopsy as a therapeutic diagnosis was done. Microscopic examination showed monomorphic population of discohesive, hyperchromatic small round cells having high N : C ratio, coarse chromatin, conspicuous nucleoli, and sometimes angulated nuclei lying in sheets. Immunohistochemistry was done to rule out possible differential diagnosis. Fine needle aspiration from the swelling showed predominant population of blast cells. Myeloperoxidase and PBO were strongly positive, and diagnosis of granulocytic sarcoma was confirmed.

Molecular interactions, proton exchange, and photoinduced processes prompted by an inclusion process and a [2]pseudorotaxane formation.

Appropriate design of the host and guest components allows formation of a novel [2]pseudorotaxane complex with an interrupted photoinduced electron transfer (PET)-coupled fluorescence resonance energy transfer (FRET) response. This is the first example of an inclusion complex with NO6-based azacrown ether as the host unit (H). Different guest molecules (G1, G2, G3, and G4) with varying stopper size are used for the studies. Unlike G1, G2, and G3, G4 with a relatively bulkier stopper fails to form a [2]pseudorotaxane complex. Isothermal titration microcalorimetry measurements reveal a systematic increase in the association constant for H·G1, H·G2, and H·G3 with a change in the stopper size. Thermodynamic data suggest that the formation of H·G1/H·G2/H·G3 is exclusively driven by a large positive entropic gain (TΔS = 19.69/26.80/21.81 kJ·mol(-1)), while the enthalpy change is slightly negative for H·G1/H·G3 (-2.61/-1.97 kJ·mol(-1)) and slightly positive for H·G2 (ΔH = 5.98 kJ·mol(-1)). For these three inclusion complexes, an interrupted PET-coupled FRET response is observed with varying efficiency, which is attributed to the subtle differences in acidity of the NH2(+) unit of the guest molecules and thus the proton exchange ability between the host and respective guest. This is substantiated by the results of the computational studies.

Impact of expression of EMP enzymes on glucose metabolism in Zymomonas mobilis.

Zymomonas mobilis is the only known microorganism that utilizes the Entner-Doudoroff (ED) pathway anaerobically. In this work, we investigated whether the overexpression of a phosphofructokinase (PFK), the only missing Embden-Meyerhof-Parnas (EMP) pathway enzyme, could establish the pathway in this organism. Introduction of a pyrophosphate-dependent PFK, along with co-expression of homologous fructose-1,6-bisphosphate aldolase and triosephosphate isomerase, did not result in an EMP flux to any appreciable level. However, the metabolism of glucose was impacted significantly. Eight percent of glucose was metabolized to form a new metabolite, dihydroxyacetone. Reducing flux through the ED pathway by as much as 40 % through antisense of a key enzyme, ED aldolase, did not result in a fully functional EMP pathway, suggesting that the ED pathway, especially the lower arm, downstream from glyceraldehyde-3-phosphate, is very rigid, possibly due to redox balance.

Engineering efficient xylose metabolism into an acetic acid-tolerant Zymomonas mobilis strain by introducing adaptation-induced mutations.

The impact of the two adaptation-induced mutations in an improved xylose-fermenting Zymomonas mobilis strain was investigated. The chromosomal mutation at the xylose reductase gene was critical to xylose metabolism by reducing xylitol formation. Together with the plasmid-borne mutation impacting xylose isomerase activity, these two mutations accounted for 80 % of the improvement achieved by adaptation. To generate a strain fermenting xylose in the presence of high acetic acid concentrations, we transferred the two mutations to an acetic acid-tolerant strain. The resulting strain fermented glucose + xylose (each at 5 % w/v) with 1 % (w/v) acetic acid at pH 5.8 to completion with an ethanol yield of 93.4 %, outperforming other reported strains. This work demonstrated the power of applying molecular understanding in strain improvement.

Discovery and characterization of a xylose reductase from Zymomonas mobilis ZM4.

Formation of xylitol, a byproduct from xylose fermentation, is a major limiting factor in ethanol production from xylose in engineered Zymomonas strains, yet the postulated xylose reductase remains elusive. We report here the discovery of xylose reductase in Zymomonas mobilis and, for the first time, to associate the enzyme function with its gene. Besides xylose and xylulose, the enzyme was active towards benzaldehyde, furfural, 5-hydroxymethyl furfural, and acetaldehyde, exhibiting nearly 150-times higher affinity with benzaldehyde than xylose. The discovery of xylose reductase paves the way for further improvement of xylose fermentation in Z. mobilis. The enzyme may also be used to mitigate toxicity of furfural and other inhibitors from plant biomass.

Adaptation yields a highly efficient xylose-fermenting Zymomonas mobilis strain.

Zymomonas mobilis is a superb ethanol producer with productivity exceeding yeast strains by several fold. Although metabolic engineering was successfully applied to expand its substrate range to include xylose, xylose fermentation lagged far behind glucose. In addition, xylose fermentation was often incomplete when its initial concentration was higher than 5%. Improvement of xylose fermentation is therefore necessary. In this work, we applied adaptation to improve xylose fermentation in metabolically engineered strains. As a result of adaptation over 80 days and 30 serial transfers in a medium containing high concentration of xylose, a strain, referred as A3, with markedly improved xylose metabolism was obtained. The strain was able to grow on 10% (w/v) xylose and rapidly ferment xylose to ethanol within 2 days and retained high ethanol yield. Similarly, in mixed glucose-xylose fermentation, a total of 9% (w/v) ethanol was obtained from two doses of 5% glucose and 5% xylose (or a total of 10% glucose and 10% xylose). Further investigation reveals evidence for an altered xylitol metabolism in A3 with reduced xylitol formation. Additionally xylitol tolerance in A3 was increased. Furthermore, xylose isomerase activity was increased by several times in A3, allowing cells to channel more xylose to ethanol than to xylitol. Taken together, these results strongly suggest that altered xylitol metabolism is key to improved xylose metabolism in adapted A3 strain. This work further demonstrates that adaptation and metabolic engineering can be used synergistically for strain improvement.

Halonium ion-assisted deiodination of styrene-based vicinal iodohydrins followed by rearrangement through phenyl migration.

Acid activation of bromate/bromide couple at 0-10 degrees C was found to trigger the deiodination of styrene-based vicinal iodohydrins. Violet coloration of the organic layer was ascribed to formation of IBr. Deiodination was followed by phenyl migration and deprotonation leading to formation of phenyl acetone and 2-phenylpropanal in good yields from 1-iodo-2-phenylpropan-2-ol and 2-iodo-1-phenylpropan-1-ol, respectively. Phenyl acetaldehyde--which was obtained in 92% GC yield from styrene iodohydrin--was also presumably formed in analogous manner. NBS and HOCl too were effective for transformation of styrene iodohydrin into phenyl acetaldehyde.