Recent Developments and Application of Mass Spectrometry Imaging in N-Glycosylation Studies: An Overview.

Among the most typical posttranslational modifications is glycosylation, which often involves the covalent binding of an oligosaccharide (glycan) to either an asparagine (N-linked) or a serine/threonine (O-linked) residue. Studies imply that the N-glycan portion of a glycoprotein could serve as a particular disease biomarker rather than the protein itself because N-linked glycans have been widely recognized to evolve with the advancement of tumors and other diseases. N-glycans found on protein asparagine sites have been especially significant. Since N-glycans play clearly defined functions in the folding of proteins, cellular transport, and transmission of signals, modifications to them have been linked to several illnesses. However, because these N-glycans' production is not template driven, they have a substantial morphological range, rendering it difficult to distinguish the species that are most relevant to biology and medicine using standard techniques. Mass spectrometry (MS) techniques have emerged as effective analytical tools for investigating the role of glycosylation in health and illness. This is due to developments in MS equipment, data collection, and sample handling techniques. By recording the spatial dimension of a glycan's distribution in situ, mass spectrometry imaging (MSI) builds atop existing methods while offering added knowledge concerning the structure and functionality of biomolecules. In this review article, we address the current development of glycan MSI, starting with the most used tissue imaging techniques and ionization sources before proceeding on to a discussion on applications and concluding with implications for clinical research.

Inferior polar nephrectomy and vesicocalicostomy for complete ureteric stricture following antibody-mediated rejection in ABO-incompatible living donor kidney transplant: a report of a rare case.

Renal transplant recipients are prone to urological complications, the most common of which is stricture of the transplant ureter. We present a rare case of complete ureteric stricture in a 37-year-old man who had undergone spousal living donor kidney transplantation with ABO incompatibility. Initially, treatment involved creating an anastomosis between the native right ureter and the renal pelvis of the transplanted kidney. However, the stricture recurred. Subsequently, the patient was successfully treated with inferior polar nephrectomy and vesicocalicostomy, which entailed anastomosing the lower calyx of the transplanted kidney to the bladder. After 7 months of follow-up, the patient continued to exhibit stable renal function without stricture recurrence.

Recent developments and applications of ambient mass spectrometry imaging in pharmaceutical research: an overview.

The application of ambient mass spectrometry imaging "MSI" is expanding in the areas of fundamental research on drug delivery and multiple phases of the process of identifying and developing drugs. Precise monitoring of a drug's pharmacological workflows, such as intake, distribution, metabolism, and discharge, is made easier by MSI's ability to determine the concentrations of the initiating drug and its metabolites across dosed samples without losing spatial data. Lipids, glycans, and proteins are just a few of the many phenotypes that MSI may be used to concurrently examine. Each of these substances has a particular distribution pattern and biological function throughout the body. MSI offers the perfect analytical tool for examining a drug's pharmacological features, especially in vitro and in vivo effectiveness, security, probable toxic effects, and putative molecular pathways, because of its high responsiveness in chemical and physical environments. The utilization of MSI in the field of pharmacy has further extended from the traditional tissue examination to the early stages of drug discovery and development, including examining the structure-function connection, high-throughput capabilities in vitro examination, and ex vivo research on individual cells or tumor spheroids. Additionally, an enormous array of endogenous substances that may function as tissue diagnostics can be scanned simultaneously, giving the specimen a highly thorough characterization. Ambient MSI techniques are soft enough to allow for easy examination of the native sample to gather data on exterior chemical compositions. This paper provides a scientific and methodological overview of ambient MSI utilization in research on pharmaceuticals.

Recent Advances and Applications of Ambient Mass Spectrometry Imaging in Cancer Research: An Overview.

Cancer metabolic variability has a significant impact on both diagnosis and treatment outcomes. The discovery of novel biological indicators and metabolic dysregulation, can significantly rely on comprehension of the modified metabolism in cancer, is a research focus. Tissue histology is a critical feature in the diagnostic testing of many ailments, such as cancer. To assess the surgical margin of the tumour on patients, frozen section histology is a tedious, laborious, and typically arbitrary method. Concurrent monitoring of ion images in tissues facilitated by the latest advancements in mass spectrometry imaging (MSI) is far more efficient than optical tissue image analysis utilized in conventional histopathology examination. This article focuses on the "desorption electrospray ionization (DESI)-MSI" technique's most recent advancements and uses in cancer research. DESI-MSI can provide wealthy information based on the variances in metabolites and lipids in normal and cancerous tissues by acquiring ion images of the lipid and metabolite variances on biopsy samples. As opposed to a systematic review, this article offers a synopsis of the most widely employed cutting-edge DESI-MSI techniques in cancer research.

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) in disease diagnosis: an overview.

Tissue analysis, which is essential to histology and is considered the benchmark for the diagnosis and prognosis of many illnesses, including cancer, is significant. During surgery, the surgical margin of the tumor is assessed using the labor-intensive, challenging, and commonly subjective technique known as frozen section histopathology. In the biopsy section, large numbers of molecules can now be visualized at once (ion images) following recent developments in [MSI] mass spectrometry imaging under atmospheric conditions. This is vastly superior to and different from the single optical tissue image processing used in traditional histopathology. This review article will focus on the advancement of desorption electrospray ionization mass spectrometry imaging [DESI-MSI] technique, which is label-free and requires little to no sample preparation. Since the proportion of molecular species in normal and abnormal tissues is different, DESI-MSI can capture ion images of the distributions of lipids and metabolites on biopsy sections, which can provide rich diagnostic information. This is not a systematic review but a summary of well-known, cutting-edge and recent DESI-MSI applications in cancer research between 2018 and 2023.

Primary adenocarcinoma with yolk sac differentiation in the transplant ureter and salvage of the transplant kidney: a rare case report.

Renal transplant recipients are prone to a high risk of subsequent upper tract urothelial carcinoma, occurring in both native and transplant ureters. We report a rare case of adenocarcinoma with yolk sac differentiation of the transplant ureter, which was managed successfully with transplant ureterectomy and pyelovesicostomy, thereby salvaging the functioning transplant kidney.

Hemophagocytic lymphohistiocytosis: A scourge for the physician and bane to the bone marrow.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a condition characterized by hyperinflammation. It can occur due to primary genetic defect or secondary to other etiology such as infection and rheumatological conditions. Clinical features include fever, cytopenia, organomegaly and several laboratory abnormalities. It can be a life-threatening condition secondary to worsening cytopenia and multiorgan dysfunction. Aims and Objectives: To study the clinical profile of HLH in a tertiary care hospital in Southern India. Materials and Methods: Our study has reviewed nine cases of HLH among adult patients presented over 5 years (2017-2022). Results: The majority of our cases were secondary to infection and had a hospital stay over two weeks and with a good response to steroid and immunomodulators. Conclusion: We would like to stress upon the importance of awareness of such a condition so that there can be early suspicion and workup including bone marrow examination, enabling early initiating of specific therapy for this fatal condition.

Résumé Contexte: L'hémophagocytose lymphohistiocytaire (HLH) est une affection caractérisée par une hyperinflammation. Elle peut survenir en raison d'un défaut génétique primaire ou être secondaire à d'autres étiologies telles que l'infection et les affections rhumatologiques. Les caractéristiques cliniques comprennent de la fièvre, une cytopenie, une organomégalie et plusieurs anomalies de laboratoire. Il s'agit d'une affection potentiellement mortelle en raison de l'aggravation de la cytopenie et du dysfonctionnement multi-organes. Objectifs: Étudier le profil clinique de l'HLH dans un hôpital de soins tertiaires du sud de l'Inde. Matériel et méthodes: Notre étude a examiné neuf cas d'HLH chez des patients adultes sur une période de 5 ans (2017-2022). Résultats: La majorité de nos cas étaient secondaires à une infection et ont nécessité une hospitalisation de plus de deux semaines, avec une bonne réponse aux stéroïdes et aux immunomodulateurs. Conclusion: Nous tenons à souligner l'importance de la sensibilisation à cette affection afin qu'il puisse y avoir une suspicion précoce et des examens approfondis, y compris une ponction de moelle osseuse, permettant ainsi de démarrer rapidement une thérapie spécifique pour cette affection mortelle. Mots-clés: Score H, hémophagocytose lymphohistiocytaire, immunosuppression, hémophagocytose lymphohistiocytaire secondaire.

Bilateral Synchronous 3-Port Trans-peritoneal Laparoscopic Ureterolithotomy: a Case Report.

Trans-peritoneal laparoscopic ureterolithotomy is a well-established minimally invasive procedure for management of large impacted ureteric stones since the last 3 decades. We present a case of a 51-year old gentleman, who presented with bilateral large upper ureteric calculi with obstructive uropathy and azotemia, managed successfully with bilateral synchronous 3-port trans-peritoneal laparoscopic ureterolithotomy, and to our knowledge is the first such case to be reported in literature. Supplementary Information: The online version contains supplementary material available at 10.1007/s42399-022-01190-5.

Change in attitudes and perceptions of undergraduate health profession students towards inter-professional education following an educational experience in post natal care.

BACKGROUND: Inter-professional Education (IPE) has been identified as an educational program aimed at increasing collaboration among health professionals, and improving health care outcomes. IPE programs have been incorporated in several countries and have shown positive results. The same may not be true for Asian cultures which are typically more hierarchical than others. The purpose of this study was to examine the impact of IPE on undergraduate health professional students' attitudes and perceptions in an Indian context. METHODS: Following an IPE experience undergraduate health professional students (n = 96) from three professions (Medicine, Nursing and Physiotherapy) completed a validated retro-pre questionnaire. Paired-sample t test was used to compare pre-test and post-test scores and ANOVA was used to compare the magnitude of change. Qualitative analysis was done for the open ended questions. RESULTS: The three professions showed a significant improvement in attitude (p < 0.001). The physiotherapists were more comfortable (p = 0.021) with questioning and being questioned and the nurses showed a significantly (p = 0.012) greater increase in extent of reliability as compared to the other two professionals. Participants identified the concepts of "team work", "knowledge of roles of other professionals" and "communication" as important to their learning and practice. CONCLUSIONS: The study identified a positive attitude among students and the given intervention resulted in a significant improvement in their comfort levels and reliability on other professionals. It would be reasonable to conclude therefore that acceptability for Inter professional education in the Indian context is high in spite of the cultural differences and hierarchical nuances.

Urethral stricture after bipolar transurethral resection of prostate - truth vs hype: A randomized controlled trial.

INTRODUCTION: Bipolar transurethral resection of prostate (B-TURP) was introduced as an alternative procedure to minimize the surgical complications of monopolar TURP (M-TURP). However, there are concerns about increased incidence of stricture urethra (SU) post B-TURP. This study was designed to analyze the incidence of SU among patients undergoing M-TURP versus B-TURP. MATERIALS AND METHODS: This is a randomized controlled, single-blinded study; randomization was performed using a stratified permuted randomization algorithm (1:1 ratio) and only the patients were blinded. Both M-TURP and B-TURP were performed with a 26 Fr resectoscope; the electrosurgical generators were Karl Storz Autocon II 400 and Olympus UES-40 SurgMaster (TUR in saline [TURIS] method), respectively. Follow-up visits were scheduled at 3, 6, and 12 months post surgery and patients with lower urinary tract symptoms and a maximum urinary flow rate of <10 ml/sec on uroflowmetry underwent retrograde urethrography to assess for development of SU. RESULTS: Forty patients were randomised to each arm. None developed SU in the monopolar group, whereas there were three cases in the bipolar group (P = 0.2). Among these three patients, two belonged to the failed medical management subgroup and one to the refractory urinary retention subgroup (P = 1.0). CONCLUSION: The incidence of SU following B-TURP using the TURIS system was comparable to the conventional M-TURP. Moreover, the incidence of SU was same for both the techniques when sub-grouped according to the indication for surgery that is failed medical management versus refractory urinary retention.

Evaluation of a call center to assess post-discharge maternal and early neonatal outcomes of facility-based childbirth in Uttar Pradesh, India.

BACKGROUND: Maternal and neonatal outcomes in the immediate post-delivery period are critical indicators of quality of care. Data on childbirth outcomes in low-income settings usually require home visits, which can be constrained by cost and access. We report on the use of a call center to measure post-discharge outcomes within a multi-site improvement study of facility-based childbirth in Uttar Pradesh, India. METHODS: Of women delivering at study sites eligible for inclusion, 97.9% (n = 157,689) consented to follow-up. All consenting women delivering at study facilities were eligible to receive a phone call between days eight and 42 post-partum to obtain outcomes for the seven-day period after birth. Women unable to be contacted via phone were visited at home. Outcomes, including maternal and early neonatal mortality and maternal morbidity, were ascertained using a standardized script developed from validated survey questions. Data Quality Assurance (DQA) included accuracy (double coding of calls) and validity (consistency between two calls to the same household). Regression models were used to identify factors associated with inconsistency. FINDINGS: Over 23 months, outcomes were obtained by the call center for 98.0% (154,494/157,689) consenting women and their neonates. 87.9% of call center-obtained outcomes were captured by phone call alone and 12.1% required the assistance of a field worker. An additional 1.7% were obtained only by a field worker, 0.3% were lost-to-follow-up, and only 0.1% retracted consent. The call center captured outcomes with a median of 1 call (IQR 1-2). DQA found 98.0% accuracy; data validation demonstrated 93.7% consistency between the first and second call. In a regression model, significant predictors of inconsistency included cases with adverse outcomes (p<0.001), and different respondents on the first and validation call (p<0.001). CONCLUSIONS: In areas with widespread mobile cell phone access and coverage, a call center is a viable and efficient approach for measurement of post-discharge childbirth outcomes.

Periplasmic flagella in Borrelia burgdoferi function to maintain cellular integrity upon external stress.

Tapping mode atomic force microscopy (AFM) in solution was used to analyze the role of the internally located periplasmic flagella (PFs) of the Lyme disease spirochete Borrelia burgdorferi in withstanding externally applied cellular stresses. By systematically imaging immobilized spirochetes with increasing tapping forces, we found that mutants that lack PFs are more readily compressed and damaged by the imaging process compared to wild-type cells. This finding suggest that the PFs, aside from being essential for motility and involved in cell shape, play a cytoskeletal role in dissipating energy and maintaining cellular integrity in the presence of external stress.

Mesh erosion into urinary bladder following laparoscopic inguinal hernia repair.

Along with advantages, evolving surgical techniques bring unique complications. A young male developed urinary symptoms a few months after undergoing laparoscopic inguinal hernia repair. On evaluation, mesh erosion into the urinary bladder was found. Removal of mesh with repair of bladder was done. A vesico-cutaneous fistula resulted which was managed with repeat surgery. We review all such cases reported in literature; discuss the etiopathogenesis, presentation, management and possible preventive measures. To the best of our knowledge, this is only the 12th case being reported.

Effectiveness of the WHO Safe Childbirth Checklist program in reducing severe maternal, fetal, and newborn harm in Uttar Pradesh, India: study protocol for a matched-pair, cluster-randomized controlled trial.

BACKGROUND: Effective, scalable strategies to improve maternal, fetal, and newborn health and reduce preventable morbidity and mortality are urgently needed in low- and middle-income countries. Building on the successes of previous checklist-based programs, the World Health Organization (WHO) and partners led the development of the Safe Childbirth Checklist (SCC), a 28-item list of evidence-based practices linked with improved maternal and newborn outcomes. Pilot-testing of the Checklist in Southern India demonstrated dramatic improvements in adherence by health workers to essential childbirth-related practices (EBPs). The BetterBirth Trial seeks to measure the effectiveness of SCC impact on EBPs, deaths, and complications at a larger scale. METHODS/DESIGN: This matched-pair, cluster-randomized controlled, adaptive trial will be conducted in 120 facilities across 24 districts in Uttar Pradesh, India. Study sites, identified according to predefined eligibility criteria, were matched by measured covariates before randomization. The intervention, the SCC embedded in a quality improvement program, consists of leadership engagement, a 2-day educational launch of the SCC, and support through placement of a trained peer "coach" to provide supportive supervision and real-time data feedback over an 8-month period with decreasing intensity. A facility-based childbirth quality coordinator is trained and supported to drive sustained behavior change after the BetterBirth team leaves the facility. Study participants are birth attendants and women and their newborns who present to the study facilities for childbirth at 60 intervention and 60 control sites. The primary outcome is a composite measure including maternal death, maternal severe morbidity, stillbirth, and newborn death, occurring within 7 days after birth. The sample size (n = 171,964) was calculated to detect a 15% reduction in the primary outcome. Adherence by health workers to EBPs will be measured in a subset of births (n = 6000). The trial will be conducted in close collaboration with key partners including the Governments of India and Uttar Pradesh, the World Health Organization, an expert Scientific Advisory Committee, an experienced local implementing organization (Population Services International, PSI), and frontline facility leaders and workers. DISCUSSION: If effective, the WHO Safe Childbirth Checklist program could be a powerful health facility-strengthening intervention to improve quality of care and reduce preventable harm to women and newborns, with millions of potential beneficiaries. TRIAL REGISTRATION: BetterBirth Study Protocol dated: 13 February 2014; ClinicalTrials.gov: NCT02148952 ; Universal Trial Number: U1111-1131-5647.

Highly time resolved chemical characterization of submicron organic aerosols at a polluted urban location.

Non-refractory submicron (NR-PM1) aerosols were measured during the late winter period (February-March) via an Aerodyne High Resolution Time of Flight Aerosols Mass Spectrometer (HR-ToF-AMS) along with Black Carbon (BC) and trace gasses in an industrial city, Kanpur, situated in the Gangetic Plain (GP) of India. The composition of NR-PM1 aerosols was dominated by organics (54%), followed by inorganics (36%), and BC (10%). Source apportionment via Positive Matrix Factorization (PMF) of AMS measured organic aerosols (OAs) revealed 6 factors. Factors are identified as 2 types of oxidized organic aerosols (OOAs), 2 types of biomass burning organic aerosols (BBOAs), freshly emitted hydrocarbon-like organic aerosols (HOAs) and oxygenated primary organic aerosols (OPOAs). A substantial increase in relative OOA contributions (200%) and O/C ratio (26%) has been observed from the high loading events (HLE) to the low loading events (LLE). Back trajectory analysis indicated that the study location received contributions from regional and long-range transported aerosols. OA composition and evolution during this study period were also very different from those observed during a fog influenced peak winter period of December-January. This is the first study to present detailed aerosol composition during the late winter period in India highlighting the changes in OA composition and chemistry within the same winter season.

Surgical Adjustment of the Guide Pin to Perform a Correct Tibial Tunnel in Anatomical Anterior Cruciate Ligament Single-Bundle Reconstruction.

Anatomical positioning of the graft in anterior cruciate ligament reconstruction is important to restore normal knee kinematics and prevent early joint degeneration. Inadequate position of a first attempt to place the guide pin within the center of the tibial footprint may occur. Therefore, its adjustment is important to achieve the anatomical positioning of the graft within the tibial footprint. When the guide pin exits eccentrically in an inadequate position, it is possible to correct it to the center of the footprint. A small tunnel with a 4.5-mm reamer is made and the guide pin is shifted to the center of the footprint. The center of the tunnel can be corrected until 50% and in all direction in relation to the initial drilled tunnel, without additional associated morbidity. Once the correct position of the center is achieved, the guide pin is fixed in the femoral notch roof to guarantee the accurate correction of the axis, without toggling of the guide pin inside the tunnel and metal dusting. The final tunnel is then drilled with the same size of the graft. With this technique it is possible to adjust an eccentrically misplaced guide pin to the center of the footprint without additional morbidity.

Association analysis of genes involved in maize (Zea mays L.) root development with seedling and agronomic traits under contrasting nitrogen levels.

A better understanding of the genetic control of root development might allow one to develop lines with root systems with the potential to adapt to soils with limited nutrient availability. For this purpose, an association study (AS) panel consisting of 74 diverse set of inbred maize lines were screened for seedling root traits and adult plant root traits under two contrasting nitrogen (N) levels (low and high N). Allele re-sequencing of RTCL, RTH3, RUM1, and RUL1 genes related to root development was carried out for AS panel lines. Association analysis was carried out between individual polymorphisms, and both seedling and adult plant traits, while controlling for spurious associations due to population structure and kinship relations. Based on the SNPs identified in RTCL, RTH3, RUM1, and RUL1, lines within the AS panel were grouped into 16, 9, 22, and 7 haplotypes, respectively. Association analysis revealed several polymorphisms within root genes putatively associated with the variability in seedling root and adult plant traits development under contrasting N levels. The highest number of significantly associated SNPs with seedling root traits were found in RTCL (19 SNPs) followed by RUM1 (4 SNPs) and in case of RTH3 and RUL1, two and three SNPs, respectively, were significantly associated with root traits. RTCL and RTH3 were also found to be associated with grain yield. Thus considerable allelic diversity is present within the candidate genes studied and can be utilized to develop functional markers that allow identification of maize lines with improved root architecture and yield under N stress conditions.

Genetic and agronomic assessment of cob traits in corn under low and normal nitrogen management conditions.

KEY MESSAGE: Exploring and understanding the genetic basis of cob biomass in relation to grain yield under varying nitrogen management regimes will help breeders to develop dual-purpose maize. With rising energy demands and costs for fossil fuels, alternative energy from renewable sources such as maize cobs will become competitive. Maize cobs have beneficial characteristics for utilization as feedstock including compact tissue, high cellulose content, and low ash and nitrogen content. Nitrogen is quantitatively the most important nutrient for plant growth. However, the influence of nitrogen fertilization on maize cob production is unclear. In this study, quantitative trait loci (QTL) have been analyzed for cob morphological traits such as cob weight, volume, length, diameter and cob tissue density, and grain yield under normal and low nitrogen regimes. 213 doubled-haploid lines of the intermated B73 × Mo17 (IBM) Syn10 population have been resequenced for 8575 bins, based on SNP markers. A total of 138 QTL were found for six traits across six trials using composite interval mapping with ten cofactors and empirical comparison-wise thresholds (P = 0.001). Despite moderate to high repeatabilities across trials, few QTL were consistent across trials and overall levels of explained phenotypic variance were lower than expected some of the cob trait × trial combinations (R (2) = 7.3-43.1 %). Variation for cob traits was less affected by nitrogen conditions than by grain yield. Thus, the economics of cob usage under low nitrogen regimes is promising.