Truncated Albumins as Novel Surrogate Biomarkers in Diabetes Therapy: Epiphenomena and Potential Clinical Applications.

Among various albumin posttranslational modifications (PTMs), N- and C-terminal truncations (HSA-DA and HSA-L) have also shown biomarker potential in disease states. We examined albumin truncation longitudinal trends and correlations during diabetes therapy toward possible future clinical applications. In a preliminary longitudinal therapy investigation, mass spectrometry was employed to track PTMs of human serum albumin (HSA), including glycation (GA), cysteinylation (CA or HNA1; reversible), di/trioxidation (OA or HNA2; irreversible), and truncation (TA).

Parathyroid Carcinoma Complicated by Parathyromatosis and Refractory Hypercalcemia.

Parathyroid carcinoma (PC) is a rare malignancy. In January 2022, a 41-year-old woman presented with weight loss, proximal muscle weakness, and bone pain. She was diagnosed with severe hypercalcemia with serum calcium of 15.

Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu.

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes).

Accelerated microbial identification "directly" from positive blood cultures using MALDI-TOF MS: Local clinical laboratory challenges.

Rapid identification of microbial pathogens "directly" from positive blood cultures (PBCs) is critical for prompt initiation of empirical antibiotic therapy and clinical outcomes. Towards higher microbial identification rates, we modified a published initial serum separator tubes-based MALDI-TOF-MS protocol, for blood culture specimens received at a non-hospital based standalone diagnostic laboratory, Bangalore, India: (a) "Initial" protocol #1: From 28 PBCs, identification= 39% (Gram-negative= 43%: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa; Gram-positive: 36%: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus haemolyticus); mis-identification= 14%; non-identification= 47%. (b) "Modified" protocol #2: Quality controls (ATCC colonies spiked in negative blood cultures) From 7 analysis, identification= 100% (Escherichia coli, Klebsiella pneumonia, Klebsiella oxytoca, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus); From 7 PBCs, identification= 57%; mis-identification= 14%; non-identification= 29%.

Albumin Oxidation and Albumin Glycation Discordance During Type 2 Diabetes Therapy: Biological and Clinical Implications.

Cys34 albumin redox modifications (reversible "cysteinylation" and irreversible "di/trioxidation"), besides being just oxidative stress biomarkers, may have primary pathogenetic roles to initiate and/or aggravate cell, tissue, and vascular damage in diabetes. In an exploratory "proof-of-concept" pilot study, we examined longitudinal changes in albumin oxidation during diabetes therapy. Mass spectrometric analysis was utilized to monitor changes in human serum albumin (HSA) post-translational modifications {glycation [glycated albumin (GA)], cysteinylation [cysteinylated albumin (CA) or human non-mercaptalbumin-1; reversible], di/trioxidation (di/trioxidized albumin or human non-mercaptalbumin-2; irreversible), and truncation (truncated albumin)} during ongoing therapy.

Differential Spectrum of Albumin Glycation, Oxidation, and Truncation in Type 2 and Type 1 Diabetes: Clinical and Biological Implications.

Albumin, the most abundant and physiologically vital serum protein, accumulates a range of chemical modifications, as consequence of encounters with large number of reactive molecules whose concentrations increase in serum under pathological conditions. In a "proof of concept" study, mass spectrometric analysis was utilized to quantitate albumin post-translational modifications (glycation, oxidation, and truncation; individual isoforms and total) in four informative subject groups [type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity and healthy; all with estimated glomerular filtration rate ≥60 mL/(min·m)]. Besides glycated albumin (GA/mass spectrometry), glycated serum protein (GSP/nitro blue tetrazolium colorimetry), and glycated hemoglobin (HbA1c/high-performance liquid chromatography) were also measured.

Deubiquitinases: key regulators of the circadian clock.

All living organisms experience daily environmental cycles and have consequently evolved to synchronize and adapt to this changing environment. Biological processes such as hormonal secretion, body temperature, and sleep follow daily cycles called circadian rhythms that are driven by a molecular clock running in most cells and tissues of the body. This clock is composed of transcriptional-translational negative feedback loops involving clock genes and proteins.

Chronic Exposure to Dim Light at Night or Irregular Lighting Conditions Impact Circadian Behavior, Motor Coordination, and Neuronal Morphology.

Mistimed exposure to light has been demonstrated to negatively affect multiple aspects of physiology and behavior. Here we analyzed the effects of chronic exposure to abnormal lighting conditions in mice. We exposed mice for 1 year to either: a standard light/dark cycle, a "light-pollution" condition in which low levels of light were present in the dark phase of the circadian cycle (dim light at night, DLAN), or altered light cycles in which the length of the weekday and weekend light phase differed by 6 h ("social jetlag").

Multicentric evaluation of a novel point of care electrochemical ELISA platform for SARS-CoV-2 specific IgG and IgM antibody assay.

New diagnostics technologies for the efficient detection and quantification of SARS-CoV-2 antibodies are very crucial to manage the COVID-19 pandemic, especially in the context of emerging vaccination paradigms. Herein, we report on a novel point-of-care Electrochemical ELISA platform with disposable screen printed electrodes functionalized with SARS-CoV-2 Spike Glycoprotein S1, to enable fast and accurate quantitative estimation of total antibody concentration (IgG and IgM) in clinical samples. The quantification is performed with a comparison of electrochemical redox current against the current produced by the spiked monoclonal antibodies with known concentration.

Behavioral phenotyping of mice lacking the deubiquitinase USP2.

Ubiquitin specific peptidase 2 (USP2) is a deubiquitinating enzyme expressed almost ubiquitously in the body, including in multiple brain regions. We previously showed that mice lacking USP2 present altered locomotor activity rhythms and response of the clock to light. However, the possible implication of USP2 in regulating other behaviors has yet to be tested.

To Ub or not to Ub: Regulation of circadian clocks by ubiquitination and deubiquitination.

Circadian clocks are internal timing systems that enable organisms to adjust their behavioral and physiological rhythms to the daily changes of their environment. These clocks generate self-sustained oscillations at the cellular, tissue, and behavioral level. The rhythm-generating mechanism is based on a gene expression network with a delayed negative feedback loop that causes the transcripts to oscillate with a period of approximately 24 hr.

Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study.

Aims: To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries.

Methods: People with type 2 diabetes treated in out-patient settings aged 18-65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress.

More anxious than depressed: prevalence and correlates in a 15-nation study of anxiety disorders in people with type 2 diabetes mellitus.

Background: Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited.

Aims: To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries.

Application of a Nanotechnology-Based, Point-of-Care Diagnostic Device in Diabetic Kidney Disease.

Introduction: Early detection of diabetes mellitus (DM) and diabetic kidney disease (DKD) is important for preventing end-stage renal failure and reducing cardiovascular complications. Availability of a validated point-of-care (PoC) device that can measure various DKD markers would be useful in this respect, especially in resource-poor parts of the world.

Methods: We validated a novel nanotechnology-based multianalyte PoC device (minimally invasive and does not require trained medical personnel) against laboratory gold standard tests for the detection of 5 biomarkers related to management of DM and DKD.

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study, a collaborative study carried out in 14 countries.

Aims: To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries.

Methods: People with diabetes aged 18-65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale.

Aza-heterocyclic Receptors for Direct Electron Transfer Hemoglobin Biosensor.

Direct Electron Transfer biosensors, facilitating direct communication between the biomolecule of interest and electrode surface, are preferable compared to enzymatic and mediator based sensors. Although hemoglobin (Hb) contains four redox active iron centres, direct detection is not possible due to inaccessibility of iron centres and formation of dimers, blocking electron transfer. Through the coordination of iron with aza-heterocyclic receptors - pyridine and imidazole - we report a cost effective, highly sensitive and simple electrochemical Hb sensor using cyclic voltammetry and chronoamperometry.

Management of anemia in patients with diabetic kidney disease: A consensus statement.

This consensus statement focuses on the window of opportunity, which exists while treating patients with diabetic kidney disease and anemia.

Type 1 diabetes: Awareness, management and challenges: Current scenario in India.

Type 1 diabetes mellitus (T1DM) has a wide presence in children and has a high mortality rates. The disease, if left unmanaged, poses various challenges to the patient and healthcare providers, including development of diabetic complications and thus decreasing the life expectancy of the affected child. The challenges of T1DM include awareness of the disease that is very poor among the general public and also in parents of T1DM children along with the health care professionals.

Type 1 diabetes pathogenesis - Prevention???

Pathogenesis of type 1 diabetes is multi-faceted, including, autoimmunity, genetics and environment. Autoimmunity directed against pancreatic islet cells results in slowly progressive selective beta-cell destruction ("Primary autoimmune insulitis"), culminating over years in clinically manifested insulin-dependent diabetes mellitus (IDDM). Circulating serum autoantibodies directed against the endocrine cells of the islets of Langerhans (Islet cell autoantibodies - ICAb) are an important hallmark of this disease.

The INTERPRET-DD study of diabetes and depression: a protocol.

Aim: People with diabetes are at an increased risk of developing depression and other psychological disorders. However, little is known about the prevalence, correlates or care pathways in countries other than the UK and the USA. A new study, the International Prevalence and Treatment of Diabetes and Depression Study (INTERPRET-DD) aims to address this dearth of knowledge and identify optimal pathways to care across the globe.

Feasibility of rapid parathormone assay for enabling minimally invasive parathyroid excision.

There is no doubt that the success of minimally invasive parathyroidectomy (MIP) has changed the whole treatment of patients with primary hyperparathyroidism, especially the approach towards traditional bilateral neck exploration. A single adenoma is the most common cause of primary hyperparathyroidism and its removal results in cure. Hence, it is worth the effort to localise and excise the single adenoma using modern technologies such as high-quality sestamibi scans and to confirm complete excision using rapid intra operative parathormone (IOPTH) assays.

'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing.

Post-transcriptional switches are flexible effectors of dynamic changes in gene expression. Here we report a new post-transcriptional switch that dictates the spatiotemporal and mutually exclusive expression of two alternative gene products from a single transcript. Expression of primate-specific exonic microRNA-198 (miR-198), located in the 3'-untranslated region of follistatin-like 1 (FSTL1) messenger RNA, switches to expression of the linked open reading frame of FSTL1 upon wounding in a human ex vivo organ culture system.

Precocious puberty and large multicystic ovaries in young girls with primary hypothyroidism.

Objective: To describe 2 cases of primary hypothyroidism, precocious puberty, large multicystic ovaries, possible diagnostic dilemma, unilateral oophorectomies, and subsequent response to levothyroxine replacement therapy.

Methods: We present the clinical, biochemical, radiologic, and histopathologic findings in 2 patients with rare cases of Van Wyk-Grumbach syndrome and megaovaries, who underwent unilateral oophorectomy.

Results: Two patients, an 8-year-old girl and a 3-year-old girl (cases 1 and 2, respectively), were referred to our center.