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Aim To develop an evidence-based expert group opinion on the role of insulin motivation to overcome insulin distress during different stages of insulin therapy and to propose a practitioner’s toolkit for insulin motivation in the management of diabetes mellitus (DM). Background Insulin distress, an emotional response of the patient to the suggested use of insulin, acts as a major barrier to insulin therapy in the management of DM. Addressing patient-, physician- and drug-related factors is important to overcome insulin distress. Strengthening of communication between physicians and patients with diabetes and enhancing the patients' coping skills are prerequisites to create a sense of comfort with the use of insulin. Insulin motivation is key to achieving targeted goals in diabetes care. A group of endocrinologists came together at an international meeting held in India to develop tool kits that would aid a practitioner in implementing insulin motivation strategies at different stages of the journey through insulin therapy, including pre-initiation, initiation, titration and intensification. During the meeting, emphasis was placed on the challenges and limitations faced by both physicians and patients with diabetes during each stage of the journey through insulinization. Review Results After review of evidence and discussions, the expert group provided recommendations on strategies for improved insulin acceptance, empowering behavior change in patients with DM, approaches for motivating patients to initiate and maintain insulin therapy and best practices for insulin motivation at the pre-initiation, initiation, titration and intensification stages of insulin therapy. Conclusions In the management of DM, bringing in positive behavioral change by motivating the patient to improve treatment adherence helps overcome insulin distress and achieve treatment goals.

Aim The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management. Background The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations. Review Results After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most. Conclusion Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.

Prevalence of addictive disorders among persons with diabetes mellitus (DM) (type 1 and type 2) ranges from 9.6 to 29%. Excessive and problematic use of psychoactive substances in persons with diabetes results in poor glycemic control with frequent hyperglycemic crisis. Tobacco, alcohol, cannabis, benzodiazepines, inhalants, and stimulants are common psychoactive substances used among persons with diabetes in India. The daily use of alcohol by men and women with DM should not exceed 15 and 30 g of ethanol, respectively. Use of other psychoactive substances is not recommended for persons with DM. Various screening tools exist for assessing substance abuse like WHO-ASSIST, Alcohol Use Disorders Identification Test (AUDIT), Fagerström Test for Nicotine Dependence (FTND), and Opioid Risk Tool. Integrated management of co-occurring addictive disorder and DM is recommended. Psychosocial treatments for substances include brief interventions (BIs), motivational interviewing, contingency management, relapse prevention, and cognitive behavior therapy

Aim The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). Background The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. Review results The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. Conclusion Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.

Medicinal nuts like hirada and ritha have many medicinal properties and used for many pharmaceutical operations. Presently shelling of hirada ( Terminalia chebula ) and ritha (Sapindus mukorossi) nuts is done manually, which is labour intensive, slow and tedious operation. Therefore, a power operated medicinal nut sheller was developed on the basis of shear principle. The capacity of the machine has been observed to be 114 kg-h -1 and 170 kg-h -1 for hirada and ritha nuts, respectively. Shelling efficiency of nuts was 83 per cent and 80.66 per cent for hirada and ritha, respectively. Per cent broken seeds were observed as 28.9 per cent and 7.9 per cent for hirada and ritha, respectively.

The paper presents the results of evaluation of compliance of the bag net fishery of Maharashtra coast, India with the relevant clauses of Article 7 (Fisheries management) of the Code of Conduct for Responsible Fisheries (CCRF). Questionnaire-based approach that covered ten categories of stakeholders responsible wholly or partially for the management of the bag net fishery was used in the present study. Evaluation of the Code revealed an overall compliance level of 67.52%. The study identified the critical areas of low compliance levels that require immediate attention. Though the bag net fishery is the most common and traditional fishery of Maharashtra that supports livelihood of several fishers, there is no specific policy to regulate, develop and ensure sustainability of the bag net fish resources. Therefore the Code could be taken as a reference document to facilitate responsible management of the bag net fishery taking the local conditions into account. The findings of the present study could be used as a diagnostic tool to help in suggesting measures to ensure sustainability of the bag net fishery resources achievable by making amendments to the fisheries policies of the State.

Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial etiology. The first-line therapy includes monotherapy (with metformin), which often fails to provide effective glycemic control, necessitating the addition of add-on therapy. In this regard, multiple single-dose agents formulated as a single-dose form called fixed-dose combinations (FDCs) have been evaluated for their safety, efficacy, and tolerability. The primary objective of this review is to develop practice-based expert group opinion on the current status and the causes of concern regarding the irrational use of FDCs, in Indian settings. After due discussions, the expert group analyzed the results from several clinical evidence in which various fixed combinations were used in T2DM management. The panel opined that FDCs (double or triple) improve patient adherence, reduce cost, and provide effective glycemic control and, thereby, play an important role in the management of T2DM. The expert group strongly recommended that the irrational metformin FDC's, banned by Indian government, should be stopped and could be achieved through active participation from the government, regulatory bodies, and health ministry, and through continuous education of primary care physicians and pharmacists. In T2DM management, FDCs play a crucial role in achieving glycemic targets effectively. However, understanding the difference between rational and irrational FDC combinations is necessary from the safety, efficacy, and tolerability perspective. In this regard, primary care physicians will have to use a multistep approach so that they can take informed decisions.

Cerebral autoregulation and vasomotor responsiveness to carbon dioxide were measured quantitatively in normal baboons and after intravertebral or intravenous of the beta-adrenergic blocking agent, propranolol hydrochloride (Inderal). Continuous measurements were made of cerebral blood flow (CBF: measured as bilateral internal jugular venous outflow using an electromagnetic flowmeter), cerebral perfusion pressure (CPP), arterial Po2 and Pco2 and venous Po2, cerebral arteriovenous oxygen difference and endotracheal Pco2. The autoregulation index (A.I. = deltaCBF/deltaCPP) and the chemical index (C.I.= deltaCBF/deltaPaco2), were used as quantitative measures.

Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem.

This study presents ultrastructural confirmation of the embolic method of producing an ischemic lesion. The embolic method was shown to produce more advanced parenchymal changes than those reported for the same postocclusion period following vascular clipping. With this method there was less alteration in the morphological intergrity of occluded extraparenchymatous areas of the arterial bed, especially in the associated nerve bundles.

Cerebral blood flow (CBF) and metabolism were measured before and after withdrawal of 5 to 6 ml of cerebrospinal fluid (CSF) in 17 baboons. The measurements were made before and after infusion of tyrosine, the precursor amino acid of the putative neurotransmitters, dopamine and norepinephrine, in the brain. The same observations were made in another experimental group, i.e., before and after acute cerebral multiembolization induced by microfil emboli. In the steady state CBF was unaltered following reduction of intracranial pressure by removal of CSF. After infusion of tyrosine, CBF was decreased, and cerebrovascular resistance increased significantly on removal of CSF. Cerebral embolization did not influence changes in CBF at reduced intracranial pressure. It appears that the cerebral resistance vessels constrict following reduction of intracranial pressure by removal of CSF and that cerebrospinal fluid pressure-CBF autoregulatory mechanisms are resistant to cerebral ischemia induced by middle cerebral artery embolization.

Cerebral hemispheric blood flow (HBF) and metabolism were measured before and after withdrawal of 20 to 30 ml of cerebrospinal fluid (CSF) over a 10-minute interval in eight patients with recent cerebral infarction and in four patients with Alzheimer's disease (AD). Immediately after CSF removal HBF decreased significantly in the AD group (-14%) but showed no significant change in the stroke group (-5%). There was rapid reduction in cerebral venous O2 content and some increase in cerebral venous PCO2 appearing within 60 seconds of CSF withdrawal, interpreted as a rapid reduction of cerebral blood flow (CBF) as judged by cerebral A-VO2 differences. The reduction in CBF was confirmed by the hydrogen clearance method. Reduction of CBF in response to lowering CSF pressure is presumably of neurogenic origin since it was rapid and occurred without changes in PaCO2 or MABP. Furthermore, measurement of HBF demonstrated that cerebral metabolism constant after CSF removal. It is postulated that in AD, reduction of HBF following CSF withdrawal is mediated by a disordered neurogenic veno-arterial vasoconstriction reflex which is stimulated by rapid reduction in CSF pressure (CSFP). In patients with stroke, when cerebral perfusion pressure is increased by lowering CSFP, CBF is maintained constant most likely by a physiological cerebral veno-arterial vasoconstrictive reflex. Apparently, this vasocontrictive reflex becomes excessive in Alzheimer's disease, possibly due to cerebral neurogenic imbalance.

A clinical method for noninvasive measurement of regional cerebral blood flow (rCBF) and blood volume (rCBV) is described, based on Obrist's 10 minute, desaturation method after 1 minute inhalation of 133Xe. Sixteen collimated probes are placed over both hemispheres and brain stem-cerebellar regions. End-tidal 133Xe curves are used for correction of recirculation. KEV discriminators are set to record gamma and x-ray activity separately. Values are printed out automatically by a computer on a brain map. Extracerebral contamination is reduced by 1) computing curves from gamma activity, 2) applying pressure on the scalp beneath the probes, 3) 1 minute inhalation of 133Xe and recording desaturation curves for 10 minutes, thereby minimizing slow clearance from extracranial tissues. Normal values for both fast and slow compartments are reproducible and are in good agreement with the carotid injection method. The speech dominant hemishpere has higher flow than the right under conditions described. Posterior portions of the cranium over the cerebellum and brain stem appear to have higher flow gray values than the cerebral cortex. Gray matter flow decreases with advancing age.

Investigations concerned with the pathogenesis of hypertensive encephalopathy have reported two opposing changes in cerebral hemodynamics during induced hypertension: (1) vasospasm or vasoconstriction of the leptomeningeal arteries and (2) increase of cerebral blood flow which has been termed "breakthrough" of the cerebral autoregulation. To resolve this apparent conflict, continuous measurements of focal cerebral flow and oxygen availability were made in 17 baboons by the use of implanted platinum electrodes placed in both gray and white matter during induced hypertension. Autoregulation was initially well maintained in gray matter followed by "breakthrough" but the autoregulatory response was poorly maintained in the cerebral white matter. The vasoconstriction of the leptomeningeal arteries reported in earlier investigations from observations made through a skull window appears to be due to a marked autoregulatory response to hypertension rather than vasospasm. The autoregulatory response appears to be efficient in gray matter but relatively deficient in white matter.