Rethinking PICO in the Machine Learning Era: ML-PICO

Background  Machine learning (ML) has captured the attention of many clinicians who may not have formal training in this area but are otherwise increasingly exposed to ML literature that may be relevant to their clinical specialties. ML papers that follow an outcomes-based research format can be assessed using clinical research appraisal frameworks such as PICO (Population, Intervention, Comparison, Outcome). However, the PICO frameworks strain when applied to ML papers that create new ML models, which are akin to diagnostic tests. There is a need for a new framework to help assess such papers. Objective  We propose a new framework to help clinicians systematically read and evaluate medical ML papers whose aim is to create a new ML model: ML-PICO (Machine Learning, Population, Identification, Crosscheck, Outcomes). We describe how the ML-PICO framework can be applied toward appraising literature describing ML models for health care. Conclusion  The relevance of ML to practitioners of clinical medicine is steadily increasing with a growing body of literature. Therefore, it is increasingly important for clinicians to be familiar with how to assess and best utilize these tools. In this paper we have described a practical framework on how to read ML papers that create a new ML model (or diagnostic test): ML-PICO. We hope that this can be used by clinicians to better evaluate the quality and utility of ML papers.     

Inducible protective processes in animal systems. X. Influence of nicotinamide in methyl methanesulfonate-adapted mouse bone marrow cells.

The adaptive response is an error-free DNA repair mechanism induced by low levels of physical or chemical agents. Cells pre-exposed to such agents are resistant to genetic damage induced by subsequent treatment at a high dose. There are many reports on such adaptive responses. Recently we have shown the existence of adaptive responses in vivo in the grasshopper Poecilocerus pictus and the mouse and in vitro in human lymphocytes. Different enzymes are implicated in this DNA repair pathway. In an attempt to understand the molecular mechanism of the methyl methanesulfonate (MMS)-induced adaptive response, the present investigations have been undertaken employing nicotinamide, an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). Pre-, inter- and post-treatments with nicotinamide of MMS-treated mouse bone marrow cells were carried out. The results revealed that there is a significant reduction in the frequency of chromosomal aberrations compared with combined treatment, suggesting an enhancement of the adaptive response by nicotinamide. Further, the results of NAD+ assay in the inter-treatment experiment showed that there is no depletion of NAD+. Thus, it can be stated that PARP is not involved in the MMS-induced adaptive response in mouse bone marrow cells.     

Ileocolic mucormycosis – an unusual cause of a mass in the right iliac fossa

Mucormycosis is a relatively uncommon, aggressive and lethal mycosis. Fungi from the order Mucorales are the etiological agents of mucormycosis. The condition is more common among the immunocompromised, diabetic patients with ketoacidosis and people with iron overload syndromes. Diagnosis of mucormycosis requires a high index of suspicion regarding the possibility of the condition in high-risk individuals. Timely diagnosis is critical to survival and minimization of morbidity. A favourable outcome is possible only if appropriate treatment is initiated as early as possible. The present article reports a case of ileocolic mucormycosis involving a patient with chronic renal failure and familial hyperuricemia.     

Parkinson’s Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects

Purpose of Review

Gastrointestinal disturbances are seen in nearly all patients with Parkinson’s disease and lead to impaired quality of life, affect drug pharmacodynamics, and potentially worsen patient’s existing motor fluctuations, leading to further disability. Recent evidence links abnormal accumulations of α-synuclein aggregates in the periphery (gut) as seen in the cortex which causes dysfunctions impacting every level of the gastrointestinal tract from the esophagus, to the stomach, small bowel, colon, and rectum and can even predate the onset of the central neurologic disorder itself. Many treatments exist for the clinical phenotypes that result from the autonomic dysfunction and neuropathy involved in this neurodegenerative disorder.

Recent findings/summary

The treatments for the gut dysfunction seen in Parkinson’s disease (PD) depend on the specific area of the gastrointestinal tract affected. For dysphagia, behavioral therapies with speech pathology, neuromuscular electrical stimulation, or botulinum toxin injection may be helpful. For gastroparesis, domperidone may serve as an antiemetic while also blunting the hypotensive potential of Levodopa while new treatments such as ghrelin agonists may prove beneficial to help appetite, satiety, gastric emptying in those with constipation, and even improve constipation. Antibiotics such as rifaximin with poor systemic absorption may be used to treat small bacterial overgrowth also found in those with PD while the benefits of probiotics is yet to be determined. Finally, constipation in PD can be a reflection of pelvic floor dyssynergia, slow transit constipation, or both, thus treatments targeting the specific anorectal dysfunction is necessary for better outcomes.

     

Oligomeric proanthocyanidins protect myocardium by mitigating left ventricular remodeling in isoproterenol‐induced postmyocardial infarction

Extracellular matrix (ECM) remodeling is a major pathophysiological process during post‐myocardial infarction (MI). The activation, differentiation, and proliferation of cardiac fibroblasts to myofibroblasts regulate the expression of ECM proteins. The signaling by bone morphogenetic protein (BMP‐4), an extracellular ligand of the TGF‐β family, has recently been identified as an essential pathway in regulating cardiovascular dysfunctions including myocardial fibrosis. Oligomeric proanthocyanidins (OPC) are well known for their cardioprotective activity. The primary aim of the study was to investigate BMP‐4‐mediated ECM turnover in cardiac fibrosis during isoproterenol‐induced post‐MI and its downregulation by OPC. Myocardial injury was evaluated by assaying serum markers LDH and CK. Oxidative stress and the enzymatic and nonenzymatic antioxidant levels were assessed to support the cardioprotective nature of OPC. The total collagen level was analyzed by measuring hydroxyproline levels. The ISO‐induced group showed a significant decrease in the levels of antioxidants due to severe oxidative stress and increased expression of BMP‐4 which reflects the increased expression of MMP 2 and 9 with a concomitant increase and deposition of fibrillary collagens type I and III responsible for the fibrotic scar formation as evidenced in the histological analysis.BMP‐4 activation, thus, is strongly associated with cardiac fibrosis which was downregulated upon OPC supplementation. This study provides an evidence supporting the antifibrotic effect of OPC via regulation of BMP‐4‐mediated ECM turnover and also substantiates the remarkable antioxidant efficacy of OPC against isoproterenol induced severe oxidative stress and subsequent post‐MI cardiac fibrosis.     

Comparison of the efficacy of liraglutide with pioglitazone on dexamethasone induced hepatic steatosis,dyslipidemia and hyperglycaemia in albino rats

Objectives:To evaluate the efficacy of liraglutide with pioglitazone for prevention of dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycemia in Albino rats.Results:Dexamethasone caused hepatomegaly, dyslipidemia, and hyperglycemia. Both pioglitazone and liraglutide significantly reduced hepatomegaly, dyslipidemia and hyperglycemia (P < 0.01). Reduction of blood sugar levels after glucose load was significant with pioglitazone when compared with liraglutide (P < 0.01).Conclusion:Liraglutide has comparable efficacy to pioglitazone in prevention of dexamethasone induced hepatomegaly, dyslipidemia and fasting hyperglycemia.KEY WORDS: Dexamethasone, hepatomegaly, hyperglycemia, liraglutide, pioglitazone, prevention     

Mechanistic insight into the improved Li ion conductivity of solid polymer electrolytes

Polymer based solid electrolytes (SEs) are envisaged as futuristic components of safer solid state energy devices. But the semi-crystalline nature and slow dynamics of the host polymer matrix are found to hamper the ion transport through the solid polymer network and hence solid state devices are still far beyond the scope of practical application. In this study, we unravel the synergistic roles of Li salt (LiClO₄) and two different polymers – polyethylene oxide (PEO) and polydimethyl siloxane (PDMS), in the Li ion transport through their solid blend based electrolyte. A detailed study using dielectric spectroscopy and thermo-mechanical analysis is conducted to understand the tunability of the PEO chain dynamics with LiClO₄ and the mechanism of hopping of Li ions by forming ion pairs with oxygen dipoles on the PEO backbone is established. Despite the lack of PDMS''s capability to solvate ions and promote ion transport directly, its proper mixing within the PEO host matrix is demonstrated to enhance ion transport due to the influence of PDMS on the segmental dynamics of PEO. A detailed molecular dynamics study supported by experimental validation suggests that even inert polymers can affect the dynamics of the active host matrix and increase ion transport, leading to next generation high ionic conductivity solid matrices, and opens new avenues in designing polymer based transparent electrolytes.

The studies shown here prove that both the Li salt and ‘inert-polymer’ mixing have paramount importance in the tunability of Li ion conductivity in solid electrolytes for batteries.     

Impression tray designs and techniques for complete dentures in cases of microstomia--a review

ObjectivesThe present paper aims to review the literature on various approaches in the tray designs and different techniques used to overcome difficulties in making impressions of patients with severely limited mouth opening published from 1984 to 2009.Study designA search in the National Library of Medicine's Pub Med database, Google search and Science Direct was performed to include all case reports and reviews on prosthodontic rehabilitation of patients with microstomia. A total of 17 articles were included for discussion in the review out of the 22 articles found to be giving new tray designs.ConclusionsDifferent tray designs and impression techniques which can be useful in management of difficult cases causing little discomfort to the patient and help in getting back such patients to a comfortable social living.     

Online selling of wildlife part with spurious name: a serious challenge for wildlife crime enforcement

International Journal of Legal Medicine - We examined an online sold product “Hatha Jodi” synonym of “paired arm” for the confirmation of its biological source. It was...