Mechanisms Behind the Pharmacological Application of Biochanin-A: A review.

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when administered for neurological disorders, diabetes, hyperlipidaemia, and other chronic diseases/disorders. Isoflavones are considered phenomenal due to their high efficiency in modifying the physiological functions of the human body. Biochanin-A is one among the prominent isoflavones found in soy (glycine max), red clover (Trifolium pratense), and alfalfa sprouts, etc., with proven potency in modulating vital cellular mechanisms in various diseases. It has been popular for ages among menopausal women in controlling symptoms. In view of the multi-targeted functions of biochanin-A, it is essential to summarize it's mechanism of action in various disorders. The safety and efficacy of biochanin-A needs to be established in clinical trials involving human subjects. Biochanin-A might be able to modify various systems of the human body like the cardiovascular system, CNS, respiratory system, etc. It has shown a remarkable effect on hormonal cancers and other cancers. Many types of research on biochanin-A, particularly in breast, lung, colon, prostate, and pancreatic cancers, have shown a positive impact. Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action. The diverse molecular mechanistic pathways involved in the pharmacological ability of biochanin-A indicate that it is a very promising molecule and can play a major impact in modifying several physiological functions.

Parkinson's disease - genetic cause.

PURPOSE OF REVIEW: Our knowledge of the genetic architecture underlying Parkinson's disease has vastly improved in the past quarter century. About 5-10% of all patients suffer from a monogenic form of Parkinson's disease. RECENT FINDINGS: Mutations in autosomal dominant genes (e.g. SNCA, LRRK2, VPS35) or autosomal recessive genes (e.g. PRKN, PINK1, DJ-1) can cause genetic Parkinson's disease. Recessive DNAJC6 mutations can present predominantly as atypical parkinsonism, but also rarely as typical Parkinson's disease. Majority of Parkinson's disease is genetically complex. Mutation in RIC3 , a chaperone of neuronal nicotinic acetylcholine receptor subunit α-7 (CHRNA7), provides strong evidence for the role of cholinergic pathway, for the first time, in cause of Parkinson's disease. X-linked parkinsonism manifests at a young age accompanied by many (atypical) features such as intellectual disability, spasticity, seizures, myoclonus, dystonia, and have poor response to levodopa. SUMMARY: This review article aims to provide a comprehensive overview on Parkinson's disease genetics. MAPT , which encodes the microtubule associated protein tau, TMEM230, LRP10, NUS1 and ARSA are the five new putative disease-causing genes in Parkinson's disease. The validation of novel genes and its association with Parkinson's disease remains extremely challenging, as genetically affected families are sparse and globally widespread. In the near future, genetic discoveries in Parkinson's disease will influence our ability to predict and prognosticate the disease, help in defining etiological subtypes that are critical in implementation of precision medicine.

Efficacy of Lornoxicam as a Pre-emptive Analgesic in Mandibular Third Molar Surgery - A Comparative Study.

Introduction: The most common complication following third molar surgery is pain. The purpose of the study is to determine the efficacy of lornoxicam as a preventive analgesic in patients undergoing surgical removal of impacted mandibular third molars. Materials and Methods: This study included 26 participants aged 18-28 years with bilateral symmetrical third molars. Group A, the control group, received lornoxicam 8 mg 1 h after surgery, whereas Group B, the study group, received lornoxicam 8 mg 1 h before surgery. All patients were evaluated for pain at the 1st, 2nd, 4th, 6th, 8th and 12th post-operative hours. The number of rescue analgesics taken within 24 h of the procedure, as well as the first occurrence of pain postoperatively, was recorded and analysed. Results: Using the Mann-Whitney U-test and Friedman's analysis, the resulting data were statistically analysed. When Group B was compared to Group A, there was a significant difference in pain reduction levels in the immediate post-operative hours. When compared to Group A, Group B had a lower need for rescue analgesics within the first 24 h postoperatively. Discussion: Following mandibular third molar surgery, pre-emptive use of lornoxicam is effective in reducing post-operative pain and reducing the need for rescue analgesic consumption.

Sexual health and safety of adolescents with intellectual disability: Challenges and concerns among special educators in India.

Sexual health education among adolescents with intellectual disabilities is an area of concern among parents and educators. Special educators play a vital role in teaching sexual health and safety to their students with disabilities. The present study explores special educators' concerns in teaching sexual health among adolescents with intellectual disabilities. The participants included 35 special educators working with adolescents with intellectual disabilities in India. Summative content analysis of the data collected using a semi-structured interview schedule highlights the neglect of the issues related to sexual health among adolescents with disabilities. Special educators reported the challenges in providing sexual health education. Teachers lacked skills in imparting sexual health education. Developmentally and culturally appropriate sexual health education can help adolescents with a disability learn healthy life skills. The paper emphasizes the need for professional support and training among special educators on sexual health education.

Pearls & Oy-sters: SCA21 Due to TMEM240 Variation Presenting as Myoclonus Dystonia Syndrome.

Spinocerebellar ataxia 21 due to TMEM240 disease-associated variation characteristically presents insidiously with a delay in language, motor, and social skill acquisition. The condition typically progresses to severe cognitive impairment. We report a patient with SCA21 who presented with myoclonus dystonia (M-D) syndrome and whose dystonia showed a modest response to levodopa. Affected family members (mother and sibling of the proband) also had a similar phenotype. Neuropsychology evaluation of the proband and afflicted family members revealed moderate impairments in attention, executive function, short-term and episodic memory, and marked impairments in planning, abstract reasoning, language, and visuospatial functions. Normal EEG, α-fetoprotein levels, and somatosensory evoked potentials helped to delineate SCA21 from other differential diagnoses. Motor impairment, pyramidal signs, and sensory impairment are usually absent in SCA21. This case highlights the importance of genetic testing in patients with M-D syndrome and supports a trial of levodopa for patients with dystonia from SCA21 due to TMEM240 variation.

Sirtuins as therapeutic targets for improving delayed wound healing in diabetes.

Sirtuins are a vast family of histone deacetylases, which are NAD+ dependent enzymes, consisting of seven members, namely SIRT 1, SIRT 6 and SIRT 7 located within the nucleus, SIRT 2 in the cytoplasm and SIRT 3, SIRT 4 and SIRT 5 in the mitochondria. They have vital roles in regulating various biological functions such as age-related metabolic disorders, inflammation, stress response, cardiovascular and neuronal functions. Delayed wound healing is one of the complication of diabetes, which can lead to lower limb amputation if not treated timely. SIRT 1, 3 and 6 are potent targets for diabetic wound healing. SIRT 1 deficiency reduces recruitment of fibroblasts, macrophages, mast cells, neutrophils to wound site and delays wound healing; negatively expressing MMP-9. The SIRT 1 mediated signalling pathway in diabetic wound healing is the SIRT 1-FOXO-c-Myc pathway. On the contrary, SIRT 3 deficiency impairs proliferation and migration of fibroblasts and SIRT 6 deficiency impairs wound closure rate and interrupts the vascular remodelling. This review focuses on the role of sirtuins in improving delayed wound healing in diabetes and its natural modulators with their specific functions towards healing diabetic wounds.

Pearls & Oy-sters: Grisel Syndrome Presenting as Pseudodystonia: A Twist in the Neck.

Pseudodystonia is a term that describes abnormal postures, repetitive movements, or both, where clinical analysis, imaging, laboratory, or electrophysiologic investigations indicate that these movements are not consistent with dystonia. Grisel syndrome (GS), characterized by rotatory subluxation of the atlantoaxial joint (AAJ) due to nontraumatic causes, is a cause of pseudodystonia. GS is seen in children less than 12 years of age and should be suspected in patients with acute onset of painful torticollis. We report 2 girls, aged 9 and 6 years, who developed painful torticollis following upper respiratory tract infection. They were thought to have cervical dystonia and referred to a movement disorder specialist for botulinum neurotoxin therapy (BoNT). MRI of the cervical spine showed type I and type II rotary AAJ subluxation, respectively, which confirmed the diagnosis of GS. Short tau inversion recovery hyperintensity was noted suggesting AAJ edema without any bone erosion or cord compression. Abruptness of onset, presence of severe pain, resistance to passive neck movements, fixed postures present equally in rest and action, absence of sensory trick, and persistence in sleep favor pseudodystonia. Both subjects improved with conservative treatment, which included temporary immobilization of the cervical spine and anti-inflammatory drugs. Early identification and treatment is imperative to avoid neurologic complications, like high cervical compressive myelopathy, which can lead to quadriplegia and respiratory distress. Prominent sternocleidomastoid contraction ipsilateral to the rotated chin helps to clinically identify GS.

Emergency Department and Urgent Care Medical Malpractice Claims 2001-15.

INTRODUCTION: This study reviews malpractice, also called medical professional liability (MPL), claims involving adult patients cared for in emergency departments (ED) and urgent care settings. METHODS: We conducted a retrospective review of closed MPL claims of adults over 18 years, from the Medical Professional Liability Association's Data Sharing Project database from 2001-2015, identifying 6,779 closed claims. Data included the total amount, origin, top medical specialties named, chief medical factors, top medical conditions, severity of injury, resolution, average indemnity, and defense costs of closed claims. RESULTS: Of 6,779 closed claims, 65.9% were dropped, withdrawn, or dismissed. Another 22.8% of claims settled for an average indemnity of $297,709. Of the 515 (7.6%) cases that went to trial, juries returned verdicts for the defendant in 92.6% of cases (477/515). The remaining 7.4% of cases (38/515) were jury verdicts for the plaintiff, with an average indemnity of $816,909. The most common resulting medical condition cited in paid claims was cardiac or cardiorespiratory arrest (10.4%). Error in diagnosis was the most common chief medical error cited in closed claims. Death was the most common level of severity listed in closed (38.5%) and paid (42.8%) claims. Claims reporting major permanent injury had the highest paid-to-closed ratio, and those reporting grave injury had the highest average indemnity of $686,239. CONCLUSION: This retrospective review updates the body of knowledge surrounding medical professional liability and represents the most recent analysis of claims in emergency medicine. As the majority of emergency providers will be named in a MPL claim during their career, it is essential to have a better understanding of the most common factors resulting in MPL claims.

"FLAMES: A novel burning entity in MOG IgG associated disease".

FLAMES is a new clinico-radiological sub entity of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD). FLAMES is characterized by fluid attenuated inversion recovery (FLAIR) imaging showing hyperintense cortical lesions, in MOG associated Encephalitis with Seizures. MOGAD usually presents with optic neuritis, myelitis or acute disseminated encephalomyelitis and such rare focal cortical encephalitis like presentation can be mistaken as due to viral aetiology. FLAMES can present with unilateral or bilateral cortical encephalitis and we report a case where magnetic resonance angiography, susceptibility weighted imaging and perfusion studies were done and the utility of these additional imaging markers in diagnosing FLAMES is discussed.

Pediatric Malpractice Claims in the Emergency Department and Urgent Care Settings From 2001 to 2015.

OBJECTIVES: This study aimed to provide an assessment of medical malpractice claims involving pediatric patients cared for in emergency department and urgent care settings. METHODS: We performed a retrospective review of all closed malpractice claims involving children (0-17 years old) originating from emergency department or urgent care centers from the Physician Insurers Association of America's Data Sharing Project database for a 15-year period (2001-2015). Reported data collected include medical specialty involved, medical diagnoses, chief medical factors, severity of resulting injury, claim disposition, average indemnity, and average defense costs. RESULTS: A total of 728 closed claims in pediatric emergency care settings were reviewed. Money was paid to the claimant in 30% of cases (220/728), with a total of US $70.3 million (average $319,513) paid to patients or families during the 15-year period. The most common resulting medical conditions were cardiac or cardiorespiratory arrest, appendicitis, and disorder of male genital organs. Error in diagnosis was the most common chief medical factor (41%), whereas those that involved failure or delay in admission to the hospital, which was the eighth most common chief medical factor, resulted in the highest average indemnity. Of the 728 closed claims, 220 involved a patient death (30%), but claims involving major permanent injury more often resulted in a payment. Of the 57 cases that went to trial, verdicts favored the physician in 47 cases (82%). CONCLUSIONS: Cardiac conditions, appendicitis, and disorder of the male genital organs are the most common medical conditions, and error in diagnosis is the most common chief medical factor in pediatric emergency care malpractice suits. It is important for providers practicing in these settings to be familiar with the common diagnoses and chief medical factors involved in these claims.

Radionuclide activity concentration in soil, granites and water in a fluorosis endemic area of India: An oral health perspective.

BACKGROUND: The idea that hilly areas have a high background radiation which in turn is linked to dental fluorosis is widely held by many in India. There is little evidence to confirm this. OBJECTIVE: The study aimed to investigate the level of environmental radionuclide in order to determine any interrelationship between radionuclide and dental fluorosis in Pavagada, a fluorosis endemic area of Karnataka, India. METHODS: Gamma radionuclides (Th232, Ra226 and K40) were determined by high purity germanium (HPGe) gamma-ray spectrometer (Bq Kg-1) using a 50% relative efficiency p-type broad energy HPGe detector. Fluoride was estimated using fluoride Ion-selective electrode (ISE). Fluorosis was assessed using WHO diagnostic criteria. RESULTS: The average mean +_SD activity concentration in soil for K40 was detected between 416.6 ± 9.3 and 769.1 ± 15.0. Th232 was estimated between 13.6 ± 0.6 and 57.6 ± 1.3; and Ra226 was found between 6.4 ± 0.4 and 21.6 ± 0.7. Similarly, the mean activity concentration detected (Bq kg-1) in granite for K40 ranged between 259.8 ± 6.9 and 1608.5 ± 26.9. The activity concentration of Th232 ranged between 26.4 ± 0.8 and 57.6 ± 1.3: and that of Ra226 was between 6.6 ± 0.3 and 21.6 ± 07. Drinking water contains 2.98 ppm of fluoride. Dental fluorosis was diagnosed as mild to moderate. CONCLUSION: The radionuclide activity in water, soil and granites were below the detection limit. Hence, the study revealed no association of fluorosis and radionuclide level in Pavagada, Karnataka, India. This helps resolve an ambiguity.

Treatable cerebellar ataxias.

Cerebellar ataxic syndrome is a heterogenous class of disorders which can result from a miscellany of causes- genetic or acquired. There are a few metabolic, immune mediated, inflammatory and hereditary causes of ataxia which can be diagnosed from the gamut of possibilities, offering great relief to the ailing patient, their family and the treating physician. A pragmatic algorithm for diagnosing treatable causes of ataxia includes a thorough clinical history, meticulous examination for associated signs and an investigative mind to clinch the diagnosis. With novel diagnostic techniques and targeted therapies, early diagnosis and treatment can lead to favourable outcomes. In this review, diseases presenting predominantly as cerebellar ataxia and are treatable by targeted therapies are discussed.

Factors influencing fluoride release in atraumatic restorative treatment (ART) materials: A review.

OBJECTIVES: The purpose of this article was to review the fluoride release and uptake ability of some restorative materials which are used for minimally invasive procedures. METHODS: The literature search on published researches and review articles were carried out by using PubMed, Trip and Cochrane library databases. The search terms used were fluoride, restorative materials, atraumatic restorative treatment or ART, glass ionomer or GIC, resin modified glass ionomer cement or RMGIC. The articles included were between 2000 and 2015. CONCLUSION: Fluoride release varies with m factors including the type of restorative materials used and also the media in which it is stored. Fluoride uptake is dependent on the type of the cement and the availability of fluoride including fluoride releasing capacity in the material.

Review of Ophthalmology Medical Professional Liability Claims in the United States from 2006 through 2015.

PURPOSE: To describe characteristics of closed medical professional liability (MPL) claims against ophthalmologists in the United States. DESIGN: Retrospective analysis of MPL claims from 2006-2015. Data were obtained from the Physician Insurers Association of America (PIAA) Data Sharing Project (DSP). Comparison was made between ophthalmology and all healthcare specialties for physician demographics, prevalence and costs associated with closed claims, and resolution of claims. The most prevalent chief medical factor, presenting medical condition, operative procedure, outcomes, and resolution of ophthalmology claims were compared between the 2006-2010 and 2011-2015 periods. PARTICIPANTS: From 2006-2015, 90 743 MPL claims were closed: 2.6% (2325/90 743) of closed claims and 2.2% (564/24 670) of all paid claims were against ophthalmologists. METHODS: Retrospective analysis of MPL claims captured by the PIAA DSP over a 10-year period. MAIN OUTCOME MEASURES: Subspecialty pertaining to the claim, number of claims closed and paid, indemnity paid, allocated loss adjustment expenses, chief medical factor, presenting medical condition, operative procedure, outcome, and resolution. RESULTS: Only 24% of closed claims against ophthalmologists resulted in payment. Two-thirds were dropped, withdrawn, or dismissed. Ninety percent of claims that received a verdict were favorable toward the ophthalmologist. Cataract and cornea surgeries were the most prevalent and most costly operative procedures, accounting for 50% of all claims and $47 641 376 and $32 570 148 in total paid indemnity, respectively. Average indemnity was higher for corneal procedures ($304 476) than vitreoretinal procedures ($270 141) or oculoplastic procedures on the eyelid ($222 471) or orbit and eyeball ($183 467). The prevalence and cost of claims related to endophthalmitis declined from 2006-2010 (n = 38/1160 [3.3%]; average indemnity, $516 875) period to the 2011-2015 (n = 26/1165 [2.2%]; average indemnity, $247 083) period. Average indemnity paid ($280 227 vs. $335 578) and amount spent on legal defense ($41 450 vs. $46 391) was slightly lower among ophthalmologists compared with all healthcare specialties, respectively. CONCLUSIONS: Ophthalmology has a relatively low number of malpractice claims reported compared with other healthcare specialties and shows less spending on average indemnity and defense. Further studies are needed to investigate the reasons for the higher prevalence of claims related to cataract and corneal surgeries and the higher average indemnity paid for corneal procedures relative to vitreoretinal or oculoplastic procedures.

Prevalence and risk factors for scrub typhus in South India.

OBJECTIVE: To determine the prevalence and risk factors of scrub typhus in Tamil Nadu, South India. METHODS: We performed a clustered seroprevalence study of the areas around Vellore. All participants completed a risk factor survey, with seropositive and seronegative participants acting as cases and controls, respectively, in a risk factor analysis. After univariate analysis, variables found to be significant underwent multivariate analysis. RESULTS: Of 721 people participating in this study, 31.8% tested seropositive. By univariate analysis, after accounting for clustering, having a house that was clustered with other houses, having a fewer rooms in a house, having fewer people living in a household, defecating outside, female sex, age >60 years, shorter height, lower weight, smaller body mass index and smaller mid-upper arm circumference were found to be significantly associated with seropositivity. After multivariate regression modelling, living in a house clustered with other houses, female sex and age >60 years were significantly associated with scrub typhus exposure. CONCLUSIONS: Overall, scrub typhus is much more common than previously thought. Previously described individual environmental and habitual risk factors seem to have less importance in South India, perhaps because of the overall scrub typhus-conducive nature of the environment in this region.

Characteristics of Orthopaedic Malpractice Claims of Pediatric and Adult Patients in Private Practice.

BACKGROUND: Medical liability exposure varies based on scope of practice, patient demographics, and location of practice. There is a generally held belief that treatment of pediatric patients increases one's medicolegal risk. We examined a large national database of orthopaedic malpractice claims to determine if pediatric malpractice claims were associated with a less favorable medicolegal outcome compared with adults. METHODS: Physician Insurers Association of America is an association of medical liability insurance carriers providing liability coverage for 60% of private practice physicians in the United States. The Physician Insurers Association of America data registry of closed medical liability claims was examined, including all orthopaedic claims between 1985 and 2012 in this review. Claims were categorized based on the age of the claimant (pediatric: less than 21 y, adult: 21 y or older). These groups were compared based on percentage of claims resulting in payment, indemnity paid, and years between occurrence of incident and filing of claim. In addition, the top 10 most prevalent claims were identified and compared between groups. RESULTS: A total of 25,702 closed orthopaedic claims were included. Pediatric claims accounted for 13% of the data. The average time from incident to claim filing was 1.92 years for pediatrics and 1.59 years for adults. Pediatric claims resulted in a higher percent of payment (33% vs. 30%) and average indemnity paid ($189,732 vs. $180,171) compared with adults. Five of the top 10 conditions resulting in a claim in each group were the same. Comparing these 5 conditions, in general there were minimal differences in the average time to claim filing between the groups, but larger average indemnity paid in the pediatric group. CONCLUSIONS: There appear to be moderate differences in outcomes of orthopaedic malpractice claims between adult and pediatric patients. The longer statute of limitations associated with pediatric claims does not appear to portend a less favorable medicolegal outcome or excessively longer time to claims filing for pediatric patients.