Correlation Between Serum and CSF Concentrations of Midazolam and 1-Hydroxy-Midazolam in Critically Ill Neurosurgical Patients.

BACKGROUND: Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized. OBJECTIVE: This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation. METHODS: Adults in the neurosurgical intensive care unit (ICU) with external ventricular drains receiving MZ via continuous infusion were prospectively studied. Serum and CSF samples were obtained 12-24 h and 72-96 h after initiation, and concentrations were determined in duplicate by high-performance liquid chromatography with tandem mass spectrometry. Bivariate correlation analyses used Pearson coefficient. RESULTS: A total of 31 serum and CSF samples were obtained from 18 subjects. At sampling, mean MZ infusion rate was 3.9 ± 4.4 mg/h, and previous 12-h cumulative dose was 51.4 ± 78.2 mg. Mean concentrations of MZ and 1-OH-MZ in serum and CSF were similar between timepoints. Similarly, ratios of 1-OH-MZ to MZ in serum and CSF remained stable over time. Serum MZ (126.2 ± 89.3 ng/mL) showed moderate correlation (r2 = 0.68, P < 0.001) with serum 1-OH-MZ (17.7 ± 17.6 ng/mL) but not CSF MZ (3.9 ± 2.5 ng/mL; r2 = 0.24, P = 0.005) or CSF 1-OH-MZ (2.5 ± 0.6 ng/mL; r2 = 0.47, P = 0.30). CSF MZ did not correlate with CSF 1-OH-MZ (r2 = 0.003, P < 0.001). Mean serum ratio of 1-OH-MZ to MZ (0.14 ± 0.2 ng/mL) did not correlate with CSF ratio (1.06 ± 0.83 ng/mL; r2 = 0.06, P = 0.19). Concentrations and ratios were unrelated to MZ infusion rate or 12-h cumulative dose. Sedation was weakly correlated with CSF 1-OH-MZ, but not with serum MZ, serum 1-OH-MZ, or CSF MZ. CONCLUSION AND RELEVANCE: Continuous infusions of MZ result in measurable concentrations of MZ and 1-OH-MZ in CSF; however, CSF concentrations of MZ and 1-OH-MZ poorly represent serum concentrations or dosages. Accumulation of MZ and 1-OH-MZ in serum or CSF over time was not evident. Concentrations of MZ and 1-OH-MZ do not predict sedation levels, reinforcing that pharmacodynamic assessments are warranted.

Frequency and Risk Factors Association with Metabolic Syndrome among the Hypertensive Patients in Jashore, Bangladesh.

Metabolic Syndrome (METS) plays a pivotal role in the development of diabetes mellitus, coronary artery diseases and stroke. Due to the scarcity of data in this issue, this study aims to assess the frequency and risk factors association of METS among the hypertensive patients. This cross-sectional study recruited 667 eligible hypertensive patients aged between 20 and 70 years using non-probability purposive sampling method conducted from 1st January 2019 to 30th June 2019. Hypertensive patients with the known history of diabetes, thyroid, renal, cardiac, or hepatic disease, Cushing syndrome or malignancy and secondary causes of obesity, confirmed pregnancy, bed ridden, taking lipid lowering drugs or drugs that affect lipid and glucose metabolism were excluded from the study. METS among the hypertensive patients (DE novo or established hypertensive patients) of this study was demonstrated by NCEP-ATPIII (National Cholesterol Education Program-Adult Treatment Panel III) criteria having two or more of the following points [a) increased waist circumference ≥102cm in men and ≥88cm in women, b) hypertriglyceridemia: ≥150mg/dl, c) reduced High density lipoprotein cholesterol (HDL-C) <40mg/dL (1.04mmol/L) in men and <50mg/dL (1.29mmol/L) in women, d) high fasting blood glucose: 110mg/dl]. Significantly high frequency (69.9%, p<0.001) of METS was found with a significant female preponderance (52.5%, p<0.001) where the mean age of the study population was 48±11 years. Sex (p<0.001), education (p=0.041), occupation (p<0.001), Body mass index (BMI) (p<0.001) and hypertensive status (p=0.002) showed a highly significant role in the development of METS. Following binary logistic regression analysis after adjusting for confounders, the female sex was 17 times higher than the male [Adjusted odd ratio (AOR) =16.96, 95% CI=4.91-58.66, p<0.001)], obesity 4 times higher than non-obese [BMI (obese AOR=4.24, 95% CI=2.55-7.98, p<0.001)], hypertensive status [established hypertension two times higher than de novo (de-novo AOR=0.60, 95% CI=0.037-0.97, p=0.037)] were significant and independent predictors of METS. Significantly high BMI (27.7±4.2 and p<0.001), high waist circumference (60.4%, p<0.001) and hyper tri-glyceridaemia and reduced HDL (46.0%, p<0.001 and 51.3%, p<0.001) were found in the subjects with METS. In conclusion, high frequency of METS among the hypertensive patients was found in Jashore, Bangladesh with significant risk factors related to female sex, education, occupation, BMI and hypertensive status. So, a holistic evaluation of metabolic components among the hypertensive patients may reduce premature cardiovascular morbidity and mortality.

Validation of a German version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID-G) in Down's syndrome.

BACKGROUND: People with Down's syndrome (DS) are at high risk of developing Alzheimer dementia (DS-AD) due to a triplication of the amyloid precursor protein gene. While several tools to diagnose and screen for DS-AD, such as the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID), are available in English, validated German versions of such instruments are scarce. METHODS: A German version of the DSQIID questionnaire (DSQIID-G) was completed by caregivers before attending our specialist outpatient department for DS-AD. All participants were assessed blind to DSQIID-G scoring using clinical and neuropsychological examinations, including the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). ICD-10 and amyloid/tau/neurodegeneration (A/T/N) criteria were applied to detect and categorise cognitive decline. RESULTS: Of 86 participants, 43 (50%) showed evidence of cognitive decline. A definite diagnosis of DS-AD was reached in 17 (19.8%) and mild cognitive impairment in seven (8.3%) participants. Secondary causes of cognitive decline were determined among 13 (15.1%) participants, and in six (7%) cases, the diagnosis remained unclassifiable due to co-morbidities. Compared with cognitively stable individuals, participants with cognitive decline (n = 43) displayed higher DSQIID-G total scores [median (range): 3 (0-21) vs. 19 (0-48), P < 0.001]. A total score of >7 provided a sensitivity of 0.94 against a specificity of 0.76, to discriminate DS-AD and participants without cognitive decline according to ROC analysis. The convergent validity against the CAMDEX-DS interview score was good (r = 0.74), and split-half reliability (r = 0.96), internal consistency (Cronbach's α r = 0.96), test-retest reliability (r = 0.88) (n = 25) and interrater reliability (r = 0.81) (n = 31) were excellent. CONCLUSIONS: The DSQIID-G showed excellent psychometric properties, including concurrent and internal validity and reliability. The cut-off value for screening was lower than in the original English validation study. For a screening instrument like DSQIID-G, a lower cut-off is preferable to increase case detection.

Bayesian approach for evaluation of lactation curve in cross bred cattle based on monthly and bimonthly test day milk yield.

In field progeny testing program milk recording at monthly or bimonthly intervals and prediction of first lactation 305-day milk yield (FL305DMY) from these test day yields have been adapted as an alternative to daily milk recording. Wood's incomplete gamma function is the one of the commonly used nonlinear lactation curve model. In recent years Bayesian approach of fitting nonlinear biological models is gaining attention among researchers. In this study Wood's incomplete gamma function was fitted using Bayesian approach using monthly (MTDY) and bimonthly test day (BTDY) yields. The lactation curve parameters thus obtained were used for prediction of FL305DMY. Efficiency of prediction based on monthly and bimonthly test day milk yield were compared using error of prediction. It was found to be 5.78% and 7.59% as root mean square error (RMSE) based on MTDY and BTDY respectively.The Breeding values of 97 Karan Fries sires were estimated using BLUP-AM based on actual and predicted FL305DMY thus obtained. The RMSE was calculated as the difference between estimated breeding values based on actual and predicted yield. It was found that RMSE calculated based on MTDY showed only a marginal superiority of 0.79% over BTDY and showed high degree of correlation with actual yield. Therefore, recording at bimonthly intervals could be an economical alternative without compromising the efficiency.

Obstructive sleep apnea induced bilateral tonic- clonic seizure of unknown origin: A case series of a novel association.

Background: Obstructive sleep apnea is a highly prevalent disorder, characterized by recurrent events of upper airway obstruction during sleep and associated with recurrent cycles of desaturation and re-oxygenation, sympathetic hyperactivity, and intra-thoracic pressure fluctuations, resulting in fragmentation of sleep and subsequent daytime fatigue with excessive sleepiness. Obstructive sleep apnea-induced bilateral tonic-clonic seizures are unheard of. We aimed to report 3 patients with previously undiagnosed obstructive sleep apnea who presented to the emergency department with new onset bilateral tonic-clonic seizure without any evidential neurological or metabolic cause. Methods: Patient data were obtained from medical records from the Department of Internal Medicine, IPGMER and SSKM Hospital, Kolkata, and Belle Vue Clinic, Kolkata, India. Results: Three male patients (67, 58, and 44 years old) presented with bilateral tonic-clonic seizure disorder without any underlying cause of seizures after rigorous investigations except for moderate to severe obstructive sleep apnea on polysomnography. All 2 patients were seizure-free after being treated with levetiracetam, chronic continuous positive airway pressure therapy in 2, and only continuous positive airway pressure in the other. The patients remained seizure-free on continuous positive airway pressure, even when levetiracetam was withdrawn, suggesting obstructive sleep apnea's causality in their new-onset acute seizures. Conclusion: Although further investigation is required to clarify this association, underlying obstructive sleep apnea should be ruled out in patients with a first-ever bilateral tonic-clonic seizure. Whether or not continuous positive airway pressure alone could effectively treat hypoxia and deranged cortical excitability, which may lead to seizures in cases with longstanding obstructive sleep apnea, is yet to be explored.

Introducción: La apnea obstructiva del sueño es una enfermedad con una alta prevalencia que se caracteriza por episodios recurrentes de obstrucción de las vías respiratorias altas durante el sueño, lo que conlleva ciclos repetidos de hipoxia y reoxigenación, hiperactividad simpática y fluctuaciones en la presión intratorácica. Todos estos procesos dan lugar a una fragmentación del sueño, lo que provoca fatiga diurna y somnolencia excesiva. Las crisis tónico-clónicas bilaterales inducidas por apnea obstructiva del sueño son poco conocidas. Presentamos los casos de tres pacientes con apnea obstructiva del sueño sin diagnosticar previamente que acudieron a urgencias por crisis tónico-clónicas de nueva aparición sin causa neurológica o metabólica aparente. Métodos: Los datos de nuestros pacientes se recogieron de los historiales médicos del servicio de Medicina Interna del Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital y de la Belle Vue Clinic, ambos en Kolkata (India). Resultados: Tres pacientes varones de 67, 58 y 44 años de edad presentaron convulsiones tónico-clónicas bilaterales sin causa identificada tras examen riguroso, exceptuando una apnea obstructiva del sueño de gravedad moderada a grave observada en la polisomnografía. Los tres pacientes recibieron tratamiento con levetiracetam durante el ingreso; al alta, se pautó tratamiento crónico con presión positiva continua de las vías respiratorias más levetiracetam en dos pacientes, y en el tercero solo presión positiva continua de las vías respiratorias. Ninguno presentó nuevas crisis tras la retirada de levetiracetam, lo que sugiere que la causa de las convulsiones era la apnea obstructiva del sueño. Conclusión: Aunque es necesario realizar más estudios para aclarar esta asociación, debemos descartar la apnea obstructiva del sueño en pacientes con crisis tónico-clónicas bilaterales de nueva aparición. Queda aún por determinar si la presión positiva continua podría tratar de forma efectiva la hipoxia y las alteraciones en la excitabilidad cortical, que podrían provocar crisis en casos de apnea obstructiva del sueño de larga evolución.

Training support workers about the overmedication of people with intellectual disabilities: an Australian pre-post pilot study.

BACKGROUND: There is evidence that psychotropic medications are overprescribed and overused to manage behaviours of concern for people with intellectual disabilities. Disability support workers and support staff lack education and training on the administration and safety of psychotropic medication use. This study aimed to test the applicability and preliminary efficacy of SPECTROM, an education programme developed in the UK, in an Australian context. METHODS: The training comprises two parts: Module 1 encompasses psychotropic medications, their use and side effects. Module 2 focuses on non-pharmacological interventions for supporting people with behaviours of concern. Thirty-three participants attended the training course and completed pre-training and post-training surveys on the Psychotropic Knowledge Questionnaire and Management of Aggression and Violence Attitude Scale-Revised at four time points: pre-training, 2 weeks, 3 months and 5 months post-training. RESULTS: Psychotropic Knowledge Questionnaire scores showed statistically significant post-training improvement at all post-training time points (P < 0.05). Management of Aggression and Violence Attitude Scale-Revised scores were high at pre-training and did not change significantly at any of the post-training survey time points. A 2-week post-training feedback questionnaire reported 80% agreement that the training programme was appropriate, useful and valid. Only 36% of participants completed questionnaires at all time points. CONCLUSIONS: SPECTROM training increased staff knowledge of psychotropic medications, yet loss of participants was high. Further refinement of the applicability of the training for the Australian context and evaluation of the feasibility of implementation, clinical and cost-effectiveness of the programme are required.

Psychological Assessment of Health-Care Workers Working during COVID-19 Pandemic Condition in Bangladesh.

The study was aimed to assess the psychological aspects and relevant factors of the health-care workers (HCWs) working in COVID 19 pandemic condition in Bangladesh. This online cross-sectional survey was conducted from different tertiary, secondary and primary hospitals in Bangladesh. Eligible 638 HCWs who were directly involved in the caring of confirmed or suspected COVID-19 patients were recruited in this study. The mental health was assessed by the Patient Health Questionnare-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Athens Insomnia Scale (AIS). High frequency of depression 536(84.0%), anxiety 386(60.5%) and insomnia 302(47.3%) was found among the HCWs, which were significantly higher in physicians (p<0.001) than nurses. Moderate to severe depression was significantly higher in female, whereas minimal to mild depression was significant in male HCWs (p=0.014). Symptoms of depression (p<0.001), anxiety (p<0.001) and insomnia (p=0.004) were significantly higher among the HCWs of primary and secondary compared to the tertiary level. The HCWs developed psychological trauma due to family health (45.3%) and contagious disease property (66.6%). After adjusting confounders, multivariable logistic regression analysis showed that physicians and HCWs of secondary hospital had significant symptoms of severe depression (OR=2.95, 95% CI=0.50-17.24; p<0.001), anxiety (OR=2.64, 95% CI=0.80-8.72; p<0.001) and insomnia (OR=2.67, 95% CI=1.23-5.84; p=0.018); whereas female HCWs had more risk of developing symptoms of severe insomnia (OR= 1.84; 95% CI=1.23-2.75; p=0.003). High rate of depression, anxiety and insomnia was found among HCWs working in the COVID-19 pandemic condition in this survey.

Bis[2-(Methacryloyloxy) Ethyl] Phosphate as a Primer for Enamel and Dentine.

Dental resin composites are commonly used in the restorative management of teeth via adhesive bonding, which has evolved significantly over the past few decades. Although current self-etch bonding systems decrease the number of clinical steps, the acidic functional monomers employed exhibit a limited extent of demineralization of enamel in comparison to phosphoric acid etchants, and the resultant superficial ionic interactions are prone to hydrolysis. This study evaluates the etching of primers constituted with bis[2-(methacryloyloxy) ethyl] phosphate (BMEP) of dental hard tissue, interfacial characteristics, and inhibition of endogenous enzymes. We examine the incorporation of 2 concentrations of BMEP in the formulation of experimental primers used with a hydrophobic adhesive to constitute a 2-step self-etching bonding system and compare to a commercial 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP)-containing system. The interaction of the primer with enamel and dentine was characterized using scanning electron, confocal laser scanning, and Raman microscopy while the polymerization reaction between the BMEP primers and hydroxyapatite was evaluated by Fourier-transform infrared spectroscopy. The inhibitory effect against matrix metalloproteinase (MMP) enzymes of these primers was studied and percentage of inhibition analyzed using 1-way analysis of variance and Tukey's post hoc test (P < 0.05). Results of the scanning electron microscopy micrographs demonstrated potent etching of both enamel and dentine with the formation of longer resin tags with BMEP primers compared to the 10-MDP-based system. The BMEP polymerized on interaction with pure hydroxyapatite in the dark, while the 10-MDP primer exhibited the formation of salts. Furthermore, BMEP primers were able to inhibit MMP activity in a dose-dependent manner. BMEP could be used as a self-etching primer on enamel and dentine, and the high degree of polymerization in the presence of hydroxyapatite can contribute to an increased quality of the resin polymer network, prompting resistance to gelatinolytic and collagenolytic degradation.

A laboratory study to assess the formation of effluent volatile compounds and disinfection by-products during chemomechanical preparation of infected root canals and application of activated carbon for their removal.

AIM: To assess in a laboratory setting using extracted teeth the formation of volatile compounds (VOCs) and disinfection by-products (DBPs) in effluent aliquots, during chemomechanical preparation of artificially infected root canal specimens, and determine the role of silver-impregnated activated carbon (Ag-AC) in their removal. METHODOLOGY: Single-rooted human teeth were decoronated to obtain 15 mm-long root specimens and a nutrient-stressed multispecies biofilm was grown in the root canals. Specimens were randomly assigned into three groups [Group 1; instrumentation with rotary files and irrigation with sterile saline, Groups 2 and 3; instrumentation with rotary files and irrigation with 2.5% NaOCl and 17% EDTA]. A portable medical suction device was used to collect the effluent aliquots during root canal irrigation. In Groups 1 and 2, the reaction products of the collected effluents were analysed by selected ion flow tube mass spectrometry (SIFT-MS). The effluents from Group 3 were treated with Ag-AC prior to SIFT-MS analysis, to assess the removal capacity of Ag-AC against the reaction products. The synthesis of Ag-AC was characterized with scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS). Two-way analysis of variance (anova) with post hoc Tukey tests was used for data analysis and determination of a significant difference (P < 0.05). RESULTS: In Group 1, effluent VOCs and DBPs were detectable at very low levels. In Group 2, the collected effluent aliquots released high concentrations of methanol, propanol, ammonia, chloroform and formaldehyde, which were significantly greater compared to Group 1 (P < 0.001). SEM/EDS analysis confirmed impregnation of Ag within the AC matrix. The treatment of effluent aliquots with Ag-AC (Group 3) resulted in a significant reduction in concentrations of acetone, acetic acid, propanol, acetaldehyde, acetonitrile and chloroform, compared to Group 2 (P < 0.001). The concentration levels of ethanol, methanol, ammonia and formaldehyde remained unaffected (P > 0.05). CONCLUSIONS: In this laboratory setting using extracted human teeth, the chemomechanical preparation of artificially infected root canals resulted in the formation of toxic VOCs and DBPs as effluent suspensions. Their release during aspiration with dental suction indicates that potential environmental hazards should be investigated. The use of silver-impregnated activated carbon had potential for the point-of-use treatment of post-irrigation effluent aliquots.

Adverse childhood experiences: association with physical and mental health conditions among older adults in Bhutan.

OBJECTIVES: Adverse childhood experiences (ACEs) are events stressful, traumatic, and related to the development of a wide range of health conditions throughout the person's lifespan. This study explored the relationship between ACEs and health conditions among older adults in Bhutan. STUDY DESIGN: Cross-sectional survey. METHODS: Older adults aged 60-101 years (n = 337) completed a face-to-face interview in a convenient community setting in the four major towns of Bhutan. Measurements included the modified World Health Organization Adverse Childhood Experiences International Questionnaire and the checklist of chronic health conditions. RESULTS: Commonest ACEs reported by the sample were related to the contribution of physical labour in childhood (n = 284 [84.3%]) and witnessing of community violence (n = 185 [54.9%]). Assuming an adult role while still a child highly co-occur with other forms of ACEs. Compared to 0-2 ACEs, participants with ≥7 ACEs had the higher odds of reporting lung disease (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.03-4.49), visual impairment (OR = 2.38, 95%CI: 1.16-4.85), insomnia (OR = 2.35, 95%CI: 1.11-4.98), and memory decline (OR = 2.30, 95%CI: 1.10-4.78) by twofold and high blood pressure by threefold (OR = 3.21, 95%CI: 1.39-7.38). Overall, the odds of self-rated poor health conditions among those ≥7 ACEs compared to 0-2 ACEs was high by almost twofold (OR = 1.97; 95%CI: 1.04-3.73). CONCLUSIONS: The influence of ACEs on health conditions persisted into late adulthood, and older people in Bhutan have had a complex variety of chronic health conditions implicating greater demand on the free healthcare system in Bhutan. ACEs prevention is critical to promote better health for a country like Bhutan, where the healthcare services are provided free of cost to its citizens.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Ex vivo detection and quantification of apically extruded volatile compounds and disinfection by-products by SIFT-MS, during chemomechanical preparation of infected root canals.

OBJECTIVES: To assess the release and apical extrusion of toxic volatile compounds and disinfection by-products during instrumentation and irrigation of artificially infected root canal specimens, with sodium hypochlorite and ethylene diamine tetra acetic acid. METHODS: Forty-two single-rooted human teeth were decoronated to obtain 15mm-long root specimens and working length was determined 1mm short of root apex. All specimens were initially preflared, to create sufficient conical space for the development of a nutrient-stressed multispecies biofilm. The specimens were randomly assigned into three groups [Group 1; no endodontic intervention, Group 2; instrumentation with rotary files and irrigation with sterile saline, Group 3; instrumentation with rotary files and irrigation with 2.5% sodium hypochlorite (NaOCl) and 17% ethylene diamine tetra acetic acid (EDTA)]. A customised experimental model apparatus was fabricated for each specimen. The apical root third was inserted in a glass vial filled with sterile ultrapure water, to simulate high-compliance periradicular space. The reaction products of the aliquots obtained from the glass vials were analysed in real time, by selected ion flow tube mass spectrometry (SIFT-MS) in triplicates. Two-way analysis of variance (ANOVA) with post hoc Tukey tests were used for data analysis. The level of statistical significance was set at P<0.05. RESULTS: The group of teeth that were not subjected to endodontic intervention did not show any volatile compounds (VOCs) or disinfection by products (DBPs) whilst instrumentation and irrigation of root canals (Groups 2 and 3) resulted in the apical extrusion of VOCs and DBPs. In Group 3, the aliquots obtained from periradicular space released high concentrations of methanol, propanol, ammonia, chloroform, together with unexpected higher levels of formaldehyde, which were statistically significant compared to Group 2 (P<0.05). SIGNIFICANCE: The mechanical preparation and irrigation of artificially infected root canals with rotary files, 2.5% NaOCl and 17% EDTA resulted in the formation of toxic VOCs and DBPs in a water-closed periradicular space. The chemical interaction of NaOCl and EDTA resulted in the generation of high concentrations of formaldehyde. The formation of chloroform and formaldehyde indicate that risk assessment of the potential hazards to health should be carried out.

High dose Nitrate ingestion does not improve 40 km cycling time trial performance in trained cyclists.

This study evaluated the chronic effects of nitrate (NO3-) ingestion over three days, on 40 km TT performance in 11trained cyclists (VO2max: 60.8 ± 7.4 ml.kg-1.min-1; age: 36 ± 9 years; height: 1.80 ± 0.06 m; body mass: 87.2 ± 12.0 kg). Utilising a double-blind randomised cross-over design, participants completed three 40 km TT on a Velotron® ergometer following the ingestion of either a 140 ml of "BEET It sport®" NO3- shot containing 12.8 mmol or 800 mg of NO3-, a placebo drink or nothing (control). Performance, oxygen consumption (VO2), blood bicarbonate (HCO3-), pH and lactate (BLa) and ratings of perceived exertion (RPE) were measured every 10 km throughout the TT. The present findings show that NO3- ingestion had no effect on TT performance (NO3-: 4098.0 ± 209.8 vs. Placebo: 4161.9 ± 263.3 s, p = 0.296, ES = 0.11), or VO2 (p = 0.253, ES = 0.13). Similarly, blood lactate and RPE were also unaffected by the experimental conditions (p = 0.522, ES = 0.06; p = 0.085, ES = 0.30) respectively. Therefore, these results suggest that a high dose of NO3- over three days has limited efficacy as an ergogenic aid for 40 km TT cycling performance in trained cyclists.

A Novel Etchant System for Orthodontic Bracket Bonding.

Orthodontic treatment is widely used to correct irregular teeth and/or jaw discrepancies to improve oral function and facial aesthetics. However, it is frequently associated with enamel damage that include chipping, demineralisation, and white spot formation. So far, current bonding systems that can maintain shear bond strengths (SBS) suitable for clinical performance are unable to limit enamel demineralisation, adhesive remnants and damage caused on removal of brackets after treatment. This study reports a novel "safe enamel etch" clinically viable procedure that was accomplished via application of novel etchant pastes developed with ß-tricalcium phosphate and monocalcium phosphate monohydrate powders mixed with citric acid (5 M) or phosphoric acid (37% PA) to yield BCA and BPA etchants respectively. Although enamel etched with clinically used PA gel yielded higher SBS than the BCA/BPA etchants, it exhibited greater adhesive remnants with evidence of enamel damage. In contrast, the experimental etchants resulted in unblemished enamel surfaces with zero or minimal adhesive residue and clinically acceptable SBS. Furthermore, the BPA etchant caused lower enamel decalcification with extensive calcium-phosphate precipitation. The study conclusively showed that BPA facilitated in vitro enamel adhesion without detrimental effects of the aggressive PA gel with potential for remineralisation and saving time at the post-debonding step.

Ray sum image: its efficacy in renal tract calculus detection.

AIM: To determine the efficacy of a ray sum image derived from computed tomography of the kidneys, ureters and bladder (CT KUB) in detecting renal tract calculi and whether this can replace the baseline abdominal radiograph (AXR). MATERIALS AND METHODS: This is a retrospective study performed at a tertiary referral centre examining adult patients referred for urolithiasis who had undergone AXR within 24 hours of the diagnostic CT KUB. AXR and ray sum image for calculus visibility were reviewed blindly by two readers. Anteroposterior thickness of the patient, presence of excess gas/faecal material, calculus size, location, and mean attenuation were analysed to determine effect on the AXR and ray sum sensitivity. RESULTS: One hundred and fifty-two calculi were examined with ray sum image sensitivity of 44% (95% confidence interval [CI]: 36-52) and AXR 30% (95% CI: 22-38). Calculus size and mean attenuation significantly affected sensitivities of both ray sum and AXR. There was substantial agreement between the two techniques with κ(Kappa)=0.70 (95% CI: 0.58-0.81, p<0.001). CONCLUSION: Ray sum image as a post-processed image derived from CT KUB dataset may be a viable alternative to the baseline AXR in patients with CT proven urolithiasis. This would reduce patient radiation dose and streamline workflow in busy radiology and emergency departments.

Establishing gene Amelogenin as sex-specific marker in yak by genomic approach.

Yak, an economically important bovine species considered as lifeline of the Himalaya. Indeed, this gigantic bovine is neglected because of the scientific intervention for its conservation as well as research documentation for a long time. Amelogenin is an essential protein for tooth enamel which eutherian mammals contain two copies in both X and Y chromosome each. In bovine, the deletion of a fragment of the nucleotide sequence in Y chromosome copy of exon 6 made Amelogenin an excellent sex-specific marker. Thus, an attempt was made to use the gene as an advanced molecular marker of sexing of the yak to improve breeding strategies and reproduction. The present study confirmed that the polymerase chain reaction amplification of the Amelogenin gene with a unique primer is useful in sex identification of the yak. The test is further refined with qPCR validation by quantifying the DNA copy number of the Amelogenin gene in male and female. We observed a high level of sequence polymorphisms of AMELX and AMELY in yak considered as novel identification. These tests can be further extended into several other specialized fields including forensics, meat production and processing, and quality control.

Controlled dissolution of freeform 3D printed carbohydrate glass scaffolds in hydrogels using a hydrophobic spray coating.

Freeform 3D printing combined with sacrificial molding promises to lead advances in production of highly complex tubular systems for biomedical applications. Here we leverage a purpose-built isomalt 3D printer to generate complex channel geometries in hydrogels which would be inaccessible with other techniques. To control the dissolution of the scaffold, we propose an enabling technology consisting of an automated nebulizer coating system which applies octadecane to isomalt scaffolds. Octadecane, a saturated hydrocarbon, protects the rigid mold from dissolution and provides ample time for gels to set around the sacrificial structure. With a simplified model of the nebulizer system, the robotic motion was optimized for uniform coating. Using a combination of stimulated Raman scattering (SRS) microscopy and X-ray computed tomography, the coating was characterized to assess surface roughness and consistency. Colorimetric measurements of dissolution rates allowed optimization of sprayer parameters, yielding a decrease in dissolution rates by at least 4 orders of magnitude. High fidelity channels are ensured by surfactant treatment of the coating, which prevents bubbles from clinging to the surface. Spontaneous Raman scattering microspectroscopy and white light microscopy indicate cleared channels are free of octadecane following gentle flushing. The capabilities of the workflow are highlighted with several complex channel architectures including helices, blind channels, and multiple independent channels within polyacrylamide hydrogels of varying stiffnesses.

Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care: a population-based study.

OBJECTIVES: To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care. DESIGN: Population-based pregnancy cohort. SETTING: Medical records (CPRD-GOLD) from England. POPULATION: 417 028 pregnancies during 1998-2014. METHODS: Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment, and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics. MAIN OUTCOME MEASURES: NVP/HG diagnoses, treatments, and hospital admissions. RESULTS: Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998-2013 (trend P < 0.001). Younger age, deprivation, Black/Asian/mixed ethnicity, and multiple pregnancy were associated with NVP/HG generally across all levels, but associations were strongest for hospital admissions. Most comorbidities had patterns of association with NVP/HG levels. Among women with NVP/HG who had no hospital admissions, 49% were prescribed antiemetics, mainly from first-line treatment (21% prochlorperazine, 15% promethazine, 13% cyclizine) and metoclopramide (10%). Of those admitted, 38% had prior antiemetic prescriptions (34% first-line, 9% second-line, 1% third-line treatment). CONCLUSION: Previous focus on hospital admissions has greatly underestimated the NVP/HG burden. Although primary care prescribing has increased, most women admitted to hospital have no antiemetics prescribed before this. An urgent call is made to assess whether admissions could be prevented with better primary care recognition and timely treatment. TWEETABLE ABSTRACT: The NVP/HG burden is increasing over time and management optimisation should be high priority to help reduce hospital admissions.

Filament Nucleation Tunes Mechanical Memory in Active Polymer Networks.

Incorporating growth into contemporary material functionality presents a grand challenge in materials design. The F-actin cytoskeleton is an active polymer network which serves as the mechanical scaffolding for eukaryotic cells, growing and remodeling in order to determine changes in cell shape. Nucleated from the membrane, filaments polymerize and grow into a dense network whose dynamics of assembly and disassembly, or 'turnover', coordinates both fluidity and rigidity. Here, we vary the extent of F-actin nucleation from a membrane surface in a biomimetic model of the cytoskeleton constructed from purified protein. We find that nucleation of F-actin mediates the accumulation and dissipation of polymerization-induced F-actin bending energy. At high and low nucleation, bending energies are low and easily relaxed yielding an isotropic material. However, at an intermediate critical nucleation, stresses are not relaxed by turnover and the internal energy accumulates 100-fold. In this case, high filament curvatures template further assembly of F-actin, driving the formation and stabilization of vortex-like topological defects. Thus, nucleation coordinates mechanical and chemical timescales to encode shape memory into active materials.