Model based analysis of trace metal dosing strategies to improve methane yield in anaerobic digestion systems.

Favourable effects of trace metals (TMs) on regulating anaerobic digestion (AD) performance are extensively utilised to improve methane yield. This study discusses a model-based approach to find out the best TM dosing strategies. The model has been applied to compare continuous, preloading, pulse dosing and in-situ loading. Simulations were also carried out to comprehend appropriate dosing form, dosing time and quantity of metals to be dosed. Model results show that the best way to dose TMs is repeated pulse dosing at low concentration levels in the optimum range with high frequency. Best dosing strategy for the system in this study was found to be 5 µM pulse loading at 5 days intervals as it gave maximum methane production and low effluent metal loss. Preferable dosing form depends on reactor configuration and this has been verified after model calibration with experimental data. Easily dissociable metal chlorides are ideal for continuous reactors.

Paradigm shift in transfusion practices during early COVID-19 pandemic: A single center retrospective study.

BACKGROUND: The advent of coronavirus disease 2019 (COVID-19) unveiled the worst national blood crisis that the United States had witnessed in over a decade. With the pandemic influencing the different stages of the acquisition of blood products outside the hospital setting, we aimed to explore the possible barriers contributing to the shortage of blood products within the medical community. AIM: To assess the adherence to restrictive blood transfusion practices for patients in the COVID era and pre-COVID era. METHODS: We conducted a retrospective cross-sectional study on hospitalized patients distinguishing the pattern of blood transfusion during the COVID and pre-COVID era in a community hospital. Data was tabulated to include the number of red blood cell (RBC) transfusions and if transfusions met restrictive blood transfusion criteria as per institutional guidelines. Chi-square was applied to test the statistical association between qualitative variables. Unpaired t test and Mann Whitney U test were applied respectively to test the mean difference of quantitative variables. RESULTS: A total of 208 patients were included in the study, of which 108 were during COVID era and 100 were during pre-COVID era. The leading reason for admission in both the COVID era and pre-COVID era transfused patients was shortness of breath (53.7% and 36% P = 0.001), followed by gastrointestinal bleeding (25.9% and 21% P = 0.001). There was a higher percentage of RBC transfusions in the intensive care unit in the COVID-era group than in the pre-COVID era group (38.9% vs 22%, P = 0.008). The restrictive transfusion criteria were met in 62% vs 79% in the COVID and pre-COVID eras, respectively (P = 0.008). CONCLUSION: The COVID-era group received RBC transfusions with less stringent adherence to restrictive blood transfusion practices in comparison to pre-COVID era group.

Δ9-Tetrahydrocannabinol does not upregulate an aversive dopamine receptor mechanism in adolescent brain unlike in adults.

Earlier age of cannabis usage poses higher risk of Cannabis Use Disorder and adverse consequences, such as addiction, anxiety, dysphoria, psychosis, largely attributed to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC) and altered dopaminergic function. As dopamine D1-D2 receptor heteromer activation causes anxiety and anhedonia, this signaling complex was postulated to contribute to THC-induced affective symptoms. To investigate this, we administered THC repeatedly to adolescent monkeys and adolescent or adult rats. Drug-naïve adolescent rat had lower striatal densities of D1-D2 heteromer compared to adult rat. Repeated administration of THC to adolescent rat or adolescent monkey did not alter D1-D2 heteromer expression in nucleus accumbens or dorsal striatum but upregulated it in adult rat. Behaviourally, THC-treated adult, but not adolescent rat manifested anxiety and anhedonia-like behaviour, with elevated composite negative emotionality scores that correlated with striatal D1-D2 density. THC modified downstream markers of D1-D2 activation in adult, but not adolescent striatum. THC administered with cannabidiol did not alter D1-D2 expression. In adult rat, co-administration of CB1 receptor (CB1R) inverse agonist with THC attenuated D1-D2 upregulation, implicating cannabinoids in the regulation of striatal D1-D2 heteromer expression. THC exposure revealed an adaptable age-specific, anxiogenic, anti-reward mechanism operant in adult striatum but deficient in adolescent rat and monkey striatum that may confer increased sensitivity to THC reward in adolescence while limiting its negative effects, thus promoting continued use and increasing vulnerability to long-term adverse cannabis effects.

Daily Δ9-Tetrahydrocannabinol and Withdrawal Increase Dopamine D1-D2 Receptor Heteromer to Mediate Anhedonia- and Anxiogenic-like Behavior Through a Dynorphin and Kappa Opioid Receptor Mechanism.

Background: Frequent cannabis use is associated with a higher risk of developing cannabis use disorder and other adverse consequences. However, rodent models studying the underlying mechanisms of the reinforcing and withdrawal effects of the primary constituent of cannabis, Δ9-tetrahydrocannabinol (THC), have been limited. Methods: This study investigated the effects of daily THC (1 mg/kg, intraperitoneal, 9 days) and spontaneous withdrawal (7 days) on hedonic and aversion-like behaviors in male rats. In parallel, underlying neuroadaptive changes in dopaminergic, opioidergic, and cannabinoid signaling in the nucleus accumbens were evaluated, along with a candidate peptide designed to reverse altered signaling. Results: Chronic THC administration induced anhedonic- and anxiogenic-like behaviors not attributable to altered locomotor activity. These effects persisted after drug cessation. In the nucleus accumbens, THC treatment and withdrawal catalyzed increased cannabinoid CB1 receptor activity without modifying receptor expression. Dopamine D1-D2 receptor heteromer expression rose steeply with THC, accompanied by increased calcium-linked signaling, activation of BDNF/TrkB (brain-derived neurotrophic factor/tropomyosin receptor kinase B) pathway, dynorphin expression, and kappa opioid receptor signaling. Disruption of the D1-D2 heteromer by an interfering peptide during withdrawal reversed the anxiogenic-like and anhedonic-like behaviors as well as the neurochemical changes. Conclusions: Chronic THC increases nucleus accumbens dopamine D1-D2 receptor heteromer expression and function, which results in increased dynorphin expression and kappa opioid receptor activation. These changes plausibly reduce dopamine release to trigger anxiogenic- and anhedonic-like behaviors after daily THC administration that persist for at least 7 days after drug cessation. These findings conceivably provide a therapeutic strategy to alleviate negative symptoms associated with cannabis use and withdrawal.

Dynamic modelling the effects of ionic strength and ion complexation on trace metal speciation during anaerobic digestion.

Dosing trace metals into anaerobic digestors is proven to improve biogas production rate and yield by stimulating microorganisms involved in the metabolic pathways. Trace metal effects are governed by metal speciation and bioavailability. Though chemical equilibrium speciation models are well-established and widely used to understand metal speciation, the development of kinetic models considering biological and physicochemical processes has recently gained attention. This work proposes a dynamic model for metal speciation during anaerobic digestion which is based on a system of ordinary differential equations aimed to describe the kinetics of biological, precipitation/dissolution, gas transfer processes and, a system of algebraic equations to define fast ion complexation processes. The model also considers ion activity corrections to define effects of ionic strength. Results from this study shows the inaccuracy in predicting trace metal effects on anaerobic digestion by typical metal speciation models and the significance of considering non-ideal aqueous phase chemistry (ionic strength and ion pairing/complexation) to define speciation and metal labile fractions. Model results show a decrease in metal precipitation and increase in metal dissolved fraction and methane production yield with increase in ionic strength. Capability of the model to dynamically predict trace metal effects on anaerobic digestion under different conditions, like changing dosing conditions and initial iron to sulphide ratio, was also tested and verified. Dosing iron increases methane production and decreases hydrogen sulphide production. However, when iron to sulphide ratio is greater than 1, methane production decreases due to increase in dissolved iron which reaches inhibitory concentration levels.

Comparison of mathematically arterialised venous blood gas sampling with arterial, capillary, and venous sampling in adult patients with hypercapnic respiratory failure: a single-centre longitudinal cohort study.

BACKGROUND: Accurate arterial blood gas (ABG) analysis is essential in the management of patients with hypercapnic respiratory failure, but repeated sampling requires technical expertise and is painful. Missed sampling is common and has a negative impact on patient care. A newer venous to arterial conversion method (v-TAC, Roche) uses mathematical models of acid-base chemistry, a venous blood gas sample and peripheral blood oxygen saturation to calculate arterial acid-base status. It has the potential to replace routine ABG sampling for selected patient cohorts. The aim of this study was to compare v-TAC with ABG, capillary and venous sampling in a patient cohort referred to start non-invasive ventilation (NIV). METHODS: Recruited patients underwent near simultaneous ABG, capillary blood gas (CBG) and venous blood gas (VBG) sampling at day 0, and up to two further occasions (day 1 NIV and discharge). The primary outcome was the reliability of v-TAC sampling compared with ABG, via Bland-Altman analysis, to identify respiratory failure (via PaCO2) and to detect changes in PaCO2 in response to NIV. Secondary outcomes included agreements with pH, sampling success rates and pain. RESULTS: The agreement between ABG and v-TAC/venous PaCO2 was assessed for 119 matched sampling episodes and 105 between ABG and CBG. Close agreement was shown for v-TAC (mean difference (SD) 0.01 (0.5) kPa), but not for CBG (-0.75 (0.69) kPa) or VBG (+1.00 (0.90) kPa). Longitudinal data for 32 patients started on NIV showed the closest agreement for ABG and v-TAC (R2=0.61). v-TAC sampling had the highest first-time success rate (88%) and was less painful than arterial (p<0.0001). CONCLUSION: Mathematical arterialisation of venous samples was easier to obtain and less painful than ABG sampling. Results showed close agreement for PaCO2 and pH and tracked well longitudinally such that the v-TAC method could replace routine ABG testing to recognise and monitor patients with hypercapnic respiratory failure. TRIAL REGISTRATION NUMBER: NCT04072848; www. CLINICALTRIALS: gov.

Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review.

Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components-tetrahydrocannabinol (THC) and cannabidiol (CBD)-or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement.

Predictive Drug Release Modeling Across Dissolution Apparatuses I and II using Computational Fluid Dynamics.

A modeling process is developed and validated with which active pharmaceutical ingredient (API) release is predicted across the United States Pharmacopeia (USP) dissolution apparatuses I and II based on limited experimental dissolution data (at minimum two dissolution profiles at different apparatus settings). The process accounts for formulation-specific drug release behavior and hydrodynamics in the apparatuses over the range of typical agitation rates and medium volumes. This modeling process involves measurement of experimental mass transfer coefficients via a conventional mass balance and the relationship of said mass transfer coefficients to hydrodynamics and apparatus setting via computational fluid dynamics (CFD). A novel 1-D model is hence established, which provided calibration data for a particular formulation, can model mass transfer coefficients and their corresponding drug release at apparatus configurations of interest. Based on validation against experimental data produced from five erosion-based formulations over a range of apparatus configurations, accuracy within 8 %LA (labelled amount of API) and an average root mean square deviation of 3 %LA is achieved. With this predictive capability, minimizing the number of dissolution experiments and the amount of chemical materials needed during method development appears feasible.

Outcomes of COVID-19 in heart failure, LVAD, and heart transplant patients in an advanced heart failure practice.

Background: Patients with heart failure face increased morbidity and mortality when infected with COVID-19. The objective of this study was to evaluate the outcomes of patients with Heart Failure (HF), Left Ventricular Assist Devices (LVADs), or Heart Transplants (HTx) diagnosed with COVID-19 within an advanced HF practice. Methods: Out of 2635 patients followed, 96 patients were diagnosed with COVID-19 between March 2020 and January 2021. Median hospital length of stay (LOS), requirement for mechanical ventilation (MV), and mortality rate were evaluated. Results: The distribution of COVID-19 among the 96 patients was: HF = 43 (45 %), LVAD = 16 (17 %) and HTx = 37 (38 %). Among 43 HF patients, 5 (12 %) died, 18 (42 %) required hospitalization with an LOS of 7 days, 5 (12 %) required ICU and 4 (9 %) required MV. Of the 16 LVAD patients, 2 (13 %) died, 8 (50 %) required hospitalization with an LOS of 11 days, 3 (19 %) required ICU and 3 (19 %) required MV. Among 37 HTx patients, 7 (19 %) died, 23 (62 %) required hospitalization with an LOS of 9 days, 6 (16 %) required ICU and 6 (16 %) required MV. Conclusion: This report is among the first to describe the impact of COVID-19 on a diverse advanced HF practice. It highlights the risks associated with COVID-19 faced by the HF, LVAD and HTx patients. A 90-day mortality rate of 19 % with HTx patients acquiring COVID-19 is ominous as is a mortality rate of 12 % each for HF and LVAD patients. This clinical impact should serve as a reminder of unique challenges with these populations.

A Case-Control Study of Distinguishing Between Stroke Mimics and True Strokes.

This study was conducted with the primary aim to distinguish patients with a true stroke versus a stroke mimic based on clinical features and imaging. We conducted a retrospective case-control study on 116 adult patients who received alteplase (tPA) to treat acute stroke at our hospital. We further analyzed 79 patients with a normal computed tomography angiography (CTA). Based on their magnetic resonance imaging (MRI) of the brain, they were divided into cases (stroke mimics) and controls (true strokes). Data were collected retrospectively by reviewing individual medical charts on the electronic medical record (EMR), including age, gender, history of stroke, seizure, hypertension, diabetes, atrial fibrillation, hyperlipidemia, presenting NIH Stroke Scale/Score, hemorrhagic conversion, history of migraine, history of depression, sidedness of symptoms and aphasia. Data were categorized to separate those who were later diagnosed to be stroke mimics by being-postictal, encephalopathic, in acute migraine, suffered post-stroke recrudescence (PSR) due to metabolic insult, or had conversion disorder when symptoms could not be attributed to any medical condition or mental illness. Of the 79 study subjects, 48 (60%) were stroke mimics. The mean age of the cohort was 68.67 years, and 46.8% of the study subjects were females. Based on the multivariate logistic regression analysis, factors associated with being a stroke mimic were older age, history of migraine, and a history of prior stroke. In conclusion, increased attention to history and clinical examination as the first step can aid in the proper diagnosis of strokes versus stroke mimics. Identifying stroke mimics early could help expedite hospital workup and prevent inadvertent investigations, reducing hospital occupancy during the ongoing COVID-19 pandemic. We could potentially avoid the administration of tPA to such patients, reducing both the cost and adverse effects of it. Every stroke can cause neurological deficits, but every deficit need not be a stroke.

Harms and Contributors of Leaving Against Medical Advice in Patients With Infective Endocarditis.

INTRODUCTION: Patients leaving against medical advice (AMA) are commonly encountered in hospital medicine. The problem is prevalent worldwide and across all fields of medicine. A retrospective study of 47,583 patients reported a 3.3% AMA rate in 2015. OBJECTIVES: In this retrospective study, we aimed (1) to study the demographic, clinical, and laboratory parameters of infective endocarditis (IE) patients leaving AMA. We also compared (2) the various risk factors and outcomes of these patients with IE patients who completed treatment. RESULTS: A total of 111 patients diagnosed with IE were recruited for 36 months. Of the 74 patients with available details, 32 patients (29%) left AMA during their treatment. The mean age of patients leaving AMA was 39, and among those who left AMA, 66% were females. As compared with patients completing therapy, patients leaving AMA tend to have higher comorbidities, including injection drug use (68.1% versus 31.9%), prior IE (83.3% versus 16.7%), and chronic hepatitis C (72.4% versus 27.8%). Rates of consumption of substances of abuse were higher among those who left AMA. Patients leaving AMA also had higher psychiatric comorbidities (63% versus 37.5%), history of leaving AMA (70.5% versus 29.5%), and consumption of more than 2 substances of abuse. Morbidity was higher in patients leaving AMA. There was a statistically significant association between the development of distal embolus ( P < 0.001), the need for recurrent admissions ( P = 0.002), recurrent bacteremia ( P < 0.001), developing new embolus ( P < 0.001), and overall morbidity ( P = 0.002) among IE patients leaving AMA. CONCLUSIONS: Infective endocarditis patients leaving AMA tend to be younger females. These patients have prior comorbidities of injection drug use, prior IE, multiple psychiatric comorbidities, drug use, and multiple socioeconomic issues. Patients leaving AMA tend to develop further non-Central nervous system embolic events, recurrent bacteremia, and require frequent admissions. Morbidity in these patients was higher.

Predictors, patterns and outcomes following Infective endocarditis and stroke.

Patients with infective endocarditis can have multiple neurological manifestations.  Cerebrovascular events (CVE) in patients with IE can be hemorrhagic or embolic.  Multiple factors are known to predispose to CVE and increased mortality in patients with IE.  In this study, we aimed to describe various outcomes among patients with IE and CVE.  We retrospectively analyzed 160 patients with definite IE.  Among these, patients with radiological evidence of CVE were included.  Clinical, radiological, echocardiographic details were obtained.  Outcome studied were the requirement of intensive care unit care, the requirement of mechanical ventilation, prolonged course of antibiotics, prolonged duration of hospital stay, the requirement of surgical intervention, and mortality.  In this study, 16 [10%] of patients with IE were identified to have a CVE.  The mean age of the patients was 55, and 87.5% of them were male.  25% of patients had prior IE.  IE involving left-sided valves were predominant, with the involvement of mitral valve reported in 62.5% of patients.  More than half of the patient's had details of magnetic resonance imaging (MRI) of the brain.  CVE were mostly ischemic, anterior circulation predominant, multiple, and bilateral.  In patients with IE and CVE morbidity including the requirement of ICU care, prolonged antibiotics course, and the requirement of surgical intervention contributed to increased duration of hospital stay.  In conclusion, CVE in patients with IE tends to present as multiple infarcts predominantly located over anterior circulation.  IE patients with CVE tend to have higher morbidity and mortality.

Administration of BDNF in the ventral tegmental area produces a switch from a nicotine-non-dependent D1R-mediated motivational state to a nicotine-dependent-like D2R-mediated motivational state.

Brain-derived neurotrophic factor (BDNF) has been implicated in the transition from a non-dependent motivational state to a drug-dependent and drug-withdrawn motivational state. Chronic nicotine can increase BDNF in the rodent brain and is associated with smoking severity in humans; however, it is unknown whether this increased BDNF is linked functionally to the switch from a nicotine-non-dependent to a nicotine-dependent state. We used a place conditioning paradigm to measure the conditioned responses to nicotine, showing that a dose of acute nicotine that non-dependent male mice find aversive is found rewarding in chronic nicotine-treated mice experiencing withdrawal. A single BDNF injection in the ventral tegmental area (in the absence of chronic nicotine treatment) caused mice to behave as if they were nicotine dependent and in withdrawal, switching the neurobiological substrate mediating the conditioned motivational effects from dopamine D1 receptors to D2 receptors. Quantification of gene expression of BDNF and its receptor, tropomyosin-receptor-kinase B (TrkB), revealed an increase in TrkB mRNA but not BDNF mRNA in the VTA in nicotine-dependent and nicotine-withdrawn mice. These results suggest that BDNF signalling in the VTA is a critical neurobiological substrate for the transition to nicotine dependence. The modulation of BDNF signalling may be a promising new pharmacological avenue for the treatment of addictive behaviour.

Oncostatin M: a Potential Biomarker to Predict Infection in Patients with Left Ventricular Assist Devices.

Infection is a serious adverse event limiting left ventricular assist device (LVAD) therapy in advanced heart failure patients, but a reliable means to identify patients at increased risk of infection is still lacking. We hypothesized that preoperative elevated levels of plasma Oncostatin M (OSM), a cytokine marker of leukocyte activation and inflammation, would be predictive of subsequent infection. We measured plasma OSM in 41 LVAD patients one day before LVAD implantation and postoperatively over two months. Preoperative plasma OSM levels were normal in 27 patients (group A, 4.9 ± 3.2 pg/ml) but elevated in 14 patients (group B, 1649.0 ± 458.9 pg/ml) ( p = 0.003). Early postoperative levels rose in both groups and declined rapidly in group A, with group B declining slowly over two months. Significantly more infections developed in group B than group A patients over two months postimplantation ( p = 0.004). No other routine clinical assessment or laboratory testing afforded this differentiation. These findings suggest that preoperative plasma OSM levels may assist in identifying patients at increased risk of infections after LVAD implantation.

To study the contributing factors and outcomes of Clostridioides difficile infection in patients with solid tumors.

BACKGROUND: Clostridioides difficile infection (CDI) is a considerable healthcare burden, and now identified as the leading cause of acquired diarrheal illness in patients receiving antibiotics. Patients with malignancies are more prone to acquire CDI, owing to their frequent exposure to risk factors. OBJECTIVE: This study aims to investigate the factors affecting the outcome of Clostridioides Difficile Infection in patients with solid tumors at our community healthcare center. METHODS: This is a retrospective study that included a total of 59 patients with solid tumors who were hospitalized for Clostridioides difficile infection. RESULTS: The median age of the study population was 79 years with 39 males and 20 females. The patients had a diagnosis of a malignancy involving the following sites: prostate (25), lung (19), colon (7), bladder (4), breast (3), and renal (1). There were 52 cases of first time and 7 cases of recurrent CDI admissions. 40 patients were detected to have CDI at presentation while 19 patients were diagnosed with CDI after admission. CDI was categorized as follows: non-severe (29), severe (28), and very severe (2). There were 33 patients on chemotherapy and 20 patients undergoing radiotherapy. Twenty-seven patients had a recent history of cancer care-related procedures or interventions. Twenty-nine patients were from either a rehabilitation center or a long-term nursing care facility. There were 39 recent hospitalizations with 29 patients receiving antibiotics. Almost half of the patients were on proton pump inhibitors (29) and 12 were on steroids (20.3%) at the time of developing CDI. Patients with a high-risk qSOFA score of 2 or more (p-value = 0.008) or a high white blood cell count of >15 × 109/L (p-value = 0.016) at the time of admission were found to have higher in-hospital mortality. Critical care data suggested that 9 patients required intensive care, 7 patients required vasopressor support, and 6 needed mechanical ventilation. Patients were treated with either vancomycin alone (13), or metronidazole alone (25), or combination therapy with vancomycin + metronidazole (21). The median duration of hospital stay was 6 days with 11 fatalities (18.64%). CONCLUSIONS: CDI causes significant morbidity in patients with malignancies. A high qSOFA score and leukocytosis are significantly associated with high morbidity and thus should be used to prioritize and intensify inpatient care of these patients.

Factors contributing to poor outcome in patients on warfarin receiving 4-factor prothrombin complex concentrate in critically ill.

AIM: To compare the demographical profile, indications, efficacy, and contributors to adverse outcome following administration of 4F-PCC in patients on warfarin with supratherapeutic INR. METHODOLOGY: Retrospective cross-sectional study was performed in a community based teaching hospital. All patients 18 years and older on warfarin with supratherapeutic INR, who had received 4F-PCC between January 2014 and December 2018 were eligible and included in the study. RESULTS: 44 patients were included in the analysis. The mean age of the patients was 79.5 years. The male to female ratio was 1:1. Patients were on warfarin for atrial fibrillation, thromboembolism in 79.5% (N-35), and 20.5% (N-9) respectively. Indications for use of 4F-PCC were active bleeding in 93% (N-41) of patients. The common sites of bleeding were gastrointestinal, intracranial, and musculoskeletal which were seen in 54.5% (N-24), 29.5% (N-13) and 6.8% (N-3) respectively. The median number of doses of 4F-PCC administered was 1 per patient. The mean dose administered was 2,883u. Clinical improvement was documented in 84% (N-37) of patients. Mortality was seen in 16% (N-7) of patients. BMI greater than 30, anemia, hypotension, presence of intracranial bleed, the requirement of blood products, and mechanical ventilation were associated with higher odds for mortality. Hypotension and requirement of mechanical ventilation were statistically significant. CONCLUSION: 4F-PCC continues to be an effective agent in the rapid reversal of warfarin therapy in patients with supratherapeutic INR presenting with major bleeding events. Most patients have clinical improvement with a single, weight-adjusted dose.

Sex Differences in Dopamine Receptors and Relevance to Neuropsychiatric Disorders.

Dopamine is an important neurotransmitter that plays a key role in neuropsychiatric illness. Sex differences in dopaminergic signaling have been acknowledged for decades and have been linked to sex-specific heterogeneity in both dopamine-related behaviours as well as in various neuropsychiatric disorders. However, the overall number of studies that have evaluated sex differences in dopamine signaling, both in health and in these disorders, is low. This review will bring together what is known regarding sex differences in innate dopamine receptor expression and function, as well as highlight the known sex-specific roles of dopamine in addiction, depression, anxiety, schizophrenia, and attention deficit hyperactivity disorder. Due to differences in prognosis, diagnosis, and symptomatology between male and female subjects in disorders that involve dopamine signaling, or in responses that utilize pharmacological interventions that target dopamine receptors, understanding the fundamental sex differences in dopamine receptors is of vital importance for the personalization of therapeutic treatment strategies.

Optimal Blood Glucose Monitoring Interval for Insulin Infusion in Critically Ill Non-Cardiothoracic Patients: A Pilot Study.

OBJECTIVE: The American Diabetes Association and the Society of Critical Care Medicine recommend monitoring blood glucose (BG) every 1-2 hours in patients receiving insulin infusion to guide titration of insulin infusion to maintain serum glucose in the target range; however, this is based on weak evidence. We evaluated the compliance of hourly BG monitoring and relation of less frequent BG monitoring to glycemic status. MATERIALS AND METHODS: Retrospective chart review performed on 56 consecutive adult patients who received intravenous insulin infusion for persistent hyperglycemia in the ICU at Saint Vincent Hospital, a tertiary care community hospital an urban setting in Northeast region of USA. The frequency of fingerstick blood glucose (FSBG) readings was reviewed for compliance with hourly FSBG monitoring per protocol and the impact of FSBG testing at different time intervals on the glycemic status. Depending on time interval of FSBG monitoring, the data was divided into three groups: Group A (<90 min), Group B (91-179 min) and Group C (≥180 min). RESULTS: The mean age was 69 years (48% were males), 77% patients had preexisting type 2 diabetes mellitus (T2DM). The mean MPM II score was 41. Of the 1411 readings for BG monitoring on insulin infusion, 467 (33%) were in group A, 806 (57%) in group B and 138 (10%) in group C; hourly BG monitoring compliance was 12.6%. The overall glycemic status was similar among all groups. There were 14 (0.99%) hypoglycemic episodes observed. The rate of hypoglycemic episodes was similar in all three groups (p=0.55). CONCLUSION: In patients requiring insulin infusion for sustained hyperglycemia in ICU, the risk of hypoglycemic episodes was not significantly different with less frequent BG monitoring. The compliance to hourly blood glucose monitoring and ICU was variable, and hypoglycemic episodes were similar across the groups despite the variation in monitoring.

Effects of daily Δ9-Tetrahydrocannabinol (THC) alone or combined with cannabidiol (CBD) on cognition-based behavior and activity in adolescent nonhuman primates.

BACKGROUND: Daily use of marijuana is rising in adolescents, along with consumption of high potency marijuana products (high % Δ-9-tetrahydrocannabinol or THC). These dual, related trends have opened gaps in understanding the long-term effects of daily consumption of a high dose of THC in adolescents and whether a therapeutic dose of cannabidiol (CBD) modulates THC effects. METHODS: Adolescent squirrel monkeys (Saimiri boliviensis) were treated daily for four months with vehicle (n = 4), a high THC dose (1 mg/kg i.m.; n = 4), or THC + CBD (1 mg/kg +3 mg/kg i.m.; n = 4), to investigate whether: (1) a daily high THC dose affects performance in tasks of cognition (repeated acquisition, discrimination reversal); (2) a daily high THC dose affects spontaneous behavior and day/night activity (3) tolerance develops to the behavioral effects of THC; (4) whether CBD modulates THC effects. RESULTS: THC impaired performance of adolescent monkeys in a cognitive test initially, but not performance on a task of cognitive flexibility. THC reduced motor activity and increased sedentary behavior, with tolerance developing after weeks of daily treatment. Co-administered with THC, CBD did not modulate THC effects on cognitive performance, activity or tolerance, but prevented THC-induced emesis on the first day of daily treatment. CONCLUSIONS: Daily high dosing with THC compromised performance on a task of cognition, and reduced activity in adolescent primates, with tolerance developing within weeks. Whether our observations are relevant to a broader range of cognitive tasks vital for daily function in human adolescents is uncertain.