Mechanistic account of distinct change in organic anion transporting polypeptide 1B (OATP1B) substrate pharmacokinetics during OATP1B-mediated drug-drug interactions using physiologically-based pharmacokinetic modeling.

The role of transporters in drug clearance is widely acknowledged, directly and indirectly by facilitating tissue/enzyme exposure. Through the latter, transporters also affect volume of distribution. Drug-drug interactions (DDIs) involving organic anion transporting polypeptides (OATPs) 1B1/1B3 and SLCO1B1 pharmacogenetics lead to altered pharmacokinetics of OATP1B substrates; however, several factors may confound direct interpretation of pharmacokinetic parameters from these clinical studies using noncompartmental analysis (NCA). A review of clinical data herein indicates a single dose of OATP1B inhibitor rifampin almost never leads to increased substrate half-life but often a decrease, and that most clinical OATP1B substrates are CYP3A4 substrates and/or undergo enterohepatic cycling (EHC). Using hypothetically simple OATP1B substrate physiologically-based pharmacokinetic (PBPK) models, simulated effect of rifampin differed from specific OATP1B inhibition, due to short rifampin half-life causing dissipation of OATP1B inhibition over time combined with CYP3A4 induction. Calculated using simulated tissue data, volume of distribution indeed decreased with OATP1B inhibition and was expectedly limited to the contribution of liver volume. However, an apparent and counterintuitive effect of rifampin on volume greater than that on clearance resulted for CYP3A4 substrates, using NCA. Effect of OATP1B inhibition and rifampin on OATP1B substrate models incorporating EHC +/- renal clearance was distinct compared to simpler models. Using PBPK models incorporating reversible lactone metabolism for clinical OATP1B substrates atorvastatin and pitavastatin, DDIs reporting decreased half-life with rifampin were reproduced. These simulations provide explanation for the distinct change in OATP1B substrate pharmacokinetics observed in clinical studies, including changes in volume of distribution and additional mechanisms. Significance Statement Transporters are involved in both drug clearance and volume of distribution and distinct changes in OATP1B substrate pharmacokinetics are observed with OATP1B inhibitor rifampin. Using hypothetical and validated PBPK models and simulations we address the limitations of single-dose rifampin and complicated clinical OATP1B substrate disposition in evaluating the pharmacokinetic parameters of OATP1B substrates during rifampin DDIs. These models account for the change in volume of distribution and identify additional mechanisms underlying apparent pharmacokinetic changes in OATP1B DDIs.

Rapid differentiation of estrogen receptor status in patient biopsy breast cancer aspirates with an optical nanosensor.

Breast cancer is a substantial source of morbidity and mortality worldwide. It is particularly more difficult to treat at later stages, and treatment regimens depend heavily on both staging and the molecular subtype of the tumor. However, both detection and molecular analyses rely on standard imaging and histological method, which are costly, time-consuming, and lack necessary sensitivity/specificity. The estrogen receptor (ER) is, along with the progesterone receptor (PR) and human epidermal growth factor (HER-2), among the primary molecular markers which inform treatment. Patients who are negative for all three markers (triple negative breast cancer, TNBC), have fewer treatment options and a poorer prognosis. Therapeutics for ER+ patients are effective at preventing disease progression, though it is necessary to improve the speed of subtyping and distribution of rapid detection methods. In this work, we designed a near-infrared optical nanosensor using single-walled carbon nanotubes (SWCNT) as the transducer and an anti-ERα antibody as the recognition element. The nanosensor was evaluated for its response to recombinant ERα in buffer and serum prior to evaluation with ER- and ER+ immortal cell lines. We then used a minimal volume of just 10 µL from 26 breast cancer biopsy samples which were aspirated to mimic fine needle aspirates. 20 samples were ER+, while 6 were ER-, representing 13 unique patients. We evaluated the potential of the nanosensor by investigating several SWCNT chiralities through direct incubation or fractionation deployment methods. We found that the nanosensor can differentiate ER- from ER+ patient biopsies through a shift in its center wavelength upon sample addition. This was true regardless of which of the three SWCNT chiralities we observed. Receiver operating characteristic area under the curve analyses determined that the strongest classifier with an AUC of 0.94 was the (7,5) chirality after direct incubation and measurement, and without further processing. We anticipate that further testing and development of this nanosensor may push its utility toward field-deployable, rapid ER subtyping with potential for additional molecular marker profiling.

Recent advances in cardiovascular risk assessment: The added value of non-invasive anatomic imaging.

In 2022, multiple original research studies were conducted highlighting the utility of coronary artery calcium (CAC) imaging in young individuals and provided further evidence for the role of CAC to improve atherosclerotic cardiovascular disease (ASCVD) risk assessment. Mean calcium density was shown to be a more reliable predictor than peak density in risk assessment. Additionally, in light of the ACC/AHA/Multispecialty Chest Pain Guideline's recent elevation of coronary computed tomography angiography (CCTA) to a Class I (level of evidence A) recommendation as an index diagnostic test for acute or stable chest pain, several studies support the utility of CCTA and guided future directions. This review summarizes recent studies that highlight the role of non-invasive imaging in enhancing ASCVD risk assessment across different populations.

Agro-Waste Valorization into Carbonaceous Eco-Hydrogel: A Circular Economy and Zero Waste Tactic for Doxorubicin Removal in Water/Wastewater.

The existing work aims to evaluate the efficiency of eco-hydrogel for adsorption of pollutants prepared from biopolymeric matrix and agricultural waste-derived biochar. An efficient and reusable adsorbent, designed from the integration of maize stalk activated carbon into a gelatin-alginate composite (MSAC@GE-SA) was explored for removal of doxorubicin hydrochloride (Doxo.HCL) from polluted water. The structural properties, presence of surface functional groups, and elemental composition were explored using XRD, SEM, BET, FTIR, and XPS techniques. The key adsorption parameters such as Doxo.HCL concentration, MSAC@GE-SA amount, solution pH, and the contact time between adsorbate and adsorbents were successfully optimized for the effective removal of Doxo.HCL (qmax = 239.41 mg g-1). The kinetic mechanism of MSAC@GE-SA fits well with a pseudo-second-order rate model (R2 = 0.980), followed by mono- and multilayered Langmuir and Freundlich isotherms with R2 values 0.991 and 0.993, respectively. The recyclability of MSAC@GE-SA showed great stability without any physical damage and having sustained removal efficiency up to 10 cycles (96.32 to 55.66%). The versatility of MSAC@GE-SA was further investigated for river, canal, and sewage water samples under identical experimental conditions. The practicality of the MSAC@GE-SA was evaluated by spiking Doxo.HCL into industrial effluents via the standard addition method. Subsequently, the chemical oxygen demand (COD) of the treated pollutants exhibited a notable reduction, decreasing significantly from 128 to 80 mg L-1. Following 10 successful adsorption-desorption cycles, the spent MSAC@GE-SA was utilized as a fertilizer for Vigna radiata plants, positively contributing to overall plant growth without causing harm. Hence, proposed adsorbent (MSAC@GE-SA) emerges as a viable and sustainable solution, demonstrating features of reusability and cost-effectiveness. It holds significant promise for the removal of pharmaceutical pollutants, aligning with the principles of circular economy and zero-waste tactics.

Evaluation of Remineralization Potential of Natural Substances on Artificially Induced Carious Lesions in Primary Teeth: An In Vitro Study.

Aim: To evaluate the remineralizing potential of natural substances on artificially induced caries lesions in primary teeth. Materials and methods: A total of 50 primary molar teeth were selected and subjected to a demineralization process. Then samples were randomly divided into five groups for the remineralization process. Group I-colophony, group II-5% sodium fluoride (NaF) + colophony, group III-grape seed extract (GSE) + colophony, group IV-5% NaF + colophony + 10% peptide, and group V- GSE + colophony + 10% peptide. All the groups were subjected to remineralization using a brushing stimulator for 3,000 cycles. Assessment was done using Vickers hardness testing machine for evaluating the enamel surface microhardness (SMH) and scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDX) for evaluating the surface morphology and mineral content, before and after demineralization and after remineralization, the obtained data was analyzed statistically using IBM Statistical Package for the Social Sciences (SPSS) software version 25. Results: The enamel microhardness results of this study revealed that remineralization of enamel was highest in group V (212.83 ± 64.416) and least in group II (137.83 ± 26.324) p-value of 0.038. SEM-EDX analysis revealed high calcium (Ca) and fluoride (F) content in groups II and IV, which was significant (p-value of 0.001) from other groups. Surface morphology evaluated with SEM revealed spherical globular agglomerates and scaffolding deposits on the enamel surface in groups III and V resembling the remineralization process. Conclusion: Grape seed extract (GSE) with colophony and peptide is a superior natural alternative to NaF. Colophony also exhibited remineralizing potential in primary enamel. Clinical significance: Natural remineralizing agents like GSE, colophony, and its combination serves as a potential alternative to overcome the toxic effect on long-term usage of F. These natural substances can be applicable in clinical conditions by incorporating toothpaste and varnish, which can be used as an alternative or adjuvant to the topical application of F. How to cite this article: Pooja V Ravi, Rajakumar S, Kavitha Ramar. Evaluation of Remineralization Potential of Natural Substances on Artificially Induced Carious Lesions in Primary Teeth: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(2):244-250.

Biogenic Fabrication of Silver Nanoparticles Using Calotropis procera Flower Extract with Enhanced Biomimetics Attributes.

There have been some reports demonstrating the biogenic synthesis of silver nanoparticles (AgNPs) using Calotropis procera (CP) plant extract; however, detailed in-depth debriefing of the vital synthesis parameter for rapid, facile, efficacious synthesis at varied temperatures with effectual characterization of nanoparticles and biomimetic attribute is lacking. This study presents a comprehensive demarcation of the sustainable fabrication of biogenic C. procera flower extract capped and stabilized silver nanoparticles (CP-AgNPs) synthesis with thorough phytochemical characterization and potential biological application. The results revealed that the successful synthesis of CP-AgNPs was instantaneous with the maximum intensity of the plasmonic peak ~400 nm, while morphological results revealed the cubic shape of nanoparticles. CP-AgNPs were found to present stable, well-dispersed, uniform, high anionic zeta potential, and crystalline nanoparticles with a crystallite size of ~23.8 nm. The FTIR spectra indicated that CP-AgNPs were properly capped by the bioactive of C. procera. Moreover, the synthesized CP-AgNPs exhibited hydrogen peroxide scavenging efficacy. In addition, CP-AgNPs showed antibacterial and antifungal activity against pathogenic bacteria. CP-AgNPs displayed significant in vitro antidiabetic and anti-inflammatory activity. An efficient and convenient approach for synthesizing AgNPs using C. procera flower has been developed with enhanced biomimetic attributes that may be further utilized for water treatment, biosensors, biomedicine, and in allied science.

Flow Cytometry of Synaptoneurosomes (FCS) Reveals Increased Ribosomal S6 and Calcineurin Proteins in Activated Medial Prefrontal Cortex to Nucleus Accumbens Synapses.

Learning and behavior activate cue-specific patterns of sparsely distributed cells and synapses called ensembles that undergo memory-encoding engram alterations. While Fos is often used to label selectively activated cell bodies and identify neuronal ensembles, there is no comparable endogenous marker to label activated synapses and identify synaptic ensembles. For the purpose of identifying candidate synaptic activity markers, we optimized a flow cytometry of synaptoneurosome (FCS) procedure for assessing protein alterations in activated synapses from male and female rats. After injecting yellow fluorescent protein (YFP)-expressing adeno-associated virus into medial prefrontal cortex (mPFC) to label terminals in nucleus accumbens (NAc) of rats, we injected 20 mg/kg cocaine in a novel context (cocaine+novelty) to activate synapses, and prepared NAc synaptoneurosomes 0-60 min following injections. For FCS, we used commercially available antibodies to label presynaptic and postsynaptic markers synaptophysin and PSD-95 as well as candidate markers of synaptic activity [activity-regulated cytoskeleton protein (Arc), CaMKII and phospho-CaMKII, ribosomal protein S6 (S6) and phospho-S6, and calcineurin and phospho-calcineurin] in YFP-labeled synaptoneurosomes. Cocaine+novelty increased the percentage of S6-positive synaptoneurosomes at 5-60 min and calcineurin-positive synaptoneurosomes at 5-10 min. Electron microscopy verified that S6 and calcineurin levels in synaptoneurosomes were increased 10 min after cocaine+novelty. Pretreatment with the anesthetic chloral hydrate blocked cocaine+novelty-induced S6 and calcineurin increases in synaptoneurosomes, and novel context exposure alone (without cocaine) increased S6, both of which indicate that these increases were due to neural activity per se. Overall, FCS can be used to study protein alterations in activated synapses coming from specifically labeled mPFC projections to NAc.SIGNIFICANCE STATEMENT Memories are formed during learning and are stored in the brain by long-lasting molecular and cellular alterations called engrams formed within specific patterns of cue-activated neurons called neuronal ensembles. While Fos has been used to identify activated ensemble neurons and the engrams within them, we have not had a similar marker for activated synapses that can be used to identify synaptic engrams. Here we developed a procedure for high-throughput in-line analysis of flow cytometry of synaptoneurosome (FCS) and found that ribosomal S6 protein and calcineurin were increased in activated mPFC-NAc synapses. FCS can be used to study protein alterations in activated synapses within specifically labeled circuits.

Sensitivity of WRF/Chem simulated PM2.5 to initial/boundary conditions and planetary boundary layer parameterization schemes over the Indo-Gangetic Plain.

The ability of a chemical transport model to simulate accurate meteorological and chemical processes depends upon the physical parametrizations and quality of meteorological input data such as initial/boundary conditions. In this study, weather research and forecasting model coupled with chemistry (WRF-Chem) is used to test the sensitivity of PM2.5 predictions to planetary boundary layer (PBL) parameterization schemes (YSU, MYJ, MYNN, ACM2, and Boulac) and meteorological initial/boundary conditions (FNL, ERA-Interim, GDAS, and NCMRWF) over Indo-Gangetic Plain (Delhi, Punjab, Haryana, Uttar Pradesh, and Rajasthan) during the winter period (December 2017 to January 2018). The aim is to select the model configuration for simulating PM2.5 which shows the lowest errors and best agreement with the observed data. The best results were achieved with initial/boundary conditions from ERA and GDAS datasets and local PBL parameterization (MYJ and MYNN). It was also found that PM2.5 concentrations are relatively less sensitive to changes in initial/boundary conditions but in contrast show a stronger sensitivity to changes in the PBL scheme. Moreover, the sensitivity of the simulated PM2.5 to the choice of PBL scheme is more during the polluted hours of the day (evening to early morning), while that to the choice of the meteorological input data is more uniform and subdued over the day. This work indicates the optimal model setup in terms of choice of initial/boundary conditions datasets and PBL parameterization schemes for future air quality simulations. It also highlights the importance of the choice of PBL scheme over the choice of meteorological data set to the simulated PM2.5 by a chemical transport model.

Structure activity relationship of pyrazinoic acid analogs as potential antimycobacterial agents.

Tuberculosis (TB) remains a leading cause of infectious disease-related mortality and morbidity. Pyrazinamide (PZA) is a critical component of the first-line TB treatment regimen because of its sterilizing activity against non-replicating Mycobacterium tuberculosis (Mtb), but its mechanism of action has remained enigmatic. PZA is a prodrug converted by pyrazinamidase encoded by pncA within Mtb to the active moiety, pyrazinoic acid (POA) and PZA resistance is caused by loss-of-function mutations to pyrazinamidase. We have recently shown that POA induces targeted protein degradation of the enzyme PanD, a crucial component of the coenzyme A biosynthetic pathway essential in Mtb. Based on the newly identified mechanism of action of POA, along with the crystal structure of PanD bound to POA, we designed several POA analogs using structure for interpretation to improve potency and overcome PZA resistance. We prepared and tested ring and carboxylic acid bioisosteres as well as 3, 5, 6 substitutions on the ring to study the structure activity relationships of the POA scaffold. All the analogs were evaluated for their whole cell antimycobacterial activity, and a few representative molecules were evaluated for their binding affinity, towards PanD, through isothermal titration calorimetry. We report that analogs with ring and carboxylic acid bioisosteres did not significantly enhance the antimicrobial activity, whereas the alkylamino-group substitutions at the 3 and 5 position of POA were found to be up to 5 to 10-fold more potent than POA. Further development and mechanistic analysis of these analogs may lead to a next generation POA analog for treating TB.

ß-Lactamase-Mediated Fragmentation: Historical Perspectives and Recent Advances in Diagnostics, Imaging, and Antibacterial Design.

The discovery of ß-lactam (BL) antibiotics in the early 20th century represented a remarkable advancement in human medicine, allowing for the widespread treatment of infectious diseases that had plagued humanity throughout history. Yet, this triumph was followed closely by the emergence of ß-lactamase (BLase), a bacterial weapon to destroy BLs. BLase production is a primary mechanism of resistance to BL antibiotics, and the spread of new homologues with expanded hydrolytic activity represents a pressing threat to global health. Nonetheless, researchers have developed strategies that take advantage of this defense mechanism, exploiting BLase activity in the creation of probes, diagnostic tools, and even novel antibiotics selective for resistant organisms. Early discoveries in the 1960s and 1970s demonstrating that certain BLs expel a leaving group upon BLase cleavage have spawned an entire field dedicated to employing this selective release mechanism, termed BLase-mediated fragmentation. Chemical probes have been developed for imaging and studying BLase-expressing organisms in the laboratory and diagnosing BL-resistant infections in the clinic. Perhaps most promising, new antibiotics have been developed that use BLase-mediated fragmentation to selectively release cytotoxic chemical "warheads" at the site of infection, reducing off-target effects and allowing for the repurposing of putative antibiotics against resistant organisms. This Review will provide some historical background to the emergence of this field and highlight some exciting recent reports that demonstrate the promise of this unique release mechanism.

Dexamethasone Intravitreal Implant for the Treatment of Macular Edema and Uveitis: A Comprehensive Narrative Review.

Purpose: The purpose of this review article is to provide a comprehensive review of the current applications of intravitreal DEX implant (Ozurdex®, Allergan Inc, Irvine, CA) for a variety of ophthalmic conditions - ranging from FDA approved indications to off-label uses. We have attempted to provide relevant evidence from the literature to help a reader develop an understanding of the biological and pharmacokinetic properties of DEX implant, its uses, and potential side effects. Methods: PubMed searches were performed using the terms "Ozurdex", or "intravitreal DEX implant", AND "retinal vein occlusion", or "diabetic macular edema", or "uveitis". The search was performed in July of 2021, with an additional search in October 2021. All original English language articles were considered for this review. Results: DEX implant has evidence of efficacy in a variety of clinical situations including macular edema associated with retinal vein occlusion, diabetes, uveitis, and others. Safety concerns include cataract formation and progression, intraocular pressure elevation, complications related to intravitreal injection, and opportunistic infections secondary to steroid-induced immune suppression. Conclusion: DEX implant is a useful tool in the management of several retinal disorders. Further studies are needed for head-to-head comparison with other treatment modalities and to determine its precise place in clinical practice.

Synthesis and biological evaluation of orally active prodrugs and analogs of para-aminosalicylic acid (PAS).

Tuberculosis (TB) is one of the world's most deadly infectious diseases resulting in nearly 1.3 million deaths annually and infecting nearly one-quarter of the population. para-Aminosalicylic acid (PAS), an important second-line agent for treating drug-resistant Mycobacterium tuberculosis, has moderate bioavailability and rapid clearance that necessitate high daily doses of up to 12 g per day, which in turn causes severe gastrointestinal disturbances presumably by disruption of gut microbiota and host epithelial cells. We first synthesized a series of alkyl, acyloxy and alkyloxycarbonyloxyalkyl ester prodrugs to increase the oral bioavailability and thereby prevent intestinal accumulation as well as undesirable bioactivation by the gut microbiome to non-natural folate species that exhibit cytotoxicity. The pivoxyl prodrug of PAS was superior to all of the prodrugs examined and showed nearly quantitative absorption. While the conceptually simple prodrug approach improved the oral bioavailability of PAS, it did not address the intrinsic rapid clearance of PAS mediated by N-acetyltransferase-1 (NAT-1). Thus, we next modified the PAS scaffold to reduce NAT-1 catalyzed inactivation by introduction of groups to sterically block N-acetylation and fluorination of the aryl ring of PAS to attenuate N-acetylation by electronically deactivating the para-amino group. Among the mono-fluorinated analogs prepared, 5-fluoro-PAS, exhibited the best activity and an 11-fold decreased rate of inactivation by NAT-1 that translated to a 5-fold improved exposure as measured by area-under-the-curve (AUC) following oral dosing to CD-1 mice. The pivoxyl prodrug and fluorination at the 5-position of PAS address the primary limitations of PAS and have the potential to revitalize this second-line TB drug.

Burnout and resilience in doctors in clinical and preclinical departments in a tertiary care teaching and dedicated COVID-19 hospital.

BACKGROUND: The worldwide COVID-19 pandemic has significantly altered our life. Doctors more so than the general public because of their involvement in managing the COVID-infected individuals, some of them 24/7 end in burnout. Burnout in doctors can lead to reduced care of patients, increased medical errors, and poor health. Burnout among frontline health-care workers has become a major problem in this ongoing epidemic. On the other hand, doctors in preclinical department have a lack of interaction with patients, with not much nonclinical professional work to boot, find the profession less gratifying which perhaps increase their stress level. AIM: The aim was to study the prevalence of burnout and measure resilience in doctors in clinical and in preclinical departments. MATERIALS AND METHODS: This observational, cross-sectional, comparative study was carried out in a tertiary care teaching hospital and COVID care center. By purposive sampling 60 preclinical and 60 clinical doctors in a tertiary health care center were included in the study. After obtaining the Institutional Ethics Committee approval and informed consent, the doctors were administered a self made socio-demographic questionnaire, the Copenhagen Burnout Inventory, and the Connor-Davidson Resilience Scale. Doctors were given a self-made questionnaire, the Copenhagen Burnout Inventory, and the Connor-Davidson Resilience Scale. RESULTS: The prevalence of burnout was seen more in clinical doctors (55.47) and the resilience was observed more in preclinical doctors (88.9). DISCUSSION: Resident doctors are a major force to combat COVID-19 as frontline health workers; hence, one can visualize burnout amongst them. On an individual basis, the work-related burnout was severely high in the clinical group owing to the workload which has been corresponding to a number of western studies. Nonclinical department doctors from pathology, community medicine, and microbiology did show burnout but showed a greater score in resilience. Psychological resilience has been identified as a component in preventing burnout. CONCLUSION: Therapy sessions can be used in clinical doctors facing burnout to build up their resilience.

Assessment of Depression, Anxiety, Stress, and quality of life in rheumatoid arthritis patients and comparison with healthy individuals.

BACKGROUND: Rheumatoid arthritis (RA) is a disabling condition that results in considerable suffering and negatively impacts an individual's psychological, financial, social, and quality of life (QoL). Pain, fatigue, and disabilities, which may be considered as stress factors, are common challenges that may subsequently lead to psychological distress. AIM: Assessment of Depression, Anxiety, Stress, and QoL in RA patients and Comparison with healthy individuals. MATERIALS AND METHODS: This cross-sectional analytical study included 50 RA patients who have reported to a tertiary health care center on outpatient basis and an equal number of age- and sex-matched healthy individuals. The study was conducted after obtaining Institutional Ethics Committee approval and informed consent of the participants. Patients were assessed based on Disease Activity Score incorporating erythrocyte sedimentation rates, Depression Anxiety Stress Scale (DAS21), Health Assessment questionnaire, Visual Analog Scale, and Multidimensional scale of Perceived Social Support. RESULTS: Levels of anxiety, depression, and stress in patients with RA were significantly higher as compared to age- and sex-matched healthy controls. RA patients had significantly lower scores on total social support, as well as social support of family and friends. However, there was no difference between RA patients and healthy controls on social support from significant others. CONCLUSION: Patients with RA had significantly higher levels of anxiety, depression, and stress and significantly lower levels of social support compared to age- and sex-matched healthy controls. The therapeutic implications of these findings need further evaluation.

Differentiation of hepatic encephalopathy from delirium tremens: A case series and review.

Hepatic encephalopathy (HE) is an important and potentially life threatening complication in alcoholic patients with decompensated liver function that develop even as they continue drinking. Delirium tremens, on the other hand, is an acute condition resulting from alcohol abstinence in a person dependent on alcohol, making it a life threatening diagnosis that requires intensive care and successful management of the withdrawal. Often in medical wards, these two conditions are mistaken and so is the management plan confused with each other. Making the right diagnosis early on during the hospital course is extremely important in these critical conditions so as to make an appropriate schedule for treatment and a better outcome for the same. A case series of patients who presented with a diagnostic dilemma is reported. Clinical examinations, diagnostic tools to measure the levels of ammonia and liver function tests and hemogram, West Haven criteria and Child-Pugh grading, and clinical scales of these patients are reported. Increased levels of ammonia were present in all the cases. The subtle similarities in the presentation of the two conditions often make it confusing for the clinician to distinguish between them. Using a simple test of measuring ammonia levels in the blood helps in such situations. The detection of raised levels of ammonia in cases of chronic liver disease helps in not just the diagnosis but also is an important prognostic indicator for development of HE.

Psychogenic vomiting: A case series.

Psychogenic vomiting is a syndrome in of recurrent vomiting without any organic pathology. It must be differentiated from cyclical vomiting syndrome, functional vomiting, and chronic idiopathic nausea. It occurs as a result of an emotional or psychic disturbance. This condition is highly disabling, increasingly recognized, and under-researched. In India, the number of patients reporting to the psychiatric outpatient department with eating disorders is comparatively very less. We describe how two patients with diagnostic dilemmas who were treated successfully after psychiatric intervention.

Management of psychotic and mood disorders in intellectual disability: A case series.

People with intellectual disability (ID) have a greater frequency of psychiatric illnesses, ranging from 10% to 80%, as compared to the general population. It has been proven that mood stabilizers are beneficial in the management of behavior issues in people with ID. Here, we report a series of five cases with mild and moderate ID with behavioral disturbances including mood and psychotic symptoms managed successfully with sodium valproate as the part of the treatment.

Prelimbic cortex is a common brain area activated during cue-induced reinstatement of cocaine and heroin seeking in a polydrug self-administration rat model.

Many preclinical studies examined cue-induced relapse to heroin and cocaine seeking in animal models, but most of these studies examined only one drug at a time. In human addicts, however, polydrug use of cocaine and heroin is common. We used a polydrug self-administration relapse model in rats to determine similarities and differences in brain areas activated during cue-induced reinstatement of heroin and cocaine seeking. We trained rats to lever press for cocaine (1.0 mg/kg per infusion, 3-hr/day, 18 day) or heroin (0.03 mg/kg per infusion) on alternating days (9 day for each drug); drug infusions were paired with either intermittent or continuous light cue. Next, the rats underwent extinction training followed by tests for cue-induced reinstatement where they were exposed to either heroin- or cocaine-associated cues. We observed cue-selective reinstatement of drug seeking: the heroin cue selectively reinstated heroin seeking and the cocaine cue selectively reinstated cocaine seeking. We used Fos immunohistochemistry to assess cue-induced neuronal activation in different subregions of the medial prefrontal cortex, dorsal striatum, nucleus accumbens, and amygdala. Fos expression results indicated that only the prelimbic cortex (PL) was activated by both heroin and cocaine cues; in contrast, no significant cue-induced neuronal activation was observed in other brain areas. RNA in situ hybridization indicated that the proportion of glutamatergic and GABAergic markers in PL Fos-expressing cells was similar for the heroin and cocaine cue-activated neurons. Overall, the results indicate that PL may be a common brain area involved in both heroin and cocaine seeking during polydrug use.

The correlation between intensive care unit attending physician continuity of care with financial and clinical outcomes.

PURPOSE: "Attending rotations" on intensive care unit (ICU) services have been in place in most teaching hospitals for decades. However, the ideal frequency of patient care handoffs is unknown. Frequent attending physician handoffs could result in delays in care and other complications, while too few handoffs can lead to provider burnout and exhaustion. Therefore, we sought to determine the correlation between frequency of attending shifts with ICU charges, 30-day readmission rates, and mortality rates. METHODS: We performed a retrospective cohort study at a large, urban, academic community hospital in Baltimore, MD. We included patients admitted into the cardiac or medical ICUs between September 1, 2012, and December 10, 2015. We tracked the number of attending shifts for each patient and correlated shifts with financial outcomes as a primary measure. RESULTS: For any given ICU length of stay, we found no distinct association between handoff frequency and charges, 30-day readmission rates, or mortality rates. CONCLUSIONS: Despite frequent handoffs in care, there was no objective evidence of care compromise or differences in cost. Further validation of these observations in a larger cohort is justified.