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Byline: P. Suresh, R. Kapoor, B. Kapur Sir, A 37-year-old male presented with lower abdominal pain and hematochezia. Colonoscopy showed a mass extending from 16 to 18 cm of the [...]

Climate change poses significant threats to agricultural systems, necessitating a comprehensive understanding of its impact for effective adaptation strategies. This study examines the influence of climate change on agriculture in the United States, primarily focusing on temperature shifts and precipitation variations. Utilizing historical data and climate projections, we analyse trends in mean temperature and precipitation patterns from 1950 to 2020. The results indicate a noteworthy increase in annual mean temperature over the years, attributed to climate change. This rise in temperature has multifaceted implications, including heat stress in crops and exacerbation of drought conditions. The study also explores the complex relationship between precipitation patterns and climate change, highlighting regional variations and potential shifts in future precipitation trends. By projecting data under SSP 1-1.9 emission scenario, we assess potential changes in mean temperatures, hot days, and precipitation for 2040-2059 periods. In conclusion, this study sheds light on the interplay between climate change and agricultural systems, emphasizing the need for adaptive strategies to secure food production and mitigate potential risks. The findings underscore the urgency of proactive measures to safeguard agricultural sustainability and resilience in the face of evolving climatic conditions.

A retrospective review of 143 cases of carcinoma of the gall bladder is presented. The disease was more common in females in the 5th and 6th decades. Pain, anorexia, weight loss and jaundice were the common presenting symptoms, and hepatomegaly and palpable gall bladder the common signs. Laboratory and radiological investigations were merely confirmatory as the diagnosis in a majority of the cases was clinically obvious. Aspiration cytology and laparoscopic biopsy were of help in obtaining histological diagnosis. Only 47 patients were considered fit enough to undergo laparotomy. In a majority of these patients biopsy alone was possible while palliative procedures were performed in the others. The operative mortality was 18% even in this selected group of patients, due to the poor general condition and the advanced stage of the disease at the time of diagnosis. Curative resection may be possible and long term survival is expected in incidentally found carcinoma at cholecystectomy. The only hope lies in prevention by prompt treatment of patients with benign biliary disease. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 37-year-old male diagnosed with irreversible cerebellar toxicity. Topics discussed include the medical record of the patient, the diagnosis of his irreversible cerebellar toxicity through magnetic resonance imaging, his physical examinations, his treatment through chemotherapy, and an overview of the disease.

Proton-sensing G Protein Coupled Receptors (GPCRs) sense changes in the extracellular pH to effect cell signaling for cellular homeostasis. They tend to be overexpressed in solid tumors associated with acidic extracellular pH, and are of direct interest as drug targets. How proton-sensing GPCRs sense extracellular acidification and activate upon protonation change is important to understand, because it may guide the design of therapeutics. Lack of publicly available experimental structures make it challenging to discriminate between conflicting mechanisms proposed for proton-binding, as main roles have been assigned to either an extracellular histidine cluster or to an internal carboxylic triad. Here we present a protocol to derive and evaluate structural models of the proton-sensing GPR68. This approach integrates state-of-the-art homology modeling with microsecond-timescale atomistic simulations, and with a detailed assessment of the compatibility of the structural models with known structural features of class A GPCRs. To decipher structural elements of potential interest for protonation-coupled conformational changes of GPR68, we used the best-compatible model as a starting point for independent atomistic simulations of GPR68 with different protonation states, and graph computations to characterize the response of GPR68 to changes in protonation. We found that GPR68 hosts an extended hydrogen-bond network that inter-connects the extracellular histidine cluster to the internal carboxylic triad, and which can even reach groups at the cytoplasmic G-protein binding site. Taken together, results suggest that GPR68 relies on dynamic, hydrogen-bond networks to inter-connect extracellular and internal proton-binding sites, and to elicit conformational changes at the cytoplasmic G-protein binding site., Competing Interests: G.S. and H.N. are employees of Boehringer Ingelheim Pharma GmbH & Co. KG., (© 2023 The Authors.)

Introduction: Advancing Quality (AQ) has high reliability and is effective at reducing unwarranted variation in care programme operated by the Advancing Quality Alliance (AQuA). Established in 2008, AQ aims to support NHS healthcare organisations toimprove the reliability of clinical practices so that every patient consistently
receives the highest quality care possible, every time. Our work with
dedicated clinical teams and managers aims to improve health outcomes for
patients and the population whilst reducing unwarranted variation in highly prevalent conditions., Methods: The population is identified retrospectively using ICD1-0 codes and a standardised data collection tool is used to assess management of people >60 years of age with a HFR, either on arrival to hospital or during their admission., Results: 7317 patients had a nutritional screen recorded using the MUST score between January 2015 and December 2016. In hospital mortality for patients receiving nutritional screen within 24 h was 6.1% compared to 9.3% for screens after 24 h, p < 0.001 (Fisher's exact test). Mortality rate for those patients without a risk score recorded was 9.4%.The number of patients receiving nutritional screen within 24 h, improved from 86% to 94%., Conclusion: Inpatient mortality was significantly lower in patients who had their MUST score within 24 h of admission. This is likely attributed to the improvement of the overall package of care if their assessment is performed early in those patients who are admitted to an orthopaedic or neck of femur ward. An early MUST score identifies nutritional deficiency and those at risk allowing measures can be taken to address malnutrition early during the inpatient stay., Competing Interests: None., (© 2019 Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.)

Background: The impact of messaging campaigns on influencing urgent care- and emergent care-seeking behaviors, including the use of in-network providers, is not well-understood. Although out-of-network healthcare utilization can have negative financial consequences for patients in narrow network Affordable Care Act plans, individuals with time-sensitive medical conditions, and especially patients visiting the emergency department, may not think about out-of-network issues. Inappropriate or avoidable emergency department visits can also create unnecessary costs for patients., Objective: To evaluate the impact of 5 messaging strategies to educate individuals about the use of in-network providers and when care should be sought in the emergency department, urgent care center, or other sites of care., Methods: Using a retrospective analysis, individuals aged ≥18 years who were enrolled in an individually purchased Affordable Care Act-compliant Humana plan as of July 1, 2015, were randomized to 1 of 5 messaging arms (e-mail, magnet mailer with or without e-mail, and key-tag mailer with or without e-mail) or to a control group. The outreach was implemented and evaluated in 2 distinct, geographically defined populations of Orlando, Palm Beach, and Tampa, Florida (Population 1); and Atlanta, Georgia, and San Antonio and Austin, Texas (Population 2). The relative number of each emergency department, urgent care, and out-of-network visits during follow-up was modeled using negative binomial regression. Cox proportional hazard models were used to calculate the risk for ≥1 of each visit type (assessed separately) and high emergency department utilization (defined as ≥3 visits during follow-up) relative to the control, while accounting for variable follow-up time., Results: The relative numbers of each visit type assessed were not significantly different for any message group compared with the control in either population. The risk for an emergency department visit was 4% lower in the e-mail arm of Population 2 (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.99; P = .005) and 7% lower in the e-mail/key-tag arm of Population 1 (HR, 0.93; 95% CI, 0.89-0.97; P = .001). The risk for high emergency department utilization was significantly reduced by the key-tag, magnet, and e-mail/key-tag strategies in Population 1, but no impact was found in Population 2., Conclusion: Despite the mixed results, the study provides new insights into how different messaging strategies could be used to educate patients and influence healthcare utilization decisions by people with health insurance.

Objective: To conduct a systematic review evaluating the effectiveness of a folate-fortified oral contraceptive preparation in increasing blood folate concentrations to levels providing optimal protection against neural tube defects (> 906 nmol/L)., Methods: We searched Medline, EMBASE, Web of Science, and the Cochrane Library for human studies published from inception to June 2013 that evaluated oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. Efficacy and bioequivalence data were evaluated from included studies., Results: Overall, efficacy and bioequivalence data for the folate-fortified oral contraceptive show that it is at least as effective as folic acid alone in raising blood folate concentrations, and that the concomitant administration of folate with the oral contraceptive component does not affect its absorption or kinetics., Conclusion: A folate-fortified oral contraceptive preparation provides an option for women to maintain blood folate levels, especially those who may be planning a family after the cessation of oral contraceptive therapy.

Objective: To conduct a systematic review and meta-analysis of the effect of oral contraceptive use on plasma and red blood cell (RBC) folate concentrations., Methods: We searched Medline, EMBASE, Web of Science, and the Cochrane library for human studies published from inception to June 2013 evaluating oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. A random-effects model of outcomes was used for the meta-analysis., Results: A total of 2831 women in 17 studies were included in the analysis. In those whose plasma folate concentrations were available, there was a significant folate-lowering effect of oral contraceptives observed (mean reduction 1.27 µg/L; 95% CI 1.85 to 0.69, P < 0.001). Similarly, after analyzing data from 1389 women in 12 studies whose RBC folate concentrations were available, significantly lower folate status was observed among oral contraceptive users (mean reduction 59.32 µg/L; 95% CI 58.03 to 23.04, P < 0.001)., Conclusion: Because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is critical for women of childbearing age to continue folate supplementation during oral contraceptive use.

Introduction: The analysis of pediatric and adult hair is a useful non-invasive biomarker to effectively detect long term exposure to various xenobiotics, specifically drugs of abuse such as cocaine, opiates and amphetamines. Very often individuals are using, or are exposed to multiple drugs simultaneously and therefore it is important to be able to detect them in the same analysis. We have developed a sensitive and specific solid phase micro extraction (SPME) coupled with gas chromatography mass spectrometry (GC/MS) to detect 17 different analytes in hair using a single extraction method., Method: Five milligrams of hair is extracted overnight, subjected to solid phase extraction (SPE) and then to SPME-GC/MS. The aimed analytes include amphetamine, methamphetamine, MDA, MDMA, cocaine, benzoylecognine, norcocaine, cocaethylene, methadone, codeine, morphine, 6-AM, oxycodone, oxymorphone, hydrocodone, hydromorphone and meperidone., Results: The following are the LOD of the various drugs: 0.2ng/mg hair for amphetamine, methamphetamine, MDA, MDMA, morphine, codeine, 6-AM, oxycodone, oxymorphone, hydromorphone, hydrocodone, meperidine and 0.13ng/mg hair for cocaine, benzoylecognine, cocaethylene, norcocaine and methadone., Conclusion: This GC/MS method is sensitive and specific to detect the presence of these 17 analytes in as little as 5mg of hair and is especially useful for newborn and child hair analysis where the amount of hair is often very limited., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine folic acid dosage requirements for individuals across a broad range of BMI values, using dose per kilogram lean body weight (LBW) as a primary predictor of systemic exposure. Steady-state folate concentrations of ≥ 15.9 nmol/L were assumed to be sufficient for reducing the risk for neural tube defects in the general population., Methods: Data from a recent study of single-dose folic acid pharmacokinetics among 12 obese and 12 non-obese women of childbearing age were analyzed to determine expected steady-state concentrations. The mean folic acid dose per kilogram LBW that achieved serum folate concentrations of ≥ 15.9 nmol/L was applied to a broad range of BMI values to evaluate daily dose requirements., Results: Modest differences in folic acid requirements were noted for individuals among the non-obese, overweight, and obese categories. The current supplementation guidelines suggesting a daily dose of 0.4 mg appear to satisfy the needs of women at even the upper extremes of obesity. However, because even with appropriate folate supplementation obese women have an increased risk of neural tube defects, and they may benefit from higher intake and higher serum concentrations of folic acid., Conclusion: Current guidelines recommend an adequate folic acid dose for obese women of childbearing age. Thus, it is unlikely that folate deficiency is associated with the elevated risk for neural tube defects in this population.

Background: Synthetic folic acid (0.4-1.0 mg) consumed during the periconceptional period has been shown to reduce the risk of neural tube defects. Women with poor supplement adherence or a previous pregnancy affected by a neural tube defect may need to take higher doses of folic acid (4-5 mg). However, there are limited data on the pharmacokinetics of higher folic acid doses., Objective: Our aim was to compare steady state folate concentrations in women of childbearing age who took 5 or 1.1 mg folic acid daily for 30 wk., Design: Forty nonpregnant women aged between 18 and 45 y, who did not take folic acid supplements, were enrolled in the study. Subjects were randomly assigned to take either 5 or 1.1 mg folic acid daily for 30 wk. Plasma and red blood cell (RBC) folate concentrations were measured at baseline and at weeks 2, 4, 6, 12, and 30., Results: There was no significant difference in baseline RBC folate concentrations between the 2 groups (1121 +/- 410 and 1035 +/- 273 nmol/L for the 5- and 1.1-mg folic acid groups, respectively). Significant differences in RBC folate were detected between groups at weeks 4, 6, 12, and 30. RBC folate concentrations by week 30 were 2339 +/- 782 and 1625 +/- 339 nmol/L for the 5- and 1.1-mg folic acid groups, respectively., Conclusion: The use of 5 mg folic acid among women of childbearing age produced higher blood folate concentrations, with a faster rate of folate accumulation, compared with 1.1 mg folic acid.

Background: Severe exacerbation of chronic neuropathic pain often requires morphine in patients already treated with drugs such as tricyclic antidepressants, carbamazepine and gabapentin. However, it is unclear if a combination of these drugs intensifies the effects of morphine on the respiratory system and, if so, whether these effects are due to pharmacokinetic or pharmacodynamic interaction., Methods: We gave rabbits (n=6 per group) the following drugs daily for 4 days: subcutaneous normal saline 1 mL (control); amitriptyline subcutaneously 7 mg/kg; carbamazepine orally 100 mg/kg; gabapentin subcutaneously 25 mg/kg; and all three drugs concurrently (combination). On the fifth day, morphine 5 mg/kg was given IV, and Paco2, Pao2 and pH were measured. Morphine, morphine 3-glucoronide and morphine 6-glucoronide concentrations were measured in the plasma over the 4 h period after morphine injection., Results: Compared with controls, premorphine baseline Paco2 was significantly higher (P<0.05) in the amitriptyline group. Postmorphine Paco2 was significantly higher in the amitriptyline and combination groups at all time points over the 240 min, and in the gabapentin group at 10 and 30 min after morphine injection (P<0.05). Peak Paco2 was significantly higher in the amitriptyline group (58.4+/-1.6 mm Hg; mean SD, P<0.005) and in the combination group (57.4+/-1.0 mm Hg, P<0.02) than in the control group (50.2+/-5.2 mm Hg). Similarly, the area under the curve of Paco2 from zero to 240 min was significantly higher in the amitriptyline and combination groups than in the control (P<0.001). There were no significant differences among the groups in plasma concentrations of morphine and its metabolites., Conclusions: We conclude that pretreatment with amitriptyline increases morphine- induced hypercarbia through pharmacodynamic processes. The effects of carbamazepine or gabapentin were not obvious in this model.

Aims: To compare the incorporation rate (ICR) of fatty acid ethyl esters (FAEE) in hair between guinea pigs and humans, and to assess the relationship between ethanol exposure and FAEE concentrations in hair., Methods: Published data from pregnant guinea pigs, including maximum blood ethanol concentration (BEC), dosage regimen, and total hair FAEE concentration, were compared with published data from alcoholic patients, where dose of ethanol consumed and total hair FAEE concentration were reported. Mean values of ethanol Vmax for pregnant guinea pigs and humans were obtained from published data (26.2 and 24 mg/dl/h, respectively)., Results: Total and individual FAEE ICRs, defined as the ratio of hair FAEE to the area under the BEC-time curve (total systemic ethanol exposure), were found to be on average an order of magnitude lower in the guinea pig than in the human. The profiles of ester incorporation also differed slightly between species, with ethyl stearate being highly incorporated in guinea pig hair and less so in human hair. The results may reflect in the human greater FAEE production, greater FAEE deposition in hair, slower FAEE catabolism, differential sebum production and composition, or a combination thereof. Also, ethyl oleate was found to correlate with total systemic ethanol exposure for both guinea pigs and humans, correlation coefficients equalling 0.67 (P < 0.05) and 0.49 (P < 0.05), respectively. No other ethyl esters, nor total FAEE, were found to correlate with systemic ethanol exposure., Conclusion: When extrapolating FAEE concentrations in hair from guinea pigs to humans, an order of magnitude difference should be considered, with humans incorporating more FAEE per unit of ethanol exposure. Also, the results suggest caution should be taken when interpreting values of single esters because of their differential incorporation among species. Lastly, our findings suggest ethyl oleate may be of keen interest in FAEE hair analysis, particularly across species.

A newborn infant whose mother had used venlafaxine, a selective inhibitor of both norepinephrine and serotonin reuptake, throughout pregnancy exhibited signs consistent with the norepinephrine and serotonin reuptake withdrawal syndrome. Is it possible that mother's milk can help mitigate the effects of norepinephrine and serotonin reuptake withdrawal? Pharmacokinetic analysis and review of the only published case with active treatment of a baby with venlafaxine suggest that breastfeeding may mitigate the neonatal withdrawal syndrome.

Question: In the 1960s, Dr Cameron, a Montreal, Que, psychiatrist, experimented with drug-induced sleep and electroconvulsive therapy for psychiatric patients, believing that this method "wipes them clean of harmful memories." In 1992 the government of Canada settled lawsuits by former patients of Dr Cameron, awarding them large payments. The government rejected a similar claim by Lloyd Schrier, whose mother had been treated by Dr Cameron while she was carrying Lloyd, arguing that Lloyd was not Cameron's patient. Or was he?, Answer: The fetus was exposed to the medications taken by his mother, (eg, barbiturates) and thus qualifies as an unconsenting patient.

Objective: To compare iron absorption of a prenatal multivitamin supplement containing both iron and calcium (HICA) to that of another multivitamin containing a lower iron dose and no calcium (LI)., Methods: In a crossover study, serum iron was measured in 12 healthy women administered HICA and LI separately on 2 different occasions. Blood samples were taken at 0, 1, 2, 3, 4, 6, and 8 hours after administration of each supplement., Results: The values of the area under the concentration-time curve (AUC) were not significantly different between LI (79.1 +/- 36.0 micro M*h) and HICA (91.4 +/- 50.4 micro M*h) (P =.37). After standardizing the AUC for dose, the relative absorption over the 8-hour time period was significantly higher for LI (2.3 +/-.0 micro M*h/mg) than for HICA (1.5 +/- 0.8 micro M*h/mg) (P =.021)., Conclusion: The absorption of iron from a low-iron-containing supplement was similar to that from a supplement with almost twice the amount of iron, due possibly to the exclusion of calcium in the LI product. Thus, while offering similar amounts of iron, the LI supplement may be better tolerated by women who are sensitive to iron-induced adverse effects.

The nutritional status of 24 patients of carcinoma oesophagus was assessed before and after central hyperalimentation with a liquid blenderized diet containing 3000-3500 cal and 100-120 g protein. The overall prevalence of malnutrition was found to be 70.8 per cent before the initiation of therapy. Of the various parameters used for assessment of nutritional status weight loss was the most common finding (91.6%) followed by alteration in midarm circumference, haemoglobin, triceps skin fold thickness, midarm muscle circumference and serum albumin. Enteral hyperalimentation for 10 days improved nutritional status by inducing significant gain in body weight (74.1%), triceps skin fold thickness (50%), midarm circumference (58%), midarm muscle circumference (62.5%) and serum albumin levels (91.6%). There was no significant change in haemoglobin levels.

In the present paper, major issues related to drug testing are discussed. For example, drug-testing techniques measure the presence of a drug or drugs but are not sophisticated enough to measure impairment from drug use. Moreover, it is difficult to determine the route of drug administration, quantity or frequency, as well as when the drug was taken, on the basis of the laboratory results. Selection of the drug to be tested should depend on the local availability of the drug, its abuse potential and clinical effects, as well as on the availability of analytical technology and expertise in testing and in interpreting laboratory results. The most sophisticated drug-testing approach is gas chromatography coupled with mass spectrometry (GC/MS), which is regarded as a "gold standard"; it is used in confirmatory testing. Typically, GC/MS is preceded by a rapid immunoassay method to eliminate the majority of the "negative" samples. Despite the existence of sophisticated drug-testing methods, it is still possible to obtain incorrect test results. Such results may be caused by the presence of interfering substances or adulteration of the urine sample. A number of techniques can be employed to reduce the likelihood of obtaining erroneous results and to detect adulterated urine samples. A "positive" drug finding can have a serious impact on the livelihood of an individual, therefore, persons conducting such tests should adhere to the strictest standards of laboratory performance. Only qualified and experienced individuals with proper laboratory equipment should perform these analyses. The standards of laboratory performance must meet local legal and forensic requirements. Access to patient samples and laboratory records must be restricted in order to prevent the tampering of samples and results. In order to maintain confidentiality, the results must be communicated only to the medical review officer. Chain-of-custody documents and all file so that they can be examined in case of a legal challenge. The laboratory must have a complete record on quality control. Finally, specific initial and confirmatory testing requirements should be met.