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Aim: Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression. Materials & methods: Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established via preliminary screening against A549 based lung cancer cell line at 5 μM. Results & conclusion: Compound 4b exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC 50 against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound 4p has been selected for further studies, as it demonstrated significant cytotoxicity, while compound 4b showed no effect on AKT gene expression but upregulated IGF-1R gene expression, suggesting a role in managing diabetes. Compound 4p exhibited the ability to decrease AKT expression and increase IGF-1R expression, indicating its potential for treating both diabetes and cancer.

The ionic current blockage from a nanopore sensor is a fundamental metric for characterizing its dimensions and identifying molecules translocating through it. Yet, most analytical models predicting the conductance of a nanopore in both open and obstructed states remain inaccurate. Here, using an oblate spheroidal coordinate framework to study the electrical response of nanopore access regions, we reveal that the widely used model from Kowalczyk et al. significantly overestimates access region contributions when blocked by a cylindrical object, like DNA. To address this, we present an improved analytical model for the obstructed access resistance, which we establish as highly accurate through finite-element simulations, especially for ultrathin membranes and long narrow channels. Equipped with an improved nanopore conductance model, this work provides tools for more accurate calculation of the pore size and for the expected blockade from DNA, of high practical value for many biosensing applications.

Introduction: Severe acute respiratory virus syndrome coronavirus 2 (SARS-CoV-2) was responsible for coronavirus disease (COVID-19) pandemic. As patients recovered from COVID-19 infection, hair loss was increasingly observed as a distressing symptom., Methods: This was a cross-sectional study of patients with post COVID-19 hair loss between July to December 2021 at a tertiary care center. Detailed history, clinical examination, trichoscopy and biochemical tests were performed and recorded. COVID-19 disease severity was assessed based on duration of COVID-19 infection and place of management., Results: The study included 120 patients with a mean age of 39.6 years. The majority of the patients were females treated at home and had COVID-19 infection for >2 weeks. The mean visual analog scale (VAS) score for stress was 5.25. Vitamin D deficiency was present in 56.7% and low ferritin in 30% of cases. The mean time of onset of hair loss post COVID-19 was 49 days. Patients mainly presented with diffuse hair loss. Trichodynia was present in 15.8% of cases. The degree of hair loss was severe in 55.8% of the subjects. Positive hair pull test was seen in 65% of patients. Most common trichoscopic features included single hair follicles (81.7%) and vellus hair >10% (60%)., Conclusions: The mean time of onset of hair loss post COVID-19 infection was less than 2 months. Majority patients had diffuse pattern and severe degree of hair loss. Trichoscopy can aid in unmasking co-existing patterned hair loss in patients presenting clinically with diffuse hair loss.

Introduction: The purpose of this study was to determine the level of nitric oxide (NO) in both serum and saliva of smokers and nonsmokers with chronic periodontitis before and after scaling and root planing, as well as to compare the same (NO levels) with the severity of periodontitis., Materials and Methods: Sixty people took part in the study and were divided into three groups. The control group (Group I) involved 20 patients who were nonsmokers with healthy periodontium. The other two groups included 20 patients each, where Group II was nonsmokers with chronic periodontitis and Group III was smokers with chronic periodontitis. In addition, NO generation was quantified indirectly in this study using the Griess reaction to determine the nitrite level in serum and saliva., Results: The mean value of salivary and serum NO was higher in Group III than in Group II, and NO decreased considerably ( P < 0.01) in both Groups II and III after treatment compared to before treatment., Conclusion: Serum and salivary NO levels can be used as a good predictor of the inflammatory condition of the periodontium in smokers., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 National Journal of Maxillofacial Surgery.)

Study of 35 days was conducted to evaluate citric acid (CA) as an additive in poultry broiler feed with lower mineral content of calcium (Ca) and total phosphorus (TP) in commercial broiler poultry birds for its effect on growth, nutrient utilization, carcass characteristics, and economics. Vancobb-400 strain day old broiler chicks were divided into four main treatment groups T 0, T 1 , T 2 , and T 3. Treatment groups were further divided into eight replicates with ten chicks in each. T 0 served as control, given standard corn-soy flakes-based ration (Pre-starter %: Crude protein (CP)-23, Ca-1.00, TP-0.70; Starter %: CP-22, Ca-1.10, TP-0.72, and Finisher %: CP-20, Ca-0.99, TP-0.70). Treatment T 1 served as positive control with added 0.5% CA (Pre-starter %: CP-23, Ca-1.00, TP-0.70; Starter %: CP-22, Ca-1.10, TP-0.72 and Finisher %: CP-20, Ca-0.99, TP-0.70). Treatment T 2 was given feed containing 0.5% CA with low Ca and TP content (Pre-starter %: CP-23, Ca-0.90, TP-0.66; Starter %: CP-22, Ca-0.99, TP-0.71 and Finisher %: CP-20, Ca-0.90, TP-0.69), whereas treatment T 3 was given feed containing 0.5% CA with moderately low Ca and TP content (Pre-starter %: CP-23, Ca-0.80, TP-0.65; Starter %: CP-22, Ca-0.88, TP-0.70 and Finisher %: CP-20, Ca-0.79, TP-0.68). Birds offered moderately low Ca and TP with 0.5% CA addition, exhibited higher growth rate (P < 0.05), better nutrient utilization with positive influence on dressing percentage and forequarters weight. Economics of broiler feeding revealed that 0.5% CA supplementation fetched highest gross return above feed cost in broiler birds offered feed with moderately low Ca and TP content whereas lowest profit was recorded in feed with low content of Ca and TP. In conclusion, supplementation of 0.5% CA in feed with low and moderately low Ca and TP content positively influenced overall growth, and carcass characteristics. Economics of broiler feeding with moderately low Ca and TP content revealed highest profit with CA (0.5%) supplementation., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe's worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.

Heterocyclic compounds are considered to be one of the most established structural classes due to their extensive application in agrochemicals, pharmaceuticals and organic materials. Over the past few years, the development of heterocyclic compounds has gone through a considerable renaissance from conventional traditional methodologies to non-conventional electro-organic synthesis. Replacing metal catalysts, strong oxidants and multi-step methodologies with metal and strong oxidant-free single-step protocols has revolutionized the field of sustainable organic synthesis. Electro-organic synthesis has evolved as a scalable and sustainable approach in different synthetic protocols in an environment-benign manner. The current review outlines the recent developments in C-C, C-N, C-S and C-O/Se bond formation for heterocycle synthesis using electrochemical methods. Different synthetic strategies and their detailed mechanistic description are presented to enlighten the future applications of electrochemistry in heterocycle synthesis.

Weber's law states that the ratio of the smallest perceptual change in an input signal and the background signal is constant. The law is observed across the perception of weight, light intensity, and sound intensity and pitch. To explain Weber's law observed in steady-state responses, two models of perception have been proposed, namely the logarithmic and the linear model. This paper argues in favour of the linear model, which requires the sensory system to generate linear input-output relationship over several orders of magnitude. To this end, a four-node motif (FNM) is constructed from first principles whose series provides almost linear relationship between input signal and the output over arbitrary range of input signal. Mathematical analysis into the origin of this quasi-linear relationship shows that the series of coherent type-1 feed-forward loop (C1-FFL) is able to provide perfectly linear input-output relationship over arbitrary range of input signal. FNM also reproduces the neuronal data of numerosity detection study on the monkey. The series of FNM also provides a mechanism for sensitive detection over arbitrary range of input signal when the output has an upper limit. Further, the series of FNM provides a general basis for a class of bow-tie architecture where the number of receptors is much lower than the range of input signal and the "decoded output". Besides (quasi-)linear input-output relationship, another example of this class of bow-tie architecture that the series of FNM is able to produce is absorption spectra of cone opsins of humans. Further, the series of FNM and C1-FFL, both, can compute logarithm over arbitrary range of input signal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Novel coronavirus is a disease that can propagate easily with very minute carelessness and with very little physical contact between people. Presently, the world's central health institution called the World Health Organization has approved and advised the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) swab test as the most important and effective diagnostic method to confirm if a patient has COVID-19 symptoms or not. This test takes at least a day for revealing the results, depending on the feasible resources in the neighborhood. Moreover, the RT-PCR test gives sometimes false positive results and slow in the process. To keep the potential virus carriers and potential causes of the disease quarantined as early as possible, there is still a requirement for a much faster and more accurate diagnostic process to supplement RT-PCR test of finding the patients affected by the virus. In this regard, radiological images such as X-ray and CT (Computerized Tomography) scan are found to be useful. The X-ray and CT scan have good screening modality; they are quick at capturing and finding and widely available around the world. Therefore, a deep learning model, which makes use of CT scan and X-ray images, has been proposed to automate and analyze the diagnostic process by utilizing Convolutional Neural Network (CNN). This model makes use of InceptionV3 deep learning model, a type of CNN. It is a lightweight deep learning model that is apt for mobile, laptop, and tablet platforms. The proposed model requires low memory space and gives an accuracy of about 96%, sensitivity of 93.48% for CXRs (Chest X-rays) and accuracy of 93%, sensitivity of 89.81 % for the CT scan images respectively. The proposed model is also compared with other deep learning models like VGG 16 (Visual Geometry Group), ResNet50V2 (Residual Network) and other existing deep learning models and it is found to be better in terms of accuracy and other performance parameters. Further, a web application has been developed from the proposed model. The web application is able to detect COVID-19 cases from the CT scan and X-ray images with significant accuracy., Competing Interests: Conflict of interestWe hereby confirm that there is no conflict of interest related to this manuscript and no financial funds has been received for this work from any organization which can influence the results., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Drugs are the imperial part of modern society, but along with their therapeutic effects, drugs can also cause adverse effects, which can be mild to morbid. Pharmacovigilance is the process of collection, detection, assessment, monitoring and prevention of adverse drug events in both clinical trials as well as in the post-marketing phase. The recent trends in increasing unknown adverse events, known as signals, have raised the need to develop an ideal system for monitoring and detecting the potential signals timely. The process of signal management comprises of techniques to identify individual case safety reports systematically. Automated signal detection is highly based upon the data mining of the spontaneous reporting system such as reports from health care professional, observational studies, medical literature or from social media. If a signal is not managed properly, it can become an identical risk associated with the drug which can be hazardous for the patient safety and may have fatal outcomes which may impact health care system adversely. Once a signal is detected quantitatively, it can be further processed by the signal management team for the qualitative analysis and further evaluations. The main components of automated signal detection are data extraction, data acquisition, data selection, and data analysis and data evaluation. This system must be developed in the correct format and context, which eventually emphasizes the quality of data collected and leads to the optimal decision-making based upon the scientific evaluation., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting., Patients and Methods: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1 : 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks)., Results: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001)., Conclusions: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker., Competing Interests: Disclosures KNC reports honoraria and/or consulting fees from Astellas, AstraZeneca, Constellation Pharmaceuticals, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, Sanofi, and grants and research funding from Astellas, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi. AWW reports a commercial research grant from Janssen and honoraria from AstraZeneca, Astellas, Janssen, and Merck. AAA reports honoraria, consulting fees, and/or research funding from Astellas, AstraZeneca, Janssen, Novartis, Sanofi, Tolmar, Telix, Merck Serono, Bristol Myers Squibb (BMS), Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Aptevo Therapeutics, Glaxo Smith Kline, MedImmune, SYNthorx, Bionomics, Merck Sharpe Dome, and Sanofi Aventis. LAW reports serving on advisory boards (with no personal financial contribution) for Pfizer, EISAI, AstraZeneca, Merck, BMS, and Ipsen, and grants from Pfizer, Merck, AstraZeneca, Roche, and BMS. BT reports grants and personal fees from Amgen, AstraZeneca, BMS, Janssen, Pfizer, MDS, Ipsen and Bayer, grants from Astellas, and personal fees from Sanofi, Tolmar, Novartis, IQVIA, and Roche. All other authors have declared no conflicts of interest., (Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate factors associated with continuation of systemic anti-cancer therapy (SACT) after palliative care consultation, and SACT administration in the last 30 days of life, in outpatients with cancer referred to palliative care. Timing of referral was of particular interest., Methods: Patient, disease, and treatment-related factors associated with SACT before and after palliative care, and in the last 30 days of life, were identified using 3-level multinomial logistic regression. Referral to palliative care was categorized by time from death as early (>12 months), intermediate (6-12 months), and late (≤6 months)., Results: Of the 337 patients, 240 (71.2%) received SACT for advanced cancer; of these, 126 (52.5%) received SACT only prior to palliative care while 114 (47.5%) also received SACT afterward. Only 35/337 (10.4%) received SACT in the last 30 days of life. On multivariable analysis, factors associated with continuing SACT after palliative care consultation were a cancer diagnosis for <1 year (OR 3.09, p = 0.01), breast primary (OR 11.88, p = 0.0008), and early (OR 28.8, p < 0.001) or intermediate (OR 6.67, p < 0.001) referral timing. No factors were significantly associated with receiving SACT in the last 30 days versus earlier, but the median time from palliative care referral to death in those receiving SACT in the last 30 days versus stopping SACT earlier was 1.78 versus 4.27 months., Conclusion: Patients who received SACT following palliative care consultation were more likely to be referred early; however, patients receiving SACT in their last 30 days tended to be referred late.

Background: Evidence from randomized controlled trials has demonstrated benefits in quality of life outcomes from early palliative care concurrent with standard oncology care in patients with advanced cancer. We hypothesized that there would be earlier referral to outpatient palliative care at a comprehensive cancer center following this evidence., Materials and Methods: Administrative databases were reviewed for two cohorts of patients: the pre-evidence cohort was seen in outpatient palliative care between June and November 2006, and the post-evidence cohort was seen between June and November 2015. Timing of referral was categorized, according to time from referral to death, as early (>12 months), intermediate (>6 months to 12 months), and late (≤6 months from referral to death). Univariable and multivariable ordinal logistic regression analyses were used to determine demographic and medical factors associated with timing of referral., Results: Late referrals decreased from 68.8% pre-evidence to 44.8% post-evidence; early referrals increased from 13.4% to 31.1% (p < .0001). The median time from palliative care referral to death increased from 3.5 to 7.0 months (p < .0001); time from diagnosis to referral was also reduced (p < .05). On multivariable regression analysis, earlier referral to palliative care was associated with post-evidence group (p < .0001), adjusting for shorter time since diagnosis (p < .0001), referral for pain and symptom management (p = .002), and patient sex (p = .04). Late referrals were reduced to <50% in the breast, gynecological, genitourinary, lung, and gastrointestinal tumor sites., Conclusions: Following robust evidence from trials supporting early palliative care for patients with advanced cancer, patients were referred substantially earlier to outpatient palliative care., Implications for Practice: Following published evidence demonstrating the benefit of early referral to palliative care for patients with advanced cancer, there was a substantial increase in early referrals to outpatient palliative care at a comprehensive cancer center. The increase in early referrals occurred mainly in tumor sites that have been included in trials of early palliative care. These results indicate that oncologists' referral practices can change if positive consequences of earlier referral are demonstrated. Future research should focus on demonstrating benefits of early palliative care for tumor sites that have tended to be omitted from early palliative care trials., (© 2020 AlphaMed Press.)

Paraneoplastic Pemphigus (PNP), a rare autoimmune blistering disease, can be accompanied by both benign and malignant neoplasms. The most frequently reported associated malignancies include lymphomatoid and hematologic malignancies, Castleman's disease, carcinoma, thymoma. In a patient suspected of PNP, with no known history of malignancy, an extensive workup is suggested to look for underlying malignancy, which has to be treated to induce PNP remission. In this clinical case report, cross sectional imaging of a young female diagnosed with PNP, unveiled a pericardial mass lesion extending into transverse pericardial sinus. Excisional biopsy was performed. Histopathology revealed pericardial ectopic thymoma., (© 2020 Wiley Periodicals LLC.)

Background: Indian data on potential hepatorenal toxic effects of highly active antiretroviral therapy (HAART) in HIV/AIDS-affected persons is lacking., Objectives: To assess hepatorenal abnormalities in HIV-infected persons on HAART in a hospital-based mixed cohort study using concurrent and nonconcurrent data analysis., Methods: Hepatorenal function tests, urinalysis and ultrasonogaphy for liver/kidneys (when applicable) were assessed in 400 (men 185; women 215) persons aged 2-84 (mean 47.8) years on HAART. Acute liver toxicity, acute kidney injury and chronic kidney disease were defined depending upon abnormal serum alanine aminotransferase, urea and creatinine levels/clearance as per standard guidelines., Results: The duration of HAART was 1 month to 9 years (mean 3.7 years) with 284 (71%) individuals being on treatment for ≤5years. The major HAART regimens included zidovudine + lamivudine + nevirapine in 175 (43.8%), tenofovir + lamivudine + efavirenz in 174 (43.5%) and zidovudine + lamivudine + efavirenz in 20 (5%) individuals and were associated with grade-1 hepatic dysfunction in 57 (14.3%) individuals, with men aged between 31 and 45 years on antiretroviral therapy for >5 years being mainly affected. Forty two (17.1%) of 246 individuals with anemia and 15 (9.7%) of 154 individuals without anemia showed hepatic dysfunction. None had acute kidney injury, chronic kidney disease or abnormal urinalysis or ultrasonography. In contrast, the pretreatment elevated serum alanine amiotranerase in 99 (22.3%) and blood urea and/or creatinine levels in 16 (4%) individuals decreased significantly post highly active antiretroviral therapy., Conclusions: The study reflects the low frequency of regimen based highly active antiretroviral therapy-associated hepatic or nephrotoxicity despite prolonged use, especially in the absence of other risk factors. Preexisting anemia appears an important risk factor for highly active antiretroviral therapy-induced hepatotoxicity (OR 1.90, Cl 95% CI 1.02-3.57, P = 0.04). Highly active antiretroviral therapy-associated nephrotoxicity was not a significant problem. Study of viral load or other risk factors and potential of each drug for hepatorenal toxicity/dysfunction in HIV affected were not part of the study. A small number of subjects and retrospective analysis of biochemical parameters were other important limitations., Competing Interests: None

Paclitaxel-induced photodermatitis is extremely rare despite the frequent use of paclitaxel-trastuzumab combination chemotherapy. A 70-year-old woman with infiltrating intraductal breast cancer developed photodermatitis after ten treatment courses of weekly paclitaxel-trastuzumab combination chemotherapy. Withdrawal of paclitaxel and sun avoidance led to its resolution. A combined effect of solar radiation and enhanced porphyrin synthesis is speculated for photodermatitis in paclitaxel. However, the issue of aberrant porphyrin biosynthesis being causal or an epiphenomenon remains unsettled as elevated porphyrins synthesis does not necessarily cause photosensitivity in all treated cases. The relevant literature on paclitaxel-induced photodermatitis and pathomechanism involved is reviewed., Competing Interests: None

Objective: To evaluate the feasibility and effect on marginal adaptation in class II composite restoration reinforced with polyethylene fibres in teeth with affected dentine using scanning electron microscopy., Method and Material: Class II cavities with dimension 1.5 +0 .25 pulpal depth and 4 ± 0.25 mm buccolingual width/.were prepared on proximal surfaces extracted human molars or premolar with affected/sound dentine on gingival margin. The etching priming and restorations were done in prepared samples as per manufacture directions. The samples were divided in 2 groups depending on use of ribbond inserts in composite restorative material. Samples were finished, stored in distilled water and then thermocycled manually and then sectioned longitudinally through the restorations. The marginal adaptation was evaluated using scanning electron microscope (SEM)., Result: The result showed that there was a definite gap all along the interface between caries affected dentine and the composite material in both the groups. The bigger gap was present in group II compared to group I., (© 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Background: In Tanzania, strong tobacco control measures that would lead to a reduction in prevalence (consumption) have so far not been implemented due to concern about possible economic effects on gross domestic product and employment. The aim of this study is to analyse the economic effects of reducing tobacco consumption in Tanzania., Methods: The study uses computable general equilibrium (CGE) modelling to arrive at the effects of decreasing tobacco prevalence. A full-fledged global CGE model was developed, including comprehensive details on tobacco and tobacco products/sectors using the Global Trade Analysis Program-Environment model and database., Results: The results indicate that a 30% reduction in prevalence could lead to employment losses of about 20.8% in tobacco and 7.8% in the tobacco products sector. However, when compensated by increases in other sectors the overall decline in employment is only 0.5%. The decline in the economy as a whole is negligible at -0.3%., Conclusion: Initially, some assistance from the Tanzanian government may be needed for the displaced workers from the tobacco sector as a result of the decline in smoking prevalence. However, these results should be taken as a lower bound since the economic burden of diseases caused by tobacco may be far higher than the sectoral losses. The results do not include the health benefits of lower smoking prevalence. In addition, the revenues from higher taxes, as part of measures to decrease prevalence, would provide more fiscal space that can be used to finance assistance for displaced tobacco farmers and workers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Abiraterone acetate plus prednisone and enzalutamide are both used for the treatment of metastatic castration-resistant prostate cancer. We aimed to determine the best sequence in which to use both drugs, as well as their second-line efficacy., Methods: In this multicentre, randomised, open-label, phase 2, crossover trial done in six cancer centres in British Columbia, Canada, we recruited patients aged 18 years or older with newly-diagnosed metastatic castration-resistant prostate cancer without neuroendocrine differentiation and Eastern Cooperative Oncology Group performance status 2 or less. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either abiraterone acetate 1000 mg orally once daily plus prednisone 5 mg orally twice daily until PSA progression followed by crossover to enzalutamide 160 mg orally once daily (group A), or the opposite sequence (group B). Treatment was not masked to investigators or participants. Primary endpoints were time to second PSA progression and PSA response (≥30% decline from baseline) on second-line therapy, analysed by intention-to-treat in all randomly assigned patients and in patients who crossed over, respectively. The trial is registered with ClinicalTrials.gov, NCT02125357., Findings: Between Oct 21, 2014, and Dec 13, 2016, 202 patients were enrolled and randomly assigned to either group A (n=101) or group B (n=101). At the time of data cutoff, 73 (72%) patients in group A and 75 (74%) patients in group B had crossed over. Time to second PSA progression was longer in group A than in group B (median 19·3 months [95% CI 16·0-30·5] vs 15·2 months [95% CI 11·9-19·8] months; hazard ratio 0·66, 95% CI 0·45-0·97, p=0·036), at a median follow-up of 22·8 months (IQR 10·3-33·4). PSA responses to second-line therapy were seen in 26 (36%) of 73 patients for enzalutamide and three (4%) of 75 for abiraterone (χ 2 p<0·0001). The most common grade 3-4 adverse events throughout the trial were hypertension (27 [27%] of 101 patients in group A vs 18 [18%] of 101 patients in group B) and fatigue (six [10%] vs four [4%]). Serious adverse events were reported in 15 (15%) of 101 patients in group A and 20 (20%) of 101 patients in group B. There were no treatment-related deaths., Interpretation: Enzalutamide showed activity as a second-line novel androgen receptor pathway inhibitor, whereas abiraterone acetate did not, leading to a longer time to second PSA progression for the sequence of abiraterone followed by enzalutamide than with the opposite treatment sequence. Our data suggest that using a sequencing strategy of abiraterone acetate followed by enzalutamide provides the greatest clinical benefit., Funding: Canadian Cancer Society Research Institute, Prostate Cancer Canada, Movember Foundation, Prostate Cancer Foundation, Terry Fox New Frontiers Program, BC Cancer Foundation, Jane and Aatos Erkko Foundation, Janssen, and Astellas., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Activated coagulation cascade is implicated in urticaria pathogenesis marked by high plasma D-dimer, a marker of fibrinolysis, levels correlating with high urticaria activity score (UAS) and poor therapeutic outcome., Methods: Quantitative plasma D-dimer levels and coagulation parameters in 100 (male:female ratio 1:3) Indian patients with chronic spontaneous urticaria and age- and gender-matched healthy controls were compared. The clinicoepidemiologic features of chronic urticaria were then compared among patients with normal (≤0.2 mg/L) and elevated (≥0.3 mg/L) plasma D-dimer levels., Results: Plasma D-dimer in 23% patients and 4% controls and prothrombin time and activated partial thromboplastin time in 63% and 5% patients, respectively, were significantly higher compared with 58% and 1% of controls, respectively. About 18 of 72 (25%) patients with high UAS of ≥16-42 were compared with 5 of 28 (17.8%) patients with UAS7 of ≤15. Patients with elevated plasma D-dimer levels had significantly more systemic symptoms (86.9% vs. 81.8%) compared with patients with normal plasma D-dimer levels., Conclusion: A subset of patients with chronic urticaria have elevated plasma D-dimer levels and exhibit higher UAS7 and systemic symptoms that may influence long-term prognosis and therapeutic choices. Small number of patients, a cross-sectional nature of study, lack of treatment outcome measures, information on self-medication, and unavailability of specific parameters for coagulation pathway activation remain few limitations of this study., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Dermatology Online Journal.)

Competing Interests: There are no conflicts of interest.

Psoriasis is now recognized as an immune-mediated inflammatory dermatosis with increased risk for metabolic syndrome, its individual components, and cardiovascular disease. We quantitatively estimated malondialdehyde (MDA), lipoprotein-a (LP-a), lipoprotein ratios, comprehensive lipid tetrad index (CLTI), and atherogenic index (AI), and evaluated cardiovascular risk in 132 (M:F 94:38) patients with psoriasis aged 20-79 years with chronic plaque psoriasis and equal number of age and gender-matched controls. Lipoprotein ratios, CLTI and AI were calculated using standard formulae. Cardiovascular 10-year risk was graded by Framingham risk score (FRS) as low, intermediate and severe. Mild-to-moderate and severe psoriasis was present in 125 (94.7%), and 7 (5.3%) patients, respectively, and 19 (14.39%) patients had psoriatic arthritis. Statistically significant differences were noted for LDL, LDL/HDL, non-HDL/HDL, MDA, LP-a, AI and CLTI. There was a significantly positive correlation between PASI with LP-a (p = 0.003, r = 0.25) and AI (p = 0.012, r = 0.22). Serum levels of MDA correlated positively with LP-a (p < 0.001, r = 0.55), AI (p < 0.001, r = 0.51) and CLTI (p = 0.006, r = 0.24). FRS was low, intermediate and severe in 78%, 18.9%, and 3% patients compared to 85.6%, 13.6%, and 0.8% controls, respectively, and the difference was not statistically significant. Psoriasis appears to be an independent risk factor for elevated serum MDA, LP-a, CLTI and AI. However, whether they can be used as surrogate markers for enhanced cardiovascular risk in patients with psoriasis, remains conjectural.

Background: Common pesticides used in the region by agricultural workers may cause contact allergy., Methods: Thirty agricultural workers with a history of pesticide exposure and dermatitis involving the face, neck, trunk or extremities, and 20 controls comprising 2 groups of 10 subjects each, group 1 with dermatitis and no exposure to pesticides, and group 2 with neither exposure to pesticides nor dermatitis, were patch tested with 10 pesticides commonly used in the region by use of the Finn Chamber method., Results: The 30 patients, 20 of whom were male, aged 30-77 years, had dermatitis for 1 month to 18 years, with relapses and remissions. Seasonal exacerbation was present in 18 patients. Six patients attributed aggravation of their dermatitis to pesticide exposure, and 2 of these reacted positively to propiconazole. Positive patch test reactions to pesticides occurred in 10 patients, but not in controls. Thiuram was the commonest sensitizer (4 patients). Three patients were sensitized to propiconazole, and 2 patients reacted positively to metaldehyde. Formaldehyde, mercaptobenzothiazole, cypermethrin and isoproturon gave positive reactions in 1 patient each., Conclusion: The sensitizing potential of pesticides remains a concern. Apparently, pesticide contact dermatitis is more common than expected, but remains under-reported, as the implicated pesticides vary across regions and according to the crop patterns., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although timely palliative care is recommended for patients with advanced cancer, referrals to palliative care services are often late., Objectives: To identify factors associated with early referral to an oncology palliative care clinic and to describe symptom severity according to timing of referral., Design: We conducted a retrospective review of 337 patients with advanced cancer referred to outpatient palliative care at a comprehensive cancer center. We gathered data related to patient demographics, diagnosis, and referral. Timing of referral was categorized as early (>12 months before death), intermediate (6-12 months before death), or late (<6 months before death). Ordinal logistic regression was used to determine factors related to referral timing, and the Kruskal-Wallis test to determine symptom severity in each referral timing category., Results: Of the 337 patients, 232 (69%) referrals were late, 60 (18%) intermediate, and 45 (13%) early. On multivariable analysis, earlier referral was associated with earlier primary cancer diagnosis (p = 0.004), and referral for pain and symptom management (p = 0.001). Patients who were referred late had worse overall Edmonton Symptom Assessment System distress scores, as well as worse tiredness, nausea, drowsiness, appetite, and wellbeing (all p ≤ 0.001). Severity of pain, shortness of breath, anxiety, and depression did not differ based on time of referral., Conclusions: A longer disease course and referral for symptom management were associated with earlier referral, whereas overall symptom burden was higher for late referrals. Further research is required on combining symptom screening with timely referral to improve symptom management in advanced cancer.

Purpose: Elevated central venous pressure (CVP) has deleterious effects on several organ systems in patients with Fontan circulation. However, the relationship between CVP and estimated glomerular filtration rate (eGFR) has not been assessed in patients with Fontan circulation., Methods: Patients with Fontan circulation whose hemodynamics were assessed by catheterization between 1987 and 2015 and had a serum creatinine measured within 72 hours prior to the procedure were included for analysis. Patients with primary kidney disease were excluded. Renal function was calculated by "bedside Schwartz" equation in children (< 18 years) and Modification of Diet in Renal Disease equation in adults. Renal dysfunction (RD) was defined by eGFR < 90mL/min/1.73m 2 . Fontan patients with and without RD were compared based on demographics, co-morbidities, medication use, echocardiographic findings, hemodynamics assessed at time of catheterization, and laboratory testing values., Results: Sixty-seven patients with Fontan circulation met inclusion criteria and 15 patients (22%) had RD; eGFR (mL/min/1.73m 2 ) was 60-89in 13 (87%), 45-59in 1 (7%), and 30-45in 1 (7%). Compared to patients with eGFR equal to or greater than 90, patients with RD had higher CVP (18.0 [15.0-21.0] mm Hg vs 13.5 [12.3-16.0] mm Hg (P = 0.001), lower pulmonary blood flow 2.2 [1.9-2.6] L/min/m 2 vs 2.8 [2.3-3.7] L/min/m 2 , higher ventricular end-diastolic pressure 10.5 [7.0-17.3] mm Hg vs 8.0 [6.0-10.0] mm Hg (P = 0.050), were more likely to have worse atrioventricular valve regurgitation (P = 0.02) and were more likely to be African American (P = 0.009)., Conclusions: In this study population, renal dysfunction in patients with Fontan circulation is associated with increased CVP and factors that affect CVP. African Americans with Fontan circulation may be at particular risk for renal dysfunction. Continued investigation of the effects of venous congestion on kidneys and other factors associated with renal dysfunction in patients with Fontan circulation is warranted., (© 2018 Wiley Periodicals, Inc.)

The objective of this study was to investigate the impact of clinical syndrome-wise categorisation of antimicrobials on the antibiotic susceptibility of nosocomial bacteria at a tertiary care hospital in Delhi, India. The susceptibility of 226 nosocomial bacterial isolates collected during 2008-2011 to meropenem, piperacillin/tazobactam, cefepime, tigecycline, amoxicillin/clavulanic acid (AMC), amikacin, ceftriaxone and ciprofloxacin was monitored and was compared with the antibiotic susceptibility profiles of 72 isolates collected during 2002-2007. During 2008-2011, the isolates included 85% Gram-negative isolates and 15% meticillin-sensitive staphylococci. There was no difference in the susceptibility of the isolates between 2002 and 2007 and 2008-2011, except for a significant increase in Escherichia coli isolates susceptible to AMC (from 73% to 100%), amikacin (70-100%) and cefepime (22-86%), in Klebsiella isolates susceptible to ciprofloxacin (from 25% to 80%) and cefepime (45-75%) and in Pseudomonas isolates susceptible to AMC (from 25% to 86%). In conclusion, during the past decade a clinical syndrome-wise categorisation of antimicrobials in frequent usage as well as culture-based categorisation of infections into nosocomial/community-acquired was useful in establishing the generally insignificant change in the susceptibility of nosocomial isolates and an upsurge in the susceptibility of some isolates to a few antimicrobials. Regular updates on drifts in the antimicrobial susceptibility of local isolates and surveillance of nosocomial infections would be valuable for tackling the emergence of antibiotic-resistant bacteria., (Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Purpose: Cigarette smoking is a major risk factor in periodontal diseases. The pathogenesis of periodontal diseases may be affected by alterations of the inflammatory response by smoke. Nitric oxide (NO) is a gaseous, colorless, highly reactive, short-lived free radical with a pivotal role in the regulation of various physiological and pathological mechanisms in the body. It is important in host defense and homeostasis, on the one hand, whereas, on the other hand, it modulates the inflammatory response in periodontitis, leading to harmful effects. The aim of this study was to assess the levels of NO in both the serum and saliva of smokers and nonsmokers having chronic periodontitis and to compare them with periodontally healthy controls., Methods: SIXTY SUBJECTS PARTICIPATED IN THE STUDY AND WERE DIVIDED INTO THREE GROUPS: group I, healthy nonsmoking subjects; group II, nonsmoking patients with chronic periodontitis; group III, smoking patients with chronic periodontitis. Each group consisted of twenty subjects. The biochemical estimation of NO in the collected serum and in the saliva was performed using the Griess colorimetric reaction., Results: The results showed that the mean value of the salivary and serum NO was greater in group II than in group I, and also greater in group III than in group II., Conclusions: NO appears to play an important and rather complex role in the immuno-inflammatory process and in the remodeling and maintenance of osseous structures. It is therefore logical that modulation of this mediator has potential for the treatment of a number of inflammatory conditions including periodontal disease.

Objective: This study evaluates the quality of life (QOL) and mental health (MH) of caregivers of patients with advanced cancer who are receiving ambulatory oncology care and associations with patient, caregiver and care-related characteristics., Methods: Patients with advanced gastrointestinal, genitourinary, breast, lung or gynaecologic cancer, and their caregivers, were recruited from 24 medical oncology clinics for a cluster-randomized trial of early palliative care. Caregivers completed the Caregiver QOL--Cancer scale and the Medical Outcomes Study Short Form, version 2, and a questionnaire including care-related factors such as hours/day providing care and change in work situation. Patients completed a demographic questionnaire and measures of their QOL and symptom severity. Associations of these factors with caregiver QOL and MH were examined using linear regression analyses., Results: Of the 191 caregivers, 84% were spouses/partners, 90% cohabited with the patient, half were working and 25% had a change in work situation since the patient's diagnosis. On multiple regression analysis, better caregiver QOL was associated with better caregiver MH and patient physical well-being and with not providing care for other dependents. Worse caregiver MH was associated with female caregiver sex, worse patient emotional well-being, more hours spent caregiving and change in the caregiver's work situation., Conclusions: Caregivers of ambulatory patients with advanced cancer may have compromised QOL and MH associated with worse patient physical and emotional well-being and with simultaneously caring for others and working outside the home. Early palliative care interventions directed at patient symptoms and caregiver support may improve QOL in this population., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates (1,4-DHP) have now been recognized as vital drugs. Some of these derivatives such as amlodipine, felodipine, isradipine, etc. have been commercialized. In view of wide range of biological properties associated with 1,4-DHP and owing to the biological importance of the oxidation step of 1,4-DHP, we carried out the synthesis and antimicrobial evaluation of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) and diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g)., Results: Synthesis of a series of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) has been accomplished by multicomponent cyclocondensation reaction of ethyl acetoacetate, 3-aryl-1-phenyl pyrazole-4-carboxaldehyde (1a-g) and ammonium acetate. The dihydropyridines 2a-g were smoothly converted to new diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g) using HTIB ([Hydroxy (tosyloxy)iodo]benzene, Koser's reagent) as the oxidizing agent. The antimicrobial studies of the title compounds, 2a-g &3a-g, are also described.

Background The incidence and management of trastuzumab-mediated cardiotoxicity outside of clinical trials has not been well described. Objective and methods The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI, in a population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results Out of 152 patients (mean age 52 +/- 10 years), 36 (24%) developed trastuzumab mediated cardiomyopathy, the majority asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a pre-existing history of hypertension, smoking history, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, there was a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction (61 +/- 5% vs. 51 +/- 8%, P < 0.01). During the 6-month-followup, 34/36 patients demonstrated subepicardial linear delayed enhancement of the lateral wall of the left ventricle on cardiac MRI, suggesting trastuzumab induced myocarditis. Conclusion Approximately 1 in 4 women may develop LV systolic dysfunction after treatment with adjuvant trastuzumab, necessitating careful patient selection and close serial monitoring using noninvasive cardiac imaging.

Entamoeba histolytica, the causative agent of human amoebiasis, is essentially anaerobic, requiring a small amount of oxygen for growth. It cannot tolerate the higher concentration of oxygen present in human tissues or blood. However, during tissue invasion it is exposed to a higher level of oxygen, leading to oxygen stress. Cysteine, which is a vital thiol in E. histolytica, plays an essential role in its oxygen-defence mechanisms. The major route of cysteine biosynthesis in this parasite is the condensation of O-acetylserine with sulfide by the de novo cysteine-biosynthetic pathway, which involves cysteine synthase (EhCS) as a key enzyme. In this study, EhCS was cloned, expressed in Escherichia coli and purified by affinity and size-exclusion chromatography. The purified protein was crystallized in space group P4(1) with two molecules per asymmetric unit and a complete data set was collected to a resolution of 1.86 A. A molecular-replacement solution was obtained using the Salmonella typhimurium O-acetylserine sulfhydrylase structure as a probe and had a correlation coefficient of 37.7% and an R factor of 48.8%.

The reticulorumen is now recognised to be an important site of net absorption of phosphate ions from ruminal fluid containing phosphate concentrations appropriate to those found in normal farming practice. These rates of absorption were measured in vivo from solutions placed in the washed reticulorumen, isolated in situ, in conscious, trained sheep. Reducing the ruminal sodium concentration led to reduced absorption of phosphate, suggestive that phosphate and sodium fluxes across the apical wall of the ruminal epithelial cell are linked, as they are in the kidney. Increased absorption of short chain fatty acids led to enhanced absorption of phosphate ions. Conversely, inhibition of carbonic anhydrase activity, by the addition of 1 mM acetazolamide to the ruminal fluid, led to a reduction in phosphate absorption. An increase in the acidity of the ruminal fluid also increased the absorption of phosphate, as did an increase in the ruminal Ca(2+) concentration over the range 1-4 mmol per litre. It is suggested that these effects can be accounted for by a Na(+)/H(+) antiporter coupled with a phosphate/proton symporter in the apical membrane of the ruminal epithelial cell., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

A new approach to evaluating feeds has been developed based on in vitro estimates of rumen acid load (acidogenicity value). The present work was conducted to establish effects of rumen acid load on dry matter intake and milk production of early-lactation dairy cows fed corn silage-based diets. The effects of diet acidogenicity were investigated independently of ingredient composition using a series of isoenergetic and isonitrogenous concentrates that used different raw materials to achieve the same acidogenicity value. Six concentrates were formulated to be fed at 7 kg/d, and two at 10 kg/d. Continuous culture equipment, which had been modified to control and record infusions of acid and alkali to maintain pH in the range 6.2 to 6.3, confirmed the ranking of concentrates based on the in vitro technique. The concentrates were offered to dairy cows in early lactation with corn silage available ad libitum. Forage intake declined with increasing concentrate acidogenicity, particularly at the higher level of concentrate feeding. However, concentrate acidogenicity had a significant negative effect on dry matter intake even at 7 kg/d. Feed intakes were similar for concentrates that were formulated to be isoacidogenic, but using different raw materials. There were only small and inconsistent effects of concentrate acidogenicity value on milk yield and milk fat percentage, while milk protein percentage was higher with the high AV concentrates. Effects on milk composition likely reflect differences in nutrient supply and there was no evidence for effects of rumen acid load per se on milk composition.

Earlier studies developed a new approach to feed evaluation, measuring the net acid load that develops during rumen fermentation. Two concentrates were formulated to be isoenergetic and isonitrogenous, with extremes of rumen acid load. A third treatment comprised a 50:50 mixture of these concentrates. These concentrates were evaluated along with ryegrass silage and corn silage. The feeds were evaluated in a continuous culture system adapted to deliver and record the quantities of acid or alkali needed to maintain a constant pH (6.2 to 6.3). This study confirmed the anticipated ranking of concentrates for rumen acid load, as well as the highly acidogenic nature of corn silage. The concentrates were formulated to balance corn silage and were offered to early-lactation Holstein-Friesian cows at 50% of dry matter intake, with either ryegrass silage or corn silage. Feed intake was lower for animals offered corn silage-based diets (17.4 vs. 22.2 kg of dry matter/d). Increasing concentrate acid load led to a large decline in dry matter intake for corn silage, although not for grass silage. Feed intake effects were reflected in significant effects on yield of milk (31.0, 29.9, and 26.9 kg/d for low-, medium-, and high-acid load concentrates, respectively) and milk solids. Milk protein concentration was unaffected by concentrate type with corn silage diets but tended to be higher when high acid load concentrates were fed with grass silage. This may reflect the effect of the high starch concentrate rectifying a shortage of glucogenic precursors or microbial protein with the grass silage-based diet.

The objective of these experiments was to develop a simple in vitro technique for evaluating the production and neutralization of acid as feeds ferment in the rumen. An in vitro approach was adopted to eliminate animal factors. The procedure was based on the method of Tilley and Terry, with some modifications developed in this project. Residual acidity (acidogenicity value) was determined by the dissolution of Ca from CaCO3 powder added to the media at the end of 24-h incubations. Acidogenicity values (AV) were higher when 20% strength buffer was used, while lowering buffer pH increased values, equally across all feeds. There was no effect of donor animal diet, but considerable day-to-day variation in the fermentation activity of rumen fluid. This variation likely reflected the substrate preferences of differing microbial populations, so that several standard feeds may be required to account for this effect. A series of 28 diverse feed ingredients was evaluated for AV using a mixture design, with 85 combinations of ingredients: 100% of each ingredient (n = 28); 50% of each ingredient and an equal mixture of all others (n = 28); equal mixture of all ingredients, excluding one (n = 28); and an equal mixture of all ingredients (n = 1). The effects of most ingredients on AV were essentially linear, though some extreme ingredients showed nonlinear effects. Protein sources had low AV, forages intermediate AV and starchy feeds high AV. Calcium contained within feeds contributed to AV, particularly for legumes, sugar beet pulp, and citrus pulp, and must be accounted for.

Net Ca2+ and Mg2+ absorption rates were measured in vivo from buffer solutions placed in the washed reticulo-rumen, isolated in situ in 30 conscious, trained sheep. An increase in concentration of short chain fatty acids (SCFA) in the buffer, over the range 0-50 mM, was shown to stimulate the net rates of absorption of Ca2+ and Mg2+ ions from the rumen. Similarly, the results of in vitro experiments, carried out with ovine rumen epithelium mounted in short-circuited Ussing chambers, showed that the absence of SCFA from the chamber fluid resulted in a reduction in Jnet Ca2+ caused by reduced flux of Ca2+ ions in the mucosal to serosal direction (Jms Ca2+). The addition of 1 mM acetazolamide, an inhibitor of carbonic anhydrase, to the ruminal buffer used in the in vivo experiments led to significant reductions in the net absorption rates of Ca2+ and Mg2+ ions in the presence of SCFA (50 mmol x l(-1)) but not in the absence of SCFA. However, in the in vitro experiments, the addition of 60 microM ethoxyzolamide had no significant effect on Jnet Ca2+. A reduction in pH of the intraruminal buffer in vivo from 6.8 to 5.4 led to significant increases in the net absorption rates of Ca2+ and Mg2+ ions, an effect which was duplicated for Ca2+ in preliminary in vitro experiments in which the pH of the mucosal buffer was reduced from 7.4 to 5.4. This stimulatory effect was confined to Jms Ca2+ and Jnet Ca2+. Ussing chambers were also used to demonstrate that Jnet Ca2+ was reduced by a high transmural potential difference (PD), caused by voltage clamping, independently of the mucosal K+ concentration. Both unidirectional Ca2+ fluxes consisted of a PD-dependent and a K+-insensitive PD-independent component. The latter may be represented by a Ca2+/ 2H+ antiporter. It is postulated that SCFA, and to a lesser extent H2CO3, can stimulate Jms Ca2+ by activation of an apical Ca2+/2H+ antiporter through the provision of protons within the ruminal epithelial cell. A mild reduction in ruminal pH may also lead to a similar stimulation of this putative electroneutral exchange.

The net absorption rates of strontium ions from the ovine reticulo-rumen, isolated in situ in trained conscious animals, were measured under controlled conditions. A linear positive response was obtained from the addition of Sr2+ ions to the artificial rumen fluid. This increase in the absorption of Sr was reflected in an increase in the plasma Sr concentration. In contrast to the discrimination observed elsewhere in favour of the absorption of Ca relative to Sr, the absorption rate of Sr from the reticulo-rumen was significantly greater than that of Ca, from solutions containing the same molar concentration. A graded increase in the Sr concentration in the ruminal fluid from 1 mmol/l to 4 mmol/l led to a corresponding reduction in the absorption rate of Ca but an increase in that of phosphate. The latter result is similar to that observed when the intra-ruminal concentration of Ca2+ ions is increased. It is suggested that Ca and Sr share a common pathway for absorption from the reticulo-rumen and that this may involve coupling with the absorption of phosphate ions.

Oak poisoning occurred in crossbred cattle due to eating immature tender oak (Quercus incana) leaves. Mortality was 70%. The animals exhibited anorexia, severe constipation and brisket edema. The feces were hard, pelleted and coated with blood and mucous. Significant reductions in blood hemoglobin and mean corpuscular hemoglobin, and significant elevations in serum bilirubin were observed. Serum urea nitrogen and creatinine were greatly increased. There was bilirubinuria, proteinuria, hypoproteinemia and hypocalcemia, and greatly increased activities of serum aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase. The levels of tannins and condensed tannins were 97.7 mg tannic acid equivalent and 5.8 mg catechin equivalent/g of dry leaves. There was extensive nephro- and hepatotoxicity in the affected cattle due to hydrolysable tannins and simple phenols in the oak leaves.