Postoperative continuous non-invasive cardiac output monitoring on the ward: a feasibility study.

Postoperative hypotension is common (occurring in one third of patients) and is associated with worse clinical outcomes. The LiDCO CNAP (continuous non-invasive arterial pressure) device measures haemodynamics but has not been widely adopted in ward environments. Improved early detection of hypotension by CNAP might guide interventions to improve clinical outcomes. We aimed to find the proportion of patients who tolerated LiDCO CNAP for 12 h postoperatively, to unmask episodes of hypotension detected by continuous monitoring and to characterise the haemodynamic profile at the time of hypotension. In this feasibility study, patients undergoing major elective surgery were continuously postoperatively monitored using CNAP. Haemodynamic data gathered from CNAP, including nSVRI (nominal systemic vascular resistance index), nSVI (nominal stroke volume index), SVV (stroke volume variation) and blood pressure, were analysed using Microsoft Excel and GraphPad Prism 8. 104 patients (age (mean ± sd): 68 ± 14, male (56%)) had CNAP sited postoperatively. 39% tolerated the CNAP device for at least 12 h. Within the 104 patients a mean of 81.2 min of hypotension detected by CNAP was not detected by usual care. The proportion of low/normal/high nSVI was 71%, 27% and 2%, nSVRI was 43%, 17% and 40%, respectively. CNAP monitoring was not tolerated for 12 h in the majority of patients. There were many episodes of hypotension unmasked through continuous monitoring. Based on the advanced haemodynamic data provided it is possible that the underlying cause of a third of postoperative hypotensive episodes is vasodilation rather than hypovolaemia.Trial registry number: NCT04010058 (ClinicalTrials.gov) Date of registration: 08/07/2019.

HbA1C in Management of Type II Diabetes Mellitus: A Cross-sectional Survey of Indian Physicians.

OBJECTIVES: Hemoglobin A1C (HbA1C) estimation is the standard and commonly used method for diagnosis and monitoring of diabetes therapy. We conducted a questionnaire based survey to understand the Indian physician's adherence to HbA1C for effectively managing Type 2 diabetes mellitus (T2DM) patients and its influence on the decision making process. METHODS: A validated questionnaire comprising of 10 questions was administered to physicians/endocrinologists at the 44th Annual Conference of RSSDI-2016, Hyderabad. The questions of the survey were designed to understand average cutoff HbA1C level for physicians to start the mono-therapy or combination therapy with or without insulin along with preferred class of Oral anti-diabetic drugs (OAD) in Indian T2DM patients. RESULTS: 41% physicians selected HbA1C level in between 7.0-7.4% to start mono-therapy while 94.5% chose metformin as the first line OAD. In metformin uncontrolled patients, 56.8% responders chose to start a DPP4 inhibitor. To initiate dual therapy 42.9% responders chose HbA1c level of 8.0-8.4% while for triple therapy 37.1% responders selected HbA1c level of 9.0-9.4%. CONCLUSION: This survey shows the management patterns of T2DM patients by Indian physicians are in line with western guidelines especially AACE. Though guidelines do not offer stringent recommendation on first/second add-on class of OADs, DPP4i emerged as preferred choice for mono-therapy in metforminintolerant patients and as first add-on in patients uncontrolled on metformin alone.

Characterizing the hypertolerance potential of two indigenous bacterial strains (Bacillus flexus and Acinetobacter junii) and their efficacy in arsenic bioremediation.

AIMS: The aims of the study were to (i) isolate and characterize arsenic-tolerant bacterial strains, (ii) study the plant growth-promoting traits and (iii) explore their bioremediation potential. METHODS AND RESULTS: Indigenous arsenic hypertolerant bacterial isolates NM02 and NM03 were screened as they were capable of growing at 150 mmol l-1 As (V) and 70 mmol l-1 As (III). They were identified on the basis of morphological, physiological and biochemical parameter and 16sDNA sequence as Bacillus flexus and Acinetobacter junii respectively. Genomic DNA analysis for the investigation of ars operon revealed the presence of metalloregulatory arsC gene, suggesting their ability to detoxify arsenic. The analysis for siderophore, phosphate solubilization, indole acetic acid (IAA) and ACC deaminase highlighted the intrinsic plant growth-promoting rhizobacteria traits of both the bacterial strains. The energy dispersive spectroscopy analysis proved the potential of cellular arsenic sequestration within the strains. Moreover, Fourier-transform infrared spectra revealed the repositioning of the spectral bands in As presence, indicating the presence of those functional groups on the bacterial surface that is involved in As adsorption. CONCLUSIONS: Our results indicate that bacterial strains NM02 and NM03 were identified as potent applicants for arsenic bioremediation and possess the ability to facilitate plant growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The bacterial strains are proficient in As detoxification and can be employed for arsenic bioremediation; a cost-effective and in situ remediation technique for the polluted soil.

A Crossover Study Evaluating Effect of Timing of Levothyroxine on Thyroid Hormone Status in Patients of Hypothyroidism.

OBJECTIVE: Current literature shows a definite benefit of fasting state Levothyroxine administration. However, superiority of any specific timing is not yet established. Our study was designed to compare the effect of timing of levothyroxine administration, morning versus evening dose, on thyroid profile control in patients of hypothyroidism. METHODOLOGY: :A randomized double-blind crossover study was performed on 60 patients with primary hypothyroidism, euthyroid on stable levothyroxine regime of 100 µg daily, randomized into two sequence groups, morning dose first (AB sequence) versus evening dose first (BA sequence) with switch over after 6 weeks. Primary endpoints were change in thyroid function tests. RESULTS: There was an insignificant rise in TSH in morning dose first group (AB) at 6 weeks which reduced significantly in evening dose, [2.36(1.11) to 2.45(1.19) mIU/L (p=0.56)], [2.07(0.99) (p=0.006)] respectively. Levothyroxine evening dose first group (BA) showed significant reduction of TSH levels at 6 weeks followed by non significant increase [2.63(0.96) to 1.85(1.35) mIU/L, (p=0.002)], [2.14(1.16), (p=0.15)]. Group AB showed mild followed by significant rise in FT4 at 6 and 12 weeks respectively, [1.06(0.30) to 1.14(0.33) ng/dl (p=0.18)], [1.24(0.36) (p=0.008)]. FT4 of BA sequence significantly increased at 6 weeks followed by mild increase, [1.10(0.29) to 1.20(0.28) ng/dl (p=0.01)] [1.23(0.31) ng/dl (p=0.58)]. FT3 of AB revealed initial reduction (p=0.87), followed by significant rise (p=0.02). Group BA showed a significant rise (p=0.04) in FT3 followed by fall (p=0.63). CONCLUSION: Bedtime dosing of Levothyroxine showed improved thyroid hormone status control and could be a viable option in treatment of patients with hypothyroidism.

Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer.

Matrix metalloproteinase 20 (MMP-20), widely regarded as tooth specific, participates with MMP-2 in processing dentin sialophosphoprotein (DSPP) into dentin sialoprotein, dentin phosphoprotein, and dentin glycoprotein. In biochemical system, MMP-2, MMP-3, and MMP-9 bind with high affinity to, and are activated by, specific small integrin-binding ligand N-linked glycoproteins (SIBLINGs): bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. Subsequent reports documented possible biological relevance of SIBLING-MMP interaction in vivo by showing that SIBLINGs are always coexpressed with their MMP partners. However, the cognate MMPs for 2 other SIBLINGs-DSPP and matrix extracellular phosphogylcoprotein-are yet to be identified. Our goal was to investigate MMP-20 expression and to explore preliminary evidence of its interaction with DSPP in oral squamous cell carcinomas (OSCCs). Immunohistochemistry analysis of sections from 21 cases of archived human OSCC tissues showed immunoreactivity for MMP-20 in 18 (86%) and coexpression with DSPP in all 15 cases (71%) positive for DSPP. Similarly, 28 (93%) of 30 cases of oral epithelial dysplasia were positive for MMP-20. Western blot and quantitative real-time polymerase chain reaction analysis on OSCC cell lines showed upregulation of MMP-20 protein and mRNA, respectively, while immunofluorescence showed coexpression of MMP-20 and DSPP. Colocalization and potential interaction of MMP-20 with dentin sialoprotein was confirmed by coimmunoprecipitation and mass spectrometry analysis of immunoprecipitation product from OSCC cell lysate, and in situ proximity ligation assays. Significantly, results of chromatin immunoprecipation revealed a 9-fold enrichment of DSPP at MMP-20 promoter-proximal elements. Our data provide evidence that MMP-20 has a wider tissue distribution than previously acknowledged. MMP-20-DSPP specific interaction, excluding other MMP-20-SIBLING pairings, identifies MMP-20 as DSPP cognate MMP. Furthermore, the strong DSPP enrichment at the MMP-20 promoter suggests a regulatory role in MMP-20 transcription. These novel findings provide the foundation to explore the mechanisms and significance of DSPP-MMP-20 interaction in oral carcinogenesis.

Comparing the efficacy and safety profile of sitagliptin versus glimepiride in patients of type 2 diabetes mellitus inadequately controlled with metformin alone.

OBJECTIVE: To compare the efficacy and safety of sitagliptin and glimepiride in treatment of patients with type 2 diabetes mellitus inadequately controlled with metformin alone. RESEARCH DESIGN AND METHODS: In an 18 week, randomized parallel group interventional trial, 50 subjects who were only on metformin as antidiabetic agent, with inadequate glycemic control, were randomized to either sitagliptin 50/100mg or glimepiride 1/2 mg per day. Dose of drugs was adjusted after 4 weeks if glycemic control was not reached. RESULTS: At 18 weeks both groups (sitagliptin and glimepiride) produced significant (P < 0.001) reduction in HbA1C (-0.636% and -1.172% respectively), with 12% patients in sitagliptin group and 36% patients in glimepiride group achieving target HbA1C. Reduction was also significant (P < 0.001) in both groups in FPG (-15.49 mg and -29.84 mg respectively) and 2HPPG (-34.28 mg and -44.83 mg respectively). Sitagliptin group showed net decrease in bodyweight by 0.102 kg whereas glimepiride group showed net increase in body weight by 0.493 kg. Incidence of hypoglycemia was 4% in sitagliptin group and 8% in glimepiride group. CONCLUSION: In this study addition of sitagliptin and glimepiride to metformin monotherapy, produced significant improvement in glycemic control. Benefits were more with glimepiride in comparison to sitagliptin. Sitagliptin was well tolerated, with lower risk of hypoglycemia than glimepiride, and produced weight loss as compared to weight gain with glimepiride.

Isolation and pathotyping of H9N2 avian influenza viruses in Indian poultry.

A total of 1246 faecal and tissue samples collected/received from 119 farms located in various states of India were processed for isolation of avian influenza viruses (AIV) during 2003-2004 as part of a program to monitor AIV infection in Indian poultry population. Avian influenza virus was isolated for the first time in India from poultry farms with history of drop in egg production, respiratory illness and increased mortality in Haryana state. A total of 29 H9N2 AIV isolates were obtained from the states of Punjab, Haryana, Uttar Pradesh, Gujarat, and Orissa and Union Territory Delhi. Subtyping was done by HI, RT-PCR and neuraminidase inhibition assay. Pathotyping of six representative isolates by intravenous pathogenicity index (0.0/3.0) in 6-8 weeks old chicken, trypsin dependency in cell culture and HA cleavage site analysis (335RSSR*GLF341) confirmed that these isolates are low pathogenic. Nucleotide sequence analysis of the HA gene showed that the Indian isolates are very closely related (95.0-99.6%) and shared a homology of 92-96% with H9N2 isolates from Germany and Asian regions other than that of mainland China. Deduced amino acid sequences showed the presence of L226 (234 in H9 numbering) which indicates a preference to binding of alpha (2-6) sialic acid receptors. Two of the six isolates had 7 glycosylation sites in the HA1 cleaved protein and the remaining four had 5 sites. Phylogenetic analysis showed that they share a common ancestor Qa/HK/G1/97 isolate which had contributed internal genes of H5N1 virus circulating in Vietnam. Further characterization of Indian H9N2 isolates is required to understand their nature and evolution.

Arsenic and lead induced free radical generation and their reversibility following chelation.

Health hazards caused by heavy metals have become a great concern to the population. Lead and arsenic are one of the most important current global environmental toxicants. Their toxic manifestations are being considered caused primarily due to the imbalance between pro-oxidant and antioxidant homeostasis and also due to a high affinity of these metals for thiol groups on functional proteins. They also interfere with a number of other body functions and are known to affect central nervous system (CNS), hematopoietic system, liver and kidneys and produce serious disorders. They produce both acute and chronic poisoning, of which chronic poisoning is more dangerous as its very difficult to revert back to normal condition after chronic exposure to these insidious metals present in our life. Despite many years of research, we are still far from an effective treatment of chronic plumbism and arsenicosis. Current approved treatment lies in the administration of chelating agents that forms an insoluble complex with the metal and removes it. They have been used clinically as antidotes for treating acute and chronic poisoning. The most widely used chelating agents are calcium disodium ethylenediamine tetra acetic acid (CaNa2EDTA), D-penicillamine and British anti-lewisite (BAL). Meso 2,3 dimercaptosuccinic acid (DMSA), an analogue of BAL, has been tried successfully in animals as well as in humans. But it is unable to remove the metal from intracellular sites. Effective chelation therapy for intoxication by heavy metals depends on whether the chelating agents are able to reach the intracellular site where the heavy metal is firmly bound. One of the important approaches has been the use of combination therapy. This includes use of structurally different chelators or a combination of an adjuvant/ antioxidant/ herbal extracts and a chelator to provide better clinical/ biochemical recovery. A number of other strategies have been suggested to minimize the numerous problems. This article presents the recent development made in this area with possible directions for future research.

Burden of organochlorine pesticides in blood and its effect on thyroid hormones in women.

Man has utilized a wide variety of pesticides to combat the crop pests and vectors of human diseases. However, in this process, he has overlooked the darker side of these noxious chemicals, the concentrations of which have reached the environment and pose serious threats, such as mutagenesis, teratogenesis, carcinogenesis and endocrine dysfunction in various components of the ecosystem. The present study was planned to assess the burden of organochlorine pesticides and their influence on thyroid function in women. The study included a total of 123 women from Jaipur City who visited the Thyroid clinic in SMS Medical College and Hospital. One hundred women showed normal thyroid hormone levels while the remaining 23 women had depleted T4 and high TSH levels. The qualitative and quantitative estimation of organochlorine pesticides was carried out by gas chromatography. Out of the analyzed pesticides, the concentration of p,p'-DDT and its metabolites was higher in all the subjects, but dieldrin was found to be significantly high in the hypothyroid women. The correlation analysis for dieldrin and depleted T4 levels in hypothyroid women elicited an inverse relationship between them.

Granulomatous angiitis of the central nervous system associated with herpes zoster.

Granulomatous angiitis of central nervous system (CNS) is a rare inflammatory disease of blood vessels mostly confined to CNS. We describe a case which presented with right sided hemiplegia with aphasia, after herpes zoster ophthalmicus. CT scan and MRI brain showed a large left sided infarct in the left middle cerebral artery (MCA) territory. MRI angiography revealed narrowing and thinning of left internal carotid artery (ICA) and to a lesser extent, left MCA suggestive of granulomatous vasculitis. Herpes zoster is often associated with major CNS involvement and a vascular etiology was previously postulated. Recent pathological reports suggest that cerebral angiitis secondary to herpes virus infection may be more common than realised.

A rare foreign body on penis leading to incarceration.

Foreign body on penis is usually put himself or by his female partner by adults for sexual gratification and in children as an innocent childish play. We have managed a 10 years shepherd who put on a bark of tree with successful outcome which is not being reported in literature.

Novel natural products from soil DNA libraries in a streptomycete host.

As a route to accessing the potential chemical diversity of uncultivable microbes from the soil, combinatorial biosynthetic libraries were constructed by cloning large fragments of DNA isolated from soil into a Streptomyces lividans host. Four novel compounds, terragines A (1), B (2), C (3), and D (4), were isolated from recombinant 436-s4-5b1, and another novel compound, terragine E (5), was isolated from 446-s3-102g1. The structures were determined by a combination of spectroscopic techniques, primarily 2D NMR.

An efficient in vitro procedure for micropropagation and generation of somaclones of rose scented Pelargonium.

Efficient protocols have been established for both direct and indirect regeneration of plants in Pelargonium graveolens Indian cultivar Hemanti (Algerian type). Murashige and Skoog's (MS) medium [T. Murashige, F. Skoog, A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol. Plant. 15 (1962) 473-497] supplemented with 5.0 mg/l kinetin and 1.0 mg/l NAA was optimal for direct regeneration of plants from leaf explants while 8.0 mg/l kinetin and 1.0 mg/l NAA proved optimum for nodal explants for maximum number of shoots per explant. Callus induction was observed from nodal explants on MS medium supplemented with 10 mg/l kinetin and 1.0 mg/l NAA. Callus on further transfer to MS medium with 0.5 mg/l BAP and 0.1 mg/l NAA exhibited regeneration of maximum number of shoots. In vitro grown shoots of both direct and indirect origin rooted within 7-10 days following transfer to half strength MS medium with 1.0 mg/l IBA. Plantlets were acclimatized under glass house conditions with 90% survival. Randomly selected 85 individual Calliclones were subjected to field trial with 85-95% survival for two successive years along with control in randomized block design with three replicates. Screening of these calliclones revealed two distinct morphotypes, one with parental type highly dentated leaves (HDL) and the other with less dentated, round leaves (LDL). Only HDL calliclones flowered under field conditions. The LDL clones differed in several herb related agronomic characteristics such as plant height, herb yield, canopy size and number of branches per plant from the parental type as well as from the parent, which seems advantageous for commercial exploitation of such clones. The HDL clones closely resemble the parent in having higher content of citronellol than geraniol while the LDL clones contain almost equal contents of citronellol and geraniol in their essential oils as revealed by gas chromatography analysis. It is noticeable that the variability both in terms of agronomic characters and essential oil profiles among the clones were stable over 2 years of field trials.

An open study to evaluate the efficacy of artemether in severe falciparum malaria.

An open clinical trial was conducted in 30 patients of severe falciparum malaria with heavy parasitaemia (parasitized erythrocytes above 5%). Artemether (methyl ether of dihydroartemisinin-active principle isolated from Chinese plant Qinghaosu) was administered as 80 mg intramuscular injection twice on first day and then single dose of 80 mg intramuscular on 2nd to 5th day. The trial could be completed in 28 patients and two patients expired. In our observation falciparum malaria affected the young adults in their most productive period of life i.e. 25-44 yrs. All patients became afebrile by the 4th day with fever clearance time approximately 31.92 +/- 15.30 hr. Twenty-five patients (83.33%) became parasite free by 5th day with mean parasite clearance time approximately 47.04 +/- 19.95 hr. Deranged liver function and renal profile was observed in 63% and 50% patients respectively. Two patients, who died had very high degree of parasitaemia (50% and 16%) with cerebral malaria. One died due to multiorgan failure and other due to massive hematemesis and shock. The type of response achieved by artemether therapy was analysed as per WHO criteria suggested for chloroquine resistance. S response was observed in 25 patients (cure rate 83.33%). Two patients (6.66%) patients showed R II response, one patient (3.33%) showed R III response and R I response was not observed in any patient. No significant side effects were noted. This pilot study demonstrated that intramuscular artemether is a useful addition to antimalarial drugs in this era of multidrug resistant P. falciparum malaria showing high clinical potency with virtually no side effect.

Antihypertensive efficacy and tolerability of once-daily sustained-release diltiazem alone and in combination with ramipril in hypertension.

This study assessed once-daily (OD), sustained-release (SR) diltiazem alone and in combination with ramipril in essential hypertension. Fifty patients with supine diastolic blood pressure (DBP) > or = 95-< or = 114 mm Hg were entered into the active treatment phase of the study after 2 weeks of placebo run-in. Sustained-release diltiazem 180 mg OD was administered for 2 weeks, then optimally titrated, at 2 week intervals, to SR diltiazem 240 mg OD and then SR diltiazem 180 mg + ramipril 2.5 mg OD to achieve supine DBP < or = 90 mm Hg. After 4 weeks of diltiazem monotherapy (SR diltiazem 180 mg or 240 mg OD) mean supine DBP was reduced from 102.84 +/- 3.81 mm Hg to 90.15 +/- 5.02 mm Hg (P < 0.01) and mean supine heart rate was reduced from 85.15 +/- 11.02 bpm to 77.62 +/- 11.45 bpm (p < 0.01). Diltiazem monotherapy reduced supine DBP to < or = 90 mm Hg in 35/45 (77.77%) patients. Combination therapy (SR diltiazem 180 mg + ramipril 2.5 mg OD), received by non-responders to diltiazem monotherapy, reduced supine DBP to < or = 90 mm Hg in 3/10 (30%) patients. Sinus bradycardia was observed in one patient. Sustained-release diltiazem alone and in combination with ramipril reduce blood pressure in a dose related manner and is well tolerated.

Antimycobacterial polyynes of Devil's Club (Oplopanax horridus), a North American native medicinal plant.

Two new (3 and 5), as well as three known (1, 2, and 4), polyynes were isolated from Devil's Club (Oplopanax horridus; Araliaceae), a medicinal plant of North America. The structures were established by 1H and 13C NMR. The absolute configurations of 2 and 5 were determined by application of Mosher's method. All the polyynes exhibited significant anti-Candida, antibacterial, and antimycobacterial activity, with an ability to kill Mycobacterium tuberculosis and isoniazid-resistant Mycobacterium avium at 10 micrograms/disk in a disk diffusion assay.

Antibacterial and antifungal polyine compounds from Glehnia littoralis ssp. leiocarpa.

Glehnia littoralis F. Schmidt ssp. leiocarpa (Mathias) Hult. (Apiaceae), a species of ethnopharmacological interest in British Columbia, has antibacterial and antifungal properties. Antibacterial and antifungal compounds include two hitherto unreported polyine compounds, (9Z)1,9-heptadecadiene-4,6-diyne-3,8,11-triol and (10E)1,10-heptadecadiene-4,6-diyne-3,8,9-triol.

An antibacterial thiophene from Balsamorhiza sagittata.

Balsamorhiza sagittata, a species of ethnopharmacological interest in British Columbia, is reported to have antibacterial and antifungal properties. An antibacterial compound isolated from this species was identified as 7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol based on the HMQC and HMBC experiments.

Chlorochimaphilin: a new antibiotic from Moneses uniflora.

A study of the antimicrobial compounds from Moneses uniflora resulted in the isolation of a novel compound, 8-chloro-2,7-dimethyl-1,4-naphthoquinone (8-chlorochimaphilin) (1), together with chimaphilin (2) and 3-hydroxychimaphilin (3) as the antimicrobial components. 2,7-Dimethyl-1,3-dihydroxynaphthyl 4-O-alpha-L-rhamnopyranoside (4) and 2,7-dimethoxy-1,4,8-trihydroxynaphthalene (6) were also isolated and identified.