Effect of high-flow nasal oxygen on hypoxaemia during procedural sedation: a systematic review and meta-analysis.

We conducted a systematic review to evaluate the effect of high-flow nasal oxygen and conventional oxygen therapy during procedural sedation amongst adults and children. We searched MEDLINE, EMBASE and CINAHL for randomised controlled trials that reported the effects of high-flow nasal oxygen during procedural sedation. The primary outcome measure was hypoxaemia and the secondary outcomes were minimum oxygen saturation; hypercarbia; requirement for airway manoeuvres; and procedure interruptions. The quality of evidence was assessed using the revised Cochrane risk-of bias tool and grading of recommendations, assessment, development and evaluation (GRADE). Nineteen randomised controlled trials (4121 patients) including three in children were included. Administration of high-flow nasal oxygen reduced hypoxaemia, risk ratio (95%CI) 0.37 (0.24-0.56), p < 0.001; minor airway manoeuvre requirements, risk ratio (95%CI) 0.26 (0.11-0.59), p < 0.001; procedural interruptions, risk ratio (95%CI) 0.17 (0.05-0.53), p = 0.002; and increased minimum oxygen saturation, mean difference (95%CI) 4.1 (2.70-5.50), p < 0.001; as compared with the control group. High-flow nasal oxygen had no impact on hypercarbia, risk ratio (95%CI) 1.24 (0.97-1.58), p = 0.09, I2 = 0%. High-flow nasal oxygen reduced the incidence of hypoxaemia regardless of the procedure involved, degree of fractional inspired oxygen, risk-profile of patients and mode of propofol administration. The evidence was ascertained as moderate for all outcomes except for procedure interruptions. In summary, high-flow nasal oxygen compared with conventional oxygenation techniques reduced the risk of hypoxaemia, increased minimum oxygen saturation and reduced the requirement for airway manoeuvres. High-flow nasal oxygen should be considered in patients at risk of hypoxaemia during procedural sedation.

Infectious causes of acute encephalitis syndrome hospitalizations in Central India, 2018-20.

BACKGROUND: We enhanced surveillance of hospitalizations of all ages for acute encephalitis syndrome (AES) along with infectious aetiologies, including the Japanese encephalitis virus (JEV). METHODS: From October 2018 to September 2020, we screened neurological patients for AES in all age groups in Maharashtra and Telangana States. AES cases were enrolled at study hospitals along with other referrals and sampled with cerebrospinal fluid, acute and convalescent sera. We tested specimens for non-viral aetiologies viz. leptospirosis, typhoid, scrub typhus, malaria and acute bacterial meningitis, along with viruses - JEV, Dengue virus (DENV), Chikungunya virus (CHIKV), Chandipura virus (CHPV) and Herpes simplex virus (HSV). RESULTS: Among 4977 neurological hospitalizations at three study site hospitals over two years period, 857 (17.2%) were AES. However, only 287 (33.5%) AES cases were eligible. Among 278 (96.9%) enrolled AES cases, infectious aetiologies were identified in 115 (41.4%) cases, including non-viral in 17 (6.1%) cases - leptospirosis (8), scrub-typhus (3) and typhoid (6); and viral in 98 (35.3%) cases - JEV (58, 20.9%), HSV (22, 7.9%), DENV (15, 5.4%) and CHPV (3, 1.1%). JEV confirmation was significantly higher in enrolled cases than referred cases (10.2%) (p < 0.05). However, the contribution of JEV in AES cases was similar in both children and adults. JE was reported year-round and from adjacent non-endemic districts. CONCLUSIONS: The Japanese encephalitis virus continues to be the leading cause of acute encephalitis syndrome in central India despite vaccination among children. Surveillance needs to be strengthened along with advanced diagnostic testing for assessing the impact of vaccination.

Studying the Relation Between Fibromyalgia Severity and Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume.

BACKGROUND: Fibromyalgia is characterized by chronic widespread pain, which has been linked to neuroinflammation. Hematological indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) have been shown to be effective markers in neurological diseases like depression. AIMS: To study the association between fibromyalgia severity and the hematological indices (NLR, PLR, and MPV). SUBJECTS AND METHODS: This was a hospital-based cross-sectional study of fibromyalgia patients satisfying the 2016 modification of the 2010/11 ACR criteria. Demographic and clinical characteristics were recorded along with fibromyalgia outcomes and hematological indices. Statistical analysis was done using descriptive statistics, ROC analysis using the Youden index, and Pearson and Spearman correlations. RESULTS: A total of 266 patients were recruited. The (mean ± S.D) NLR, MPV, and PLR were 1.92 ± 1.26, 8.94 ± 1.25, and 119.48 ± 76.91, respectively. Patients with severe visual analog scale (VAS) pain scores had lower MPV (8.8 ± 1.3) than those with mild/moderate pain (9.2 ± 1.1, p = 0.016). MPV showed a mild negative correlation with the Fibromyalgia Impact Questionnaire-Revised (FIQR) score (R2 -0.31 p 0.004). MPV threshold of 8.95 was discriminated severely from mild/moderate VAS-pain score with a sensitivity of 52.3 % and specificity of 66.7%. CONCLUSIONS: MPV can possibly be considered as a biomarker for predicting pain severity in fibromyalgia. Given its inexpensive nature, MPV can be used as a cost-effective method to assess fibromyalgia severity in rural India.

A new biodegradable nano cellulose-based drug delivery system for pH-controlled delivery of curcumin.

Targeted delivery and controlled release of drugs are attractive methods for avoiding the drug's leakage during blood circulation and burst release of the drug. We prepared a nano cellulose-based drug delivery system (DDS) for the effective delivery of curcumin (CUR). In the present scenario, the role of nanoparticles in fabricating the DDS is an important one and was characterized using various techniques. The drug loading capacity was high as 89.2% at pH = 8.0, and also the maximum drug release takes place at pH = 5.5. In vitro cell viability studies of DDS on MDA MB-231; breast cancer cells demonstrated its cytotoxicity towards cancer cells. The prepared DDS was also examined for apoptosis, hemocompatibility, and Chorioallantoic membrane (CAM) studies to assess its pharmaceutical field application and the investigation results recommended that it may serve as a potential device for targeted delivery and controlled release of CUR for cancer treatment.

Staring at an abscess, but lupus stares back .

We report a case of a 12-year-old male who initially presented with active systemic lupus erythematosus (SLE) with lupus nephritis and secondary macrophage activation syndrome (MAS). He went on to develop left-sided upper motor neuron (UMN) facial palsy secondary to lupus-related tumefactive demyelination. Tumefactive lesions secondary to demyelination are a very rare manifestation in neuropsychiatric SLE. This child responded to aggressive immunosuppression with steroids and cyclophosphamide.

Graphene oxide based functionalized chitosan polyelectrolyte nanocomposite for targeted and pH responsive drug delivery.

Graphene oxide (GO) was first modified to amine functionalized GO (AGO) and acts as a cationic polyelectrolyte. Chitosan (CS) was conjugated with folic acid (FA) through N, N´ -Dicyclohexylcarbodiimide coupling to form FA-CS. After this, itaconic acid and acrylic acid monomers are grafted to the hydroxyl group of CS using ethyleneglycol dimethacrylate as cross linker and potassium peroxydisulfate as an initiator to generate -COOH functional groups and forming chemically modified chitosan (CMCS). Further doxorubicin (DOX) loaded into the FA-CMCS/AGO through π-π stacking interactions. The resulting nanocomposite was characterized by FTIR, SEM, TEM, Raman, AFM, DLS and ZP. The drug loading capacity was as high as 95.0% and the drug release rate at pH 5.3 was significantly higher than that under physiological conditions of pH 7.4. Cell viability of L929, HeLa and MCF7 cells was studied. The studies suggest the drug carrier has potential clinical applications for anticancer drug delivery.

Bio-modified carbon paste electrode for the detection of Pb(II) ions in wastewater.

Heavy metal pollution in water is a serious environmental concern. Lead is one of the highly toxic heavy metals, and its toxicity is due to its non-degradation characteristic in living organisms. The monitoring of Pb(II) ions concentrations in drinking water is essential for human health and a safe environment. In this work, bio-modified carbon paste electrodes were constructed with live cells and thermally dried biomass (extracted protein) from Pseudomonas aeruginosa cells and employed for the detection of Pb(II) ions from wastewater. The biomass and biosensor preparation and optimization, and the performance of modified biosensors in the detection of Pb(II) ions are discussed here. The effect of various parameters, like pH, biomass composition, scan rate, and metal ion concentration, were studied to obtain the best electrochemical response. Further, the active surface of the electrode and solution characteristics were studies using chronocoulometry and electrochemical impedance spectroscopy. Fourier transform infrared spectroscopy (FTIR) analysis was done to find the functional groups present in the thermally dried biomass. From the present study, it is clear that the thermally dried protein biomass electrode has more sensitivity than the bare carbon paste electrode.

Moffett's muted mules: the science of laryngology in the art of war.

BACKGROUND: Mules and other equine species have been used in warfare for thousands of years to transport goods and supplies. Mules are known for 'braying', which is disadvantageous in warfare operations. This article explores the fascinating development of surgical techniques to stop military mules from braying, with particular emphasis on the key role played by the otolaryngologist Arthur James Moffett in devoicing the mules of the second Chindit expedition of World War II. METHOD: The PubMed database (1900-2017) and Google search engine were used to identify articles related to devoicing mules in the medical and veterinary literature, along with information and images on the Chindit expedition. RESULTS: This paper reviews the surgical techniques aimed at treating braying in mules, ranging from ventriculectomy and arytenoidectomy to Moffett's approach of vocal cordectomy. CONCLUSION: Moffett's technique of vocal cordectomy provided a quick, reproducible and safe solution for devoicing mules. It proved to be advantageous on the battlefield and demonstrated his achievements outside the field of medicine.

Leaching of ions from materials used in alternative restorative technique under neutral and acidic conditions: a comparative evaluation.

This study was undertaken to gain an insight into the interaction of conventional glass ionomers (GC Fuji II, GC Fuji IX GP and Chem Flex restorative materials) commonly used in Alternative Restorative Technique (ART) with aqueous solutions in terms of water sorption, solution buffering and ion release. Both immature and mature specimens of all materials evaluated, showed a substantial increase in mass, pH and release of Na, Ca, Sr, Al, Si, P and F following immersion in deionized water lactic acid (pH 2.7) and lactic acid (pH 5.2). However the ion release profiles were found to be greater in acidic media (Lactic Acid pH 2.7 > Lactic Acid pH 5.2) than in deionized water.

Polychaete worms--a vector for white spot syndrome virus (WSSV).

The present work provides the first evidence of polychaete worms as passive vectors of white spot syndrome virus (WSSV) in the transmission of white spot disease to Penaeus monodon broodstocks. The study was based on live polychaete worms, Marphysa spp., obtained from worm suppliers/worm fishers as well as samples collected from 8 stations on the northern coast of Tamilnadu (India). Tiger shrimp Penaeus monodon broodstock with undeveloped ovaries were experimentally infected with WSSV by feeding with polychaete worms exposed to WSSV. Fifty percent of polychaete worms obtained from worm suppliers were found to be WSSV positive by 2-step PCR, indicating high prevalence of WSSV in the live polychaetes used as broodstock feed by hatcheries in this area. Of 8 stations surveyed, 5 had WSSV positive worms with prevalence ranging from 16.7 to 75%. Polychaetes collected from areas near shrimp farms showed a higher level of contamination. Laboratory challenge experiments confirmed the field observations, and > 60% of worms exposed to WSSV inoculum were proved to be WSSV positive after a 7 d exposure. It was also confirmed that P. monodon broodstock could be infected with WSSV by feeding on WSSV contaminated polychaete worms. Though the present study indicates only a low level infectivity in wild polychaetes, laboratory experiments clearly indicated the possibility of WSSV transfer from the live feed to shrimp broodstock, suggesting that polychaete worms could play a role in the epizootiology of WSSV.

Synthesis and biological evaluation of [4-(2-phenylethenesulfonylmethyl)phenyl]-quinazolin-4-yl-amines as orally active anti-cancer agents.

A new series of [4-(2-phenylethenesulfonylmethyl)phenyl]quinazolin-4-yl-amines was prepared and tested for its in vitro cytotoxic activity against a panel of 12 human cancer cell lines. Compounds 9, 15, 24 and 31 showed good in vitro activity and were further tested for their in vivo efficacy in the HT-29 human colon adeno carcinoma xenograft model. Compound 9 exhibited promising activity in this model. Dose-response studies for this compound against HT-29 human colon adeno carcinoma xenografts at 100, 200 and 400mg/kg doses were performed.

Novel 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues as cytotoxic agents.

A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21 and 28 exhibited good pharmacokinetic properties. These compounds were further evaluated for their in vivo efficacy in modified hollow fibre assay (HFA).

Pesticide induced changes of nitric oxide synthase in rat brain in vitro.

Organic insecticides are well known neurotoxicants. Nitric oxide (NO) is a neurotransmitter formed stoicheometrically with citrulline from L-arqinine through mediation of the enzyme nitric oxide synthase (NOS). We measured NOS activity in rat brain in vitro in the presence of selected organic insecticides such as, 10-200 microM conc carbaryl, kepone and malathion. All these three compounds inhibited NOS activity of rat brain in vitro in a concentration dependent manner. In most cases the changes observed were statistically significant. The order of potency, based on IC50 values of these insecticides, to inhibit NOS activity of rat brain, is carbaryl (105 microM) > Kepone (144 microM) > malathion (170 microM). We further demonstrated that these insecticides inhibit calmodulin (CaM)-stimulated NOS activity without affecting the basal enzyme activity. It is reported that the observed inhibition of NOS by selected insecticides may be due to interaction of these insecticides with Ca2+/CaM on which the NOS activity is well known to be dependent. This ultimately may lead to neurotoxicity of rat brain.

Inhibition of rat brain nitric oxide synthase activity by cyclosporin-A.

Cyclosporin-A, a potent immunosuppressive agent is known to induce cellular toxic side effects by way of altering calcium homeostasis, including calcium/calmodulin mediated events. We studied the in vitro and in vivo effects of cyclosporin-A on rat brain nitric oxide synthase activity (the enzyme that mediates the conversion of L-arginine to citrulline and NO). CsA in concentrations of 22-4400 nM inhibited rat brain NOS activity in vitro and in 10 or 25 mg/kg wt/4 weeks of CsA treated rat brains in vivo. We report here that CsA by way of interfering with rat brain Ca2+/CaM mediated events may inhibit its NOS activity which ultimately may result in neurotoxicity.

Cercal sensory regulation of ganglionic protein metabolism in the field cricket, Gryllotalpa africana.

The effect of cercal deafferentation (cercectomy) on the ganglionic protein metabolism of the cricket, Gryllotalpa africana was studied. Significant changes in the activities of the enzymes acetylcholinesterase, glutamate dehydrogenase, alanine aminotransferase and aspartate aminotransferase were observed in the terminal ganglion following unilateral and bilateral cercectomy.

Cercal sensory regulation of acetylcholinesterase in nervous system of the cockroach, Periplaneta americana.

Cercal ablation caused a significant loss in acetylcholinesterase (AChE) activity of the cercal nerves and terminal ganglion within 12 hr while a similar reduction in enzyme activity of connectives was noticed at least one day after cercectomy. The decrease in AChE activity of the nervous tissues showed a recovery toward control levels from 20 days of unilateral cercectomy whereas the bilateral cercectomy produced a continuous and irreversible decline in enzyme activity. These localized changes in AChE activity of the abdominal nervous system of the cockroach were attributed to be regulated by the cercal sensory innervation.

Rate constants for a mechanism including intermediates in the interconversion of ternary complexes by horse liver alcohol dehydrogenase.

Transient kinetic data for partial reactions of alcohol dehydrogenase and simulations of progress curves have led to estimates of rate constants for the following mechanism, at pH 8.0 and 25 degrees C: E in equilibrium E-NAD+ in equilibrium *E-NAD+ in equilibrium E-NAD(+)-RCH2OH in equilibrium E-NAD+-RCH2O- in equilibrium *E-NADH-RCHO in equilibrium E-NADH-RCHO in equilibrium E-NADH in equilibrium E. Previous results show that the E-NAD+ complex isomerizes with a forward rate constant of 620 s-1 [Sekhar, V. C., & Plapp, B. V. (1988) Biochemistry 27, 5082-5088]. The enzyme-NAD(+)-alcohol complex has a pK value of 7.2 and loses a proton rapidly (greater than 1000 s-1). The transient oxidation of ethanol is 2-fold faster in D2O, and proton inventory results suggest that the transition state has a charge of -0.3 on the substrate oxygen. Rate constants for hydride ion transfer in the forward or reverse reactions were similar for short-chain aliphatic substrates (400-600 s-1). A small deuterium isotope effect for transient oxidation of longer chain alcohols is apparently due to the isomerization of the E-NAD+ complex. The transient reduction of aliphatic aldehydes showed no primary deuterium isotope effect; thus, an isomerization of the E-NADH-aldehyde complex is postulated, as isomerization of the E-NADH complex was too fast to be detected. The estimated microscopic rate constants show that the observed transient reactions are controlled by multiple steps.

Nuclear magnetic resonance spectroscopy of plasma for the detection of head and neck cancer.

The plasma of 15 normal volunteers, four patients with benign head and neck disease, and 12 patients with biopsy proven head and neck malignancies were evaluated using water-suppressed nuclear magnetic resonance (NMR) spectroscopy. While the mean full width at half height (HHLW) of the NMR spectra showed a significant difference between groups (P less than .05), the predictive value of a positive test was only 57% the sensitivity was only 33%, and individual values in all groups demonstrated considerable overlap. The mean HHLW of the control group was 38.5 Hz +/- 3.5 compared with 35.2 Hz +/- 4.7 for the cancer group and 35.0 Hz +/- 10 for the benign disease group. This method was not able to distinguish patients with malignancy from those with benign disease or controls. Its use as a specific screening method for head and neck malignancy cannot be recommended.

Mechanism of binding of horse liver alcohol dehydrogenase and nicotinamide adenine dinucleotide.

The binding of NAD+ to liver alcohol dehydrogenase was studied by stopped-flow techniques in the pH range from 6.1 to 10.9 at 25 degrees C. Varying the concentrations of NAD+ and a substrate analogue used to trap the enzyme-NAD+ complex gave saturation kinetics. The same maximum rate constants were obtained with or without the trapping agent and by following the reaction with protein fluorescence or absorbance of a ternary complex. The data fit a mechanism with diffusion-controlled association of enzyme and NAD+, followed by an isomerization with a forward rate constant of 500 s-1 at pH 8: E E-NAD+ *E-NAD+. The isomerization may be related to the conformational change determined by X-ray crystallography of free enzyme and enzyme-coenzyme complexes. Overall bimolecular rate constants for NAD+ binding show a bell-shaped pH dependence with apparent pK values at 6.9 and 9.0. Acetimidylation of epsilon-amino groups shifts the upper pK to a value of 11 or higher, suggesting that Lys-228 is responsible for the pK of 9.0. Formation of the enzyme-imidazole complex abolishes the pK value of 6.9, suggesting that a hydrogen-bonded system extending from the zinc-bound water to His-51 is responsible for this pK value. The rates of isomerization of E-NAD+ and of pyrazole binding were maximal at pH below a pK of about 8, which is attributable to the hydrogen-bonded system. Acetimidylation of lysines or displacement of zinc-water with imidazole had little effect on the rate of isomerization of the E-NAD+ complex.(ABSTRACT TRUNCATED AT 250 WORDS)