Synthesis of Quinazolinones and Benzothiazoles Using α-Keto Acids under Ball Milling.

Mechanochemistry refers to the initiation of chemical reactions via mechanical forces such as milling, grinding, or shearing to achieve the chemical transformations. As a manifestation of mechanocatalysis, herein, an oxidant-free and solvent-free approach for the synthesis of quinazolinones (23 derivatives) and benzothiazoles (23 derivatives) has been developed through stainless-steel-driven decarboxylative acyl radical generation from α-keto acids. A library of 2-arylquinazolinones and 2-arylbenzothiazoles has been prepared in moderate to good yields at room temperature. Moreover, control experiments and XPS studies supported the reduction (by zerovalent iron) of molecular oxygen through the moderate abrasion of balls, which promoted the generation of a superoxide radical anion via a SET process.

Assessing testicular germ cell DNA damage in the comet assay; introduction of a proof-of-concept.

The in vivo comet assay is widely used to measure genotoxicity; however, the current OECD test guideline (TG 489) does not recommend using the assay to assess testicular germ cells, due to the presence of testicular somatic cells. An adapted approach to specifically assess testicular germ cells within the comet assay is certainly warranted, considering regulatory needs for germ cell-specific genotoxicity data in relation to the increasing global production of and exposure to potentially hazardous chemicals. Here, we provide a proof-of-concept to selectively analyze round spermatids and primary spermatocytes, distinguishing them from other cells of the testicle. Utilizing the comet assay recordings of DNA content (total fluorescence intensity) and DNA damage (% tail intensity) of individual comets, we developed a framework to distinguish testicular cell populations based on differences in DNA content/ploidy and appearance. Haploid round spermatid comets are identified through (1) visual inspection of DNA content distributions, (2) setting DNA content thresholds, and (3) modeling DNA content distributions using a normal mixture distribution function. We also describe an approach to distinguish primary spermatocytes during comet scoring, based on their high DNA content and large physical size. Our concept allows both somatic and germ cells to be analyzed in the same animal, adding a versatile, sensitive, rapid, and resource-efficient assay to the limited genotoxicity assessment toolbox for germ cells. An adaptation of TG 489 facilitates accumulation of valuable information regarding distribution of substances to germ cells and their potential for inducing germ cell gene mutations and structural chromosomal aberrations.

A comparative clinical trial for evaluating the posterior palatal seal developed from the conventional method and a novel functional swallow method.

Aims: The aim of this in vivo study was to compare the influence of posterior palatal seal (PPS) developed from the conventional method and a novel functional swallow method on the retention of custom tray and heat cure denture base. Settings and Design: This was a nonrandomized crossover clinical trial. Materials and Methods: Twenty patients requiring maxillary complete dentures were selected. In Group 1, for all twenty patients, the PPS was developed with the conventional functional method during border molding and a conventional cast scoring was performed before processing the denture base. In Group 2, for all the twenty patients, the PPS was developed with a novel functional swallow method and the master cast was "not" scored before processing the denture base. The retention was objectively measured using a dynamometer after border molding and also after processing the denture base for both groups. Statistical Analysis Used: Independent Student's t-test and paired t-test were used for analysis. Results: The mean retention value of Group 2 was significantly higher (P < 0.001) than Group 1 at border molding and after denture base processing. Within Group 1, the retention value significantly increased (P < 0.001) from border molding to the denture base stage, whereas within Group 2, there was no significant change (P > 0.001) between the stages. Conclusions: Within the limitations of the study, the novel functional swallow method of establishing the PPS demonstrated higher retention than the conventional method both during border molding and after processing the denture base.

Pulmonary toxicity, genotoxicity, and carcinogenicity evaluation of molybdenum, lithium, and tungsten: A review.

Molybdenum, lithium, and tungsten are constituents of many products, and exposure to these elements potentially occurs at work. Therefore it is important to determine at what levels they are toxic, and thus we set out to review their pulmonary toxicity, genotoxicity, and carcinogenicity. After pulmonary exposure, molybdenum and tungsten are increased in multiple tissues; data on the distribution of lithium are limited. Excretion of all three elements is both via faeces and urine. Molybdenum trioxide exerted pulmonary toxicity in a 2-year inhalation study in rats and mice with a lowest-observed-adverse-effect concentration (LOAEC) of 6.6 mg Mo/m3. Lithium chloride had a LOAEC of 1.9 mg Li/m3 after subacute inhalation in rabbits. Tungsten oxide nanoparticles resulted in a no-observed-adverse-effect concentration (NOAEC) of 5 mg/m3 after inhalation in hamsters. In another study, tungsten blue oxide had a LOAEC of 63 mg W/m3 in rats. Concerning genotoxicity, for molybdenum, the in vivo genotoxicity after inhalation remains unknown; however, there was some evidence of carcinogenicity of molybdenum trioxide. The data on the genotoxicity of lithium are equivocal, and one carcinogenicity study was negative. Tungsten seems to have a genotoxic potential, but the data on carcinogenicity are equivocal. In conclusion, for all three elements, dose descriptors for inhalation toxicity were identified, and the potential for genotoxicity and carcinogenicity was assessed.

Distribution, metabolism, excretion, and toxicity of implanted silver: a review.

Some implantable medical devices contain silver. We aimed to assess at what amount implanted silver becomes toxic. Silver was elevated in bodily fluids and tissues surrounding silver-containing implants. Silver released from implants also distributes to blood and other tissues; there is evidence to suggest silver can pass the blood-brain-barrier. Silver can be deposited as nano-sized particles in various tissues. Such particles, in addition to silver, often contain other elements too, e.g., selenium and sulfur. Silver released from implants seems to stay in the body for long periods (years). Reported excretion pathways following implantation are urinary and fecal ones. Reported toxicological effects were virtually all local reactions surrounding the implants. Argyria is a blue-gray discoloration of the skin due to deposited silver granules. Localized argyria has been described after the implantation of acupuncture needles and silver-coated prostheses, although the presence of silver was tested only for and shown in the former. Other toxicological effects include local tissue reactivity and examples of neurotoxic and vascular effects. We did not include genotoxicity studies in the present publication as we recently evaluated silver to be genotoxic. Carcinogenicity studies were absent. We conclude that local toxicity of implanted silver can be foreseen in some situations.

Toxicity of boric acid, borax and other boron containing compounds: A review.

Boron, often in the form of boric acid, is widely used as a flame retardant in insulation products, and although humans ingest boron through food, high exposure may lead to unwanted health effects. We assessed the toxicity of boric acid, borax and other forms of boron, after inhalation, dermal and oral exposure. After oral exposure, boron is absorbed over the gastrointestinal tract. Intact skin seems to pose a more effective barrier to boron than compromised skin. Boron excretion seems to mainly occur via the urine, although after skin exposure boron has been demonstrated in bile and gastrointestinal contents. Inhalation toxicity data are sparse, but one animal study showed reduced foetal weight after inhalation of cellulose that had a boric acid content of 20%. Skin exposure to boric acid has proven fatal in some cases, and the range of toxicity effects include abdominal as well as local effects on the skin. Fatalities from boric acid also have occurred after oral ingestion, and the endpoints in animals are weight loss and reproductive toxicity. Concerning genotoxicity studies, the overall picture indicates that boron-containing compounds are not genotoxic. There was no evidence of the carcinogenicity of boric acid in a 2-year study in mice.

Pulmonary toxicity of silver vapours, nanoparticles and fine dusts: A review.

Silver is used in a wide range of products, and during their production and use, humans may be exposed through inhalation. Therefore, it is critical to know the concentration levels at which adverse effects may occur. In rodents, inhalation of silver nanoparticles has resulted in increased silver in the lungs, lymph nodes, liver, kidney, spleen, ovaries, and testes. Reported excretion pathways of pulmonary silver are urinary and faecal excretion. Acute effects in humans of the inhalation of silver include lung failure that involved increased heart rate and decreased arterial blood oxygen pressure. Argyria-a blue-grey discoloration of skin due to deposited silver-was observed after pulmonary exposure in 3 individuals; however, the presence of silver in the discolorations was not tested. Argyria after inhalation seems to be less likely than after oral or dermal exposure. Repeated inhalation findings in rodents have shown effects on lung function, pulmonary inflammation, bile duct hyperplasia, and genotoxicity. In our evaluation, the range of NOAEC values was 0.11-0.75 mg/m3. Silver in the ionic form is likely more toxic than in the nanoparticle form but that difference could reflect their different biokinetics. However, silver nanoparticles and ions have a similar pattern of toxicity, probably reflecting that the effect of silver nanoparticles is primarily mediated by released ions. Concerning genotoxicity studies, we evaluated silver to be positive based on studies in mammalian cells in vitro and in vivo when considering various exposure routes. Carcinogenicity data are absent; therefore, no conclusion can be provided on this endpoint.

Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens.

While regulatory requirements for carcinogenicity testing of chemicals vary according to product sector and regulatory jurisdiction, the standard approach starts with a battery of genotoxicity tests (which include mutagenicity assays). If any of the in vivo genotoxicity tests are positive, a lifetime rodent cancer bioassay may be requested, but under most chemical regulations (except plant protection, biocides, pharmaceuticals), this is rare. The decision to conduct further testing based on genotoxicity test outcomes creates a regulatory gap for the identification of non-genotoxic carcinogens (NGTxC). With the objective of addressing this gap, in 2016, the Organization of Economic Cooperation and Development (OECD) established an expert group to develop an integrated approach to the testing and assessment (IATA) of NGTxC. Through that work, a definition of NGTxC in a regulatory context was agreed. Using the adverse outcome pathway (AOP) concept, various cancer models were developed, and overarching mechanisms and modes of action were identified. After further refining and structuring with respect to the common hallmarks of cancer and knowing that NGTxC act through a large variety of specific mechanisms, with cell proliferation commonly being a unifying element, it became evident that a panel of tests covering multiple biological traits will be needed to populate the IATA. Consequently, in addition to literature and database investigation, the OECD opened a call for relevant assays in 2018 to receive suggestions. Here, we report on the definition of NGTxC, on the development of the overarching NGTxC IATA, and on the development of ranking parameters to evaluate the assays. Ultimately the intent is to select the best scoring assays for integration in an NGTxC IATA to better identify carcinogens and reduce public health hazards.

Toxicity of silver ions, metallic silver, and silver nanoparticle materials after in vivo dermal and mucosal surface exposure: A review.

Silver is used in different applications that result in contact with skin and mucosal surfaces (e.g., jewelry, wound dressings, or eye drops). Intact skin poses an effective barrier against the absorption of silver. Mucosal surfaces are observed to be less effective barriers and compromised skin is often a poor barrier. Silver can deposit as particles in the human body causing a blue-gray discoloration known as argyria. Urine and feces are reported pathways of excretion. Acute human mortality has been observed following an abortion procedure involving the intrauterine administration of 7 g silver nitrate (64 mg silver/kg body weight). Localized argyria has been reported with exposure to silver ions, metallic surfaces, and nanocrystalline silver. Generalized argyria was observed with ionic and nanocrystalline silver in humans at cumulative doses in the range of 70-1500 mg silver/kg body weight. Silver is observed to have a low potential for skin irritation. Eye irritation and some cases of allergic contact dermatitis have been reported. Silver may cause genotoxicity, but additional data are required to assess its carcinogenic potential. Other reported toxicities include hepatic, renal, neurological, and hematological effects.

Temporomandibular Joint Ankylosis: "A Pediatric Difficult Airway Management".

Intubating a pediatric patient with temporomandibular joint ankylosis is a daunting task, and it becomes more challenging with limited mouth opening. Fiberoptic nasotracheal intubation technique is considered a gold standard. We describe an improvised technique of securing airway in the absence of appropriate-sized fiberoptic scope. The endotracheal tube inserted in the left nostril for maintaining depth of anesthesia was advanced under vision by the fiberoptic scope inserted into the right nostril, and with external laryngeal manipulation, the airway was secured with no complications.

The handheld blood lactate analyser versus the blood gas based analyser for measurement of serum lactate and its prognostic significance in severe sepsis.

BACKGROUND: This study was done to compare the accuracy of the Lactate Pro LT 1710 (Arkray Inc., Kyoto, Japan) with the Combiline Plus (Eschweiler GmbH & Co. KG Holzkoppelweg, Kiel, Germany), and also, to analyze the prognostic significance of serum lactates and Simplified Acute Physiology Score 3 (SAPS 3) in patients of severe sepsis. METHODS: 106 patients of severe sepsis admitted to the ICU were screened. The serum lactate from an arterial sample analyzed in both the machines was recorded at admission and at 48 h. These patients were then followed up to the 28th day for mortality. RESULTS: The Lactate Pro LT 1710 handheld point of care lactate meter provides consistent results comparable to the Eschweiler Combiline blood gas analyser. Serum lactate concentration was significantly higher in nonsurvivors at the time of admission (3.30 ± 1.26) and at 48 h (4.34 ± 1.73). Lactate clearance at 48 h appears to be a better predictor of mortality than the lactate levels at 0 h and 48 h. The mean SAPS 3 at admission amongst survivors was significantly less as compared to nonsurvivors. The SAPS 3 had improved to 47.44 (±11.79) in survivors at 48 h, while in nonsurvivors it had worsened to 81.98 (±12.32) (p = 0.00); thus, a worsening SAPS 3 at 48 h had a poorer prognosis. CONCLUSIONS: The Lactate Pro LT 1710 provides similar results to the Combiline Eschweiler blood gas analyser and is a cheaper alternative. It would prove to be a boon in peripheral hospitals in the aggressive management of critically ill patients.

An evaluation of brachial plexus block using a nerve stimulator versus ultrasound guidance: A randomized controlled trial.

BACKGROUND AND AIMS: This study was carried out to evaluate the difference in efficacy, safety, and complications of performing brachial plexus nerve blocks by using a nerve locator when compared to ultrasound (US) guidance. MATERIAL AND METHODS: A total of 102 patients undergoing upper limb surgery under supraclavicular brachial plexus blocks were randomly divided into two groups, one with US and the other with nerve stimulator (NS). In Group US, "Titan" Portable US Machine, Sonosite, Inc. Kensington, UK with a 9.0 MHz probe was used to visualize the brachial plexus and 40 ml of 0.25% bupivacaine solution was deposited around the brachial plexus in a graded manner. In Group (NS), the needle was inserted 1-1.5 cm above mid-point of clavicle. Once hand or wrist motion was detected at a current intensity of less than 0.4 mA 40 ml of 0.25% bupivacaine was administered. Onset of sensory and motor block of radial, ulnar and median nerves was recorded at 5-min intervals for 30-min. Block execution time, duration of block (time to first analgesic), inadvertent vascular puncture, and neurological complications were taken as the secondary outcome variables. RESULTS: About 90% patients in US group and 73.1% in NS group, had successful blocks P = 0.028. The onset of block was faster in the Group US as compared to Group NS and this difference was significant (P 0.007) only in the radial nerve territory. The mean duration of the block was longer in Group US, 286.22 ± 42.339 compared to 204.37 ± 28.54-min in Group NS (P < 0.05). Accidental vascular punctures occurred in 7 patients in the NS group and only 1 patient in the US group. CONCLUSION: Ultrasound guidance for supraclavicular brachial plexus blockade provides a block that is faster in onset, has a better quality and lasts longer when compared with an equal dose delivered by conventional means.

Toxicological risk assessment of elemental gold following oral exposure to sheets and nanoparticles - A review.

Elemental gold is used as a food coloring agent and in dental fillings. In addition, gold nanoparticles are gaining increasing attention due to their potential use as inert carriers for medical purposes. Although elemental gold is considered to be inert, there is evidence to suggest the release of gold ions from its surface. Elemental gold, or the released ions, is, to some extent, absorbed in the gastrointestinal tract. Gold is distributed to organs such as the liver, heart, kidneys and lungs. The main excretion route of absorbed gold is through urine. Data on the oral toxicity of elemental gold is limited. The acute toxicity of elemental gold seems to be low, as rats were unaffected by a single dose of 2000mg nanoparticles/kg of body weight. Information on repeated dose toxicity is very limited. Skin rashes have been reported in humans following the ingestion of liquors containing gold. In addition, gold released from dental restorations has been reported to increase the risk of developing gold hypersensitivity. Regarding genotoxicity, in vitro studies indicate that gold nanoparticles induce DNA damage in mammalian cells. In vivo, gold nanoparticles induce genotoxic effects in Drosophila melanogaster; however, genotoxicity studies in mammals are lacking. Overall, based on the literature and taking low human exposure into account, elemental gold via the oral route is not considered to pose a health concern to humans in general.

Control of hospital acquired infections in the ICU: A service perspective.

BACKGROUND: The service setting has some unique strengths and weaknesses that must be kept in mind when organizing Hospital acquired infections (HAI) prevention interventions. METHODS: Following an initial study to gather data regarding HAI in the Surgical intensive care unit (ICU) we put into place various infection control interventions. The present study was carried out to analyse the effect of these interventions on the incidence of HAI in the ICU. RESULTS: The total admissions to the ICU were 253 patients. Eighty eight patients (34.78%) were admitted for more than 48 hr, 165 patients stayed for less than 48 h. The frequency of HAI was 7.95% (95% CI 3.54, 15). Hospital acquired pneumonia was observed in 2 of the 88 patients (2.27%) (95% CI 0.38, 7.30) which amounted to 9.70 infections per 1000 ventilator days. Bloodstream infection was detected in 3 out of 88 patients (3.4%) (95% CI 0.87, 8.99) amounting to 6.54 fresh infections per 1000 Central Venous Catheter days. Urinary tract infection was observed in 2 (2.27%) (95% CI 0.38, 7.30) at 2.86 fresh infections per 1000 catheter days. As compared to the previous study we found that there was a decline of HAI ranging from 60 to 70%. CONCLUSION: Our study demonstrated that by meticulously following infection control protocols especially tailored to the service setting the incidence of HAI's can be reduced. However, the challenge is in maintaining the gains achieved since there is a rapid turnover of manpower in the ICU and a lack of a structured ICU design model.

In vivo Comet assay--statistical analysis and power calculations of mice testicular cells.

The in vivo Comet assay is a sensitive method for evaluating DNA damage. A recurrent concern is how to analyze the data appropriately and efficiently. A popular approach is to summarize the raw data into a summary statistic prior to the statistical analysis. However, consensus on which summary statistic to use has yet to be reached. Another important consideration concerns the assessment of proper sample sizes in the design of Comet assay studies. This study aims to identify a statistic suitably summarizing the % tail DNA of mice testicular samples in Comet assay studies. A second aim is to provide curves for this statistic outlining the number of animals and gels to use. The current study was based on 11 compounds administered via oral gavage in three doses to male mice: CAS no. 110-26-9, CAS no. 512-56-1, CAS no. 111873-33-7, CAS no. 79-94-7, CAS no. 115-96-8, CAS no. 598-55-0, CAS no. 636-97-5, CAS no. 85-28-9, CAS no. 13674-87-8, CAS no. 43100-38-5 and CAS no. 60965-26-6. Testicular cells were examined using the alkaline version of the Comet assay and the DNA damage was quantified as % tail DNA using a fully automatic scoring system. From the raw data 23 summary statistics were examined. A linear mixed-effects model was fitted to the summarized data and the estimated variance components were used to generate power curves as a function of sample size. The statistic that most appropriately summarized the within-sample distributions was the median of the log-transformed data, as it most consistently conformed to the assumptions of the statistical model. Power curves for 1.5-, 2-, and 2.5-fold changes of the highest dose group compared to the control group when 50 and 100 cells were scored per gel are provided to aid in the design of future Comet assay studies on testicular cells.

Role of antibiotics on surgical site infection in cases of open and laparoscopic cholecystectomy: a comparative observational study.

INTRODUCTION: Surgical site infection (SSI) comes as third most common healthcare related infection which produces morbidity and deaths at large. Still many authors believe that it is better not to use prophylactic antibiotics in simple and uncomplicated cases. Laparoscope, now-a-days is a much used instrument for abdominal surgeries. Even after new aseptic techniques SSI remains to be a major problem. AIMS AND OBJECTIVES: To study the effect of antibiotics on superficial SSI in the cases of open and laparoscopic cholecystectomy. OBSERVATION AND RESULTS: One hundred patients were enrolled for cholecystectomy. The patients were divided into two groups, A and B. Group A consisted of patients in whom laparoscopic cholecystectomy was done and group B in whom open cholecystectomy was done. The male female ratio was 1: 2.23. The mean age of patients in Group A was 46 years and in Group B was 44; Standard deviation (SD) for age was 14.8% and 13.8% in groups A and B respectively; t-value was 0.654 and P value was 0.515 and they were not significant. The number of males and females was 16 and 26 respectively in Group A and 11 and 31 in Group B. The Chi square X(2) = 1.36 and P value was 0.248 and both were insignificant. The rate of superficial surgical site infection was 2.63% in both the groups. CONCLUSION: Our study concludes that there is no difference in the outcome of patients in cases of open as well as laparoscopic cholecystectomy. There is no significant difference in the surgical site infection rate in cases of open as well as laparoscopic cholecystectomy.

Abscess mimicking pre-cervical and submandibular cystic hygroma in a newborn.

Pre-cervical inflammation is rarely seen in a newborn. Those swellings that are seen are usually congenital, such as vascular malformations, teratoma, dermoid cyst, thyroglossal cyst, cystic hygroma (abnormal lymphatic tissue), and very rarely, inflammation secondary to infection. Being able to differentiate between each condition is important because the course, treatment and prognosis for each condition are different. This case of a neck abscess in a newborn is reported due to its resemblance to cystic hygroma and highlights the similarities between the two conditions.