Brucella infection presenting as infective endocarditis complicated by embolic stroke.

Brucellosis (undulant fever) is a zoonotic infection caused by Brucella species. It typically presents with fever, malaise, night sweats, and arthralgia. One of its rare complications is infective endocarditis, which occurs in approximately 1.3% of patients and can be further complicated by embolic stroke. This report describes a rare occurrence of Brucella endocarditis presenting as an embolic stroke. A 34-year-old male presented with sudden left-sided weakness and fever. He reported headaches, fever, and generalized weakness in the preceding week. The patient worked on a farm and hence had animal contact. A neurological exam showed left-sided facial weakness, and power of 0/5 and 1/5 in the left upper and lower extremities, respectively. CT scan of the head revealed a right middle cerebral artery (MCA) territory infarct with penumbra and a right MCA occlusion. He underwent a cerebral artery thrombectomy with successful recanalization. However, he continued to have fever and high inflammatory markers. Echocardiography showed aortic valve vegetation and blood cultures grew Brucella melitensis. A multidisciplinary meeting was held to determine the optimal management, which included a course of rifampicin and doxycycline.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents

Abstract Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of chloro group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Resumo Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo cloro tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Synthesis and evaluation of 2-phenylamino-1, 4-naphthoquinones derivatives as potential hypoglycaemic agents / Síntese e avaliação de derivados de 2-fenilamino-1, 4-naftoquinonas como potenciais agentes hipoglicemiantes

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Anemia and Hypoxia Impact on Chronic Kidney Disease Onset and Progression: Review and Updates.

Chronic kidney disease (CKD) is caused by hypoxia in the renal tissue, leading to inflammation and increased migration of pathogenic cells. Studies showed that leukocytes directly sense hypoxia and respond by initiating gene transcription, encoding the 2-integrin adhesion molecules. Moreover, other mechanisms participate in hypoxia, including anemia. CKD-associated anemia is common, which induces and worsens hypoxia, contributing to CKD progression. Anemia correction can slow CKD progression, but it should be cautiously approached. In this comprehensive review, the underlying pathophysiology mechanisms and the impact of renal tissue hypoxia and anemia in CKD onset and progression will be reviewed and discussed in detail. Searching for the latest updates in PubMed Central, Medline, PubMed database, Google Scholar, and Google search engines were conducted for original studies, including cross-sectional studies, cohort studies, clinical trials, and review articles using different keywords, phrases, and texts such as "CKD progression, anemia in CKD, CKD, anemia effect on CKD progression, anemia effect on CKD progression, and hypoxia and CKD progression". Kidney tissue hypoxia and anemia have an impact on CKD onset and progression. Hypoxia causes nephron cell death, enhancing fibrosis by increasing interstitium protein deposition, inflammatory cell activation, and apoptosis. Severe anemia correction improves life quality and may delay CKD progression. Detection and avoidance of the risk factors of hypoxia prevent recurrent acute kidney injury (AKI) and reduce the CKD rate. A better understanding of kidney hypoxia would prevent AKI and CKD and lead to new therapeutic strategies.

Isolated Sixth Cranial Nerve Palsy as Initial Presentation of Pituitary Apoplexy: A Case Report.

Pituitary apoplexy is a serious condition, which if left untreated, might lead to irreversible life-long complications. Hence, pituitary apoplexy should always be included in the differential diagnoses of a patient with an isolated sixth cranial nerve (CN) palsy. This report highlights the case of a patient presenting with isolated CN palsy associated with pituitary apoplexy. Although pituitary adenomas are common, they seldom present with isolated abducent nerve palsy without any other CN involvement. The 47-year-old female patient presented with acute right eye pain, diplopia, and a squint. Examination revealed an isolated unilateral sixth CN palsy. Brain MRI showed a sellar and suprasellar mass suggestive of hemorrhagic pituitary apoplexy. The patient was transferred to neurosurgery and underwent transsphenoidal resection of a pituitary macroadenoma. Postoperative follow-up showed clinical improvement. It is, thus, imperative for physicians to have the knowledge to recognize an isolated sixth cranial nerve palsy and its associated causes.

Effects of Nondipping Blood Pressure Changes: A Nephrologist Prospect.

Blood pressure (BP) variations depend on various internal, environmental, and behavioral factors. BP fluctuations occur both in normotensive and hypertensive people. Although it fluctuates over the 24-hr day and night, the morning BP increases after waking up and declines throughout sleep. It is typical for BP to decrease by 10% to 20%, while sleeping, known as dipping BP. However, if there is no decrease in nighttime mean systolic BP or a drop of less than 10 mmHg, it is called nondipping BP. Conversely, reverse dipping BP means an increase in mean systolic BP instead of a drop during the night. Reverse dipping is observed in hypertension (HTN), diabetes mellitus (DM), chronic kidney disease (CKD), and obstructive sleep apnea (OSA) syndrome. The introduction of ambulatory BP monitoring (ABPM) led to the emergence of identifying normal and elevated BP patterns. Non-dipping BP increases the risk of cardiovascular system (CVS) complications such as left ventricular hypertrophy, proteinuria, glomerular filtration rate (GFR) reduction, and CKD progression. A loss or blunting of the normal BP profile is recognized as a deleterious variant, and restoring abnormal BP patterns has been reported to significantly impact end-organ damage, morbidity, and mortality. In this non-systematic clinically-oriented, comprehensive review, we aim to update the BP variables and the pathophysiology of nondipping BP and point out the areas which need more investigation from a nephrology perspective because the nondipping BP increases the risk of proteinuria, GFR reduction, and CKD progression. A literature search of PubMed, Google, EMBASE, and Google Scholar was conducted. Checks of selected papers and relevant reviews complemented the electronic search. With improved BP measurement methods, the physiology of BP profile variations is readily detectable during the day and night. A nondipping BP profile is a distinct BP pattern that may have significant end-organ damage effects and therapeutic importance for nephrologists. The pathophysiology of the nondipping BP variant must be clarified to prevent complications, and further investigations are required. Furthermore, there is debate about the best BP index to utilize: systolic BP, diastolic BP, mean arterial pressure, or a mixture of all. All these areas are important and need new research projects.

Flexible Sigmoidoscopy Utility in the Diagnosis of Pediatric Gastrointestinal Disorders.

AIM:  Although flexible sigmoidoscopy (FS) is utilized in children for the diagnosis of pediatric gastrointestinal conditions, such as inflammatory bowel disease and juvenile polyp disorders, the diagnostic yield of FS in pediatric patients is unknown. MATERIALS AND METHODS:  We retrospectively reviewed FS cases in children under 18 years of age over a five-year period at our institution. Indications for the procedure, endoscopic visual findings, histologic findings, final diagnosis, and any management changes based on FS findings were included. RESULTS:  A total of 354 cases were included in the analysis for which 40 cases (11.3%) had abnormal visual findings, 48 cases (13.6%) had abnormal histologic findings, and 13 cases (3.7%) had both abnormal endoscopic visual and histologic findings. Of the 88 cases with abnormal visual and/or histologic abnormalities, only the results of 34 of these FS cases led to a change in management based on endoscopic findings (9.6%). Most patients with a non-diagnostic FS had a final diagnosis of functional abdominal pain; most patients with a diagnostic FS had a final diagnosis of colitis, not otherwise specified. CONCLUSION:  Our findings suggest that FS is not a helpful diagnostic endoscopic intervention in pediatric patients, especially in children with reassuring history and physical exam findings.

Global Profiling of Differentiating Macrophages Identifies Novel Functional Long Non-coding RNAs Regulating Polarization and Innate Immune Responses.

Macrophages (Mφ) are functionally dynamic immune cells that bridge innate and adaptive immune responses. However, the underlying epigenetic mechanisms that control the macrophage plasticity and innate immune functions are not well-elucidated. Here we performed transcriptome profiling of differentiating M1Mφ and M2Mφ and identified thousands of previously known and novel lncRNAs. We characterized three Mφ-enriched lncRNAs (LRRC75A-As1, GAPLINC and AL139099.5) with novel functions in Mφ differentiation, polarization and innate immunity. Knockdown of LRRC75A-As1, and GAPLINC downregulated Mφ differentiation markers CDw93 and CD68, and skewed macrophage polarization by decreasing M1 markers but had no significant impact on M2 markers. LRRC75A-As1, and GAPLINC RNAi in Mφ attenuated bacterial phagocytosis, antigen processing and inflammatory cytokine secretion supporting their functional role in potentiating innate immune functions. Mechanistically, lncRNA knockdown perturbed the expression of multiple cytoskeleton signaling thereby impairing Mφ migration suggesting their critical role in regulating macrophage polarity and motility. Together, our results show that Mφ acquire a unique repertoire of lncRNAs to shape differentiation, polarization and innate immune functions.

Prevalence and risk factors associated with human Intestinal Parasitic Infections (IPIs) in rural and urban areas of Quetta, Pakistan.

Intestinal parasitic infections (IPIs) are endemic worldwide and more prevalent in countries with unhygienic conditions. The objective of the research was to identify the prevalence of intestinal parasitic infections in rural and urban areas of Quetta, Balochistan and to check their associated risk factors including; age, gender, educational status, sanitary system and any other immunodeficiency. For this instance 204 stool samples were collected from the urban and rural population of Quetta, Balochistan. The participants with positive results for Intestinal Parasitic Infections were interviewed using close-ended questionnaire. From the findings of this study, it has been revealed that prevalence of Intestinal parasitic infections in rural and urban areas was 21%. Males were found more prevalent (66%) as compared to females (34%) due to higher risk of contacting to outer environment. The prevalence was higher in rural areas (23%). The most prevalent intestinal parasite was Entamoeba histolytica (48%). Other prevailing parasites were Hymenolepis nana (26%), Giardia Intestinalis (17%), Trichomonas hominis (5%) and Trichuris trichiura (5%). The majority of patients were having lower socio-economic (52%) and educational status (48%). Educational status of 48% patients was primary or below primary. Most of the participants with positive results did not have hand washing habit (62%) and didn't have the closed sanitary system (71%). The intestinal parasitic infections were more prevalent among children aged from 1-10 (33%). This may be a result of poor hygiene in children. The study will contribute to lower down the prevalence in the studied areas by the application of different preventive measures in future.

Variations in growth performance of Catla (Cattla cattla), Rohu (Labeo rohita) and Mrigal (Cirhinus mrigala) fed with varying levels of fishmeal based diets in intensive farming.

A one year feeding trial was conducted on carps i.e. Catla (Cattla cattla), Mrigal (Cirhinus mrigala) and Rohu (Labeo rohita) to find out appropriate level of fishmeal in diet and their effects on growth, survival and biomass in intensive polyculture. Three different inclusions of fishmeal were used in experimental diets (25%, 35% and 45%). Highest average daily growth was observed by 25% fish meal diet (2.18g, 2.19g and 2.34g for catla, rohu and mrigal respectively), whereas 35% fish meal based diet was next by showing 1.63g average daily growth for catla, 1.73g for rohu and 1.67g for mrigal. Mean values of monthly weight again and average daily growth showed significant differences among treatments. Growth was found to be higher in C. mrigala in case of 25% and 45% and L. rohita in case of 35% fish meal. Minimum FCR was obtained by 25% FM based diets as 3.53±0.41 followed by 45% (3.82±0.33) and 35% (4.05±0.45). The findings of this research trial determine the optimum dietary level of fishmeal and its effectiveness as an important ingredient in diets of Indian major carps. It is proved that a feed by the combination of animal and plant protein is much preferable by carps as compare to a feed with higher concentration of fish meal.

Comparison of the Efficacy and Safety of Metformin-Based Combination Therapy Versus Metformin Alone in Children and Adolescents With Type 2 Diabetes Mellitus: A Meta-Analysis.

The aim of this meta-analysis is to synthesize and critically evaluate the available evidence on the comparison of the efficacy and safety of metformin-based combination therapy versus metformin alone in children and adolescents with type 2 diabetes mellitus (T2DM). We performed the present meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible studies were identified using electronic searches for randomized controlled trials (RCTs) using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrial.gov from inception to 31 January 2023. The outcomes examined in this meta-analysis included change from baseline in glycated hemoglobin (HbA1C) (%), fasting plasma sugar (FPG) (mg/dl), and the number of individuals experiencing adverse events. Three studies met the criteria and were included in the meta-analysis. The reduction of HbA1C was significantly higher in metformin-based combination therapy (MD: -1.19, 95% CI: -2.05, -0.33, p-value: 0.007). No significant difference was reported between patients randomized in metformin-based combination therapy and metformin alone (MD: -18.67, 95% CI: -50.17, 12.84, p-value: 0.25). In conclusion, the present meta-analysis found that the reduction in HbA1C was significantly higher in patients receiving metformin-based combination therapy compared to metformin alone. No significant difference was found between the two groups in terms of the change in fasting plasma glucose (FPG) from the baseline. In relation to safety, no significant difference was found in the incidence of adverse events and serious adverse events between the two groups.

Assessment of proline function in higher plants under extreme temperatures.

Climate change and abiotic stress factors are key players in crop losses worldwide. Among which, extreme temperatures (heat and cold) disturb plant growth and development, reduce productivity and, in severe cases, lead to plant death. Plants have developed numerous strategies to mitigate the detrimental impact of temperature stress. Exposure to stress leads to the accumulation of various metabolites, e.g. sugars, sugar alcohols, organic acids and amino acids. Plants accumulate the amino acid 'proline' in response to several abiotic stresses, including temperature stress. Proline abundance may result from de novo synthesis, hydrolysis of proteins, reduced utilization or degradation. Proline also leads to stress tolerance by maintaining the osmotic balance (still controversial), cell turgidity and indirectly modulating metabolism of reactive oxygen species. Furthermore, the crosstalk of proline with other osmoprotectants and signalling molecules, e.g. glycine betaine, abscisic acid, nitric oxide, hydrogen sulfide, soluble sugars, helps to strengthen protective mechanisms in stressful environments. Development of less temperature-responsive cultivars can be achieved by manipulating the biosynthesis of proline through genetic engineering. This review presents an overview of plant responses to extreme temperatures and an outline of proline metabolism under such temperatures. The exogenous application of proline as a protective molecule under extreme temperatures is also presented. Proline crosstalk and interaction with other molecules is also discussed. Finally, the potential of genetic engineering of proline-related genes is explained to develop 'temperature-smart' plants. In short, exogenous application of proline and genetic engineering of proline genes promise ways forward for developing 'temperature-smart' future crop plants.

Antioxidant associated chemoprophylaxis effect of natural spice and green vegetable on hepatotoxicity.

This is a case control and cohort study, conducted at Department of Biochemistry in FUAST, compressing 24 number of albino Wistar rats. Illicium verum (star anise) natural spice and green vegetable broccoli are used for chemo-preventive herbal treatment in relation with vitamin C antioxidant activity. Hepatotoxicity was induced in liver of model rats by giving interperitoneally single injection of 200 mg/kg bod weight (B.W) of N-nitrosodiethylamine and orally giving 1 mg/kg BW phenobarbital for 14 days during disease prorogation period. The vitamin C analysis from Illicium verum (star anise), green broccoli, orange juice, orange peel and orange pulp was done by iodometric quantitative and qualitative titration method. Rats were given compound according to their bodyweight as 1 mg/kg B.W. After 14 days (Disease Promotion and Propagation Period) and 28 days (Disease cure period) of treatment behavioral activity was monitored by locomotors activity in open field experiment, stimulatory activity in home cage and anxiolytic effects observed in light and dark apparatus and also in T maze. Behavioral activity were significantly increased in Illicium verum and green broccoli treated rats. Hematological study including hemoglobin (Hb), white blood cells (WBC), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW) and Platelets was done by abbot laboratory analyzer cell. The value of Hb and RBC was also significantly increased in star anise and broccoli treated rats, showed proper function of RBC in microcirculation. WBC was also in normal range revealed that no disease regards to bone marrow and leukemia's. The biochemical activity of rats including urea, creatinine, total protein, albumin, globulin, A/G ratio, amylase and calcium in blood serum were analyzed while, liver health or performance was also determined by LFT (liver function test). Behavioral and laboratorial variables were analyzed by using SPSS v. 20 and p-value < 0.05 was considered statistically significant. The study report noticeable significant effect of Illicium verum and broccoli on hepatotoxicity of experimental model. Recent experimental study statistical outcomes show reciprocal relationship between the consumption of vegetable diet and natural spice with the risk of Hepatotoxicity. Thus, the aim of the study is to enhance the function of star anise or illicium verum natural spice and green vegetable broccoli as an anticancer or chemoprophylaxis agent.

Growth, physiological, biochemical and molecular changes in plants induced by magnetic fields: A review.

The Earth's geomagnetic field (GMF) is an inescapable environmental factor for plants that affects all growth and yield parameters. Both strong and weak magnetic fields (MF), as compared to the GMF, have specific roles in plant growth and development. MF technology is an eco-friendly technique that does not emit waste or generate harmful radiation, nor require any external power supply, so it can be used in sustainable modern agriculture. Thus, exposure of plants to MF is a potential affordable, reusable and safe practice for enhancing crop productivity by changing physiological and biochemical processes. However, the effect of MF on plant physiological and biochemical processes is not yet well understood. This review describes the effects of altering MF conditions (higher or lower values than the GMF) on physiological and biochemical processes of plants. The current contradictory and inconsistent outcomes from studies on varying effects of MF on plants could be related to species and/or MF exposure time and intensity. The reviewed literature suggests MF have a role in changing physiological processes, such as respiration, photosynthesis, nutrient uptake, water relations and biochemical attributes, including genes involved in ROS, antioxidants, enzymes, proteins and secondary metabolites. MF application might efficiently increase growth and yield of many crops, and as such, should be the focus for future research.

The feasibility of academic detailing for acute oral pain management in outpatient dentistry: A pilot study.

BACKGROUND: Opioids are overprescribed in the outpatient dental setting. Therefore, opportunities exist for opioid stewardship. OBJECTIVES: The purpose of this pilot study was to test the feasibility of an academic detailing (AD) intervention to promote appropriate prescribing of opioids in outpatient dentistry. METHODS: We implemented an AD intervention targeting management of acute oral pain in a Midwestern Veterans Affairs outpatient dental facility. The intervention targeted dentists who actively prescribed opioids at the time of the study. The pilot study tested feasibility, adoption, and acceptance of the AD campaign. Visit-based prescribing rates were obtained from the Veterans Health Administration's Corporate Data Warehouse for baseline and postintervention using difference-in-differences analyses to detect potential changes in health service outcomes. RESULTS: Results indicate moderate levels of feasibility through participation rates (n = 5, 55.5%) and high levels of organizational readiness for change (average of 88.6% agree to strongly agree). Furthermore, fidelity of the AD intervention was high. Adoption measures show moderate indication of motivation to change, and trends suggest that participating dentists decreased their visit-based opioid prescribing rates (P > 0.05). CONCLUSION: The intervention demonstrated feasibility with some indications of adoption of intervention techniques and decrease in opioid prescribing. We further recommend working closely with frontline providers to gather feedback and buy-in before scaling and implementing the AD campaign.

Characterization of laser-induced shock waves generated during infrared laser ablation of copper by the optical beam deflection method.

The shock waves generated during laser ablation of a copper target are investigated using the optical beam deflection method. The fluence of nanosecond pulsed infrared laser beam was in the range of 15-700J/cm2. The density jumps related with the influx of the shock wave at two interaction points were detected with the help of He-Ne laser probes. In general, a supersonic shock wave is produced, which propagates through air and gradually decays into an acoustic wave. Experiments were carried out to study the impact of laser fluence and propagation distance on the shock wave velocity and pressure. The shock wave velocity varies with laser fluence as v∝Fl0.3 and with propagation distance as v∝d-1.5. These results are compared with the predictions of the theoretical models. In the investigated fluence range, shock wave pressure rises by an order of magnitude (∼1-10MPa). We demonstrated that shock wave pressure and ablated mass can be related, yielding mass-specific shock wave pressure that increases linearly with laser fluence. We have also noticed the shock-wave-induced probe beam focusing under certain conditions, which indicates that the shock wave modifies the refractive index of the compressed layer of air. The reported results are useful for the fundamental understanding and pave the way for new applications of laser-induced shock waves.

"I've never been able to burp": Preliminary description of retrograde cricopharyngeal dysfunction in children.

OBJECTIVE: Retrograde cricopharyngeal dysfunction was recently described by Bastian in 2019 and is characterized by an inability to belch, abdominal or chest pressure, odd gurgling noises, and occasional difficulty vomiting. Symptoms tend to worsen with carbonated beverages. Currently, the recommended treatment is cricopharyngeus muscle botulinum toxin injections. Prior studies have included few pediatric patients within larger datasets comprised primarily of adults. We describe our preliminary experience in pediatric patients, including presenting symptoms, treatment approach, and post-treatment outcomes. METHODS: Retrospective chart review of pediatric patients (aged <18 years) diagnosed with retrograde cricopharyngeal dysfunction based on clinical history by the senior author. Medical records were reviewed for presenting symptoms, prior testing and treatment, details of treatment, and postoperative outcomes. RESULTS: Five patients with average age of 14 ± 4 (3 females, 2 males) were included. Presenting symptoms included lifelong or nearly lifelong inability to burp (n = 5), bloating (n = 5), awkward gurgling noises (n = 3), and worsening of symptoms with carbonated beverages (n = 5). Two patients had prior normal upper endoscopy. All patients underwent cricopharyngeal botulinum toxin injection under general anesthesia, with 25-50 units of botulinum toxin injected to the posterior cricopharyngeus across 4-5 locations. All patients had resolution of symptoms with follow-up of 1.5-10 months. CONCLUSIONS: Retrograde cricopharyngeal dysfunction may be underdiagnosed due to lack of awareness of the condition. Now that the phenomenon of inability to belch has a name and is being reported in the literature, we will likely see more adult and pediatric patients with these symptoms. Pediatric patients may respond similarly to adults. Larger studies with longer-term follow-up and targeted patient-reported outcome measures are needed to characterize disease presentation and treatment outcomes.

Williamson magneto nanofluid flow over partially slip and convective cylinder with thermal radiation and variable conductivity.

This article is concerned with the study of MHD non-Newtonian nanofluid flow over a stretching/shrinking cylinder along with thermal radiation effects. Two-component slip mechanism models, namely Brownian motion and thermophoresis of nanofluid for the mass and energy transportation, developed by Buongiorno, are used. Convective heat transfer and nonuniform magnetic field are retained for the expanding/contracting cylinder. Variable thermal conductivity and heat generation effects along with slip boundary conditions are utilized over the cylinder surface. By utilizing the similarity transformation, these governing partial differential equations are converted into nonlinear ordinary differential equations (ODEs). To obtain numerical results, these ODE'S are solved by the shooting method using MATLAB software. The impact of different parameters like variable thermal conductivity, radiation parameter, magnetic parameter, Prandtl number, Brownian motion parameter, the magnetic parameter, Weissenberg number, the viscosity ratio parameter and mass transfer parameter, on the velocity, temperature and concentration is discussed graphically. Further, the Sherwood number, Nusselt number, the skin friction coefficient are also discussed through figures. It is noted through analysis that the speed of the nanofluid reduces for the higher Weissenberg number and expanding cylinder. For the contracting cylinder, i.e., for the negative unsteadiness parameter, the velocity increases.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents.

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Hydrogen sulfide: an emerging component against abiotic stress in plants.

As a result of climate change, abiotic stresses are the most common cause of crop losses worldwide. Abiotic stresses significantly impair plants' physiological, biochemical, molecular and cellular mechanisms, limiting crop productivity under adverse climate conditions. However, plants can implement essential mechanisms against abiotic stressors to maintain their growth and persistence under such stressful environments. In nature, plants have developed several adaptations and defence mechanisms to mitigate abiotic stress. Moreover, recent research has revealed that signalling molecules like hydrogen sulfide (H2 S) play a crucial role in mitigating the adverse effects of environmental stresses in plants by implementing several physiological and biochemical mechanisms. Mainly, H2 S helps to implement antioxidant defence systems, and interacts with other molecules like nitric oxide (NO), reactive oxygen species (ROS), phytohormones, etc. These molecules are well-known as the key players that moderate the adverse effects of abiotic stresses. Currently, little progress has been made in understanding the molecular basis of the protective role of H2 S; however, it is imperative to understand the molecular basis using the state-of-the-art CRISPR-Cas gene-editing tool. Subsequently, genetic engineering could provide a promising approach to unravelling the molecular basis of stress tolerance mediated by exogenous/endogenous H2 S. Here, we review recent advances in understanding the beneficial roles of H2 S in conferring multiple abiotic stress tolerance in plants. Further, we also discuss the interaction and crosstalk between H2 S and other signal molecules; as well as highlighting some genetic engineering-based current and future directions.