Synthesis and characterization of organoselenium based BODIPY and its application in living cells.

Phenylselenide based BODIPY probe was successfully synthesized and characterized by NMR spectroscopic techniques (1H, 13C and 77Se NMR), mass spectrometry and single crystal XRD. Surprisingly, crystal packing diagram of the probe showed formation of 1-D strip through intermolecular F---H interaction. The probe was screened with various Reactive Oxygen Species (ROS) and found to be selective for superoxide ion over other ROS via "turn-on" fluorescence response. The probe selectively and sensitively detects superoxide with a lower detection limit (43.34 nM) without interfering with other ROS. The quantum yield of the probe was found to increase from 0.091 % to 30.4 % (334-fold) after oxidation. Theoretical calculations (DFT and TD-DFT) were also performed to understand the sensing mechanism of the probe. The probe was able to effectively detect superoxide inside living cells without any toxic effect.

A Review of the Occurrence of Intraventricular Hemorrhage in Preterm Newborns and its Future Neurodevelopmental Consequences.

Intraventricular hemorrhage (IVH) is a type of bleeding that occurs through the germinal matrix and comes through the ependymal cells into the ventricular cavity. It is mostly seen in preterm neonates but can also be seen sometimes in term neonates. Various factors predispose to preterm delivery; it can be spontaneous or medically induced. Spontaneous IVH occurs in cases of intrauterine infections in the mother, and it can be induced in cases of medical emergencies such as preeclampsia and eclampsia. The brain of a preterm newborn is not fully developed as it does not have pericytes and proteins, so it can bleed very quickly, which can cause IVH. Also, the vessels supplying the germinal matrix are immature and highly vascularized. IVH has four grades based on findings detected on cranial ultrasound and MRI. Management includes medical and surgical management; medical management includes phenobarbitone used for seizures and prophylaxis. Surgical management includes drainage, irrigation, and fibrinolytic therapy (DRIFT), and neuro-endoscopic lavage. IVH causes various short-term and long-term neurodevelopmental consequences. Long-term complications include cerebral palsy and intellectual disability, which hamper the life of the child. It mainly presents with seizures, flaccidity, decerebrate posture, etc. Various preventive measures can be taken to tackle IVH in newborns. First of all, preterm delivery should be avoided, and intrauterine infections in mothers should be treated. The administration of corticosteroids should be done for all preterm deliveries as it helps in the maturation of organs. The administration of magnesium sulfate should be done as it is neuroprotective and reduces cerebral palsy in the future. Delayed cord clamping is to be done to reduce recurrent blood transfusions and decrease the risk of IVH. This article explains the pathogenesis, management, prevention, and future outcomes of IVH.

Need to rethink tDCS protocols for the treatment of alcohol use disorder: Insights from a randomized sham-controlled clinical trial among detoxified inpatients.

OBJECTIVES: Alcohol use disorder (AUD) is a chronic disorder with various health problems. Reduced functioning of the Dorsolateral Prefrontal Cortex (DLPFC) is associated with impaired regulation of alcohol-seeking behaviors and increased cravings in individuals with AUD. This study aimed to investigate whether 10 add-on sessions of tDCS, over the left DLPFC in detoxified inpatients with AUD could reduce cravings and increase abstinence rates at three months. METHODS: Detoxified inpatients with AUD were randomly assigned to either treatment as usual (TAU) plus ten sessions of active tDCS over left DLPFC, or TAU plus ten sessions of sham tDCS treatment twice daily for five consecutive days. RESULTS: The results from the generalized linear mixed model (GLMM) revealed that time had a significant effect on OCDS scores, but neither treatment nor interaction between these two factors had a significant effect on OCDS scores The Chi-square test in the intention- to- treat analysis did not show a significant difference in complete abstinence rates between the active treatment group and the sham treatment group. CONCLUSIONS: we found that adding ten sessions of active tDCS over left DLPFC tDCS to the treatment as usual for AUD did not result in improved abstinence rates or reduced craving.

Arthroscopic Single-Bundle Anterior Cruciate Ligament Reconstruction Using the Quadrupled Hamstring Tendon Graft: A Single-Institution Experience From North-Eastern India.

Background There is a lack of literature regarding the arthroscopic approach to a single-bundle anterior cruciate ligament (ACL) reconstruction using the quadrupled hamstring tendon graft in the north-eastern Indian population. Methodology A prospective, single-center study was planned for patients with ACL tears according to the eligibility criteria and with a defined surgical protocol. Patients were followed up from the preoperative period for at least one year, and knee function was evaluated using the International Knee Documentation Committee (IKDC) subjective knee score and the Lysholm knee score. Results A total of 29 patients were followed up for a mean of 14.6 months (12-22 months). The mean age of patients was 26.83 ± 7.50 years, with a male:female ratio of 4.8:1 and almost equal involvement of both knees. There was statistically significant improvement (p<0.001) in results in the Lachman test, anterior drawer test, pivot shift test, IKDC score, and Lysholm score. No intraoperative or postoperative complications were found in the present study. Discussion The study shows that arthroscopic anatomical single-bundle ACL reconstruction using quadrupled hamstring tendon grafts is a minimally invasive, safe, and effective procedure that provides anteroposterior and rotational stability and good to excellent functional outcomes.

Transdisciplinary pragmatic melioration for the plastic life cycle: Why the social, natural, and technical sciences should prioritize reducing harm.

Plastics underpin modern society but also threaten to choke it. Only 9 % of all plastic waste is recycled, usually with loss of quality ("downcycling"); the rest is landfilled or dumped (79 %) or incinerated (12 %). Put bluntly, the "plastic age" needs a "sustainable plastic culture." Consequently, we urgently need to develop a global and transdisciplinary approach not only to fully recycle plastics but also to manage the harms across their life cycle. The past decade has witnessed an explosion in research on new technologies and interventions that purport to help solve the plastic waste challenge; however, this work has, in most cases, been carried forward within single disciplines (for example, researching novel chemical and bio-based technologies for plastic degradation, engineering processing equipment innovations, and mapping recycling behaviours). In particular, although there has been vast progress within individual scientific fields, such work does not address the complexities of various plastic types and waste management systems. Meanwhile, research on the social contexts (and constraints) of plastic use and disposal is rarely in conversation with the sciences to drive innovation. In short, research on plastics typically lacks a transdisciplinary perspective. In this review, we urge the adoption of a transdisciplinary approach that focuses on pragmatic melioration; such an approach combines the natural and technical sciences with the social sciences to focus on the mitigation of harms across the plastic life cycle. To illustrate our case, we review the status of plastic recycling from these three scientific perspectives. Based on this, we advocate 1) foundational studies to identify sources of harm and 2) global/local interventions aimed at those plastics and aspects of the plastic life cycle that cause maximal harm, both in terms of planetary welfare and social justice. We believe this approach to plastic stewardship can be a showcase for tackling other environmental challenges.

The Application of Enhanced Recovery After Surgery Protocols in Patients With Perforated Duodenal Ulcer.

Background Enhanced recovery after surgery (ERAS) protocols are nowadays considered the standard of care for various elective surgical procedures. However, its utilization remains low in tier-two and tier-three cities of India, and there exists a significant variation in the practice. In the present study, we have investigated the safety and feasibility of these protocols or pathways in emergency surgery for perforated duodenal ulcer disease. Methods A total of 41 patients with perforated duodenal ulcers were randomly divided into two groups. All the patients across the study were treated surgically with the open Graham patch repair technique. Patients in group A were managed with ERAS protocols, while patients in group B were managed with conventional peri-operative practices. A comparison was established between the two groups in terms of the duration of hospital stay and other postoperative parameters. Results The study was conducted on 41 patients who presented during the study period. Group A patients (n=19) were managed with standard protocols, and group B patients (n=22) were managed with conventional standard protocols. As compared to the standard care group, patients in the ERAS group showed quicker postoperative recovery and lesser complications. The need for nasogastric (NG) tube reinsertion, postoperative pain, postoperative ileus, and surgical site infections (SSI) were all significantly lower in the patients of the ERAS group. A significant reduction in the length of hospital stay (LOHS) was found in the ERAS group when compared to the standard care group (relative risk {RR}=61.2; p=0.000). Conclusions The application of ERAS protocols with certain modifications in the management of perforated duodenal ulcers yields significant outcomes in terms of reduced duration of hospital stay and fewer postoperative complications in a selected subgroup of patients. However, the application of ERAS pathways in an emergency setup needs to be further evaluated to develop standardized protocols for a surgical emergency group of patients.

Laser Treatment Modalities for Diabetic Retinopathy.

Diabetes is a chronic progressive metabolic disorder that is caused by the body's inability to regulate blood glucose levels. If uncontrolled, it can lead to various complications. Among its various complications, long-term diabetes leads to diabetic retinopathy (DR). It is a disease involving blood vessels and the destruction of retinal nerves. It is usually classified into two types: proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR). It progresses and causes loss of vision. The leading cause of loss of vision is diabetic macular edema (DME). The argon laser is used as a modality in the management of PDR. There are various types of laser photocoagulation, such as peripheral retinal laser photocoagulation, focal macular laser photocoagulation, and grid photocoagulation. DR results in various adverse consequences such as vitreous hemorrhage, fibrosis, traction, detachment of the retina, and glaucoma. To assess DR, a detailed fundus examination with a slit lamp biomicroscope needs to be done. Seven-standard field stereoscopic-color fundus photography needs to be done for documentation and follow-up. Patients with diabetes mellitus (DM) type 1 have a greater risk of suffering from DR. Another major complication of the condition is DME, which is characterized by an increase in the permeability of vessels and the thickening of the central part of the retina along with the accumulation of hard exudates on the macula. This article discusses various laser therapy modalities for the treatment of DR, their types, mechanisms, and aims. Clinical features of DR include abnormal dilatation of capillaries, and outpouchings in the form of microaneurysm from the capillary wall are one of the earliest and most dangerous changes; later, non-perfusion of the retina occurs, which is associated with cotton wool spots and blot hemorrhages. In patients suffering from PDR and maculopathy, peripheral retinal laser photocoagulation is used as a mode of intervention.

Label-free affinity screening, design and synthesis of inhibitors targeting the Mycobacterium tuberculosis L-alanine dehydrogenase.

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.

Analysis and Interpretation of metagenomics data: an approach.

Advances in next-generation sequencing technologies have accelerated the momentum of metagenomic studies, which is increasing yearly. The metagenomics field is one of the versatile applications in microbiology, where any interaction in the environment involving microorganisms can be the topic of study. Due to this versatility, the number of applications of this omics technology reached its horizons. Agriculture is a crucial sector involving crop plants and microorganisms interacting together. Hence, studying these interactions through the lenses of metagenomics would completely disclose a new meaning to crop health and development. The rhizosphere is an essential reservoir of the microbial community for agricultural soil. Hence, we focus on the R&D of metagenomic studies on the rhizosphere of crops such as rice, wheat, legumes, chickpea, and sorghum. These recent developments are impossible without the continuous advancement seen in the next-generation sequencing platforms; thus, a brief introduction and analysis of the available sequencing platforms are presented here to have a clear picture of the workflow. Concluding the topic is the discussion about different pipelines applied to analyze data produced by sequencing techniques and have a significant role in interpreting the outcome of a particular experiment. A plethora of different software and tools are incorporated in the automated pipelines or individually available to perform manual metagenomic analysis. Here we describe 8-10 advanced, efficient pipelines used for analysis that explain their respective workflows to simplify the whole analysis process.

A Prospective Observational Study of Ventral Hernia.

Background Ventral hernias are commonly encountered problems in the field of general surgery. Incisional hernia is a common complication following abdominal surgery that requires reoperation. This study was conducted to understand the incidence of various types of ventral hernia in both sexes and various age groups, predisposing factors, clinical features, and complications. Methods This prospective observational study was conducted in the Department of Surgery, Dr. Hedgewar Hospital, Aurangabad, Maharashtra, India, on a total of 100 patients diagnosed with anterior abdominal wall hernia between September 2020 to February 2021. Data collection included thorough history taking and clinical examination along with relevant investigations. The data collected was entered in a proforma, tabulated, and analyzed with the IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States). Results Incisional hernia (43%) was the most common of all ventral hernias. Females were much more affected than males. Out of these types studied, epigastric hernia showed more incidence among males. The average age of presentation was 52 years. Obesity was the most common predisposing factor (34%) with female preponderance. Obese patients were also associated with a higher rate of postoperative complications like wound infection and seroma. In the cases of incisional hernia, 32.6% of the patients gave a history of previous surgery complicated by a wound infection. Incisional hernias were more common in lower midline incisions (34.9%) and after gynecological surgery (55.81%) like total abdominal hysterectomy, cesarean section, or tubal ligation. In the majority of the patients (62.8%), the incisional hernia occurred within three years of the previous surgery. Wound infection following ventral hernia repair occurred in 11% of the cases, wound dehiscence in 3%, and seroma in 2 % of the cases. Conclusions The most common ventral hernias in decreasing order of their frequency are incisional hernia, umbilical hernia, para-umbilical hernia, and epigastric hernia. Epigastric and umbilical hernias are more common in males whereas incisional hernia is more common in females. Obesity and constipation were found to be the major predisposing risk factors. Incisional hernia is more common in females after gynecological and obstetrics surgery. The lower midline segment is the most common site for developing an incisional hernia.

Synthesis and single crystal X-ray study of phenylselenyl embedded coumarin-based sensors for selective detection of superoxide.

Selenium-coumarin based probe 4 was synthesized from the reaction of a bromo derivative of coumarin with in situ prepared sodium phenyl selenide. Esterification of probe 4 resulted in the formation of probe 5. In the single crystal X-ray structure of probe 4, the phenylselenide group was placed parallel to the coumarin moiety whereas in probe 5, the phenylselenide group was perpendicular to the coumarin group. Hydrogen bonding interactions have been observed in the crystal packing of both the probes. Both the probes selectively detect superoxide over other reactive oxygen species (ROS). A kinetic study of the probes was performed, which suggested that probe 4 achieved maximum fluorescence intensity in less than 1 s while probe 5 required 30 min to attain maximum fluorescence intensity. Both probes 4 and 5 showed 37 fold and 48 fold increase in fluorescence intensity after the reaction with superoxide, respectively. The detection limits of probes 4 and 5 were found to be 46.4 nM and 48.9 nM, respectively. Both the probes showed reversibility with biothiols such as glutathione (GSH) and N-acetyl-L-cysteine (NAC). Probe 5 underwent more redox cycles with GSH compared to probe 4.

A BOPHY based fluorescent probe for Hg2+via NTe2 chelation.

A BOPHY-based organotellurium-containing probe was synthesized and characterized via single crystal XRD for the selective and sensitive detection of Hg2+ over other metal ions. The probe detects Hg2+ in less than 1 s with a 2.5-fold enhancement in fluorescent intensity. Due to the chalcogenophilicity of mercury, Hg2+ was facilely trapped in the NTe2 chelating cavity of the probe. The probe can detect Hg2+ in the nanomolar range (62 nM) and it showed reversibility with S2- ions. The sensitivity of the probe for the detection of Hg2+ was confirmed in living HeLa cells.

Giant Pilomatrixoma of the Scrotum: A Rare Case Presentation.

Pilomatrixoma is a benign adnexal skin tumor involving the hair follicle matrix. It is found in children, predominantly involving the face. We report here an interesting and rare case of a 52-year-old male presenting with a large, firm, and painless mass over the scrotum considered to be a sebaceous cyst. The mass was completely excised and a biopsy report revealed it to be a pilomatrixoma of the scrotum. The patient recovered well postoperatively with no recurrence over two years.

Epidemiology, Microbiology, and Genetics of Contact Lens-Related and Non-Contact Lens-Related Infectious Keratitis.

ABSTRACT: Infectious keratitis is a rare but severe condition associated with a range of ocular and systemic predisposing conditions, including ocular trauma, prior surgery, surface disease, and contact lens (CL) wear. This review explores the epidemiology of infectious keratitis, specifically the differences in disease incidence and risk factors, causative organism profile and virulence characteristics and host microbiome, genetics, gene expression, proteomics, and metabolomic characteristics in CL-related and non-CL-related diseases. Differences exist in the epidemiology, demographics, causative organisms, and their virulence characteristics in CL-related and non-CL-related diseases, and there is less evidence to support differences between these groups of individuals in the ocular surface microbiome, genetics, and pathways of disease. Genetic variations, however, in the host immune profile are implicated in both the onset and severity of infectious keratitis in CL and non-CL wearers. As technologies in metabolomics, proteomics, and genomics improved to be better able to process small-volume samples from the ocular surface, there will be improved understanding of the interplay between the CL, ocular surface, host immune profile, and the microbial environment. This may result in a more personalized approach in the management of disease to reduce disease severity.

An efficient chemodosimeter for the detection of Hg(II) via diselenide oxidation.

Mercury ions are toxic and exhibit hazardous effects on the environment and biological systems, and thus demand for the selective and sensitive detection of mercury has become considerably an important issue. Here, we have developed a diselenide containing coumarin-based probe 3 for the selective detection of Hg(II) with a "turn-on" response (a 48 fold increase in fluorescence intensity) at 438 nm. The probe could quantitatively detect Hg(II) with a detection limit of 1.32 µM in PBS solution. Moreover, the probe has operable efficiency over the physiological range with an increase in the quantum yield from 1.2% to 57.3%. The reaction of the probe with Hg(II) yielded a novel monoselenide based coumarin 4via diselenide oxidation, which was confirmed by single crystal XRD. Furthermore, the biological use of the probe for the detection of Hg(II) was confirmed in the MCF-7 cell line. To the best of our knowledge, this is the first reaction-based probe for Hg(II) via diselenide oxidation.

Anti-Microbial Activity of Aliphatic Alcohols from Chinese Black Cardamom (Amomum tsao-ko) against Mycobacterium tuberculosis H37Rv

The fruits of Amomun tsao-ko (Chinese black cardamom; Zingiberaceae) contain an abundance of essential oils, which have previously demonstrated significant antimicrobial activity. In our preliminary search for natural anti-tuberculosis agents, an acetone extract of A. tsao-ko (AAE) exhibited strong antibacterial activity against Mycobacterium tuberculosis H37Rv. Therefore, the aim of this study was to find the principal compounds in an AAE against M. tuberculosis. Nine aliphatic compounds (1−9) including a new compound (1, tsaokol B) and a new natural unsaturated aliphatic diester (6), together with three acyclic terpenoids (10−12), were isolated from an AAE by repetitive chromatography. The structures of the isolates were determined by spectroscopic data analysis. All isolates were evaluated for activity against M. tuberculosis H37Rv. Isolated compounds 1−6, and 11 had MICs ranging from 0.6−89 µg/mL. In contrast, compounds 7 to 10, and 12 had MICs that were >100 µg/mL. Tsaokol A (3) was the most active compound with MICs of 0.6 µg/mL and 1.4 µg/mL, respectively, against replicating and nonreplicating M. tuberculosis. These results are the first to illustrate the potency of tsaokol A (3) as a natural drug candidate with good selectivity for treating tuberculosis.

Prevalence of Dental Fear and Anxiety and Its Triggering Factors in the Dental Office among School-going Children in Al Ahsa.

AIMS AND OBJECTIVES: To estimate the prevalence of dental fear and anxiety (DFA) among school-going children in Al Ahsa.To identify the factors that trigger DFA in the dental office. MATERIALS AND METHODS: A cross-sectional questionnaire-based study was conducted. Eight hundred and sixteen, 7-12-year-old children studying in government and private schools spread across the city of Al-Ahsa, Saudi Arabia, participated in the study. A self-reported questionnaire with 15 close-ended questions pertaining to DFA in logical order was distributed to all the participants. Each question had three options as responses with images. The children were asked to choose the option that best fitted their response. RESULTS AND CONCLUSION: The prevalence of DFA among boys and girls was found to be 50.4 and 71.28%, respectively. The majority of the boys studying in government schools reported DFA when informed about the treatment in advance, while most of those studying in private schools reported DFA at the sight of the dental chair and dental injections, while walking into the clinic, in the waiting room, when informed about the treatment in advance and their tooth being drilled. On the contrary, the responses were very similar among girls irrespective of their school. Most of the boys and girls did not experience any DFA when their parents were allowed to accompany them. Hence, a tailor-made approach for the management of the child in the dental office is warranted. CLINICAL SIGNIFICANCE: A tailor-made approach for the management of DFA in the dental office plays a significant role in successful treatment. HOW TO CITE THIS ARTICLE: Alshuaibi AF, Aldarwish M, Almulhim AN, et a l. Prevalence of Dental Fear and Anxiety and Its Triggering Factors in the Dental Office among School-going Children in Al Ahsa. Int J Clin Pediatr Dent 2021;14(2):286-292.

In Vitro Profiling of Antitubercular Compounds by Rapid, Efficient, and Nondestructive Assays Using Autoluminescent Mycobacterium tuberculosis.

Anti-infective drug discovery is greatly facilitated by the availability of in vitro assays that are more proficient at predicting the preclinical success of screening hits. Tuberculosis (TB) drug discovery is hindered by the relatively slow growth rate of Mycobacterium tuberculosis and the use of whole-cell-based in vitro assays that are inherently time-consuming, and for these reasons, rapid, noninvasive bioluminescence-based assays have been widely used in anti-TB drug discovery and development. In this study, in vitro assays that employ autoluminescent M. tuberculosis were optimized to determine MIC, minimum bactericidal concentration (MBC), time-kill curves, activity against macrophage internalized M. tuberculosis (90% effective concentration [EC90]), and postantibiotic effect (PAE) to provide rapid and dynamic biological information. Standardization of the luminescence-based MIC, MBC, time-kill, EC90, and PAE assays was accomplished by comparing results of established TB drugs and two ClpC1-targeting TB leads, ecumicin and rufomycin, to those obtained from conventional assays and/or to previous studies. Cumulatively, the use of the various streamlined luminescence-based in vitro assays has reduced the time for comprehensive in vitro profiling (MIC, MBC, time-kill, EC90, and PAE) by 2 months. The luminescence-based in vitro MBC and EC90 assays yield time and concentration-dependent kill information that can be used for pharmacokinetic-pharmacodynamic (PK-PD) modeling. The MBC and EC90 time-kill graphs revealed a significantly more rapid bactericidal activity for ecumicin than rufomycin. The PAEs of both ecumicin and rufomycin were comparable to that of the first-line TB drug rifampin. The optimization of several nondestructive, luminescence-based TB assays facilitates the in vitro profiling of TB drug leads in an efficient manner.