[18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO).

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

The Outcome of Electrical Cardioversion in Hyperthyroid Induced Atrial Fibrillation.

Hyperthyroidism is a prevalent cause of atrial fibrillation (AF). High cardiac output with low systemic vascular resistance, driven by hyperthyroidism, is associated with a rapid heartbeat, enhanced left ventricular systolic and diastolic function, and a higher incidence of supraventricular tachyarrhythmias. After returning to euthyroid status, hyperthyroidism-induced AF generally spontaneously reverts to sinus rhythm (SR), and a significant number of patients remain in chronic AF and require electrical cardioversion (ECV). After effective cardioversion, the long-term outcome of hyperthyroidism-induced persistent AF is unknown. Early ECV before the antithyroid medication should be explored for hyperthyroidism-induced AF to reduce the risk of thromboembolic consequences. The recurrence rate of AF between Hyperthyroid and Euthyroid Patients after ECV did not significantly differ. This review article compares the recurrence rate of AF as an outcome of ECV in Hyperthyroid induced atrial fibrillation.

The Role of Gut-Microbiota in the Pathophysiology and Therapy of Irritable Bowel Syndrome: A Systematic Review.

Irritable Bowel Syndrome (IBS) is one of the most prevalent chronic gastrointestinal diseases, which is characterized by recurrent abdominal pain and altered bowel habits. The pathophysiological mechanisms are not completely clear for IBS, multiple factors such as genetic, psychosocial, environmental, visceral hypersensitivity, low-grade inflammation, gastrointestinal motility changes, food components, and intestinal microbiota are thought to play a role in the disease process of IBS. The rapid progression of recent microbiome research using advanced microbiological technologies has shed light on dysbiosis related to the pathophysiology of IBS. We used PubMed, PubMed Central, and Medline as our primary databases to search for articles using keywords and medical subject heading (MeSH) keywords on April 30, 2022, to render a total of 4062 articles. Then, a total of 10 articles were selected following a quality assessment. Despite the variable findings in different studies, most studies have concluded that IBS patients have a reduction in bacterial diversity and an increase in the temporal instability of the microbiota. IBS is known as a stress disorder, and the gut-microbiome-brain axis has been associated with the pathogenesis of the disease. Additionally, the potential of dietary manipulation of gut microbiota and the use of probiotics, prebiotics, and synbiotics in the treatment of IBS has been studied in recent years and shown promising results. We concluded that the gut microbiome plays a substantial role in the pathophysiology of IBS.

The Efficacy of Bezlotoxumab in the Prevention of Recurrent Clostridium difficile: A Systematic Review.

Clostridium difficile infection (CDI) is the most common nosocomial infection in hospitals. Despite the fact that CDI has treatment options, recurrence is common after the treatment, recurrence will occur in approximately 20%-35% of people initially affected, with 40%-60% of these having a second recurrence. Patients are more likely to have several recurrences after the second, which can lead to antibiotic overuse, and as a result, CDI-related health care expenses, hospitalizations, and mortality are on the rise. The first treatment to receive Food and Drug Administration (FDA) approval for the prevention of C. difficile recurrence is bezlotoxumab, a novel human monoclonal antibody against C. difficile toxin B. In the present systematic review, we assessed various studies from PubMed, PubMed Central (PMC), Google Scholar, and Science direct that evaluated the efficacy of bezlotoxumab in the prevention of recurrent C. difficile (rCDI), and we also briefly discussed the pathophysiology of C. difficile and the risk factors for recurrence of C. difficile. The major MODIFY trial has proven the efficacy, pooled analysis of MODIFY 1 AND 2 trials demonstrated the following results as compared to placebo (bezlotoxumab: 129/781 [16.5] placebo:206/773 [26.6] -10.0% [95% CI -14.0 to -6.0], p<0.0001) with number needed to treat (NNT) of 10. All other observational studies also showed a positive response with bezlotoxumab in the prevention of C. difficile. In conclusion, bezlotoxumab is a great option adjunctive with standard of care CDI antibiotics for the prevention of rCDI in high-risk adults.

Increased Threat of Thyroid Diseases in Patients With Sjogren's Syndrome: A Systematic Review.

Sjogren's syndrome is an autoimmune disorder of the body's exocrine glands; however, it is known to have numerous extra-glandular and endocrine manifestations in the body. Moreover, other autoimmune have also been reported with high prevalence in patients with Sjogren's syndrome, including thyroid diseases. Therefore in this study, we aimed to ascertain the increased risk of developing thyroid disorders in patients with pre-existing Sjogren's syndrome. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Online searches on PubMed, PubMed Central (PMC), Google Scholar, and Cochrane were done till 5th June 2022 to filter out studies published in the last twenty years. Based on the inclusion-exclusion criteria, 167 studies were initially selected. They were screened and assessed by quality assessment tools that yielded seven studies, including one meta-analysis, three non-randomized control trials, and three systematic reviews. The study proved that patients with Sjogren's syndrome are at significant risk of developing thyroid disorders, especially autoimmune thyroiditis. This also highlights the need for advanced research and better diagnostic and screening protocols for these patients to reduce the seriousness of the disease.

Cardiotoxicity Associated With Chimeric Antigen Receptor (CAR)-T Cell Therapy for Hematologic Malignancies: A Systematic Review.

Chimeric Antigen Receptor (CAR)-T cell therapy has been one of the most important breakthroughs for treating hematologic malignancies. On the other hand, the therapy had many toxicities. One of the toxicities of the CAR-T therapy is cardiotoxicity. The goal of the systematic review is to elaborate on the cardiotoxicities related to CAR-T therapy for hematologic malignancies. The systematic review is following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. The systematic search was done using PubMed, PubMed Central (PMC), Google Scholar, Cochrane Library, ScienceDirect, and clinicaltrial.gov. The search and selection of studies were done on April 28, 2022, and May 6, 2022, respectively. The studies were selected based upon participants, intervention, and outcomes (PIO) elements and the articles that were included were, full-text articles published within the last ten years, clinical trials, meta-analyses, randomized controlled trial, review, and systematic review. The exclusion criteria were non-hematologic malignancy, non-English-language articles. The initial search had 2,159 publications. The publications were assessed with assessment tools of Scale of the Assessment of Narrative Review Articles (SANRA), Newcastle-Ottawa Scale (NCOS), and Cochrane Collaboration Risk of Bias Tool (CCRBT), which led to selection of eight publications. The systematic review concludes that cardiotoxicity happened in adults and pediatric patients receiving the CAR-T cell therapy and that those cardiac adverse events had many risk factors. Therefore, monitoring these cardiotoxicities is highly essential.

Ni-Catalyzed Arylbenzylation of Alkenylarenes: Kinetic Studies Reveal Autocatalysis by ZnX2 *.

We report a Ni-catalyzed regioselective arylbenzylation of alkenylarenes with benzyl halides and arylzinc reagents. The reaction furnishes differently substituted 1,1,3-triarylpropyl structures that are reminiscent of the cores of oligoresveratrol natural products. The reaction is also compatible for the coupling of internal alkenes, secondary benzyl halides and variously substituted arylzinc reagents. Kinetic studies reveal that the reaction proceeds with a rate-limiting single-electron-transfer process and is autocatalyzed by in-situ-generated ZnX2 . The reaction rate is amplified by a factor of three through autocatalysis upon addition of ZnX2 .

Prevalence and Related Risk Factors of Intestinal Parasitosis among Private School-Going Pupils of Dharan Submetropolitan City, Nepal.

INTRODUCTION: Intestinal parasitic infections are most common and prevalent among children and accounts for great morbidity and mortality. OBJECTIVE: This research is aimed at studying the prevalence and related risk factors of parasitic infections among private school-going pupils of Dharan Submetropolitan City. METHODS AND MATERIALS: This was a cross-sectional laboratory-based study conducted from 13 November 2018 to 26 February 2019 among 400 private school pupils. The stool samples were collected and microscopically examined for parasites using the formalin ethyl acetate sedimentation technique. Data Analysis. Statistical analysis was performed by using SPSS version 16.0. Pearson's Chi-square test was used to establish association between dependent and independent variables. The association was also determined using crude and adjusted odds ratio, and the test considered a P value < 0.05 as statistically significant with 95% confidence interval. RESULT: In this study, 46 (11.5%) children were positive for intestinal parasites. In this study, 3 protozoans (Entamoeba histolytica = 3 (0.75%)) and 43 helminths (Ascaris lumbricoides = 22 (5.5%); Enterobiusvermicularis = 6 (1.5%); Ancylostoma duodenale = 2 (0.5%); and Trichuris trichiura = 13 (3.25%)) were isolated and identified. Statistically, significant difference in the parasitic prevalence with respect to age and gender was not seen (P > 0.05). However, the prevalence of parasitic infection was strongly associated with the ethnicity of the pupils (P = 0.001). The strong associated risk factors of intestinal parasitic infections were nail-biting habit, source of drinking water, biannual deworming, thumb-sucking, hand sanitation before having food and after toilet, knowledge of parents on parasitosis, health and sanitation, keeping cat/dog as pet, and wearing protective shoes during play (P = 0.001). Bowel syndromes like abdominal cramp and constipation also had a strong statistical association (P = 0.001) with the prevalence of parasitic infection. According to binary and multivariate logistic regression analyses, the parents without awareness, pupils with a nail-biting habit, pupils not wearing shoes during play, lack of deworming, drinking direct tap water, and pupils with poor hand sanitation were more likely to be infested with intestinal parasitic infections. CONCLUSION: This study concludes that intestinal parasites are still prevalent among private school-going pupils of Dharan Submetropolitan City. The poor sanitation and sanitary habits like biting nails, consumption of untreated drinking water, and failure to practice proper hand washing were studied as contributors to the acquisition of intestinal parasitic infections. Therefore, integration of control measures such as provision of clean and safe drinking water, improved sanitation and hygiene, with biannual administration of drugs are necessary for effective eradication of parasitic infections.

A Unified Strategy for the Asymmetric Synthesis of Highly Substituted 1,2-Amino Alcohols Leading to Highly Substituted Bisoxazoline Ligands.

A general procedure for the asymmetric synthesis of highly substituted 1,2-amino alcohols in high yield and diastereoselectivity is described that uses organometallic additions of a wide range of nucleophiles to tert-butylsulfinimines as the key step. The addition of organolithium reagents to these imines follows a modified Davis model. The diastereoselectivity for this reaction depends significantly on both the nucleophile and electrophile. These highly substituted 1,2-amino alcohols are used to synthesize stereochemically diverse and structurally novel, polysubstituted 2,2'-methylene(bisoxazoline) ligands in high yields.

K2CO3-Catalyzed Synthesis of 2,5-Dialkyl-4,6,7-tricyano-Decorated Indoles via Carbon-Carbon Bond Cleavage.

We describe a novel method to synthesize 2,5-dialkyl-4,6,7-tricyanoindole derivatives from a base-catalyzed reaction of 1,3-diketones with fumaronitrile. The reaction proceeds by the condensation of two molecules of fumaronitrile and one molecule of 1,3-diketone in a remarkable process that involves the cleavage of one C(sp3)-C(sp2) bond in 1,3-diketones and the formation of one carbon-nitrogen bond and four carbon-carbon bonds to construct both the aryl and pyrrole rings of the indole in one step.

An Expedient Route to 9-arylmethylanthracene Derivatives via Tandem Ni-catalyzed Alkene Dicarbofunctionalization and Acid-promoted Cyclization-aromatization.

We report a nickel-catalyzed one pot synthesis of 9-arylmethylanthracene motifs, which find applications in medicinal and material chemistry. In this synthesis, we apply three component alkene dicarbofunctionalization of 2-vinylaldimines with aryl iodides and arylzinc reagent to generate a 1,1,2-diarylethyl scaffold, which then undergoes an acidpromoted cyclization followed by aromatization to furnish 9-arylmethylanthracene cores. With the new method, a number of differently-substituted 9-arylmethylanthracene derivatives can be synthesized in good yields.

Synergistic Bimetallic Ni/Ag and Ni/Cu Catalysis for Regioselective γ,δ-Diarylation of Alkenyl Ketimines: Addressing ß-H Elimination by in Situ Generation of Cationic Ni(II) Catalysts.

We disclose unprecedented synergistic bimetallic Ni/Ag and Ni/Cu catalysts for regioselective γ,δ-diarylation of unactivated alkenes in simple ketimines with aryl halides and arylzinc reagents. The bimetallic synergy, which generates cationic Ni(II) species during reaction, promotes migratory insertion and transmetalation steps and suppresses ß-H elimination and cross-coupling, the major side reactions that cause serious problems during alkene difunctionalization. This diarylation reaction proceeds at remote locations to imines to afford, after simple H+ workup, diversely substituted γ,δ-diaryl ketones that are otherwise difficult to access readily with existing methods.

Ni-Catalyzed Regioselective Alkylarylation of Vinylarenes via C(sp3)-C(sp3)/C(sp3)-C(sp2) Bond Formation and Mechanistic Studies.

We report a Ni-catalyzed regioselective alkylarylation of vinylarenes with alkyl halides and arylzinc reagents to generate 1,1-diarylalkanes. The reaction proceeds well with primary, secondary and tertiary alkyl halides, and electronically diverse arylzinc reagents. Mechanistic investigations by radical probes, competition studies and quantitative kinetics reveal that the current reaction proceeds via a Ni(0)/Ni(I)/Ni(II) catalytic cycle by a rate-limiting direct halogen atom abstraction via single electron transfer to alkyl halides by a Ni(0)-catalyst.

Ni-Catalyzed Regioselective ß,δ-Diarylation of Unactivated Olefins in Ketimines via Ligand-Enabled Contraction of Transient Nickellacycles: Rapid Access to Remotely Diarylated Ketones.

We disclose a [(PhO)3P]/NiBr2-catalyzed regioselective ß,δ-diarylation of unactivated olefins in ketimines with aryl halides and arylzinc reagents. This diarylation proceeds at remote locations to the carbonyl group to afford, after simple H+ workup, diversely substituted ß,δ-diarylketones that are otherwise difficult to access readily with existing methods. Deuterium-labeling and crossover experiments indicate that diarylation proceeds by ligand-enabled contraction of transient nickellacycles.

Ni-catalysed regioselective 1,2-diarylation of unactivated olefins by stabilizing Heck intermediates as pyridylsilyl-coordinated transient metallacycles.

We report a Ni-catalysed diarylation of unactivated olefins in dimethylpyridylvinylsilane by intercepting Heck C(sp3)-NiX intermediates, derived from aryl halides, with arylzinc reagents. This approach utilizes a modifiable pyridylsilyl moiety as a coordinating group that plays a dual role of intercepting oxidative addition species to promote Heck carbometallation, and stabilizing the Heck C(sp3)-NiX intermediates as transient metallacycles to suppress ß-hydride elimination, and facilitate transmetalation/reductive elimination. This method affords 1,2-diarylethylsilanes, which can be readily oxidized to 1,2-diarylethanols that occur as structural motifs in 3-aryl-3,4-dihydroisocoumarin and dihydrostilbenoid natural products.

Ni-Catalyzed Regioselective Dicarbofunctionalization of Unactivated Olefins by Tandem Cyclization/Cross-Coupling and Application to the Concise Synthesis of Lignan Natural Products.

We disclose a (terpy)NiBr2-catalyzed reaction protocol that regioselectively difunctionalizes unactivated olefins with tethered alkyl halides and arylzinc reagents. The reaction shows an excellent functional group tolerance (such as ketones, esters, nitriles, and halides) and a moderate to good level of diastereoselectivity. The current cyclization/cross-coupling also tolerates molecules containing base-sensitive racemizable stereocenters, which are preserved without racemization during the reaction. This cyclization/cross-coupling provides a rapid access to (arylmethyl)carbo- and heterocyclic scaffolds, which occur widely as structural cores in various natural products and bioactive molecules. In order to show synthetic utility and generality, we have applied this new method in gram-scale quantities to the concise synthesis of six lignan natural products containing three different structural frameworks. We further conducted mechanistic investigations with radical probes and selectivity studies, which indicated that the current reaction proceeds via a single electron transfer (SET) process.

THE ROLE OF THE ASYMMETRIC BOLAAMPHIPHILIC CHARACTER OF VECAR ON THE KINETIC AND STRUCTURAL ASPECTS OF ITS SELF-ASSEMBLY: A MOLECULAR DYNAMICS SIMULATION STUDY.

VECAR are novel bolaamphiphilic molecules consisting of two hydrophilic molecular groups, a carnosine derivative and a chromanol group, covalently linked by a hydrophobic alkyl spacer of varying length. Despite the potential for application in various biomedical applications VECAR properties, including their bulk properties, are still largely unknown. The early stage of the self-assembly process of VECAR molecules in water is studied using molecular dynamics simulations. The study reveals that the length of the hydrophobic spacer in VECAR affects the aggregation kinetics as well as the size, shape, density, and atomistic structure of the self-assembled aggregates. A mechanism based on cooperative interactions between water, the hydrophilic hydroxyl group, and the hydrophobic benzene ring of the chromanol head is proposed to explain the ordered packings of chromanols in the self-assembled aggregate structures at the aggregate-water interface.

Ni-Catalyzed Regioselective 1,2-Dicarbofunctionalization of Olefins by Intercepting Heck Intermediates as Imine-Stabilized Transient Metallacycles.

We disclose a strategy for Ni-catalyzed dicarbofunctionalization of olefins in styrenes by intercepting Heck C(sp3)-NiX intermediates with arylzinc reagents. This approach utilizes a readily removable imine as a coordinating group that plays a dual role of intercepting oxidative addition species derived from aryl halides and triflates to promote Heck carbometalation and stabilizing the Heck C(sp3)-NiX intermediates as transient metallacycles to suppress ß-hydride elimination and facilitate transmetalation/reductive elimination steps. This method affords diversely substituted 1,1,2-triarylethyl products that occur as structural motifs in various natural products.

Pd-Catalyzed Regioselective 1,2-Dicarbofunctionalization of Unactivated Olefins by a Heck Reaction/Enolate Cyclization Cascade.

We disclose a Pd-catalyzed reaction protocol that regioselectively difunctionalizes unactivated olefins with aryl iodides and tethered enolates. The current method allows the rapid synthesis of a variety of 1,3,4-trisubstituted pyrrolidinones from simple and readily available amides. We further demonstrate this new method's application by postsynthetically modifying the arylacetic acid side chains of two commercial nonsteroidal anti-inflammatory drugs, indomethacin and tolmetin, to highly decorated 4-benzylpyrrolidinone frameworks. Mechanistic studies reveal that the reaction proceeds via a Heck reaction/enolate cyclization cascade, a process that exploits ß-H elimination in a constructive mode for regioselective 1,2-difunctionalization of unactivated olefins.

General Copper-Catalyzed Coupling of Alkyl-, Aryl-, and Alkynylaluminum Reagents with Organohalides.

We report the first example of a very general Cu-catalyzed cross-coupling of organoaluminum reagents with organohalides. The reactions proceed for the couplings of alkyl-, aryl-, and alkynylaluminum reagents with aryl and heteroaryl halides and vinyl bromides, affording the cross-coupled products in good to excellent yields. Both primary and secondary alkylaluminum reagents can be utilized as organometallic coupling partners. These reactions are not complicated by ß-hydride elimination, and as a result rearranged products are not observed with secondary alkylaluminum reagents even for couplings with heteroaryl halides under "ligand-free" conditions. Radical clock experiment with a radical probe and relative reactivity study of Ph3Al with two haloarenes, 1-bromonaphthalene and 4-chlorobenzonitrile, having two different redox potentials indicates that the reaction does not involve free aryl radicals and radical anions as intermediates. These results combined with the result of the Hammett plot obtained by reacting Ph3Al with iodoarenes containing p-H, p-Me, p-F, and p-CF3 substituents, which shows a linear curve (R(2) = 0.99) with a ρ value of +1.06, suggest that the current transformation follows an oxidative addition-reductive elimination pathway.