Instigation of neurosporaxanthin from Rhodococcus ruber O16N isolated from Gulf of Khambhat.

Compounds of natural origin are in burgeoning demand driven by heightened awareness of their health benefits. We present the maiden study on the production of neurosporaxanthin, a carotenoid, from marine Rhodococcus ruber O16N. Analysing various physical parameters including carbon source, agitation speed, temperature, salt and pH, we found that agitation adversely affects biomass and carotenoid production. Isolate O16N grew well, when medium was supplemented with mannitol or sorbitol, CaCl2, at pH 6 and best carotenoid production was observed when sorbitol or fructose and CaCl2 was supplemented in media at pH 7 at 37 °C in static condition with the maximum carotenoid yield of 1097 mg/L, whopping 18-fold more as compared to nutrient medium. Furthermore, thorough characterisation identified the produced carotenoid as neurosporoxanthin. These findings highlight the potential of marine Rhodococcus ruber O16N as a valuable source for neurosporaxanthin production and emphasise the importance of optimising physical parameters for maximising carotenoid yield.

Flexible and Rigid Bronchoscopy for Critically Ill Children on Extracorporeal Membrane Oxygenation.

BACKGROUND: We aim to describe our experience with bronchoscopy to diagnose and relieve tracheobronchial obstruction in anticipation of decannulation in children on extracorporeal membrane oxygenation (ECMO) support. METHODS: A retrospective cohort study of children on ECMO between 1/2018 and 12/2022. RESULTS: A total of 107 children required ECMO support during the study period for cardiac (n = 48, 45%), pulmonary (n = 38, 36%), or cardiopulmonary dysfunction (n = 21, 20%). Thirty-seven (35%) patients underwent 99 bronchoscopies while on ECMO. Most (76%, n = 75) experienced no improvement or worsening of chest radiography 24 hours following bronchoscopy. Clinical improvement in tidal volumes 48 hours after the first bronchoscopy was noted in 13/25 patients with available data (p = 0.05). Adverse events were seen in 18 (49%) patients who underwent bronchoscopy, including pneumothorax (n = 8, 22%), pneumonia (n = 7, 19%), pulmonary hemorrhage (n = 6, 16%), and sepsis (n = 5, 14%). ECMO courses were longer (25.4 ± 37.2 vs 6.1 ± 8.8 days, p < 0.0001) and more likely to be complicated by pneumonia (p = 0.0004) and sepsis (p = 0.047) in patients who underwent bronchoscopy compared with those who did not. Adverse events following bronchoscopy were associated with the number of bronchoscopies (p = 0.0003) and the presence of obstructive materials but not with the type of bronchoscopy or indication for ECMO. Mortality rates were similar between patients who underwent bronchoscopy and those who did not. CONCLUSION: Children requiring bronchoscopy represent a subset of the sickest children on ECMO. Bronchoscopy may provide benefit in children with persistent cardiopulmonary failure who could not otherwise be decannulated. Adverse events are associated with the number of bronchoscopies and the presence of obstructive material. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Fluorescent MOF and Its Gel Composite for the Fluorescence Recovery "Turn-On" Detection of Al3+ Ions and "Turn-Off" Detection of Oxo-Anions.

The exploration of smart sensors is of great significance for the selectivity, sensitivity, and ability to show the low detection limit for the target analyte. Here, we have used the linker H2L (5-((anthracen-9-ylmethyl)amino)isophthalic acid) for the construction of {[Cd(L)(DMF)(H2O)2]·H2O}n (1) which is in order with the chromophore anthracene moiety and the free -NH functionality as a guest interaction site. This framework showed the luminescence recovery "turn-on" detection of the Al3+ ion in an aqueous solution. An exhaustive mechanism study disclosed that the Lewis acid-base-type interaction between the Al3+ ion and the -NH functionality of the linker in the framework revealed that the absorbance caused an enhancement for the "turn-on" sensing event. Besides the "turn-on" sensing event, the "turn-off" sensing phenomenon of 1 is also noticed when it detects the hazardous oxo-anions (MnO4- and CrO42-) with limit of detection values of 17.08 and 19.91 ppb, respectively. The detection of these diverse analytes are very fast (10 s) and they can also be recognized through a colorimetric response. The sensing mechanisms for these analytes are established by photoinduced electron transfer, Forster resonance energy transfer, and inert filter effect along with theoretical investigation. Furthermore, to show the sensing application of 1 in a versatile podium, a MOF gel composite, 1@AA (AA = Agar-Agar), was developed from 1 with AA. Interestingly, 1@AA showed the colorimetric detection of these analytes under UV light. Therefore, sensor 1 behaves as a smart sensory material for the recognition of the above analytes through a simultaneous "turn-on" and "turn-off" effect.

Management of Tracheobronchial Stenosis in Chondrodysplasia Punctata.

Chondrodysplasia punctata (CDP) is a rare congenital syndrome characterized by aberrant, punctate deposition of calcium during endochondral bone formation, resulting in the characteristic finding of epiphyseal stippling on radiographs. While otolaryngologic manifestations such as nasomaxillary hypoplasia and mixed hearing loss are common, tracheobronchial calcification occurs rarely in neonates with CDP. The management of CDP-related airway stenosis is complex and there is limited literature pertaining to outcomes of airway interventions. Herein, we describe the clinical course and outcome of tracheal dilation for a newborn patient with CDP. Laryngoscope, 134:1464-1468, 2024.

Moonlighting Proteins: Diverse Functions Found in Fungi.

Moonlighting proteins combine multiple functions in one polypeptide chain. An increasing number of moonlighting proteins are being found in diverse fungal taxa that vary in morphology, life cycle, and ecological niche. In this mini-review we discuss examples of moonlighting proteins in fungi that illustrate their roles in transcription and DNA metabolism, translation and RNA metabolism, protein folding, and regulation of protein function, and their interaction with other cell types and host proteins.

Surgical and Biochemical Outcomes in Nerve Monitored Reoperation Surgery for Recurrent Papillary Thyroid Carcinoma.

OBJECTIVE: To study the surgical and biochemical outcomes in nerve-monitored reoperation or revision surgery for recurrent thyroid cancers. STUDY DESIGN: A single-center retrospective study. SETTING: Tertiary center. METHODS: We identified patients with recurrent papillary thyroid carcinoma (PTC) who underwent reoperation/revision surgery. Study outcomes were surgical complications frequency, recurrence, distant metastasis, and biological complete response (BCR) by comparing preoperative and postoperative thyroglobulin (Tg) levels. RESULTS: Out of 227 patients, 33.9% presented for ≥2 reoperation surgeries. Nineteen (8.4%) had permanent preoperative hypoparathyroidism while 22 patients (9.7%) had preoperative vocal cord paralysis (VCP). Following reoperation surgery, there were 12 cases (5.3%) of permanent hypocalcemia and no cases of unexpected postoperative VCP. BCR was achieved in 31 patients (35.2%) with complete Tg data. Mean preoperative Tg was 47.7 ng/mL and was 19.7 ng/mL postoperatively (p = .003). The cervical nodal recurrence rate after final surgery was 7.0% (n = 16). CONCLUSION: Reoperation surgery for recurrent PTC may help achieve biochemical remission regardless of age or the number of prior surgeries.

A Review of the Therapeutic Importance of Indole Scaffold in Drug Discovery.

Indole is known as a versatile heterocyclic building block for its multiple pharmacological activities and has a high probability of success in the race for drug candidates. Many natural products, alkaloids, and bioactive heterocycles contain indole as the active principle pharmacophore. These encourage the researchers to explore it as a lead in the drug development process. The current manuscript will serve as a torchbearer for understanding the structurally diverse class of indole derivatives with extensive pharmacological activity. The current manuscript describes the intermediates and their functional groups responsible for superior biological activity compared to the standard. The review is written to help researchers to choose leads against their target but also to provide crucial insight into the design of a hybrid pharmacophore-based approach in drug design with enhanced potential. The present reviews on the indole derivatives correlate the structures with biological activities as well as essential pharmacophores, which were highlighted. The discussion was explored under challenging targets like dengue, chikungunya (anti-viral), antihypertensive, diuretic, immunomodulator, CNS stimulant, antihyperlipidemic, antiarrhythmic, anti-Alzheimer's, and neuroprotective, along with anticancer, antitubercular, antimicrobial, anti-HIV, antimalarial, anti-inflammatory, antileishmanial, antianthelmintic, and enzyme inhibitors. So, this review includes a discussion of 19 different pharmacological targets for indole derivatives that could be utilized to derive extensive information needed for ligand-based drug design. The article will guide the researchers in the selection, design of lead and pharmacophore, and ligand-based drug design using indole moiety.

Development of an interdisciplinary microtia-atresia care model: A single-center 20-year experience.

Objectives: Microtia and aural atresia are congenital ear anomalies with a wide-ranging spectrum of phenotypes and varied functional and psychosocial consequences for patients. This study seeks to analyze the management of microtia-atresia patients at our center over a 20-year period and to propose recommendations for advancing microtia-atresia care at a national level. Methods: We performed a retrospective analysis of data from patients presenting to the Massachusetts Eye and Ear (Boston, MA) for initial otolaryngology consultation for congenital microtia and/or aural atresia between 1999 and 2018. Results: Over the 20-year study period, 229 patients presented to our microtia-atresia center at a median age of 7 years. The severity of microtia was most commonly classified as grade III (n = 87, 38%), 61% (n = 140) of patients had complete atresia, the median Jahrsdoerfer grading scale score was 6 (range 0-10), and 81 patients (35%) underwent surgery for microtia repair. For hearing rehabilitation, 30 patients (64%) underwent bone conduction device implantation and 17 patients (36%) underwent atresiaplasty. The implementation of an interdisciplinary, longitudinal care model resulted in an increase in patient (r = 0.819, p < .001) and surgical volume (microtia surgeries, r = 0.521, p = .019; otologic surgeries, r = 0.767, p < .001) at our center over time. Conclusion: An interdisciplinary team approach to microtia-atresia patient care may result in increased patient volume, which could improve aesthetic and hearing outcomes over time by concentrating care and surgical expertise. Future work should aim to establish standardized clinical consensus recommendations to guide the creation of high-quality microtia-atresia care programs. Level of Evidence: 4.

Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1-3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4-7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage.

Assessment of potential drug-drug interactions among outpatients in a tertiary care hospital: focusing on the role of P-glycoprotein and CYP3A4 (retrospective observational study).

Background: Selecting a medicine has a significant impact on the quality of therapy including efficacy and safety. P-glycoprotein and CYP3A4 share several common substrates known as bi-substrates. Both play major role in the pharmacokinetics and pharmacodynamics when over or under expressed. Objective: The study aimed to assess the Drug-Drug Interaction (DDI) related to P-glycoprotein (P-gp) and Cytochrome P450-3A4 (CYP3A4), to predict their clinical outcomes and also to discover prospective predictors of pDDIs. Methods: The subjects in this retrospective study ranged in age from 18 to 95 years with polypharmacy prescriptions. Information was gathered through patient medical records. Based on Micromedex and previous literature studies, medications prescribed to the patients were observed for pDDIs according to risk rating scale for drug interactions. Results: A total of 504 patients (160 males and 344 females) were included in the study. The mean of pDDI seen in the patients was 1.66 ± 1.48 and total 825 pDDIs were discovered. The factors significantly associated with having ≥1 pDDIs included: taking ≥5 medicines (OR 1.747), increased age (OR 1.026) increased comorbidities (OR 1.73). Conclusion: In prescriptions, a considerable number of probable DDI were discovered. Therefore, careful selection of drugs and identification of mechanisms for DDI is needed to lower the frequency of pDDI.

Hemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis, cytomegalovirus viremia, and nontuberculous mycobacteria bacteremia in a patient with recently diagnosed AIDS.

A 30-year-old Honduran male with recently diagnosed AIDS presented with a 1-month history of worsening abdominal pain, diarrhea, and fever. Initial investigations were notable for Cytomegalovirus viremia and diffuse lymphadenopathy. Axillary lymph node biopsy demonstrated necrotizing lymphadenitis with disseminated histoplasmosis. Despite aggressive antimicrobial therapy he continued to clinically deteriorate raising suspicion for hemophagocytic lymphohistiocytosis. The patient met 5 of 8 HLH-2004 diagnostic criteria and was successfully treated with dexamethasone and etoposide per the HLH-94 protocol. Despite the high mortality rates and poor clinical outcomes of hemophagocytic lymphohistiocytosis in patients living with HIV/AIDS, this case demonstrates that this high-risk patient population can be successfully treated and survive acquired hemophagocytic lymphohistiocytosis. Furthermore, our case stresses the importance of maintaining a broad differential diagnosis in patients living with HIV/AIDS who present with sepsis.

Burden of Psychiatric Disorders in Moyamoya Disease: A National Inpatient Perspective From 2007-2014.

Objective: Moyamoya disease is a cerebrovascular illness that causes progressive stenosis of the intracranial internal carotid arteries and their proximal branches, increasing the risk of stroke. Moyamoya disease is associated with a small number of neuropsychiatric symptoms. The objective of this study was to investigate psychiatric comorbidities and trends in patients with Moyamoya disease in the United States.Methods: US National Inpatient Sample data from 2007 to 2014 were used for analyses in this cross-sectional study. The frequency of psychiatric and nonpsychiatric disorders among adult patients with known Moyamoya disease was assessed. Baseline demographics included in the analysis and diagnostic codes used to identify psychiatric disorders were determined. Categorical and continuous data were assessed using Pearson χ2 test and Mann-Whitney U test, respectively. All analyses were conducted using SPSS version 22.0.Results: The prevalence of psychiatric comorbidities was 38.7% (7,861/20,289). The most common psychiatric disorders were mood disorders (17.8%) and anxiety disorders (8%). Psychosis and drug abuse were present in 4.4% and 4.1% of patients, respectively. Approximately 1 in 4 patients (22.2%) with Moyamoya disease had previously been screened for mental health or substance abuse. The rate of suicide or self-inflicted injury was 0.8%.Conclusions: The impact of Moyamoya disease on mental health services is expected to grow, as the condition's prevalence is increasing at a rate of approximately 1.5- to 2-fold. A multidisciplinary approach between neurology, psychiatry, and primary care can improve screening and management of comorbid psychiatric disorders.

Emerging trends in rhinoplasty education: accelerated adoption of digital tools and virtual learning platforms.

PURPOSE OF REVIEW: The COVID-19 pandemic catalyzed the rapid adoption of digital tools and virtual learning platforms by rhinoplasty educators and trainees alike. This review provides an overview of the variety of digital software and web-based tools rhinoplasty educators have adopted and highlights the advantages and potential drawbacks of virtual learning via e-content. RECENT FINDINGS: Medical education including subspecialty surgical training has recently undergone a dramatic digital transformation. Rhinoplasty surgeon-educators have been forced to embrace new digital tools, including videoconferencing, podcasts, virtual simulation and social media to reach and teach trainees. Recognizing the advantages of this new, limitless digital space, rhinoplasty surgeons are also engaging in virtual transcontinental collaboration and distance mentorship. SUMMARY: The dramatic evolution in how clinical educational materials are now digitally created, curated, disseminated and consumed is likely to far outlast the COVID-19 pandemic itself. Rapid, exponential growth of this digital library, however, places increased responsibility on educators to guide trainees towards evidence-based and state-of-the-art content.

Hepatocellular carcinoma surveillance, incidence, and tumor doubling times in patients cured of hepatitis C.

BACKGROUND: Hepatocellular carcinoma (HCC) incidence and mortality vary by race/ethnicity and both are higher in Black patients than in Whites. For HCC surveillance, all cirrhotic patients are advised to undergo lifelong twice-annual abdominal imaging. We investigated factors associated with surveillance and HCC incidence in a diverse HCC risk group, cirrhotic patients recently cured of hepatitis C virus (HCV) infection. METHODS: In this observational cohort study, all participants (n = 357) had advanced fibrosis/cirrhosis and were cured of HCV with antiviral treatment. None had Liver Imaging Reporting and Data System (LI-RADS) 2-5 lesions prior to HCV cure. Ultrasound, computed tomography, and/or magnetic resonance imaging were used for surveillance. RESULTS: At a median follow-up of 40 months [interquartile range (IQR) = 28-48], the median percentage of time up-to-date with surveillance was 49% (IQR) = 30%-71%. The likelihood of receiving a first surveillance examination was not significantly associated with race/ethnicity, but was higher for patients with more advanced cirrhosis, for example, bilirubin [odds ratio (OR) = 3.8/mg/dL, p = 0.002], private insurance (OR = 3.4, p = 0.006), and women (OR = 2.3, p = 0.008). The likelihood of receiving two or three examinations was significantly lower for non-Hispanic Blacks and Hispanics versus non-Hispanic Whites (OR = 0.39, and OR = 0.40, respectively, p < 0.005 for both) and for patients with higher platelet counts (OR = 0.99/10,000 cells/µl, p = 0.01), but higher for patients with private insurance (OR = 2.8, p < 0.001). Incident HCC was associated with higher bilirubin (OR = 1.7, p = 0.02) and lower lymphocyte counts (OR = 0.16, p = 0.01). CONCLUSIONS: Contrary to best practices, HCC surveillance was associated with sociodemographic factors (insurance status and race/ethnicity) among patients cured of HCV. Guideline-concordant surveillance is needed to address healthcare disparities.

Chronic exposure to the anti-M3 muscarinic acetylcholine receptor autoantibody in pemphigus vulgaris contributes to disease pathophysiology.

Pemphigus vulgaris (PV) is a potentially lethal autoimmune mucocutaneous blistering disease characterized by binding of IgG autoantibodies (AuAbs) to keratinocytes (KCs). In addition to AuAbs against adhesion molecules desmogleins 1 and 3, PV patients also produce an AuAb against the M3 muscarinic acetylcholine (ACh) receptor (M3AR) that plays an important role in regulation of vital functions of KCs upon binding endogenous ACh. This anti-M3AR AuAb is pathogenic because its adsorption eliminates the acantholytic activity of PV IgG; however, the molecular mechanism of its action is unclear. In the present study, we sought to elucidate the mode of immunopharmacologic action of the anti-M3AR AuAb in PV. Short-term exposures of cultured KCs to PV IgG or the muscarinic agonist muscarine both induced changes in the expression of keratins 5 and 10, consistent with the inhibition of proliferation and upregulated differentiation and in keeping with the biological function of M3AR. In contrast, long-term incubations induced a keratin expression pattern consistent with upregulated proliferation and decreased differentiation, in keeping with the hyperproliferative state of KCs in PV. This change could result from desensitization of the M3AR, representing the net antagonist-like effect of the AuAb. Therefore, chronic exposure of KCs to the anti-M3AR AuAb interrupts the physiological regulation of KCs by endogenous ACh, contributing to the onset of acantholysis. Since cholinergic agents have already demonstrated antiacantholytic activity in a mouse model of PV and in PV patients, our results have translational significance and can guide future development of therapies for PV patients employing cholinergic drugs.

Differences in fatigability of muscles involved in fecal continence: Potential clinical ramifications.

INTRODUCTION: Fatigue of the anal sphincter complex has been demonstrated using high-resolution anorectal manometry (HRAM). However, the fatigability of individual muscles such as the external anal sphincter (EAS) and puborectalis muscles (PRM) has not been described. Vaginal manometry has been used to study contractile activity of the PRM. By applying both modalities, we attempted to differentiate the fatigability between the PRM and the EAS under different exercise conditions. METHODS: We studied two groups: group 1, 12 healthy women (21 ± 2.7 years) with HRAM and group 2, 10 healthy (20 ± 3 years) women with vaginal manometry. All subjects performed 40 repetitive contractions with and without an intra-anal resistive load. In group 1, areas under the curve (AUC) of the anal canal high-pressure zone (HPZ) including the caudal and rostral halves were compared. In group 2, the maximum and mean pressures of the vaginal HPZ were compared. RESULTS: The AUC decreased significantly only after repetitive contractions against a resistive load (462 ± 129 vs. 390 ± 131 mmHg-cm, p = 0.02), indicating fatigue. The caudal half (EAS) decreased significantly after contractions against a load (288 ± 75 vs. 239 ± 82 mmHg-cm, p = 0.02), while the rostral half (PRM) did not. The vaginal pressures (PRM) also decreased only after repetitive contractions against a load (maximum pressures, 358 ± 171 vs. 239 ± 109 mmHg, p = 0.02). CONCLUSIONS: The EAS and PRM both exhibit fatigue with contractions only against a resistive load. These findings may guide the development of appropriate exercise regimens to target specific muscles involved in fecal continence.