The emergence of non-infectious epiglottitis after the era of Hemophilus influenza type B universal vaccination: two case reports and literature review.

Objective: Following the global dissemination of vaccination protocols for Hemophilus influenza type B, the occurrence rate and burden of infectious epiglottitis decreased rapidly and substantially. However, this gave space to the rise of non-infectious causes, with children being more vulnerable than adults. This report aims to divert the clinician's attention to the existence of other non-infectious causes of epiglottitis, all of which require careful attention and timely management for favorable clinical outcomes. Case summary: Two cases with positive vaccination history were encountered in our practice. The first case was a 4-year-old girl, presenting with stridor drooling, and dyspnea, later complication by apnea. The fiberoptic exam revealed severe epiglottitic swelling with near-complete injury of the vocal cords with a circumferential burn. She did not respond to racemic epinephrine, and a tracheostomy was done. She was discharged after 6 days with minimal soft palate swelling. The second case was a 2-year-old boy presenting after exposure to an alkaline solution. The case exhibited similar symptoms but with white plaques and edema of the soft palate. The fiberoptic exam showed swelling and erythema of the supraglottic structures with partial obstruction. Although the blood culture was negative, he was intubated and given four intravenous boluses of dexamethasone and penicillin. On the fifth day, the patient was discharged after a normal fiberoptic examination. Discussion: These cases highlight a crucial shift in the etiology of epiglottitis post widespread Hemophilus influenza type B vaccination, underscoring the emergence of non-infectious causes, particularly in children. The two cases presented, both with vaccination histories, demonstrate diverse non-infectious triggers leading to severe epiglottitis. The first case, involving thermal injury, and the second, chemical exposure, both necessitated intensive interventions, including tracheostomy and intubation. These instances emphasize the need for heightened clinical vigilance for non-infectious epiglottitis, demanding prompt recognition and management to ensure positive outcomes. This shift in etiology calls for a reevaluation of traditional diagnostic and therapeutic approaches to pediatric epiglottitis.

Optical properties investigation and multicolor behavior of neodymium (Nd3+)-doped oxyfluoride silicate glasses SiO2-PbO-PbF2.

The aim of this research is to investigate novel compositions of oxyfluoride glasses doped with Neodymium (Nd3+) rare earth ions in the visible spectrum. This area has not been extensively studied in the existing literature, so it is vital to understand the favorable photoluminescence characteristics within this part of the electromagnetic spectrum. Therefore, we synthesized and characterized SiO2-PbO-PbF2 (SPF) doped with 1% neodymium (Nd3+) ions glasses. Spectroscopic analyses, based on Judd-Ofelt theory, were conducted on absorption spectra. These analyses enabled to determine absorption cross-sections, transition probabilities, and Judd-Ofelt intensity parameters Ω2, Ω4, and Ω6 for the different transition. Additionally, we calculated various radiative properties, such as branching ratios, integrated cross-sections, radiative lifetimes, emission cross-section, optical gain, and the multicolor behavior (chromaticity coordinates, CIE diagram) under different excitation wavelengths. The results suggest promising prospects for using these oxyfluoride silicate glasses doped with Nd3+ as a fluorophore, potentially for lasing materials around 630-nm emission and in other photonic applications.

A prospective, observational, multicentre study to evaluate the efficacy of brivaracetam as adjuvant therapy for epilepsy: The Bravo study.

Background: Epilepsy is a persistent tendency to experience epileptic seizures and can lead to various neurobiological disorders, with an elevated risk of premature mortality. This study evaluates the efficacy of brivaracetam adjuvant therapy in patients with epilepsy. Methods: A prospective observational multicentre study that was conducted in Pakistan from March to September 2022, by using a non-probability convenience sampling technique. The population consisted of 543 individuals with a diagnosis of epilepsy for whom adjunctive brivaracetam (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) was recommended by the treating physician. The research sample was drawn from various private neurology clinics of Karachi, Lahore, Rawalpindi, Islamabad and Peshawar. Data originating from routine patient visits, and assessments at three study time points, were recorded in the study case report form. Results: Across 18 clinical sites, 543 individuals participated, with a mean age of 32.9 years. The most prescribed dosages were 50 mg BD, followed by 100 mg BD. Notably, brivaracetam combined with divalproex sodium was the most prevalent treatment, followed by brivaracetam with levetiracetam. At both the 14th and 90th day assessments, a significant reduction in seizure frequency was observed, with 63.1% of individuals showing a favourable response by day 90. Treatment-naive individuals exhibited higher rates of seizure freedom and response compared with treatment-resistant individuals. Conclusions: The study demonstrates the effectiveness of brivaracetam combination therapy in epilepsy management, with notable reductions in seizure frequency and favourable clinical responses observed, particularly in treatment-naive individuals.

Is Piezosurgery Associated with Improved Patient Outcomes Compared to Conventional Osteotomy in Rhinoplasty? A Systematic Review and Meta-Analysis of RCTs.

Background: Rhinoplasty is a common plastic surgery procedure with evolving surgical techniques. This systematic review and meta-analysis compares the outcomes of piezosurgery versus conventional osteotomy in rhinoplasty. Methods: A comprehensive search of six databases yielded 12 randomized controlled trials (RCTs) comparing piezosurgery (292 cases) to conventional osteotomy (338 cases) in rhinoplasty patients. The examined outcomes included postoperative edema, ecchymosis, complications, pain (using the Visual Analogue Scale-VAS), and operative time. Subgroup analyses were conducted based on the assessment timepoint, surgical approach, and outcome grade. The risk of bias was evaluated using the revised Cochrane tool. Results: Piezosurgery showed a significant reduction in the degree of postoperative edema (second and seventh postoperative days) and ecchymosis (second, fourth, and seventh postoperative days). The external approach in piezosurgery demonstrated greater benefits for both outcomes. Piezosurgery was associated with a significant reduction in overall complications, especially mucosal injuries, compared to conventional osteotomy, with no significant difference regarding postoperative hemorrhage. A significant reduction in pain scores and the need for analgesia was observed with piezosurgery. No significant difference was found in operative time. Conclusions: Piezosurgery offers significant benefits in patient outcomes, with similar operative time between both techniques. However, long-term investigations are still needed.

Memantine to Reduce Cognitive Impairment After Radiation in Children: A Pilot Study Evaluating the Feasibility of Memantine in Reducing Cognitive Impairment in Pediatric Patients after Radiation Therapy for Central Nervous System Tumors.

PURPOSE: Memantine is standard in certain adults receiving brain radiation therapy (RT) to decrease cognitive impacts, but it is unknown whether pediatric patients can take, tolerate, and/or benefit from memantine. In this prospective single-arm feasibility study, we hypothesized that pediatric patients receiving central nervous system (CNS) RT would tolerate memantine with good adherence. METHODS AND MATERIALS: Patients aged 4 to 18 years with a primary CNS malignancy (excluding World Health Organization grade 4 astrocytoma, glioblastoma) receiving intracranial RT were eligible. A 6-month memantine course was given during and after RT, with dose titration in 5 mg increments over 4 weeks targeting a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg twice a day. The primary endpoint was to achieve 80% drug adherence rate in 80% of patients measured 1 month after RT. Secondary objectives included memantine feasibility at 3 and 6 months. RESULTS: Eighteen patients enrolled from 2020 to 2022 and were prescribed memantine with RT. The study closed early to avoid competing with the phase 3 randomized Children's Oncology Group study AACL2031. No predefined stopping rules were met. One patient withdrew for cognition-altering substance use, leaving 17 patients available for analysis. One patient discontinued memantine after one dose due to nausea. For the remaining 16 patients, there was a median of 100% pill completion rate (range, 74%-100%; n = 9/17 with 100% adherence) at 1 month after RT, with 15/16 (94%) with adherence rates >80%. At the 3- and 6-month post-RT time points for secondary endpoints, the median adherence rates were 100% (range, 55%-100%) and 96% (range, 33%-100%), respectively. Grade 1 to 2 fatigue, headache, and nausea were the most common toxicity events, at least possibly related to the study drug (n = 27), without attributable grade 3+ events. CONCLUSIONS: Memantine is a feasible, safe, and well-tolerated addition to multimodality treatment for pediatric CNS malignancies. Results of "Anonymized for Review" are awaited to define the value of memantine in this population.

Meta-Analysis Comparing Drug-Coated Balloon Versus Plain Old Balloon Angioplasty for In-stent Restenosis of Coronaries.

BACKGROUND: Despite the advent of newer stents, in-stent restenosis has been a persistent and formidable challenge. Trials have demonstrated the superiority of drug-coated balloons (DCB) over plain-old balloon angioplasty (POBA). A recent AGENT IDE trial highlighted the need for a more comprehensive understanding hence we conducted a meta-analysis aimed at elucidating their respective clinical outcomes. METHODS: A literature search was conducted by 2 investigators (SS and MH) using MEDLINE (EMBASE and PubMed) using a systematic search strategy by PRISMA till November 01, 2023. CRAN-R software was used for statistical analysis. The quality assessment was performed using the Cochrane Risk of Bias tool (Supplemental Table 5). RESULTS: We included 6 studies with a total of 1171 patients. Our analysis showed decreased odds of multiple outcomes with statistically significant results including TVR (OR 0.33, CI 0.19-0.57), TVF (OR 0.30, CI 0.09-0.99), TLR (OR 0.22, CI 0.10-0.46), restenosis (OR 0.1343, CI 0.06-0.27), and MACE (OR 0.2 CI 0.12-0.37). Although MI and all-cause mortality showed decreased odds with all-cause mortality at 0.8 (95% CI: 0.363-2.09), and MI at 0.6 (95% CI: 0.0349-1.07), the reductions did not reach statistical significance. CONCLUSION: Our analysis by scrutinizing six RCTs favored DCB over POBA. However, extensive research for deeper understanding cannot be overemphasized.

Estimation of kidney doses from [177Lu]Lu-DOTA-TATE PRRT using single time point post-treatment SPECT/CT.

BACKGROUND: Dosimetry after [177Lu]Lu-DOTA-TATE therapy can be demanding for both patients and the clinical service due to the need for imaging at several time points. In this work we compare three methods of single time point (STP) kidney dosimetry after [177Lu]Lu-DOTA-TATE therapy with a multiple time point (MTP) dosimetry method. METHOD: Method 1 (MTP): Kidney doses were calculated from 31 patients including 107 therapy cycles. Post-therapy SPECT images were acquired on day 0, 4 and 7 along with a CT scan on day 4. A mono-exponential fit was used to calculate kidney doses using cycle specific data. Method 2 (Consistent effective half-life): The effective half-life [Formula: see text] calculated in cycle 1 was assumed consistent for subsequent cycles of therapy and the activity scaled using a single day 3-5 SPECT/CT. Methods 3 and 4 (Hänscheid and Madsen approximations): The Hänscheid approximation and Madsen approximation were both evaluated using a single SPECT/CT acquired on day 0, 4 and 7. All STP methods were compared to the MTP method for accuracy. RESULTS: Using the MTP method, mean right and left kidney doses were calculated to be 2.9 ± 1.1 Gy and 2.8 ± 0.9 Gy respectively and the population [Formula: see text] was 56 ± 13 h. For the consistent [Formula: see text], Hänscheid and Madsen methods, the percentage of results within ± 20% of MTP method were 96% (n = 70), 95% (n = 80) and 94% (n = 80) respectively. CONCLUSION: All three single time point methods had > 94% of results within ± 20% of the MTP method, however the consistent [Formula: see text] method resulted in the highest alignment with the MTP method and is the only method which allows for calculation of the patient-specific [Formula: see text]. If only a single scan can be performed, day 4 is optimal for kidney dosimetry where the Hänscheid or Madsen approximation can be implemented with good accuracy.

Identification of Anastatica hierochuntica L. Methanolic-Leaf-Extract-Derived Metabolites Exhibiting Xanthine Oxidase Inhibitory Activities: In Vitro and In Silico Approaches.

There is a growing interest in the discovery of novel xanthine oxidase inhibitors for gout prevention and treatment with fewer side effects. This study aimed to identify the xanthine oxidase (XO) inhibitory potential and drug-likeness of the metabolites present in the methanolic leaf extract of Anastatica (A.) hierochuntica L. using in vitro and in silico models. The extract-derived metabolites were identified by liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry (LC-QTOF-MS). Molecular docking predicted the XO inhibitory activity of the identified metabolites and validated the best scored in vitro XO inhibitory activities for experimental verification, as well as predictions of their anticancer, pharmacokinetic, and toxic properties; oral bioavailability; and endocrine disruption using SwissADMET, PASS, ProTox-II, and Endocrine Disruptome web servers. A total of 12 metabolites, with a majority of flavonoids, were identified. Rutin, quercetin, and luteolin flavonoids demonstrated the highest ranked docking scores of -12.39, -11.15, and -10.43, respectively, while the half-maximal inhibitory concentration (IC50) values of these metabolites against XO activity were 11.35 µM, 11.1 µM, and 21.58 µM, respectively. In addition, SwissADMET generated data related to the physicochemical properties and drug-likeness of the metabolites. Similarly, the PASS, ProTox-II, and Endocrine Disruptome prediction models stated the safe and potential use of these natural compounds. However, in vivo studies are necessary to support the development of the prominent and promising therapeutic use of A. hierochuntica methanolic-leaf-extract-derived metabolites as XO inhibitors for the prevention and treatment of hyperuricemic and gout patients. Furthermore, the predicted findings of the present study open a new paradigm for these extract-derived metabolites by revealing novel oncogenic targets for the potential treatment of human malignancies.

Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

How does a Saccharomyces cerevisiae extract influence the components of isolated rotavirus particles from stool samples collected in a clinical setting from children?

Human Rotavirus (HRV) is the causative pathogen of severe acute enteric infections that cause mortality among children worldwide. This study focuses on developing a new and effective treatment for rotavirus infection using an extract from Saccharomyces cerevisiae, aiming to make this treatment easily accessible to everyone. 15 antigens and 26 antibodies were detected in serum and stool using ELISA. The titers of HRVq1, HRVq2, HRVC1, and HRVC2 on Vero cells were determined to be 1.2x106, 3.0x106, 4.2x106, and 7.5x105 (Plaque forming unit, PFU/ml) four days after infection, respectively. The HRVq1 isolate induced cytopathic effects, i.e., forming multinucleated, rounded, enlarged, and expanding gigantic cells. RT-PCR identified this isolate, and the accession number 2691714 was assigned to GeneBank. The molecular docking analysis revealed that nonstructural proteins (NSPs) NSP1, NSP2, NSP3, NSP4, NSP5, and NSP6 exhibited significant binding with RNA. NSP2 demonstrated the highest binding affinity and the lowest binding energy (-8.9 kcal/mol). This affinity was maintained via hydrophobic interactions and hydrogen bonds spanning in length from 1.12 Å to 3.11 Å. The ADMET and bioactivity predictions indicated that the yeast extract possessed ideal solubility, was nontoxic, and did not cause cancer. The inhibitory constant values predicted for the S. cerevisiae extract in the presence of HRV vital proteins varied from 5.32 to 7.45 mM, indicating its potential as a viable drug candidate. Saccharomyces cerevisiae extract could be utilized as a dietary supplement to combat HRV as an alternative dietary supplement.

Outlier detection for keystroke biometric user authentication.

User authentication is a fundamental aspect of information security, requiring robust measures against identity fraud and data breaches. In the domain of keystroke dynamics research, a significant challenge lies in the reliance on imposter datasets, particularly evident in real-world scenarios where obtaining authentic imposter data is exceedingly difficult. This article presents a novel approach to keystroke dynamics-based authentication, utilizing unsupervised outlier detection techniques, notably exemplified by the histogram-based outlier score (HBOS), eliminating the necessity for imposter samples. A comprehensive evaluation, comparing HBOS with 15 alternative outlier detection methods, highlights its superior performance. This departure from traditional dependence on imposter datasets signifies a substantial advancement in keystroke dynamics research. Key innovations include the introduction of an alternative outlier detection paradigm with HBOS, increased practical applicability by reducing reliance on extensive imposter data, resolution of real-world challenges in simulating fraudulent keystrokes, and addressing critical gaps in existing authentication methodologies. Rigorous testing on Carnegie Mellon University's (CMU) keystroke biometrics dataset validates the effectiveness of the proposed approach, yielding an impressive equal error rate (EER) of 5.97%, a notable area under the ROC curve of 97.79%, and a robust accuracy (ACC) of 89.23%. This article represents a significant advancement in keystroke dynamics-based authentication, offering a reliable and efficient solution characterized by substantial improvements in accuracy and practical applicability.

Low phase noise self-injection-locked diode laser with a high-Q fiber resonator: model and experiment: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 1933 (2024)10.1364/OL.514778.

Safety Evaluation of Unibody Endografts for Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis.

BACKGROUND: The unibody bifurcated aortic endograft (AFX/AFX2) has emerged as a treatment option for abdominal aortic aneurysms (AAAs). This systematic review and meta-analysis aimed to evaluate the safety of the unibody endograft. METHODS: A literature search was conducted in Cochrane Library, Scopus, Web of Science, and PubMed. Studies assessing the unibody endograft for abdominal aortic aneurysm repair between 2014 and 2023 were included. The defined primary outcomes were the incidences of type I, II, and III endoleaks. The secondary outcomes were access site problems, aneurysm-related mortality, aneurysm rupture, all-cause mortality, aneurysm sac growth, limb occlusion, stent graft migration, and technical success rate. RESULTS: 14 studies including 12 observational studies and two randomized controlled trials (RCTs) were included in the systematic review. The meta-analysis included 10 studies with 12,690 patients that reported the measured outcomes, and excluded four studies that did not. Type II endoleaks had the highest incidence of 12% (95% CI: 4-20%), followed by type III endoleaks with an incidence of 3% (95% CI: 1-5). The incidence of type I endoleaks was 1% (95% CI: 0-2%). A subgroup analysis by follow-up duration showed that type II endoleak incidence was higher after one to two years of follow-up than three to four years of follow-up. The incidence of aneurysmal mortality was 2% (95% CI: 0-7%); limb occlusion was 1% (95% CI: 0-1%); stent graft migration was 1% (95% CI: 0-2%); aneurysmal rupture was 6% (95% CI: 2-11%); access site problems were 7% (95% CI: 2-13%); aneurysm sac growth was 2% (95% CI: 0-4%);, all-cause mortality was 21% (95% CI: 4-38%), and technical success rate was 100% (95% CI: 98-100%). CONCLUSION: The unibody endograft is a safe and minimally invasive approach for AAA repair. However, potential complications necessitate close patient follow-up after the intervention.

Obstructive Sleep Apnea and Its Cardiac Implications in the United States: An Age-Stratified Analysis Between Young and Older Adults.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder associated with cardiovascular risks. This study aimed to assess the prevalence of probable OSA and its relationship with cardiovascular risks and diseases focusing on age-stratified young adults (20-40 years) and older (>40 years). METHODS AND RESULTS: The study used a cross-sectional design, analyzing data from the National Health and Nutrition Examination Survey conducted between 2013 and 2018, comprising 9887 community-dwelling adults aged ≥20 years. Probable OSA was determined on the basis of self-report of OSA-related symptoms (eg, snoring, gasping/breath cessation while sleeping). Cardiovascular risk factors, including hypertension, diabetes, hyperlipidemia, and metabolic syndrome, were evaluated according to established guidelines. Cardiovascular diseases (CVDs) included self-reported heart conditions, including congestive heart failure, coronary heart disease, angina, heart attacks, and strokes. Individuals with probable OSA showed a significantly higher prevalence of health conditions, including hypertension (adjusted prevalence ratio [aPR], 1.19; P<0.001), diabetes (aPR, 1.17; P: 0.01), metabolic syndrome (aPR, 1.14; P<0.001), heart attack (aPR, 1.63; P<0.01), stroke (aPR, 1.41; P: 0.03), and any CVD event (aPR, 1.36; P: 0.01) after adjusting for relevant factors. Young adults with probable OSA showed higher prevalence rates of any CVD events (aPR, 3.44; P<0.001), hypertension (aPR, 1.45; P<0.001), metabolic syndrome (aPR, 1.25; P<0.001), and angina (aPR, 10.39; P<0.001). CONCLUSIONS: The study suggests early identification and management of OSA in individuals at risk for CVD. While cross-sectional, it emphasizes that health care providers should recognize OSA as significantly associated with CVDs and its precursor risks in young adults, stressing proactive care and screening to reduce CVD risk in this population.

Amitriptyline-Induced Hyperprolactinemia in a Pediatric Patient.

Hyperprolactinemia is an endocrinological disorder that might arise from various physiologic or pathologic conditions, as well as from pharmacologic sources. These pharmacologic sources include antidepressants, antipsychotics, and dopamine receptor-blocking agents. Amitriptyline is classified as a tricyclic antidepressant. While it is FDA-approved primarily for the treatment of depression, amitriptyline also demonstrates efficacy in managing various other conditions, such as anxiety, post-traumatic stress disorder, insomnia, chronic and neuropathic pain, and migraine prevention. We present a case of a 10-year-old patient with a history of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and migraine headaches who was incidentally found to have elevated prolactin levels while taking amitriptyline for migraine prophylaxis. While risperidone, an antipsychotic that can be used for ASD management, is commonly known to induce hyperprolactinemia, the association between amitriptyline and elevated prolactin is less frequently described in the literature. This case underscores the necessity for healthcare providers across various specialties to be aware of amitriptyline-induced hyperprolactinemia.

Comparison of Various Therapeutic Approaches to Manage Infertility in Polycystic Ovarian Syndrome.

OBJECTIVE: To compare the efficacies of common therapeutic regimens and their combinations, used in polycystic ovarian syndrome (PCOS) to improve fertility in reproductive-age women. STUDY DESIGN: A descriptive study. Place and Duration of the Study: Department of Obstetric Gynaecologist, Medicare Cardiac and General Hospital, Karachi, Pakistan, from November 2022 to July 2023. METHODOLOGY: Out of 300 patients with the symptoms of menstrual irregularities and infertility, 152 were diagnosed as PCOS patients based on the ultrasound and hormonal assays and selected for study purpose. They were divided according to their therapeutic regimen into four treatment groups, treated by different therapeutic agents. Group A received metformin 500 mg/day (n = 38); Group B received metformin + myo-inositol 1g (n = 49); Group C received metformin + letrozole 2.5 mg (n = 36), and Group D received metformin + letrozole + myo-inositol (n = 29), orally for three months. All continuous variables, such as body mass index (BMI), FSH, LH, FT4, and FSI were analysed by applying t-test to all therapeutic groups, keeping p ≤0.05 as the level of significance. RESULTS: HCG-positive was found as 86% (n = 33) in Group A, 63% (n = 31) in Group B, 52% (n = 19) in Group C, and 27% (n = 08) in Group D. There were statistically significant (p <0.001) changes in BMI, FSH, LH, FT4, and FSI as well. Metformin alone and metformin plus myo-inositol came out to be more effective than other regimens. CONCLUSION: Metformin alone and myo-inositol plus metformin are effective therapeutic options in PCOS-induced infertility problems. KEY WORDS: Polycystic ovarian syndrome, Infertility, Metformin, Myo-inositol, Letrozole, Menstrual irregularities.

Mechanisms of neutralization of toxSAS from toxin-antitoxin modules.

Toxic small alarmone synthetase (toxSAS) enzymes constitute a family of bacterial effectors present in toxin-antitoxin and secretion systems. toxSASs act through either translation inhibition mediated by pyrophosphorylation of transfer RNA (tRNA) CCA ends or synthesis of the toxic alarmone adenosine pentaphosphate ((pp)pApp) and adenosine triphosphate (ATP) depletion, exemplified by FaRel2 and FaRel, respectively. However, structural bases of toxSAS neutralization are missing. Here we show that the pseudo-Zn2+ finger domain (pZFD) of the ATfaRel2 antitoxin precludes access of ATP to the pyrophosphate donor site of the FaRel2 toxin, without affecting recruitment of the tRNA pyrophosphate acceptor. By contrast, (pp)pApp-producing toxSASs are inhibited by Tis1 antitoxin domains though occlusion of the pyrophosphate acceptor-binding site. Consequently, the auxiliary pZFD of AT2faRel is dispensable for FaRel neutralization. Collectively, our study establishes the general principles of toxSAS inhibition by structured antitoxin domains, with the control strategy directly coupled to toxSAS substrate specificity.

Optimization of a fiber Fabry-Perot resonator for low-threshold modulation instability Kerr frequency combs.

We report a theoretical and experimental investigation of fiber Fabry-Perot cavities aimed at enhancing Kerr frequency comb generation. The modulation instability (MI) power threshold is derived from the linear stability analysis of a generalized Lugiato-Lefever equation. By combining this analysis with the concepts of power enhancement factor (PEF) and optimal coupling, we predict the ideal manufacturing parameters of fiber Fabry-Perot (FFP) cavities for the MI Kerr frequency comb generation. Our findings reveal a distinction between the optimal coupling for modulation instability and that of the cold cavity. Consequently, mirror reflectivity must be adjusted to suit the specific application. We verified the predictions of our theory by measuring the MI power threshold as a function of detuning for three different cavities.