Sacubitril/Valsartan in Patients With Heart Failure and Deterioration in eGFR to <30 mL/min/1.73 m2.

BACKGROUND: Sacubitril/valsartan is a foundational therapy for patients with heart failure. Although current U.S. Food and Drug Administration labeling does not provide guidance regarding initiation or continuation of sacubitril/valsartan in patients with worsening kidney function, guidelines identify estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 as a contraindication to therapy. OBJECTIVES: This study aims to assess the safety and efficacy of continuing sacubitril/valsartan in patients with deterioration of kidney function below an eGFR of 30 mL/min/1.73 m2. METHODS: The association between a deterioration in eGFR <30 mL/min/1.73 m2, efficacy and safety outcomes, and treatment with sacubitril/valsartan vs renin-angiotensin system inhibitor were evaluated using time updated Cox models in a post hoc parallel trial analyses of PARADIGM-HF and PARAGON-HF. RESULTS: Among 8,346 randomized patients in PARADIGM-HF and 4,746 in PARAGON-HF, 691 (8.3%) and 613 (12.9%), respectively, had an eGFR <30 mL/min/1.73 m2 at least once in follow-up. Patients experiencing such deterioration were at higher risk of the primary outcome in both PARADIGM-HF and PARAGON-HF. However, the incidence of the primary outcome remained lower with sacubitril/valsartan vs renin-angiotensin system inhibitor, regardless of deterioration in kidney function in both PARADIGM-HF (Pinteraction = 0.50) and PARAGON-HF (Pinteraction = 0.64). Rates of key safety outcomes were higher among patients experiencing eGFR deterioration; however, rates were similar between treatment groups including among those who remained on treatment. CONCLUSIONS: Patients experiencing deterioration of kidney function to a value below eGFR 30 mL/min/1.73 m2 faced high risk of cardiovascular and kidney disease outcomes. Continuation of sacubitril/valsartan was associated with persistent clinical benefit and no incremental safety risk. These data support continuation of sacubitril/valsartan for heart failure treatment even when eGFR declines below this threshold (PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], NCT01035255; and PARAGON-HF [Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction], NCT01920711).

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.

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.

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.

Construction, Features and Regulatory Aspects of Organ-Chip for Drug Delivery Applications: Advances and Prospective.

Organ-on-chip is an innovative technique that emerged from tissue engineering and microfluidic technologies. Organ-on-chip devices (OoCs) are anticipated to provide efficient resolutions to dealing with challenges in pharmaceutical advancement and individualized illness therapies. Organ-on-chip is an advanced method that can replicate human organs' physiological conditions and functions on a small chip. It possesses the capacity to greatly transform the drug development process by enabling the simulation of diseases and the testing of drugs. Effective integration of this advanced technical platform with common pharmaceutical and medical contexts is still a challenge. Microfluidic technology, a micro-level technique, has become a potent tool for biomedical engineering research. As a result, it has revolutionized disciplines including physiological material interpreting, compound detection, cell-based assay, tissue engineering, biological diagnostics, and pharmaceutical identification. This article aims to offer an overview of newly developed organ-on-a-chip systems. It includes single-organ platforms, emphasizing the most researched organs, including the heart, liver, blood arteries, and lungs. Subsequently, it provides a concise overview of tumour-on-a-chip systems and emphasizes their use in the evaluation of anti-cancer medications.

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.

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.

Robust 3D object watermarking scheme using shape features for copyright protection.

This article utilizes the discrete wavelet transformation to introduce an advanced 3D object watermarking model depending on the characteristics of the object's vertices. The model entails two different phases: integration and extraction. In the integration phase, a novel technique is proposed, which embeds the secret grayscale image three times using both the encrypted pixels and the vertices' coefficients of the original 3D object. In the extraction phase, the secret image is randomly extracted and recaptured using the inverse phase of the integration technique. Four common 3D objects (Stanford bunny, horse, cat figurine, and angel), with different faces and different vertices, are used in this model as a dataset. The performance of the proposed technique is evaluated using different metrics to show its superiority in terms of execution time and imperceptibility. The results demonstrated that the proposed method achieved high imperceptibility and transparency with low distortion. Moreover, the extracted secret grayscale image perfectly matched the original watermark with a structural similarity index of 1 for all testing models.

Erosion of the Capital City Advantage in Child Survival and Reproductive, Maternal, Newborn, and Child Health Intervention Coverage in Sub-Saharan Africa.

The place of residence is a major determinant of RMNCH outcomes, with rural areas often lagging in sub-Saharan Africa. This long-held pattern may be changing given differential progress across areas and increasing urbanization. We assessed inequalities in child mortality and RMNCH coverage across capital cities and other urban and rural areas. We analyzed mortality data from 163 DHS and MICS in 39 countries with the most recent survey conducted between 1990 and 2020 and RMNCH coverage data from 39 countries. We assessed inequality trends in neonatal and under-five mortality and in RMNCH coverage using multilevel linear regression models. Under-five mortality rates and RMNCH service coverage inequalities by place of residence have reduced substantially in sub-Saharan Africa, with rural areas experiencing faster progress than other areas. The absolute gap in child mortality between rural areas and capital cities and that between rural and other urban areas reduced respectively from 41 and 26 deaths per 1000 live births in 2000 to 23 and 15 by 2015. Capital cities are losing their primacy in child survival and RMNCH coverage over other urban areas and rural areas, especially in Eastern Africa where under-five mortality gap between capital cities and rural areas closed almost completely by 2015. While child mortality and RMNCH coverage inequalities are closing rapidly by place of residence, slower trends in capital cities and urban areas suggest gradual erosion of capital city and urban health advantage. Monitoring child mortality and RMNCH coverage trends in urban areas, especially among the urban poor, and addressing factors of within urban inequalities are urgently needed.

Insights into the Biological Activities and Substituent Effects of Pyrrole Derivatives: The Chemistry-Biology Connection.

Pyrrole, with its versatile heterocyclic ring structure, serves as a valuable template for generating a diverse range of lead compounds with various pharmacophores. Researchers and scientists globally are intrigued by pyrrole and its analogues for their broad pharmacological potential, prompting thorough investigations aimed at advancing human welfare. This comprehensive review delves into the diverse activities exhibited by pyrrole compounds, encompassing their synthesis, reactions, and pharmacological properties alongside their derivatives. In addition to detailing the characteristics of pyrrole and its derivatives within the context of green chemistry, the review also examines microwave-assisted reactions. It provides insights into their chemical structures, natural occurrences, and potential applications across various domains. Furthermore, the article investigates structural alterations of pyrrole compounds and their implications on their functionality, highlighting their versatility as foundational elements for both functional materials and bioactive compounds. Ultimately, the review underscores the imperative for continued research and development in the realm of pyrrole compounds to unearth novel activities and advantages.

A retrospective, descriptive analysis identifying non­small cell lung cancer molecular markers.

Non-small-cell lung cancer (NSCLC) remains one of the leading causes of cancer mortality worldwide. The aim of the present study was to review the histologic patterns and molecular drivers of NSCLC in patients with lung cancer. The electronic health records (EHR) of all patients diagnosed with lung cancer between April 2015 and September 2022 were obtained from a tertiary care hospital and retrospectively analysed. A total of 224 patients were identified of which 192 (138 males and 54 females) were included in the final analysis. Adenocarcinoma was the most common type of lung cancer identified, and accounted for 134 patients (70%), followed by squamous cell carcinoma in 47 (24%) patients, while large cell lung cancer was noted in only 5 (3%) patients. The most common mutations were EGFR mutations and were detected in 29 (15%) patients, followed by PD-L1 expression which was present in 56 (24.7%) patients, KRAS in 16 (8.3%) patients, ALK1 in 8 (4.2%) patients and BRAF, ROS1 and MET were present in 3 (1.6%), 2 (1%) and 1 (0.5%), respectively. The findings from the present study offer important insights into the epidemiological, clinical and molecular characteristics of NSCLC. Further research is warranted to explore the clinical implications of these findings.

Both endothelial mineralocorticoid receptor expression and hyperleptinemia are required for clinical characteristics of placental ischemia in mice.

BACKGROUND: One of the initiating events in preeclampsia (PE) is placental ischemia. Rodent models of placental ischemia do not present with vascular endothelial dysfunction, a hallmark of PE. We previously demonstrated a role for leptin in endothelial dysfunction in pregnancy in the absence of placental ischemia. We hypothesized that placental ischemia requires hyperleptinemia and endothelial mineralocorticoid receptor (ECMR) expression to induce PE-associated endothelial dysfunction in pregnant mice. METHODS: We induced placental ischemia via the reduced uterine perfusion pressure (RUPP) procedure in pregnant ECMR-intact (ECMR+/+) and ECMR deletion (ECMR-/-) mice at gestational day (GD) 13. ECMR+/+ RUPP pregnant mice also received concurrent leptin infusion via miniosmotic pump (0.9mg/kg/day). RESULTS: RUPP increased blood pressure via radiotelemetry and decreased fetal growth in ECMR+/+ pregnant mice. Both increases in blood pressure and reduced fetal growth were abolished in RUPP ECMR-/- mice. Placental ischemia did not decrease endothelial-dependent relaxation to acetylcholine (ACh) but increased phenylephrine (Phe) contraction in mesenteric arteries of pregnant mice, which was ablated by ECMR deletion. Addition of leptin to RUPP mice significantly reduced ACh relaxation in ECMR+/+ pregnant mice, accompanied by an increase in soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) ratio. CONCLUSIONS: Our data indicate that high leptin levels drive endothelial dysfunction inPE and that ECMR is required for clinical characteristics of hypertension and fetal growth restriction in placental ischemia PE. Collectively, we show that both ECMR and leptin play a role to mediate PE.

Nature exposure and mental health during the COVID-19 pandemic: A Navigation Guide systematic review with meta-analysis.

Prior reviews have highlighted that nature exposure was a valuable coping strategy enchancing mental health during the COVID-19 pandemic. However, no existing reviews have determined the quality of evidence and risk of bias of the empirical studies supporting this claim. To address this gap, we employed a Navigation Guide systematic review and meta-analysis approach to investigate associations between nature exposure and mental health during the pandemic. Searches in PubMed, Web of Science, Scopus, CINAHL, and PsycInfo retrieved relevant articles published between January 1, 2020, and March 4, 2024. We used the Navigation Guide methodology to assess the risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessment to evaluate the overall quality of evidence. Our search retrieved 113 studies that met the inclusion criteria and reported diverse types of exposure, including nature availability, nature visit frequency, green space accessibility, and green space type, alongside associations with 12 mental health outcomes. Meta-analyses found access to gardens was associated with lower odds of depression [(Pooled OR=0.71, 95%CI=0.61, 0.82), I2=0%, n=3] and anxiety [(Pooled odds ratio [OR]=0.73, 95%CI=0.63, 0.84), I2=0%, n=3]. Increased time in green spaces were associated with lower level of stress [(Pooled Corr=-0.11, 95%CI=-0.17, -0.05), I2=0%, n=2]. Higher frequency of visits to nature was associated with improved mental well-being [(Pooled standardized beta estimate during COVID-19 period [ES]=0.10, 95%CI=0.07, 0.14), I2=0%, n=2] and general mental health [(Pooled standardized beta estimate [ES]=0.11, 95%CI=0.03-0.38), I2=82%, n=2]. However, the number of pooled studies was small and the overall quality of evidence was "very low" for all outcomes, and high levels of bias were observed (26% of studies had high, 71% probably high). Nonetheless, given the trends in the results, nature-based solutions emphasizing exposure to gardens and green spaces near the home may have promoted psychological resilience during this public health crisis.

Functional selection in SH3-mediated activation of the PI3 kinase.

The phosphoinositide-3 kinase (PI3K), a heterodimeric enzyme, plays a pivotal role in cellular metabolism and survival. Its deregulation is associated with major human diseases, particularly cancer. The p85 regulatory subunit of PI3K binds to the catalytic p110 subunit via its C-terminal domains, stabilising it in an inhibited state. Certain Src homology 3 (SH3) domains can activate p110 by binding to the proline-rich (PR) 1 motif located at the N-terminus of p85. However, the mechanism by which this N-terminal interaction activates the C-terminally bound p110 remains elusive. Moreover, the intrinsically poor ligand selectivity of SH3 domains raises the question of how they can control PI3K. Combining structural, biophysical, and functional methods, we demonstrate that the answers to both these unknown issues are linked: PI3K-activating SH3 domains engage in additional "tertiary" interactions with the C-terminal domains of p85, thereby relieving their inhibition of p110. SH3 domains lacking these tertiary interactions may still bind to p85 but cannot activate PI3K. Thus, p85 uses a functional selection mechanism that precludes nonspecific activation rather than nonspecific binding. This separation of binding and activation may provide a general mechanism for how biological activities can be controlled by promiscuous protein-protein interaction domains.

Effective multi-sectoral approach for rapid reduction in maternal and neonatal mortality: the exceptional case of Bangladesh.

BACKGROUND: Bangladesh experienced impressive reductions in maternal and neonatal mortality over the past several decades with annual rates of decline surpassing 4% since 2000. We comprehensively assessed health system and non-health factors that drove Bangladesh's success in mortality reduction. METHODS: We operationalised a comprehensive conceptual framework and analysed available household surveys for trends and inequalities in mortality, intervention coverage and quality of care. These include 12 household surveys totalling over 1.3 million births in the 15 years preceding the surveys. Literature and desk reviews permitted a reconstruction of policy and programme development and financing since 1990. These were supplemented with key informant interviews to understand implementation decisions and strategies. RESULTS: Bangladesh prioritised early population policies to manage its rapidly growing population through community-based family planning programmes initiated in mid-1970s. These were followed in the 1990s and 2000s by priority to increase access to health facilities leading to rapid increases in facility delivery, intervention coverage and access to emergency obstetric care, with large contribution from private facilities. A decentralised health system organisation, from communities to the central level, openness to private for-profit sector growth, and efficient financing allocation to maternal and newborn health enabled rapid progress. Other critical levers included poverty reduction, women empowerment, rural development, and culture of data generation and use. However, recent empirical data suggest a slowing down of mortality reductions. CONCLUSION: Bangladesh demonstrated effective multi-sectoral approach and persistent programming, testing and implementation to achieve rapid gains in maternal and neonatal mortality reduction. The slowing down of recent mortality trends suggests that the country will need to revise its strategies to achieve the Sustainable Development Goals. As fertility reached replacement level, further gains in maternal and neonatal mortality will require prioritising universal access to quality facility delivery, and addressing inequalities, including reaching the rural poor.

Challenges in reducing maternal and neonatal mortality in Niger: an in-depth case study.

INTRODUCTION: Recent modelled estimates suggest that Niger made progress in maternal mortality since 2000. However, neonatal mortality has not declined since 2012 and maternal mortality estimates were based on limited data. We researched the drivers of progress and challenges. METHODS: We reviewed two decades of health policies, analysed mortality trends from United Nations data and six national household surveys between 1998 and 2021 and assessed coverage and inequalities of maternal and newborn health indicators. Quality of care was evaluated from health facility surveys in 2015 and 2019 and emergency obstetric assessments in 2011 and 2017. We determined the impact of intervention coverage on maternal and neonatal lives saved between 2000 and 2020. We interviewed 31 key informants to understand the factors underpinning policy implementation. RESULTS: Empirical maternal mortality ratio declined from 709 to 520 per 100 000 live births during 2000-2011, while neonatal mortality rate declined from 46 to 23 per 1000 live births during 2000-2012 then increased to 43 in 2018. Inequalities in neonatal mortality were reduced across socioeconomic and demographic strata. Key maternal and newborn health indicators improved over 2000-2012, except for caesarean sections, although the overall levels were low. Interventions delivered during childbirth saved most maternal and newborn lives. Progress came from health centre expansion, emergency care and the 2006 fee exemptions policy. During the past decade, challenges included expansion of emergency care, continued high fertility, security issues, financing and health workforce. Social determinants saw minimal change. CONCLUSIONS: Niger reduced maternal and neonatal mortality during 2000-2012, but progress has stalled. Further reductions require strategies targeting comprehensive care, referrals, quality of care, fertility reduction, social determinants and improved security nationwide.

Efhamni: A Deep Learning-Based Saudi Sign Language Recognition Application.

Deaf and hard-of-hearing people mainly communicate using sign language, which is a set of signs made using hand gestures combined with facial expressions to make meaningful and complete sentences. The problem that faces deaf and hard-of-hearing people is the lack of automatic tools that translate sign languages into written or spoken text, which has led to a communication gap between them and their communities. Most state-of-the-art vision-based sign language recognition approaches focus on translating non-Arabic sign languages, with few targeting the Arabic Sign Language (ArSL) and even fewer targeting the Saudi Sign Language (SSL). This paper proposes a mobile application that helps deaf and hard-of-hearing people in Saudi Arabia to communicate efficiently with their communities. The prototype is an Android-based mobile application that applies deep learning techniques to translate isolated SSL to text and audio and includes unique features that are not available in other related applications targeting ArSL. The proposed approach, when evaluated on a comprehensive dataset, has demonstrated its effectiveness by outperforming several state-of-the-art approaches and producing results that are comparable to these approaches. Moreover, testing the prototype on several deaf and hard-of-hearing users, in addition to hearing users, proved its usefulness. In the future, we aim to improve the accuracy of the model and enrich the application with more features.

Comparing Intradermal (ID) Rabies Vaccination with Conventional IM Regimen on Humoral Response of New Zealand White Rabbits for the Production of Animal-Derived Polyclonal Antibodies.

In developing countries, it is imperative to implement cost-effective strategies for animal humoral response development in the production of antiserum. This study compared the effect of immunization regimens on the humoral immune response of New Zealand White (NZW) rabbits (N = 24) using cell culture rabies vaccine (CCRV) through intradermal (ID) and traditional intramuscular (IM) routes. The rabbits were divided into three experimental groups: (a) IPC-R2 with a two-site one-week regimen; (b) TRC-R3 with a two-site twenty-eight-day regimen; and (c) Alternate-R4 with a four-site one-week regimen. These regimens were then compared to the standard IM schedule of five doses of rabies vaccine administered at days 0, 3, 7, 14, and 28 in control group R-1. The results were evaluated at days 14 and 35 postvaccination using rabies-specific Platelia II™ ELISA kit method. The results showed a better response to the ID regimen than the IM route regarding immunogenicity and volume consumption of the vaccine. The three selected ID regimes showed significantly higher mean titer values than the control IM regimen group R-1 (p < 0.001). The study aims to explore simple immunization strategies to enhance the RV-specific antibody titers for immunization donor animals. This method would produce polyclonal antibodies and strengthen local production of polyclonal antibodies in Pakistan to deal with vaccine and rabies immunoglobulin (RIG) shortage, thus providing effective postexposure prophylaxis (PEP) for better control of rabies in developing countries.

Unilateral laser ventriculocordectomy results in increased arytenoid stability in horses with severe left sided recurrent laryngeal neuropathy.

BACKGROUND: There is no objective information reporting the effect of unilateral laser ventriculocordectomy (VeC) on arytenoid abduction or stability. OBJECTIVES: To evaluate arytenoid stability and abduction in horses with severe recurrent laryngeal neuropathy (RLN) before and after unilateral laser VeC. STUDY DESIGN: Prospective cohort. METHODS: Eight horses with grade C or D exercising laryngeal function that underwent unilateral laser VeC were included. Exercising endoscopy was performed before and ≥6 weeks after left-sided laser VeC. Arytenoid stability at maximal exercise was calculated by measuring the left-to-right quotient angle ratio (LRQ) of the corniculate processes at the points of maximal arytenoid abduction (expiration) and maximal arytenoid collapse (inspiration). For each horse, means of measurements obtained for four breaths pre- and post-operatively were used for statistical analysis. RESULTS: The difference in LRQ between inspiration and expiration was lower post-operatively (median 0.039; interquartile range [IQR] 0.032-0.047) compared with pre-operatively (median 0.158; IQR 0.083-0.249; p = 0.01) confirming the left arytenoid was more stable following unilateral laser VeC. The degree of improvement was significantly greater for grade D horses compared with grade C horses (p = 0.04). The LRQ measured on maximal abduction was also lower post-operatively (median 0.467; IQR 0.444-0.506) compared with pre-operatively (median 0.578; IQR 0.554-0.655; p = 0.02) indicating the left arytenoid was less abducted following surgery. MAIN LIMITATIONS: The sample size was small, no racehorses were included and post-operative assessment was conducted at a variable time after surgery. CONCLUSION: Unilateral laser VeC in grade C and D RLN-affected horses results in slightly reduced left arytenoid abduction but increased arytenoid stability.

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

Low phase noise and narrow linewidth lasers are achieved by implementing self-injection locking of a DFB laser on two distinct fiber Fabry-Perot resonators. More than 45 dB improvement of the laser phase or frequency noise is observed when the laser is locked. In both cases, a frequency noise floor below 1 Hz2/Hz is measured. The integrated linewidth of the best of the two lasers is computed to be in the range of 400 Hz and appears to be dominated by vibration noise close to the carrier. The results are then compared with a model based on the retro-injected power and the Q factors ratio between the DFB laser and the resonator. This straightforward model facilitates the extraction of the theoretical performance of these sources close to the carrier, a characteristic still hidden by vibration noise.