Rapid total sialic acid monitoring during cell culture process using a machine learning model based soft sensor.

Total sialic acid content (TSA) in biotherapeutic proteins is often a critical quality attribute as it impacts the drug efficacy. Traditional wet chemical assays to quantify TSA in biotherapeutic proteins during cell culture typically takes several hours or longer due to the complexity of the assay which involves isolation of sialic acid from the protein of interest, followed by sample preparation and chromatographic based separation for analysis. Here, we developed a machine learning model-based technology to rapidly predict TSA during cell culture by using typically measured process parameters. The technology features a user interface, where the users only have to upload cell culture process parameters as input variables and TSA values are instantly displayed on a dashboard platform based on the model predictions. In this study, multiple machine learning algorithms were assessed on our dataset, with the Random Forest model being identified as the most promising model. Feature importance analysis from the Random Forest model revealed that attributes like viable cell density (VCD), glutamate, ammonium, phosphate, and basal medium type are critical for predictions. Notably, while the model demonstrated strong predictability by Day 14 of observation, challenges remain in forecasting TSA values at the edges of the calibration range. This research not only emphasizes the transformative power of machine learning and soft sensors in bioprocessing but also introduces a rapid and efficient tool for sialic acid prediction, signaling significant advancements in bioprocessing. Future endeavors may focus on data augmentation to further enhance model precision and exploration of process control capabilities.

Impact of Targeted Systemic Therapy and Radiotherapy on Patients Undergoing Spine Surgery for Metastatic Renal Cell Carcinoma.

BACKGROUND: In patients undergoing spine surgery for renal cell carcinoma (RCC), we sought to: (1) describe patterns of postoperative targeted systemic therapy and radiotherapy (RT), (2) compare perioperative outcomes among those treated with targeted systemic therapy to those without, and (3) evaluate the impact of targeted systemic therapy and/or RT on overall survival (OS) and local recurrence (LR). METHODS: A single-institution, retrospective cohort study of patients undergoing spine surgery for metastatic RCC from 2010 to 2021 was undertaken. Treatment groups were RT alone, targeted systemic therapy alone, dual therapy consisting of RT and targeted systemic therapy, and neither therapy. Multivariable Cox regression controlled for age, race, sex, insurance, and preoperative targeted systemic therapy. RESULTS: Forty-nine patients underwent spine surgery for RCC. Postoperatively, 4 patients (8%) received RT alone, 19 (38.8%) targeted systemic therapy alone, 12 (24.5%) dual therapy, and 13 (28.6%) neither. All groups were similar in demographics, preoperative Karnofsky Performance Score (P = 0.372), tumor size (P = 0.413), readmissions (P = 0.884), complications (P = 0.272), Karnofsky Performance Score (P = 0.466), and Modified McCormick Scale (P = 0.980) at last follow-up. Higher 1-year survival was found in dual therapy (83.3%) compared with other therapies. OS was significantly longer in patients with dual therapy compared with other therapies (log-rank; P = 0.010). Multivariate Cox regression (HR = 0.08, 95% CI = 0.02-0.31, P < 0.001) showed longer OS in dual therapy compared with other therapies. Seven patients (14.3%) experienced LR, and a similar time to LR was found between groups (log-rank; P = 0.190). CONCLUSION: In patients undergoing metastatic spine surgery for RCC, postoperative dual therapy demonstrated significantly higher 1-year survival and OS compared with other therapies. CLINICAL RELEVANCE: Multidisciplinary management of metastatic RCC is necessary to ensure timely implementation of targeted systemic therapy and RT to improve outcomes.

Assessment of climate change on river streamflow under different representative concentration pathways.

Climate change and excessive greenhouse gas emissions profoundly impact hydrological cycles, particularly in arid and semi-arid regions, necessitating assessments of their effects on water resource management, agriculture, soil fertility, nutrient transport, hydropower generation, and flood risk. This study investigates climate change repercussions on streamflow in the Zarrineh River Basin, Iran, across three decadal intervals (2020-2029, 2055-2064, and 2090-2099) aiming to develop effective adaptation and mitigation strategies. Four General Circulation Models (GCMs), chosen based on distinct Representative Concentration Pathways (RCPs) determined by the annual mean temperature gradient, are employed. These models generate daily maximum (Tmax) and minimum (Tmin) temperatures along with precipitation data. Subsequently, these variables are integrated into the Soil and Water Assessment Tool (SWAT) model to analyze river flow alterations for each decadal timeframe. Comparison between future projections and observed climate data reveals a gradual decline in precipitation and Tmax, coupled with a substantial increase in Tmin. The average precipitation diminishes from 0.77 mm in the period 1985-1994 to a range of 0.42-0.28 mm in 2090-2099. The simulated flow at the basin outlet highlights that the GCM with the highest annual mean temperature gradient yields the lowest streamflow, while conversely, the model with the lowest gradient generates the highest. Consequently, streamflow experiences a decline from 52 m3/s in 1985-1994 to a range of 41-20 m3/s in 2090-2099.

Iron protoporphyrin IX-hyaluronan hydrogel-supported luminol chemiluminescence for the detection of nitric oxide in physiological solutions.

Due to its role as a free radical signal-transducing agent with a short lifespan, precise measurement of nitric oxide (●NO) levels presents significant challenges. Various analytical techniques offer distinct advantages and disadvantages for ●NO detection. This research aims to simplify the detection process by developing a hydrogel system using iron(III)-protoporphyrin IX (hemin)-loaded hyaluronan for the detection of ●NO in solution. Various hydrogel formulations were created, and the effects of their components on hydrogel-supported luminol chemiluminescence (CL) kinetics, radical scavenging, and physicochemical properties were analysed through factorial analysis. The candidate formulations were then evaluated using two ●NO donors. An increase in the degree of crosslinking in unloaded formulations enhanced interactions with the CL reaction components, hydrogen peroxide (H2O2) and luminol, thereby affecting light generation. However, hemin loading negated these effects, resulting in more prominent luminescence kinetics in formulations with lower crosslinking degrees. Similarly, ●NO influenced the kinetics differently, interacting with both the CL reaction and hydrogel components. Hemin-loaded formulations exhibited enhanced signal propagation when exposed to ●NO, followed by H2O2 and luminol, whereas reversing the order of addition inhibited this propagation. The magnitude of these luminescence changes depended on the type and concentration of the ●NO donor, demonstrating greater sensitivity to ●NO levels compared to amperometric sensing. These findings suggest that the studied hydrogel platform has potential for the facile and accurate detection of ●NO in solution, requiring minimal sample sizes.

Transcription Attenuation in Synthetic Promoters in Nonoverlapping Tandem Formation.

Closely spaced promoters are ubiquitous in prokaryotic and eukaryotic genomes. How their structure and dynamics relate remains unclear, particularly for tandem formations. To study their transcriptional interference, we engineered two pairs and one trio of synthetic promoters in nonoverlapping, tandem formation, in single-copy plasmids transformed into Escherichia coli cells. From in vivo measurements, we found that these promoters in tandem formation can have attenuated transcription rates. The attenuation strength can be widely fine-tuned by the promoters' positioning, natural regulatory mechanisms, and other factors, including the antibiotic rifampicin, which is known to hamper RNAP promoter escape. From this, and supported by in silico models, we concluded that the attenuation in these constructs emerges from premature terminations generated by collisions between RNAPs elongating from upstream promoters and RNAPs occupying downstream promoters. Moreover, we found that these collisions can cause one or both RNAPs to falloff. Finally, the broad spectrum of possible, externally regulated, attenuation strengths observed in our synthetic tandem promoters suggests that they could become useful as externally controllable regulators of future synthetic circuits.

Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage.

Tissue regeneration and remodeling involve many complex stages. Macrophages are critical in maintaining micro-environmental homeostasis by regulating inflammation and orchestrating wound healing. They display high plasticity in response to various stimuli, showing a spectrum of functional phenotypes that vary from M1 (pro-inflammatory) to M2 (anti-inflammatory) macrophages. While transient inflammation is an essential trigger for tissue healing following an injury, sustained inflammation (e.g., in foreign body response to implants, diabetes or inflammatory diseases) can hinder tissue healing and cause tissue damage. Modulating macrophage polarization has emerged as an effective strategy for enhancing immune-mediated tissue regeneration and promoting better integration of implantable materials in the host. This article provides an overview of macrophages' functional properties followed by discussing different strategies for modulating macrophage polarization. Advances in the use of synthetic and natural biomaterials to fabricate immune-modulatory materials are highlighted. This reveals that the development and clinical application of more effective immunomodulatory systems targeting macrophage polarization under pathological conditions will be driven by a detailed understanding of the factors that regulate macrophage polarization and biological function in order to optimize existing methods and generate novel strategies to control cell phenotype.

Rapid determination of uracil in biological fluids at mercury thin film electrode for early detection of potential 5-fluorouracil toxicity due to dihydropyrimidine dehydrogenase deficiency.

Determination of plasma uracil was reported as a method for evaluation of Dihydropyrimidine dehydrogenase (DPD) activity that is highly demanded to ensure the safe administration of 5-fluorouracil (5-FU)-based therapies to cancer patients. This work reports the development of a simple electroanalytical method based on adsorptive stripping square wave voltammetry (AdSWV) at mercury film-coated glassy carbon electrode (MF/GCE) for the highly sensitive determination of uracil in biological fluids that can be used for diagnosis of decreased DPD activity. Due to the formation of the HgII-Uracil complex at the electrode surface, the accuracy of the measurement was not affected by the complicated matrices in biological fluids including human serum, plasma, and urine. The high sensitivity of the developed method results in a low limit of detection (≈1.3 nM) in human plasma samples, falling below the practical cut-off level of 15 ng mL-1 (≈0.14 µM). This threshold concentration is crucial for predicting 5-FU toxicity, as reported in buffer, and ≤1.15% in biological samples), and accuracy (recovery percentage close to 100%).

Costs of Community-Based Viral Hepatitis Screening in Cameroon Using Point-of-Care Technologies.

This cost analysis of a community-based viral hepatitis screening program in Cameroon found an investment of $3.52 per person screened, $50.63 per new diagnosis of hepatitis B, $159.45 per new diagnosis of hepatitis C, and $47.97 per new diagnosis of either hepatitis B or C.

Ocular syphilis in patients with nonreactive RPR and positive treponemal serologies: a retrospective observational cohort study.

BACKGROUND: Screening for syphilis increasingly relies on positive treponemal rather than nontreponemal tests (rapid plasma reagin [RPR]). We compared ocular syphilis in patients with nonreactive versus positive RPR. METHODS: We conducted a retrospective observational cohort study of ocular syphilis treated at two New England hospitals 1996-2021 based on ophthalmologist-diagnosed eye findings and positive treponemal serology, regardless of RPR. We excluded patients with alternative diagnoses. We categorized RPR into nonreactive RPR, low-titer RPR (<1:8), and high-titer RPR (≥1:8) and compared early and long-term response to therapy. RESULTS: Our sample included 115 patients with ocular syphilis (median follow-up 2.5 years): 25 (22%) nonreactive RPR, 21 (18%) low-titer RPR, 69 (60%) high-titer RPR. Compared with nonreactive and low-titer RPR, people with high-titer RPR were younger (mean 47 years, p<0.001), more likely male (93%, p<0.001) and more likely to be living with HIV (49%, p<0.001). People with nonreactive and low-titer RPR were less likely than high-titer RPR to have posterior/panuveitis (32% and 29% versus 75%, p<0.001) or abnormal CSF (26% and 35% versus 75%, p<0.001), and more likely to present with chronic eye findings (20% and 29% versus 1%, p<0.001). In long-term follow up, eye findings improved and did not recur in most patients (62% nonreactive, 68% low-titer, 96% high-titer RPR); improved but recurred in 29%, 11%, and 4%, respectively; and were stable in 10%, 21%, and 0%, respectively. CONCLUSION: Patients with ocular syphilis and nonreactive RPR are similar to patients with low-titer RPR, and antibiotic therapy is beneficial in most.

Fetal bradycardia in open versus fetoscopic prenatal repair of spina bifida.

OBJECTIVE: To compare the occurrence of fetal bradycardia in open versus fetoscopic fetal spina bifida surgery. METHODS: This is a single-institution retrospective cohort study of patients undergoing open (n = 25) or fetoscopic (n = 26) spina bifida repair between 2017 and 2022. From October 2017 to June 2020, spina bifida repairs were performed via an open classical hysterotomy, and from November 2020 to June 2022 fetoscopic repairs were performed following transition to this technique. Fetal heart rate (FHR) in beats per minute (bpm) was recorded via echocardiography every 15 min during the procedure. Cohort characteristics, fetal bradycardia and maternal physiologic parameters were compared between the groups. RESULTS: Fetuses undergoing an open repair more frequently developed bradycardia defined as <110 bpm (32% vs. 3.8%, p = 0.008), and a trend was observed for FHR decreases more than 25 bpm from baseline (20% vs. 3.8%, p = 0.073). Profound bradycardia less than 80 bpm was rare, occurring in only three operations (two in open, one in fetoscopic repair) with two fetuses (one in each group) requiring emergency cesarean delivery. CONCLUSION: When compared to open fetal surgery, fetal bradycardia occurred less frequently in fetoscopic surgery despite a significantly greater anesthetic exposure and the use of the intraamniotic carbon dioxide insufflation.

Prevalence of Hypertension and Its Associated Risk Factors Among Adults Attending Medical Outpatient Clinics at Ibn Sina General Hospital Authority in Mukalla City, Yemen.

BACKGROUND: Hypertension (HTN) is the most generally acknowledged modifiable risk factor for cardiovascular disease, cerebrovascular disease, and end-stage renal disease. Accordingly, the World Health Organization has listed HTN as the third greatest cause of death globally. OBJECTIVES: The objective of this study was to assess the prevalence of HTN and its associated risk factors among adults attending medical clinics at Ibn Sina Hospital Authority in Mukalla City, Yemen. METHODS: A cross-sectional descriptive survey was conducted using a self-administered questionnaire applied to 384 male and female adults aged ≥18 years attending Ibn Sina General Hospital Authority outpatient clinics in Mukalla City, Yemen, between December 2022 and May 2023. The participant's body weight, height, and waist circumference were measured. The data were analyzed using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 25.0, Armonk, NY). P values of <0.05 were considered statistically significant. RESULTS: Among the 384 participants, 20.5% had HTN, and the remaining (79.5%) did not have HTN, with a substantial proportion (47.2%) reporting a positive family history of HTN. Diabetes mellitus was present in 16.1% of the participants, whereas dyslipidemia and other chronic diseases were reported by 9.3% and 15.8% of the participants, respectively. A total of 75.6% of the participants had never smoked, and 11.7% were past smokers. More than half of the participants (57.29%) had never chewed khat, 20.57% were former khat chewers, and 22.14% were currently chewing khat. Nutritional status, as indicated by body mass index, showed that 29.8% were overweight. CONCLUSIONS: HTN was found to be prevalent among the study participants. However, the respondents' awareness of the problem and the overall control rates were very low. Certain factors, such as family history of HTN, diabetes mellitus, and high body mass index, were found to be associated with HTN. Therefore, intervention measures are warranted emphasizing modifiable risk factors to prevent HTN.

Obstacles to receiving postoperative radiation therapy following separation surgery for metastatic spine disease.

OBJECTIVE: Obtaining timely postoperative radiotherapy (RT) following separation surgery is critical to avoid local recurrence of disease yet can be a challenge due to scheduling conflicts, insurance denials, and travel arrangements. In patients undergoing metastatic spine surgery for spinal cord compression, the authors sought to: 1) report the rate of postoperative RT, 2) describe reasons for patients not receiving postoperative RT, and 3) investigate factors that may predict whether a patient receives postoperative RT. METHODS: A single-center retrospective case series was undertaken of all patients who underwent metastatic spine surgery for extradural disease between January 2010 and January 2021. Inclusion criteria were patients with intermediate or radioresistant tumors with evidence of spinal cord compression who underwent surgery. The primary outcome was the occurrence of RT within 3 months following surgery. Multivariable logistic regression analysis was performed controlling for age, BMI, race, total number of decompressed levels, tumor size, other organ metastasis, and preoperative RT or chemotherapy to predict patients receiving postoperative RT. RESULTS: Of 239 patients undergoing spine surgery for metastatic disease, 113 (47.3%) received postoperative RT while 126 (52.7%) did not. In the postoperative RT group, 24 (21.2%) received stereotactic body radiation therapy while 89 (78.8%) received conventional external-beam radiation therapy. The most common reasons for patients not receiving postoperative RT included death or transfer to hospice (31.0%), RT not being recommended by radiation oncology (30.2%), and loss to follow-up (23.8%). On critical review with the radiation oncology department, the authors estimated that 101 of 126 (80.2%) patients who did not receive postoperative RT were potential candidates for postoperative RT. Patients who received postoperative RT had more documented inpatient (48.7% vs 32.5%, p < 0.001) and outpatient (100.0% vs 65.1%, p < 0.001) radiation oncology consultations than those who did not. Additionally, patients who received postoperative RT had a higher rate of postoperative chemotherapy (53.1% vs 25.4%, p < 0.001), while patients who did not receive postoperative RT had a higher rate of preoperative RT (7.1% vs 31.0%, p < 0.001). Multivariable analysis confirmed that patients who received preoperative RT had lower odds of undergoing postoperative RT (OR 0.14, 95% CI 0.06-0.34; p < 0.001), and patients who underwent postoperative chemotherapy had higher odds of undergoing postoperative RT (OR 3.83, 95% CI 2.05-7.17; p < 0.001). CONCLUSIONS: In the current study reflecting real-world care of patients with metastatic spine disease after undergoing separation surgery, 47% of patients did not receive postoperative RT, and 80% of those patients were potential candidates for postoperative RT. Radiation oncology consultation and postoperative chemotherapy were significantly associated with receiving postoperative RT, whereas preoperative RT was significantly associated with not receiving postoperative RT. The lack of timely postoperative RT highlights a potential gap in metastatic spine tumor care and underscores the necessity for prompt radiation oncology consultation and effective planning.

Comparing the Upper Instrumented Vertebrae Tilt Angle vs Screw Angle in the Development of Proximal Junction Kyphosis After Adult Spinal Deformity Surgery: Which Matters More?

BACKGROUND: We sought to determine which aspect of the upper instrumented vertebrae (UIV)-tilt angle or screw angle-was more strongly associated with: (1) proximal junctional kyphosis/failure (PJK/F), (2) other mechanical complications and reoperations, and (3) patient-reported outcome measures (PROMs). METHODS: A single-institution, retrospective cohort study was undertaken for patients undergoing adult spinal deformity (ASD) surgery from 2011 to 2017. Only patients with UIV at T7 or below were included. The primary exposure variables were UIV tilt angle (the angle of the UIV inferior endplate and the horizontal) and UIV screw angle (the angle of the UIV screws and superior endplate). Multivariable logistic regression included age, body mass index, osteopenia/osteoporosis, postoperative sagittal vertical axis, postoperative pelvic-incidence lumbar lordosis mismatch, UIV tilt angle, and UIV screw angle. RESULTS: One hundred and seventeen patients underwent adult spinal deformity surgery with a minimum of 2-year follow-up. A total of 41 patients (35.0%) had PJK and 26 (22.2%) had PJF. (1) UIV tilt angle: 96 (82.1%) had lordotic UIV tilt angles, 6 (5.1%) were neutral, and 15 (12.8%) were kyphotic. (2) UIV screw angle: 38 (32.5%) had cranially directed screws, 4 (3.4%) were neutral, and 75 (64.1%) were caudally directed. Both lordotic-angled UIV endplate (OR = 1.06, 95% CI = 1.01-1.12, and P = 0.020) and cranially directed screws (OR = 1.19, 95% CI = 1.07-1.33, and P < 0.001) were associated with higher odds of PJK, with a more pronounced effect of UIV screw angle compared with UIV tilt angle (Wald test, 9.40 vs 4.42). Similar results were found for PJF. Neither parameter was associated with other mechanical complications, reoperations, or patient-reported outcome measures. CONCLUSIONS: UIV screw angle was more strongly associated with development of PJK/F compared with tilt angle. Overall, these modifiable parameters are directly under the surgeon's control and can mitigate the development of PJK/F. CLINICAL RELEVANCE: Surgeons may consider selecting a UIV with a neutral or kyphotically directed UIV tilt angle when performing ASD surgery with a UIV in the lower thoracic or lumbar region, as well as use UIV screw angles that are caudally directed, for the purprose of decreasing the risk of developing PJK/F.

Objective monitoring of loneliness levels using smart devices: A multi-device approach for mental health applications.

Loneliness is linked to wide ranging physical and mental health problems, including increased rates of mortality. Understanding how loneliness manifests is important for targeted public health treatment and intervention. With advances in mobile sending and wearable technologies, it is possible to collect data on human phenomena in a continuous and uninterrupted way. In doing so, such approaches can be used to monitor physiological and behavioral aspects relevant to an individual's loneliness. In this study, we proposed a method for continuous detection of loneliness using fully objective data from smart devices and passive mobile sensing. We also investigated whether physiological and behavioral features differed in their importance in predicting loneliness across individuals. Finally, we examined how informative data from each device is for loneliness detection tasks. We assessed subjective feelings of loneliness while monitoring behavioral and physiological patterns in 30 college students over a 2-month period. We used smartphones to monitor behavioral patterns (e.g., location changes, type of notifications, in-coming and out-going calls/text messages) and smart watches and rings to monitor physiology and sleep patterns (e.g., heart-rate, heart-rate variability, sleep duration). Participants reported their loneliness feeling multiple times a day through a questionnaire app on their phone. Using the data collected from their devices, we trained a random forest machine learning based model to detect loneliness levels. We found support for loneliness prediction using a multi-device and fully-objective approach. Furthermore, behavioral data collected by smartphones generally were the most important features across all participants. The study provides promising results for using objective data to monitor mental health indicators, which could provide a continuous and uninterrupted source of information in mental healthcare applications.

Feasibility of continuous smart health monitoring in pregnant population: A mixed-method approach.

The utilization of smart monitoring technology offers potential for enhancing health outcomes, yet its feasibility and acceptance among Hispanic pregnant individuals remain uncertain. This is particularly crucial to investigate within the context of apparently healthy individuals identified as low risk, who still face a 10% likelihood of complications. Given their frequent underrepresentation in healthcare services and relative lack of attention, improving the feasibility of remote monitoring in this population could yield significant benefits. To address this gap, our study aimed to adapt and evaluate the practicality of a smart monitoring platform among healthy Hispanic pregnant women during the second and third trimesters of pregnancy, as well as one week following childbirth, a period when complications often arise. This longitudinal study followed n = 16 participants for an average of 17 weeks. Participants were instructed to wear the Oura ring for objective data collection, including activity, sleep, and heart rate, and to complete survey questions through REDcap to assess mental health and lifestyle factors. The study framework utilized the RE-AIM approach, with acceptability and adherence as key components of the feasibility evaluation. Our findings revealed that completion rates for biweekly and monthly surveys remained consistently high until after childbirth (approximately 80%), while daily question completion remained above 80% until 38th week of gestation, declining thereafter. The wearing rate of the Oura ring remained consistently above 80% until the 35th gestational week, decreasing to around 31% postpartum. Participants cited barriers to wearing the ring during the postpartum period, including difficulties managing the newborn, forgetfulness, and concerns about scratching the baby's skin. The enrollment rate was 71.42%, with an attrition rate of 6.25%. Thematic analysis of one-on-one interviews identified three main themes: personal desire for health improvement, social acceptability and support, and conditions influencing device/platform efficiency. In conclusion, while adherence varied based on gestational week and survey frequency, the study demonstrated strong acceptability of the smart monitoring platform among the study population, indicated by the high enrollment rate. Qualitative insights underscored the significance of personal motivation, social support, and device/platform efficiency in enhancing patient engagement with digital health monitoring during pregnancy, offering valuable considerations for future healthcare interventions in this domain.

Enhancing the substrate selectivity of enzyme mimetics in biosensing and bioassay: Novel approaches.

A substantial development in nanoscale materials possessing catalytic activities comparable with natural enzymes has been accomplished. Their advantages were owing to the excellent sturdiness in an extreme environment, possibilities of their large-scale production resulting in higher profitability, and easy manipulation for modification. Despite these advantages, the main challenge for artificial enzyme mimetics is the lack of substrate selectivity where natural enzymes flourish. This review addresses this vital problem by introducing substrate selectivity strategies to three classes of artificial enzymes: molecularly imprinted polymers, nanozymes (NZs), and DNAzymes. These rationally designed strategies enhance the substrate selectivity and are discussed and exemplified throughout the review. Various functional mechanisms associated with applying enzyme mimetics in biosensing and bioassays are also given. Eventually, future directives toward enhancing the substrate selectivity of biomimetics and related challenges are discussed and evaluated based on their efficiency and convenience in biosensing and bioassays.

Hemin as a Molecular Probe for Nitric Oxide Detection in Physiological Solutions: Experimental and Theoretical Assessment.

Given its pivotal role in modulating various pathological processes, precise measurement of nitric oxide (●NO) levels in physiological solutions is imperative. The key techniques include the ozone-based chemiluminescence (CL) reactions, amperometric ●NO sensing, and Griess assay, each with its advantages and drawbacks. In this study, a hemin/H2O2/luminol CL reaction was employed for accurately detecting ●NO in diverse solutions. We investigated how the luminescence kinetics was influenced by ●NO from two donors, nitrite and peroxynitrite, while also assessing the impact of culture medium components and reactive species quenchers. Furthermore, we experimentally and theoretically explored the mechanism of hemin oxidation responsible for the initiation of light generation. Although both hemin and ●NO enhanced the H2O2/luminol-based luminescence reactions with distinct kinetics, hemin's interference with ●NO/peroxynitrite- modulated their individual effects. Leveraging the propagated signal due to hemin, the ●NO levels in solution were estimated, observing parallel changes to those detected via amperometric detection in response to varying concentrations of the ●NO-donor. The examined reactions aid in comprehending the mechanism of ●NO/hemin/H2O2/luminol interactions and how these can be used for detecting ●NO in solution with minimal sample size demands. Moreover, the selectivity across different solutions can be improved by incorporating certain quenchers for reactive species into the reaction.

Needle Fetal Thoracoscopy: A Technique to Assist with Ultrasound-Guided Placement of Challenging Thoracoamniotic Shunts.

INTRODUCTION: Fetal thoracoamniotic shunts are common lifesaving interventions but frequently require replacement. Needle fetal thoracoscopy is a technique that uses standard thoracoamniotic shunt introducer sheaths to permit direct visualization and even instrument manipulation during shunt deployment to facilitate optimal positioning and primary shunt function in the most challenging cases. CASE PRESENTATION: In this study, 5 patients who underwent needle fetal thoracoscopy-assisted thoracoamniotic shunt placement were reviewed. Three patients with large, macrocystic congenital pulmonary airway malformations (CPAMs) with evidence of worsening mediastinal shift and/or hydrops and 2 patients with large chylothorax with fetal hydrops were treated. Four cases had previous shunts that failed due to poor sonographic visualization during initial placement, cyst septations, shunt obstruction, or dislodgment. Needle fetal thoracoscopy was used to disrupt cyst walls and septations, clear hematoma, and confirm the optimal initial position of the shunt. In this series, 1 severe CPAM patient with a short cervix developed preterm labor postoperatively resulting in neonatal demise. The remaining 4 patients experienced resolution of hydrops and progressed to successful delivery with excellent neonatal outcomes. CONCLUSION: Needle fetal thoracoscopy is a procedure that may be selectively deployed in challenging thoracoamniotic shunt cases impacted by recurrent failure, poor sonographic windows, and challenging fetal positioning.

Clinical Characteristics and Outcomes of Disseminated Strongyloidiasis in the United States-A Multicenter Network Analysis.

Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with disseminated strongyloidiasis. We conducted a U.S.-based multicenter retrospective cohort study to determine 90-day clinical outcomes for people diagnosed with Strongyloides infection in the TriNetX patient database. We identified adult patients with the International Classification of Diseases (10th revision, clinical modification) code for Strongyloides infection (B78) or a positive Strongyloides IgG antibody test and captured outcomes at 90 days. We identified 5,434 patients with strongyloidiasis, of whom 48 had disseminated strongyloidiasis for 0.9% prevalence of disseminated disease. Systemic connective tissue disorders, pulmonary eosinophilia, liver cirrhosis, blood disorders (monoclonal gammopathy, aplastic anemia, and lymphoid malignancy), malnutrition, alcohol use disorder, and transplantation status were frequent in patients with disseminated disease. Mortality was significantly higher in people with disseminated disease at 30 days (21%). The 90-day risk of hospitalization, bacteremia, and acute respiratory distress syndrome (ARDS) was higher in those with disseminated infection. People with disseminated strongyloidiasis had a heightened risk of hospitalization, bacteremia, acute respiratory distress syndrome, and mortality. The population at risk for severe strongyloidiasis infection is evolving, reflecting conditions in which glucocorticoids or additional immunosuppressive medications are commonly used for treatment.