Molecular and physiological changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match those of long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiological and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Fagopyrin F fraction from Fagopyrum tataricum demonstrates photodynamic inactivation of skin infecting bacterium and squamous cell carcinoma (A431) cells.

Photodynamic therapy (PDT) stands out as a noteworthy development as an alternative targeted treatment against skin ailments. While PDT has advanced significantly, research into photo-activatable "Green drugs" derived from plants which are less toxic than the synthetic drugs has not kept pace. This study investigates the potential of Fagopyrin F Containing Fraction (FCF) derived from Fagopyrum tataricum in mediating PDT against Staphylococcus aureus and skin cancer cells (A431). FCF was isolated from the plant extract using thin-layer chromatography, followed by identification of the compound through high-performance liquid chromatography and high-resolution liquid chromatography-mass spectrometry. FCF was tested to determine its antibacterial and anticancer efficacy. Results revealed that FCF-mediated PDT exhibited potent action against S. aureus, significantly reducing bacterial viability (MIC 19.5 µg/100 µL). Moreover, FCF-mediated PDT showed good efficacy against A431 cells, resulting in a notable reduction in cell viability (IC50 29.08 µg/mL). Given the known association between S. aureus and squamous cell carcinoma (SCC), FCF shows the potential to effectively target and eradicate both SCC and the related S. aureus present within the lesions. In silico study reveals that Fagopyrin F effectively binds with the epidermal growth factor (EGFR), one among the highly expressed proteins in the A431 cells, with a binding energy of - 9.6 kcal/mol. The affinity of Fagopyrin F for EGFR on A431 cancer cells along with its cytotoxicity against skin cancer cells while safeguarding the normal cells (L929) plays a major part in the way it targets cancer cells. However, its safety, efficacy, and long-term advantages in treating skin conditions require more investigation, including in vivo investigations and clinical trials.

InCl3 catalyzed simultaneous reductive sulfoximination and O-silylation: synthesis of silyloxy benzylsulfoximine.

This article describes the synthesis of ortho-silyloxy benzylsulfoximine via the reaction of salicylaldehyde and sulfoximine in the presence of silane and InCl3. The steps include simultaneous reductive sulfoximination and an O-silylation process. To the best of our knowledge, this is the first report of this kind of reaction, where both reductive amination (here sulfoximination) and O-silylation occur concurrently.

Facile synthesis of N-(α-furanyl) alkyl sulfoximines via gold catalyzed Michael addition/cyclization of enynones and sulfoximines.

Herein, we prepare a new array of N-(α-furanyl) alkyl sulfoximines via a gold catalyzed reaction of enynone with sulfoximine in moderate to very good yields. The reaction involves Michael addition of sulfoximine to enynone, followed by intramolecular cyclization. The presence of two chiral centres led to the formation of a mixture of diastereomers approximately in a 1 : 1 ratio. The salient features of the protocol include broad substrate scope, high efficiency and high yields. The synthetic utility of the protocol is explored using Suzuki-Miyaura cross-coupling and mild, metal-free opening of the furan ring.

Assessment of cyclone risk and case study of Gaja cyclone using GIS techniques and machine learning algorithms in coastal zone of Tamil Nadu, India.

Cyclones can cause devastating impacts, including strong winds, heavy rainfall, storm surges, and flooding. The aftermath includes infrastructure damage, loss of life, displacement of communities, and ecological disruptions. Timely response and recovery efforts are crucial to minimize the socio-economic and environmental consequences of cyclones. To accelerate the time-consuming risk assessment process, particularly in geographically diverse regions, a blend of multi-criteria decision-making and machine learning models was utilized. This novel approach swiftly assessed cyclone risk and the impact of the Gaja cyclone in Nagapattinam, India. The method involved assigning weights to distinct criteria, unveiling notable vulnerability aspects like elevation, slope, proximity to the coast, distance from cyclone tracts, Lu/Lc, population density, proximity to cyclone shelters, household density, accessibility to healthcare facilities, NDVI, and levels of awareness. Daddavari, Ettugudi, Kodikarai, Vedharanyam, Velankanni, and Thirupoondi face high/extreme cyclone risk. Nagore, Nagapattinam, Pillai, Enangudi, and Sannanllur have low/no threat. To further enhance the precision of the study, machine learning algorithms like SVM, SAM, and MLC were deployed. These models were instrumental in generating pre- and post-cyclone land use maps. The influence of Gaja cyclones effects shows decreasing of agriculture land from 34% to 30%, aquaculture increase 1%, barren land decrease from 8% to 6%, Built-up land decrease from 15% to 13%, land with scrub and salt pan also decrease from 21% to 17% and 10%-8%. Mostly effect of Gaja cyclone is dramatic increase of water body from 8% to 21%. Conducting cyclone risk zone analysis and pre/post-cyclone Land Use Land Cover (LULC) detection in Nagapattinam offers valuable insights for disaster preparedness, infrastructure planning, and climate resilience. This study can enhance understanding of vulnerability and aid in formulating strategies to mitigate cyclone impacts, ensuring sustainable development in the region.

Palmoplantar Pustulosis: Therapy Update.

Palmoplantar pustulosis is a variant of psoriasis and a chronic skin disorder in which pruritic pustular eruptions appear on the palms and soles. It is thought to arise from a variety of genetic and environmental factors, is limited in prevalence, and has proven quite difficult to treat. The symptoms it inflicts on those affected are quite debilitating and the treatment landscape is constantly evolving, thus emphasizing the need for updates of the literature as time passes. Current treatments include topical agents, oral therapies, and phototherapy, amongst other treatments. In this systemic review, we explore newer literature from 2015 to 2022 on various treatment regimens for palmoplantar pustulosis. J Drugs Dermatol. 2024;23(8):626-631.     doi:10.36849/JDD.doi:10.36849/7612R1.

The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. METHODS: Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array. RESULTS: Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1ß, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = -0.55), sTNFR1 (r = -0.352) and IL-6 (r = -0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05. CONCLUSIONS: Pain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.

Pressure Injuries: Prevention, Evaluation, and Management.

Pressure injuries are localized damage to skin or soft tissue. They commonly occur over bony prominences and often present as an intact or open wound. Pressure injuries are common and costly, and they significantly impact patient quality of life. Comprehensive skin assessments are crucial for evaluating pressure injuries. Staging of pressure injuries should follow the updated staging system of the National Pressure Injury Advisory Panel. Risk assessments allow for appropriate prevention and care planning, and physicians should use a structured, repeatable approach. Prevention of pressure injuries focuses on assessing and optimizing nutritional status, repositioning the patient, and providing appropriate support surfaces. Treatment involves pressure off-loading, nutritional optimization, appropriate bandage selection, and wound site management. Pressure injuries and surrounding areas should be cleaned, with additional debridement of devitalized tissue and biofilm if necessary. All injuries should be monitored for local infection, biofilms, and osteomyelitis. Appropriate wound dressings should be selected based on injury stage and the quality and volume of exudate.

Non-REM Apnea and Hypopnea Duration Varies across Population Groups and Physiologic Traits.

Rationale: Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea-hypopnea index (AHI). Respiratory event duration is a heritable trait associated with mortality that may further characterize OSA.Objectives: We evaluated how hypopnea and apnea durations in non-REM (NREM) sleep vary across demographic groups and quantified their associations with physiological traits (loop gain, arousal threshold, circulatory delay, and pharyngeal collapsibility).Methods: Data were analyzed from 1,546 participants from the Multi-Ethnic Study of Atherosclerosis with an AHI ≥5. Physiological traits were derived using a validated model fit to the polysomnographic airflow signal. Multiple linear regression models were used to evaluate associations of event duration with demographic and physiological factors.Measurements and Main Results: Participants had a mean age ± SD of 68.9 ± 9.2 years, mean NREM hypopnea duration of 21.73 ± 5.60, and mean NREM apnea duration of 23.87 ± 7.44 seconds. In adjusted analyses, shorter events were associated with younger age, female sex, higher body mass index (P < 0.01, all), and Black race (P < 0.05). Longer events were associated with Asian race (P < 0.01). Shorter event durations were associated with lower circulatory delay (2.53 ± 0.13 s, P < 0.01), lower arousal threshold (1.39 ± 0.15 s, P < 0.01), reduced collapsibility (-0.71 ± 0.16 s, P < 0.01), and higher loop gain (-0.27 ± 0.11 s, P < 0.05) per SD change. Adjustment for physiological traits attenuated age, sex, and obesity associations and eliminated racial differences in event duration.Conclusions: Average event duration varies across population groups and provides information on ventilatory features and airway collapsibility not captured by the AHI.

Neighborhoods with Greater Prevalence of Minority Residents Have Lower Continuous Positive Airway Pressure Adherence.

Rationale: Limited data suggest racial disparities in continuous positive airway pressure (CPAP) adherence exist.Objectives: To assess whether CPAP adherence varies by neighborhood racial composition at a national scale.Methods: Telemonitoring data from a CPAP manufacturer database were used to assess adherence in adult patients initiating CPAP therapy between November 2015 and October 2018. Mapping ZIP code to ZIP code tabulation areas, age- and sex-adjusted CPAP adherence data at a neighborhood level was computed as a function of neighborhood racial composition. Secondary analyses adjusted for neighborhood education and poverty.Measurements and Main Results: Among 787,236 patients living in 26,180 ZIP code tabulation areas, the prevalence of CPAP adherence was 1.3% (95% confidence interval [CI], 1.0-1.6%) lower in neighborhoods with high (⩾25%) versus low (<1%) percentages of Black residents and 1.2% (95% CI, 0.9-1.5%) lower in neighborhoods with high versus low percentages of Hispanic residents (P < 0.001 for both), even after adjusting for neighborhood differences in poverty and education. Mean CPAP usage was similar across neighborhoods for the first 2 days, but by 90 days, differences in CPAP usage increased to 22 minutes (95% CI, 18-27 min) between neighborhoods with high versus low percentages of Black residents and 22 minutes (95% CI 17-27 min) between neighborhoods with high versus low percentages of Hispanic residents (P < 0.001 for both).Conclusions: CPAP adherence is lower in neighborhoods with greater proportions of Black and Hispanic residents, independent of education or poverty. These differences lead to a lower likelihood of meeting insurance coverage requirements for CPAP therapy, potentially exacerbating sleep health disparities.

ANETT: PhAse II trial of NEoadjuvant TAK-228 plus Tamoxifen in patients with hormone receptor-positive breast cancer.

INTRODUCTION: Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer. METHODS: In this single-arm, open-label trial, pre- and post-menopausal women were enrolled to receive neoadjuvant tamoxifen (20 mg daily) with TAK-228 (30 mg weekly) for 16 weeks prior to surgery. Patient had tissue sampling at baseline, week 6, and week 16. The primary endpoint was change in Ki-67 from baseline to 6 weeks. The toxicity, change in tumor size, pathologic complete response rate, PEPI score, and baseline Oncotype Dx score were also assessed. RESULTS: Twenty-eight women were enrolled on the trial, and 25 completed the entire study course. The combination of tamoxifen and TAK-228 resulted in a significant reduction in Ki-67 from 18.3 to 15.2% (p = 0.0023). The drug was also found to be safe and tolerable. While nausea and hyperglycemia were common side effects, these were manageable. The tumor size also significantly decreased with the treatment, with a median decrease of 0.75 cm (p < 0.0001). There were no pathologic complete responses. CONCLUSION: Tamoxifen and TAK-228 was safe and well tolerated neoadjuvant treatment for ER+ breast cancer, preliminary evidence of activity with significant reduction in both Ki-67 and tumor size, warranting further evaluation in a larger study.

Foreign Body Esophageal Perforation Leading to Multifocal Brain Abscesses: A Case Report.

BACKGROUND: Among those aged 5 years or younger, foreign bodies are the fourth most common pediatric exposure reported to the American Association of Poison Control Centers. Although the majority of ingested foreign bodies pass through the gastrointestinal tract without complication, those that do not spontaneously pass can lead to a number of serious complications, such as gastrointestinal obstruction or perforation, which can be complicated by bleeding from aortoesophageal fistula, secondary mediastinitis, peritonitis, esophageal or gastrointestinal fistula formation, and abscesses. CASE REPORT: We present the case of a 10-month-old child who presented with new-onset focal seizure in the setting of multiple brain abscesses, ultimately found to be due to esophageal perforation from a retained, metallic esophageal foreign body. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Foreign bodies that are retained for longer than 24 h after ingestion have been associated with a higher risk of complications because they are less likely to pass spontaneously through the gastrointestinal tract. Early identification and removal of foreign bodies is necessary to prevent subsequent complications. In patients who have a subacute history of cough, gagging, vomiting, and decreased oral intake with an otherwise unknown cause, foreign-body ingestion or aspiration should be considered. In addition, central nervous system abscess and infection should be considered in patients with concerns about previous foreign body ingestion or aspiration and who are newly presenting with fever, focal neurologic changes, and irritability.

The relationship between educational attainment and hiv prevalence among pregnant women attending antenatal clinics in six states of India: Sentinel surveillance from 2010 to 2017.

BACKGROUND: The National AIDS Control Programme provides support for HIV prevention services to pregnant women attending antenatal care (ANC) clinics through testing, kit delivery, counseling, and treatment services. The impact of HIV prevention programs in the general population is assessed by monitoring trends and progress made against the HIV epidemic among pregnant women attending ANC clinics during HIV Sentinel Surveillance (HSS). OBJECTIVES: This study explores the association of HIV risk with educational attainment for Indian women across different age groups from four repeated cross-sectional surveillance of antenatal clinics in six states from the southern part of India. METHODS: Data collected from the repeated cross-sectional HSS conducted during the year 2010-2011 (baseline) and 2016-2017 (end line) across six states were used for this analysis. The total sample size was 94,266 at baseline and 99,434 at end line. In the logistic regression analysis, we focused on identifying the association between educational attainment, and HIV prevalence adjusting for period effects across two age groups for women attending ANC clinics. RESULTS: The analysis showed an inverse association between education and HIV risk across different age groups. The age-segregated and survey period adjusted analysist showed that for older women (≥25 years), the HIV risk in 2010 ranged from 41% lower among 5th Grade to 80% lower among postgraduates than illiterates. For the <25 year age group, this risk of HIV for pregnant women was 35% to 49% lower. CONCLUSIONS: To ensure an effective national response to control and prevent HIV infection, policymakers in India need to focus on ≥25 years' age group of women attending ANC for designing educational interventions to reduce HIV risk as well as the prevention of mother-to-child transmission of HIV.

Cervical Ectopic Pregnancy: A Rare Site of Implantation.

BACKGROUND: Cervical ectopic pregnancies are rare, comprising < 1% of ectopic pregnancies, and life threatening if there is a delay in treatment or a misdiagnosis. CASE REPORT: This case report describes a presentation of cervical ectopic pregnancy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case report reviews nonsurgical and surgical treatment options for patients with cervical ectopic pregnancies.

Lymphotoxin ß receptor-mediated NFκB signaling promotes glial lineage differentiation and inhibits neuronal lineage differentiation in mouse brain neural stem/progenitor cells.

BACKGROUND: Lymphotoxin (LT) is a lymphokine mainly expressed in lymphocytes. LTα binds one or two membrane-associated LTß to form LTα2ß1 or LTα1ß2 heterotrimers. The predominant LTα1ß2 binds to LTß receptor (LTßR) primarily expressed in epithelial and stromal cells. Most studies on LTßR signaling have focused on the organization, development, and maintenance of lymphoid tissues. However, the roles of LTßR signaling in the nervous system, particularly in neurogenesis, remain unknown. Here, we investigated the role of LTßR-mediated NFκB signaling in regulating neural lineage differentiation. METHODS: The C57BL/6J wild-type and GFAP-dnIκBα transgenic mice were used. Serum-free embryoid bodies were cultured from mouse embryonic stem cells and further induced into neural stem/progenitor cells (NSCs/NPCs). Primary neurospheres were cultured from embryonic and adult mouse brains followed by monolayer culture for amplification/passage. NFκB activation was determined by adenovirus-mediated NFκB-firefly-luciferase reporter assay and p65/RelB/p52 nuclear translocation assay. LTßR mRNA expression was evaluated by quantitative RT-PCR and LTßR protein expression was determined by immunohistochemistry and Western blot analysis. Multilabeled immunocytochemistry or immunohistochemistry followed by fluorescent confocal microscopy and quantitative analysis of neural lineage differentiation were performed. Graphing and statistical analysis were performed with GraphPad Prism software. RESULTS: In cultured NSCs/NPCs, LTα1ß2 stimulation induced an activation of classical and non-classical NFκB signaling. The expression of LTßR-like immunoreactivity in GFAP+/Sox2+ NSCs was identified in well-established neurogenic zones of adult mouse brain. Quantitative RT-PCR and Western blot analysis validated the expression of LTßR in cultured NSCs/NPCs and brain neurogenic regions. LTßR expression was significantly increased during neural induction. LTα1ß2 stimulation in cultured NSCs/NPCs promoted astroglial and oligodendrocytic lineage differentiation, but inhibited neuronal lineage differentiation. Astroglial NFκB inactivation in GFAP-dnIκBα transgenic mice rescued LTßR-mediated abnormal phenotypes of cultured NSCs/NPCs. CONCLUSION: This study provides the first evidence for the expression and function of LTßR signaling in NSCs/NPCs. Activation of LTßR signaling promotes glial lineage differentiation. Our results suggest that neurogenesis is regulated by the adaptive immunity and inflammatory responses.