Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as 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-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel 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 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, physiologic, 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.

Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway.

Dengue virus (DENV) belongs to the family Flaviviridae and can cause major health problems worldwide, including dengue fever and dengue shock syndrome. DENV replicon in human cells inhibits interferon α and ß with the help of its non-structural proteins. Non-structural protein 5 (NS5) of DENV is responsible for the proteasome-mediated degradation of signal transducer and activator of transcription (STAT) 2 protein, which has been implicated in the development of resistance against interferon-mediated antiviral effect. This degradation of STAT2 primarily occurs with the help of E3 ubiquitin ligases. Seven in absentia homologue (SIAH) 2 is a host protein that can mediate the ubiquitination of proteins and is known for its interaction with NS5. In this study, comprehensive computational analysis was performed to characterize the protein-protein interactions between NS5, SIAH2, and STAT2 to gain insight into the residues and sites of interaction between these proteins. The objective of the study was to structurally characterize the NS5-STAT2, SIAH2-STAT2, and NS5-SIAH2 interactions along with the determination of the possible reaction pattern for the degradation of STAT2. Docking and physicochemical studies indicated that DENV NS5 may first interact with the host SIAH2, which can then proceed towards binding with STAT2 from the side of SIAH2. These implications are reported for the first time and require validation by wet-lab studies.

Cell membrane enveloped polymeric nanosponge for detoxification of chlorpyrifos poison: In vitro and in vivo studies.

Organophosphates are highly toxic compounds as they are involved in irreversible inhibition of acetylcholinesterase, causing various neurotoxic effects via acetylcholine accumulation throughout the nervous system. Traditional treatments for organophosphate poisoning are not effective enough to overcome all the toxic effects. There is a need for alternate treatment of life threatening poisoning of organophosphates. For this purpose a biomimetic nanosponge of poly (lactic-co-glycolic acid) is prepared, characterized and analysed as an antidote for organophosphate poisoning. In this nanosponge red blood cell membranes are used for coating poly lactic co-glycolic acid nanoparticles. In vitro studies are conducted to investigate the retention of acetylcholinesterase activity on the prepared nanosponge as well as to assess the scavenging ability of prepared nanosponge for model organophosphate, chlorpyrifos. In vivo studies are conducted to evaluate the detoxification potential of nanosponge in rabbit model, poisoned with chlorpyrifos. Hepatotoxicity and renal toxicity of nanosponge/chlorpyrifos complex is also studied in survived rabbits and the data is analysed statistically.

Synthesis, characterization and properties of novel polyamides derived from 4 4' bis(4-carboxy methylene) biphenyl and various diamines.

Novel aromatic aliphatic diacid monomer, 4 4' bis(4-carboxy methylene) biphenyl was synthesized via friedel craft acylation with acetic anhydride followed by willgerodot reaction and used in the preparation of polyamides by direct polycondensation using the Yamazaki phosphorylation reaction with commercial aromatic diamines. These polyamides were obtained in good yield with moderate-to-high-molecular-weight build up as evidenced by inherent viscosities in the range of 0.52-0.96 dlg-1. The XRD studies showed that all the polyamides were amorphous in nature and these polymers dissolved in polar aprotic solvents such as N-methyl-2-pyrrolidone(NMP),N,N-dimethylsulfoxide(DMSO), N,N-dimethyl formamide (DMF) and N,N-dimethyl acetamide. The resulting polyamides were characterized by inherent viscocity measurements, FT-IR, 1H NMR and 13C NMR spectroscopy, solubility, thermogravimetry, X-ray diffraction studies. These polyamides had glass transition temperatures between 210°C and 261°C, and their temperatures at a 10% weight loss were 620 to 710°C and 497 to 597°C in nitrogen and air atmospheres, respectively, which indicates thermally stable polymers.

Intravenous sedation in accident and emergency departments: a nationwide survey.

Anonymous questionnaires regarding the practice of intravenous sedation were sent to all accident and emergency departments in England and Wales. The response rate was 63%. Intravenous sedation was used by 94% of the departments who replied. In 19% of these departments it was administered only by middle grade or senior grade clinicians, while in the remaining 81% sedation was also administered by junior grade clinicians. Diazepam, midazolam and opioids were the most commonly used agents. The use of monitoring was variable. In 16% of the units no monitoring was used routinely. ECG monitoring was carried out by 48% of the departments, non-invasive blood pressure monitoring by 67% and pulse oximetry by 65%. Our findings indicate there is a need for guidelines regarding patient selection, the choice of drugs and the monitoring of patients.

Eye tracking disturbances in schizophrenia.

PURPOSE: To study the frequency of different types of eye tracking disturbances in schizophrenia. MATERIALS AND METHODS: Smooth pursuit eye movements were studied by electro-oculography (EOG) in 22 schizophrenic patients (ICD-10 criteria) and 15 age and sex-matched controls. The studied parameters included average pursuit gain, number of saccades, the frequency of different types of saccades (catch-up, back-up, anticipatory saccades), and disturbances during fixation. The results were analysed statistically. RESULTS: The average pursuit gain was significantly affected in patients for target velocity of 30 degrees/sec (p = 0.007). The catch-up and back-up saccades were more common in cases than controls but the difference was not significant (p = 0.39 and 0.36 respectively). The anticipatory saccades were significantly more frequent in cases than controls (p < 0.0001) for both 15 degrees/sec and 30 degrees/sec target velocities. This was also correlated with the duration of illness. CONCLUSION: Anticipatory saccades are significantly more frequent during eye tracking in schizophrenia and appear to be an objective marker for the disease.

Eye tracking disturbances in schizophrenia.

PURPOSE: To study the frequency of different types of eye tracking disturbances in schizophrenia. MATERIALS AND METHODS: Smooth pursuit eye movements were studied by electro-oculography (EOG) in 22 schizophrenic patients (ICD-10 criteria) and 15 age and sex-matched controls. The studied parameters included average pursuit gain, number of saccades, the frequency of different types of saccades (catch-up, back-up, anticipatory saccades), and disturbances during fixation. The results were analysed statistically. RESULTS: The average pursuit gain was significantly affected in patients for target velocity of 30 degrees/sec (p = 0.007). The catch-up and back-up saccades were more common in cases than controls but the difference was not significant (p = 0.39 and 0.36 respectively). The anticipatory saccades were significantly more frequent in cases than controls (p < 0.0001) for both 15 degrees/sec and 30 degrees/sec target velocities. This was also correlated with the duration of illness. CONCLUSION: Anticipatory saccades are significantly more frequent during eye tracking in schizophrenia and appear to be an objective marker for the disease.