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.

Bi-allelic PRRT2 variants may predispose to Self-limited Familial Infantile Epilepsy.

Heterozygous PRRT2 variants are frequently implicated in Self-limited Infantile Epilepsy, whereas homozygous variants are so far linked to severe presentations including developmental and epileptic encephalopathy, movement disorders, and intellectual disability. In a study aiming to explore the genetics of epilepsy in the Sudanese population, we investigated several families including a consanguineous family with three siblings diagnosed with self-limited infantile epilepsy. We evaluated both dominant and recessive inheritance using whole exome sequencing and genomic arrays. We identified a pathogenic homozygous splice-site variant in the first intron of PRRT2 [NC_000016.10(NM_145239.3):c.-65-1G > A] that segregated with the phenotype in this family. This work taps into the genetics of epilepsy in an underrepresented African population and suggests that the phenotypes of homozygous PRRT2 variants may include milder epilepsy presentations without movement disorders.

Factors impacting quality of life in multiple system atrophy.

Background: Multiple system atrophy (MSA) is an atypical parkinsonian disorder marked by autonomic dysfunction, parkinsonism, cerebellar dysfunction, and poor response to dopaminergic medications such as levodopa. Patient-reported quality of life is an important benchmark for clinicians and clinical trials. The Unified Multiple System Atrophy Rating Scale (UMSARS) allows healthcare providers to rate and assess MSA progression. The MSA-QoL questionnaire is a health-related quality of life scale intended to provide patient-reported outcome measures. In this article, we investigated inter-scale correlations between the MSA-QoL and UMSARS to determine factors impacting the quality of life of patients with MSA. Methods: Twenty patients at the Johns Hopkins Atypical Parkinsonism Center's Multidisciplinary Clinic with a diagnosis of clinically probable MSA and who filled out the MSA-QoL and UMSARS questionnaires within 2 weeks of each other were included. Inter-scale correlations between MSA-QoL and UMSARS responses were examined. Linear regressions were also performed to examine relationships between both scales. Results: Significant inter-scale correlations were found between the MSA-QoL and UMSARS, both between MSA-QoL total score and UMSARS Part I subtotal scores and for individual scale items. There were no significant correlations between MSA-QoL life satisfaction rating and UMSARS subtotal scores or any specific UMSARS items. Linear regression analysis found significant associations between MSA-QoL total score and UMSARS Part I and total scores, and between MSA-QoL life satisfaction rating and UMSARS Part I, Part II, and total scores (after adjustment for age). Conclusions: Our study demonstrates significant inter-scale correlations between MSA-QoL and UMSARS, particularly relating to activities of daily living and hygiene. MSA-QoL total score and UMSARS Part I subtotal scores, which assess patients' functional status, were significantly correlated. The lack of significant associations between MSA-QoL life satisfaction rating and any UMSARS item suggests there may be aspects to quality of life that are not fully captured by this assessment. Larger cross-sectional and longitudinal analyses utilizing UMSARS and MSA-QoL are warranted and modification of the UMSARS should be considered.

Value of acute neurovascular imaging in patients with suspected transient ischemic attack.

PURPOSE: Acute neurovascular imaging including MRA and/or CTA are routinely performed in the emergency departments (ED) for patients who present with suspected transient ischemic attacks (TIA). Given the current emphasis on mitigating the rising cost of health care nationally, and promoting high value practice, we sought to determine 1) the value of acute neurovascular imaging in patients presenting to the ED with TIA-like symptoms, and 2) whether these neurovascular studies led to a difference in management strategies. METHOD: We retrospectively reviewed 398 ED patients who presented with transient neurological deficits and underwent neurovascular imaging from 2015 to 2018. We reviewed diffusion weighted imaging (DWI) and neurovascular results by patient demographics, baseline risk factors, final diagnosis, treatment/management dispositions and three-month follow-up. RESULTS: 28.1% (112/398) of patients were diagnosed with true TIA, whereas 71.9% patients were deemed to have a non-vascular etiology. Total rates of positive MRA/CTA for severe intracranial (>50%) and cervical vessel (>70%) stenosis were 10.5% and 1.7%. Patients with positive DWI scans had significantly higher rates of severe vascular stenosis (24.4% versus 7.8% intracranially and 2.4% versus 0.9% in the neck) compared to those with negative DWI scans. All patients were treated with multi-pronged medical therapies with no immediate surgical intervention. A follow-up stroke was equally likely in TIA patients with or without severe vascular stenosis. CONCLUSIONS: In patients presenting with TIA-like symptoms and DWI negative scans, the overall rate of positive neurovascular studies is very low. Triaging with DWI can reduce the frequency of unnecessary neurovascular imaging.

A Qualitative Exploration of Gaps and Challenges in Knowledge and Practices of Electroconvulsive Therapy by Key Personnel in Public and Private Mental Health Units in Kenya.

Background: Evidence-based research for electroconvulsive therapy (ECT) practice in Kenya is scarce. This has seemingly stifled knowledge with regard to ECT practice among key personnel in the country. Research shows that evidence-based guidelines not only harmonize clinical practice in a certain region but also improve health outcomes and quality of clinical decisions made by key personnel. This study aimed at assessing knowledge and administration of ECT by key personnel in psychiatric units in Kenya. Method: This is a qualitative study targeting multiple stakeholders in mental health facilities. The study was undertaken in three counties: Nairobi, Nakuru and Eldoret. Snowballing sampling method was used to interview 33 targeted respondents who work in ECT departments or actively interacted with the procedure in both private and public facilities. Researcher-designed respondent profile questionnaire and interview guides focusing on knowledge, practice and barriers in delivery of ECT were used as tools. Data collected were transcribed from the audio recordings. Thematic and content analyses of these semi-structured interviews were carried out based on the patterns that were noted across the data collected. The interviews were read by the research team and re-read to highlight the core ideas. Findings were presented in form of themes, which were illustrated along with representative verbatim quotations. Results: Overall, the key personnel were knowledgeable about ECT in different stages of the procedure, but we noticed methodological incongruence in their practice with regard to the pre-ECT preparation, stimulus dose calculation adequacy of seizure and in the procedure for dose adjustment of psychotropic medication before and after ECT sessions. The identified barriers to the uptake of evidence-based practice were lack of infrastructure, inadequate funding, lack of adequate training and negative perception by patients, relatives and even some participants. Conclusion: Though key personnel in this study showed that they had knowledge on ECT administration, lack of standard guidelines on ECT practice led to lack of standardized training on the procedure hence the methodological incongruence. Inadequate infrastructure, knowledge and negative perception towards the procedure seemed to interfere with uptake of ECT as an intervention. Recommendations: The study makes the following recommendations: adoption of a guideline by psychiatrists, intense training on ECT, specialized training for nurses in ECT and dose calculation for psychiatrists and registrars. Funding should be made available for new ECT machines. Lastly, education and awareness creation should be done about ECT to help deal with negative perception towards the intervention.

Evaluation of poly-aromatic hydrocarbons (PAHs) in the aquatic species of Suez Gulf water along El-Sokhna area to the Suez refineries.

The Egyptian Red Sea environment especially along El-Sokhna area to the Suez refineries (Suez) is severely contaminated with organic compounds, as well as overfishing. This may be well contributory to recent serious declines in fish stocks. Fish embryos are also particularly vulnerable to oil exposure, even at extremely low concentrations of less than one part per billion. Consequently, even traces of oil pollution at levels often considered safe for wildlife can cause severe damage to fish. Sixteen polycyclic aromatic hydrocarbons (PAHs) were investigated in ten fish species of aquatic species by high performance liquid chromatography (HPLC). The compositions of PAHs determined in all samples were measured in order to use them as chemical markers for identifying different sources of PAH pollutants in the studied region. The total content of these16 PAHs ranged from 399.616 up to 67,631.779 ng/g wet weight. The data show that these values are considered to be alarmingly high enough to cause lethal toxicity effect by accumulation. All studied aquatic species samples are characterized by relatively high concentrations of the six-membered ring PAHs. The origin of PAHs in the collected samples is either petrogenic, biogenic, or mixed petrogenic and biogenic.

The safety profile and acceptability of a disposable male circumcision device in Kenyan men undergoing voluntary medical male circumcision.

PURPOSE: We established the safety and effectiveness as well as the acceptability of the Alisklamp® device for male circumcision among Kenyan men. MATERIALS AND METHODS: To qualify for this hospital based, prospective, interventional cohort study one needed to be an uncircumcised adult male who was HIV negative with no comorbid factors or genitourinary anomalies precluding circumcision. A total of 58 men were recruited from a population of 90. Outcome measures were the safety profile of Alisklamp and its efficiency and acceptability by participants. RESULTS: All 58 procedures were completed without device malfunction, hemorrhage or undesirable preputial excision. Mean ± SD procedure time was 2.43 ± 1.36 minutes and mean device removal time was 15.8 ± 7.4 seconds. There were 2 adverse events, including mild edema and superficial wound infection related to poor hygiene in 1 case each. All men resumed routine activity immediately after circumcision. Of the 58 participants 25.9% experienced mild nocturnal erectile pains that required no medication. During 6-week followup all men were satisfied with the procedure, tolerated the device well and would recommend it to a friend. CONCLUSIONS: Alisklamp has an excellent safety profile and excellent acceptability among men who undergo circumcision using the device. This technique is easy to teach and it would prove to be a handy device to scale up the rate of male circumcision. Based on these findings the device merits a comparative clinical trial.