Approximately one-third of patients with early psychosis disengage from services before the end of treatment. We sought to understand patient and family perspectives on early psychosis intervention (EPI) service engagement and use these findings to elucidate factors associated with early disengagement, defined as dropout from EPI in the first 9 months. Patients aged 16-29 referred to a large EPI program between July 2018-February 2020 and their family members were invited to complete a survey exploring facilitators and barriers to service engagement. A prospective chart review was conducted for 225 patients consecutively enrolled in the same EPI program, receiving the NAVIGATE model of coordinated specialty care, between July 2018-May 2019. We conducted a survival analysis, generating Kaplan-Meier curves depicting time to disengagement and Cox proportional hazards models to determine rate of disengagement controlling for demographic, clinical, and program factors. The survey was completed by 167 patients and 79 family members. The top endorsed engagement facilitator was related to the therapeutic relationship in both patients (36.5%) and families (43.0%). The top endorsed barrier to engagement was medication side effects in both patients (28.7%) and families (39.2%). In Cox proportional hazards models, medication nonadherence (HR = 2.37, 95% CI = 1.17-4.80) and use of individual psychotherapy (HR = .460, 95% CI = 0.220-0.962) were associated with early disengagement, but some of the health equity factors expected to affect engagement were not. Findings suggest that delivery of standardized treatment may buffer the effects of health disparities on service disengagement in early psychosis.

Timely and comprehensive treatment in the form of early psychosis intervention (EPI) has become the standard of care for youth with psychosis. While EPI services were designed to be delivered in person, the COVID-19 pandemic required many EPI programs to rapidly transition to virtual delivery, with little evidence to guide intervention adaptations or to support the effectiveness and satisfaction with virtual EPI services.

No abstract available

Lymphocytes are some of the most motile cells of vertebrates, constantly navigating through various organ systems. Their specific positioning in the body is delicately controlled by site-specific directional cues such as chemokines. While it has long been suspected that an intrinsic molecular pilot, akin to a ship's pilot, guides lymphocyte navigation, the nature of this pilot is unknown. Here we show that the TIPE (TNF-α-induced protein 8-like) family of proteins pilot lymphocytes by steering them toward chemokines. TIPE proteins are carriers of lipid second messengers. They mediate chemokine-induced local generation of phosphoinositide second messengers, but inhibit global activation of the small GTPase Rac. TIPE-deficient T lymphocytes are completely pilot-less: they are unable to migrate toward chemokines despite their normal ability to move randomly. As a consequence, TIPE-deficient mice have a marked defect in positioning their T lymphocytes to various tissues, both at the steady-state and during inflammation. Thus, TIPE proteins pilot lymphocytes during migration and may be targeted for the treatment of lymphocyte-related disorders.

Health systems worldwide are facing shortages in health professional workforce. Several studies have demonstrated the direct correlation between the availability of health workers, coverage of health services, and population health outcomes. To address this shortage, online eLearning is increasingly being adopted in health professionals' education. To inform policy-making, in online eLearning, we need to determine its effectiveness.

Metabolic syndrome (MetS) has been proposed as a clinically identifiable high-risk state for the prediction and prevention of cardiovascular diseases and type 2 diabetes mellitus. As a promising "omics" technology, metabolomics provides an innovative strategy to gain a deeper understanding of the pathophysiology of MetS. The study aimed to systematically investigate the metabolic alterations in MetS and identify biomarker panels for the identification of MetS using machine learning methods.

For some people, COVID-19 infection leads to negative health impacts that can last into the medium or long term. The long-term sequelae of COVID-19 infection, or 'long COVID', negatively affects not only physical health, but also mental health, cognition or psychological well-being. Complex, integrated interventions are recommended for long COVID, including psychological components; however, the effectiveness of such interventions has yet to be critically evaluated. This protocol describes a systematic review to be conducted of scientific literature reporting on clinical trials of interventions to promote mental health, cognition or psychological well-being among individuals with long COVID.

Current recommendations for physical exercise include information about the frequency, intensity, type, and duration of exercise. However, to date, there are no recommendations on what time of day one should exercise. The aim was to perform a systematic review with meta-analysis to investigate if the time of day of exercise training in intervention studies influences the degree of improvements in physical performance or health-related outcomes.

Angiogenic growth mediators (AGMs) and oxidative stress (OS) both play essential roles in normal placental vascular development and as such, placental alterations in these factors contribute to pre-eclampsia (PE). Suboptimal health status (SHS), an intermediate between health and disease, has been associated with imbalanced AGMs and OS biomarkers. Thus, SHS pregnant women may be at increased risk of developing PE and may present abnormal placental alteration and expression of AGMs and OS compared to optimal health status (OHS) pregnant women. We examined the histopathological morphology, immunohistochemical expression of AGMs antibodies and oxidative DNA damage marker in the placentae of SHS and OHS pregnant women who developed early-onset PE (EO-PE) and late-onset (LO-PE) compared to normotensive pregnancy (NTN-P).

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.

The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 along with its high number of mutations in the spike gene has raised alarm about the effectiveness of current medical countermeasures. To address this concern, we measured neutralizing antibodies against Omicron in three important settings: (1) post-vaccination sera after two and three immunizations with the Pfizer/BNT162b2 vaccine, (2) convalescent sera from unvaccinated individuals infected by different variants, and (3) clinical-stage therapeutic antibodies. Using a pseudovirus neutralization assay, we found that titers against Omicron were low or undetectable after two immunizations and in most convalescent sera. A booster vaccination significantly increased titers against Omicron to levels comparable to those seen against the ancestral (D614G) variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. Only three of 24 therapeutic antibodies tested retained their full potency against Omicron and high-level resistance was seen against fifteen. These findings underscore the potential benefit of booster mRNA vaccines for protection against Omicron and the need for additional therapeutic antibodies that are more robust to highly mutated variants.

While nearly half of all new psychotic disorders are diagnosed in the emergency department (ED), most young people who present to the ED with psychosis do not receive timely follow-up with a psychiatrist, and even fewer with evidence-based early psychosis intervention (EPI) services. We aim to test an intervention delivered using short message service (SMS), a low-cost, low-complexity, youth-friendly approach, to improve transitions from the ED to EPI services.

We investigated whether in human head and neck squamous cell carcinoma (HNSCC) high levels of expression of stress keratin 17 (K17) are associated with poor survival and resistance to immunotherapy.

To determine whether the female gender is a barrier for the access to cataract surgery services in South Asia in the last two decades.

Brain-computer interface (BCI) technology aims to help individuals with disability to control assistive devices and reanimate paralyzed limbs. Our study investigated the feasibility of an electrocorticography (ECoG)-based BCI system in an individual with tetraplegia caused by C4 level spinal cord injury. ECoG signals were recorded with a high-density 32-electrode grid over the hand and arm area of the left sensorimotor cortex. The participant was able to voluntarily activate his sensorimotor cortex using attempted movements, with distinct cortical activity patterns for different segments of the upper limb. Using only brain activity, the participant achieved robust control of 3D cursor movement. The ECoG grid was explanted 28 days post-implantation with no adverse effect. This study demonstrates that ECoG signals recorded from the sensorimotor cortex can be used for real-time device control in paralyzed individuals.

Human respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015-2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A (RSV-A) was the predominant subgroup during this research period except in 2016. Totally, 535 sequences of the second hypervariable region (HVR-2) of the G gene were obtained. Combined with 182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1 (512), NA1 (6) and GA5 (3), respectively; while 196 RSV-B sequences fell in BA9 (193) and SAB4 (3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258Q and H266L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than 10%, while the sequences with T290I and T312I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites (296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015-2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

Utilization of somatic healthcare services is highly predictive of the development of chronic physical illnesses and increased mortality risks. The objective of this study was to assess the differences in healthcare utilization among patients with schizophrenia spectrum disorders (SSD), major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) and the general population in Croatia.

The myeloid differentiation factor 2 (MD-2)-related lipid-recognition protein is involved in immune responses through recognizing bacteria lipopolysaccharide in mammals, arthropods and plants. However, the physiological roles of MD-2 in other biological processes are largely unknown. Here, we identified three homologue MD-2 genes (NlML1, NlML2 and NlML3) by searching the genome and transcriptome databases of the brown planthopper Nilaparvata lugens, a hemipteran insect species. Temporospatial analysis showed that the NlML1 gene was highly expressed in the fat body but much less so in the other tissues, while the NlML2 and NlML3 genes were highly expressed in the testis or digestive tract. RNA interference-mediated depletion of the NlML1 gene significantly downregulated the transcription of numerous integument protein genes. The NlML1 knockdown led to moulting failure and mortality at the nymph-adult transition phase, impaired egg laying and hatching, and reduced 20-hydroxyecdysone (20E) production in the nymphs. 20E could rescue the deficient moulting phenotypes derived from dsNlML1 RNAi. These novel findings indicate that NlML1 is required for nymphal moulting and female reproductive success as it plays an important role in regulating 20E synthesis, lipid and chitin metabolisms in N. lugens, thus contributing to our understanding of developmental and reproductive mechanisms in insects.

Disturbed sleep represents a potentially important modifiable risk factor for the development of depression in children and youth. This protocol for a systematic review proposes to investigate whether insomnia and/or sleep disturbances predict child and youth depression in community and clinical-based samples.