Effect of national cultural dimensions and HIV prevalence rates on stigma towards people living with HIV/AIDS.

This paper examines the main and interactive effects of national culture dimensions and HIV prevalence rates on stigma towards people living with HIV/AIDS (PLHIVA). We examined these various relationships using data from a sample of 68,041 individuals from 49 countries, obtained from the World Values Survey. We used Hierarchical Linear Modeling to conduct our cross-level analyses. Our results indicated that collectivistic societies were positively associated while egalitarian and performance-oriented societies were negatively associated with stigma towards PLHIVA. Additionally, HIV prevalence rates interact with several cultural dimensions to worsen stigma towards PLHIVA. Our findings indicate the need to tailor stigma reduction strategies by taking the national culture dimensions of a given society into consideration when designing and implementing programs.

High Prevalence of Vaccine-Type Infections Among Children with Pneumococcal Pneumonia and Effusion After 13-Valent Pneumococcal Conjugate Vaccine Introduction in the Dominican Republic.

BACKGROUND: In 2013, the Dominican Republic introduced 13-valent pneumococcal conjugate vaccine (PCV13) using a 3-dose schedule (at 2, 4 and 12 months of age). We evaluated the impact of PCV13 on serotypes causing pneumococcal pneumonia with pleural effusion. METHODS: Surveillance data after PCV13 introduction (July 2014 to June 2016) were compared with data before PCV13 introduction (July 2009 to June 2011). Cases were defined as radiologic evidence of pneumonia with pleural effusion in a child aged <15 years. Pneumococcus was detected in pleural fluid by either culture or polymerase chain reaction, and serotyping was performed. The Ministry of Health's PCV13 uptake data for 2014-2016 were obtained. RESULTS: The prevalence of pneumococcus among cases was similar before and after PCV13 introduction (56.4% and 52.8%, respectively). The proportion of pneumococcal cases caused by vaccine serotypes was 86% for children <2 years old both before and PCV13 introduction. Compared with before PCV13, serotype 14 accounted for a smaller (28% vs 13%, respectively; P = .02) and serotype 1 for a larger (23% vs 37%; P = .09) proportion of pneumococcal cases after PCV13 introduction. National uptake for the first, second, and third PCV13 doses was 94%, 81%, and 28%, respectively, in 2014 and 75%, 61%, and 26% in 2015. DISCUSSION: While the decrease in pneumococcal pneumonia with pleural effusion caused by serotype 14 may reflect an early effect of PCV13 implementation, other vaccine serotypes, including serotype 1, are not well controlled. Better PCV13 coverage for all 3 doses is needed.

Modulation of Heart and Brain Function by Surah Al-Rehman Recitation Among Distressed Diabetic Patients in Pakistan.

Distress causes psychophysiological alterations that affect autonomic function. The current study explores psychophysiological modulation in diabetic distress in response to Surah Al-Rehman recitation. A single-group experimental study with before and after intervention assessments was conducted during April 2018 to February 2019 in which participants (n = 10) listened to Surah Al-Rehman recitation. Blood pressure, blood glucose, cortisol, ECG and EEG were recorded before and after recitation. Significant reduction in systolic blood pressure, increase in low frequency and absolute alpha power at Fp2 were observed. Heartbeat evoked potentials (HEP) were also significantly modulated at Fp1, Fp2 and F4. These findings suggest that Surah Al-Rehman modulated baroreflex activity thereby reducing sympathetic activity and improved heart brain coherence as reflected by HEP.

Evaluation of Test to Stay Strategy on Secondary and Tertiary Transmission of SARS-CoV-2 in K-12 Schools - Lake County, Illinois, August 9-October 29, 2021.

The COVID-19 pandemic has resulted in school closures and reduction of in-person learning (1). In August 2021, the Lake County Health Department (LCHD) in Illinois introduced a Test to Stay (TTS) strategy, whereby unvaccinated students, teachers, and staff members with certain school-related COVID-19 exposures could remain in school and participate in school-related extracurricular activities. Eligibility to participate in TTS required the following conditions to be met: 1) the exposure occurred while both the person with COVID-19 (index patient) and the close contact were masked; 2) the close contact remained asymptomatic, practiced consistent mask wearing, and maintained physical distancing; and 3) the close contact underwent testing for SARS-CoV-2 (the virus that causes COVID-19) on days 1, 3, 5, and 7 after exposure to the index patient. LCHD permitted kindergarten through grade 12 (K-12) schools in Lake County to implement TTS; 90 schools, representing 31 school districts in Lake County, implemented TTS during August 9-October 29, 2021. During the implementation period, 258 COVID-19 cases were reported. Among 1,035 students and staff members enrolled in TTS, the secondary attack risk (number of close contacts who received a positive SARS-CoV-2 test result within 14 days after exposure to an index patient, divided by total number of close contacts) was 1.5% (16 of 1,035). Among the 16 secondary cases identified, all were in students, and none appeared to transmit SARS-CoV-2 to other school-based contacts. However, nine tertiary cases were identified among household contacts of the 16 secondary cases, and four of the nine were fully vaccinated. Assuming a maximum of 8 missed school days for every 10-day quarantine period, up to 8,152 in-person learning days were saved among TTS participants. Implementation of TTS with other concurrent prevention strategies, including masking and physical distancing, limited further spread of SARS-CoV-2 within K-12 schools and allowed students to safely sustain in-person learning. Although vaccination remains the leading public health recommendation to protect against COVID-19 for those aged ≥5 years, schools might consider TTS as an option for allowing close contacts who are not fully vaccinated to remain in the classroom as an alternative to home quarantine.

Effect of glecaprevir/pibrentasvir on weight-adjusted tacrolimus trough/dose ratios in heart and kidney transplant recipients.

OBJECTIVE: The pharmacokinetic implications of direct-acting antiviral (DAA) use on tacrolimus posttransplant are unknown. This study sought to investigate the effects of glecaprevir/pibrentasvir (G/P), a CYP3A4 substrate and inhibitor, on weight-adjusted tacrolimus (FK) trough/dose ratio (T/D) following heart or kidney transplantation. MATERIAL AND METHODS: This was a single-center, retrospective analysis of hepatitis C virus (HCV) viremic donors to HCV negative heart or kidney transplant recipients who received 12 weeks of G/P therapy. Weight-adjusted T/D was assessed while patients were at steady-state before, during, and after G/P treatment. Forty-one HCV negative recipients (three heart, 38 kidney) were evaluated. RESULTS: The weight-adjusted T/D significantly increased during G/P treatment (119.31, IQR 88-173.8) compared to before G/P treatment (67.4, IQR 53.4-115.9) (p < 0.01), but decreased after completion of treatment (90.1, IQR 52.9-122.7) (p < 0.01). There was no difference in weight-adjusted T/D before and after G/P treatment (p = 0.42). Four patients experienced acute rejection. CONCLUSION: Initiation of G/P in heart or kidney transplant recipients induces a reversible change in tacrolimus metabolism. A 33%-50% tacrolimus dose reduction may be considered at the time of G/P initiation. Regardless of tacrolimus dose adjustment, tacrolimus trough levels should be monitored 3 days after initiation of G/P. No clear relationship between HCV viremic organ transplantation and rejection risk was found. Larger studies are warranted to validate these findings.

Consensus-based recommendations for titrating cannabinoids and tapering opioids for chronic pain control.

AIMS: Opioid misuse and overuse have contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five-step modified Delphi process, we aimed to develop consensus-based recommendations on: 1) when and how to safely initiate and titrate cannabinoids in the presence of opioids, 2) when and how to safely taper opioids in the presence of cannabinoids and 3) how to monitor patients and evaluate outcomes when treating with opioids and cannabinoids. RESULTS: In patients with chronic pain taking opioids not reaching treatment goals, there was consensus that cannabinoids may be considered for patients experiencing or displaying opioid-related complications, despite psychological or physical interventions. There was consensus observed to initiate with a cannabidiol (CBD)-predominant oral extract in the daytime and consider adding tetrahydrocannabinol (THC). When adding THC, start with 0.5-3 mg, and increase by 1-2 mg once or twice weekly up to 30-40 mg/day. Initiate opioid tapering when the patient reports a minor/major improvement in function, seeks less as-needed medication to control pain and/or the cannabis dose has been optimised. The opioid tapering schedule may be 5%-10% of the morphine equivalent dose (MED) every 1 to 4 weeks. Clinical success could be defined by an improvement in function/quality of life, a ≥30% reduction in pain intensity, a ≥25% reduction in opioid dose, a reduction in opioid dose to <90 mg MED and/or reduction in opioid-related adverse events. CONCLUSIONS: This five-stage modified Delphi process led to the development of consensus-based recommendations surrounding the safe introduction and titration of cannabinoids in concert with tapering opioids.

Early Impact of 13-Valent Pneumococcal Conjugate Vaccine Use on Invasive Pneumococcal Disease Among Adults With and Without Underlying Medical Conditions-United States.

BACKGROUND: The 13-valent pneumococcal vaccine (PCV13) was introduced for US children in 2010 and for immunocompromised adults ≥19 years old in series with the 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated PCV13 indirect effects on invasive pneumococcal disease (IPD) among adults with and without PCV13 indications. METHODS: Using Active Bacterial Core surveillance and the National Health Survey, using Active Bacterial Core surveillance and the National Health Interview Survey, we estimated and compared IPD incidence in 2013-2014 and 2007-2008, by age and serotype group (PCV13, PPSV23-unique, or nonvaccine types [NVTs]), among adults with and without PCV13 indications. RESULTS: IPD incidence declined among all adults. Among adults 19-64 years, PCV13-type IPD declined 57% (95% confidence interval [CI], -68% to -43%) in adults with immunocompromising conditions (indication for PCV13 use), 57% (95% CI, -62% to -52%) in immunocompetent adults with chronic medical conditions (CMCs, indications for PPSV23 use alone), and 74% (95% CI, -78% to -70%) in adults with neither vaccine indication. Among adults aged ≥65 years, PCV13-type IPD decreased 68% (95% CI, -76% to -60%) in those with immunocompromising conditions, 68% (95% CI, -72% to -63%) in those with CMCs, and 71% (95% CI, -77% to -64%) in healthy adults. PPSV23-unique types increased in adults 19‒64 years with CMCs, and NVTs did not change among adults with or without PCV13 indications. From 2013 to 2014, non-PCV13 serotypes accounted for 80% of IPD. CONCLUSIONS: IPD incidence among US adults declined after PCV13 introduction in children. Similar reductions in PCV13-type IPD in those with and without PCV13 indications suggest that observed benefits are largely due to indirect effects from pediatric PCV13 use rather than direct use among adults.

Anhydrous Ammonia Chemical Release - Lake County, Illinois, April 2019.

On April 25, 2019, a farm tractor towing two 2-ton ammonia tanks on a county road in Lake County, Illinois, experienced a mechanical failure that resulted in the release of anhydrous ammonia, a colorless, pungent, irritating gas that can cause severe respiratory and ocular damage (1). Approximately 80% of anhydrous ammonia produced in the United States is used as a fertilizer in agriculture (1). Eighty-three persons, including first responders, motorists, and neighborhood residents, were evaluated at area hospitals because of exposure to the gas. Two weeks after the release, the Agency for Toxic Substances and Disease Registry (ATSDR) and CDC's National Center for Environmental Health (NCEH) collaborated with the Lake County Health Department and the Illinois Department of Public Health on an investigation using ATSDR's Assessment of Chemical Exposures program to describe the release, review the emergency response, and determine health effects associated with the exposure. First responders, community residents, and hospital personnel reported communication challenges related to the nature of the gas release and effective protective measures. Among the 83 persons evaluated at six area hospitals for effects of the chemical release, 14 (17%) were hospitalized, including eight (10%) who were admitted to the intensive care unit (ICU), seven (8%) of whom required endotracheal intubation and mechanical ventilation; no deaths occurred. In addition, ICU health care providers experienced symptoms of secondary exposure. The National Institute for Occupational Safety and Health's Emergency Responder Health Monitoring and Surveillance Program has specific recommendations and tools to protect responders during all phases of a response (2). Hospitals also need to review institutional policies and procedures for chemical mass casualty events, including decontamination (3). Prompt and correct identification of hazardous material (hazmat) events, and clear communication among responding entities, including on-scene and hospital responders, is important to ensure effective response after a chemical release.

Effect of gender and clinical-financial vulnerability on mental distress due to COVID-19.

The COVID-19 pandemic has had an enormous impact on people's mental health. This study examines whether gender influences the mental distress in people from at-risk populations (clinically high risk and financially vulnerable). A cross-sectional survey was administered between the 23rd and 28th of April 2020 to 15,691 individuals from 32,596 households in the UK. Our findings confirmed that individuals who are clinically high risk or financially vulnerable or a combination of both experience significantly higher levels of mental distress. Additionally, we also found that females experienced higher levels of mental distress than males across various categories.

Hydrophobic Polyampholytes and Nonfreezing Cold Temperature Stimulate Internalization of Au Nanoparticles to Zwitterionic Liposomes.

Nanomedicine relies on the effective internalization of nanoparticles combined with polymeric nanocarriers into living cells. Thus, exploration of internalization is essential for improving the efficacy of nanoparticle-based strategies in clinical practice. Here, we investigated the physicochemical internalization of gold nanoparticles (AuNPs) conjugated with hydrophobic polyampholytes into cell-sized liposomes at a low but nonfrozen temperature. The hydrophobic polyampholytes localized in the disordered phase of the membrane, and internalization of AuNPs was enhanced in the presence of hydrophobic polyampholytes together with incubation at -3 °C as compared to 25 °C. These results contribute toward a mechanistic understanding for developing a model nanomaterials-driven delivery system based on hydrophobic polyampholytes and low temperature.

pH-Responsive Polyion Complex Vesicle with Polyphosphobetaine Shells.

When a bioactive molecule is taken into cells by endocytosis, it is sometimes unable to escape from the lysosomes, resulting in inefficient drug release. We prepared pH-responsive polyion complex (PIC) vesicles that collapse under acidic conditions such as those inside a lysosome. Furthermore, under acidic conditions, cationic polymer was released from the PIC vesicles to break the lysosome membranes. Diblock copolymers (P20M167 and P20A190) consisting of water-soluble zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) block and cationic or anionic blocks were synthesized via reversible addition-fragmentation chain transfer (RAFT) radical polymerization. Poly(3-(methacrylamidopropyl) trimethylammonium chloride) (PMAPTAC) and poly(sodium 6-acrylamidohexanoate) (PAaH) were used as the cationic and anionic blocks, respectively. The pendant hexanoate groups in the PAaH block are ionized in basic water and in phosphate buffered saline (PBS), while the hexanoate groups are protonated in acidic water. In basic water, PIC vesicles were formed from a charge neutralized mixture of oppositely charged diblock copolymers. At the interface of PIC vesicle and water exists biocompatible PMPC shells. Under acidic conditions, the PIC vesicles collapsed, because the charge balance shifted due to protonation of the PAaH block. After collapse of the PIC vesicles, P20A190 formed micelles composed of protonated PAaH core and PMPC shells, while P20M167 was released as unimers. PIC vesicles can encapsulate hydrophilic nonionic guest molecules into their hollow core. Under acidic conditions, the PIC vesicles can release the guest molecules and P20M167. The cationic P20M167 can break the lysosome membrane to efficiently release the guest molecules from the lysosomes to the cytoplasm.

Enhanced Adsorption of a Protein-Nanocarrier Complex onto Cell Membranes through a High Freeze Concentration by a Polyampholyte Cryoprotectant.

The transportation of biomolecules into cells is of great importance in tissue engineering and as stimulation for antitumor immune cells. Previous freezing strategies at ultracold temperatures (-80 °C) used for intracellular transportation exhibit certain limitations such as extended time requirements and harsh delivery system conditions. Thus, the need remains to develop simplified methods for safe nanomaterial delivery. Here, we demonstrated a unique strategy based on the ice-crystallization-induced freeze concentration for protein intracellular delivery in combination with a polyampholyte cryoprotectant. We found that upon sustained lowering of the temperature from -6 to -20 °C over a short duration, the adsorption of proteins onto the peripheral cell membrane was markedly increased through the facile ice-crystallization-induced freeze concentration. Furthermore, we proposed a freeze concentration factor (α) that depends on the freezing-point depression and is estimated from an analysis of the fraction of frozen water. Notably, the α values of the polyampholyte cryoprotectant were 8-fold higher than those of the currently used cryoprotectant dimethyl sulfoxide (DMSO) at particular temperatures of interest. Our results illustrate that the presence of a polyampholyte cryoprotectant significantly enhanced the adsorption of the protein/nanocarrier complex onto membranes compared to that obtained with DMSO because of the high freeze concentration. The present study demonstrated the direct relationship between freezing and the penetration of proteins across the periphery of the cell membrane by means of increased concentration during freezing. These results may be useful in providing a guideline for the intracellular delivery of biomacromolecules using ice-crystallization-induced continuous freezing combined with polyampholyte cryoprotectants.

Common Questions About Oppositional Defiant Disorder.

Oppositional defiant disorder (ODD) is a disruptive behavior disorder characterized by a pattern of angry or irritable mood, argumentative or defiant behavior, or vindictiveness lasting for at least six months. Children and adolescents with ODD may have trouble controlling their temper and are often disobedient and defiant toward others. There are no tools specifically designed for diagnosing ODD, but multiple questionnaires can aid in diagnosis while assessing for other psychiatric conditions. ODD is often comorbid with attention-deficit/hyperactivity disorder, conduct disorder, and mood disorders, including anxiety and depression. Behavioral therapy for the child and family members improves symptoms of ODD. Medications are not recommended as first-line treatment for ODD; however, treatment of comorbid mental health conditions with medications often improves ODD symptoms. Adults and adolescents with a history of ODD have a greater than 90% chance of being diagnosed with another mental illness in their lifetime. They are at high risk of developing social and emotional problems as adults, including suicide and substance use disorders. Early intervention seeks to prevent the development of conduct disorder, substance abuse, and delinquency that can cause lifelong social, occupational, and academic impairments.

Senescence related alteration in hippocampal biogenic amines produces neuropsychological deficits in rats.

Aging is a natural complex process that is regulated at genetic, cellular, molecular and systemic levels and leads to the development of a variety of changes including structural, chemical and genetic in the senescent brain. The major goal of the present study was to investigate the age associated cognitive dysfunction and other behavioral changes and their association with age related alterations in levels of neurotransmitters, such as dopamine (DA) and serotonin (5-HT) in the hippocampal region. Twelve male Albino Wistar rats were taken for the study including six young rats (04-05 months old) and six aged (20-22 months old) rats in each group. The learning and memory performance of rats was assessed by passive avoidance test (PA) and novel objective recognition task (NOR). Ambulatory activity was monitored by Open field test. Light/Dark transition test was used to monitor anxiety, whereas depression like symptoms was examined by Forced Swim Test (FST). Results showed that aged rats exhibited learning and memory impairment in PA and NOR. There was a negative relation between aging process and locomotion, consistent with previous findings. Moreover, an augmented increase in level of anxiety and depression was also observed in senescent rats. A marked decrease in DA and 5-HT was observed in the hippocampus of aged rats. Similarly, levels of 5-HIAA and DOPAC were also found to be decreased in aged rats. It is therefore concluded that age has a negative influence on cognitive function, depression, anxiety and locomotion in rats. Cells in all brain regions, especially hippocampus are affected by aging. In general aging exhibits a decline in sensory, motor and cognitive functions. These behavioral changes or functional deficits may be attributed to the age related decline in the levels of different neurotransmitters in brain/hippocampus. The present findings of behavioral deficits and altered neurotransmission in hippocampus of aged rats suggest a relationship between senescence, altered brain neurotransmitters and behavioral deficits.

AAA ATPase protein-protein interactions as therapeutic targets in cancer.

AAA ATPases are a conserved group of enzymes that couple ATP hydrolysis to diverse activities critical for cellular homeostasis by targeted protein-protein interactions. Some of these interactions are potential therapeutic targets because of their role in cancers which rely on increased AAA ATPase activities for maintenance of genomic stability. Two well-characterized members of this family are p97/VCP and RUVBL ATPases where there is a growing understanding of their structure and function, as well as an emerging landscape of selective inhibitors. Here we highlight recent progress in this field, with particular emphasis on structural advances enabled by cryo-electron microscopy (cryo-EM).

Sentiment analysis of financial Twitter posts on Twitter with the machine learning classifiers.

This paper presents a sentiment analysis combining the lexicon-based and machine learning (ML)-based approaches in Turkish to investigate the public mood for the prediction of stock market behavior in BIST30, Borsa Istanbul. Our main motivation behind this study is to apply sentiment analysis to financial-related tweets in Turkish. We import 17189 tweets posted as "#Borsaistanbul, #Bist, #Bist30, #Bist100″ on Twitter between November 7, 2022, and November 15, 2022, via a MAXQDA 2020, a qualitative data analysis program. For the lexicon-based side, we use a multilingual sentiment offered by the Orange program to label the polarities of the 17189 samples as positive, negative, and neutral labels. Neutral labels are discarded for the machine learning experiments. For the machine learning side, we select 9076 data as positive and negative to implement the classification problem with six different supervised machine learning classifiers conducted in Python 3.6 with the sklearn library. In experiments, 80 % of the selected data is used for the training phase and the rest is used for the testing and validation phase. Results of the experiments show that the Support Vector Machine and Multilayer Perceptron classifier perform better than other classifiers with 0.89 and 0.88 accuracy and AUC values of 0.8729 and 0.8647 respectively. Other classifiers obtain approximately a 78,5 % accuracy rate. It is possible to increase sentiment analysis accuracy with parameter optimization on a larger, cleaner, and more balanced dataset by changing the pre-processing steps. This work can be expanded in the future to develop better sentiment analysis using deep learning approaches.

Unlocking the Potential: Millets and Their Impact on Diabetes Management.

Many studies, including case studies, meta-analyses, and randomized trials, have demonstrated the benefits of a low-carb diet in the management of obesity, diabetes, and pre-diabetes. Numerous studies suggest that diets low in carbohydrates are safe and can greatly enhance the management of both forms of diabetes as well as the general health of those who have the disease. When used in conjunction with effective therapy, this diet can result in weight loss, decreased prescription dosages, and in certain cases, remission from type 2 diabetes. Globally, there has been a notable surge in the prevalence of diabetes cases as a result of factors such as population growth, aging, urbanization, rising obesity rates, and declining physical activity. Diabetes can be controlled in large part by diet, and millets having low-glycemic index (GI) have become more significant as they release glucose into the bloodstream at a very slow rate. Creating a low-glycemic meal mix with locally sourced ingredients is crucial for daily diet plans. Dietary changes, particularly the addition of millet, can help prevent and manage diabetes mellitus. Eating practices have long been acknowledged for their important role in promoting health and wellness through the consumption of nutrient-dense meals. The health benefits of millet, an underappreciated food crop, are numerous and include low GI, high-fiber content, non-acid-forming potential, polyunsaturated fatty acids (PUFAs), and gluten-free status. Apart from staple crops like wheat and rice, millets are also very healthy and useful, and they have an immense amount of opportunity to aid in the global fight against food insecurity, which is a problem that many countries now confront. Millets are high on the list of recommended foods because of their many health advantages and antioxidant characteristics. Diets that are low in carbohydrates, low in GI, Mediterranean, and very low in calories are now popular. Diabetes can be managed with a nutritious diet, regular exercise, cessation of smoking, and maintenance of a healthy body weight. Furthermore, calorie restriction, the use of low-GI meals, and an increase in fiber content are all possible nutritional strategies in the management of diabetes.

Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein.

The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success of XBB.1.5 stems from mutations within its spike glycoprotein, causing immune evasion and enhanced receptor binding. We present receptor binding studies that demonstrate retention of binding contacts with the human ACE2 receptor and a striking decrease in binding to mouse ACE2 due to the revertant R493Q mutation. Despite extensive evasion of antibody binding, we highlight a region on the XBB.1.5 spike protein receptor binding domain (RBD) that is recognized by serum antibodies from a donor with hybrid immunity, collected prior to the emergence of the XBB.1.5 variant. T cell assays reveal high frequencies of XBB.1.5 spike-specific CD4+ and CD8+ T cells amongst donors with hybrid immunity, with the CD4+ T cells skewed towards a Th1 cell phenotype and having attenuated effector cytokine secretion as compared to ancestral spike protein-specific cells. Thus, while the XBB.1.5 variant has retained efficient human receptor binding and gained antigenic alterations, it remains susceptible to recognition by T cells induced via vaccination and previous infection.

Using Liver Organoids as Models to Study the Pathobiology of Rare Liver Diseases.

Liver organoids take advantage of several important features of pluripotent stem cells that self-assemble in a three-dimensional culture matrix and reproduce many aspects of the complex organization found within their native tissue or organ counterparts. Compared to other 2D or 3D in vitro models, organoids are widely believed to be genetically stable or docile structures that can be programmed to virtually recapitulate certain biological, physiological, or pathophysiological features of original tissues or organs in vitro. Therefore, organoids can be exploited as effective substitutes or miniaturized models for the study of the developmental mechanisms of rare liver diseases, drug discovery, the accurate evaluation of personalized drug responses, and regenerative medicine applications. However, the bioengineering of organoids currently faces many groundbreaking challenges, including a need for a reasonable tissue size, structured organization, vascularization, functional maturity, and reproducibility. In this review, we outlined basic methodologies and supplements to establish organoids and summarized recent technological advances for experimental liver biology. Finally, we discussed the therapeutic applications and current limitations.

Psychometric Properties of the PANS 31-Item Symptom Rating Scale.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS (N = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS (r = 0.81) and PANS Total and GIS (r = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.