Probiotic, Paraprobiotic, and Hydrolyzed Yeast Mixture Supplementation Has Comparable Effects to Zinc Oxide in Improving Growth Performance and Ameliorating Post-weaning Diarrhea in Weaned Piglets.

A total of 150 21-day-old weaned piglets [(Yorkshire × Landrace) × Duroc] were randomly assigned to 3 groups (CON, TRT1, TRT2) to evaluate the effects of dietary supplementation of probiotic, paraprobiotic, and hydrolyzed yeast mixture (PPY) on growth performance, nutrient digestibility, fecal bacterial counts, fecal calprotectin contents, and diarrhea rate in a 42-day experiment (phase 1: days 1-14; phase 2: days 15-42). There were 10 replicate pens per treatment with 5 pigs per pen (three gilts and two barrows). Pigs in CON were only provided with a basal diet. Pigs in TRT1 were provided with a basal diet + 3000 mg/kg zinc oxide during phase 1 and a basal diet during phase 2. Pigs in TRT2 were provided with a basal diet + 200 mg/kg probiotic (Saccharomyces cerevisiae boulardii) + 800 mg/kg paraprobiotic (inactivated yeast strains of Saccharomyces cerevisiae and Cyberlindnera jadinii) + 10 g/kg hydrolyzed yeast mixture during phase 1, and a basal diet + 100 mg/kg probiotic + 400 mg/kg paraprobiotic mixture during phase 2. Pigs in TRT1 and TRT2 were significantly heavier at day 14 and 42 than CON pigs. Growth rate during days 1-14, 15-42, and 1-42 and feed efficiency during days 1-14 were similarly affected by treatment while feed efficiency was significantly higher for TRT2 pigs between 15-42 and 1-42 days. Moreover, nitrogen and energy digestibility in both TRT1 and TRT2 were higher than that in CON. During experimental periods, diarrhea rate in TRT1 and TRT2 was lower than that in CON. Therefore, we demonstrated that PPY supplementation had comparable effects as ZnO in improving growth performance and nutrient digestibility as well as ameliorating post-weaning diarrhea in weaned piglets.

Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy.

Activation of hypoxia-inducible factor 1α (HIF1α) contributes to blood-retinal barrier (BRB) breakdown and pathological neovascularization responsible for vision loss in ischemic retinal diseases. During disease progression, mitochondrial biology is altered to adapt to the ischemic environment created by initial vascular dysfunction, but the mitochondrial adaptive mechanisms, which ultimately contribute to the pathogenesis of ischemic retinopathy, remain incompletely understood. In the present study, it is identified that expression of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) is essential for BRB breakdown and pathologic retinal neovascularization in mouse models mimicking ischemic retinopathies. Genetic Trap1 ablation or treatment with small molecule TRAP1 inhibitors, such as mitoquinone (MitoQ) and SB-U015, alleviate retinal pathologies via proteolytic HIF1α degradation, which is mediated by opening of the mitochondrial permeability transition pore and activation of calcium-dependent protease calpain-1. These findings suggest that TRAP1 can be a promising target for the development of new treatments against ischemic retinopathy, such as retinopathy of prematurity and proliferative diabetic retinopathy.

Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells.

Although tamoxifen (TAM) is widely used in patients with estrogen receptor-positive breast cancer, the development of tamoxifen resistance is common. The previous finding suggests that the development of tamoxifen resistance is driven by epiregulin or hypoxia-inducible factor-1α-dependent glycolysis activation. Nonetheless, the mechanisms responsible for cancer cell survival and growth in a lactic acid-rich environment remain elusive. We found that the growth and survival of tamoxifen-resistant MCF-7 cells (TAMR-MCF-7) depend on glycolysis rather than oxidative phosphorylation. The levels of the glycolytic enzymes were higher in TAMR-MCF-7 cells than in parental MCF-7 cells, whereas the mitochondrial number and complex I level were decreased. Importantly, TAMR-MCF-7 cells were more resistant to low glucose and high lactate growth conditions. Isotope tracing analysis using 13C-lactate confirmed that lactate conversion to pyruvate was enhanced in TAMR-MCF-7 cells. We identified monocarboxylate transporter1 (MCT1) and lactate dehydrogenase B (LDHB) as important mediators of lactate influx and its conversion to pyruvate, respectively. Consistently, AR-C155858 (MCT1 inhibitor) inhibited the proliferation, migration, spheroid formation, and in vivo tumor growth of TAMR-MCF-7 cells. Our findings suggest that TAMR-MCF-7 cells depend on glycolysis and glutaminolysis for energy and support that targeting MCT1- and LDHB-dependent lactate recycling may be a promising strategy to treat patients with TAM-resistant breast cancer.

Dupuytren contracture after acute traumatic hand injury in an adolescent: A case report.

Dupuytren's disease is a fibroproliferative disease that affects the palmar hand, causing progressive, permanent, and symptomatic flexion contracture of the digits. It is a disorder of polygenetic and multifactorial origin, usually affecting middle-aged males. Dupuytren's disease developing as a result of hand trauma in younger ages is rarely reported. In this case, we present a 14-year-old male patient with Dupuytren's disease following acute traumatic injury. We performed the fasciectomy and Z-plasty with full thickness skin graft. He recovered completely additional injection of triamcinolone for one year.

Microplastic polyamide toxicity: Neurotoxicity, stress indicators and immune responses in crucian carp, Carassius carassius.

This study aimed to determine the toxicity standard and potential risks and effects of polyamide (PA) exposure on neurotoxicity, stress indicators, and immune responses in juvenile crucian carp Carassius carassius. Numerous microplastics (MPs) exists within aquatic environments, leading to diverse detrimental impacts on aquatic organisms. The C. carassius (mean weight, 23.7 ± 1.6 g; mean length, 13.9 ± 1.4 cm) were exposed to PA concentrations of 0, 4, 8, 16, 32 and 64 mg/L for 2 weeks. Among the neurotransmitters, the acetylcholinesterase (AChE) activity in the liver, gill, and intestine of C. carassius was significantly inhibited by PA exposure. Stress indicators such as cortisol and heat shock protein 70 (HSP70) in the liver, gill, and intestine of C. carassius were significantly increased, while immune responses to lysozyme and immunoglobulin M (IgM) were significantly decreased. Our study demonstrates the toxic effects of MP exposure on crucian carp's neurotoxicity, stress indicators, and immune responses.

Abdominal displacement of breast filler after previous trans-umbilical breast augmentation (TUBA): a case report.

Background: Breast augmentation is one of the most commonly performed aesthetic procedures in the world. Aquafilling filler, since its introduction in 2005 has been used for breast or buttock augmentation in several countries. Aquafilling filler is composed of 2% polyacrylamide with 98% sodium chloride 0.9% solution, and is known to have a similar composition with polyacrylamide hydrogel (PAAG) filler, which is also related to a variety of complications. Although many studies have warned against the complications of aquafilling filler, it is still being used for aesthetic purposes. Case Description: In this case report, we share our experience of a 36-year-old female patient complaining of smaller left breast and bulging mass in her left upper abdomen. She had a history of transumbilical breast augmentation (TUBA) 11 years prior, which she had had removed via the transumbilical incision 6 years ago. To compensate for the removal of implants, the patient had received large volumes of aquafilling filler injection 2 years after implant removal. Surprisingly, we found out that the filler in the left breast had displaced to the abdominal area. Conclusions: Accidently displacement may occur, especially in patients who have had previous procedures breaching the inframammary fold including TUBA. Therefore, it is required to observe carefully for those patients who have received breast augmentation or the breast filler injections.

Structural impairment in superficial and deep white matter in schizophrenia.

OBJECTIVE: Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects. METHODS: We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman's rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing. RESULTS: Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial-occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing. CONCLUSION: We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.

Orbital Reconstruction Using a Polyetheretherketone Patient-Specific Implant After Removal of a Mucocele Developing After Orbital Fracture Repair.

A few mucoceles developing secondary to facial bone fractures have been reported. Mucocele formation is thought to be attributable to displacement of the respiratory mucosa with obstruction of the sinus opening, especially if untreated. Accurate diagnosis and management are required; a growing mucocele will gradually destroy adjacent bony structures and cause irreversible complications. The authors describe a patient who presented with diplopia and mild discomfort when gazing upward. She had undergone reconstruction of medial and inferior orbital fractures 20 years previously. The patient was diagnosed with a mucocele developing after orbital fracture repair. The patient underwent mucocele removal and orbital reconstruction using a polyetheretherketone patient-specific implant. In a patient with orbital symptoms but without acute trauma, a mucocele should be among the differential diagnoses if history-taking reveals past orbital trauma and surgery. A polyetheretherketone patient-specific implant was effective for orbital reconstruction after mucocele removal.

Giant lipoma in the index finger of the dominant hand of a swimmer: A case report.

Lipoma is a very common benign tumor that occurs in areas of adipose tissue and is commonly found on the whole body, although its occurrence in the hand and finger is rare. Giant lipoma, defined as over 5 cm long in diameter, is a rare benign tumor of abundant soft tissue in the finger. A 24-year-old male patient presented with a giant lipoma on the volar aspect of the index finger of his right hand. Magnetic resonance imaging (MRI) showed an encased multilobulated mass that measured 7.1x1.2x2.3 cm, and histopathological examination revealed lipoma without malignant transformation. Surgical resection of the tumor with a longitudinal and zig-zag incision of the palm was performed exposing the mass surrounding the palmar digital branch of the median nerve. The mass was completely removed, and neurorrhaphy was performed via the microscope to repair the damaged neurovascular bundle. At four months of postoperative follow-up, the patient was completely recovered with no finger paresthesia or limitation of range of motion. As a professional swimmer, the patient has experienced no subsequent difficulty in swimming due to his finger.

The application and future of biofloc technology (BFT) in aquaculture industry: A review.

This review describes the applicability of biofloc technology (BFT) to future aquaculture technologies. BFT is considered an innovative alternative for solving the problems of traditional aquaculture (for example, environmental pollution, high maintenance costs, and low productivity). Extensive research is being conducted to apply BFT to breed and raise many aquatic animal species. In BFT, maintaining an appropriate C:N ratio by adding a carbon source promotes the growth of microorganisms in water and maintains the aquaculture water quality through microbial processes such as nitrification. For the efficient use and sustainability of BFT, various factors such as total suspended solids, water turbidity, temperature, dissolved oxygen, pH, and salinity, stocking density, and light should be considered. The application of the transformative fourth industrial revolution technologies, Information and Communications Technology (ICT) and Internet of Things (IoT), to aquaculture can reduce the risk factors and manual interventions in aquaculture through automation and intelligence. The combination of ICT/IoT with BFT can enable real-time monitoring of the necessary elements of BFT farming using various sensors, which is expected to increase productivity by ensuring the growth and health of the organisms being reared.

Impact of the early phase of the COVID-19 pandemic on the use of mental health services in South Korea: a nationwide, health insurance data-based study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the utilization of mental health services. Existing evidence investigating this issue at the nationwide level is lacking, and it is uncertain whether the effects of the COVID-19 pandemic on the use of psychiatric services differs based on psychiatric diagnosis. METHODS: Data from the claims database between October 2015 and August 2020 was obtained from the Health Insurance Review and Assessment agency in South Korea. Based on the main diagnostic codes, psychiatric patients were identified and categorized into diagnostic groups (anxiety disorders, bipolar and related disorders, depressive disorders, and schizophrenia spectrum disorders). We calculated the number of psychiatric inpatients and outpatients and the medication adherence of patients for each month. We compared the actual and predicted values of outcomes during the COVID-19 pandemic and performed interrupted time-series analyses to test the statistical significance of the impact of the pandemic. RESULTS: During the COVID-19 pandemic, the number of inpatients and admissions to psychiatric hospitals decreased for bipolar and related disorders and depressive disorders. In addition, the number of patients admitted to psychiatric hospitals for schizophrenia spectrum disorders decreased. The number of psychiatric outpatients showed no significant change in all diagnostic groups. Increased medication adherence was observed for depressive, schizophrenia spectrum, and bipolar and related disorders. CONCLUSIONS: In the early phase of the COVID-19 pandemic, there was a trend of a decreasing number of psychiatric inpatients and increasing medication adherence; however, the number of psychiatric outpatients remained unaltered.

Antipsychotic treatment and risk of discontinuation and hospitalization in first-episode schizophrenia: a nationwide population-based study.

BACKGROUND: Current evidence on antipsychotic treatment and risk of psychiatric hospitalization in first-episode schizophrenia (FES) is largely based on the findings from randomized clinical trials (RCTs). However, the generalization of the findings to real-world patients is limited due to inherent caveats of the RCT. We aimed to investigate the treatment discontinuation and risk of psychiatric hospitalization using a nationwide population database. METHODS: The Health Insurance Review Agency database in South Korea was obtained, and the observation period started from 1 January 2009 to 31 December 2016. We defined the maintenance period as the period from 6-month after the diagnosis of schizophrenia, which is utilized for the main results. For a total of 44 396 patients with FES, a within-individual Cox regression model was used to compare the risk of the treatment discontinuation and psychiatric hospitalization. RESULTS: In group comparison, a long-acting injectable (LAI) antipsychotic group was associated with the lowest risk of the treatment discontinuation (0.64, 0.55-0.75) and psychiatric hospitalization (0.29, 0.22-0.38) in comparison with a typical antipsychotic group and no use, respectively. Among individual antipsychotics, the lowest risk of the treatment discontinuation was observed in LAI paliperidone (0.46, 0.37-0.66) compared to olanzapine. Clozapine was found to be the most effective antipsychotic in lowering the risk of psychiatric hospitalization as monotherapy compared to no use (0.23, 0.18-0.31). CONCLUSIONS: In real-world patients with FES, LAI paliperidone and clozapine were associated with low treatment discontinuation and better effectiveness in lowering the risk of psychiatric hospitalization.

Left Atrial Appendage Aneurysm: A Case Report.

Left atrial appendage aneurysm (LAAA) is a rare heart anomaly caused by congenital dysplasia of the pectinate muscle or by an acquired pathological condition of the mitral valve or cardiac muscle. It is often incidentally discovered during chest CT or echocardiography as an abnormal dilatation of the LAA. LAAA is associated with life-threatening complications and most patients require surgical treatment. Therefore, it is important to evaluate associated complications as well as precise diagnoses. This report presents the case of a surgically confirmed LAAA in a 53-year-old female. We also discuss the pathophysiology of LAAA and significant findings related to mortality that can be detected on CT and MRI.

Delay in psychiatric hospitalization from the diagnosis of first-episode schizophrenia and its association with clinical outcomes and direct medical costs: a nationwide, health insurance data-based study.

BACKGROUND: Early intervention is essential for improving the prognosis in patients with first-episode schizophrenia (FES). The Mental Health Act limits involuntary hospitalization in South Korea to cases where an individual exhibits both a mental disorder and a potential for harming themselves or others, which could result in a delay in the required treatment in FES. We investigated the effect of delay in the first psychiatric hospitalization on clinical outcomes in FES. METHODS: The South Korean Health Insurance Review Agency database (2012-2019) was used. We identified 15,994 patients with FES who had a record of at least one psychiatric hospitalization within 1 year from their diagnosis. A multivariate linear regression model and a generalized linear model with a gamma distribution and log link were used to examine associations between the duration from the diagnosis to the first psychiatric admission and clinical outcomes as well as direct medical costs after 2 and 5 years. RESULTS: Within both the 2-year and the 5-year period, longer durations from the diagnosis to the first psychiatric admission were associated with an increase in the number of psychiatric hospitalizations (2-y: B = 0.003, p = 0.003, 5-y: B = 0.007, p = 0.001) and an increase in direct medical costs (total: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.005; inpatient care: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.017). CONCLUSIONS: Earlier psychiatric admission from the diagnosis is associated with a decrease in the number of psychiatric admissions as well as in direct medical costs in patients with FES.

One-Year Clinical Outcomes Following Electroconvulsive Therapy for Patients with Schizophrenia: A Nationwide Health Insurance Data-Based Study.

Background: Although the use of electroconvulsive therapy (ECT) in the treatment of schizophrenia has decreased since the advent of antipsychotic drugs, ECT is still implemented in several clinical indications. However, a few population-based studies have examined its real-world effectiveness in schizophrenia. Methods: We used data from 2010 to 2019 from the Health Insurance Review and Assessment Service database in the Republic of Korea. We selected 380 schizophrenia patients having more than six ECT sessions and 1140 patient controls matched for age, sex, calendar year at entry, and the number of psychiatric hospitalizations before the time point of start of psychiatric hospitalization for ECT. Antipsychotic treatment discontinuation, psychiatric hospitalization, and direct medical costs were used as measures of clinical outcomes. Multiple regression analysis was used for any group-by-time interaction effect, and 1-year pre- and post-ECT periods were compared within and between the groups. Results: We found a significantly lower number of antipsychotic treatment discontinuations in the ECT group during the 1-year post-ECT period (t=2.195, p=0.028). A larger decrease was found in the number of psychiatric hospitalizations in the ECT group, with a group-by-time interaction effect (p=0.043). The direct medical costs in the 1-year pre- (t=-8.782, p<0.001) and post-ECT periods (t=-9.107, p<0.001) were higher in the ECT group than in the control group, with no significant change across both periods. Conclusion: We found that the ECT group had a larger decrease in the number of psychiatric hospitalizations in the 1-year post-ECT period than the control group.

Neck Pain Caused by Giant Dorsal Lipoma.

Giant lipomas are uncommon in the neck or craniofacial region. A 55-year-old male presented with a large pendulous mass arising from the dorsal aspect of his neck, which he had known about for 20 years. Discomfort during sleeping, frequent headaches, and chronic neck pain were his chief complaints. Computed topography revealed a well-circumscribed lipomatous lesion. A decrease in cervical spine lordosis was noted on sagittal x-rays. Surgical excision with local flap coverage was performed. The specimen weighed 2800 g. The patient reported immediate resolution of neck pain, and complete resolution of headaches following surgery. An increase in the degree of lordosis was seen in sagittal x-rays. Histopathological results confirmed the diagnosis of lipoma. Although most giant dorsal neck lipomas are benign, they may be a cause for neck pain, headaches and degenerative changes in the cervical spine, undermining the quality of life. Such symptoms should be assessed, and removal recommended.

Comparative effectiveness of antipsychotic monotherapy and polypharmacy in schizophrenia patients with clozapine treatment: A nationwide, health insurance data-based study.

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia (TRS). However, it remains uncertain whether antipsychotic augmentation to clozapine has the superior effectiveness over clozapine alone and the effect size of clozapine compared to other antipsychotic drugs in TRS. Therefore, we examined the comparative effectiveness of antipsychotic monotherapy and polypharmacy on the risk of psychiatric admission and treatment discontinuation in TRS. Data were collected from the Health Insurance Review Agency database between January 2010 and December 2019 in South Korea. Among prevalent patients with schizophrenia, we defined 22,327 patients with TRS as those who had been prescribed with clozapine at least once during the entire observation period. Stratified Cox proportional hazards regressions were performed using data on all antipsychotic prescriptions of patients with TRS to investigate the risk of psychiatric hospitalization and treatment discontinuation associated with antipsychotic treatment. In individual comparisons, clozapine monotherapy was the most effective for the risk of psychiatric hospitalization compared to no use (hazard ratio [HR] = 0.23, 95% confidence interval [CI] = 0.22-0.25). In group comparisons, clozapine with long-acting injectable (LAI) second-generation antipsychotics (SGA) was superior to clozapine monotherapy for the risk of psychiatric hospitalization (HR = 0.60, 95%CI = 0.41-0.88). Clozapine monotherapy was associated with the lowest risk of treatment discontinuation in the individual and group comparisons. This retrospective observational population-based study reports that clozapine with LAI SGA is more effective in lowering the risk of psychiatric hospitalization in antipsychotic group comparison with the reference of clozapine monotherapy.

Development of human pluripotent stem cell-derived hepatic organoids as an alternative model for drug safety assessment.

Human in vitro hepatic models that faithfully recapitulate liver function are essential for successful basic and translational research. A limitation of current in vitro models, which are extensively used for drug discovery and toxicity testing, is the loss of drug metabolic function due to the low expression and activity of cytochrome P450 (CYP450) enzymes. Here, we aimed to generate human pluripotent stem cell-derived hepatic organoids (hHOs) with a high drug metabolic ability. We established a two-step protocol to produce hHOs from human pluripotent stem cells for long-term expansion and drug testing. Fully differentiated hHOs had multicellular composition and exhibited cellular polarity and hepatobiliary structures. They also displayed remarkable CYP450 activity and recapitulated the metabolic clearance, CYP450-mediated drug toxicity, and metabolism. Furthermore, hHOs successfully modeled Wilson's disease in terms of Cu metabolism, drug responses, and diagnostic marker expression and secretion. In conclusion, hHOs exhibit high capacity for drug testing and disease modeling. Hence, this hepatic model system provides an advanced tool for studying hepatic drug metabolism and diseases.