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Loneliness and social isolation pose significant public health concerns globally, with adverse effects on mental health and well-being. Although the terms are often used interchangeably, loneliness refers to the subjective feeling of lacking social connections, whereas social isolation is the objective absence of social support or networks.
Aims
To investigate the prevalence of loneliness and social isolation and their associations with psychiatric disorders.
Method
This study used data from the Republic of Korea National Mental Health Survey 2021, a nationally representative survey. A total of 5511 adults aged 18–79 residing in South Korea participated in the survey. Loneliness and social isolation were assessed using the Loneliness and Social Isolation Scale, whereas psychiatric disorders were evaluated using the Korean version of the Composite International Diagnostic Interview. Multivariate logistic regressions were performed after adjustment for sociodemographic variables.
Results
Among the participants, 11.8% reported experiencing loneliness, 4.3% reported social isolation and 3.4% reported both. Co-occurrence of loneliness and social isolation was significantly associated with psychiatric disorders (adjusted odds ratio (AOR) 7.59, 95% CI: 5.48–10.52). Loneliness alone was associated with greater prevalence and higher probability of psychiatric disorders (AOR 3.12, 95% CI: 2.63–3.71), whereas social isolation did not show any significant association (AOR 0.88, 95% CI: 0.64–1.22).
Conclusion
The co-occurrence of loneliness and social isolation is particularly detrimental to mental health. This finding emphasises the need for targeted interventions to promote social connection and reduce feelings of isolation.
Increasing evidence has established a strong association between social anxiety disorder and suicidal behaviours, including suicidal ideation and suicide attempts. However, the association between social anxiety disorder and suicide mortality remains unclear.
Methods
This study analysed data from 15,776 patients with social anxiety disorder, extracted from a nationwide Taiwanese cohort between 2003 and 2017. Two unexposed groups without social anxiety disorder, matched by birth year and sex in 1:4 and 1:10 ratios, respectively, were used for comparison. Suicide deaths during the same period were examined. Psychiatric comorbidities commonly associated with social anxiety disorder, including schizophrenia, bipolar disorder, major depression, alcohol use disorder (AUD), substance use disorder (SUD), obsessive-compulsive disorder, autism, and attention deficit hyperactivity disorder, were identified.
Results
Time-dependent Cox regression models, adjusted for demographic factors and psychiatric comorbidities, revealed that individuals with social anxiety disorder had an increased risk of suicide (hazard ratio: 3.49 in the 1:4 matched analysis and 2.84 in the 1:10 matched analysis) compared with those without the disorder. Comorbidities such as schizophrenia, bipolar disorder, major depression, AUD, and SUD further increased the risk of suicide in patients with social anxiety disorder.
Conclusion
Social anxiety disorder is an independent risk factor for suicide death. Additional psychiatric comorbidities, including schizophrenia, major affective disorders, and AUD, further increased social anxiety disorder-related suicide risk. Therefore, mental health officers and clinicians should develop targeted suicide prevention strategies for individuals with social anxiety disorder.
Panic disorder (PD) may increase the likelihood of suicidal ideation and behaviors because of psychiatric comorbidities such as major depressive disorder (MDD). However, research has yet to demonstrate a direct relationship between PD and suicide mortality.
Method
Using data from Taiwan’s National Health Insurance Research Database, we identified 171,737 individuals with PD and 686,948 age- and sex-matched individuals without PD during 2003–2017. We assessed the risk of suicide within the same period. Psychiatric comorbidities such as schizophrenia, bipolar disorder, MDD, obsessive-compulsive disorder (OCD), autism, alcohol use disorder (AUD), and substance use disorder (SUD) were also evaluated. Time-dependent Cox regression models were used to compare the risk of suicide in different groups after adjustment for demographic data and psychiatric comorbidities.
Results
Our Cox regression model revealed that PD was an independent risk factor for suicide (hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.59–2.14), regardless of psychiatric comorbidities. Among all comorbidities, MDD with PD was associated with the highest risk of suicide (HR = 6.08, 95% CI = 5.48–6.74), followed by autism (HR = 4.52, 95% CI = 1.66–12.29), schizophrenia (HR = 3.34, 95% CI = 2.7–4.13), bipolar disorder (HR = 3.20, 95% CI = 2.71–3.79), AUD (HR = 2.99, 95% CI = 2.41–3.72), SUD (HR = 2.82, 95% CI = 2.28–3.47), and OCD (HR = 2.10, 95% CI = 1.64–2.67).
Discussion
PD is an independent risk factor for suicide. Psychiatric comorbidities (i.e. schizophrenia, bipolar disorder, MDD, OCD, AUD, SUD, and autism) with PD increase the risk of suicide.
Research evidence has established an association of obsessive-compulsive disorder (OCD) with suicidal thoughts and suicide attempts. However, further investigation is required to determine whether individuals with OCD have higher risk of death by suicide compared with those without OCD.
Methods
Of the entire Taiwanese population, between 2003 and 2017, 56,977 individuals with OCD were identified; they were then matched at a 1:4 ratio with 227,908 non-OCD individuals on the basis of their birth year and sex. Suicide mortality was assessed between 2003 and 2017 for both groups. Time-dependent Cox regression models were used to investigate the difference in suicide risk between individuals with versus without OCD.
Results
After adjustment for major psychiatric comorbidities (i.e., schizophrenia, bipolar disorder and major depressive disorder), the OCD group had higher risk of suicide (hazard ratio: 1.97, 95% confidence interval: 1.57–2.48) during the follow-up compared with the comparison group. Furthermore, OCD severity, as indicated by psychiatric hospitalizations due to OCD, was positively correlated with suicide risk.
Conclusions
Regardless of the existence of major psychiatric comorbidities, OCD was found to be an independent risk factor for death by suicide. A suicide prevention program specific to individuals with OCD may be developed in clinical practice in the future.
Bipolar disorder (BD) shows heterogeneous illness presentation both cross-sectionally and longitudinally. This phenotypic heterogeneity might reflect underlying genetic heterogeneity. At the same time, overlapping characteristics between BD and other psychiatric illnesses are observed at clinical and biomarker levels, which implies a shared biological mechanism between them. Incorporating these two issues in a single study design, this study investigated whether phenotypically heterogeneous subtypes of BD have a distinct polygenic basis shared with other psychiatric illnesses.
Methods
Six lifetime phenotype dimensions of BD identified in our previous study were used as target phenotypes. Associations between these phenotype dimensions and polygenic risk scores (PRSs) of major psychiatric illnesses from East Asian (EA) and other available populations were analyzed.
Results
Each phenotype dimension showed a different association pattern with PRSs of mental illnesses. PRS for EA schizophrenia showed a significant negative association with the cyclicity dimension (p = 0.044) but a significant positive association with the psychotic/irritable mania dimension (p = 0.001). PRS of EA major depressive disorder demonstrated a significant negative association with the elation dimension (p = 0.003) but a significant positive association with the comorbidity dimension (p = 0.028).
Conclusion
This study demonstrates that well-defined phenotype dimensions of lifetime-basis in BD have distinct genetic risks shared with other major mental illnesses. This finding supports genetic heterogeneity in BD and suggests a pleiotropy among BD subtypes and other psychiatric disorders beyond BD. Further genomic analyses adopting deep phenotyping across mental illnesses in ancestrally diverse populations are warranted to clarify intra-diagnosis heterogeneity and inter-diagnoses commonality issues in psychiatry.
This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents.
Design:
Population-based mortality follow-back study.
Setting:
Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used.
Participants:
All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents.
Methods:
Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends.
Results:
Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P <.001). Over the study period, although narrow spectrum antibiotics were used less, utilization and prescription of broad-spectrum antibiotics steadily increased, and prescription rates were higher in cancer decedents compared to non-cancer controls. Specifically, carbapenem prescription rates increased from 5.6% to 18.5%, (RR 1.087, 95% CI 1.085–1.088, P <.001) in cancer decedents and from 2.9% to 13.2% (RR 1.115, 95% CI 1.113–1.116, P <.001) in non-cancer decedents.
Conclusions:
Our findings show that patients at the EOL, especially those with cancer, are increasingly and highly exposed to broad-spectrum antibiotics. Measures of antibiotic stewardship are required among this population.
OBJECTIVES/GOALS: In the U.S., over 4 million people including children experience transient periods of undernutrition annually. Cardio-metabolic and renal diseases are more prevalent in this population. We are investigating therapeutic strategies to reverse the long-term risk of these diseases in a rat model of transient undernutrition followed by refeeding. METHODS/STUDY POPULATION: Thirty six female Fischer rats (3-months of age) were initially divided into 2 groups. Half were fed regular chow (CT) while the other half were severely food restricted (sFR) by 60% from 0-2 weeks (wks) followed by refeeding from 2-14 wks (sFR-Refed). These 2 groups were then subdivided and treated ± metformin (Met) from wk 7 to wk 12 (n=9/group). High precision ultrasound was conducted on live rats to assess heart and kidney function immediately after the sFR period ended (wk 2) and at the end of the study (wk 14). At the conclusion of the experiment, the rats were sacrificed and the histology of the kidney and heart tissues were analyzed in hematoxylin and eosin-stained sections. The protein to DNA ratio was also calculated in homogenates from these tissues. RESULTS/ANTICIPATED RESULTS: In sFR-Refed rats, cardiac output (CO), heart rate (HR) and renal artery blood flow (RBF) were decreased by 11 ± 1.5%#, 7.0 ± 6.0% and 22 ± 0.6%#, respectively, compared to control (CT) rats; #p<0.05. Mean glomerular diameter was reduced in the kidneys of sFR-refed rats compared to CT and this effect was attenuated by metformin treatment [(µm): CT, 406 ± 31; sFR-Refed, 383 ± 11, p<0.06; CT+Met, 393 ± 18; sFR-Refed+Met, 407 ± 18*]. Furthermore, the mean cardiomyocyte thickness was reduced in sFR-Refed rats compared to controls while metformin treatment prevented this effect [(µm): CT, 16.4 ± 3.6; sFR-Refed, 11.5 ± 2.3#; CT+Met, 16.4 ± 3.6; sFR-Refed+Met, 15.9 ± 3.2*]. #p<0.05 vs. CT, same treatment; *p<0.05 vs. Met, same diet; two-way ANOVA. DISCUSSION/SIGNIFICANCE: These findings have promising implications for metformin use to mitigate long-term impairments in heart and kidney structure and function in individuals who have experienced bouts of undernutrition earlier in life for either voluntarily (e.g., very low calorie dieting) or involuntary (e.g., very low food security) reasons.
OBJECTIVES/GOALS: Hypertension is a major risk factor for coronavirus disease 2019 (COVID-19) severity. Our goal was to determine if hypertension worsens lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters. METHODS/STUDY POPULATION: Male hamsters (7-8 weeks old) were infused with angiotensin II (AII; 200 ng/kg/min via osmotic minipump) for 4 weeks to induce hypertension. During the last week of the infusion, the hamsters were inoculated intranasally with vehicle (V) or SARS-CoV-2 (S; 1 x 105 plaque forming units/ml). Half of the hamsters were sacrificed 1 day post-inoculation (dpi-1) and the other half on dpi-6. Two scoring systems were applied to lung tissue sections stained with hematoxylin and eosin to determine the degree and severity of lung pathology: the first system assessed all pertinent alterations in the lungs, while the second system only assessed the pathology related to the pulmonary vasculature. Lung histopathology scores were calculated as the sum of the airway and lung alveolar scores in arbitrary units (AU). RESULTS/ANTICIPATED RESULTS: Studies revealed that the SARS-CoV-2-infected hamsters exhibited a 76-fold higher total airway score compared to vehicle controls [(AU): V, 0.25 ± 0.1; S, 19.00 ±1.35; p<0.05; n=4]. Total lung alveolar scores (27-fold) [(AU): V, 0.30 ± 0.11; S, 8.0 ± 4.1; p<0.05; n=4] and total vascular scores (17-fold) [(AU): V, 0.35 ± 0.2; S, 6.0 ±1.4; p<0.05; n=4] were also markedly higher compared to controls on dpi-1. AII increased blood pressure, which was sustained through the 4-week infusion period. Under these conditions, body weight slightly dropped by 4.5%. Ongoing studies are assessing the effect of hypertension on the % of airway, alveoli and vessels affected, airway and alveolar severity, and bronchiolar epithelial and type II pneumocyte hyperplasia. DISCUSSION/SIGNIFICANCE: Establishing the hypertensive hamster as a small animal model of COVID-19 will facilitate investigations into why preexisting hypertension is a risk factor for disease severity. These studies could lead to the development of novel therapeuticsfor treating COVID-19 patients with hypertension.
Although various clinical indicators of suicide have been recorded, the previous suicide attempt is meaningful as one of the most robust risk factors predicting subsequent suicide attempts but there are lacking in biomarkers for evaluating suicide attempts. This study aimed to analyze the correlation of changes in oxygenated hemoglobin concentration with lifetime suicide attempt during verbal fluency test.
Method:
A total of 60 patients with major depressive disorder (MDD) were enrolled. Demographic, clinical, physical, and psychological evaluations were conducted. We evaluated the suicidal behaviors through MINI suicidality item. We indicated verbal fluency test to examine prefrontal activation during the cognitive execution while fNIRS was observed.
Results:
54 of enrolled patient with MDD (23 those with a lifetime history of suicide attempt; 31 those without a lifetime history of suicide attempt) are eligible for the subject. The patients were 35.19% of those with a lifetime history of suicide attempt. The values of the changes in oxygenated hemoglobin involving the entire regions of prefrontal cortex were smaller in those with a lifetime history of suicide attempt. The biggest difference is in right VMPFC, the mean score of those with a lifetime history of suicide attempt and those without a lifetime history of suicide attempt were 0.095(SD, 1.032) and 0.610(SD, 1.038) although the statistically non-significance. We discovered that a small value of changes in oxygenated hemoglobin was related to lifetime suicide attempt through multivariable logistic regression analysis. After adjusting for age, sex, years of education, and HAMD, there was a significant difference in the right VMPFC [OR = 0.491(95% CI=0.235~0.916), p = 0.036].
Conclusions:
Study result indicated that the values of the changes in oxygenated hemoglobin were smaller in who attempted suicide before during cognitive execution. The adjusted regression analysis was presented significant result in right VMPFC. Therefore, the changes in oxygenated hemoglobin measured by fNIRS can be applied as a biomarker for suicidal behavior such as lifetime suicide attempt.
Although, attempts to apply virtual reality (VR) in mental healthcare are rapidly increasing, it is still unclear whether VR relaxation can reduce stress more than conventional biofeedback.
Methods:
Participants consisted of 83 healthy adult volunteers with high stress, which was defined as a score of 20 or more on the Perceived Stress Scale-10 (PSS-10). This study used an open, randomized, crossover design with baseline, stress, and relaxation phases. During the stress phase, participants experienced an intentionally generated shaking VR and serial-7 subtraction. For the relaxation phase, participants underwent a randomly assigned relaxation session on day 1 among VR relaxation and biofeedack, and the other type of relaxation session was applied on day 2. We compared the StateTrait Anxiety Inventory-X1 (STAI-X1), STAI-X2, the Numeric Rating Scale (NRS), and physiological parameters including heart rate variability (HRV) indexes in the stress and relaxation phases.
Results:
A total of 74 participants were included in the analyses. The median age of participants was 39 years, STAI-X1 was 47.27 (SD = 9.92), and NRS was 55.51 (SD = 24.48) at baseline. VR and biofeedback significantly decreased STAI-X1 and NRS from the stress phase to the relaxation phase, while the difference of effect between VR and biofeedback was not significant. However, there was a significant difference in electromyography, LF/HF ratio, LF total, and NN50 between VR relaxation and biofeedback
Conclusion:
VR relaxation was effective in reducing subjectively reported stress in individuals with high stress.
Virtual Reality (VR)-based Biofeedback (BF), a relatively new intervention, is rapidly increasing for the treatment of mood disorders. However, research on whether VR-based BF is more effective than traditional BF is still lacking.
Methods:
A total of 131 adults from the community enrolled in the study. Participants scored ≥10 on Patient Health Questionnaire-9 (PHQ-9) or ≥9 on Panic Disorder Severity Scale (PDSS) were randomly assigned to VR or BF group. Those who have not met the criteria of PHQ-9 and PDSS were classified as the control group. All participants visited three times across 3 months and received either VR-based or conventional BF intervention. The control group received the same treatment as the VR group. Also, on each visit, the participants completed Montgomery-Asberg Depression Rating Scale (MADRS), State-Trait Anxiety Inventory (STAI), and Visual Analogue Scale (VAS).
Results:
The analysis included 118 participants in total (VR: 40, BF: 38, Control: 40). There was no significant difference in demographic variables among the 3 groups. After the treatment, VR and BF groups exhibited significant decreases in MADRS, PHQ-9, STAI, and VAS compared to the baseline within each group (p<0.005). Importantly, compared to the BF group, the VR group showed a significantly greater decrease in STAI (p<0.05). Further analyses revealed that scores of MADRD, PHQ-9, STAI, and VAS also significantly decreased in highly stressed group compared to the control group.
Conclusion:
Findings suggest that the application of VR-based BF was effective in reducing anxiety and depressive symptoms in highly stressed people. Compared to conventional BF, VR-based BF can be a cost-effective treatment option especially for relieving anxiety.
Although people who attempted suicide tend to repeat suicide attempts, there is a lack of evidence on the association between psychiatric service factors and suicide reattempt among them.
Methods:
We used a nationwide, population-based medical record database of South Korea to investigate the use of psychiatric services before and after the index suicide attempt and the association between psychiatric service factors after the index suicide attempt with the risk of suicide reattempt.
Results:
Among 5,874 people who had attempted suicide, the all-cause mortality within 3 months after the suicide attempt was 11.6%. Among all subjects who attempted suicide, 30.6% of them had used psychiatric services within 6 months before the suicide attempt; 43.7% of them had used psychiatric services within 3 months after the suicide attempt. Among individuals who had visited clinics following attempted suicide, the cumulative incidence of suicide reattempt over a mean follow-up period of 5.1 years was 3.4%. About half of suicide reattempts occurred within 1 year after the index suicide attempt. Referral to psychiatric services within 7 days was associated with a decreased risk of suicide reattempt (adjusted hazard ratio, 0.51; 95% confidence intervals, 0.29-0.89).
Conclusion:
An early psychiatric referral within 1 week after a suicide attempt was associated with a decreased risk of suicide reattempt.
This study aimed to investigate the structural and metabolic changes in cumulus cells of underweight women and their effects on oocyte maturation and fertilization. The cytoplasmic ultrastructure was analyzed by electron microscopy, mitochondrial membrane potential by immunofluorescence, and mitochondrial DNA copy number by relative quantitative polymerase chain reaction. The expression of various proteins including the oxidative stress-derived product 4-hydroxynonenal (4-HNE) and autophagy and apoptosis markers such as Vps34, Atg-5, Beclin 1, Lc3-I, II, Bax, and Bcl-2 was assessed and compared between groups. Oocyte maturation and fertilization rates were lower in underweight women (P < 0.05), who presented with cumulus cells showing abnormal mitochondrial morphology and increased cell autophagy. Compared with the mitochondrial DNA copies of the control group, those of the underweight group increased but not significantly. The mitochondrial membrane potential was similar between the groups (P = 0.8). Vps34, Atg-5, Lc3-II, Bax, and Bcl-2 expression and 4-HNE levels were higher in the underweight group compared with the control group (P < 0.01); however, the Bax/Bcl-2 ratio was lower in the underweight group compared with the control group (P = 0.031). Additionally, Beclin 1 protein levels were higher in the underweight group compared with the control group but without statistical significance. In conclusion, malnutrition and other conditions in underweight women may adversely affect ovulation, and the development, and fertilization of oocytes resulting from changes to the intracellular structure of cumulus cells and metabolic processes. These changes may lead to reduced fertility or unsatisfactory reproduction outcomes in women.
During the past century, protest has become a shared experience around the world, as citizens across the continents have taken to the streets to demand political, social, and economic changes. In Asia—from China to India, Thailand to Myanmar—people have organized mass demonstrations to express their dissatisfaction with colonial and state governments and their policies. Often, people shared news and supported protests in neighboring countries, using it as an opportunity to mobilize and coordinate their efforts for protest and leading to a growing sense of regional solidarity. Solidarity is possible despite differences in culture, history, and language because the citizens in the region share universal values.
The “Fast track” protocol is an early extubation strategy to reduce ventilator-associated complications and induce early recovery after open-heart surgery. This study compared clinical outcomes between operating room extubation and ICU extubation after open-heart surgery in patients with CHD.
Methods:
We retrospectively reviewed 215 patients who underwent open-heart surgery for CHDs under the scheduled “Fast track” protocol between September 2016 and April 2022. The clinical endpoints were post-operative complications, including bleeding, respiratory and neurological complications, and hospital/ICU stays.
Results:
The patients were divided into operating room extubation (group O, n = 124) and ICU extubation (group I, n=91) groups. The most frequently performed procedures were patch closures of the atrial septal (107/215, 49.8%) and ventricular septal (89/215, 41.4%) defects. There were no significant differences in major post-operative complications or ICU and hospital stay duration between the two groups; however, patients in group I showed longer mechanical ventilatory support (0.0 min vs. 59.0 min (interquartile range: 17.0–169.0), p < 0.001). Patients in Group O showed higher initial lactate levels (3.2 ± 1.7 mg/dL versus 2.5 ± 2.0 mg/dL, p = 0.007) and more frequently used additional sedatives and opioid analgesics (33.1% versus 19.8%, p = 0.031).
Conclusions:
Extubation in the operating room was not beneficial for patients during post-operative ICU or hospital stay. Early extubation in the ICU resulted in more stable hemodynamics in the immediate post-operative period and required less use of sedatives and analgesics.
Evidence suggests a familial coaggregation of major psychiatric disorders, including schizophrenia, bipolar disorder, major depression (MDD), autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Those disorders are further related to suicide and accidental death. However, whether death by suicide may coaggregate with accidental death and major psychiatric disorders within families remains unclear.
Aims
To clarify the familial coaggregation of deaths by suicide with accidental death and five major psychiatric disorders.
Method
Using a database linked to the entire Taiwanese population, 68 214 first-degree relatives of individuals who died by suicide between 2003 and 2017 and 272 856 age- and gender-matched controls were assessed for the risks of death by suicide, accidental death and major psychiatric disorders.
Results
A Poisson regression model showed that the first-degree relatives of individuals who died by suicide were more likely to die by suicide (relative risk RR = 4.61, 95% CI 4.02–5.29) or accident (RR = 1.62, 95% CI 1.43–1.84) or to be diagnosed with schizophrenia (RR = 1.53, 95% CI 1.40–1.66), bipolar disorder (RR = 1.99, 95% CI 1.83–2.16), MDD (RR = 1.98, 95% CI 1.89–2.08) or ADHD (RR = 1.34, 95% CI 1.24–1.44).
Conclusions
Our findings identified a familial coaggregation of death by suicide with accidental death, schizophrenia, major affective disorders and ADHD. Further studies would be required to elucidate the pathological mechanisms underlying this coaggregation.
OBJECTIVES/GOALS: Hamsters develop COVID-19 similarly to people because the SARS-CoV-2 spike protein binds with high affinity to hamster ACE2 resulting in host cell entry and replication. Our goal was to establish a hamster model that mirrors the lung and brain pathophysiology observed in COVID-19. METHODS/STUDY POPULATION: Hamsters infected with SARS CoV-2 are sacrificed on day 1 and day 6 postinfection. Lung histopathology scoring model was implemented for assessment all pathological relevant changes in the lungs of infected animals on tissue sections stained with hematoxylin and eosin. To quantify the extent and severity of lung pathology, two scoring systems were used: the first evaluated all relevant changes in the lungs of the infected animals and the second evaluated only the pathology associated with the pulmonary vasculature. Percentage of airway affected, airway severity, bronchiolar epithelial hyperplasia, alveoli affected, alveolar severity, type II pneumocyte hyperplasia and vessels affected were analyzed. Total airway score plus total lung alveolar score give lung histopathology score. RESULTS/ANTICIPATED RESULTS: Compared to the control hamster, the hamsters day 1 postinfection, exhibited a higher total airway score [9.00 ± 1.35 vs. 0.25 ± 0.1; p DISCUSSION/SIGNIFICANCE: Establishing this outstanding small animal model of COVID-19 will facilitate studies investigating diagnostics, prognosis and response to treatment in COVID-19 disease. These studies will provide insights that will complement on-going clinical trials on angiotensin type 1 receptor (AT1R) blockers (ARBs) in COVID-19.
OBJECTIVES/GOALS: Rodents are the most widely used experimental animals to study disease mechanisms due to their availability and cost-effectiveness. An international drive to investigate the pathophysiology of COVID-19 is inhibited by the resistance of rats and mice to SARS-CoV-2 infection. Our goal was to establish an appropriate small animal model. METHODS/STUDY POPULATION: To recreate the cytokine storm that is associated with COVID-19, we injected angiotensin converting enzyme 2 knockout (ACE2KO) mice (C57BI/6 strain) with lipopolysaccharide (LPS) intraperitoneally and measured the expression of multiple cytokines as a function of time and LPS dose. We then chose a minimum dose (500ug/kg) and time (3h) when multiple cytokines were elevated to measure lung injury scores using a point-counting technique on tissue sections stained with hematoxylin and eosin. The data are expressed as mean percentage of grid points lying within the peribronchial and superficial area in up to 20 fields. Percentage of peribronchial and superficial intrapulmonary hemorrhage, congestion, neutrophil infiltration and area of alveolar space were all assessed. RESULTS/ANTICIPATED RESULTS: Compared to the wildtype group (WT-G), the LPS-injected ACE2KO mice (LPS-G) exhibited a higher percentage of peribronchial intrapulmonary hemorrhage [(%): LPS-G, 10.56 ± 2.06 vs. WT-G, 5.59 ± 0.53; p DISCUSSION/SIGNIFICANCE: Establishing this novel mouse model of COVID-19 will facilitate studies investigating tissue-specific mechanisms of pathogenesis in this disease. This model can also be used to discover novel therapeutic targets and the design of clinical trials focusing on diagnostics, treatments and outcomes in COVID-19.
According to the public data collected from the Health Commission of Gansu Province, China, regarding the COVID-19 pandemic during the summer epidemic cycle in 2022, the epidemiological analysis showed that the pandemic spread stability and the symptom rate (the number of confirmed cases divided by the sum of the number of asymptomatic cases and the number of confirmed cases) of COVID-19 were different among 3 main epidemic regions, Lanzhou, Linxia, and Gannan; both the symptom rate and the daily instantaneous symptom rate (daily number of confirmed cases divided by the sum of daily number of asymptomatic cases and daily number of confirmed cases) in Lanzhou were substantially higher than those in Linxia and Gannan. The difference in the food sources due to the high difference of the population ethnic composition in the 3 regions was probably the main driver for the difference of the symptom rates among the 3 regions. This work provides potential values for prevention and control of COVID-19 in different regions.
The current study aims to confirm the positive effects of dietary nano-Se on nutrients deposition and muscle fibre formation in grass carp fed with high-fat diet (HFD) before overwintering and to reveal its possible molecular mechanism. The lipid deposition, protein synthesis and muscle fibre formation in grass carp fed with regular diet (RD), HFD or HFD supplemented with nano-Se (0·3 or 0·6 mg/kg) for 60 d were tested. Results show that nano-Se significantly reduced lipid content, dripping loss and fibre diameter (P < 0·05), but increased protein content, post-mortem pH24 h and muscle fibre density (P < 0·05) in muscle of grass carp fed with HFD. Notably, dietary nano-Se decreased lipid deposition in the muscle by regulating amp-activated protein kinase activity and increased protein synthesis and fibre formation in muscle by activating target of rapamycin and myogenic determining factors pathways. In summary, dietary nano-Se can regulate the nutrients deposition and muscle fibre formation in grass carp fed with HFD, which exhibit potential benefit for improving flesh quality of grass carp fed with HFD.