Repurposed dihydroorotate dehydrogenase inhibitors with efficacy against drug-resistant Acinetobacter baumannii.

New antimicrobials are needed for the treatment of extensively drug-resistant Acinetobacter baumannii. The de novo pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is a validated drug target for malaria and human autoimmune diseases. We provide genetic evidence that A. baumannii DHODH (AbDHODH) is essential for bacterial survival in rodent infection models. We chemically validate the target by repurposing a unique library of ~450 triazolopyrimidine/imidazopyrimidine analogs developed for our malaria DHODH program to identify 21 compounds with submicromolar activity on AbDHODH. The most potent (DSM186, DHODH IC50 28 nM) had a minimal inhibitory concentration of ≤1 µg/ml against geographically diverse A. baumannii strains, including meropenem-resistant isolates. A structurally related analog (DSM161) with a long in vivo half-life conferred significant protection in the neutropenic mouse thigh infection model. Encouragingly, the development of resistance to these compounds was not identified in vitro or in vivo. Lastly, the X-ray structure of AbDHODH bound to DSM186 was solved to 1.4 Å resolution. These data support the potential of AbDHODH as a drug target for the development of antimicrobials for the treatment of A. baumannii and potentially other high-risk bacterial infections.

Global monitoring of the impact of the COVID-19 pandemic through online surveys sampled from the Facebook user base.

Simultaneously tracking the global impact of COVID-19 is challenging because of regional variation in resources and reporting. Leveraging self-reported survey outcomes via an existing international social media network has the potential to provide standardized data streams to support monitoring and decision-making worldwide, in real time, and with limited local resources. The University of Maryland Global COVID-19 Trends and Impact Survey (UMD-CTIS), in partnership with Facebook, has invited daily cross-sectional samples from the social media platform's active users to participate in the survey since its launch on April 23, 2020. We analyzed UMD-CTIS survey data through December 20, 2020, from 31,142,582 responses representing 114 countries/territories weighted for nonresponse and adjusted to basic demographics. We show consistent respondent demographics over time for many countries/territories. Machine Learning models trained on national and pooled global data verified known symptom indicators. COVID-like illness (CLI) signals were correlated with government benchmark data. Importantly, the best benchmarked UMD-CTIS signal uses a single survey item whereby respondents report on CLI in their local community. In regions with strained health infrastructure but active social media users, we show it is possible to define COVID-19 impact trajectories using a remote platform independent of local government resources. This syndromic surveillance public health tool is the largest global health survey to date and, with brief participant engagement, can provide meaningful, timely insights into the global COVID-19 pandemic at a local scale.

Disparities in Implementing COVID-19 Prevention Strategies in Public Schools, United States, 2021-22 School Year.

During the COVID-19 pandemic, US schools have been encouraged to take a layered approach to prevention, incorporating multiple strategies to curb transmission of SARS-CoV-2. Using survey data representative of US public K-12 schools (N = 437), we determined prevalence estimates of COVID-19 prevention strategies early in the 2021-22 school year and describe disparities in implementing strategies by school characteristics. Prevalence of prevention strategies ranged from 9.3% (offered COVID-19 screening testing to students and staff) to 95.1% (had a school-based system to report COVID-19 outcomes). Schools with a full-time school nurse or school-based health center had significantly higher odds of implementing several strategies, including those related to COVID-19 vaccination. We identified additional disparities in prevalence of strategies by locale, school level, and poverty. Advancing school health workforce and infrastructure, ensuring schools use available COVID-19 funding effectively, and promoting efforts in schools with the lowest prevalence of infection prevention strategies are needed for pandemic preparedness.

The prevalence, hospitalization outcomes and risk factors of euthyroid sick syndrome in patients with diabetic ketosis/ketoacidosis.

BACKGROUND: To investigate the prevalence of euthyroid sick syndrome (ESS) and to evaluate the outcomes and risk factors associated with ESS among hospitalized patients with diabetic ketosis (DK) or diabetic ketoacidosis (DKA). METHODS: Laboratory and clinical data of 396 adult hospitalized DK/DKA patients with or without ESS were collected and analyzed. Spearman linear analysis and multivariable logistic regression analyses were used to evaluate correlated factors of thyroid hormones and risk factors of ESS. RESULTS: Most of the individuals were diagnosed with type 2 diabetes (359/396, 90.7%). The prevalence of ESS was 57.8% (229/396). Patients in ESS group were older and had a longer course of diabetes. Levels of thyroid hormones, serum lipids, and parameters reflecting acidosis were significantly decreased in ESS group. The proportion of patients with infection, acute renal injury and DKA was significantly higher in ESS group than in control group, accompanied by longer hospitalization stay and higher hospitalization costs. Free triiodothyronine positively correlates with albumin, eGFR, parameters reflecting acidosis and lipid profiles (All P < 0.001), and negatively correlates with age, onset age, 24-h urine albumin, hsCRP and WBC count (All P < 0.001). Hypoalbuminemia, low level of carbon dioxide combining power, high level of HbA1c and WBC, and co-infection are shown to be risk factors for ESS (OR = 0.866, 0.933, 1.112, 1.146, 1.929, respectively; All P < 0.05). CONCLUSIONS: The prevalence of ESS was high in adult DK/DKA patients. Patients with ESS had inferior clinical and socioeconomic outcomes. Early recognition and management of patients with ESS may be necessary to improve outcome.

Diagnostic Value of Radiomics Analysis Based on Multimodal MRI for Advanced Liver Fibrosis in Patients with Hepatitis B.

BACKGROUND: The goal was to explore the value of using radiomics analysis based on multimodal MRI for evaluating the advanced fibrosis in patients with hepatitis B. METHODS: One hundred and forty-three patients with hepatitis B fibrosis were randomly divided into training and validation cohorts in a 2:1 ratio. In the training cohort, a clinical model was established with logistic regression, a radiomics signature based on multimodal MRI was established with support vector machine (SVM), and a nomogram integrated the radiomics signature and clinical factors. The value of three models was assessed by ROC analysis in the training and validation cohorts. RESULTS: The nomogram demonstrated the largest area under the ROC curve. The nomogram presented good agreement in the prediction probability of advanced liver fibrosis in two cohorts. CONCLUSIONS: Radiomics analysis has good diagnostic value for advanced liver fibrosis and the nomogram can enhance the diagnostic value.

Alternative pathways utilize or circumvent putrescine for biosynthesis of putrescine-containing rhizoferrin.

The siderophore rhizoferrin (N1,N4-dicitrylputrescine) is produced in fungi and bacteria to scavenge iron. Putrescine-producing bacterium Ralstonia pickettii synthesizes rhizoferrin and encodes a single nonribosomal peptide synthetase-independent siderophore (NIS) synthetase. From biosynthetic logic, we hypothesized that this single enzyme is sufficient for rhizoferrin biosynthesis. We confirmed this by expression of R. pickettii NIS synthetase in Escherichia coli, resulting in rhizoferrin production. This was further confirmed in vitro using the recombinant NIS synthetase, synthesizing rhizoferrin from putrescine and citrate. Heterologous expression of homologous lbtA from Legionella pneumophila, required for rhizoferrin biosynthesis in that species, produced siderophore activity in E. coli. Rhizoferrin is also synthesized by Francisella tularensis and Francisella novicida, but unlike R. pickettii or L. pneumophila, Francisella species lack putrescine biosynthetic pathways because of genomic decay. Francisella encodes a NIS synthetase FslA/FigA and an ornithine decarboxylase homolog FslC/FigC, required for rhizoferrin biosynthesis. Ornithine decarboxylase produces putrescine from ornithine, but we show here in vitro that FigA synthesizes N-citrylornithine, and FigC is an N-citrylornithine decarboxylase that together synthesize rhizoferrin without using putrescine. We co-expressed F. novicida figA and figC in E. coli and produced rhizoferrin. A 2.1 Å X-ray crystal structure of the FigC N-citrylornithine decarboxylase reveals how the larger substrate is accommodated and how active site residues have changed to recognize N-citrylornithine. FigC belongs to a new subfamily of alanine racemase-fold PLP-dependent decarboxylases that are not involved in polyamine biosynthesis. These data reveal a natural product biosynthetic workaround that evolved to bypass a missing precursor and re-establish it in the final structure.

Ventilation Improvement Strategies Among K-12 Public Schools - The National School COVID-19 Prevention Study, United States, February 14-March 27, 2022.

Effective COVID-19 prevention in kindergarten through grade 12 (K-12) schools requires multicomponent prevention strategies in school buildings and school-based transportation, including improving ventilation (1). Improved ventilation can reduce the concentration of infectious aerosols and duration of potential exposures (2,3), is linked to lower COVID-19 incidence (4), and can offer other health-related benefits (e.g., better measures of respiratory health, such as reduced allergy symptoms) (5). Whereas ambient wind currents effectively dissipate SARS-CoV-2 (the virus that causes COVID-19) outdoors,* ventilation systems provide protective airflow and filtration indoors (6). CDC examined reported ventilation improvement strategies among a nationally representative sample of K-12 public schools in the United States using wave 4 (February 14-March 27, 2022) data from the National School COVID-19 Prevention Study (NSCPS) (420 schools), a web-based survey administered to school-level administrators beginning in summer 2021.† The most frequently reported ventilation improvement strategies were lower-cost strategies, including relocating activities outdoors (73.6%), inspecting and validating existing heating, ventilation and air conditioning (HVAC) systems (70.5%), and opening doors (67.3%) or windows (67.2%) when safe to do so. A smaller proportion of schools reported more resource-intensive strategies such as replacing or upgrading HVAC systems (38.5%) or using high-efficiency particulate air (HEPA) filtration systems in classrooms (28.2%) or eating areas (29.8%). Rural and mid-poverty-level schools were less likely to report several resource-intensive strategies. For example, rural schools were less likely to use portable HEPA filtration systems in classrooms (15.6%) than were city (37.7%) and suburban schools (32.9%), and mid-poverty-level schools were less likely than were high-poverty-level schools to have replaced or upgraded HVAC systems (32.4% versus 48.8%). Substantial federal resources to improve ventilation in schools are available.§ Ensuring their use might reduce SARS-CoV-2 transmission in schools. Focusing support on schools least likely to have resource-intensive ventilation strategies might facilitate equitable implementation of ventilation improvements.

The Ameliorative Effect of COST on Diet-Induced Lipid Metabolism Disorders by Regulating Intestinal Microbiota.

BACKGROUND: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders. METHODS: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation. CONCLUSIONS: intestinal microbiota plays a key role in COST inhibition of lipid metabolism disorder induced by a high fat and high sugar diet. In particular, COST may play a central regulatory role in microbiota, including Bacteroides, Akkermansia, and Desulfovibrio. Taken together, our work suggests that COST may improve the composition of gut microbes, increase the abundance of beneficial bacteria, improve lipid metabolism disorders, and inhibit the development of metabolic disorders.

[Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation]. / äº§ç§‘å‡ºé™¢åŽå› ä¸¥é‡é«˜èƒ†çº¢ç´ è¡€ç—‡ä½é™¢æ–°ç”Ÿå„¿å ¥é™¢å‰éšè®¿æƒ å†µåŠéšè®¿ä¾ä»Žæ€§å½±å“å› ç´ çš„å¤šä¸­å¿ƒè°ƒæŸ¥.

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS: Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

Incidence of microcarcinoma and non-microcarcinoma in ultrasound-found thyroid nodules.

BACKGROUNDS: The incidence of thyroid nodules is increasing year by year around the world. However, ultrasound is not recommended as a screening test for the general population or patients with a normal thyroid on palpation by the American Association of Clinical Endocrinologists (AACE). In practice, some individuals with normal thyroid palpation have nodules that can just be found out by ultrasound. No studies have directly described the risk of nodules found by ultrasound or by palpation up to now. More evidence is needed to carry out for helping us balance the over diagnosis and missed diagnosis of malignant lesions. Therefore, we carried out a retrospective study to investigate the incidence of malignant lesions in ultrasound-found nodules in a large cohort. METHODS: We conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between Jan 2013 and Dec 2019. The cytologic examinations were analyzed based on the Bethesda system. For nodules suspected to be follicular neoplasm or other malignant tumors by cytological tests, patients were recommended for surgery and histopathology examinations. RESULTS: Compared with palpation-found nodules, ultrasound-found nodules were presenting less as purely cystic nodules (10.1 % vs. 39.9 %, x2 = 355.69, p = 0.000), smaller size (17.5 ± 9.9 mm vs. 28.0 ± 12.5 mm, t = 23.876 p = 0.000), and higher TI-RADS score (5.5 ± 2.9 vs. 3.4 ± 3.3, t = 18.084, p = 0.000), respectively. More ultrasound-found nodules were diagnosed as carcinoma by histology examinations [136 (11.2 %) nodules found by ultrasound vs. 68 (3.9 %) by palpation, x2 = 59.737, p = 0.000], and 88 (64.7 %) nodules found by ultrasound were non-microcarcinoma. Among the malignant nodules confirmed by histopathology, a higher proportion of microcarcinoma was detected in ultrasound-found nodules [35.3 % (48/136) vs. 16.2 % (11/68), x2 = 8.183, p = 0.004]. CONCLUSIONS: In view of the results observed in our research, malignant nodules were more common in nodules screened out by ultrasound, and nearly two thirds of them were non-microcarcinoma. We suggest the recommendation against screening thyroid nodules by ultrasound needs to be re-evaluated.

Global trends and predictors of face mask usage during the COVID-19 pandemic.

BACKGROUND: Guidelines and recommendations from public health authorities related to face masks have been essential in containing the COVID-19 pandemic. We assessed the prevalence and correlates of mask usage during the pandemic. METHODS: We examined a total of 13,723,810 responses to a daily cross-sectional online survey in 38 countries of people who completed from April 23, 2020 to October 31, 2020 and reported having been in public at least once during the last 7 days. The outcome was individual face mask usage in public settings, and the predictors were country fixed effects, country-level mask policy stringency, calendar time, individual sociodemographic factors, and health prevention behaviors. Associations were modeled using survey-weighted multivariable logistic regression. RESULTS: Mask-wearing varied over time and across the 38 countries. While some countries consistently showed high prevalence throughout, in other countries mask usage increased gradually, and a few other countries remained at low prevalence. Controlling for time and country fixed effects, sociodemographic factors (older age, female gender, education, urbanicity) and stricter mask-related policies were significantly associated with higher mask usage in public settings. Crucially, social behaviors considered risky in the context of the pandemic (going out to large events, restaurants, shopping centers, and socializing outside of the household) were associated with lower mask use. CONCLUSION: The decision to wear a face mask in public settings is significantly associated with sociodemographic factors, risky social behaviors, and mask policies. This has important implications for health prevention policies and messaging, including the potential need for more targeted policy and messaging design.

A multicenter retrospective study on survival rate and complications of very preterm infants. / æžæ—©äº§å„¿å­˜æ´»çŽ‡å’Œå¹¶å‘ç—‡çš„å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications. METHODS: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants. RESULTS: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25+6 weeks, 26-26+6 weeks, 27-27+6 weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks, and 31-31+6 weeks had a survival rate of 32.5%, 60.6%, 68.0%, 82.9%, 90.1%, 92.3%, and 94.8% respectively. The survival rate tended to increase with the gestational age (P<0.05) and the survival rate without serious complications in each gestational age group was 7.5%, 18.1%, 34.5%, 52.2%, 66.7%, 75.7%, and 81.8% respectively, suggesting that the survival rate without serious complications increased with the gestational age (P<0.05). The multivariate logistic regression analysis showed that high gestational age, high birth weight, and prenatal use of glucocorticoids were protective factors against death in very preterm infants (P<0.05), and 1-minute Apgar score ≤3 was a risk factor for death in very preterm infants (P<0.05); high gestational age and high birth weight were protective factors against serious complications in very preterm infants who survived (P<0.05), while 5-minute Apgar score ≤3 and maternal chorioamnionitis were risk factors for serious complications in very preterm infants who survived (P<0.05). CONCLUSIONS: The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.

The Association Of Serum Cortisol Level With Microalbuminuria In Patients With Type 2 Diabetes And Prediabetes.

Whether cortisol secretion is linked with microalbuminuria remains undefined. We aimed to investigate the relationship between serum cortisol levels and the presence of microalbuminuria in patients with type 2 diabetes (T2DM) and prediabetes. A cross-sectional study was conducted with 211 patients with T2DM or prediabetes. Serum cortisol was measured at 8:00 h, 16:00 h, and 0:00 h. The level and circadian rhythm of ACTH were also evaluated. Urine excretion of albumin was measured. Patients were subdivided into microalbuminuria (MAU) group (n= 120) and normoalbuminuria (NAU) group (n = 91) according to the status of microalbuminuria. Levels of serum cortisol (8:00 h: 426.9 ± 155.0 nmol/; 16:00 h: 303.7 ± 144.7 nmol/L) were significantly higher in MAU group than in NAU group (8:00 h: 370.2 ±130.6 nmol/L, P = 0.004; 16:00 h: 234.7 ± 120.2 nmol/L, P = 0.001). After adjustment for multiple factors, the correlation between cortisol levels (both at 8:00 h (P = 0.005) and at 16:00 h (P = 0.001)) and microalbuminuria remained consistent and significant. Higher levels of cortisol (cut-off value: 390.5 nmol/L at 8:00 h, 203.5 nmol/L at 16:00 h) help to detect the development of microalbuminuria. Serum cortisol secretion is associated with the presence of microalbuminuria in patients with T2DM and patients with prediabetes. Higher levels of cortisol, even in the normal range, may be related with the development of microalbuminuria.

Autophagy: a promising process for the treatment of acetaminophen-induced liver injury.

Toxicity from drugs has become an important cause of acute liver failure. Acetaminophen, a commonly used analgesic, can cause severe acute liver injury that can worsen into acute liver failure. Autophagy, a protective cell programme, has been reported to have protective effects in a variety of diseases such as cancer, immune diseases, neurodegenerative diseases, and inflammatory diseases. In this review, we describe how an excess of acetaminophen causes liver injury step by step, from the formation of the initial protein adduct to the final hepatocyte necrosis, as well as the induction of autophagy and its beneficial effects on diseases. Emphasis is placed on the potential effect of autophagy on improving the damage of acetaminophen to hepatocytes. Finally, we are committed to providing insights into the treatment of acute liver failure through the mechanism of acetaminophen induced liver injury, the mechanism of autophagy, and the link between autophagy and liver injury.

Dose-dependent effect of human milk on Bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND AND AIM: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. METHODS: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables. RESULTS: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979). CONCLUSIONS: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.

[An investigation of severe neonatal hyperbilirubinemia in 13 hospitals of Jiangsu Province, China].

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS: Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.

Therapeutic Effect of Chitooligosaccharide Tablets on Lipids in High-Fat Diets Induced Hyperlipidemic Rats.

Chitooligosaccharide is beneficial for inhibiting dyslipidemia and reducing atherosclerotic and hyperlipidemic risk. The purpose of this study was to investigate the cholesterol-regulating effects and potential mechanisms of Chitooligosaccharide tablets (CFTs) in high-fat diet-induced hyperlipidemic rats. The results revealed that CFTs can regulate serum lipid levels in hyperlipidemic rats in a dosage-dependent manner. Synchronously, gene expressions related to cholesterol excretion were upregulated in a dosage-dependent manner, including cholesterol 7α-hydroxylase (CYP7A1), liver X receptor α (LXRA), peroxisome proliferation-activated receptor-α (PPARα) and low-density lipoprotein receptor (LDLR), whereas cholesterol synthetic gene expressions including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and sterol-responsive element binding protein-2 (SREBP2) were reduced. This work highlights that CFTs have potential as natural products to prevent and treat metabolic hyperlipidemia syndrome, probably due to the reduction of cholesterol biosynthesis and through cholesterol elimination; they also improve the pathological changes of liver tissue in rats, alleviate liver damage, maintain normal lipid metabolism in the liver, ameliorate hepatic glycolipid disorders and accelerate TC operation, and reduce blood lipid levels.

Anti-Obesity Effect of Chitosan Oligosaccharide Capsules (COSCs) in Obese Rats by Ameliorating Leptin Resistance and Adipogenesis.

Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment.

[A single-center study on the incidence and mortality of preterm infants from 2006 to 2016].

OBJECTIVE: To investigate the incidence and mortality rates of preterm infants and the main causes of death. METHODS: The basic information of preterm infants was collected from their medical records and admission/discharge records to analyze the incidence and mortality rates of preterm infants and the causes of their death. RESULTS: There were 76 812 neonates born in the Xuzhou Maternal and Child Health Hospital from January 2006 to December 2016, among whom 5 585 (7.27%) were preterm infants. The incidence rate of preterm infants tended to increase over these years (P<0.001). The overall mortality rate was 5.01% (280/5 585), and the mortality rate tended to decrease over these years (P<0.001). The mortality rate increased with the reductions in birth weight and gestational age (P<0.001). The top four causes of death in preterm infants were respiratory distress syndrome (44.3%), severe asphyxia (12.9%), neonatal malformation (4.3%), and pulmonary hemorrhage (2.9%) respectively. With the increase in birth weight, there were significant reductions in the constituent ratios of death due to respiratory distress syndrome and severe asphyxia (P<0.001). CONCLUSIONS: The incidence rate of preterm infants tended to increase and their mortality rate tended to decrease from 2006 to 2016. The mortality rate of preterm infants is associated with gestational age and birth weight. Respiratory distress syndrome and severe asphyxia are the main causes of death in preterm infants.

Association Between Social Vulnerability and SARS-CoV-2 Seroprevalence in Specimens Collected From Commercial Laboratories, United States, September 2021-February 2022.

OBJECTIVE: We conducted a national US study of SARS-CoV-2 seroprevalence by Social Vulnerability Index (SVI) that included pediatric data and compared the Delta and Omicron periods during the COVID-19 pandemic. The objective of the current study was to assess the association between SVI and seroprevalence of infection-induced SARS-CoV-2 antibodies by period (Delta vs Omicron) and age group. METHODS: We used results of infection-induced SARS-CoV-2 antibody assays of clinical sera specimens (N = 406 469) from 50 US states from September 2021 through February 2022 to estimate seroprevalence overall and by county SVI tercile. Bivariate analyses and multilevel logistic regression models assessed the association of seropositivity with SVI and its themes by age group (0-17, ≥18 y) and period (Delta: September-November 2021; Omicron: December 2021-February 2022). RESULTS: Aggregate infection-induced SARS-CoV-2 antibody seroprevalence increased at all 3 SVI levels; it ranged from 25.8% to 33.5% in September 2021 and from 53.1% to 63.5% in February 2022. Of the 4 SVI themes, socioeconomic status had the strongest association with seroprevalence. During the Delta period, we found significantly more infections per reported case among people living in a county with high SVI (odds ratio [OR] = 2.76; 95% CI, 2.31-3.21) than in a county with low SVI (OR = 1.65; 95% CI, 1.33-1.97); we found no significant difference during the Omicron period. Otherwise, findings were consistent across subanalyses by age group and period. CONCLUSIONS: Among both children and adults, and during both the Delta and Omicron periods, counties with high SVI had significantly higher SARS-CoV-2 antibody seroprevalence than counties with low SVI did. These disparities reinforce SVI's value in identifying communities that need tailored prevention efforts during public health emergencies and resources to recover from their effects.