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We aimed to comprehensively examine the association of breastfeeding, types and initial timing of complementary foods with adolescent cognitive development in low- and middle-income countries. We conducted a prospective cohort study of 745 adolescents aged 10-12 who were born to women who participated in a randomized trial of prenatal micronutrient supplementation in rural western China. An infant feeding index was constructed based on current World Health Organization (WHO) recommendations. Full-scale intelligence quotient (FSIQ) was assessed and derived by the Fourth Edition of the Wechsler Intelligence Scale for Children. The duration of exclusive or any breastfeeding was not significantly associated with adolescent cognitive development. Participants who regularly consumed iron-rich or iron-fortified foods during 6-23 months of age had higher FSIQ than those who did not (adjusted mean differences [aMDs] 4.25; 95% confidence interval [CI] 1.99, 6.51). For cow’s/goat’s milk and high protein-based food, the highest FSIQ were found in participants who initially consumed at 10-12 months and 7-9 months, respectively. A strong dose-response relationship of the composite infant feeding index was also identified, with participants in the highest tertile of overall feeding quality having 3.03 (95% CI 1.37, 4.70) points higher FSIQ than those in the lowest tertile. These findings suggest that appropriate infant feeding practices (breastfeeding plus timely introduction of appropriate complementary foods) were associated with significantly improved early adolescent cognitive development scores in rural China. In addition, improvement in iron-rich or iron-fortified foods complementary feeding may produce better adolescent cognitive development outcomes.
We established a mastitis model using exogenous infection of the mammary gland of Chinese Holstein cows with Staphylococcus aureus and extracted total RNA from S. aureus-infected and healthy mammary quarters. Differential expression of genes due to mastitis was evaluated using Affymetrix technology and results revealed a total of 1230 differentially expressed mRNAs. A subset of affected genes was verified via Q-PCR and pathway analysis. In addition, Solexa high-throughput sequencing technology was used to analyze profiles of miRNA in infected and healthy quarters. These analyses revealed a total of 52 differentially expressed miRNAs. A subset of those results was verified via Q-PCR. Bioinformatics techniques were used to predict and analyze the correlations among differentially expressed miRNA and mRNA. Results revealed a total of 329 pairs of negatively associated miRNA/mRNA, with 31 upregulated pairs of mRNA and 298 downregulated pairs of mRNA. Differential expression of miR-15a and interleukin-1 receptor-associated kinase-like 2 (IRAK2), were evaluated by western blot and luciferase reporter assays. We conclude that miR-15a and miR-15a target genes (IRAK2) constitute potential miRNA–mRNA regulatory pairs for use as biomarkers to predict a mastitis response.
Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.
The evolution of Northern Hemisphere ice sheets through the last glacial cycle is simulated with the glacial index method by using the climate forcing from one General Circulation Model, COSMOS. By comparing the simulated results to geological reconstructions, we first show that the modelled climate is capable of capturing the main features of the ice-sheet evolution. However, large deviations exist, likely due to the absence of nonlinear interactions between ice sheet and other climate components. The model uncertainties of the climate forcing are examined using the output from nine climate models from the Paleoclimate Modelling Intercomparison Project Phase III. The results show a large variability in simulated ice sheets between the different models. We find that the ice-sheet extent pattern resembles summer surface air temperature pattern at the Last Glacial Maximum, confirming the dominant role of surface ablation process for high-latitude Northern Hemisphere ice sheets. This study shows the importance of the upper boundary condition for ice-sheet modelling, and implies that careful constraints on climate output is essential for simulating realistic glacial Northern Hemisphere ice sheets.
Background: Sotos syndrome is a genetic condition caused by NSD1 alterations, characterized by overgrowth, macrocephaly, dysmorphic features, and learning disability. Approximately half of children with Sotos syndrome develop seizures. We investigated the spectrum of seizure phenotypes in these patients. Methods: Patients were recruited from clinics and referral from support groups. Those withclinical or genetic diagnosis of Sotos syndrome and seizures were included. Phenotyping data was collected via structured clinical interview and medical chart review. Results: 25 patients with typical Sotos syndrome features were included. Of 14 tested patients, 64% (n=9) had NSD1 alterations. Most had developmental impairment (80%, n=20) and neuropsychiatric comorbidities (68%, n=17). Seizure onset was variable (2 months to 12 years). Febrile and absence seizures were the most frequent types (64%, n=16). Afebrile generalized tonicclonic (40%, n=10) and atonic (24%, n=6) seizures followed. Most patients (60%, n=15) had multiple seizure types. The majority (72%, n=18) was controlled on a single antiepileptic, or none; 4% (n=1) remained refractory to antiepileptics. Conclusions: The seizure phenotype in Sotos syndrome most commonly involves febrile convulsions or absence seizures. Afebrile tonic-clonic or atonic seizures may also occur. Seizures are typically well-controlled with antiepileptics. The rate of developmental impairment and neuropsychiatric comorbidities is high.
Background: To evaluate efficacy, safety, and tolerability of ubrogepant for acute treatment of migraine attacks. Methods: Multicenter, double-blind, phase 3 study (NCT02867709). Randomized patients (1:1:1, placebo or ubrogepant 25mg or 50mg) had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints (2 hours post initial dose): headache pain freedom and absence of most bothersome migraine-associated symptom (MBS). Secondary endpoints: pain relief, sustained pain relief, sustained pain freedom, and absence of migraine-associated symptoms. Results: 1686 patients were randomized (safety population: n=1465; mITT population: n=1355). Mean age: 41 years; white: 81%; female: 89%. Significantly greater proportions of ubrogepant- than placebo-treated patients achieved 2-hour pain freedom (placebo: 14.3%; 25mg: 20.7%, adjusted P=0.0285; 50mg: 21.8%, adjusted P=0.0129) and absence of MBS for 50mg (placebo: 27.4%; 50mg: 38.9%, adjusted P=0.0129). Secondary endpoints (except absence of nausea at 2h) met statistical significance versus placebo for ubrogepant 50mg. Absence of MBS and secondary outcomes were not significant for 25mg after multiplicity adjustment. Ubrogepant’s and placebo’s AE profiles were similar. Conclusions: Co-primary endpoints were met for ubrogepant 50mg. Ubrogepant 25mg was significantly superior to placebo for 2h pain freedom. Ubrogepant was well tolerated. Results support the efficacy, tolerability, and safety of ubrogepant for acute treatment of migraine attacks.
Background: To evaluate efficacy, safety, and tolerability of ubrogepant, an oral CGRP receptor antagonist, for acute treatment of a single migraine attack. Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, phase 3 study (NCT02828020). Patients randomized 1:1:1 to placebo, ubrogepant 50mg, or ubrogepant 100mg had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints: pain freedom 2 hours post initial dose and absence of most bothersome migraine-associated symptom (MBS). Results: 1672 patients were randomized (safety population: n=1436; mITT population: n=1327). Mean age: 40.7 years; white (82.4%); female (87.5%). A significantly greater percentage of ubrogepant- than placebo-treated patients achieved pain freedom 2 hours post initial dose (50mg: 19.2%, adjusted P=0.0023; 100mg: 21.2%, adjusted P=0.0003; placebo: 11.8%). A significantly greater percentage of ubrogepant patients achieved absence of MBS (50mg: 38.6%, adjusted P=0.0023, 100mg: 37.7%, adjusted P=0.0023; placebo: 27.8%). The adverse event (AE) profile of ubrogepant was similar to placebo. The most common AEs (incidence ≥2% in any treatment group) within 48 hours of initial or optional second dose were nausea, somnolence, and dry mouth (all with incidence <5%). Conclusions: Both co-primary endpoints were met, with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well tolerated, with no identified safety concerns.
Background: Central neurocytoma’s are typically located in the lateral ventricles and are optimally treated with surgical resection. Surgical entry into the ventricles are associated with a number of complications, including subdural hygroma and shunt-dependent hydrocephalus. Methods: We report a patient who developed acute bilateral uncal herniation from progessively enlarging subdural hygromas following intraventricular tumour resection. Results: A 60-year-old female underwent minimally invasive transcortical transventricular resection of an intraventricular CN. The patient’s postoperative course was complicated by repeated presentations to the emergency department due to persistent and intractable nausea and headaches, without focal neurological deficits. Imaging demonstrated small bilateral subdural hygromas. The patient eventually presented with acute deterioration in her level of consciousness with clinical and radiologic evidence of bilateral uncal herniation, requiring urgent insertion of a subdural drain to treat elevated intracranial pressure (ICP). After insertion of a ventriculoperitoneal shunt, the patient was discharged in stable condition and is currently followed by the multi-disciplinary neuro-oncology team. Conclusions: Bilateral subdural hygroma could mask underlying external hydrocephalus post transventricular surgeries. Patients who are symptomatic from bilateral subdural hygromas after transventricular resection of tumors should be carefully monitored for radiographic or clinical progression, in order to avoid acute deterioration caused by elevated ICP.
Metacognition refers to the ability to evaluate and control our cognitive processes. While studies have investigated metacognition in schizophrenia and clinical high risk for psychosis (CHR), less is known about the potential mechanisms which result in metacognitive deficits.
We aimed to investigate whether neurocognitive functions including attention, working memory, verbal learning and executive functions predicted the tendency to focus on one’s thoughts (cognitive self-consciousness) and beliefs in the efficacy of one’s cognitive skills (cognitive confidence).
Participants (130 CHR individuals) were recruited as part of the multi-site PREDICT study. They were assessed using the Metacognitions Questionnaire (MCQ) as well as measures of executive function (WCST), attention (N-Back), working memory (LNS) and verbal learning (AVLT).
Cognitive competence was negatively correlated with N-Back while cognitive self-consciousness was positively correlated with N-Back and LNS. Linear regression analysis with N-Back, AVLT, LNS and WCST as predictors showed that neurocognition significantly predicted cognitive self-consciousness, with N-Back, LNS and WCST as significant predictors. The model accounted for 14% of the variance in cognitive self-consciousness. However, neurocognition did not result in a significant predictive model of cognitive competence.
Neurocognition was associated with an increased focus on one’s thoughts, but it was not associated with higher confidence in one’s cognitive skills. Neurocognition accounted for less than one-sixth of the variance in metacognition, suggesting that interventions that target neurocognition are unlikely to improve metacognitive abilities.
Two solid state anaerobic digesters (SSADs), 15 L each, were set up for co-digestion of switchgrass with primary digestate of a liquid anaerobic digester (LAD) and the recirculating leachate. Both the LAD and two SSADs were operated at 50°C. The results showed that the bioreactors were not started up stably until day 16 and day 47 for reactors A and B, respectively. The supplement of LAD digestate or injection of sodium hydroxide (NaOH) into the recirculating leachate readily reinitiated the biogas production to normal daily high rates of the two individual SSADs, one on day 16 and the other on day 47. In contrast to reactor A, there was a longer lag phase for bioreactor B, however, it showed 46.2% [77.9 vs 53.3 L kg−1 volatile solid (VS)] more cumulative biogas yields, and higher reduction rate of total solid, VS, cellulose and hemicellulose of 29.5, 31, 40.6 and 15%, respectively, which was likely due to optimized pH and NaOH pretreated switchgrass during start-up period. Methane contents of biogas increased gradually and stabilized at 50% for both reactors, indicating a normal operation of anaerobic digestion lasted for at least 100 days. The determined parameters of digested residues met China organic fertilizer standard (NY 525-2012) except for high moisture and low total nutrient contents. Therefore, the product of SSAD has the potential value of organic fertilizer. It is concluded that the LAD digestate can be reused as inoculums by co-digestion with agricultural residues for biogas and organic fertilizer production in SSAD.
Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.
Favourable body composition has been associated with higher dietary protein intake. However, little is known regarding this relationship in a population of Chinese Americans (CHA), who have lower BMI compared with other populations. The aim of the present study was to assess the relationship between dietary protein intake, fat mass (FM) and fat-free mass (FFM) in CHA. Data were from the Chinese American Cardiovascular Health Assessment (CHA CHA) 2010–2011 (n 1707); dietary intake was assessed using an adapted and validated FFQ. Body composition was assessed using bioelectrical impedance analysis. The associations between protein intake (% energy intake) and BMI, percentage FM (FM%), percentage FFM (FFM%), FM index (FMI) and FFM index (FFMI) were examined using multiple linear regression adjusted for age, sex, physical activity, acculturation, total energy intake, sedentary time, smoking status, education, employment and income. There was a significant positive association between dietary protein and BMI (B = 0·056, 95 % CI 0·017, 0·104; P = 0·005), FM (B = 0·106, 95 % CI 0·029, 0·184; P = 0·007), FM% (B = 0·112, 95 % CI 0·031, 0·194; P = 0·007) and FMI (B = 0·045, 95 % CI 0·016, 0·073; P = 0·002). There was a significant negative association between dietary protein and FFM% (B = −0·116, 95 % CI −0·196, −0·036; P = 0·004). In conclusion, higher dietary protein intake was associated with higher adiposity; however, absolute FFM and FFMI were not associated with dietary protein intake. Future work examining the relationship between protein source (i.e. animal) and body composition is warranted in this population of CHA.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.