Identifying developmental disability in national surveys: Addressing the knowledge gap with special education histories

BackgroundIn the United States nearly 20% of children ages 12–17 have developmental disorders. Some attain population-based developmental milestones after a delay, or increase functioning through special education, medication, technology, or therapy. Others have severe lasting impairments. An indicator identifying those groups in surveys of adults could help shape policies to improve lives.HypothesesWe hypothesized that survey histories of special education could indicate functional status levels.MethodsData were from the nationally representative Panel Study of Income Dynamics (1997–2017, n = 2745). With measures of diagnoses, behaviors, functional status, service use, and adult outcomes, we tested three special education groups as indicators of: (1) no impairment (no special education), (2) disorders, developmental diagnoses that adversely affect educational performance, but with development after a period of delay or only moderate disability, indicated by transfer from special education; and (3) severe lasting disability, the diagnoses combined with life-long needs for supports or services, with limitations in areas including self-care, mobility, and capacity for independent living, indicated by special education in the individual's final year of school.ResultsAcross the special education groups, from no impairment to severe lasting disability, there were trends of: increasing severe and lasting disability (respectively 4.8%, 35.6%, 76.4%); increasing special services use (13.5%, 43.1%, 83.7%); increasing severe emotional disorders (2.3%, 11.3%, 17.9%); lower percentages attaining at least an associate's degree by age 25 (42.1%, 20.7%, and 8.9%); and more chronic diseases.ConclusionsSpecial education histories provide a useful indicator of developmental disability impairment levels in adults.     

近端胃切除人工三角瓣成形抗反流术的力学机理仿真分析

目的:对食管胃结合部腺癌近端胃切除术（PG）人工三角瓣成形后残胃食糜进行流体动力学数值模拟，并计算不同性质胃内食糜的流动特征。方法:构建常规PG和人工三角瓣成形术术后胃仿真模型，运用Fluent软件对不同粘度胃内食糜反流问题进行数值模拟。结果:站立位姿态时，相对常规PG方案，人工三角瓣成形手术方案表现出较好的抗反流作用；卧位姿态时，当胃内食糜粘度大于0.145 2 Pa[?s，且胃内食糜不超过人工三角瓣情况下，人工三角瓣成形抗反流手术表现出较好的抗反流效果；人工三角瓣抗反流成形手术方案数值模拟结果与临床上患者表现一致。结论:本研究仿真分析为人工三角瓣成形抗反流手术方案的有效性机理分析、临床患者术后饮食及手术方案的进一步改进提供理论及数值依据。 【关键词】食管胃结合部腺癌；抗反流；人工三角瓣；计算流体力学     

Dysregulated Brain Dynamics in a Triple-Network Saliency Model of Schizophrenia and Its Relation to Psychosis

Background

Schizophrenia is a highly disabling psychiatric disorder characterized by a range of positive “psychosis” symptoms. However, the neurobiology of psychosis and associated systems-level disruptions in the brain remain poorly understood. Here, we test an aberrant saliency model of psychosis, which posits that dysregulated dynamic cross-network interactions among the salience network (SN), central executive network, and default mode network contribute to positive symptoms in patients with schizophrenia.

慢阻肺急性加重期患者延迟就医与家庭动力学的相关性研究

目的研究慢阻肺急性加重期患者延迟就医与家庭动力学的相关性,希望能够为慢阻肺急性加重期患者拟定护理措施提供科学依据。方法选取2017年1月-2019年12月我院240例诊断为慢阻肺急性加重期的患者为研究对象。根据患者入院就医的时间进行分组,时间≥24h的延迟就医的患者为观察组,时间<24h的及时就医患者为对照组。结果两组患者在文化水平、家庭年收入、在职状态、医疗保险和婚姻状况和APACHEⅡ评分比较(P<0.05)。观察组患者疾病观念、个性化、系统逻辑和家庭氛围得分比对照组高(P<0.05)。Pearman的相关性分析结果显示:慢阻肺急性加重期患者延迟就医时间与各个层面分数以及家庭动力总分呈现负相关性(P<0.05)。应变量为延迟就医为应变量,患者的一般资料为自变量,经Logistic回归分析结果表明:延迟就医的影响因素为文化水平、家庭动力评分、职业状态、家庭收入、婚姻状况和APACHEⅡ评分。结论慢阻肺急性加重期患者家庭动力总分与疾病观念、个性化、系统逻辑和家庭氛围得分与延迟就医时间呈现负相关性,患者延迟就医的影响因素是家庭动力学评分。     

Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike

Binding of the spike protein of SARS-CoV-2 to the human angiotensin-converting enzyme 2 (ACE2) receptor triggers translocation of the virus into cells. Both the ACE2 receptor and the spike protein are heavily glycosylated, including at sites near their binding interface. We built fully glycosylated models of the ACE2 receptor bound to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Using atomistic molecular dynamics (MD) simulations, we found that the glycosylation of the human ACE2 receptor contributes substantially to the binding of the virus. Interestingly, the glycans at two glycosylation sites, N90 and N322, have opposite effects on spike protein binding. The glycan at the N90 site partly covers the binding interface of the spike RBD. Therefore, this glycan can interfere with the binding of the spike protein and protect against docking of the virus to the cell. By contrast, the glycan at the N322 site interacts tightly with the RBD of the ACE2-bound spike protein and strengthens the complex. Remarkably, the N322 glycan binds to a conserved region of the spike protein identified previously as a cryptic epitope for a neutralizing antibody. By mapping the glycan binding sites, our MD simulations aid in the targeted development of neutralizing antibodies and SARS-CoV-2 fusion inhibitors.

Angiotensin-converting enzyme 2 (ACE2) is an enzyme that catalyzes the hydrolysis of angiotensin II into angiotensin (1–7) to counterbalance the ACE receptor in blood pressure control (1). A single transmembrane helix anchors ACE2 into the plasma membrane of cells in the lungs, arteries, heart, kidney, and intestines (2). The vasodilatory effect of ACE2 has made it a promising target for drugs treating cardiovascular diseases (3).ACE2 also serves as the entry point for several coronaviruses into cells, including SARS-CoV and SARS-CoV-2 (4–6). The binding of the spike protein of SARS-CoV and SARS-CoV-2 to the peptidase domain (PD) of ACE2 triggers endocytosis and translocation of both the virus and the ACE2 receptor into endosomes within cells (4). The human transmembrane serine protease 2, TMPRSS2, primes spike for efficient cell entry by cleaving its backbone at the boundary between the S1 and S2 subunits or within the S2 subunit (4). The structure of the ACE2 receptor in complex with the SARS-CoV-2 spike receptor binding domain (RBD) (7–9) reveals the major RBD interaction regions as helix H1 (Q24–Q42), a loop in a beta sheet (K353–R357), and the end of helix H2 (L79–Y83). With a 4-Å heavy-atom distance cutoff, 20 residues of ACE2 interact with 17 residues of the RBD, forming a buried interface of ∼1,700 Ų (7).The structure of full-length ACE2 has been resolved in complex with B⁰AT1 (also known as SLC6A19) (9). B⁰AT1 is a sodium-dependent neutral amino acid transporter (10). ACE2 functions as chaperone for B⁰AT1 and is responsible for its trafficking to the plasma membrane of kidney and intestine epithelial cells (11). Although it was speculated that B⁰AT1 prevents ACE2 cleavage by TMPRSS2 and thus could suppress SARS-CoV-2 infection (9, 12), other studies showed that SARS-CoV-2 can infect human small intestinal enterocytes where ACE2 is expected to be in complex with B⁰AT1 (13).Both the ACE2 receptor and the spike protein are heavily glycosylated. Several glycosylation sites are near the binding interface (7, 9, 14, 15). Whereas the focus has largely been on amino acid interactions in the ACE2–spike binding interface (16, 17), the role of glycosylation in binding has been recognized (7, 18–20). The extracellular domain of the ACE2 receptor has seven N-glycosylation sites (N53, N90, N103, N322, N432, N546, and N690) and several O-glycosylation sites (e.g., T730) (9, 14). Among ACE2 glycosylation sites, the only well-characterized position regarding the effect on the spike binding and viral infectivity is N90. It is known from earlier SARS-CoV studies that glycosylation at the N90 position might interfere with virus binding and infectivity (21). Also, recent genetic and biochemical studies showed that mutations of N90, which remove the glycosylation site directly, or of T92, which remove the glycosylation site indirectly by eliminating the glycosylation motif (NXT), increase the susceptibility to SARS-CoV-2 infection (22, 23).We use extensive molecular dynamics (MD) simulations to gain a detailed molecular-level understanding of how ACE2 glycosylation impacts the host–virus interactions. Glycosylation sites N90 and N322 of human ACE2 emerge as major determinants of its binding to SARS-CoV-2 spike. Remarkably, glycans at these sites have opposite effects, interfering with spike binding in one case, and strengthening binding in the other. Our findings provide direct guidance for the design of targeted antibodies and therapeutic inhibitors of viral entry.     

Transmissible vaccines whose dissemination rates vary through time,with applications to wildlife

Transmission is a potential property of live viral vaccines that remains largely unexploited but may lie within the realm of many engineering designs. While likely unacceptable for vaccines of humans, transmission may be highly desirable for vaccines of wildlife, both to protect natural populations and also to limit zoonotic transmissions into humans. Defying intuition, transmission alone does not guarantee that a vaccine will perform well: the benefit of transmission over no transmission depends on and increases with the basic reproductive number of the vaccine, $R_0$. The $R_0$ of an infectious agent in a homogeneous population is typically considered to be a fixed number, but some evidence suggests that dissemination of transmissible vaccines may change through time. One obvious possibility is that transmission will be greater from hosts directly vaccinated than from hosts who acquire the vaccine passively, but other types of change might also accrue. Whenever transmission changes over time, the $R_0$ estimated from directly vaccinated hosts will not reflect the vaccine’s long term impact. As there is no theory on the consequences of changing transmission rates for a vaccine, we derive conditions for a transmissible vaccine with varying transmission rates to protect a population from pathogen invasion. Being the first in the transmission chain, the $R_0$ from directly vaccinated hosts has a larger effect than those from later steps in the chain. This mathematical property reveals that a transmissible vaccine with low long term transmission may nonetheless realize a big impact if early transmission is high. Furthermore, there may be ways to artificially elevate early transmission, thereby achieving high herd immunity from transmission while ensuring that the vaccine will ultimately die out.     

四君子汤合四磨汤加减治疗出口梗阻型便秘吻合器经肛门直肠切除术后的临床疗效

目的:观察四君子汤合四磨汤加减治疗出口梗阻型便秘(OOC)吻合器经肛门直肠切除术后(STARR)的临床疗效。方法:124例患者随机按数字表法分为对照组和观察组各62例。对照组术后给予芪蓉润肠口服液,20 mL/次/,3次/d;观察组术后给予四君子汤合四磨汤加减内服,1剂/d。两组疗程均连续治疗4周,并进行8周随访。分别于手术前、治疗后2周,4周、随访8周进行便秘主要症状评分和Longo ODS评分;于手术前和治疗后4周,进行超氧化物歧化酶(SOD),丙二醛(MDA)和便秘患者生存质量自评量表(PAC-QOL)评价,并进行肛门直肠测压,记录肛管静息压(ARP),肛管最大收缩压(MSP),直肠排便压力(RSP),初始感觉阈值(FSV),排便感觉阈值(CRS)和最大耐受容量(MTV)等指标;随访记录并发症发生率、复发率和排便正常率;术后4周进行满意度评价和安全性评价。结果:治疗后4周,观察组患者临床疗效优于对照组(Z=2.096,P0.05);治疗后2周,4周和随访8周,观察组便秘主要症状积分和Longo ODS评分均低于对照组(P0.01);观察组患者ARP,FSV,FSV,CRS均低于对照组(P0.01),MSP和RSP均高于对照组(P0.01);观察组并发症发生率、复发率分别为20.97%(13/62)和4.84%(3/62),分别低于对照组的39.71%(24/62)和16.13%(10/62)(P0.05);观察组排便正常率为91.94%(57/62),高于对照组的80.65%(50/62),组间差异无统计学意义;观察组PAC-QOL总分和各因子评分均低于对照组(P0.01);观察组SOD水平高于对照组,MDA水平低于对照组(P0.01);未发现干预中药相关不良反应。结论:四君子汤合四磨汤加减用于出口梗阻型便秘STARR术后患者,可进一步减轻便秘症状和病情程度,提高生活质量,降低术后并发症发生率和复发率,并可改善肛门直肠动力学指标和氧化应激指标,提高临床疗效。     

Molecular mechanisms for the antidepressant-like effects of a low-dose ketamine treatment in a DFP-based rat model for Gulf War Illness

Exposure to organophosphates (OP) during the First Gulf War is among one of the factors for Gulf War Illness (GWI) development in veterans and it has been challenging to treat GWI symptoms with existing therapies. Ketamine produces a rapid-onset and sustained antidepressant response, but there is no evidence whether ketamine treatment is effective for GWI depression. Repeated, low-dose exposure to diisopropyl fluorophosphate (DFP) mimic Gulf War related OP exposures and produces a chronic depressive state in rats. In this study, DFP-exposed rats treated with ketamine (10 mg/kg, i.p.) exhibited antidepressant-like effect on the Forced Swim Test at 1-h. This effect persisted at 24-h post ketamine, a time-point by which it is eliminated from the brain suggesting involvement of mechanisms that affect long-term synaptic plasticity. Western blot analysis showed significantly lower Brain-Derived Neurotrophic Factor (BDNF) levels in DFP rat brains. Ketamine produced a nonsignificant increase in BDNF expression at 1-h but produced a larger, significant (2.2-fold) increase at 24-h in DFP rats. We previously reported chronic hippocampal calcium elevations ([Ca²⁺]_i) in DFP rats. Ketamine-treated DFP rats exhibited significantly lower [Ca²⁺]_i at 1-h but not at 24-h. Interestingly, treatment with ANA-12, a TrkB-BDNF receptor antagonist, in DFP rats blunted ketamine’s antidepressant-like effect at 24-h but not at 1-h. These experiments suggest that in a rat model of DFP-induced depression, inhibition of the NMDAR-Ca²⁺ contributes to the rapid-onset antidepressant effects of ketamine while the antidepressant actions that persisted at 24-h post ketamine administration involve upregulation of BDNF signaling.     

Gas,tubes and flow

Optimizing the flow of both liquids and gases is crucial to many areas of anaesthetic and critical care practice. In this article, we describe the physical principles that govern the flow of gases and present scenarios from clinical practice to illustrate these concepts. The difference between laminar and turbulent flow is explained, along with the factors that determine the nature of the fluid flow. The Venturi effect, Bernoulli principle and Coanda effect are also described with reference to their clinical applications and their relevance to medical devices.     

Unique sleep‐stage transitions determined by obstructive sleep apnea severity,age and gender

In obstructive sleep apnea, patients’ sleep is fragmented leading to excessive daytime sleepiness and co‐morbidities like arterial hypertension. However, traditional metrics are not always directly correlated with daytime sleepiness, and the association between traditional sleep quality metrics like sleep duration and arterial hypertension is still ambiguous. In a development cohort, we analysed hypnograms from mild (n = 209), moderate (n = 222) and severe (n = 272) obstructive sleep apnea patients as well as healthy controls (n = 105) from the European Sleep Apnea Database. We assessed sleep by the analysis of two‐step transitions depending on obstructive sleep apnea severity and anthropometric factors. Two‐step transition patterns were examined for an association to arterial hypertension or daytime sleepiness. We also tested cumulative distributions of wake as well as sleep‐states for power‐laws (exponent α) and exponential distributions (decay time τ) in dependency on obstructive sleep apnea severity and potential confounders. Independent of obstructive sleep apnea severity and potential confounders, wake‐state durations followed a power‐law distribution, while sleep‐state durations were characterized by an exponential distribution. Sleep‐stage transitions are influenced by obstructive sleep apnea severity, age and gender. N2 → N3 → wake transitions were associated with high diastolic blood pressure. We observed higher frequencies of alternating (symmetric) patterns (e.g. N2 → N1 → N2, N2 → wake → N2) in sleepy patients both in the development cohort and in a validation cohort (n = 425). In conclusion, effects of obstructive sleep apnea severity and potential confounders on sleep architecture are small, but transition patterns still link sleep fragmentation directly to obstructive sleep apnea‐related clinical outcomes like arterial hypertension and daytime sleepiness.