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Background: Social risk data collection is expanding in community health centers (CHCs). We explored clinicians' practices of adjusting medical care based on their awareness of patients' social risk factors-that is, changes they make to care plans to mitigate the potential impacts of social risk factors on their patients' care and health outcomes-in a set of Texas CHCs., Methods: Convergent mixed methods. Surveys/interviews explored clinician perspectives on adjusting medical care based on patient social risk factors. Survey data were analyzed with descriptive statistics; interviews were analyzed using thematic analysis and inductive coding., Results: Across 4 CHCs, we conducted 15 clinician interviews and collected 97 surveys. Interviews and surveys overall indicated support for adjustment activities. Two main themes emerged: 1) clinicians reported making frequent adjustments to patient care plans based on their awareness of patients' social contexts, while simultaneously expressing concerns about adjustment; and 2) awareness of patients' social risk factors, and clinician time, training, and experience all influenced clinician adjustments., Conclusions: Clinicians at participating CHCs described routinely adjusting patient care plans based on their patients' social contexts. These adjustments were being made without specific guidelines or training. Standardization of adjustments may facilitate the contextualization of patient care through shared decision making to improve outcomes., Competing Interests: Conflict of interest: None., (© Copyright 2024 by the American Board of Family Medicine.)

Background: Many community health centers (CHC) are scaling social risk screening in response to growing awareness of the influence of social adversity on health outcomes and concurrent incentives for social risk data collection. We studied the implementation of social risk screening in Texas CHCs to inform best practices and understand equity implications., Methods: Convergent mixed methods of 3 data sources. Using interviews and surveys with CHC providers and staff, we explored social risk screening practices to identify barriers and facilitators; we used electronic health record (EHR) data to assess screening reach and disparities in screening., Results: Across 4 urban/suburban Texas CHCs, we conducted 27 interviews (15 providers/12 staff) and collected 97 provider surveys; 2 CHCs provided EHR data on 18,672 patients screened during the study period. Data revealed 2 cross-cutting themes: 1) there was broad support for social risk screening/care integration that was rooted in CHCs' mission and positionalities, and 2) barriers to social risk screening efforts were largely a result of limited time and staffing. Though EHR data showed screens per month and screens/encounters increased peri-pandemic (4.1% of encounters in 8/2019 to 46.1% in 2/2021), there were significant differences in screening rates by patient race/ethnicity and preferred language ( P < .001 ). In surveys, 90.0% of surveyed providers reported incorporating social risk screening into patient conversations; 28.6% were unaware their clinic had an embedded screening tool., Conclusions: Study CHCs were in the early stages of standardizing social risk screening. Differences in screening reach by patient demographics raise concerns that social screening initiatives, which often serve as a path to resource/service connection, might exacerbate disparities. Overcoming barriers to reach, sustainability, and equity requires supports targeted to program design/development, workforce capacity, and quality improvement., Competing Interests: Conflict of interest: None., (© Copyright by the American Board of Family Medicine.)

Objective: The coronavirus disease (COVID-19) pandemic has presented unique challenges to pediatric emergency medicine (PEM) departments. The purpose of this study was to identify these challenges and ascertain how centers overcame barriers in creating solutions to continue to provide high-quality care and keep their workforce safe during the early pandemic., Methods: This is a qualitative study based on semi-structured interviews with physicians in leadership positions who have disaster or emergency management experience. Participants were identified through purposive sampling. Interviews were recorded and transcribed electronically. Themes and codes were extracted from the transcripts by 2 independent coders. Constant comparison analysis was performed until thematic saturation was achieved. Member-checking was completed to ensure trustworthiness., Results: Fourteen PEM-trained physicians participated in this study. Communication, leadership and planning, clinical practice, and personal adaptations were the principal themes identified. Recommendations elicited include improving communication strategies; increasing emergency department (ED) representation within hospital-wide incident command; preparing for a surge and accepting adult patients; personal protective equipment supply and usage; developing testing strategies; and adaptations individuals made to their practice to keep themselves and their families safe., Conclusions: By sharing COVID-19 experiences and offering solutions to commonly encountered problems, pediatric EDs may be better prepared for future pandemics.

Point-of-care ultrasound (POCUS) has become the standard of care for many emergency department evaluations. Low-resource settings are ideal for POCUS to help improve access to imaging for a number of indications that are obstetric, disease or trauma related. The following twelve specific tips are aimed toward organizations and individuals who aspire to initiate POCUS training in a low-resource setting.

Introduction: As the SARS-CoV-2 virus spread across the globe, hospitals around the USA began preparing for its arrival. Building on previous experience with alternative care sites (ACS) during surge events, Texas Children's Hospital (TCH) opted to redeploy their mobile paediatric emergency response teams. Simulation-based clinical systems testing (SbCST) uses simulation to test preoccupancy spaces and new processes. We developed rapid SbCST with social distancing for our deployed ACS, with collaboration between emergency management, paediatric emergency medicine and the simulation team., Methods: A two-phased approach included an initial virtual tabletop activity followed by SbCST at each campus, conducted simultaneously in-person and virtually. These activities were completed while also respecting the need for social distancing amidst a pandemic response. Each activity's discussion was facilitated using Promoting Excellence and Reflective Learning in Simulation (PEARLS) for systems integration debriefing methodology and was followed by compilation of a failure mode and effects analysis (FMEA), which was then disseminated to campus leaders., Results: Within a 2-week period, participants from 20 different departments identified 109 latent safety threats (LSTs) across the four activities, with 71 identified as being very high or high priority items. Very high and high priority threats were prioritised in mitigation efforts by hospital leadership., Discussion: SbCST can be rapidly implemented to hone pandemic responses and identify LSTs. We used SbCST to allow for virtual participation and social distancing within a rapidly accelerated timeline. With prioritised FMEA reporting, leadership was able to mitigate concerns surrounding the four Ss of surge capacity: staff, stuff, structure and systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Nanostructures of the conducting polymer poly(3,4-ethylenedioxythiophene) with large surface areas enhance the performance of energy storage devices such as electrochemical supercapacitors. However, until now, high aspect ratio nanofibers of this polymer could only be deposited from the vapor-phase, utilizing extrinsic hard templates such as electrospun nanofibers and anodized aluminum oxide. These routes result in low conductivity and require postsynthetic template removal, conditions that stifle the development of conducting polymer electronics. Here we introduce a simple process that overcomes these drawbacks and results in vertically directed high aspect ratio poly(3,4-ethylenedioxythiophene) nanofibers possessing a high conductivity of 130 S/cm. Nanofibers deposit as a freestanding mechanically robust film that is easily processable into a supercapacitor without using organic binders or conductive additives and is characterized by excellent cycling stability, retaining more than 92% of its initial capacitance after 10,000 charge/discharge cycles. Deposition of nanofibers on a hard carbon fiber paper current collector affords a highly efficient and stable electrode for a supercapacitor exhibiting gravimetric capacitance of 175 F/g and 94% capacitance retention after 1000 cycles.

A new bulky biarylphosphine ligand (L8) has been developed that allows the Pd-catalyzed C-O cross-coupling of a wide range of aryl halides and phenols under milder conditions than previously possible. A direct correlation between the size of the ligand substituents in the 2', 4', and 6' positions of the nonphosphine containing ring and the reactivity of the derived catalyst system was observed. Specifically, the rate of coupling increased with the size of these substituents., (© 2011 American Chemical Society)

Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homology between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homology model, two compounds, 11r and 25i, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.

We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 × 10(-7)). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Kinetic acidities of arenes, ArH, measured some time ago by hydrogen isotope exchange kinetics with lithium cyclohexylamide (LiCHA) in cyclohexylamine (CHA) show a wide range of reactivities that involve several electronic mechanisms. These experimental reactivities give an excellent Brønsted correlation with equilibrium lithium ion pair acidities (pK(Li)) derived as shown recently from computations of ArLi.2E (E = dimethyl ether). The various electronic mechanisms are well modeled by ab initio HF calculations with modest basis sets. Additional calculations using NH(3) as a model for CHA further characterize the TS of the exchange reactions. The slopes of Brønsted correlations of ion pair systems can vary depending on the nature of the ion pairs.

An investigation into Pd-catalyzed C-N cross-coupling reactions of aryl iodides is described. NaI is shown to have a significant inhibitory effect on these processes. By switching to a solvent system in which the iodide byproduct was insoluble, reactions of aryl iodides were accomplished with the same efficiencies as aryl chlorides and bromides. Using catalyst systems based on certain biarylphosphine ligands, aryl iodides were successfully reacted with an array of primary and secondary amines in high yields. Lastly, reactions of heteroarylamines and heteroaryliodides were also conducted in high yields.

Mutation in the EGFP domain of LDL receptor-related protein 6 (LRP6(R611C)) is associated with hypercholesterolemia and early-onset atherosclerosis, but the mechanism by which it causes disease is not known. Cholesterol uptake was examined in cells from LRP6(+/-) mice and LRP6(R611C) mutation carriers. Splenic B cells of LRP6(+/-) mice have significantly lower LRP6 expression and low-density lipoprotein (LDL) uptake than those of the wild-type littermates. Although similar levels of total LRP6 were found in lymphoblastoid cells (LCLs) of LRP6(R611C) mutation carriers and those of the unaffected family member, LDL uptake was significantly lower in the mutant cells. Mutant and wild-type receptors show similar affinities for apolipoprotein B at neutral pH. LRP6 colocalized with LDL and was coimmunoprecipitated with NPC1 (Niemann-Pick disease type C1), an endocytic regulator of LDL trafficking. However, the cellular localization of LRP6 in the mutant cells shifted from cell surface to late endosomes/lysosomes. Plasma membrane expression levels of LRP6(R611C) was lower compared to wild-type receptor and declined to a greater extent in LDL-rich medium. Further examinations revealed lower efficacy of apolipoprotein B dissociation from LRP6(R611C) compared to wild-type receptor at an acidic pH. These studies identify LRP6 as a receptor for LDL endocytosis and imply that R611C mutation results in reduced LRP6 membrane expression and decreased LDL clearance. Based on our findings, we conclude that the increased affinity of the mutant receptor for LDL in acidic pH leads to their impaired dissociation in late endosomes, which compromises their recycling to the plasma membrane.

Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS.

Substituted pyrroles were prepared by a gold(I)-catalyzed acetylenic Schmidt reaction of homopropargyl azides. The reaction allows for regiospecific substitution at each position of the pyrrole ring under mild conditions. A mechanism in which azides serve as nucleophiles toward gold(I)-activated alkynes with subsequent gold(I)-aided expulsion of dinitrogen is proposed.

[reaction: see text] The reaction of several phosphines with an acidic indicator gives both ion pairs and free ions. The value obtained for the pKa of tribenzylphosphine is shown to be reasonable by MO computations. An important limitation is demonstrated for the Fuoss equation of dissociation of ion pairs.

Objective: The purpose of this study was to evaluate the effect of induction on the route of delivery in nulliparous women laboring at term in a community hospital system., Study Design: From April 1997 to October 1999, there were 7282 deliveries in nulliparous patients who met inclusion criteria. Cesarean delivery rates were calculated for patients in spontaneous labor and for patients who underwent induction., Results: Among 4635 women (63.7%) in spontaneous labor, the cesarean delivery rate was 11.5% versus 23.7% among the 2647 (36.3%) patients who underwent induction. An important variable that affected the delivery route was the Bishop score at the initiation of the induction. The cesarean delivery rate was 31.5% among patients whose Bishop score was <5 at induction versus 18.1% for patients with a score > or =5(P <.001)., Conclusion: The induction of labor in nulliparous patients, especially those women with an unfavorable cervix as measured by Bishop score, is associated with a significantly increased risk of cesarean delivery.

Two experiments examined the ability of an added stimulus to interfere with extinction of a target excitatory fear stimulus (a predictor of shock) in human autonomic conditioning. Both experiments demonstrated disruption of extinction when the added stimulus was inhibitory (a predictor of no shock, or safety signal). Subjects showed a return of fear when the target stimulus was tested alone, on both self-reported shock expectancy and skin conductance measures. The second experiment also demonstrated disruption of extinction when the added stimulus was excitatory. This results suggests that protection from extinction may occur even when the added stimulus is not inhibitory. Additional factors that may contribute to protection from extinction include context-specificity, occasion-setting and external inhibition. The results highlight the role that concurrent stimuli play in extinction, and emphasise the need to keep concurrent stimuli as similar as possible to the desired transfer context in practical applications of extinction such as exposure therapy for anxiety.

The model is based on Mapleson's Model P for inhaled anaesthetics, but has compartments for lungs, peripheral shunt, kidneys, portal bed, liver, other viscera, muscle, other lean, fat, brain, i.m. injection site and for various blood "pools". Intracellular and extracellular fluids are represented separately in each compartment and in blood. In each fluid, four forms of the agent are distinguished: unionized dissolved in water ("standard" form), ionized dissolved in water, unionized dissolved in lipid, and bound to protein. Equations define the equilibrium between these four forms in any one fluid and between blood and tissue. After changing two of the more uncertain numbers in the quantification for pethidine, good agreement was obtained between computed and published venous concentrations after single i.v. and i.m. injections, continuous i.v. infusions and repeated i.m. injections. The model can be used to make a wide variety of "what if" predictions.

Mapleson's (1973) physiological, circulation-time model of the distribution of inhaled anaesthetics has been elaborated to be suitable for modelling agents in which hepatic metabolism and renal excretion are important factors; as well as the obvious improvement of providing separate compartments for liver and kidney, the arterial and portal supplies to the liver are separately represented, as is the portal blood pool. The separate portal pool also leads to a more realistic total circulation time for the majority of the cardiac output. The quantification for a "standard man" is fully documented and makes use of the latest (1975) report of the International Commission on Radiological Protection, Reference Man, and includes data on the water, fat and protein composition of each tissue compartment. Suggestions are included on adapting the quantification to non-standard men and to other species.

Dihydrodesmosine and dihydroisodemosine are dihydropyridines which are believed to be the immediate biosynthetic precursors of desmosine and isodesmosine, the stable pyridinium ion crosslinks of elastin. It has recently been reported that appreciably amounts of dihydrodesmosine and dihydroisodesmosine accumulate in elastin. In view of the ease with which such dihydropyridines are oxidized to the corresponding pyridinium ions by O2 and other mild oxidants, dihydrodesmosine and dihydroisodesmosine would not be expected to accumulate in elastic tissues. It therefore seemed appropriate to analyse elastin samples for dihydrodesmosine and dihydroisodesmosine using techniques different from these previously employed for this purpose. The results of these investigations indicate that dihydrodesmosine and dihydroisodesmosine do not accumulate to a measurable extent in elastin.

Between 1970 and 1987, 21 patients at St. Vincent Hospital and Medical Center underwent surgery for repair of a transected descending aorta. Nineteen of the transections were a result of trauma secondary to motor vehicle accidents, 1 was secondary to compression injury of the chest, and 1 was the result of a fall. All of the patients had diagnostic chest X-rays and all but one X-ray showed a widened mediastinum. Aortography was carried out in 20 cases. Atrio-femoral bypass was used for all but 2 patients, who had femoro-femoral bypass. The mean cross-clamp time was 53 minutes. Interposition graft was used in 16 patients, an intraluminal graft in 1 patient, and primary repair was performed in 2 patients. Survival was 71%, with 4 of the 21 patients expiring in the operating room (2 before the repair could be undertaken), one patient expiring during a laparotomy 2 days after the aortic repair, and one patient expiring 4 days after the repair. Fifteen patients were discharged alive. Survival and patient care could be improved by careful diagnostic assessment and by following a protocol agreed upon by a team of surgeons.

5-Aminolaevulinate administration to rats inhibits cerebral 5-hydroxytryptamine synthesis by decreasing tryptophan availability to the brain secondarily to activation of hepatic tryptophan pyrrolase. The results show that tryptophan metabolism and disposition can be influenced by changes in liver haem concentration, and are discussed briefly in relation to mood disorders in the hepatic porphyrias.

During in vivo maturation, and also during in vitro incubation with physiological buffers, native collagen fibers display a progressive increase in tensile strength and insolubility. Paralleling these physiologically important changes is a progressive loss of the reducible cross-links which initially join the triple-chained subunits of collagen fibers. Although there is evidence suggesting that the reducible cross-links are gradually transformed into more stable, nonreducible cross-links during maturation, the nature of the transformation process and the structure of the stable "mature" cross-links has remained a mystery. In order to test the possibility that cross-link transformation involves addition of a nucleophilic amino acid residue to the reducible cross-links, histidine, arginine, glutamate, aspartate, lysine, and hydroxylysine residues were chemically modified, and the effect of each modification procedure on the in vitro transformation of reducible cross-links was ascertained. The results of these experiments indicated that destruction of histidine, arginine, glutamate, and aspartate residues has no measurable effect on the rate and extent of reducible cross-link transformation in hard tissue collagens. In contrast, modification of lysine and hydrocylysine residues with a wide variety of specific reagents completely blocks the transformation of reducible cross-links. Removal of the reversible blocking groups from lysine and hydroxlylysine residues then allows the transformation to proceed normally. These results indicate that collagen maturation involves nucleophilic addition of lysine and/or hydroxylysine residues to the electrophilic double bond of the reducible cross-links, yielding derivatives which are not only more stable but also capable of cross-linking more collagen molecules than their reducible precursors.

From 1964 to 1986, a total of 18 valve replacement operations were performed in 15 children under 14 years of age, with 13% operative mortality. Eleven children had a mitral valve replacement, with 3 subsequently requiring reoperation. Twelve Starr-Edwards caged ball prostheses, 1 Björk-Shiley and 1 Carpentier-Edwards prosthesis were implanted in the mitral position, with 18% operative mortality. Three children underwent aortic valve replacement, 1 with a Björk-Shiley prosthesis and 2 with a Starr-Edwards. One patient had tricuspid valve replacement utilizing a Starr-Edwards valve. Thirteen patients had one or more cardiac operations prior to valve replacement. Two late deaths occurred 8 and 18 months, respectively, group, 1 from a cardiac arrhythmia and 1 from fulminating prosthetic valve endocarditis. There were no late deaths in other patients. There was one thromboembolic episode in the entire group. At follow-up, 10 patients were classified as New York Heart Association Functional Class I and 1 patient was Class III. Valve replacement in children can be carried out with low mortality and good long-term results using the Starr-Edwards caged ball prosthesis.

1. Liver 5-aminolaevulinate (ALA) synthase activity of 24 h-starved rats is maximally increased at 4 h after intraperitoneal administration of a 1.6 g/kg body wt. dose of ethanol. Larger doses cause a dose-dependent decrease in the extent of this stimulation, exhibiting a reciprocal relationship with an elevation of hepatic haem concentration, as suggested by the simultaneous increase in the haem saturation of tryptophan pyrrolase. 2. ALA synthase induction by ethanol is abolished if the above increase in pyrrolase saturation with haem is enhanced by theophylline, but is potentiated when the increase in the haem saturation is inhibited by anti-lipolytic agents. 3. ALA synthase induction by ethanol is also inhibited by inhibitors of alcohol dehydrogenase and aldehyde dehydrogenase. Acetaldehyde and acetate are, however, not responsible; they both decrease ALA synthase activity and increase the haem saturation of tryptophan pyrrolase. These latter effects of acetaldehyde are not mediated by acetate. 4. ALA synthase activity is also stimulated by succinate, which, however, also increases the haem saturation of tryptophan pyrrolase. 5. Ethanol does not influence the rate of ALA synthase degradation. 6. It is suggested that ethanol increases rat liver ALA synthase activity as a result of its own metabolism by the alcohol dehydrogenase-dependent pathway by a mechanism not involving decreased degradation of the former enzyme or the participation of the metabolites acetaldehyde and acetate.

New synthetic routes to the reduction products of several collagen cross-links and cross-link precursors are described. By the use of these routes hydroxynorleucine, 5,6-dihydroxynorleucine, hydroxylysinonorleucine and hydroxylysinohydroxynorleucine can be synthesized via one common synthetic intermediate. The synthetic routes provide a convenient source of these unusual amino acids, as well as confirming the structure of hydroxylysinohydroxynorleucine and the other lysine-derived residues found in borohydride-reduced collagens.