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Currently, the NRC amino acid (AA) requirements for pigs published in 2012 are used as a reference in variable swine industries. However, recent results in several articles suggest that the standardized ileal digestible (SID) AA-lysine (Lys) ratio significantly evolved over the last two decades, while some publications report inconsistent outcomes. Therefore, the present study used a meta-regression analysis to assess the relative ratio to lysine to maximize the feed efficiency of four essential amino acids (tryptophan, valine, isoleucine, and methionine) in pig diets. According to the PRISMA guidelines, articles examining the target AA requirement using a basal diet supplemented with varying levels of crystalline AA (tryptophan, valine, isoleucine, or methionine) were identified across Scopus, PubMed, and Science Direct. As a result, 23, 22, 16, and 9 articles using tryptophan, valine, isoleucine, and methionine were selected and categorized into experiments for inclusion in our meta-analysis. The results suggested that the requirements of tryptophan, valine, isoleucine, and methionine in our meta-regression analysis were superior to NRC recommendations, regardless of the regression models and the growth phases with significant RSQ values (RSQ ≈ 1). Also, the QUAD and CLP regression models emphasized higher requirements than the LP model for the great majority of amino acids and growth phases. The results of the QUAD and CLP models were selected as estimations of the amino acid requirements for pigs under challenged conditions, whereas the LP model was chosen to estimate the amino acid requirements of genetically improved pigs under a modern housing system. The results of this meta-regression analysis could be used to refresh the information on the NRC amino acids (AA) requirements for swine.

Background: The incidence of sudden unexpected infant death (SUID) in the United States has persisted at roughly the same level since the mid-2000s, despite intensive prevention efforts around safe sleep. Disparities in outcomes across racial and socioeconomic lines also persist. These disparities are reflected in the spatial distribution of cases across neighborhoods. Strategies for prevention should be targeted precisely in space and time to further reduce SUID and correct disparities., Objective: We sought to aid neighborhood-level prevention efforts by characterizing communities where SUID occurred in Cook County, IL, from 2015 to 2019 and predicting where it would occur in 2021-2025 using a semiautomated, reproducible workflow based on open-source software and data., Methods: This cross-sectional retrospective study queried geocoded medical examiner data from 2015-2019 to identify SUID cases in Cook County, IL, and aggregated them to "communities" as the unit of analysis. We compared demographic factors in communities affected by SUID versus those unaffected using Wilcoxon rank sum statistical testing. We used social vulnerability indicators from 2014 to train a negative binomial prediction model for SUID case counts in each given community for 2015-2019. We applied indicators from 2020 to the trained model to make predictions for 2021-2025., Results: Validation of our query of medical examiner data produced 325 finalized cases with a sensitivity of 95% (95% CI 93%-97%) and a specificity of 98% (95% CI 94%-100%). Case counts at the community level ranged from a minimum of 0 to a maximum of 17. A map of SUID case counts showed clusters of communities in the south and west regions of the county. All communities with the highest case counts were located within Chicago city limits. Communities affected by SUID exhibited lower median proportions of non-Hispanic White residents at 17% versus 60% (P<.001) and higher median proportions of non-Hispanic Black residents at 32% versus 3% (P<.001). Our predictive model showed moderate accuracy when assessed on the training data (Nagelkerke R2=70.2% and RMSE=17.49). It predicted Austin (17 cases), Englewood (14 cases), Auburn Gresham (12 cases), Chicago Lawn (12 cases), and South Shore (11 cases) would have the largest case counts between 2021 and 2025., Conclusions: Sharp racial and socioeconomic disparities in SUID incidence persisted within Cook County from 2015 to 2019. Our predictive model and maps identify precise regions within the county for local health departments to target for intervention. Other jurisdictions can adapt our coding workflows and data sources to predict which of their own communities will be most affected by SUID., (© Daniel P Riggins, Huiyuan Zhang, William E Trick. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

This work presents the development and testing of an experimental web-based SDR (software-defined radio) monitoring system for indirect solar activity detection, which has the ability to estimate and potentially predict various events in space and on earth, including solar flares, coronal mass ejections, and geomagnetic storms. The proposed system can be used to investigate the effect of solar activity on the propagation of very-low-frequency (VLF) signals. The advantages and benefits of the given approach are as follows: increasing measurement accuracy and eventual solar activity identification by combining measurements from multiple spatially distributed SDRs. The verification process involves carrying out several experiments comparing data from the GOES satellite system and the Dunksin SuperSID system with information received by the SDR monitoring system. Then, utilizing Pearson correlation coefficients, the measured data from the SDRs, along with those from the GOES satellite system and the Dunsing monitoring station, are investigated. At the time of a solar flare, the correlation value is above 90% for most of the stations used. Combining the signal-to-noise ratio via summation also shows an improvement in the results, with a correlation above 98%.

Background: Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated disease affecting the central nervous system. Natalizumab, an FDA-approved monoclonal antibody for MS, has been explored for its off-label extended interval dosing (EID), suggesting a potential reduction in the risk of progressive multifocal leukoencephalopathy (PML) compared to standard interval dosing (SID). Our objective was to assess the efficacy and safety of EID in comparison to SID for natalizumab treatment in patients with MS., Methods: We searched PubMed, Embase, WOS, Scopus, Ovid, Science Direct, Clinical trials.gov, and Cochrane Library. Our assessed outcomes were clinical relapses, MRI activity, change in expanded disability status scale [EDSS], and the risk of PML. The EID group was defined as 5 to 8 weeks [EID (Q5-8W)]. The analysis was conducted using RevMan ver. 5.4. The effect estimates were presented as a risk ratio [RR] or mean difference with 95% confidence intervals [CI] using SID group as the reference for comparisons., Results: Fourteen studies met our inclusion criteria: 2 RCTs, 1 switched single-arm trial, and 12 observational studies. No significant differences were found in all efficacy outcomes of interest. Risk of clinical relapses [RR = 0.90, (95%CI 0.80, 1.02)], risk of new or newly enlarging T2 hyperintense MRI lesions [RR = 0.78, (95%CI 0.59, 1.04)], risk gadolinium enhancing lesions [RR = 1.30, (95%CI 0.98, 1.72)], change in EDSS [MD = 0.09 (95%CI - 0.57, 0.76)], risk of PML [RR = 1.09, 95%CI (0.24, 4.94)]., Conclusion: In summary, our meta-analysis indicates that natalizumab maintains its effectiveness under extended interval dosing [up to 8 weeks], presenting comparable risks for clinical relapses, MRI lesions, EDSS, and PML. Caution is advised given study limitations and heterogeneity. Robust conclusions necessitate well-designed high-quality prospective studies., (© 2024. The Author(s).)

Background: Vocational programmes run by teachers in the special needs school context can play a significant role in the vocational development of learners with severe intellectual disability (SID). This study aimed to answer the question 'what are the challenges faced by teachers in the implementation of vocational programmes in selected public special needs schools for learners with SID in the Metropolitan (Metro) District within the City of Cape Town?', Objectives: The objectives were to describe the challenges as perceived by participants, to highlight common and contrasting challenges in the different schools and to share recommendations on support needed., Method: A qualitative descriptive study was conducted. A combination of purposive and snowball sampling strategies was used to select six teachers from six special needs schools. One-on-one semi-structured interviews with teachers were performed. An interview schedule was used as a tool and all interviews were transcribed and translated into English verbatim. Thematic analysis was applied., Results: The findings showed that teachers encounter inadequate resources, a lack of training, and poor support systems. This study highlights the issues of existing policy and the lack of a mandatory policy on vocational programmes in South Africa., Conclusion: The participants' experiences added to the existing literature by providing valuable insights into the obstacles teachers encounter in this relatively new curriculum. A multifaceted policy framework that is well funded and implemented is much needed to address the challenges identified., Contribution: The findings may contribute to the development and strengthening of policies on vocational programmes within the South African context., Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

The human immune system is a complex network of cells, tissues, and molecules that work together to defend the body against pathogens and maintain overall health. However, in some individuals, the immune system fails to function correctly, leading to immunodeficiencies. Immunodeficiencies can be classified into primary (PID) and secondary (SID) types, each with distinct underlying causes and manifestations. Toll-like receptors (TLRs), as key components of the immune system, have been implicated in the pathogenesis of both PID and SID. In this study, we aim to unravel the intricate involvement of TLR2, TLR4, TLR3, TLR7, TLR8, and TLR9 in the immunopathogenesis of common variable immunodeficiency-CVID (as PID)-and chronic lymphocytic leukemia-CLL (as SID). The obtained results indicate a significant increase in the percentage of all tested subpopulations of T lymphocytes and B lymphocytes showing positive expression of all analyzed TLRs in patients with CVID and CLL compared to healthy volunteers, constituting the control group, which is also confirmed by analysis of the concentration of soluble forms of these receptors in the plasma of patients. Furthermore, patients diagnosed with CVID are characterized by the percentage of all lymphocytes showing positive expression of the tested TLR2, TLR4, TLR3, and TLR9 and their plasma concentrations in relation to patients with CLL. By investigating the functions and interactions of TLRs within the immune system, we seek to shed light on their critical role in the development and progression of these immunodeficiencies. Through a comprehensive analysis of the literature and presented experimental data, we hope to deepen our understanding of the complex mechanisms by which TLRs contribute to the pathogenesis of PID and SID. Ultimately, our findings may provide valuable insights into developing targeted therapeutic strategies to mitigate the impact of these disorders on those affected by immunodeficiency.

Background: The range of pulmonary complications beyond infections in pediatric immunocompromised patients is broad but not well characterized. Our goal was to assess the spectrum of disorders with a focus on interstitial lung diseases (ILD) in immunodeficient patients., Methods: We reviewed 217 immunocompromised children attending a specialized pneumology service during a period of 23 years. We assigned molecular diagnoses where possible and categorized the underlying immunological conditions into inborn errors of immunity or secondary immunodeficiencies according to the IUIS and the pulmonary conditions according to the chILD-EU classification system., Results: Among a wide array of conditions, opportunistic and chronic infections were the most frequent. ILD had a 40% prevalence. Of these children, 89% had a CT available, and 66% had a lung biopsy, which supported the diagnosis of ILD in 95% of cases. Histology was often lymphocyte predominant with the histo-pattern of granulomatous and lymphocytic interstitial lung disease (GLILD), follicular bronchiolitis or lymphocytic interstitial pneumonitis. Of interest, DIP, PAP and NSIP were also diagnosed. ILD was detected in several immunological disorders not yet associated with ILD., Conclusions: Specialized pneumological expertise is necessary to manage the full spectrum of respiratory complications in pediatric immunocompromised patients.

The present study determined the independent contributions of temperature, strong ion difference ([SID]), total weak acid concentration ([Atot]) and PCO2 to changes in arterial and mixed venous [H+] and total carbon dioxide concentration ([TCO2]) during 37 min of moderate intensity exercise (~50% of heart rate max) and the first 60 min of recovery. Six horses were fitted with indwelling carotid and pulmonary artery (PA) catheters, had PA temperature measured, and had blood samples withdrawn for immediate analysis of plasma ion and gas concentrations. The increase in core temperature during exercise (+4.5 °C; p < 0.001) significantly (p < 0.05) increased PO2, PCO2, and [H+], but without a significant effect on [TCO2] (p > 0.01). The physicochemical acid-base approach was used to determine contributions of independent variables (except temperature) to the changes in [H+] and [TCO2]. In both arterial and venous blood, there was no acidosis during exercise and recovery despite significant (p < 0.05) increases in [lactate] and in venous PCO2. In arterial blood plasma, a mild alkalosis with exercise was due to primarily to a decrease in PCO2 (p < 0.05) and an increase in [SID] (p < 0.1). In venous blood plasma, a near absence of change in [H+] was due to the acidifying effects of increased PCO2 (p < 0.01) being offset by the alkalizing effects of increased [SID] (p < 0.05). The effect of temperature on PO2 (p < 0.001) resulted in an increased arterio-venous PO2 difference (p < 0.001) that would facilitate O2 transfer to contracting muscle. The simultaneous changes in the PCO2 and the concentrations of the other independent acid-base variables (contributions from individual strong and weak ions as manifest in [SID] and [Atot]) show complex, multilevel control of acid-base states in horses performing even moderate intensity exercise. Correction of acid-base variables to core body temperature presents a markedly different physiological response to exercise than that provided by variables measured and presented at an instrument temperature of 37 °C.

SIN3A, a scaffold protein has regulatory functions in tumor biology. Through its Paired amphipathic helix (PAH2) domain, SIN3A interacts with PHF12 (PF1), a protein with SIN3 interaction domain (SID) that forms a complex with MRG15 and KDM5A/B. These components are often overexpressed in cancer. In the present study, we evaluated the role of SIN3A and its interacting partner PF1 in mediating inhibition of tumor growth and invasion in triple negative breast cancer (TNBC). We found profound inhibition of invasion, migration, and induction of cellular senescence by specific disruption of the PF1/SIN3A PAH2 domain interaction in TNBC cells expressing PF1-SID transcript or peptide treatment. Genome-wide transcriptomic analysis by RNA-seq revealed that PF1-SID downregulates several gene sets and pathways linked to invasion and migration. Integrin α6 (ITGA6) and integrin ß1 (ITGB1) and their downstream target proteins were downregulated in PF1-SID cells. We further determined increased presence of SIN3A and transcriptional repressor, KLF9, on promoters of ITGA6 and ITGB1 in PF1-SID cells. Knockdown of KLF9 leads to re-expression of ITGA6 and ITGB1 and restoration of the invasive phenotype, functionally linking KLF9 to this process. Overall, these data demonstrate that specific disruption of PF1/SIN3A, inhibits tumor growth, migration, and invasion. Also, PF1-SID not only inhibits tumor growth by senescence induction and reduced proliferation, but it also targets cancer stem cell gene expression and blocks mammosphere formation. Overall, these data demonstrate a mechanism whereby invasion and metastasis of TNBC can be suppressed by inhibiting SIN3A-PF1 interaction and enhancing KLF9 mediated suppression of ITGA6 and ITGB1., (Copyright © 2021. Published by Elsevier Inc.)

Aim: While facilitated subcutaneous immunoglobulin (fSCIG) has been evaluated in pediatric patients with primary immunodeficiency diseases in clinical trials, real-world data are lacking. Materials & methods: This multicenter, retrospective, chart review study assessed fSCIG utilization in 30 patients less than 18 years old, with primary or secondary immunodeficiency diseases. Medical records were reviewed at fSCIG initiation and at 6 months. Results: Most (90%) patients received their first fSCIG infusion at a medical facility; by 6 months, all fSCIG infusions were administered at home by the patient/caregiver, the majority infusing every 3-4 weeks into a single site. No serious adverse drug reactions occurred. Conclusion: This study supports the feasibility and tolerability of administering fSCIG at home to pediatric patients with immunodeficiencies. Clinical Trial Registration: DRKS00015436 (German Clinical Trials Register).

This manuscript will review crystalloid (hypo-, iso-, and hyper-tonic) and colloid (synthetic and natural) fluids that are available for intravenous administration with a focus on their electrolyte, acid-base, colligative, and rheological effects as they relate to each solution's efficacy and safety. The goal is for the reader to better understand the differences between each fluid and the influence on plasma composition, key organ systems, and their implications when used therapeutically in animals with critical illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rudloff and Hopper.)

P4 is a mobile genetic element (MGE) that can exist as a plasmid or integrated into its Escherichia coli host genome, but becomes packaged into phage particles by a helper bacteriophage, such as P2. P4 is the original example of what we have termed "molecular piracy", the process by which one MGE usurps the life cycle of another for its own propagation. The P2 helper provides most of the structural gene products for assembly of the P4 virion. However, when P4 is mobilized by P2, the resulting capsids are smaller than those normally formed by P2 alone. The P4-encoded protein responsible for this size change is called Sid, which forms an external scaffolding cage around the P4 procapsids. We have determined the high-resolution structure of P4 procapsids, allowing us to build an atomic model for Sid as well as the gpN capsid protein. Sixty copies of Sid form an intertwined dodecahedral cage around the T = 4 procapsid, making contact with only one out of the four symmetrically non-equivalent copies of gpN. Our structure provides a basis for understanding the sir mutants in gpN that prevent small capsid formation, as well as the nms "super-sid" mutations that counteract the effect of the sir mutations, and suggests a model for capsid size redirection by Sid.

Introduction Studies on sudden infant death syndrome (SIDS) in Saudi Arabia are limited due to strict religious faith-related observances. The aim of this study was to assess Saudi mothers' awareness about SIDS. Methodology A cross-sectional online electronic survey was administered in different Saudi regions. A self-reported validated Arabic questionnaire was used for collecting data. The study sample included 363 respondents from 384 sample members. Results The final sample consisted of 363 (94.8%) respondents, a reduction in size due to 21 non-responders from the total 384 sample members. Two-hundred and thirty-two (63.9%) of the 363 respondents reported not having heard of any SIDS prevention messages, while 36.1% of them had received such messages. Most of the respondents (53.2%) correctly reported that babies should be laid on their backs while putting them to sleep, and only 5.5% reported that babies should be laid in their stomachs when being put to rest. Participants > 50 years, of urban residence, and with primary education had higher knowledge levels. Participants with an age of 18 to 29 years and those with higher education had higher knowledge levels about the correct baby position. Participants with an age between 30 and 39 years, of urban residence, and those with a primary educational level had a higher prevalence of receiving messages about SIDS. Conclusion A very good understanding of the proper way to put a baby to sleep among the participants was found, and most of them thought that messages about SIDS were not useful. This study suggests that health education messages regarding SIDS should be directed to all pregnant mothers., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Alzahrani et al.)

Background : The opioid epidemic's impact reached an increasing portion of the United States population, including pregnant women. Objectives : We sought to determine the prevalence and factors associated with opioid use disorders during pregnancy in North Carolina. Study Design : Using North Carolina's State Inpatient Sample, a retrospective study was conducted to identify pregnancy-related discharges between 2000 and 2014. Hospital discharge records associated with ICD-9-CM diagnoses codes for the use of opioids for all eligible pregnancy-related discharges were extracted. Logistic regression models were used to estimate unadjusted and adjusted bivariate and multivariate relationships. Results : Of 1,937,455 pregnancy-related hospitalization in North Carolina, 6,084 were associated with opioid use, a prevalence of 3.14 cases per 1,000 discharge. Maternal opioid use was associated with an increased odds of early onset delivery, threatened preterm labor, premature rupture of membranes, postpartum depression, stillbirth and poor fetal growth. Women who used opioids during pregnancy had prolonged hospital stays (>5 days) and were 2 times as likely to have more than 4 procedures performed during hospitalization. Compared to other racial groups, non-Hispanic whites had a notably higher prevalence of opioid use disorders (5.8/1,000 pregnancy-related discharges) ( P < 0.05 for all ). Conclusions : Very few health issues have garnered the attention of such diverse sectors of our society as the opioid epidemic. As the first state-level analysis of opioid use disorders among delivery hospitalizations, these findings suggest the need for a system-wide public health response such as improved funding for Medicaid and child welfare systems to improve the health of the opioid-exposed mother-infant dyad.

Background and Aim: Perioperative stroke is a feared and potentially disastrous complication of surgery. Postdischarge care, specifically hospital readmissions, can significantly impact postsurgical recovery and provides a useful metric for quality care. Our primary aim was examining 30-day readmissions for patients who had a perioperative stroke undergoing noncardiac non-neurosurgery., Methods: We analyzed data from the State Inpatient Database, a database of community hospital discharges, in California between 2008 and2011. Surgical patients undergoing one of the 10 highest-volume procedures were included; patients less than 18 years old, undergoing pregnancy-related procedures, or who died in-hospital were excluded. Our dataset covariates included demographic and clinical variables, comorbidities, and discharge location. After running an initial bivariate analysis using Chi-square and t-tests and testing for multicollinearity, logistical models were run to calculate adjusted odds ratios and confidence intervals for readmission predictors., Results: 30-day readmissions for patients with perioperative stroke (n = 1613) occurred at a rate of 21.08% (340 patients), compared to 6.29% (63,856 patients) for patients without perioperative stroke (adjusted OR = 1.40, 95% CI 1.23-1.59, P < .0001). Demographic predictors of 30-day readmissions included male sex and African-American race. Clinical predictors of 30-day readmissions included several comorbidities (i.e. liver disease, hypertension), and discharge to a postacute care facility. Key 30-day readmission diagnoses for perioperative stroke patients included septicemia, stroke, aspiration pneumonitis, and urinary tract infections., Conclusions: Patients with perioperative stroke have high 30-day readmissions rates. A number of demographic and clinical factors increase readmission risk in this population. Further research is warranted to better support patients with perioperative stroke undergoing care transitions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The revised legislation on medicinal cannabis has triggered a surge of research studies in this space. Yet, cannabis proteomics is lagging. In a previous study, we optimised the protein extraction of mature buds for bottom-up proteomics. In this follow-up study, we developed a top-down mass spectrometry (MS) proteomics strategy to identify intact denatured protein from cannabis apical buds. After testing different source-induced dissociation (SID), collision-induced dissociation (CID), higher-energy collisional dissociation (HCD), and electron transfer dissociation (ETD) parameters on infused known protein standards, we devised three LC-MS/MS methods for top-down sequencing of cannabis proteins. Different MS/MS modes produced distinct spectra, albeit greatly overlapping between SID, CID, and HCD. The number of fragments increased with the energy applied; however, this did not necessarily translate into greater sequence coverage. Some precursors were more amenable to fragmentation than others. Sequence coverage decreased as the mass of the protein increased. Combining all MS/MS data maximised amino acid (AA) sequence coverage, achieving 73% for myoglobin. In this experiment, most cannabis proteins were smaller than 30 kD. A total of 46 cannabis proteins were identified with 136 proteoforms bearing different post-translational modifications (PTMs), including the excision of N-terminal M, the N-terminal acetylation, methylation, and acetylation of K resides, and phosphorylation. Most identified proteins are involved in photosynthesis, translation, and ATP production. Only one protein belongs to the phytocannabinoid biosynthesis, olivetolic acid cyclase., Competing Interests: The authors declare no conflict of interest.

The aim of this study was to develop and validate the novel microLC/MS-MRM method for the simultaneous quantification of six proteins: angiopoietin 2 (Angpt-2), soluble form of fms-like tyrosine kinase 1 (sFLT-1), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA), endocan (ESM-1), soluble form of E-selectin (sE-sel), and one peptide: adrenomedullin (ADM) in mouse plasma. Two approaches were compared: a stable isotope dilution (SID) method- used as a reference and a modified SID (mSID) procedure. In SID strategy the calibration curves were used, whereas in mSID the ratio between the chromatogram peak area of endogenous tryptic peptides at unknown concentration to chromatogram peak area of exogenous, stable isotope-labelled internal standards (SISs) added to the sample at known concentration was calculated. The microLC/MS-MRM method in the SID approach was linear from 0.250 pmol/mL to 250 pmol/mL for Angpt-2; 5 pmol/mL to 5000 pmol/mL for sFLT-1; 2.5 pmol/mL to 5000 pmol/mL for PAI-1; 0.375 pmol/mL to 250 pmol/mL for t-PA; 0.375 pmol/mL to 187.5 pmol/mL for ESM-1; 2.5 pmol/mL to 5000 pmol/mL for sE-sel and 0.375 pmol/mL to 250 pmol/mL for ADM. LPS-induced changes in plasma assessed based on SID and mSID approaches gave comparable quantitative results and featured LPS-induced dysregulation of endothelial permeability (Angpt-2, sFLT-1), glycocalyx injury (SDC-1) accompanied by a pro-thrombotic response (PAI-1). In addition, we applied microLC/MS-MRM method with mSID strategy to analyze human plasma samples from patients with chronic myeloid leukemia (CML) and obstructive sleep apnoea (OSA) and demonstrated usefulness of the method to characterize endothelial function in humans. In conclusion, the microLC/MS-MRM method with mSID strategy applied for simultaneous quantification of protein biomarkers of endothelial function in plasma represents a novel targeted proteomic platform for the comprehensive evaluation of endothelial function in mice and humans., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Reasons for Performing Study: Acid-base imbalances observed in human paediatric patients are associated with outcome. Likewise, neonatal foals may have different acid-base imbalances associated with diagnosis or prognosis., Objectives: To determine acid-base imbalances by the quantitative method in ill neonatal foals and assess their association with diagnosis and prognosis., Study Design: Observational prospective clinical study., Methods: This study included 65 ill neonatal foals (32 septic, 33 nonseptic) admitted to an equine referral hospital from 2005 to 2011with acid-base parameters determined on admission and a control group of 33 healthy neonatal foals. Blood pH, pCO 2 , sodium, potassium, chloride, L-lactate, albumin and phosphate concentrations were determined. Bicarbonate, globulin, measured strong ion difference (SID m ), nonvolatile weak buffer concentrations (A tot ), base excess and its components were calculated. Analysis of covariance (ANCOVA) and multiple linear regression statistical analyses were performed. Results are summarised as mean ± s.d. for normally distributed variables and median [25-75th percentiles] for non-normally distributed ones., Results: A total of 63% of ill foals had respiratory alkalosis and 58.5% had SID m acidosis. The combination of both alterations was detected in 21 of 65 ill foals and abnormal pH was found in 24 of 65. Compared with healthy foals, ill foals had significantly lower SID m (nonseptic 31.6 ± 6.3 [P<0.01] and septic 32.0 ± 6.4 [P<0.01] vs. control 40.3 ± 3.1 mmol/l), potassium (nonseptic 3.5 [3.3-3.8; P<0.01] and septic 3.6 [3.2-4.3; P = 0.01] vs. control 4.2 [3.8-4.5] mEq/l) and higher L-lactate (nonseptic 5.1 ± 4.2 [P = 0.01] and septic 5.0 ± 3.7 [P = 0.03] vs. control 2.5 ± 1.3 mmol/l). Significantly higher L-lactate and venous pCO 2 were found in nonsurviving (6.4 ± 3.5 mmol/l [P = 0.04] and 51 ± 13 mmHg [P<0.01]) compared with surviving foals., Conclusions: The most common acid-base imbalances observed in ill foals were respiratory alkalosis, SID m acidosis or mixed respiratory alkalosis with strong ion acidosis. Increased venous pCO 2 and blood L-lactate concentration were associated with poor outcome., (© 2015 EVJ Ltd.)

Objective: To determine the strong ion difference (SIDa ) and total nonvolatile weak buffers (ATOT ) in healthy foals during the first year of life and to compare reference biochemistry laboratory with analyzers available during emergency hours., Design: Prospective study performed over 2 years., Setting: University teaching hospital., Animals: Two hundred thirty-six healthy foals distributed in 6 groups: A (21 days-2 months), B (2-3 months), C (3-6 months), D (6-9 months), E (9-12 months), and 33 neonatal foals (< 21 days old)., Interventions: Blood samples were obtained to determine L-lactate, sodium, potassium, chloride, and total plasma protein concentrations. In neonatal foals, samples were analyzed using 4 different devices. Reference intervals of SIDa and ATOT for each of the analyzers under comparison were established using mean ± 2 standard deviations. Age effect was evaluated using one-way ANOVA analysis. Linear regression in neonatal foals was employed to obtain a new equation to estimate ATOT from total plasma protein concentration., Measurements and Main Results: A significant age effect was observed for ATOT and SIDa . In all foals younger than 6 months, ATOT values were lower than in older foals (P < 0.003). A clinically and statistically significant difference in SIDa was detected only in the neonatal period (P < 0.001). The equation to estimate ATOT from total plasma protein adjusted for neonatal foals is ATOT = 2.5 × total plasma protein concentration., Conclusions: Reference intervals of ATOT should be considered different from adults during the first 6 months of life in horses. Regarding SIDa , values should be considered different only during first 21 days of life., (© Veterinary Emergency and Critical Care Society 2016.)

Background Context: There is a persistent trend for more outpatient lumbar discectomies in the United States., Purpose: To investigate the characteristics of the patients selected for ambulatory procedures., Study Design: Retrospective cohort study., Patient Sample: Forty-seven thousand one hundred twenty-five patients who underwent outpatient and 102,592 patients undergoing inpatient lumbar discectomies and were were registered in the State Ambulatory Surgery Database (SASD) and State Inpatient Database (SID), respectively, for New York, California, Florida, and North Carolina from 2005 to 2008., Outcome Measures: Rate of outpatient procedures, 30-day readmissions, and hospital charges., Methods: We performed a retrospective cohort study involving patients who underwent outpatient and inpatient lumbar discectomies and were registered in SASD and SID, respectively, for New York, California, Florida, and North Carolina from 2005 to 2008. Logistic regression models were used to demonstrate the association of socioeconomic factors with the odds of undergoing an outpatient procedure., Results: Male gender (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.08), private insurance (OR, 1.93; 95% CI, 1.86-2.01), lower Charlson Comorbidity Index (OR, 4.04; 95% CI, 3.17-5.16), and higher volume hospitals (OR, 1.06; 95% CI, 1.04-1.08) were significantly associated with outpatient procedures. Higher income (OR, 0.83; 95% CI, 0.81-0.85), older age (OR, 0.996; 95% CI, 0.995-0.997), coverage by Medicaid (OR, 0.89; 95% CI, 0.83-0.96), African Americans (OR, 0.65; 95% CI, 0.60-0.70), and other minority races were associated with decreased odds of outpatient procedures. The rate of 30-day postoperative readmissions was higher among inpatients. Institutional charges were significantly lower for outpatient lumbar discectomies. The median charge for inpatient surgery was $24,273 as compared with $11,339 for the outpatient setting (p<.0001)., Conclusions: Access to ambulatory lumbar discectomies appears to be more common for younger, white, male patients, with private insurance and less comorbidities, in the setting of higher volume hospitals. Further investigation is needed in the direction of mapping these disparities for appropriate resource utilization., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Spinal cord stimulators (SCS) are increasingly placed in the United States in both the inpatient and outpatient setting. Although these interventions appear to be safe, the characteristics of the patients selected for ambulatory procedures have not been investigated., Materials and Methods: We performed a retrospective cohort study involving 4843 patients who underwent outpatient and 4197 who underwent inpatient SCS placements and were registered in State Ambulatory Surgery Databases and State Inpatient Databases, respectively, for New York, California, Florida, and North Carolina from 2005 to 2008., Results: In a multivariate analysis, male gender (odds ratio (OR) 1.22, 95% confidence interval (CI), 1.12, 1.33), high volume hospitals (OR 2.16, 95% CI, 1.94, 2.41), and Caucasian race (OR 1.25, 95% CI, 1.10, 1.41) were significantly associated with outpatient procedures. Higher Charlson Comorbidity Index (OR 0.36, 95% CI, 0.24, 0.54) and Medicare/Medicaid insurance (OR 0.75, 95% CI, 0.67, 0.83) were associated with a decreased chance of outpatient procedures. The rate of 30-day postoperative readmissions was higher among inpatients. Institutional charges were significantly lower for outpatient lumbar discectomies. The median total charge for inpatient hospitalization after SCS placement was $60,624 as compared with $22,288 for the outpatient setting (p < 0.0001)., Conclusions: Access to ambulatory SCS placement appears to be more common for Caucasians, male patients, with private insurance, and fewer comorbidities, in the setting of higher volume hospitals. Further investigation is needed in the direction of mapping these disparities for appropriate resource utilization., (© 2013 International Neuromodulation Society.)

Background: Switching primary/secondary immunodeficiency (PID/SID) patients from intravenous immunoglobulin (IVIg) to home-based subcutaneous immunoglobulin (SCIg) therapy reduces nurse time. A nurse shortage in Canada provides an important context to estimate the net economic benefit, the number of patients needed to switch to SCIg to recoup one full-time equivalent (FTE), and potential population-wide savings of reduced nurse time to a payer., Methods: The net economic benefit was estimated by multiplying the hourly compensation for nurses in Canada by the hours required for each administration route. The number needed to switch to SCIg to gain one nurse FTE was estimated by dividing the work hours in a year by the average annual savings in nursing time in a PID population in Canada. The prevalence of treated PID/SID in Canada was calculated using provincial IgG audit data to extrapolate the potential population-wide savings of switching patients to SCIg therapy., Findings: The net economic gain from switching one patient to home-based SCIg care would be C$2,603 (Canadian Dollars) in year 1 and C$2,948 each year thereafter. Switching 37 IVIg patients to SCIg would gain one nurse FTE. Switching 50% of the estimated 5,486 PID and SID patients in Canada receiving IVIg therapy to SCIg has the potential to save 223.3 nurse FTEs (C$23.2 million in labor costs)., Conclusions: A shift from IVIg to less labor-intensive SCIg has the potential to help alleviate nurse shortages and reduce overall health care costs in Canada. Health care professionals might consider advocating for home-based SCIg therapy for PID/SID patients when clinically appropriate.

Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacent to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE-SID chimeric repressors. The TALE-SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE-SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE-SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Sevoflurane is a general anesthetic commonly used in the pediatric setting because it is sweet-smelling, nonflammable, fast acting and has a very short recovery time. Although recent clinical data suggest that early anesthesia exposure is associated with subsequent learning and memory problems, it is difficult to determine the exact scope of developmental neurotoxicity associated with exposure to specific anesthetics such as sevoflurane. This is largely due to inconsistencies in the literature. Thus, in the present studies we evaluated the effect of early life exposure to sevoflurane (1%, 2%, 3% or 4%) on adulthood memory impairment in Sprague-Dawley rats. Animals were exposed to different regimens of sevoflurane anesthesia on postnatal days (PNDs) 3, 7, or 14 or at 7 weeks (P7W) of age and spatial memory performance was assessed in adulthood using the Morris Water Maze (MWM). Rats exposed to sevoflurane exhibited significant memory impairment which was concentration and exposure duration dependent. Disruption of MWM performance was more severe in animals exposed on both PNDs 3 and 7 than in animals exposed on both PNDs 3 and 14. The younger the animal's age at the time of exposure, the more significant the effect on later MWM performance. Compared to the neonates, animals exposed at P7W were relatively insensitive to sevoflurane: memory was impaired in this group only after repeated exposures to low doses or single exposures to high doses. Early life exposure to sevoflurane can result in spatial memory impairments in adulthood and the shorter the interval between exposures, the greater the deficit., (Copyright © 2013 Elsevier Inc. All rights reserved.)