Clinical outcomes and emergence of resistance of Pseudomonas aeruginosa infections treated with ceftolozane-tazobactam versus ceftazidime-avibactam.

Few studies compare outcomes of patients with difficult-to-treat resistance (DTR) Pseudomonas aeruginosa infections treated with ceftolozane-tazobactam versus ceftazidime-avibactam. A multicenter prospective study was conducted of unique patients with DTR P. aeruginosa infections from 2018 to 2023 receiving >72 h of ceftolozane-tazobactam or ceftazidime-avibactam, with confirmation that the P. aeruginosa isolate was susceptible to the agent administered by broth microdilution. Inverse probability weighting (IPW) incorporating propensity scores was utilized to ensure balanced baseline characteristics. Regression performed on the post-IPW group determined 30-day mortality and subsequent emergence of resistance (i.e., ≥4-fold increase in MIC) to the initial treatment (i.e., ceftolozane-tazobactam or ceftazidime-avibactam). Among 186 eligible patients, 102 (55%) received ceftolozane-tazobactam and 84 (45%) received ceftazidime-avibactam. In the post-IPW cohort, balance was achieved across all variables [e.g., demographics, severity of illness, severe immunocompromise, Charlson Comorbidity Index ≥5, continuous renal replacement therapy (CRRT), source of infection, combination therapy]. Thirty-day mortality was similar between the ceftolozane-tazobactam and ceftazidime-avibactam groups [21% vs 17%; adjusted odds ratio (aOR): 1.01 (95% confidence interval, CI: 0.90-1.14)]. Emergence of resistance was higher in the ceftolozane-tazobactam group [38% vs 25%; aOR: 1.89 (95% CI: 0.98-4.88)], but did not achieve statistical significance. Prolonged treatment durations and use of CRRT were associated with increased emergence of resistance (both P = 0.04). Although the survival of patients with DTR P. aeruginosa infections appears similar regardless of whether ceftolozane-tazobactam or ceftazidime-avibactam is prescribed, the emergence of resistance may be more concerning with the former. Plausible mechanistic explanations support these findings. Modifiable risk factors were identified that may mitigate this risk.

Intermittent ozone inhalation during house dust mite-induced sensitization primes for adverse asthma phenotype.

The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O3), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 µg/kg) for 3 weeks on alternate days in parallel with once-a-week O3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O3 leads to a significant increase in peribronchial inflammation (p < 0.01), perivascular inflammation (p < 0.001) and methacholine-provoked large airway hyperreactivity (p < 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3-5 times greater in HDM + O3 co-exposure compared to PBS and O3-exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p < 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p < 0.05) were noted in the HDM + O3 group compared to HDM alone group. Concurrent O3 inhalation and HDM sensitization also caused significantly greater (p < 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O3 inhalation during allergic sensitization coalesces in generating a significantly worse TH17 asthmatic phenotype.

Patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer.

BACKGROUND: Sentinel lymph node mapping is a minimally invasive surgical staging procedure that allows identification of macro- and micrometastases. The implementation of sentinel lymph node mapping to women with low-grade endometrial cancer allows detection of lymph node metastases and avoids the morbidity of radical pelvic lymphadenectomy. The extent of myometrial invasion is highly predictive of lymph node metastases but is hard to determine precisely preoperatively. The exact rate of lymph node metastases in the large group of women with <50% myometrial invasion is low but unknown. The benefit of detecting metastases in this group should balance the risk of lymphedema. There is limited knowledge of early and late lymphedema and its impact on the quality of life in women with low-grade endometrial cancer following sentinel lymph node mapping. OBJECTIVE: The primary objective was to investigate the risk of patient-reported lymphedema after SLN mapping in women with low-grade endometrial cancer. In addition, we aimed to evaluate risk factors for lymphedema and the condition-specific quality of life (QoL) among women who reported lymphedema 12 months after surgery. STUDY DESIGN: Women with presumed stage I low-grade endometrial cancer were included in a national prospective cohort study on SLN mapping from March 2017-February 2022. Women completed a package of validated patient-reported outcome measures (PROMs) before surgery, three and 12 months after surgery. The primary outcome was the leg lymphedema domain score from the European Organisation for Research and Treatment of Cancer endometrial cancer-specific module (EORTC QLQ-EN24). The lymphedema assessment was further supplemented by seven validated single items from the EORTC item library addressing lymphedema of legs, genitals, and groin. The disease-specific QoL was assessed using the validated Lymphedema quality of life tool (LYMQOL). Scores were linearly transformed to 0-100. A change from baseline of 8 points in leg lymphedema sum-score was considered clinically important. Mean difference scores over time with 95% CI were estimated. Multiple linear regression models evaluated baseline predictors associated with the 12 month postoperative lymphedema score, and if early lymphedema predicted lymphedema at 12 months after surgery. Lymphedema condition-specific QoL was evaluated for women with lymphedema. RESULTS: Seventy-nine % (486/617) completed PROMs at baseline and 12 months. The mean difference score of leg lymphedema from baseline to 12 months was 5.0, CI [3.3, 6.8], i.e., below the threshold for clinical importance. Baseline leg lymphedema score and BMI were positively associated with the leg lymphedema score at 12 months. The leg lymphedema score at three months was associated with a higher 12-month score. High scores of lymphedema at 12 months were negatively associated with the women's daily activities, appearance, emotional functioning, and global QoL and increased their subjective symptom burden. CONCLUSIONS: Women with low-grade endometrial cancer have a low risk of lymphedema after SLN mapping. Leg swelling at baseline and BMI predicted more lymphedema at 12 months after surgery. Early lymphedema at three months predicted persistent lymphedema. A high leg lymphedema score at 12 months is associated with impairment in several aspects of QoL.

Household food insecurity and novel complementary feeding methods in New Zealand families.

Optimal nutrition during infancy is critical given its influence on lifelong health and wellbeing. Two novel methods of infant complementary feeding, commercial baby food pouch use and baby-led weaning (BLW), are becoming increasingly popular worldwide. Household food insecurity may influence complementary feeding practices adopted by families, but no studies have investigated the use of BLW and baby food pouches in families experiencing food insecurity. The First Foods New Zealand study was a multicentre, observational study in infants 7.0-9.9 months of age. Households (n = 604) were classified into one of three categories of food insecurity (severely food insecure, moderately food insecure, and food secure). The use of complementary feeding practices was assessed via a self-administered questionnaire, both at the current age (mean 8.4 months) and retrospectively at 6 months. Mothers experiencing severe food insecurity had 5.70 times the odds of currently using commercial baby food pouches frequently (≥5 times/week) compared to food secure mothers (95% CI [1.54, 21.01]), reporting that pouches were 'easy to use' (89%) and made it 'easy to get fruits and vegetables in' (64%). In contrast, no evidence of a difference in the prevalence of current BLW was observed among mothers experiencing moderate food insecurity (adjusted OR; 1.28, 95% CI [0.73, 2.24]) or severe food insecurity (adjusted OR; 1.03, 95% CI [0.44, 2.43]) compared to food secure mothers. The high prevalence of frequent commercial baby food pouch use in food insecure households underscores the need for research to determine whether frequent pouch use impacts infant health.

Obtention of viable cell suspensions from breast cancer tumor biopsies for 3D chromatin conformation and single-cell transcriptome analysis.

Molecular and cellular characterization of tumors is essential due to the complex and heterogeneous nature of cancer. In recent decades, many bioinformatic tools and experimental techniques have been developed to achieve personalized characterization of tumors. However, sample handling continues to be a major challenge as limitations such as prior treatments before sample acquisition, the amount of tissue obtained, transportation, or the inability to process fresh samples pose a hurdle for experimental strategies that require viable cell suspensions. Here, we present an optimized protocol that allows the recovery of highly viable cell suspensions from breast cancer primary tumor biopsies. Using these cell suspensions we have successfully characterized genome architecture through Hi-C. Also, we have evaluated single-cell gene expression and the tumor cellular microenvironment through single-cell RNAseq. Both technologies are key in the detailed and personalized molecular characterization of tumor samples. The protocol described here is a cost-effective alternative to obtain viable cell suspensions from biopsies simply and efficiently.

Impacts of trace level chromium on formation of superoxide within uranyl triperoxide complexes.

U(VI) peroxides are important within the nuclear fuel cycle, but reactive oxygen species (ROS) can form upon oxidation. Herein, we identified the spectral signatures of a U(VI) diperoxosuperoxide complex (KUPS-1) and observed that the transformation of U(VI) triperoxide (KUT-1) to superoxide forms occurred with trace-level Cr. U(VI) superoxide complexes were identified in EPR solution spectra without the use of spin-traps.

Communication trends over time in new-onset refractory status epilepticus (NORSE): Interim analysis from the NORSE/FIRES Family Registry.

The new-onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) Family Registry contributes to a systematic effort to collect clinical and epidemiological information on individuals affected by NORSE/FIRES. We explore diagnostic and prognostic information provided to patients and their families, their satisfaction with the communication, and utilisation of palliative care services during acute hospitalization. Communication about the diagnosis of NORSE/FIRES to families has improved since the publication of consensus definitions in 2018, with families being more likely to be told about NORSE/FIRES after 2018. Families rate the quality of prognostic information as being moderate. Palliative care services were involved in a minority of patients. Understanding and characterizing the prevalence and satisfaction of diagnostic and prognostic conversations is important for improving overall care, the quality of physician-patient-family relationships, and the recovery process for those affected by NORSE/FIRES.

Salmonella Prevalence and Quantification in Market Hog Lymph Nodes and Tonsils in Several Regions and Seasons of the United States.

Market hog lymph nodes (LNs) can contaminate carcasses with Salmonella, as well as ground and comminuted pork products. The objective of this study was to perform a qualitative and quantitative analysis of LNs from several regions and seasons in the United States to establish a Salmonella prevalence and concentration baseline. Six types of LNs (axillary, mesenteric, subiliac, tracheobronchial, superficial inguinal, pre-scapular) and tonsils were sampled from market hog carcasses from different regions (east, central, and west) and seasons (winter, spring, and summer/fall). Salmonella was detected and enumerated using BAX®-System-SalQuant® methods and the BAX®-System Real-Time Salmonella Assay. Salmonella prevalence (N=4,132) was 36% for tonsils, 35% for mesenteric LN, and less than 10% for the other LN types. Of the 601 carcasses tested, 62% were positive for Salmonella, with the highest prevalence occurring during spring in the east (90.9%), and the lowest prevalence occurring during spring in the central region (26.0%). Tonsil prevalence was greatest in the eastern region during spring. Mesenteric LN prevalence was high (>20%) regardless of season or region. Salmonella prevalence in tracheobronchial, subiliac, axillary, and superficial inguinal LNs was generally greatest during the spring or fall and in the eastern region. The median SalQuant® Salmonella concentration was 2.18 log10Salmonella cells/sample. Median SalQuant® concentration for all other sample types fell below the limit of quantification (1 log10Salmonella cells/sample). This longitudinal study can be used by the pork industry for risk assessments and risk-based decision making.

Terminalia bellirica and Andrographis paniculata dietary supplementation in mitigating heat stress-induced behavioral, metabolic and genetic alterations in broiler chickens.

BACKGROUND: Heat stress (HS) is one of the most significant environmental stressors on poultry production and welfare worldwide. Identification of innovative and effective solutions is necessary. This study evaluated the effects of phytogenic feed additives (PHY) containing Terminalia bellirica and Andrographis paniculata on behavioral patterns, hematological and biochemical parameters, Oxidative stress biomarkers, and HSP70, I-FABP2, IL10, TLR4, and mTOR genes expression in different organs of broiler chickens under chronic HS conditions. A total of 208 one-day-old Avian-480 broiler chicks were randomly allocated into four treatments (4 replicate/treatment, 52 birds/treatment): Thermoneutral control treatment (TN, fed basal diet); Thermoneutral treatment (TN, fed basal diet + 1 kg/ton feed PHY); Heat stress treatment (HS, fed basal diet); Heat stress treatment (HS, fed basal diet + 1 kg/ton feed PHY). RESULTS: The findings of the study indicate that HS led to a decrease in feeding, foraging, walking, and comfort behavior while increasing drinking and resting behavior, also HS increased red, and white blood cells (RBCs and WBCs) counts, and the heterophile/ lymphocyte (H/L) ratio (P < 0.05); while both mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were decreased (P < 0.05). In addition, HS negatively impacted lipid, protein, and glucose levels, liver and kidney function tests, and oxidative biomarkers by increasing malondialdehyde (MDA) levels and decreasing reduced glutathion (GSH) activity (P < 0.05). Heat stress (HS) caused the upregulation in HSP70, duodenal TLR4 gene expression, and the downregulation of I-FABP2, IL10, mTOR in all investigated tissues, and hepatic TLR4 (P < 0.05) compared with the TN treatment. Phytogenic feed additives (PHY) effectively mitigated heat stress's negative impacts on broilers via an improvement of broilers' behavior, hematological, biochemical, and oxidative stress biomarkers with a marked decrease in HSP70 expression levels while all tissues showed increased I-FABP2, IL10, TLR4, and mTOR (except liver) levels (P < 0.05). CONCLUSION: Phytogenic feed additives (PHY) containing Terminalia bellirica and Andrographis paniculata have ameliorated the HS-induced oxidative stress and improved the immunity as well as the gut health and welfare of broiler chickens.

Provisions Related to Health, Nutrition, and Healthy Beverage Promotion in University Pouring Rights Contracts: A Content Analysis.

PURPOSE: Many universities maintain pouring rights contracts (PRCs) with beverage companies wherein one company exchanges sponsorship payments for exclusive beverage marketing rights. Separately, universities may have healthy beverage initiatives (HBIs) to encourage healthier choices on campus. This study aimed to assess how and how frequently PRCs included provisions related to health and nutrition to examine how PRCs may support or undermine HBIs. DESIGN: Cross-sectional. SETTING: U.S. public universities with >20,000 students. SAMPLE: 131 PRCs obtained from 124 of 143 universities in 2019-2020. MEASURES: Primary outcomes were the presence of provisions that could encourage or discourage promotion of healthy beverages (water, diet soda, unsweetened coffee or tea, and 100% juice), and any other provisions explicitly or implicitly referencing health or nutrition. ANALYSIS: Descriptive statistics. RESULTS: Twelve contracts (9%) had explicit commitments from the company or university to promote healthy beverages or adhere to nutrition standards, including five committing to support HBIs, four committing to healthy vending policies, and three describing activities to promote healthy beverage brands. Ten (8%) had provisions explicitly inhibiting water promotion and 55 (42%) had provisions that could be interpreted that way. Eleven (8%) included other health and nutrition provisions, such as funding for unspecified wellness activities. CONCLUSION: Most university beverage contracts did not expressly aim to support healthy choices, and more than half had provisions potentially limiting universities' ability to implement HBIs. When present, nutrition standards were weak.

Rictor, an mTORC2 Protein, Regulates Murine Lymphatic Valve Formation Through the AKT-FOXO1 Signaling.

BACKGROUND: Lymphatic valves are specialized structures in collecting lymphatic vessels and are crucial for preventing retrograde lymph flow. Mutations in valve-forming genes have been clinically implicated in the pathology of congenital lymphedema. Lymphatic valves form when oscillatory shear stress from lymph flow signals through the PI3K/AKT pathway to promote the transcription of valve-forming genes that trigger the growth and maintenance of lymphatic valves. Conventionally, in many cell types, AKT is phosphorylated at Ser473 by the mTORC2 (mammalian target of rapamycin complex 2). However, mTORC2 has not yet been implicated in lymphatic valve formation. METHODS: In vivo and in vitro techniques were used to investigate the role of Rictor, a critical component of mTORC2, in lymphatic endothelium. RESULTS: Here, we showed that embryonic and postnatal lymphatic deletion of Rictor, a critical component of mTORC2, led to a significant decrease in lymphatic valves and prevented the maturation of collecting lymphatic vessels. RICTOR knockdown in human dermal lymphatic endothelial cells not only reduced the level of activated AKT and the expression of valve-forming genes under no-flow conditions but also abolished the upregulation of AKT activity and valve-forming genes in response to oscillatory shear stress. We further showed that the AKT target, FOXO1 (forkhead box protein O1), a repressor of lymphatic valve formation, had increased nuclear activity in Rictor knockout mesenteric lymphatic endothelial cells in vivo. Deletion of Foxo1 in Rictor knockout mice restored the number of valves to control levels in lymphatic vessels of the ear and mesentery. CONCLUSIONS: Our work identifies a novel role for RICTOR in the mechanotransduction signaling pathway, wherein it activates AKT and prevents the nuclear accumulation of the valve repressor, FOXO1, which ultimately enables the formation and maintenance of lymphatic valves.

Characterization of white matter hyperintensities in Down syndrome.

INTRODUCTION: In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. METHODS: In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. RESULTS: In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. DISCUSSION: WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. HIGHLIGHTS: White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.

The relationship and interdependence of auditory thresholds, proposed behavioural measures of hidden hearing loss, and physiological measures of auditory function.

OBJECTIVES: Standard diagnostic measures focus on threshold elevation but hearing concerns may occur independently of threshold elevation - referred to as "hidden hearing loss" (HHL). A deeper understanding of HHL requires measurements that locate dysfunction along the auditory pathway. This study aimed to describe the relationship and interdependence between certain behavioural and physiological measures of auditory function that are thought to be indicative of HHL. DESIGN: Data were collected on a battery of behavioural and physiological measures of hearing. Threshold-dependent variance was removed from each measure prior to generating a multiple regression model of the behavioural measures using the physiological measures. STUDY SAMPLE: 224 adults in the United States with audiometric thresholds ≤65 dB HL. RESULTS: Thresholds accounted for between 21 and 60% of the variance in our behavioural measures and 5-51% in our physiological measures of hearing. There was no evidence that the behavioural measures of hearing could be predicted by the selected physiological measures. CONCLUSIONS: Several proposed behavioural measures for HHL: thresholds-in-noise, frequency-modulation detection, and speech recognition in difficult listening conditions, are influenced by hearing sensitivity and are not predicted by outer hair cell or auditory nerve physiology. Therefore, these measures may not be able to assess threshold-independent hearing disorders.

Determination of gas flux of growing steers under intensive grazing conditions.

Ruminants produce one-third of the anthropogenic methane (CH 4 ) emissions worldwide, and 47% of the CH4 emissions result from ruminants under grazing conditions. However, there is limited information regarding the appropriate number of visits to accurately determine enteric CH4 emissions using the automated head-chamber system (AHCS) from growing beef cattle under intensive grazing conditions. Data from one experiment were analyzed to determine the number of visits to assess gas flux (CH4, carbon dioxide [CO 2 ], and oxygen [O 2 ]) from Angus-crossbreed steers grazing in a pivot-irrigated improved pasture. A total of 110 steers (324 ±â€…37.3 kg initial body weight) were selected and divided into two blocks. Steers were under intensive grazing management for 84 d. Depending on forage availability, steers were rotated at 2- to 4-d intervals. Pastures were predominately composed of cool-season forages. Two different databases using the same animals (n = 16) were defined to calculate the gas flux using the first 100 visits to an AHCS with 2 or more or 3 or more minutes of visitation length. The mean gas flux was estimated as the average for increasing (forward) or decreasing (reverse) the gas flux of 5-visit intervals starting with the first or the last 5 visits and increasing or decreasing until the full 100-visit dataset was utilized, respectively. Spearman and Pearson correlations were computed between the maximum visits and each shortened visit interval. Concurrently, the residual variance and the residual variance change were determined for each interval by fitting a mixed model. The minimum number of visits was defined when correlations with the total visits were greater than 0.95, and the residual variance was stabilized. The results indicated that the minimum number of visits needed to determine CH4 production varied between 45 and 70, while CO2 production and O2 consumption varied between 45 and 50 according to the visitation length. Additionally, steers that visited the AHCS for 2 or more minutes in visit duration required a greater number of visits than those that visited for 3 or more minutes. Thus, based on the average daily visitation in this experiment (1.4 visit/d), the assessment of CH4 emissions requires 32 d, while CO2 production and O2 consumption require between 32 and 36 d using 3 or more minutes of visit length from growing steers under intensive grazing conditions.

Impact of growth implants and low-level tannin supplementation on enteric emissions and nitrogen excretion in grazing steers.

The primary objective of this experiment was to evaluate the effects of a growth-hormone implant (Revalor-G, Merck Animal Health., Rahway, NJ, USA) and tannin supplementation (Silvafeed BX, Silva Team, San Michele Mondovi CN, Italy) on enteric methane (CH4) emissions and estimated nitrogen (N) excretion in grazing steers. Steers (n = 20; initial body weight [IBW] = 343 ±â€…14 kg) were acclimated to use a portable automated head-chamber system (AHCS) to measure CH4 and a SmartFeed Pro automated feeder for dietary supplementation (C-Lock Inc., Rapid City, SD, USA). After the training period, steers were randomly assigned to a 2 × 2 factorial arrangements of treatments, with 2 levels of growth-hormone implants, no-implant (NO-IMP) or implanted (IMP), and 2 levels of tannin supplementation, no tannin supplementation (NO-TAN) or tannin supplementation (TAN). This created 4 treatment groups: (1) NO-TAN and NO-IMP, (2) TAN and NO-IMP, (3) IMP and NO-TAN, and (4) TAN and IMP. Tannin was offered daily at 0.30% dry matter intake (DMI) through 0.5 kg/hd/d sweetfeed supplement (Sweetfeed Mix, AgFinity., Eaton, CO, USA) with a targeted tannin intake at 48 g/hd/d. No (P ≥ 0.05) implant × tannin interaction was detected for any dependent variable, so only the main effects of implant (NO-IMP vs. IMP) and tannin supplementation (NO-TAN vs. TAN) are discussed. Implant status did not affect (P ≥ 0.56) final body weight (FBW) or average daily gain (ADG) during the 90 d grazing period. There was no effect (P ≥ 0.15) of growth implant on CH4 production or emission intensity (EI; g CH4/kg gain). Additionally, IMP steers tended (P ≤ 0.08) to have less CH4 yield (MY; g CH4/g DMI) and higher blood urea nitrogen (BUN) than NO-IMP steers. Tannin supplementation did not impact (P ≥ 0.26) FBW or ADG. However, NO-TAN steers tended (P = 0.06) to have a greater total DMI than steers supplemented with tannin. No effect (P ≥ 0.22) of tannin supplementation was observed for CH4 production and EI. Nitrogen utilization as measured through BUN, urine N, fecal N, or fecal P was similar (P ≥ 0.12) between TAN and NO-TAN animals. The findings indicate that low-level dietary supplementation to reduce enteric emissions is difficult in grazing systems due to inconsistent animal intake and that growth implants could be used as a strategy to improve growth performance and reduce EI of steers grazing improved pasture.

Maculopathy and adult-onset ataxia in patients with biallelic MFSD8 variants.

BACKGROUND: Biallelic variants in the major facilitator superfamily domain containing 8 gene (MFSD8) are associated with distinct clinical presentations that range from typical late-infantile neuronal ceroid lipofuscinosis type 7 (CLN7 disease) to isolated adult-onset retinal dystrophy. Classic late-infantile CLN7 disease is a severe, rare neurological disorder with an age of onset typically between 2 and 6 years, presenting with seizures and/or cognitive regression. Its clinical course is progressive, leading to premature death, and often includes visual loss due to severe retinal dystrophy. In rare cases, pathogenic variants in MFSD8 can be associated with isolated non-syndromic macular dystrophy with variable age at onset, in which the disease process predominantly or exclusively affects the cones of the macula and where there are no neurological or neuropsychiatric manifestations. METHODS: Here we present longitudinal studies on four adult-onset patients who were biallelic for four MFSD8 variants. RESULTS: Two unrelated patients who presented with adult-onset ataxia and had macular dystrophy on examination were homozygous for a novel variant in MFSD8 NM_152778.4: c.935T>C p.(Ile312Thr). Two other patients presented in adulthood with visual symptoms, and one of these developed mild to moderate cerebellar ataxia years after the onset of visual symptoms. CONCLUSIONS: Our observations expand the knowledge on biallelic pathogenic MFSD8 variants and confirm that these are associated with a spectrum of more heterogeneous clinical phenotypes. In MFSD8-related disease, adult-onset recessive ataxia can be the presenting manifestation or may occur in combination with retinal dystrophy.

American society for metabolic and bariatric surgery: intra-operative care pathway for minimally invasive Roux-en-Y gastric bypass.

BACKGROUND: Clinical care pathways help guide and provide structure to clinicians and providers to improve healthcare delivery and quality. The Quality Improvement and Patient Safety Committee (QIPS) of the American Society for Metabolic and Bariatric Surgery (ASMBS) has previously published care pathways for the performance of laparoscopic sleeve gastrectomy (LSG) and pre-operative care of patients undergoing Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This current RYGB care pathway was created to address intraoperative care, defined as care occurring on the day of surgery from the preoperative holding area, through the operating room, and into the postanesthesia care unit (PACU). METHODS: PubMed queries were performed from January 2001 to December 2019 and reviewed according to Level of Evidence regarding specific key questions developed by the committee. RESULTS: Evidence-based recommendations are made for care of patients undergoing RYGB including the pre-operative holding area, intra-operative management and performance of RYGB, and concurrent procedures. CONCLUSIONS: This document may provide guidance based on recent evidence to bariatric surgeons and providers for the intra-operative care for minimally invasive RYGB.

A systematic cognitive behavioral therapy approach for pediatric disorders of gut-brain interaction.

OBJECTIVE: Cognitive Behavioral Therapy (CBT) for youth with Disorders of Gut-Brain Interaction (DGBIs) is effective; however, there are calls in the field to strengthen the evidence base and identify specific mechanisms of treatment that yield the most benefit for this patient population. A unique, systematic treatment approach of CBT with initial evidence for success for pediatric patients with DGBIs was evaluated to further demonstrate its clinical utility in this population. METHODS: This was a retrospective study of 42 pediatric patients aged 11-17 years with DGBIs, who were diagnosed and referred for CBT by pediatric gastroenterology providers. Providers also completed a survey rating acceptability and effectiveness of CBT. The systematic CBT approach included 10 sessions delivered by a psychologist at an integrated Pediatric GI Clinic. RESULTS: Review of 42 pediatric charts showed significant decreases in self-reported functional disability, abdominal pain, as well as depression and anxiety symptoms pre- to post-CBT completion. A moderation effect was observed where patients reporting higher levels of depressive symptoms and primary symptom of abdominal pain reported smaller reductions in functional impairment compared to those with lower levels of depression and primary symptom of nausea or vomiting. Pediatric Gastroenterology providers were satisfied with this psychological treatment approach. CONCLUSIONS: This study provides evidence for acceptability and effectiveness of implementation of a systematic CBT approach for pediatric DGBIs in an integrated GI clinic, as well as areas worthy of future research, including identifying the most important mechanisms of treatment and factors that influence treatment response.

A Hypercalcemic Crisis Complicating Subcutaneous Fat Necrosis of the Newborn: A Case Report and Literature Review.

Subcutaneous fat necrosis of the newborn (SFNN) is a rare panniculitis that is characterized by the presence of skin nodules. Although SFNN is a self-limited benign disease, effective follow-up is highly recommended to detect hypercalcemia and other complications early on. A male newborn was admitted twice to the neonatal intensive care unit (NICU). The first NICU admission was for hypoglycemia, and the second was due to late-onset sepsis, in which reddish nodules were detected on the back, flanks, shoulders, and posterior aspects of the legs. At 44 days old, the infant was referred to the emergency department due to a hypercalcemic crisis. Screening for other SFNN complications revealed eosinophilia, hypoglycemia, and nephrocalcinosis. The hospitalization was further complicated by a rare occurrence of deep venous thrombosis. The calcium level was followed up to ensure the patient's recovery. This case highlights the complications that might follow SFNN and emphasizes the importance of its surveillance.

Characterizing thrombus adhesion strength on common cardiovascular device materials.

Thrombus formation in blood-contacting medical devices is a major concern in the medical device industry, limiting the clinical efficacy of these devices. Further, a locally formed clot within the device has the potential to detach from the surface, posing a risk of embolization. Clot embolization from blood-contacting cardiovascular devices can result in serious complications like acute ischemic stroke and myocardial infarction. Therefore, clot embolization associated with device-induced thrombosis can be life-threatening and requires an enhanced fundamental understanding of embolization characteristics to come up with advanced intervention strategies. Therefore, this work aims to investigate the adhesive characteristics of blood clots on common biocompatible materials used in various cardiovascular devices. This study focuses on characterizing the adhesion strength of blood clots on materials such as polytetrafluoroethylene (PTFE), polyurethane (PU), polyether ether ketone (PEEK), nitinol, and titanium, frequently used in medical devices. In addition, the effect of incubation time on clot adhesion is explored. Results from this work demonstrated strongest clot adhesion to titanium with 3 h of incubation resulting in 1.06 ± 0.20 kPa detachment stresses. The clot adhesion strength on titanium was 51.5% higher than PEEK, 35.9% higher than PTFE, 63.1% higher than PU, and 35.4% higher than nitinol. Further, adhesion strength increases with incubation time for all materials. The percentage increase in detachment stress over incubation time (ranging from 30 min to 3 h) for polymers ranged from at least 108.75% (PEEK), 140.74% (PU), to 151.61% (PTFE). Whereas, for metallic surfaces, the percentage rise ranged from 70.21% (nitinol) to 89.28% (titanium). Confocal fluorescence imaging of clot remnants on the material surfaces revealed a well-bounded platelet-fibrin network at the residual region, representing a comparatively higher adhesive region than the non-residual zone of the surface.