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Loss of function variations in the dual specificity tyrosine-phosphorylation-regulated kinase 1 A (DYRK1A) gene are associated with craniofacial malformations in humans. Here we characterized the effects of deficient DYRK1A in craniofacial development using a developmental model, Xenopus laevis. Dyrk1a mRNA and protein were expressed throughout the developing head and both were enriched in the branchial arches which contribute to the face and jaw. Consistently, reduced Dyrk1a function, using dyrk1a morpholinos and pharmacological inhibitors, resulted in orofacial malformations including hypotelorism, altered mouth shape, slanted eyes, and narrower face accompanied by smaller jaw cartilage and muscle. Inhibition of Dyrk1a function resulted in misexpression of key craniofacial regulators including transcription factors and members of the retinoic acid signaling pathway. Two such regulators, sox9 and pax3 are required for neural crest development and their decreased expression corresponds with smaller neural crest domains within the branchial arches. Finally, we determined that the smaller size of the faces, jaw elements and neural crest domains in embryos deficient in Dyrk1a could be explained by increased cell death and decreased proliferation. This study is the first to provide insight into why craniofacial birth defects might arise in humans with variants of DYRK1A., (Published by Elsevier Inc.)

Objective: To compare functional and seizure outcomes in children with vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy following functional hemispherotomy or anatomic hemispherectomy., Methods: Consecutive patients satisfying inclusion criteria from 07/01/2015 to 12/01/2019 were reviewed for demographic data and seizure (Engel classification) and functional (Functional Independence Measure for Children) outcomes., Results: After a mean follow-up of 2 years 8 months (1 year 2 months), 11 of 18 patients achieved post-operative seizure freedom without significant difference between vascular (5/7) and dysplastic (6/11) etiologies (P = 0.64). Functional assessments were completed for 15 of 18 of subjects, split comparably between groups. Mean change in the Functional Independence Measure for Children from pre-operative baseline to inpatient rehabilitation admission (vascular, -35.3 [13.2]; malformation of cortical development{MCD}, -34.5 [25.0]; P = 0.69), inpatient rehabilitation admission to discharge (vascular, 18.7 [9.0]; MCD, 20.8 [11.4]; P = 0.60), and pre-operative evaluation to clinic follow-up (vascular, -7.6 [9.7]; MCD, -3.6 [19.3]; P = 0.61) did not differ between groups., Conclusion: Quantitative functional and seizure outcomes following functional hemispherotomy or anatomic hemispherectomy did not differ significantly between vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy in this study. Hemispheric surgery resulted in minor functional declines from baseline following comprehensive multidisciplinary therapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Intravenous vitamin D is standard therapy for secondary hyperparathyroidism in hemodialysis (HD) patients. In for-profit dialysis clinics, mortality was higher for patients on calcitriol compared to paricalcitol. Doxercalciferol, a second vitamin D2 analog, is currently available. We assessed mortality associated with each vitamin D analog and with lack of vitamin D therapy in patients who began HD at Dialysis Clinic Inc. (DCI), a not-for-profit dialysis provider. During the 1999-2004 study period we studied 7731 patients (calcitriol: n=3212; paricalcitol: n=2087; doxercalciferol: n=2432). Median follow-up was 37 weeks. Mortality rates (deaths/100 patient-years) were identical in patients on doxercalciferol (15.4, 95% confidence interval (13.6-17.1)) and paricalcitol (15.3 (13.6-16.9)) and higher in patients on calcitriol (19.6 (18.2-21.1)) (P<0.0001). In all models mortality was similar for paricalcitol versus doxercalciferol (hazard ratios=1.0). In unadjusted models, mortality was lower in patients on doxercalciferol (0.80 (0.66, 0.96)) and paricalcitol (0.79 (0.68, 0.92)) versus calcitriol (P<0.05). In adjusted models, this difference was not statistically significant. In all models mortality was higher for patients who did not receive vitamin D versus those who did (1.2 (1.1-1.3)). Mortality in doxercalciferol- and paricalcitol-treated patients was virtually identical. Differences in survival between vitamin D2 and D3 may be smaller than previously reported.

US Choice (Ch) and US Select (Se) beef subprimals from the rib, chuck, plate, loin, and round were obtained to conduct retail cutting tests. Subprimals were merchandised into bone-in or boneless retail cuts and associated components by experienced retail meat merchandisers. These Se subprimals had less (P<0.05) trimmable fat than their Ch counterparts: ball tip, top sirloin, outside round, inside round, and ribeye. Se inside rounds, outside rounds, eye of rounds, boneless striploins, and ball tips had greater (P<0.05) purge losses than the same cuts from Ch. The only subprimals where grade impacted total saleable yield were the top (inside) rounds (Ch=80.13%, Se=87.34%; P=0.004) and outside rounds cut into roasts, steaks, and cubed steaks (Ch=87.61%, Se=90.28%; P=0.05). Methods to increase retail yields from beef subprimals should consider minimizing purge and increasing cutting efficiencies in addition to reducing fat trim.

Background: Hypertension may play an important role in the pathogenesis of the excess cardiovascular and cerebrovascular (CV) morbidity observed in hemodialysis patients (HD). However, the optimal blood pressure (BP) range for HD patients has not been defined. We postulated that there is a "U" curve relationship between BP and CV mortality. To explore this hypothesis we studied 5,433 HD patients in Dialysis Clinic Inc., a large not-for-profit chain, over a five year period., Methods: Cox regression, with fixed and time-varying covariates, was used to assess the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP), pre- and post-dialysis, on CV mortality, while adjusting for age, gender, ethnicity, primary cause of end-stage renal disease, Kt/V, serum albumin, and antihypertensive medications., Results: The overall impact of BP on CV mortality was modest. Pre-dialysis, neither systolic nor diastolic hypertension were associated with an increase in CV mortality. Post-dialysis, SBP > or = 180 mm Hg (RR = 1.96, P < 0.015) and DBP > or = 90 mm Hg (RR = 1.73, P < 0.05) were associated with increased CV mortality. Low SBP (SBP < 110 mm Hg) was associated with increased CV mortality, pre- and post-dialysis., Conclusions: The results suggest the presence of a "U" curve relationship between SBP post-dialysis and CV mortality in HD patients.

Background: Immunosuppression with cyclosporine has improved allograft function and reduced both morbidity and mortality in organ transplantation. However, cyclosporine-induced nephrotoxicity still is a concern. The purpose of our study was to evaluate the effects of cyclosporine on renal function in orthotopic heart transplant recipients., Methods: Thirty-nine patients who received transplants from 1985 to 1991 and had at least three yearly glomerular filtration rate measurements posttransplantation by 125I-iothalamate clearance method were included in the study. In addition, serum creatinine (before and after transplantation) and cyclosporine doses were analyzed., Results: Maintenance immunosuppression at 1 year consisted of prednisone (0.1 mg/kg/day), azathioprine (2 mg/kg/day), and cyclosporine (12-hour trough level 100 to 150 ng/ml by fluorescence polarization immunoassay). The mean serum creatinine at 1 year was significantly higher than the mean pretransplantation serum creatinine (1.51 +/- 0.32 versus 1.28 +/- 0.38, p < 0.05) and stabilized after the first year. The mean glomerular filtration rate by 125I-iothalamate clearance method was 70.6 +/- 20.3 ml/min/1.73 m2 (range 32 to 105) at 1 year and remained relatively stable during the follow-up period of up to 7 years. Creatinine clearance calculated by the Cockcroft and Gault formula overestimated the true glomerular filtration rate after the third year. The mean cyclosporine dosage was significantly lower after the first-year dose of 3.9 +/- 1.8 mg/kg/day (p < 0.05). Three patients in 39 started hemodialysis at 5, 7, and 10 years after transplantation., Conclusion: Our data indicate that the adequacy of renal function is preserved with long-term cyclosporine therapy in heart transplant recipients.

Two experiments were conducted using trichinae-infected pork shoulders. In the first experiment, samples of ground pork shoulder were allocated to the following treatments: (a) sodium nitrite levels of 0, 75 or 150 ppm, and (b) chloride salt levels of 2.5% sodium chloride, 3.18% potassium chloride, 1.35% magnesium chloride and 1.58% calcium chloride (for the latter three chloride salts, ionic strengths equivalent to that of 2.5% sodium chloride were used). In the second experiment, samples of ground pork shoulder were allocated to treatments in which 0, 25, 50, 75 or 100% of the sodium chloride was replaced with a 70:30 mixture of magnesium chloride: potassium chloride. Pork sausage links were made and stored for 12 d in a refrigerated display case. All chloride salts numerically reduced total plate counts compared to controls (no added salts) and calcium chloride or magnesium chloride significantly reduced total plate counts (P<.05). However, addition of sodium nitrite (75 or 150 ppm) did not affect total plate counts. Percentages of dead trichina larvae (visually determined) were greater (P<.05) for potassium chloride and sodium chloride than for magnesium or calcium chloride. However, in the second study when salts of equivalent ionic strengths were not used, replacement of sodium chloride with a 70:30 mixture of magnesium chloride: potassium chloride did not affect (increase or decrease) pH, total plate count or juice-loss during cooking. Percentages of dead trichina larvae increased for the 75 and 100% replacement levels when compared to controls.

Two experiments were conducted to determine the effects of sodium chloride, sodium nitrite, heating and/or freezing on viability of trichinae in hams. The most effective treatment for destroying trichinae consisted of pumping hams with a curing solution containing 2.6% sodium chloride and 156 ppm sodium nitrite followed by heating of hams to 43.3°C. Six days of storage at -29°C were required to achieve 100% destruction of trichinae for control (not pumped, not heated) hams. Seven, 8 and 8 d, respectively, were required to achieve 100% destruction of trichinae for those hams that were not heated but pumped without sodium chloride or sodium nitrite, or those that were pumped with solutions containing either 1.6% sodium chloride and 120 ppm sodium nitrite or 2.6% sodium chloride and 156 ppm sodium nitrite.

The mineral composition-iron (Fe), zinc (Zn), copper (Cu), calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), fluoride (F), and phosphorus (P) (New Zealand lamb only)-of lean tissue from lamb retail cuts was studied. Twenty-four US lamb carcasses of different ages (5 to 11 months), geographical regions (Texas, Colorado and Montana) and USDA quality grades (Prime and Choice) and 27 New Zealand lamb carcasses from three weight groups (11 to 12·5 kg, 13 to 14·5 kg, and 16·5 to 18 kg), age rangining from 7 to 8 months, were selected for use in this study. Mineral concentrations were influenced more by retail cut and age than by quality grade or weigth group. Foreshank and shoulder cuts from both the US and New Zealand group consistently had the highest (P < 0·05) Zn content among the cuts. The K content of the muscle in US lambs increased as age increased, while the level of Ca and Zn in New Zealand lambs decreased as carcass weight increased. Except for Ca, the mineral concentrations of the lean tissue from US lambs were higher than the New Zealand lambs, although the differences were not always significant. US lambs had approximately 20%, 30% and 37% more Fe, Zn and Mg, respectively, but 27% less Ca than lean tissue from the New Zealand lambs., (Copyright © 1989. Published by Elsevier Ltd.)