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Caffeine, a widely consumed stimulant, is known for its effects on alertness and fatigue reduction by blockade of adenosine receptors. While it holds therapeutic potential, its diverse impacts pose risks, particularly in early development. This study explores the developmental effects of caffeine exposure using Caenorhabditis elegans (C. elegans) as a model organism. We investigated morphological and behavioral changes induced by caffeine exposure at the L1 stage and assessed their impact at the L4 stage, which roughly corresponds to human infancy and adolescence, respectively. Caffeine-exposed worms displayed increased body length, body bends, and pharyngeal pumping rates compared to control worms. These findings indicate heightened food-seeking behavior and greater food intake, leading to the observed morphological changes. While caffeine did not affect other locomotor behaviors, its stimulatory effect on growth and development highlights its significance. This study provides insights into the potential impact of early-life caffeine exposure on long-term health and development, offering a foundation for future research in vertebrates to uncover its implications on metabolism and other metrics of health., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Helicopter transport may shorten transportation times for emergent neurosurgical intervention. The usefulness of helicopter transport after spontaneous intraparenchymal hemorrhage is not well studied. This study seeks to clarify factors that are associated with urgent surgical intervention in patients with spontaneous intracerebral hemorrhage following helicopter transport., Methods: Records were reviewed for patients with spontaneous intraparenchymal hemorrhage transported by helicopter to Dartmouth-Hitchcock Medical Center between January 2008 and December 2011. Records were evaluated for factors associated with emergent tertiary-level care intervention during the first 24 hours of admission., Results: A total of 107 patients met inclusion criteria, with a mean age of 67.2 years. At presentation, 79 (75.24%) were hypertensive, 22 (21.57%) had an increased international normalized ratio, and 47 (45.19%) were intubated. Thirty-three patients (30.8%) underwent 1 or more neurosurgical interventions within 24 hours of arrival, with an additional 6 (5.6%) patients undergoing neurosurgical intervention after 24 hours after admission. On univariate analysis, age, Glasgow Coma Scale (GCS) score, and clot volume were significant predictors of neurosurgical intervention within 24 hours of interfacility helicopter transport. A lobar clot, presence of intraventricular hemorrhage, and presence of >1 cm of midline shift were also associated with neurosurgical intervention within 24 hours. On multivariate analysis, younger age, GCS score of 3-8, and lobar hemorrhage were independent predictors of neurosurgical intervention within 24 hours., Conclusions: Two thirds of patients did not undergo any surgical intervention during the first 24 hours of admission after interfacility helicopter transfer. Factors associated with urgent neurosurgical intervention included younger age, low GCS score, and presence of lobar hemorrhage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Although the primary goal of treatment of type II odontoid fracture is bony union, some advocate continued nonsurgical management of minimally symptomatic older patients who have fibrous union or minimal fracture motion. The risk of this strategy is unknown. We reviewed our long-term outcomes after dens nonunion to define the natural history of Type II odontoid fractures in elderly patients managed nonoperatively., Methods: A retrospective chart review of 50 consecutive adults aged 65 or older with Type II odontoid fracture initially managed nonsurgically from 1998 to 2012 at a single tertiary care institution was conducted. Particular attention was paid to patients who had orthosis removal despite absent bony fusion. Patients were contacted prospectively by telephone and followed until death, surgical intervention, or last known contact., Results: Fifty patients initially were managed nonsurgically; of these, 21 (42.0%) proceeded to bony fusion, 3 (6%) underwent delayed surgery for persistent instability, and 26 (52%) had orthosis removal despite the lack of solid arthrodesis on imaging. The last group had a median follow-up of 25 months (range 4-158 months), with 20 of 26 (76.9%) followed until death. Of these patients, 1 patient developed progressive quadriplegia and dysphagia 11 months after initial injury. Compared with patients with spontaneous union, patients with nonunion had shorter life expectancy, despite no significant differences between the groups with respect to age, sex, injury mechanism, radiographic variables, or follow-up duration., Conclusions: Orthosis removal despite fracture nonunion may be reasonable in elderly patients with Type II dens fractures., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The association of surgical duration with the risk of surgical site infection (SSI) has not been quantified in neurosurgery. We investigated the association of operative duration in neurosurgical procedures with the incidence of SSI., Methods: We performed a retrospective cohort study involving patients who underwent neurosurgical procedures from 2005 to 2012 and were registered in the American College of Surgeons National Quality Improvement Project registry. To control for confounding, we used multivariable regression models and propensity score conditioning., Results: During the study period there were 94,744 patients who underwent a neurosurgical procedure and met the inclusion criteria. Of these patients, 4.1% developed a postoperative SSI within 30 days. Multivariable logistic regression showed an association between longer operative duration with higher incidence of SSI (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.16-1.20). Compared with procedures of moderate duration (third quintile, 40th-60th percentile), patients undergoing the longest procedures (>80th percentile) had higher odds (OR, 2.07; 95% CI, 1.86-2.31) of developing SSI. The shortest procedures (<20th percentile) were associated with decreased incidence of SSI (OR, 0.72; 95% CI, 0.61-0.83) compared with those of moderate duration. The same associations were present in propensity score adjusted models and models stratified by subgroups of cranial, spinal, peripheral nerve, and carotid procedures., Conclusions: In a cohort of patients from a national prospective surgical registry, longer operative duration was associated with increased incidence of SSI for neurosurgical procedures. These results can be used by neurosurgeons to inform operative management and to stratify patients with regard to SSI risk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The mechanisms by which electrical stimulation (ES) of carcasses can be used to modulate meat quality are reviewed. Evidence to support an effect of ES on tenderness (and other meat quality attributes) based solely on changes in the pH/temperature profile within carcass muscles are presented. The interactions between electrical parameters and the contraction responses of carcass muscles are described to provide generalised principles to guide the design of electrical stimulation technology. The commercial risks to meat quality of inappropriate use of electrical stimulation, particularly excessive stimulation to produce PSE-like conditions, are considered.

Ensuring meat quality attributes meet the requirements of the diverse range of markets is a critical component for the continued success of the New Zealand and Australian meat industries. Developing cost-effective and flexible technologies to help meet this requirement is a central objective of a current Meat and Wool New Zealand and Meat and Livestock Australia funded programme. This initiative was developed three years ago; it is a collaborative programme that involves meat scientists, electrical engineers and commercial meat processors. To ensure this programme successfully delivers technologies and knowledge to the Australasian meat industry, the following strategies have been developed: measurement of meat quality attributes 'on-line' during processing; development of 'expert systems' that can integrate and interpret on-line measurements and development of quality-related feedback systems from the market that can be fed back to producers; and, development of methods to manipulate structural and biochemical events in meat to create new commercial opportunities for both producers and processors. This paper gives an overview of some of the new technologies that have developed from this programme that are being used commercially or, are undergoing the final stages of commercial validation.

CLC-5 is a member of the CLC family of voltage-gated chloride channels. Mutations disrupting CLC-5 lead to Dent's disease, an X-linked renal tubular disorder, characterised by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal stones. Sequence analysis of CLC-5 reveals a 746 amino acid protein with an intracellular amino-terminus, transmembrane spanning domains, and two CBS domains within its intracellular carboxy-terminus. CBS domains have been implicated in intracellular targetting and trafficking as well as protein-protein interactions. We investigate subcellular localisation of three naturally occurring CLC-5 mutants which all lead to a truncated protein, disrupting the second CBS domain. These mutants are unable to traffic normally to acidic endosomes but are retained in perinuclear compartments, colocalising with the Golgi complex. This is the first identification of the cellular pathogenesis of CBS domain mutations of CLC-5.

This paper describes the colour properties of seven hot-boned, unstimulated beef striploins during rigor attainment at 9, 14 and 24°C, during blooming at 4°C, and after storage at -1°C for 0, 2 and 8 weeks. Immediately after rigor attainment (0 weeks of storage) full blooming, as judged by L* and chroma, took at least 12 h. After 2 and 8 weeks storage, blooming was complete within about 4 h. The exponential equations describing blooming were different for 0 weeks compared with 2 and 8 weeks. This difference can be explained in terms of oxygen consumption by meat freshly in rigor. At 0 weeks, meat that entered rigor at 24°C had the best bloomed colour, whereas at 2 and 8 weeks the 9°C treatment had the best and the 24°C the worst. The data set, which spanned a range of ultimate pH values and three rigor attainment temperatures, was used to estimate the value of early colour measurements (first 24 h post-rigor) in predicting colour during display several weeks later. As judged by correlation coefficients, early measurements of hue were the only ones useful. L* and chroma were poor predictors. This result, together with the knowledge that blooming is slow in the first 24 h post-rigor, casts doubt on the value of subjective or objective colour assessments made in chillers. Temperature of rigor attainment between 9 and 24°C did not affect the time of browning onset, nor the rate of browning. It was confirmed that meat with lower pH had higher chroma before and after blooming.

Polarized monolayers of strain II Madin-Darby canine kidney cells (MDCK II) were treated with vanadate/H2O2, known inhibitors of protein tyrosine phosphatase activity. Vanadate/H2O2 treatment resulted in a rapid increase in paracellular permeability as revealed by decreased transepithelial resistance and increased permeability to inulin. These alterations in epithelial barrier function coincided with increased phosphotyrosine immunofluorescence in the vicinity of intercellular junctions and with redistribution of F-actin, the adherens junction protein E-cadherin and the tight junction protein ZO-1. The effects of vanadate/H2O2 on intercellular junction permeability and protein distribution were completely blocked by the specific protein tyrosine kinase (PTK) inhibitor tyrphostin 25 and partially inhibited by the alternative PTK inhibitor genistein. The relative potency of these two inhibitors in blocking the effects of vanadate/H2O2 on intercellular junctions correlated with their abilities to inhibit tyrosine phosphorylation. The potent ser/thr protein kinase inhibitor staurosporine had only a small influence on the vanadate/H2O2-induced increase in paracellular permeability and did not affect the observed redistribution of intercellular junction proteins or phosphotyrosine immunofluorescence. The relative potencies of these distinct protein kinase inhibitors in reversing the effects of vanadate/H2O2 indicate that these effects are directly related to tyrosine phosphorylation. In conclusion, our data provide evidence that enhanced tyrosine phosphorylation of intercellular junction proteins in MDCK epithelia increases paracellular permeability and can also induce prominent reorganization of the junctional complex.

The effect of dietary supplementation with clenbuterol for either 8 days or 55 days in lambs was studied. The 55-day treatment was combined with an immediate preslaughter exercise regime. The effect of these treatments on post-mortem calpain system activities, meat ageing and meat quality was studied. Neither short-nor long-term supplementation had an effect on the rate of pH fall post mortem. Short-term supplementation had no effect on the initial nor the final shear force values but these were higher at intermediate times. In contrast, prolonged supplementation increased shear force values at all times post mortem. Preslaughter exercise, while influencing the rate of pH decrease in both control and supplemented groups, did not affect meat tenderness. After short-term clenbuterol-supplementation, the in-vitro μ-calpain activity was significantly lower in the supplemented group at 6 and 24 hr post mortem, while m-calpain and calpastatin activities were largely unaffected. In contrast, 55-day clenbuterol supplementation resulted in significantly higher levels of calpastatin activity at all times post mortem. These data imply that clenbuterol results in toughened meat due to alterations in the calpain/calpastatin system, the mechanisms of which are dependent upon the duration of supplementation.

We have used a mouse Peyer's patch gut loop model to investigate the role of the intestinal membranous epithelial (M) cells in the pathogenesis of Salmonella typhimurium. These specialized antigen sampling cells are located in the follicle-associated epithelium (FAE) overlying the isolated and aggregated lymphoid follicles in the small and large intestines. Our studies have demonstrated that S. typhimurium adheres more frequently to the Peyer's patch FAE cells than to the villous enterocytes and that, within the FAE, this bacterium preferentially interacts with the M cells. Quantitative light microscopic studies, using the lectin Ulex europaeus 1 (UEA1) to identify M cells, revealed that 34-fold more bacteria bound per unit area of M cells than per unit area of enterocyte. Within a 30-min incubation period, some M cells had clearly been invaded by the Salmonella. We therefore propose that M cells are a major route by which S. typhimurium penetrates the intestinal epithelial barrier. Bacterial adhesion to M cells occurred in a non-uniform pattern, suggesting the existence of M-cell subtypes. The interaction of S. typhimurium with mouse Peyer's patch M cells was accompanied by membrane ruffle formation and polymerized actin redistribution similar to that observed in cultured cell lines infected by this bacterium. This study emphasizes the suitability of Salmonella as an oral vaccine delivery system since, by preferentially interacting with the M cells, these bacteria are targeted to sites where cells of the immune system are concentrated.

Direct demonstration of intact peptide transport by the intestinal H+/dipeptide carrier is limited both by luminal/cytosolic hydrolysis and the availability of suitable radiolabelled substrates. Perfusion of Val-Val (20mM) at the apical surface of human intestinal epithelial (Caco-2) cell monolayers resulted in a marked intracellular acidification, due to dipeptide-induced H(+)-flow across the apical membrane. Val-Val (20mM) also inhibited both the pH-dependent apical-to-basal transport and intracellular accumulation of [14C]Gly-Sar. Valine (20mM) had no effect on [14C]Gly-Sar transport (and intracellular accumulation) or pHi. We conclude that this novel method for studying H(+)-coupled transport clearly differentiates between the mechanisms responsible for absorption of an intact substrate and products of hydrolysis.

A total of 458 blood cultures were taken from 229 children aged 2 to 16 yr. Each 6 ml sample was taken starting at one of the following times after the extraction of a single tooth: 10 s, 30 s, 60 s, 90 s, 120 s, 180 s, 600 s and continuously over 2.5 min. The samples were cultured in the BACTEC radiometric culture system and when positive the bacteria isolated were speciated. At 30 s 56% of the samples were positive, the highest proportion, in contrast to only 38% of positive samples at 90 s and 28% at 600 s. Over 50% of the organisms found were Viridans streptococci.

[3H]Vinblastine transport across MDCK (renal epithelial) cell layers has been characterised. The basal-to-apical [3H]vinblastine flux (JA-B) (at 10 nM) exceeded apical-to-basal flux by 19.6 fold. Net vinblastine secretion (JB-A - JA-B) was inhibited by verapamil (0.1 mM) primarily by a reduction in JB-A, consistent with net vinblastine secretion resulting from an inhibition of P-glycoprotein. 1,9-Dideoxy-forskolin and forskolin (0.1 mM) both resulted in significant inhibition of JB-A and net vinblastine secretion of 64.3 +/- 3.1% and 29.1 +/- 4.8% respectively. 7 beta-deactyl-7 beta-(gamma-N-methylpiperazino)-butyryl-forskolin was ineffective. Half-maximal inhibition of vinblastine secretion by 1,9-dideoxy-forskolin was observed at 65 microM. 1,9-dideoxy-forskolin is unable to stimulate adenylate cyclase, suggesting that this forskolin derivative is a potentially important lead antagonist of P-glycoprotein for circumvention of pleiotropic drug resistance.

The efflux of the intracellular pH fluorochrome 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) was quantified in four cultured epithelial cell lines; HCT-8, T84, HGT-1 and MDCK. BCECF efflux was time-dependent, and after 5 h 45-91% of the initial BCECF loaded was extracellular, efflux being greatest in MDCK cells. Depletion of cellular ATP approximately halved BCECF efflux. BCECF efflux was inhibited by indomethacin, vinblastine and verapamil, but not by nifedipine or reserpine. Certain features of BCECF efflux resemble drug efflux in multidrug resistant cells, but inhibition of efflux displays a distinct pharmacological profile suggesting BCECF is a substrate for a novel ATP-dependent transport system.

A cytopathic agent indistinguishable from rubella virus was isolated from the synovial fluid of five patients (two male and three female). In two patients isolations were made on two separate occasions, and in two others on five separate occasions. The patients ranged in age from 9-58 years, and they presented with a variety of clinical syndromes. In particular, none had clinical features suggestive of recent rubella infection; but most cases had very high serum rubella haemagglutination inhibition titres. The identity of the cytopathic agent was shown by a variety of virological techniques to be rubella virus.