Factors affecting surgical mortality of oral squamous cell carcinoma resection.

Survival rates for oral squamous cell carcinoma (OSCC) has remained stagnant in recent years and improving surgical mortality could be an avenue to enhance outcomes. This systematic review aims to identify the causes of mortalities, determine both the modifiable and non-modifiable factors involved and target a reduction in postoperative 30-day mortality. In May 2019, a comprehensive search of key databases including PubMed, EMBASE, Cochrane Library was conducted. Blinded selection by two researchers identified papers that included participants who received oral squamous cell carcinoma resection and suffered an in-hospital or 30-day mortality. Selection identified two relevant papers that meet the inclusion criteria. One study had one death in its population sample but only had the cause of death described. Another study had an overall surgical mortality rate of 1% in a population of 21,681. Patients with multiple factors had the highest mortality rates; 4.6% in patients >85 years old and have a T4 diagnosis, 3.9% in patients with a Comorbidity Index ≥1 and a T4 diagnosis. These studies did not determine relationships between factors and causes of death. There are significant knowledge gaps in the literature, that can be addressed through further population analysis studies.

Evidence, not eminence, for surgical management during COVID-19: a multifaceted systematic review and a model for rapid clinical change.

BACKGROUND: Coronavirus (COVID-19) forced surgical evolution worldwide. The extent to which national evidence-based recommendations, produced by the current authors early in 2020, remain valid, is unclear. To inform global surgical management and a model for rapid clinical change, this study aimed to characterize surgical evolution following COVID-19 through a multifaceted systematic review. METHODS: Rapid reviews were conducted targeting intraoperative safety, personal protective equipment and triage, alongside a conventional systematic review identifying evidence-based guidance for surgical management. Targeted searches of PubMed and Embase from 31 December 2019 were repeated weekly until 7 August 2020, and systematic searches repeated monthly until 30 June 2020. Literature was stratified using Evans' hierarchy of evidence. Narrative data were analysed for consistency with earlier recommendations. The systematic review rated quality using the AGREE II and AMSTAR tools, was registered with PROSPERO, CRD42020205845. Meta-analysis was not conducted. RESULTS: From 174 targeted searches and six systematic searches, 1256 studies were identified for the rapid reviews and 21 for the conventional systematic review. Of studies within the rapid reviews, 903 (71.9 per cent) had lower-quality design, with 402 (32.0 per cent) being opinion-based. Quality of studies in the systematic review ranged from low to moderate. Consistency with recommendations made previously by the present authors was observed despite 1017 relevant subsequent publications. CONCLUSION: The evidence-based recommendations produced early in 2020 remained valid despite many subsequent publications. Weaker studies predominated and few guidelines were evidence-based. Extracted clinical solutions were globally implementable. An evidence-based model for rapid clinical change is provided that may benefit surgical management during this pandemic and future times of urgency.

A method for collecting breath samples from individual chickens for analysis of 13CO(2), H(2), and CH(4).

This study describes experiments using simple helmets to collect breath samples from individual birds for measurement of (13)CO(2), H(2), and CH(4), which form the basis for various diagnostic tests for intestinal dysfunction in humans. Peak enrichment in (13)C in breath CO(2) occurred between 5 and 30 min postingestion by 18-d-old chickens administered a gelatin capsule containing approximately 3.6 mg of (13)C-octanoic acid dissolved in vegetable oil. For 25-d-old chickens given 10 mL of homogenized cooked corn by oral gavage, peak enrichment occurred 60 to 90 min postingestion. In fully fed 25-d-old chickens, H(2) and CH(4) concentrations in breath ranged from 7 to 115 ppm and from 0 to 5.5 ppm, respectively. Following an overnight fast, H(2) and CH(4) concentrations in breath ranged from 0.5 to 7.5 ppm and 0 to 3.0 ppm, respectively, in the same chickens. Ranges in H(2) (1.0 to 56.5 ppm) and CH(4) (0 to 8.0 ppm) concentrations widened considerably 3 h after oral gavage with approximately 130 mg of lactulose (an indigestible disaccharide) dissolved in 5 mL of water. The results from these investigations indicate that collection of re-breathed air samples from chickens is plausible, which opens the way for development of noninvasive methods for evaluating gastrointestinal functions in chickens.

Bacterial modulation of small intestinal goblet cells and mucin composition during early posthatch development of poultry.

Mucins possess potential binding sites for both commensal and pathogenic organisms and may perform a defensive role during establishment of the intestinal barrier. To observe the effects of bacteria on intestinal goblet cell mucin production during posthatch development, differences in the small intestine of conventionally reared (CR) and low bacterial load (LBL) broiler chicks were examined. Jejunal and ileal goblet cells were stained with either periodic acid-Schiff stain or high iron diaminealcian blue pH 2.5 to discriminate among neutral, sulfated, and sialylated acidic mucins. Total goblet cell numbers and morphology of goblet cells containing neutral and acidic mucins did not differ significantly between CR and LBL birds. However, significant differences in acidic mucin composition from primarily sulfated to an increase in sialylated sugars at d 4 posthatch were observed in CR chicks, with greater numbers of jejunal and ileal goblet cells displaying this mucin type (CR, 0.5 +/- 0.1 x 10(3) cells/mm(2); LBL, 0.04 +/- 0.02 x10(3) cells/mm(2)). This change in mucin profile in response to bacterial colonization suggests a potential role as a protective mechanism against pathogenic invasion of the intestinal mucosa during early development.

Mandibular distraction osteogenesis for the management of upper airway obstruction in children with micrognathia: a systematic review.

Mandibular distraction osteogenesis (MDO) is increasingly used for neonates and infants with upper airway obstruction secondary to micrognathia. This systematic review was conducted to determine the effectiveness of MDO in the treatment of airway obstruction. The databases searched included PubMed, Embase, Scopus, and grey literature sources. The inclusion criteria were applied to identify studies in children with clinical evidence of micrognathia/Pierre Robin sequence (PRS) who had failed conservative treatments, including both syndromic and non-syndromic patients. Overall 66 studies were included in this review. Primary MDO for the relief of upper airway obstruction was found to be successful at preventing tracheostomy in 95% of cases. Syndromic patients were found to have a four times greater odds of failure compared to those with isolated PRS. The most common causes of failure were previously undiagnosed lower airway obstruction, central apnoea, undiagnosed neurological abnormalities, and the presence of additional cardiovascular co-morbidities. MDO was less effective (81% success rate) at facilitating decannulation of tracheostomy-dependent children (P<0.0001). Failure in these patients was most commonly due to severe preoperative gastro-oesophageal reflux disease, swallowing dysfunction, and tracheostomy-related complications. The failure rate was higher when MDO was performed at an age of ≥24 months. More studies are needed to evaluate the long-term implications of MDO on facial development and long-term complications.

Characterization of transport systems for cysteine, lysine, alanine, and leucine in wool follicles of sheep.

Aspects of the uptake of the AA Cys, Leu, Ala, and Lys into wool follicles were investigated using short-term culture of thin strips of sheep skin. Following verification of the reliability of the model system, the sites of uptake of the radiolabeled AA were shown to differ and to be consistent with their different roles in fiber production. Cysteine appeared in the zone of keratinization immediately distal to the follicle bulb. Lysine was incorporated into the germinative cells of the follicle bulb and the cells of the inner root sheath. Leucine and Ala were incorporated into the follicle bulb, inner root sheath, and keratinizing fiber. The incorporation of all AA into the dermal papilla was low. The relative rates of uptake of the AA into the wool follicle were as follows: L-Cys (100), L-Leu (5.5), L-Ala (2.5), and L-Lys (0.8). Uptake of Cys was saturable and followed Michaelis-Menten kinetics, suggesting a carrier-mediated system, with little or no diffusion. The majority (70%) of Cys uptake into follicles was via a Na-independent system that was not inhibited by alpha-(methyl-amino)isobutyric acid or 2-amino-2-norbonanecarboxylic acid and therefore is not via the normal Cys transport systems A, ASC, or L. Uptake of Cys appeared to be via a low-affinity, high-capacity transport system, which may be unique to the fiber-producing follicle. The majority of Ala transport had characteristics consistent with the functioning of system A (Na-dependent, inhibited by alpha-(methylamino)isobutyric acid, and low substrate affinity). Leucine uptake was inhibited by 2-amino-2-norbonanecarboxylic acid but was Na-dependent, suggesting that a variant of system L operates in the follicle to transport Leu. Lysine uptake was consistent with the operation of the usual Lys transporter system y+. Diets designed to maximize wool growth should provide AA profiles reflecting the relative rates of uptake demonstrated in this study. Investigations of possible polymorphisms in genes encoding AA transport proteins in follicles may reveal a source of genetic differences in wool growth potential among genotypes.

Clinical waste--the law on health and safety.

In summary, the basic legal requirements are found in the COSHH Regulations, which require the identification of hazards, the quantification of risks and appropriate action to remove or control them. Monitoring of performance is essential to ensure controls are working, and to enable you to learn from any mistakes and from what does not work. As far as new methods of treatment of waste are concerned, HSE will apply the same standards to them in judging their effectiveness at removing the hazards, and must be certain that they do not introduce risks of their own for operators or public.

Effect of pancreatic secretions upon ileal disaccharidase activities of neonatal miniature pigs.

Mechanisms by which pancreatic secretions influence disaccharidase activities in the distal small intestine have been investigated in 1-week-old miniature pigs. Using a combination of biochemical, cytochemical and morphological techniques it has been found that the decrease in lactase specific activity is due solely to a reduction in villus surface area. By contrast, the increased sucrase-isomaltase activities, which occur despite the reduction in villus surface area, are due entirely to increased enzyme expression during enterocyte differentiation.

The effect of hyperosmotic challenge upon ion transport in cultured renal epithelial layers (MDCK).

Exposure of the basal-lateral surfaces of MDCK epithelia, mounted in Ussing chambers, to medium made hyperosmotic by the non-electrolyte mannitol, resulted in a marked inhibition of the adrenaline-stimulated inward short-circuit current (Cl- secretion). This inhibition was unaccompanied by a reversal of the adrenaline-stimulated increment in tissue conductance, indicating that the inhibition was due to modulation of ion transport at the basal-lateral membranes. Loop-diuretic-sensitive 86Rb(K+) efflux mediated by the Na+ - K+ -2 Cl- cotransporter at the basal-lateral membranes was markedly stimulated by hypertonic exposure. A diuretic-sensitive K+ (Cl-) loss was observed in shrunken cells upon prolonged exposure (20 min), showing that the net direction of "cotransport" flux was outward. 86Rb(K+) efflux stimulated by adrenaline (100 microM), exogenous ATP (100 microM) and A23187 (10 microM) was attenuated in shrunken cells, suggesting that basal-lateral K+ conductance is reduced in hyperosmotic media. "Cotransport" stimulation by hyperosmotic medium was asymmetric, apical bathing hypertonicity being ineffective. These data are consistent with a low hydraulic permeability of the apical membranes.

Cytochemical analysis of single villus peptidase activities in pig intestine during neonatal development.

The present work uses a new technique of whole tissue cytochemistry and automated scanning to obtain measurements of peptidase activity and surface structure in intact villi microdissected from the jejunum of newborn and 28-day-old pigs. Intact villi from 28-day-old pigs are shown by this method to contain 30% more aminopeptidase N and 400% more dipeptidylpeptidase IV activity than is found on villi taken from newborn pig intestine. Villi taken from 28-day-old pig intestine are also half as long and twice as wide at their base as those taken from newborn animals. These changes in shape take place without significantly affecting the total surface area of the villus. Increases in peptidase activities occurring during postnatal development can be further subdivided into those dependent upon induced changes in enterocyte biochemistry and those dependent upon the changing geometry of villi. Over 90% of the total increase in peptidase activities occurring during neonatal development was shown, by this analysis, to involve enterocyte reprogramming of enzyme production. The present method of whole tissue cytochemistry appears to combine successfully the ability to measure peptidase activities at the cellular level in undisrupted tissue with a facility to relate these results to the overall shape of a single villus. These and more general applications of the method now provide new ways to analyse a variety of changes taking place in intestinal structure and function in a quantitative manner.

Administration of 3,5,3'-triiodothyronine induces a rapid increase in enterocyte lactase-phlorizin hydrolase activity of young pigs on a low energy intake.

The rapid increase in plasma concentration of 3,5,3'-triiodothyronine (T3) which occurs after feeding may invoke changes in lactase-phlorizin hydrolase (LPH) activity of the small intestine. This hypothesis has been tested in 6-week-old pigs living at thermal neutrality (26 degrees C) on a low level of energy intake. Littermate pairs were infused with either saline or T3 at 30 min intervals over a 6 h period, 18-24 h after the last meal. The activity of LPH in mucosal homogenates increased significantly in test compared with control animals (P < 0.05; T3 37% > saline). This was a specific effect on LPH since there was no effect of T3 on the activity of sucrase-isomaltase. Further, it could not be attributed to changes in intestinal morphology since there were no differences in crypt depth, villus height or villus area between the two groups. Enzyme-cytochemical analysis indicated that administration of T3 increases LPH activity at all points along the villus axis, whereas there is no effect on alpha-glucosidase (combined sucrase-isomaltase and maltase) activities. These results indicate that there is unlikely to be a simple causal relation between the immediate increase in plasma T3 after feeding and the initial decline in LPH activity observed previously in young pigs living in a cold environment. By contrast, the subsequent increase in LPH activity could be under the direct control of the food-induced increase in plasma T3 concentration, and the present results suggest a potential role for T3 as an important short-term homeostatic regulator of LPH in the small intestine.

Nutritional modulation of insulin-like growth factor-I expression in early postnatal piglets.

The roles of intrauterine growth retardation, energy intake, and food composition in determining circulating and hepatic concentrations of IGF-I in early postnatal life have been determined. Intrauterine growth-retarded, small-for-gestational-age piglets were kept at thermal neutrality and fed sow's milk replacement formula to repletion at 6-h intervals between 2 and 14 d of age. When their appropriate-for-gestational-age littermates were pair-fed this intake, there were no significant differences in plasma or hepatic concentrations of IGF-I. Thus, under conditions of controlled food intake, prenatal undernutrition does not affect the postnatal expression of IGF-I. However, when appropriate-for-gestational-age piglets were fed to repletion at 6-h intervals over the 12 d, they had a significantly greater hepatic IGF-I concentration (p < 0.002) and food intake (p < 0.001) than the small-for-gestational-age piglets, indicating a critical role for food intake regulation in catch-up growth. Striking differences in growth rate and IGF-I expression were also found between formula-fed, appropriate-for-gestational-age piglets compared with animals left with the sow. The latter grew much more rapidly (p < 0.0001) and had considerably higher levels of plasma IGF-I (p < 0.0001) despite similar hepatic IGF-I concentrations. Differences in plasma IGF-I may have been caused by the high level of IGF-I in maternal milk, by differences in hepatic synthesis and release, or by altered profiles of IGF binding proteins and hence in altered IGF-I clearance from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

An investigation of [3H]bumetanide uptake in a cultured renal cell line (MDCK).

The inhibition of ouabain-insensitive 86Rb+ (K+) flux in a cultured renal cell line (MDCK) by a series of loop diuretics, including bumetanide, (the 'cotransport' flux component) has been determined in order to define the concentration range over which [3H]bumetanide would be expected to bind to the membrane transporter involved. Half-maximal inhibition by bumetanide was observed at 0.26 +/- 0.12 (S.D.) microM. The time and concentration dependence of [3H]bumetanide uptake in intact MDCK cells has been determined in experimental conditions, which were as far as possible, identical to inhibition of K+ flux. Total cellular uptake of [3H]bumetanide (0-1 microM) may be separated into a linear component and a component displaying sigmoidal saturation kinetics with a concentration giving half-maximal uptake of 0.33 +/- 0.17 (S.D.) microM, maximal uptake of 1.17 +/- 0.47 pmol/10(6) cells, and a Hill coefficient of 1.59 +/- 0.28. There is also evidence for a second component of [3H]bumetanide uptake of lower affinity (less than 5 microM). Competition of [3H]bumetanide uptake by a series of loop diuretics at varying concentrations gives an order of potency identical to that observed for inhibition of the ouabain-insensitive 86Rb+ influx. The magnitude of the saturable component of [3H]bumetanide uptake is correlated with the magnitude of the diuretic-sensitive 86Rb+ influx in MDCK cells and in a variety of other cultured cells. The relationship between the diuretic-sensitive transport, the saturable component of [3H]bumetanide uptake and the cellular location of bumetanide uptake is discussed.

Single-villus analysis of disaccharidase expression by different regions of the mouse intestine.

1. The present results describe how a new technique of whole-tissue cytochemistry can be combined with automatic scanning of microdissected villi to measure the capacity of individual villi to hydrolyse disaccharides in different parts of the small intestine. 2. Intact villi from the mouse proximal jejunum are found to be eight times more effective than ileal villi in hydrolysing 2-naphthyl-alpha-D-glucoside, an artificial substrate for enzymes normally hydrolysing sucrose, maltose, isomaltose and trehalose in adult intestine. Homogenates of jejunal scrapings are four times more effective than ileal homogenates in hydrolysing this substrate. This discrepancy arises from relating enzyme activities to homogenate protein in cases where intestinal structure changes. 3. The eightfold difference in villus alpha-glucosidase activity is associated with a threefold difference in villus surface area. This discrepancy in turn reflects changes in the capacity of individual enterocytes to express alpha-glucosidase during migration along the crypt-villus axis. These results emphasize the futility of trying to gauge intestinal function from measurement of intestinal structure. 4. Differences between ileal and jejunal villus alpha-glucosidase activities have been further partitioned into those depending on villus structure and those depending on enterocyte development. Present results are discussed in relation to the ability of luminal nutrition to maintain a proximal-distal gradient of digestive enzyme function in the small intestine. The general applicability of this method of analysis to other studies of adaptive response is also emphasized.

M cell numbers increase after transfer of SPF mice to a normal animal house environment.

M cells present in the follicle-associated epithelium (FAE) of mouse Peyer's patches take up and transport enteric antigens to the underlying gut-associated lymphoid tissue (GALT) for subsequent processing by lymphocytes and macrophages. Present experiments use a new type of cell-labeling technique in attempts to measure the number of M cells present in the FAE of specific pathogen-free (SPF) and normal animal house reared (AH) BALB/c mice. Results show the apparent M-cell area to increase threefold 7 days after transfer of SPF mice to an AH environment. This change takes place without significantly affecting the area of FAE occupied by goblet cells. It is suggested from these results that M-cell production can be selectively increased within the FAE through the presence of foreign antigens and that this effect could have general importance in controlling the overall GALT response to enteric infection.

Compensatory increase in lactase expression by enterocytes of neonatal pigs on a low energy intake.

A restricted energy intake in the immediate postnatal period has been found to result in a significant increase in the maximal expression of lactase by enterocytes from 2-week-old pigs. Although villus size was significantly reduced on a low compared with a high food intake, total villus lactase activity was unaffected because of the compensatory increase in lactase expression by individual enterocytes.

Determinants of lactose digestion in the miniature pig.

Although lactose is an important nutrient in the diet of the infant and child, the factors contributing to its digestion have not been clarified adequately. We sought to determine the degree to which lactase activity and small intestinal transit explain lactose digestion, the average error (SEE) in estimating lactose digestion using these parameters, and the effect of age. We compared lactose digestion from both a 7% lactose-containing formula and a solution by determining lactose in ileostomy output in pig littermates at 10 days, 4 weeks, and 10 weeks of age. The entire small intestinal mucosa was assayed for lactase specific activity (micromol x min-1 x g protein-1), total activity (micromol x min-1), and whole-villus lactase activity. Transit time (min), and transit rate (cm/min) were measured. Meal type did not affect lactose digestion. Lactose digestion was explained best by lactase specific activity (formula, R2 = 0.73, SEE = 1.1; solution, R2 = 0.69, SEE = 1.0; P < 0.001). The next best parameter was total transit rate (formula, R2 = 0.69, SEE = 2.0; solution, R2 = 0.46, SEE = 1.3). The relationship with lactase specific activity was age related and there appeared to be a critical value of lactase specific activity above which essentially all the lactose was digested.

Body and intestinal growth of broiler chicks on a commercial starter diet. 1. Intestinal weight and mucosal development.

1. A study was conducted on the pattern of development of the intestinal mucosa of the Steggles x Ross (F1) strain of broiler chickens reared on a commercial starter diet. The mechanisms underlying the structural changes were also assessed. 2. In relation to body weight, small intestinal weight peaked at 7 d of age and declined subsequently. There was also a reduction in the relative weights of the gizzard and yolk sac with age. The length of the small intestine and its regions increased with age. 3. Crypt depth increased with age in the duodenum and jejunum while villus height increased significantly with age in all three regions of the small intestine. There were also significant changes in apparent villus surface area in the three regions, while interactions between age and intestinal region were significant in the case of crypt depth and villus height. 4. There were significant differences between the age groups in the mucosal protein content of jejunal and ileal homogenates, both tending to peak at 7 d of age. The DNA content of the intestinal mucosa declined with age in the three regions of the small intestine. While there was an increase in RNA content in the duodenum and ileum, there was a reduction in the jejunum. 5. Protein: DNA ratio increased between hatch and 21 d of age in all intestinal regions. Protein: RNA ratio decreased with age in the duodenum and ileum but increased in the jejunum. There were significant increases in RNA: DNA ratio in the duodenum and ileum but no changes were observed in the jejunum. The interactions between age and intestinal region were significant for all biochemical indices assessed. 6. At all ages, enterocyte proliferation at the jejunum was completed and quantifiable within 1 h of administration of 5-bromo-2'-deoxyuridine (BrDU). Subsequent assessment revealed an increase in crypt column count and number of BrDU-labelled cells. The rate of cell migration increased with age while there was a decline in the distance migrated in proportion to mucosal depth. The estimated life-span of enterocytes and time spent by enterocytes in the crypt varied with age. In d-old and 7-d-old chicks, migration was complete or nearly complete within 96 h of cell birth. 7. Although the intestinal mucosa of the strain was structurally developed at hatch, there was much change in structure with age, especially over the first 7 d post hatch. The rate of development was most rapid in the jejunum but the other regions are also important, on account of villus height or relative length of the region.