Tumour-suppressive function of SIRT4 in human colorectal cancer.

BACKGROUND: SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers. METHODS: We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry. RESULTS: SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis. CONCLUSIONS: SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.

Moral Injury Among Interventional Radiologists.

RATIONALE AND OBJECTIVES: To evaluate moral injury (MI) among interventional radiologists using validated assessment tools. MATERIALS AND METHODS: An anonymous 29-question online survey was distributed to interventional radiologists using the Society of Interventional Radiology Connect Open Forum website, Twitter, Facebook, LinkedIn, and electronic mail. The survey consisted of demographic and practice environment questions, a global quality of life (QoL) scale (scored 1-100), the MI Symptom Scale­Healthcare Professional (MISS-HP) (scored 1-100), and two open-ended questions. A MISS-HP score ≥ 36 was indicative of experiencing MI. P < .05 was considered statistically significant for all two-sided tests. RESULTS: Beginning on March 30, 2023, 365 surveys were completed over 5 days. Of the respondents, 299 (81.9%) were male, 65 (17.8%) were female, and one preferred not to disclose gender. The respondents included practicing interventional radiologists (299; 81.9%) and interventional radiologists-in-training (66; 18.1%). Practice settings included academic (146; 40.0%), community (121; 33.2%), hybrid (84; 23.0%), or other (14; 3.8%) centers. Mean QoL was 71.1 ± 17.0 (range: 0-100) suggestive of "good" QoL. Mean QoL in the MI subgroup was significantly different from that for the rest of the group (67.6 ± 17.0 vs. 76.6 ± 16.0; P < 0.05). 223 (61.1%) respondents scored ≥ 36 on the MISS-HP, and thus were categorized as having profession-related MI. Mean MISS-HP was 39.9 ± 12.6 (range: 10-83). Mean MISS-HP in the MI subgroup was significantly different from that for the rest of the group (47.4 ± 9.6 vs. 28.0 ± 5.7; P < 0.05). There was a negative correlation between MI and QoL (r = -0.4; P < 0.001). Most common themes for greatest contribution to MI were ineffective leadership, barriers to patient care, corporatization of medicine, non-physician administration, performing futile procedures, turf battles, and reduced resources. Most common themes for ways to reduce MI were more autonomy, less bureaucracy, more administrative support, physician-directed leadership, adequate staffing, changes to the medical system, physician unionization, transparency with insurance companies, more time off, and leaving medicine/retirement. CONCLUSION: MI is prevalent among interventional radiologists, and it negatively correlates with QoL. Future work should investigate causative factors and mitigating solutions.

Genetically diverse Clostridium difficile strains harboring abundant prophages in an estuarine environment.

Clostridium difficile is the leading cause of antibiotic-associated diarrheal disease in health care settings across the world. Despite its pathogenic capacity, it can be carried asymptomatically and has been found in terrestrial and marine ecosystems outside hospital environments. Little is known about these environmental strains, and few studies have been conducted on estuarine systems. Although prophage abundance and diversity are known to occur within clinical strains, prophage carriage within environmental strains of C. difficile has not previously been explored. In this study, we isolated C. difficile from sites sampled in two consecutive years in an English estuarine system. Isolates were characterized by PCR ribotype, antibiotic resistance, and motility. The prevalence and diversity of prophages were detected by transmission electron microscopy (TEM) and a phage-specific PCR assay. We show that a dynamic and diverse population of C. difficile exists within these sediments and that it includes isolates of ribotypes which are associated with severe clinical infections and those which are more frequently isolated from outside the hospital environment. Prophage carriage was found to be high (75%), demonstrating that phages play a role in the biology of these strains.

Ageing of Neurospora crassa. II. Organic hydroperoxide toxicity and the protective role of antioxidant and the antioxygenic enzymes.

Cumene hydroperoxide and tert-butyl hydroperoxide at sublethal concentrations initially prevent growth of mycelia of wild-type Neurospora crassa, but after a time the cells grow at a subnormal steady-state rate. The antioxidant nordihydroguaiaretic acid protects unadapted cells from hydroperoxide inhibition, leading to a decrease in the time before growth begins, an increase in steady-state growth rate and an increase in biomass production. The results of growth transfer experiments and enzyme measurements indicated that the acquired resistance to the hydroperoxides is physiological and most likely involves the induction of the synthesis of the antioxygenic enzymes superoxide dismutase, glutathione peroxidase and glutathione reductase. Nordihydroguaiaretic acid normalizes the levels of activities of glutathione peroxidase and glutathione reductase during culture with hydroperoxide. Molecular-induced homolysis of the hydroperoxides, a process that is induced by unsaturated fatty acids of membrane lipids, leads to lipid autoxidation in a chain reaction which produces lipid hydroperoxides, which in turn decomposes to form more free radicals. Nordihydroguaiaretic acid, a well-known free radical scavenger, probably serves to minimize hydroperoxide decomposition, lipid autoxidation and molecular damage from free radicals, whereas the coupled enzyme system glutathione peroxidase and glutathione reductase minimizes these processes by decomposing the hydroperoxides to harmless alcohols. We suggest that either free radicals derived from these processes or some consequent non-radical products may serve as the inducers of this enzyme system, rather than the hydroperoxide substrates.

Verification of Intoximeter 3000 breath alcohol concentration by magnesium perchlorate tube method in long-term field program.

The anhydrous magnesium perchlorate (MPT) breath alcohol sample collection tube was analyzed by gas chromatography (GC) to verify paired breath alcohol concentrations obtained from 18 Intoximeter 3000 (IR) instruments under normal conditions of use. This study compares the accuracy, precision, and reliability of actual driving-while-intoxicated (DWI) IR breath alcohol evidence gathered by field law enforcement personnel with the GC results of the MPT alcohol analysis. The IR and MPT-GC breath alcohol concentration results from a total of 1024 individuals were determined. Results of 530 (51.7%) MPT-GC breath alcohol analyses deviated within +/- 0.010 g/210 L from their paired IR breath alcohol result; 817 (79.7%) and 945 (92.3%) MPT-GC breath alcohol analyses deviated within +/- 0.020 and +/- 0.030 g/210 L, respectively. Confidence interval limits at various probability levels are tabulated and show expected reliability of a single predicted IR breath alcohol concentration from the IR on MPT-GC linear regression analysis.

Stimulated esophageal groove closure in adult goats.

In healthy adult goats, closure of the esophageal groove was induced by thirst, IV administered vasopressin, and intracarotid administration of hypertonic NaCl solutions. The efficiency of stimulation was tested directly by visual inspection of the course taken by orally administered solutions through a ruminal or abomasal fistula, palpation of the lips of the esophageal groove through a ruminal fistula, and indirectly by following the glucose dynamics in the blood after oral administration of glucose solution. Esophageal groove closure was observed during drinking after a 48-hour period of water deprivation. Intracarotid administration of 1.5 ml of a saturated solution or 10.5 ml of a 1.5% solution of NaCl also stimulated groove closure; however, groove closure stimulated by administration of vasopressin is the most satisfactory procedure for passing compounds of therapeutic importance directly from the cardiac orifice to the abomasum.

The performance of routine computed tomography for the detection of colorectal cancer.

INTRODUCTION: Although colonoscopy and computed tomography (CT) colonography in expert hands are the most sensitive investigations for colorectal cancer, some patients may not tolerate the necessary bowel preparation and insufflation of gas into the colon. We assessed the performance of unprepared contrast CT for the detection of colorectal cancer. METHODS: A retrospective review was undertaken of all patients who had contrast CT of the abdomen and pelvis and then went on to have colonoscopy at our institutions between 2007 and 2010. RESULTS: Overall, 96 patients were identified as having had CT prior to colonoscopy. The sensitivity of CT in detecting colorectal cancer was 100% (95% confidence interval [CI]: 19.8-100%) and the specificity was 95.7% (95% CI: 88.8-98.6%). The positive predictive value was 33.3% (95% CI: 6.0-75.9%) and the negative predictive value was 100% (95% CI: 94.8-100%). CONCLUSIONS: Non-targeted CT that is negative for colorectal malignancy is usually reassuring but the decision for further investigations should be made on a case-by-case basis, taking into account of the likelihood of underlying colorectal malignancy and the underlying co-morbidities of the patient. However, video colonoscopy is usually necessary to assess positive CT findings.

Nicorandil associated anal ulcers: an estimate of incidence.

INTRODUCTION: Nicorandil is a commonly prescribed antianginal medication that has been found to be associated with painful anal ulceration. The incidence of this complication is unknown. We have used the best data available to us to make an estimate of this figure in a health district with a remarkably stable population of approximately 200,000 people. METHODS: using an electronic search of all letters generated from colorectal and gastroenterology clinics as well as endoscopy reports from January 2004 to November 2010, patients with anal ulceration who were taking nicorandil were identified. Other causes of ulceration were excluded by biopsy in the majority of cases. The central hospital and community pharmacy database was interrogated to estimate the number of patients who were prescribed nicorandil over a six-year period (2004-2010). RESULTS: A total of 30 patients (24 men, 6 women) with a median age of 79.5 years were identified who fulfilled the criteria of: taking nicorandil; having no other identified cause for anal ulceration; and achieving eventual healing after withdrawal of nicorandil. In the six-year period an estimated mean of 1,379 patients were prescribed nicorandil each year. The mean annual incidence of anal ulcers among nicorandil users is therefore calculated to be in the region of 0.37%. CONCLUSIONS: Anal ulceration appears to occur in approximately four in every thousand patients prescribed nicorandil each year. Prescribing physicians should explain the risk of this unpleasant complication to their patients.

Incidence of lower thoracic ligamentum flavum midline gaps.

BACKGROUND: Lower thoracic epidural anaesthesia and analgesia (EDA) has gained increasing importance in perioperative pain therapy. The loss-of-resistance technique used to identify the epidural space is thought to rely on the penetration of the ligamentum flavum. Investigations at the cervical and lumbar regions have demonstrated that the ligamentum flavum frequently exhibits incomplete fusion at different vertebral levels. Therefore, the aim of this study was to directly investigate the incidence of lower thoracic ligamentum flavum midline gaps in embalmed cadavers. METHODS: Vertebral column specimens were obtained from 47 human cadavers. Ligamentum flavum midline gaps were recorded between the vertebral levels T6 and L1. RESULTS: The incidence of midline gaps/number of viable specimens at the following levels was: T6-7: 2/45 (4.4%), T7-8: 1/47 (2.1%), T8-9: 2/45 (4.4%), T9-10: 7/39 (17.9%), T10-11: 12/34 (35.2%), T11-12: 10/35 (28.5%), T12/L1: 6/38 (15.8%). CONCLUSIONS: In the present study we have determined the frequency of lower thoracic ligamentum flavum midline gaps. Gaps are less frequent than at cervical levels, but more frequent than at lumbar levels. Peak incidence was found in the region between T10 and T12. Using a strict midline approach, one cannot therefore rely on the ligamentum flavum to impede entering the epidural space in all patients.

Bloat in sheep (Ovis aries).

1. Most of the field studies on bloat are conducted with cattle and most of the laboratory experiments seeking to explain the various parameters associated with bloat are done with sheep. 2. Based on grazing behaviour, it would be expected that sheep might bloat more severely than cattle because they selectively choose to eat leaves over stems and chew what they ingest more frequently than cattle. Furthermore, sheep appear to select legumes over grasses because the legumes can be eaten more rapidly. However, because they are selective, sheep eat more slowly than cattle. Despite a higher bloat expectation, bloating in sheep is reported to be less of a problem than in cattle. 3. Although frothing of rumen ingesta was described earlier in cattle as the cause of acute legume bloat, experiments with frothy bloat in sheep preceded those in cattle. 4. Anti-frothing agents were used in sheep before cattle to treat acute legume bloat. 5. Experiments devoted to the study of eructation in ruminants were carried out on sheep, then cattle. 6. Convincing evidence that rumen motility does not cease during acute legume bloat was gathered using sheep. 7. Although the transected tracheal technique for the determination of the volume of eructated gas was developed with cattle, the pathway of eructated gas was confirmed with sheep. 8. All the current evidence accumulated from experiments with sheep supports the hypothesis that death due to legume bloat is caused by acute neural, respiratory, and cardiovascular insult resulting from the effect of the distended rumen on thoracic viscera, diaphragm, intercostal muscles, and the abdominal vena cava. 9. Experiments with sheep and cattle being fed scabrous and nonscabrous diets similar in chemical composition show that sheep are more resistant than cattle to the increase in intrarumen pressure, decline in rumen contraction amplitude, and decrease in rumen contraction frequency caused by nonscabrous diets. 10. The sequence of events in the reticulorumen during primary and secondary contractions previously described following visual and palpation experiments with cattle was confirmed by the use of myoelectrodes implanted in the various sacs of the reticulorumen of sheep. 11. Elevated intrarumen pressure is associated with an increase in the frequency of primary (mixing) and secondary (eructation) contractions (more secondaries than primaries).(ABSTRACT TRUNCATED AT 400 WORDS)

Electrical impedance measurements in the reading and monitoring of broth dilution susceptibility tests.

Electrical impedance changes in the medium were studied during traditional broth dilution tests. Tests involved clinical isolates of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter sp., Klebsiella, and enterococcus and ten antibiotics. Minimal inhibitory concentration (MIC) values from overnight visual readings were compared with MIC values determined from electrical impedance end points, using inocula of 10(6) organisms per ml. Ninety-three percent of the results were within one twofold dilution of each other. When the impedance end point was determined at 6 h, this correlation was lowered to 34%. By increasing the initial electrical impedance inoculum 10-fold, the correlation between the 6-h impedance MIC and the overnight visual MIC was improved to 74%. Ampicillin, tetracycline, and polymyxin E results accounted for most discrepancies. Continuous monitoring of impedance changes suggested that better correspondence could be obtained by adjusting the end point criteria for the 6-h impedance MIC with different antibiotics. Electrical impedance methods for reading bacterial end points in automated clinical laboratory instruments appear promising.

Premarket evaluation of commercial toxoplasmosis indirect fluorescent-antibody reagents.

The quality of commercial toxoplasmosis indirect fluorescent-antibody reagents was evaluated over a 6-year period. Seven manufacturers voluntarily submitted their products for evaluation in the Center for Disease Control Premarket Evaluation Program. Each product was tested in accordance with the Center for Disease Control performance and labeling specifications and evaluation methods. Only 49% of all of the products tested met the Center for Disease Control requirements. Performance criteria are outlined, and suggestions are offered to assist laboratorians in obtaining toxoplasmosis indirect fluorescent-antibody reagents of high quality.

Inhibition of electron transport enzymes and cholinesterases by Endrin.

Two enzymes involved in mitqchondrial electron transport in the catfish,Ictalurus melas, have been shown to be inhibited by endrin. Succinate dehydrogenase and cytochrome oxidase were both inhibited, and the extent of inhibition depended ypon endrin concentration and the specific activity ef the enzyme preparation. No appreciable effect of endrin on acetylcholinesterase or NADH-cytochrome c reductase was seen. Binding to lipoprotein components essential for mitochondrial oxidation has been proposed as a logical site for endrin action.

Elevated intra-rumen pressure and secondary rumen contractions in sheep (Ovis aries).

1. Sheep rumens were insufflated with nitrogen to 5, 10, 15, and 20 cm water pressure and sustained at each pressure for 10 min. 2. Measurements included rumen motility, reticulorumen myoelectric activity, eructation frequency and volume, changes in tracheal pressure and rumen contraction amplitude. 3. As intra-rumen pressure increased, contractions designated as special secondary contractions appeared. 4. At a pressure of approximately 15 cm water, most of the special secondary contractions became regular secondaries; therefore, the special secondaries were called pro-secondary contractions. 5. Increased intra-rumen pressure was associated with respiratory distress. The recovery phase following, rumen insufflation was accompanied by hyperpnea.