Sacrococcygeal dimensions and curvature are associated with resection quality in rectal cancer excision.

BACKGROUND: Technical factors affect oncologic outcomes in rectal cancer surgery. The anatomy of the bony pelvis can affect technical aspects of surgery, but is seldom considered preoperatively. We performed a morphometric analysis of the bony pelvis in patients having rectal cancer resection to assess its effect on surgical specimen quality. METHODS: We performed a retrospective analysis of a prospectively maintained database of patients who had resection for rectal cancer from January 2014 to December 2017. Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) images were accessed and measurements of sacrococcygeal distance, sacrococcygeal recess depth/area, sacrococcygeal angulation, anteroposterior pelvic inlet/outlet, pubic height and interspinous distance were made. Outcome measures included anatomical variation, operating time and mesorectal specimen grade. In patients having extra-levator abdominoperineal excision (eLAPE) with coccygectomy, the completeness of coccygeal resection was assessed by postoperative CT scan. Data were analysed using binomial and multinomial logistic regression and linear regression. RESULTS: One hundred and twenty-two consecutive rectal cancer resections were performed (39 open, 42 laparoscopic, 12 laparoscopic-converted and 29 robotic). The median age was 72 years (range: 29-88 years). The male:female ratio was 83:39. Eighty-one patients had anterior resection, 8 had low Hartmann's resection and 32 had APE. Of those who had APE, 21 had eLAPE (all with coccygectomy). Females had a larger pelvic inlet (female: 124.9 mm, male: 114.9 mm), interspinous diameter(female:112.8 mm, male:97.6 mm), sacrococcygeal depth (female:42.6 mm, 39.35 mm) and sacrococcygeal area recess than males (female: 3697 mm2, male: 3481.5 mm2). Males had a greater pubic height (female: 51.8 mm, male: 54.05 mm) and greater sacrococcygeal distance (female: 116.7 mm, male: 123.65 mm) than females. In patients having anterior resection, tumour distance from the anal verge (p = 0.004), sacrococcygeal distance (p = 0.006) and sacrococcygeal curvature (p = 0.002) were associated with specimen quality. In patients who had eLAPE, median preoperative coccygeal length was 41 mm (IQR: 35.1-45.5). The median length of coccygeal resection was 9 mm (IQR: 1-17.45 mm). The median length of coccyx remaining postoperatively was 33 mm (IQR: 21.35-39 mm). CONCLUSIONS: Sacrococcygeal curvature and distance as well as tumour distance from the anal margin were associated with specimen quality in anterior resection. Coccygectomy was not performed as completely as surgeons thought. Surgeons should include sacrococcygeal bony anatomy in rectal cancer surgical planning to potentially improve outcomes in both anterior resection and eLAPE approaches.

Characterization of road runoff with regard to seasonal variations, particle size distribution and the correlation of fine particles and pollutants.

Urban runoff is known to transport a significant pollutant load consisting of e.g. heavy metals, salts and hydrocarbons. Interactions between solid and dissolved compounds, proper understanding of particle size distribution, dissolved pollutant fractions and seasonal variations is crucial for the selection and development of appropriate road runoff treatment devices. Road runoff at an arterial road in Augsburg, Germany, has been studied for 3.5 years. A strong seasonal variation was observed, with increased heavy metal concentrations with doubled and tripled median concentrations for heavy metals during the cold season. Correlation analysis showed that de-icing salt is not the only factor responsible for increased pollutant concentrations in winter. During the cold period, the fraction of dissolved metals was lower compared to the warm season. In road dust, the highest metal concentrations were measured for fine particles. Metals in road runoff were found to show a significant correlation to fine particles SS63 (<63 µm). Therefore, it is debatable whether treatment devices only implementing sedimentation processes provide sufficient removal rates.

Prognostic factors and outcome in cats with thymic epithelial tumours: 64 cases (1999-2021).

OBJECTIVES: To describe the clinical presentation, treatment and outcomes of cats diagnosed with thymic epithelial tumours and to determine prognostic factors for survival and recurrence. MATERIALS AND METHODS: Clinical records of cats diagnosed with a thymic epithelial tumour between 1999 and 2021 at three referral institutions were retrospectively reviewed. RESULTS: Sixty-four cats were included. Paraneoplastic syndromes were present in nine cats and metastatic disease was seen in two cats, one at diagnosis and one at the time of recurrence. Median tumour diameter was 6 cm (range, 2 to 15) and a cystic appearance was described on imaging in 25 cats. Surgical excision was attempted in 54 cats with a perioperative mortality rate of 11%. Median survival time for cats surviving to hospital discharge was 897 days (range, 21 to 3322). The 1-, 2- and 5-year survival rates for surgically treated thymic epithelial tumour were 86%, 70% and 66%, respectively. Survival was longer for cats with Masaoka-Koga stage I and II tumours compared to stages III and IV (1366 days versus 454 days; P=0.002). Masaoka-Koga stage was the only significant prognostic factor detected on multi-variable analysis, with stage III and IV tumours associated with increased risk of death (hazard ratio: 5.67, 95% confidence interval: 1.29 to 24.91, P=.021). Tumour recurrence occurred in 11 cats at a median of 564 days (range, 93 to 1095); no significant prognostic factors for recurrence were identified. CLINICAL SIGNIFICANCE: Cats with thymic epithelial tumours had a good long-term prognosis following surgery. Tumour recurrence can occur late in the disease course and ongoing monitoring should therefore be considered. Masaoka-Koga stage may influence survival time and could be used to predict outcome.

Reporting standard for describing first responder systems, smartphone alerting systems, and AED networks.

Standardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/algorithm/strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice.

Electrically conductive metallomacrocyclic assemblies.

The design, synthesis, and study of electrically conductive molecular and polymeric substances constitute a new scientific endeavor involving the interaction of chemists, physicists, and materials scientists. The strategies, developments, and challenges in these two closely related fields are analyzed via a class of materials that bridges both: assemblies of electrically conductive metallomacrocycles. It is seen that efforts to rationally synthesize tailored, "metal-like" molecular arrays lead logically to structure-enforced polymeric assemblies of linked molecular subunits such as metallophthalocyanines. The properties of these assemblies and fragments thereof provide information on the relationship between atomic-level local architecture, electronic structure, and macroscopic transport properties. Electrcally conductive, processable polymeric materals also follow from these results.

Actinide organometallic chemistry.

The stoichiometric and catalytic chemistry of metal-organic compounds having actinide-to-carbon bonds is in a stage of rapid growth. Chemical, structural, and bonding characteristics have been identified which differ in interesting and informative ways from those of d-block transition element compounds.

Genetic control of melatonin synthesis in the pineal gland of the mouse.

Pineal melatonin may play an important role in regulation of vertebrate circadian rhythms and in human affective disorders. In some mammals, such as hamsters and sheep, melatonin is involved in photoperiodic time measurement and in control of reproduction. Although wild mice (Mus domesticus) and some wild-derived inbred strains of mice have melatonin in their pineal glands, several inbred strains of laboratory mice (for example, C57BL/6J) were found not to have detectable melatonin in their pineal glands. Genetic analysis suggests that melatonin deficiency in C57BL/6J mice results from mutations in two independently segregating, autosomal recessive genes. Synthesis of melatonin from serotonin in the pineal gland requires the enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). Pineal glands from C57BL/6J mice have neither NAT nor HIOMT activity. These results suggest that the two genes involved in melatonin deficiency are responsible for the absence of normal NAT and HIOMT enzyme activity.

New low-dimensional molecular metals: single-crystal electrical conductivity of nickel phthalocyanine iodide.

Single crystals of NiPcI(1.0) (Pc = phthalocyanine), which are composed of one-dimensional stacks of (NiPc)(+0.33) molecules and chains of I(3)(-) molecules, exhibit metallic electrical conductivity in the stacking direction. At room temperature the mean free path of the carrier is 3.3 to 8.2 angstroms.

Molecular structure of an unusual organoactinide hydride complex determined solely by neutron diffraction.

The structure of an unusual organometallic complex, {Th[(CH(3))(5)C(5)](2) H(micro-H)}(2) . C(6)H(5)CH(3), has been determined from neutron diffraction data, using only the direct-methods program MULTAN. Besides providing accurate metrical information on the first organometallic actinide hydride complex, these results have general and far-reaching implications concerning the complexity and size of crystal structures that can be elucidated solely on the basis of neutron diffraction data.

Second-generation hexavalent molybdenum oxo-amidinate precursors for atomic layer deposition.

The synthesis of molybdenum oxo-amidinate complexes MoO2(R2AMD)2 [AMD = N,N'-di-R-acetamidinate; R = Cy (2; cyclohexyl) and iPr (3)], and their characterization by 1H, 13C NMR, X-ray diffraction, and thermogravimetric analysis is reported. Quartz-crystal microbalance and X-ray photoelectron spectroscopic studies confirm that 3 is an improved ALD precursor versus the R = t-butyl derivative for MoO3 film growth. Complex 3 is accessible in higher yields (80%+), is easier to handle without mass loss, and in conjunction with O3 as the second ALD reagent, yields nitride-free MoO3 films.

Potentiation of actinomycin D or adriamycin antitumor activity with DNA.

Several antitumor agents known to bind DNA were complexed with this macromolecule and tested for activity against experimental animal tumor systems. Combination studies with these agents and DNA were carried out at the same time. Actinomycin D activity against the P388 lymphocytic leukemia in BALB/c X DBA/2 F1 mice was significantly potentiated by calf thymus DNA, both when complexed and when injected in combination. The DNA could be given as much as 4 hr before or after the antibiotic and still give potentiation. Synergism was also obtained when the DNA was autoclaved prior to complexing and/or injecting. Similarly, adriamycin activity against the L1210 lymphoid leukemia in DBA/2 mice was significantly potentiated by autoclaved herring sperm DNA, both as a complex and when injected in combination. When above-optimal levels of adriamycin were complexed with autoclaved herring sperm DNA and injected into BALB/c mice inoculated with the Madison 109 alveogenic carcinoma, the early lethality was delayed and antitumor activity was sometimes observed. Herring sperm DNA injected alone also had antitumor activity against the Madison 109 tumor. Similarly, activity was obtained against this tumor system with calf thymus DNA and actinomycin D when injected alone. In addition, DNA, in combination and when complexed with actinomycin, prevented the toxicity observed with BALB/c mice, inoculated with the Madison 109 tumor, were given injections of an above-optimal dose of this antibiotic.

Effect of the preestrogen 4-androstene-3,17-dion-19-al on the Dunning R3327 prostatic adenocarcinoma.

The purpose of this pilot study was to determine if biogenetic precursors of estrone such as 4-androstene-3,17-dion-19-al, which is virtually devoid of thrombotic potential as well as androgenic and uterotrophic activity, could replace estrogen in the treatment of the hormone-sensitive Dunning R3327 prostatic adenocarcinoma in the male Copenhagen rat. If such were the case, the way would be open to an improved form of palliative therapy of prostatic cancer with the potential for decreased estrogenic side effects and cardiovascular complications. To this end, the R3327 tumor was transplanted (Day 0) into the flank of 10-week-old male Copenhagen rats, and treatment was begun 20 weeks later at which time the tumors reached a mean volume of 2160 cu cm. In addition to 4-androstene-3,17-dion-19-al (1 and 10 mg/day), diethylstilbestrol (33 micrograms/day) and 17 beta-estradiol (3.3 and 33 micrograms/day) were studied (daily for 60 days). At 1 mg/day, 4-androstene-3,17-dion-19-al produced a 43% inhibition of tumor growth (Day 203) while, in the 10 mg/day group, a 72% inhibition of tumor growth was measured on Day 196 (roughly equivalent to that produced by estradiol at 3.3 micrograms/day), with a 50% inhibition on Day 231. It is concluded that the tumor-inhibiting activity of 4-androstene-3,17-dion-19-al, coupled with its very low thrombotic potential, indicated that orally active analogues of this steroid may offer advantages over estrogens in the palliative treatment of prostatic cancer.

Calcium currents in the A7r5 smooth muscle-derived cell line. An allosteric model for calcium channel activation and dihydropyridine agonist action.

We have investigated the gating kinetics of calcium channels in the A7r5 cell line at the level of single channels and whole cell currents, in the absence and presence of dihydropyridine (DHP) calcium channel agonists. Although latencies to first opening and macroscopic currents are strongly voltage dependent, analysis of amplitude histograms indicates that the primary open-closed transition is voltage independent. This suggests that the molecular mechanisms for voltage sensing and channel opening are distinct, but coupled. We propose a modified Monod-Wyman-Changeux (MWC) model for channel activation, where movement of a voltage sensor is analogous to ligand binding, and the closed and open channels correspond to inactive (T) and active (R) states. This model can account for the activation kinetics of the calcium channel, and is consistent with the existence of four homologous domains in the main subunit of the calcium channel protein. DHP agonists slow deactivation kinetics, shift the activation curve to more negative potentials with an increase in slope, induce intermingled fast and slow channel openings, and reduce the latency to first opening. These effects are predicted by the MWC model if we make the simple assumption that DHP agonists act as allosteric effectors to stabilize the open states of the channel.

Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology.

The calcium current of bullfrog sympathetic neurons activates and deactivates rapidly (tau less than 3 ms). For brief depolarizations, the current can be fit reasonably well by a Hodgkin-Huxley-type model with a single gating particle of charge +3. With 2 mM Ca2+ as the charge carrier, half-maximal activation occurs at approximately -5 mV, near the voltage where activation and deactivation are slowest. When extracellular divalent ion concentrations are reduced, monovalent ions (e.g., Na+ and methylammonium) produce kinetically similar inward currents. Current carried by Ba2+ is blocked by Cd2+ at micromolar concentrations, and by 100 nM omega-conotoxin. Commercially available saxitoxin blocks the current, but different batches have quantitatively different potency. The dihydropyridine agonist Bay K 8644 induces a slight shift in activation kinetics to more negative voltages, with little effect on the peak current. Nifedipine at least partially reverses the effect of Bay K 8644, but has little effect on its own. Muscarinic agonists and other ligands that inhibit the M-type potassium current of frog sympathetic neurons have weak inhibitory effects on the calcium current as well. One interpretation of these results is that the N-type calcium current predominates in these cells, with a minor contribution of L-type current.

Calcium currents in bullfrog sympathetic neurons. II. Inactivation.

Calcium currents in bullfrog sympathetic neurons inactivate slowly and partially during depolarizations lasting 0.5-1 s. There is also a slower (minutes) inactivation process with a broad voltage dependence. An irreversible loss of current (rundown) is prominent with low concentrations of intracellular Ca2+ buffers, with either Ca2+ or Ba2+ as the charge carrier. The extent and rate of the more rapid inactivation process are maximal near the voltage at which the peak inward current is generated, suggesting that inactivation might be Ca2+ dependent. However, inactivation occurs with either Ca2+ or Ba2+ as the charge carrier, is not prevented by strong buffering of intracellular Ca2+ with 10 mM BAPTA, and varies little as the peak current is changed 10-fold by changing the divalent ion concentration. That is, rapid inactivation is not explained by simple versions of voltage, Ca2+- or current-dependent inactivation models. A model in which ion binding within the channel allows a slower, rate-limiting inactivation process fits some but not all of the observed features of inactivation. A purely voltage-dependent three-state cyclic model fits the data if microscopic inactivation is favored by hyperpolarization.

The effect of severe undernutrition and subsequent refeeding on whole-body metabolism and protein synthesis in human subjects.

BACKGROUND: To determine the consequences of severe undernutrition and refeeding on whole-body metabolism and protein synthesis. METHODS: Respiratory quotient (RQ), resting energy expenditure (REE), and whole-body protein synthesis (WBPS) were assessed in undernourished patients, with anorexia nervosa (n = 8) or with coexistent disease (n = 17). Results were compared with 17 healthy controls. Six anorexic patients and 13 disease patients consented to study after nutrition support. RESULTS: Mean body mass index was 12.46 +/- 0.53 kg/m2 in the anorexia patients and 13.81 +/- 0.40 kg/m2 in the disease patients (controls 23.71 +/- 0.72 kg/m2; p < .001). Compared with controls, RQ was similar in anorexia patients (0.85 +/- 0.05 vs 0.90 +/- 0.05) but lower in the disease patients (0.76 +/- 0.03 vs 0.90 +/- 0.05; p = .02). REE was lower in the patients (anorexia 1058 +/- 134.0 kcal/d, disease 1189 +/- 101.4 kcal/d vs 1828 +/- 89.76 kcal/d; p < .001); however, expressed as kcal/kg/d, it was higher (anorexia 32.17 +/- 4.25, disease 31.30 +/- 2.14 vs 25.07 +/- 1.00; p < .05). WBPS was lower in the patients (anorexia 140.9 +/- 10.54 g/d, disease 119.8 +/- 8.57 g/d vs 305.0 +/- 21.64 g/d; p < .001); however, when expressed as g/kg/d, the anorexia patients were similar to controls, whereas the disease patients were lower (3.11 +/- 0.24 vs 4.27 +/- 0.32; p < .05). Refeeding increased RQ in the disease patients (0.84 +/- 0.03 vs 0.76 +/- 0.03; p < .05), and normalized REE (anorexia 27.65 +/- 3.05 kcal/kg/d, disease 28.90 +/- 1.85 kcal/kg/d). WBPS increased in the disease patients (173.6 +/- 16.38 g/d vs 116.5 +/- 10.15 g/d; p < .01). CONCLUSIONS: Undernutrition is associated with increased REE (kcal/kg/d). Reduction in RQ and protein synthesis (g/kg/d) was evident in those patients with coexistent disease. Refeeding resulted in normalization of RQ, REE (kcal/kg/d), and protein synthesis (g/kg/d).

Impaired gastric acid and pancreatic enzyme secretion in patients with Crohn's disease may be a consequenece of a poor nutritional state.

INTRODUCTION: Impaired pancreatic function has been reported in Crohn's disease, the cause of which is uncertain. This study investigated the effect of malnutrition, and subsequent re-feeding, on digestive function and protein synthesis in Crohn's disease patients. METHODS: Gastric acid and pancreatic secretion studies were performed on malnourished Crohn's patients before, and after a period of intensive nutritional support. Whole body, as well as pancreatic enzyme protein synthesis was investigated by [14C]leucine isotope incorporation studies. Results were evaluated in comparison to normal healthy volunteers. RESULTS: The mean body mass index (BMI) of the Crohn's patients was 14.14 kg/m2. The Crohn's patients had reduction in the secretion of gastric acid (7.36 versus 25.53 mEq/h; P < 0.01), and the pancreatic enzymes, amylase (759.6 versus 2305 U/h; P < 0.01), lipase (33.01 versus 118.6 U/h; P < 0.01) and trypsin (97.43 versus 341.4 U/h; P < 0.01). Resting energy expenditure (REE), expressed in relation to body mass, was greater in the malnourished Crohn's disease patients (38.25 versus 25.36 kcal/kg/d; P = 0.01). Total body protein synthesis was reduced (2.82 versus 4.39 g protein/kg/d; P < 0.05), with significant impairment in the synthesis of pancreatic enzymes, and reduction of zymogen stores. Following re-feeding, the BMI of the Crohn's patients improved to 16.80 +/- 0.66 kg/m2. Pancreatic enzyme synthesis improved, with significant increase in pancreatic enzyme stores and secretion, to levels similar to control values. Gastric acid secretion also improved, although still lower than the control value. CONCLUSION: Malnutrition may play a significant role in the impairment of gastric acid and pancreatic secretion in Crohn's disease patients.

Pre- to postnatal reduction in ultrasound attenuation coefficient of the liver.

A recent study showed the ultrasound attenuation coefficient of fetal liver between 26 and 40 weeks of gestation to be 26% higher than after birth. To test the hypothesis that ultrasound attenuation is sensitive to fetal liver glycogen concentration, the livers of 24 fetuses were examined at 5 MHz just prior to and just after birth. The mean pre- to post-delivery reduction in attenuation coefficient was 0.08 dB cm-1 MHz-1 +/- 0.02 (SEM), or 17% of the post-delivery mean. This is consistent with the increase in attenuation measured by others in liver homogenate when glycogen was added. An increase in measurement accuracy, correlation with glycogen content, and, possibly, control for biological variability will be required to make predictions in individual cases, as opposed to these averages. A simple test of glycogen content would be of value scientifically and in prenatal and postnatal management.

Organolanthanide-catalyzed intramolecular hydroamination/cyclization of amines tethered to 1,2-disubstituted alkenes.

[reaction: see text] This contribution reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amines tethered to 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines by using coordinatively unsaturated complexes of the type (eta(5)-Me(5)C(5))(2)LnCH(TMS)(2) (Ln = La, Sm), [Me(2)Si(eta(5)-Me(4)C(5))(2)]NdCH(TMS)(2), [Et(2)Si(eta(5)-Me(4)C(5))(eta(5)-C(5)H(4))]NdCH(TMS)(2), and [Me(2)Si(eta(5)-Me(4)C(5))((t)()BuN)]LnE(TMS)(2) (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2) mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and in good to excellent yield.