Long-term ECG monitoring in suspected Adams-Stokes disease.
Long-term ECG recording techniques have facilitated the diagnosis in atypical cases of Adams-Stockes syndrome. In the use of ambulatory ECG monitoring, new and mainly technical problems have been arisen. In 200 ECG recordings on cassette tape, 78% was considered sufficient for an accurate diagnosis. More than 50% of the unsuccessful recordings were unreadable due to electrode problems. The use of ambulatory monitoring demands that electrode fixation and placement be handled carefully and that the mechanical and electronic equipment be serviced frequently. Patients with third-degree atrioventricular block and syncopes of fainting spells run a high risk of sudden death. It is therefore not recommended to use ambulatory monitoring techniques on these patients.


Species-specificity of ethylene glycol-induced developmental toxicity: toxicokinetic and whole embryo culture studies in the rabbit.
High-dose gavage exposure to ethylene glycol (EG) is teratogenic in rats, but not rabbits. To investigate the reason for this species difference, toxicokinetic and whole embryo culture (WEC) studies were conducted in gestation day 9 New Zealand White rabbits, and the data compared to very similar data previously generated in pregnant rats. In the toxicokinetic study, maximal levels of unchanged EG in rabbits were comparable to those reported for rats. However, maximal levels of EG's teratogenic metabolite, glycolic acid (GA), in rabbit maternal blood and embryo were only 46% and 10% of the respective levels in rats. The toxicokinetic profile suggested that the lower GA levels in rabbits were due to a slower rate of maternal metabolism of EG to GA, slow uptake of GA into the yolk sac cavity fluid which surrounds the embryo, and negligible transfer via the visceral yolk sac (VYS) placenta. In the WEC study, exposure of rabbit conceptuses to high concentrations (< or = 12.5 mM) of GA was without effect, which contrasts with reported effects in rat WEC at > or = 3 mM. Overall, these data implicate toxicokinetics as an important factor underlying the species difference, although intrinsic insensitivity of the rabbit embryo might also be involved. Integration of these findings with published human data suggest that the rabbit is the more relevant model for human EG exposure, based on the negligible role of the rabbit VYS in placental transfer (humans lack a VYS) and similar rates of EG metabolism and extraembryonic fluid turnover.


Direct electrosynthesis of pure aqueous H2O2 solutions up to 20% by weight using a solid electrolyte.
Hydrogen peroxide (H2O2) synthesis generally requires substantial postreaction purification. Here, we report a direct electrosynthesis strategy that delivers separate hydrogen (H2) and oxygen (O2) streams to an anode and cathode separated by a porous solid electrolyte, wherein the electrochemically generated H+ and HO2 - recombine to form pure aqueous H2O2 solutions. By optimizing a functionalized carbon black catalyst for two-electron oxygen reduction, we achieved >90% selectivity for pure H2O2 at current densities up to 200 milliamperes per square centimeter, which represents an H2O2 productivity of 3.4 millimoles per square centimeter per hour (3660 moles per kilogram of catalyst per hour). A wide range of concentrations of pure H2O2 solutions up to 20 weight % could be obtained by tuning the water flow rate through the solid electrolyte, and the catalyst retained activity and selectivity for 100 hours.


[Ureter injury as a gynecologic surgery complication--prospects for conservative treatment].
There we presented three cases of ureteral injury after gynecological operations. In two cases partial ureteral obstruction was treated by creating percutaneous renal fistula. In the latter case, in spite of conservative treatment (double J catheter), a uretero-vaginal fistula was detected.


Biomimetic Engineering of a Scavenger-Free Nitric Oxide-Generating/Delivering System to Enhance Radiation Therapy.
Nitric oxide (NO) is a potent tumor-cell radiosensitizer but it can be readily scavenged by hemoglobin (Hb) in vivo. A biomimetic incubator that can generate and deliver NO in a scavenger (Hb)-free environment to enhance its radiosensitizing effect to maximize its efficacy in radiotherapy is proposed. This NO incubator comprises a poly(lactic-co-glycolic acid) (PLGA) hollow microsphere (HM) that contains an NO donor (NONOate) and a surfactant molecule (sodium caprate, SC) in its aqueous core. In acidic tumorous environments, the PLGA shell of the HM allows the penetration of protons from the outside, activating the hydrolytic cleavage of NONOate, spontaneously generating NO bubbles, which are immediately trapped/stabilized by SC. The SC-stabilized NO bubbles in the HM are then squeezed through the spaces of its PLGA matrices by the elevated internal pressure. Upon leaving the HM, the entrapped NO molecules may passively diffuse through their SC-stabilized/protected layer gradually to the tumor site, having a long-lasting radiosensitizing effect and inhibiting tumor growth. The entire process of NO generation and delivery is conducted in a scavenger (Hb)-free environment, mimicking the development of young ovoviviparous fish inside their mothers' bodies in the absence of predators before birth.


Prevalence of pancreatic autoantibodies in non-diabetic patients with autoimmune thyroid disease and its relation to insulin secretion and glucose tolerance.
We evaluated the prevalence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase-protein antibodies (IA2A), their titers and their relation to first phase insulin response (FPIR) and glucose tolerance in autoimmune thyroid diseases (ATDs) patients. Graves' disease (GD; n = 181) and Hashimoto's thyroiditis (HT; n = 143) patients in addition to healthy controls (n = 93) were studied. Secondly, FPIR and oral glucose tolerance tests (OGTT) were performed in 11 anti-pancreatic islet-cell (+) and in 20 anti-pancreatic-cell (-) patients. There was a non significant trend for higher prevalence of GADA positivity in GD vs HT (7.2% vs 2% p = 0.06), but the GADA titers were higher in HT. We also did not find a significant difference in IA2 prevalence (0.7% vs 0.0%) between these two groups or compared to the control group. In the subsequent analysis, low FPIR was found in 10% of these patients but without statistical difference for OGTT between pancreatic antibody-positive and -negative patients. A trend for greater prevalence of GADA was observed for GD patients than for HT or control. However, the titers of these autoantibodies were higher in HT patients, but there was no significant relation to insulin secretion and glucose tolerance at that moment and stage of autoimmune diseases.


Local recurrence of bladder cancer after cystectomy with orthotopic bladder substitution and ileal conduit.
To present the local recurrence rates after radical cystectomy for advanced bladder cancer and to compare them between patients with orthotopic neobladder and ileal conduit. 97 patients with radical cystectomy were analyzed: 75 patients with orthotopic ileal neobladder, operated from 1985. to 2006, and 22 patients with ileal conduit, operated from 2000. to 2006. Overall recurrence rate was 41.3% in the neobladder group, and 50% in the ileal conduit group. The rate of pelvic, upper urinary tract and urethral recurrence was 13.3%, 8%, and 10.6% in the neobladder group, and 9.1%, 13.6% and 9.1% in the ileal conduit group. Comparable recurrence rates, operative time, the complexity of the surgical technique and the results between two groups, strongly support the construction of orthotopic neobladder, as superior in functional, esthetic, and psychological point of view.


Trends in exposure to respirable crystalline silica (1986-2014) in Australian mining.
Respirable crystalline silica (RCS) has been associated with severe health risks. Exposures in Western Australia (WA) have been typically high in hard-rock mining and have reduced substantially since the mid-1900s. We described trends in RCS exposure in WA miners over the past 30 years. A total of 79 445 reported personal RCS exposure measurements, covering the years 1986-2014, were examined. Mixed-effects models were applied to estimate RCS exposure levels, including spline terms to estimate a time trend. An overall downward trend of about -8% per year was observed for RCS exposures in WA mining. Highest RCS exposure levels were modeled for base metal mining and exploration settings. Drilling occupations were among the highest exposed jobs. RCS exposure levels have fallen considerably in the last three decades. However, there are still mining occupations that may need further attention to avoid adverse health effects in these workers.


Gas in the kidney in asymptomatic Escherichia coli urinary tract infections in a patient with severe vesicoureteral reflex.
Diabetes mellitus (DM) is a common disease in Oman as in rest of Gulf Cooperation Council where metabolic syndrome is of high prevalence. DM is a foremost risk factor for urinary tract infections (UTIs). It is also linked to more complicated infections such as emphysematous pyelonephritis (EPN), emphysematous pyelitis (EP), renal/perirenal abscess, emphysematous cystitis, xanthogranulomatous pyelonephritis, and renal papillary necrosis. The diagnosis of these cases is frequently delayed because the clinical manifestations are generic and not different from the typical triad of upper UTI, which include fever, flank pain, and pyuria. A middle-aged female with DM and chronic kidney disease stage IV was admitted with recurrent UTI with extended-spectrum beta-lactamase-producing Escherichia coli. At presentation, she was afebrile, clinically stable, had no flank pain and there was no leukocytosis. Laboratory test for C- reactive protein done twice and was only mildly elevated at 7 and 11 mg/dL. A computed tomography scan of kidney-ureter-bladder (CT-KUB) was recommended and reported as "no KUB stone but small atrophic left kidney with dilatation of the pelvicalycial system and ureter and the presence of air in the collecting system suggestive of EP." Thus, commonly associated with DM, especially in females, debilitated immune-deficient individuals, and patients harboring obstructed urinary system with infective nidus. Air in the kidney is not always due to EPN. UTI with a gas-producing organism can ascend to the kidney in the presence of vesicoureteral reflux.


Microbial cell autofluorescence as a method for measuring the intracellular content of B2 and B6 vitamins.
Vitamins are important organic compound required for the proper functioning of cells and organisms. Vitamins of special industrial and pharmaceutical interests include riboflavin (vitamin B2) and pyridoxine (vitamin B6). Commercial production of those biological compounds has increasingly relied on microorganisms and requires simple methods for detecting and estimating their level of synthesis during the biotechnological process. In the case of yeast, methods based on autofluorescence, i.e. natural fluorescence emitted by several cellular compounds, including vitamins, may be useful. Considering that the intensity of emitted light is proportional to the intracellular concentration of riboflavin and pyridoxine, autofluorescence may be a convenient method for their quantification. In this report, we demonstrate a simple, rapid, and sufficiently trustworthy spectrofluorimetric method for determining the content of vitamins B2 and B6 in yeast cells which consists of cells growing, harvesting, washing, and resuspending in a buffer, and then measuring the emitted visible light using specific wavelength of excitation (λex=340 nm and λem=385 nm for pyridoxine; λex=460 nm and λem=535 nm for riboflavin). The limits of detection (LOD) and quantification (LOQ) estimated through measurements of vitamin fluorescence were below 0.005 μg/ml for riboflavin and below 0.05 μg/ml for pyridoxine, respectively. In turn, the smallest credible cell density for measuring autofluorescence was set at 1×108 yeast cells/ml. The relative level of the cell's autofluorescence can be expressed in mass units by applying proper calculation formulas. A comparison of the autofluorescence-based method with the reference HPLC-UV method shows that autofluorescence measurement can be used in the screening analysis of vitamin content (especially riboflavin) in microbial cells.


[Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial].
Objective: To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy. Methods: This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0-1; and (7) ASA score I-III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores). Result: [1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10-1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4-13) days. The median time to postoperative oral intake was 7 (range, 2-14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3-18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457). Conclusion: Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.


Revised cutoff values of serum aminotransferase in detecting viral hepatitis among CAPD patients: experience from Taiwan, an endemic area for hepatitis B.
To determine the best cutoff values of aspartate aminotransferase (AST) and alanine amino-transferase (ALT) in detecting viral hepatitis C infection among patients of continuous ambulatory peritoneal dialysis (CAPD). 90 (44 male and 46 female) CAPD patients and 526 adult controls (266 male, 260 female) were enrolled. Serum AST and ALT were measured by an auto-analyser monthly. Serum HBsAg was examined using a RIA method and anti-HCV by an second-generation EIA method. The best cutoff values of AST and ALT for detecting viral hepatitis were obtained from the ROC (receiver-operating characteristic) curve. The prevalence of anti-HCV(+) was significantly higher in CAPD patients (16.7%) than in normal controls (4.9%), while that of HBsAg(+) was similar in both groups. CAPD patients had significantly lower levels of serum aminotransferases compared to normal controls. Mean AST were 23.8 IU/l in normal control and 18.8 IU/l in the CAPD patients (P < 0.001). Mean ALT were 21.9 IU/l in normal controls and 15.3 IU/l in the CAPD patients (P < 0.001). CAPD patients with HCV infection had higher serum AST and ALT levels than those without. However, HBV infection did not cause significant serum aminotransferase elevation in patients. The conventional cutoff values of AST (40 IU/l) and ALT (40 IU/l) for detecting viral hepatitis yielded only a sensitivity of 27.3 and 18.2% respectively; on the contrary, our revised cutoff values of AST (24 IU/l) and ALT (17 IU/l) had better sensitivities (AST, 72.7%; ALT, 63.6%). For serial aminotransferase values, the sensitivity of AST and ALT for detecting HCV were 36.4 and 27.3% by conventional criteria, and were both 81.8%, by our newly revised criteria. Serum aminotransferase cutoff values should be modified for screening viral hepatitis in a CAPD population. Our new cutoff criteria had important clinical implications in providing benefits of earlier detection and possible prevention from chronic hepatic deteriorations.


Quantitative histological analysis of bovine small intestines before and after processing into natural sausage casings.
A histological study was undertaken to determine the efficiency in the removal of the mucosa and Peyer's patches by standard processing of bovine intestines into natural sausage casings. The second objective was to calculate the quantity of lymphoid and nervous tissue per consumable sausage. For the histological analysis, intestinal samples were collected from 80 beef cattle during the slaughter process. Fresh and cleaned intestines were compared in analyzing the thickness of the intestinal wall, weight reduction during cleaning, removal of the mucosal layer, and the presence of lymphoid and neural tissue after cleaning. The obtained data indicate a weight reduction of about 50% during standard cleaning procedures, as 90% of the mucosa and 48% of the lymphoid tissue are removed. Based on the quantitative histological image analysis, it was calculated that 1 m of cleaned casings, weighing on average 64 g, contains about 2.8 g of mucosa, 0.3 g of lymphoid tissue, and 0.1 g of neural tissue. Assuming, in a worst-case scenario, that the sausage casing is ingested when consuming 200 g of sausage at one meal, this consumption includes 0.09 g of lymphoid tissue and 0.02 g of neural tissue as part of the sausage casing. These data can be included in a risk assessment on the potentialexposure of consumers to bovine spongiform encephalopathy infectivity after eating sausages in beef casings.


Antiferromagnetic-like coupling in the cationic iron cluster of thirteen atoms.
We explore, within the density functional theory in the generalized gradient approximation to exchange and correlation, the map of spin isomers of the cationic Fe13(+) cluster in connection with recent X-ray magnetic circular dichroism spectroscopy experiments [M. Niemeyer et al., Phys. Rev. Lett. 2012, 108, 057201] which showed an anomalous low magnetic moment per number of 3d holes in this cluster. We systematically explore the low-lying magnetic excitations and correlate them with structural rearrangements and stability indicators. We obtain the observed low magnetic moment per 3d hole as the ground state of Fe13(+) and we demonstrate that, as supposed by the experimentalists, the cluster undergoes a magnetic transition from a ferromagnetic-like configuration to an antiferromagnetic-like one upon ionization. We unravel this unexpected magnetic behavior showing that it is concomitant with a Th-deformation of the icosahedral structure together with the electronic filling of this particular iron cluster. The spin-orbit interaction preserves this magnetic configuration which is essentially due to the spin. Our computed magnetic anisotropy energy supports the experimental interpretation of the cluster as fluxional due to the very weak coupling of the magnetic moment to an easy axis.


The role of acyl-glucose in anthocyanin modifications.
Higher plants can produce a wide variety of anthocyanin molecules through modification of the six common anthocyanin aglycons that they present. Thus, hydrophilic anthocyanin molecules can be formed and stabilized by glycosylation and acylation. Two types of glycosyltransferase (GT) and acyltransferase (AT) have been identified, namely cytoplasmic GT and AT and vacuolar GT and AT. Cytoplasmic GT and AT utilize UDP-sugar and acyl-CoA as donor molecules, respectively, whereas both vacuolar GT and AT use acyl-glucoses as donor molecules. In carnation plants, vacuolar GT uses aromatic acyl-glucoses as the glucose donor in vivo; independently, vacuolar AT uses malylglucose, an aliphatic acyl-glucose, as the acyl-donor. In delphinium and Arabidopsis, p-hydroxybenzoylglucose and sinapoylglucose are used in vivo as bi-functional donor molecules by vacuolar GT and AT, respectively. The evolution of these enzymes has allowed delphinium and Arabidopsis to utilize unique donor molecules for production of highly modified anthocyanins.


Donepezil in a chronic drug user--a potential treatment?
The objective of the current study was to explore the potential cognitive benefits of an anticholinesterase inhibitor, donepezil, in a former chronic drug user. A neuropsychological test battery composed of the vocabulary and matrix reasoning subtests of the Wechsler adult intelligence scale-III, measures of everyday executive functioning (behavioural assessment of the dysexecutive syndrome [BADS]), and verbal learning and memory tasks (California verbal learning test-II; Rivermead behavioural memory test) was completed at baseline, at 3 months after introducing donepezil, and at 3 months after donepezil was discontinued. After donepezil treatment, substantial improvements were found on tasks of nonverbal fluid reasoning (i.e. matrix reasoning) and other executive functioning tests (i.e. BADS). At entry into the study, poor academic performance and subjective problems with memory and concentration were reported, particularly after amphetamine use (i.e. MDMA and crystal methamphetamine); after donepezil treatment, dramatic increases in memory, concentration and academic achievement were observed. The finding of improvements in tests of executive functioning and in academic performance in this case study, together with the minimal adverse side effects of donepezil, warrants the investigation of controlled studies of cholinergic enhancement in chronic amphetamine and other drug users.


Novel 18beta-glycyrrhetinic acid analogues as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenases.
Extensive structural modifications to the 18beta-glycyrrhetinic acid template are described and their effects on the SAR of the 11beta-hydroxysteroid dehydrogenase isozymes type 1 and 2 from the rat are investigated. Isoform selective inhibitors have been discovered and compound 7 N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic acid amide is highlighted as a very potent selective inhibitor of 11beta-hydroxysteroid dehydrogenase 2 with an IC(50) = 4pM.


Early nutritional intervention can improve utilisation of vegetable-based diets in diploid and triploid Atlantic salmon (Salmo salar L.).
The present study investigated nutritional programming in Atlantic salmon to improve utilisation of a vegetable-based diet. At first exogenous feeding, fry were fed either a marine-based diet (Diet Mstimulus, 80% fishmeal (FM)/4% fish oil (FO)) or a vegetable-based diet (Diet Vstimulus, 10% FM/0% FO) for 3 weeks. Subsequently, all fish were then fed under the same conditions with a commercial, marine-based, diet for 15 weeks and thereafter challenged with a second V diet (Diet Vchallenge, 10% FM/0% FO) for 6 weeks. Diploid and triploid siblings were run in parallel to examine ploidy effects. Growth performance, feed intake, nutrient utilisation and intestinal morphology were monitored. Fish initially given Diet Vstimulus (V-fish) showed 24 % higher growth rate and 23 % better feed efficiency compared with M-fish when later challenged with Diet Vchallenge. There was no difference in feed intake between nutritional histories, but increased nutrient retentions highlighted the improved utilisation of a V diet in V-fish. There were generally few significant effects of nutritional history or ploidy on enteritis scores in the distal intestine after the challenge phase as only V-triploids showed a significant increase (P<0·05) in total score. The data highlighted that the positive effects were most likely a result of nutritional programming and the ability to respond better when challenged later in life may be attributed to physiological and/or metabolic changes induced by the stimulus. This novel study showed the potential of nutritional programming to improve the use of plant raw material ingredients in feeds for Atlantic salmon.


Nuclear forward scattering of synchrotron radiation in pulsed high magnetic fields.
We report the demonstration of nuclear forward scattering of synchrotron radiation from 57Fe in ferromagnetic alpha iron in pulsed high magnetic fields up to 30 T. The observed magnetic hyperfine field follows the calculated high field bulk magnetization within 1%, establishing the technique as a precise tool for the study of magnetic solids in very high magnetic fields. To perform these experiments in pulsed fields, we have developed a detection scheme for fully time resolved nuclear forward scattering applicable to other pump probe experiments.


Analytic evaluation of nonadiabatic coupling terms at the MR-CI level. II. Minima on the crossing seam: formaldehyde and the photodimerization of ethylene.
The method for the analytic calculation of the nonadiabatic coupling vector at the multireference configuration-interaction (MR-CI) level and its program implementation into the COLUMBUS program system described in the preceding paper [Lischka et al., J. Chem. Phys. 120, 7322 (2004)] has been combined with automatic searches for minima on the crossing seam (MXS). Based on a perturbative description of the vicinity of a conical intersection, a Lagrange formalism for the determination of MXS has been derived. Geometry optimization by direct inversion in the iterative subspace extrapolation is used to improve the convergence properties of the corresponding Newton-Raphson procedure. Three examples have been investigated: the crossing between the 1(1)B1/2(1)A1 valence states in formaldehyde, the crossing between the 2(1)A1/3(1)A1 pi-pi* valence and ny-3py Rydberg states in formaldehyde, and three crossings in the case of the photodimerization of ethylene. The methods developed allow MXS searches of significantly larger systems at the MR-CI level than have been possible before and significantly more accurate calculations as compared to previous complete-active space self-consistent field approaches.


ICGA combined with EP monitoring in microclipping of cerebral aneurysms.
Cerebral aneurysm is one of the common cerebrovascular diseases in neurosurgery, and rupture of cerebral aneurysm is the most important cause of spontaneous subarachnoid hemorrhage. How to precisely clip the aneurysm has been a topic worth discussing, so the authors explore the value of ICGA combined with electrophysiological monitoring in the microclipping of cerebral aneurysms. Using the method of retrospective analysis of cases, 661 patients with cerebral aneurysms admitted to the Department of Neurosurgery, Zhongnan Hospital of Wuhan University, from 2021.8 to 2022.10 were studied, 390 patients with aneurysm clipping were included, and patients with Hunt-Hess classification ≥ 4 were excluded, and whether to use ICGA combined with EP in microclipping of the ruptured and unruptured aneurysm in pterional approach was investigated at the time of discharge, respectively. The MRS and total hospital days were compared to investigate the value of ICGA combined with EP in the microclipping of cerebral aneurysms. All 390 patients enrolled in the group had successful aneurysm clipping, 178 patients were screened for ruptured aneurysm pterional approach and 120 patients for unruptured aneurysm pterional approach access; the MRS at discharge was significantly lower in the ICGA combined with EP group than in the no-EP group for ruptured aneurysm pterional approach microclipping (p < 0.001), and the mean number of days in hospital was significantly lower (p < 0.01). Patients in the ICGA combined with EP group in microclipping of unruptured aneurysms with pterional approach also had significantly lower MRS at discharge compared with patients in the ICGA alone group (p < 0.001), with no statistically significant difference in the mean number of days in hospital (p = 0.09). In open cerebral aneurysm microclipping, ICGA combined with EP monitoring for both ruptured and unruptured aneurysms can effectively reduce the false-negative rate of ICGA, significantly reduce the incidence of postoperative neurological deficits, and shorten the total hospital stay to some extent. ICGA combined with EP monitoring may be an effective means to reduce the rate of false clipping of the penetrating vessels and to avoid stenosis or occlusion of the aneurysm-carrying artery and is worth promoting in microclipping of cerebral aneurysms except for Hunt-Hess ≥ 4.


Periventricular forebrain mechanisms for blood pressure regulation.
Periventricular forebrain regions participate in body fluid and cardiovascular regulatory mechanisms that are intimately related to neural participation in experimental hypertension. Ablation of preoptic-hypothalamic periventricular tissue surrounding the anteroventral third ventricle (AV3V) disrupts both angiotensin (AngII) and sodium regulatory mechanisms and prevents experimental hypertension in either renin-dependent or -independent models. When AV3V is spared, and central AngII pressor mechanisms are interrupted by subfornical organ ablation or anterior hypothalamic knife cuts, renin-dependent but not renin-independent models of hypertension are prevented. Volume-expanded models of hypertension may be mediated by a natriuretic hormone that also inhibits the sodium-potassium pump in vascular smooth muscle, resulting in increased vasoconstriction. Volume expansion-induced release of this humoral ATPase inhibitor is attenuated in rats with AV3V lesions. In the renin-independent, reduced renal mass model, development of hypertension is correlated with increased plasma levels of sodium-potassium pump inhibitor. AV3V ablation blocks both the hypertension and the increase in humoral ATPase inhibitor. Thus, Thus, central angiotensin pressor and natriuretic mechanisms overlap in AV3V, and prevention of renin-dependent and volume-dependent models of experimental hypertension by AV3V ablation appears linked to disruption of these functionally separable systems.


Drugs for bone healing.
The biological process of fracture healing is complex with influences that are both patient-dependent and related to the trauma experienced and stability of the fracture. Fracture healing complications negatively affect the patient's quality of life, even more when fractures occur in the elderly osteoporotic patients. In the polytherapy for bone regeneration, a high success rate was obtained with the use of growth factors, osteogenic cells, and osteoconductive factors. There have been high expectations that treatment with drugs active on bone remodeling would be efficient for acceleration of fracture healing. A literature search was undertaken using wording like "drug or pharmacology of fracture healing." This report will review the systemic pharmacological agents for which clinical trials documenting their efficacy on bone healing have been carried out or are underway. At present the use of systemic pharmacological agents to enhance fracture healing in the clinical setting is still controversial. However, future clinical trials will offer the possibility to obtain data that will make possible the registration of a drug as a "healer."


Mitral Annular Calcification as a Possible Nidus for Endocarditis: A Descriptive Series with Bacteriological Differences Noted.
Mitral annular calcification (MAC) is a chronic inflammatory process with similarities to atherosclerosis. It is common in elderly patients and those with renal dysfunction. Although MAC is associated with cardiovascular morbidity, its relationship to infective endocarditis is unclear. The aim of this study was to test the hypothesis that MAC would be prevalent in patients with mitral valve vegetations and that vegetations would frequently occur on calcific nodules. A secondary aim was to look for possible bacteriological differences between vegetations attached to the calcified annulus versus leaflet vegetations. We retrospectively reviewed all echocardiographic studies of patients with native mitral valve vegetations from January 2007 to August 2015 (N = 56). We searched for (1) presence of MAC, (2) location of MAC, and (3) vegetation location (on calcium deposits or distant). MAC was defined as focal echo brightness in a nodular or band-like pattern. The modified Duke criteria were used to confirm the diagnosis of infective endocarditis. Transthoracic, transesophageal, and three-dimensional echocardiograms (when available) at the time of infection were evaluated by a single reader. Twenty-eight subjects were infected with Staphylococcus aureus, 17 with a streptococcal species, and five with other organisms; blood cultures were sterile in 6. Thirty-four (61%) subjects had some degree of MAC, while 22 (39%) had none. Among those with MAC, the vegetation was located on the calcium deposits in 22 (65%), versus in 12 (35%) where it was not. Among all 56 subjects, when S. aureus was the infecting organism it was present on MAC in 16/28 (57%) versus 6/28 (21%; P = .01) for other bacterial species. By contrast, streptococcal infections more frequently involved the leaflets (16/17 [94%]) versus nonstreptococcal infections (18/39 [46%]; P = .0008). MAC may act as a nidus for infection especially with S. aureus. Differences in mechanism of attachment between S. aureus and streptococci may account for the observed difference in frequency of attachment of vegetations to MAC.


Using Wavelet Analysis To Assist in Identification of Significant Events in Molecular Dynamics Simulations.
Long time scale molecular dynamics (MD) simulations of biological systems are becoming increasingly commonplace due to the availability of both large-scale computational resources and significant advances in the underlying simulation methodologies. Therefore, it is useful to investigate and develop data mining and analysis techniques to quickly and efficiently extract the biologically relevant information from the incredible amount of generated data. Wavelet analysis (WA) is a technique that can quickly reveal significant motions during an MD simulation. Here, the application of WA on well-converged long time scale (tens of μs) simulations of a DNA helix is described. We show how WA combined with a simple clustering method can be used to identify both the physical and temporal locations of events with significant motion in MD trajectories. We also show that WA can not only distinguish and quantify the locations and time scales of significant motions, but by changing the maximum time scale of WA a more complete characterization of these motions can be obtained. This allows motions of different time scales to be identified or ignored as desired.


Cross-validated maximum likelihood enhances crystallographic simulated annealing refinement.
Recently, the target function for crystallographic refinement has been improved through a maximum likelihood analysis, which makes proper allowance for the effects of data quality, model errors, and incompleteness. The maximum likelihood target reduces the significance of false local minima during the refinement process, but it does not completely eliminate them, necessitating the use of stochastic optimization methods such as simulated annealing for poor initial models. It is shown that the combination of maximum likelihood with cross-validation, which reduces overfitting, and simulated annealing by torsion angle molecular dynamics, which simplifies the conformational search problem, results in a major improvement of the radius of convergence of refinement and the accuracy of the refined structure. Torsion angle molecular dynamics and the maximum likelihood target function interact synergistically, the combination of both methods being significantly more powerful than each method individually. This is demonstrated in realistic test cases at two typical minimum Bragg spacings (dmin = 2.0 and 2.8 A, respectively), illustrating the broad applicability of the combined method. In an application to the refinement of a new crystal structure, the combined method automatically corrected a mistraced loop in a poor initial model, moving the backbone by 4 A.


Transdermal therapy for overactive bladder: present and future.
Transdermal delivery of certain pharmacologic agents offers distinct advantages, including the ability to bypass the gastrointestinal environment, fewer side effects, and increased bioavailability. For many patients with overactive bladder (OAB), transdermal therapy is more convenient than oral therapy, and the altered drug metabolism offers the advantages of an improved side-effect profile and enhanced steady-state plasma concentrations. The "newness" of transdermal delivery to physicians treating OAB is a potential limitation; however, much insight can be gained from the successful use of transdermal systems for delivery of other therapies, such as agents for chronic pain, hormone replacement therapy, and contraceptives. The transdermal oxybutynin system for OAB reduces the level of oxybutynin metabolites, resulting in a low incidence of anticholinergic side effects, and provides efficacy similar to that of standard doses of currently available oral preparations. However, there is room for improvement of the transdermal system, especially with respect to providing increased efficacy over currently available oral medications and reducing and treating local skin reactions at the application site.


All Seasons Vertical Augmentation Mastopexy: A Simple Algorithm, Clinical Experience, and Patient-reported Outcomes.
The safety of augmentation mastopexy has been questioned. Staging has been recommended for women deemed to be at higher risk, such as women with greater degrees of ptosis. Most existing studies evaluate women treated with multiple methods, including the traditional Wise pattern. This retrospective study specifically evaluates vertical augmentation mastopexy. A simple algorithm is introduced. From 2002 to 2016, 252 women underwent consecutive vertical augmentation mastopexies performed by the author, with no staged surgery. All patients underwent a vertical mastopexy using a medially based pedicle and intraoperative nipple siting. A subset of women treated from 2012 to 2016 were surveyed to obtain outcome data; 90 patients (inclusion rate, 90%) participated. The complication rate was 32.9%, including persistent ptosis, delayed wound healing, scar deformities, and asymmetry. There were no cases of nipple loss. An increased risk of complications was detected for smokers (P < 0.01), but not for combined procedures, secondary breast augmentations, or secondary mastopexies. The revision rate was 15.5%. Persistent nipple numbness was reported by 13.3% of respondents. Eighty percent of women were self-conscious about their breast appearance before surgery; 22% of respondents were self-conscious about their breasts after surgery. Seventy percent of respondents reported an improved quality of life, 94.4% would repeat the surgery, and 95.6% would recommend it. A simple algorithm may be used to guide treatment in women who desire correction of ptosis and upper pole fullness. An "all seasons" vertical augmentation mastopexy is safe and widely applicable. Staging is unnecessary.


Calcium binding by lithocholic acid derivatives.
Lithocholic acid (LCA) and its sulfate (LCS) and glucuronide (LCG) derivatives are potent cholestatic agents. During the course of LCG-induced cholestasis in rats, calcium (Ca) salts of LCG precipitate in bile. To characterize the affinity of bile salts for Ca, solutions of selected bile salts were titrated with Ca. Apparent equilibrium constants (KcaBS) were determined from the unbound Ca ion concentrations that were measured spectrophotometrically with metallochromic indicators antipyrylazo III or murexide or with a Ca-selective electrode. KCaBS values were 1.12 +/- 0.04 X 10(-4) M for LCS, 2.88 +/- 0.26 X 10(-4) M for LCG, 3.09 +/- 0.21 X 10(-4) M for LCA, 1.93 +/- 0.07 X 10(-3) M for taurocholic acid (TC), 2.69 +/- 0.08 X 10(-3) M for glycocholic acid (GC), and 6.07 +/- 0.27 X 10(-3) M for taurolithocholic acid sulfate (TLCS). The KCaBS for LCG measured by a Ca-selective electrode under identical conditions was 5.53 +/- 2.75 X 10(-4) M. Comparing relative cholestatic potential with affinity for Ca, cholestatic bile salts LCS, LCG, and LCA bind Ca 10-60 times more avidly than TC, GC, and TLCS. At the unbound Ca ion concentrations of serum or bile (approx 1 mM), only LCS, LCG, and LCA would be expected to bind significant amounts of Ca.


Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP).
Retinopathy of Prematurity (ROP) is one of the most common causes of childhood blindness worldwide. Comparisons of anti-VEGF and laser treatments in ROP are relatively lacking, and the data are scattered and limited. The objective of this meta-analysis is to compare the efficacy of both treatments in type-1 and threshold ROP. A comprehensive literature search on ROP treatment was conducted using PubMed and Embase up to March 2017 in all languages. Major evaluation indexes were extracted from the included studies by two authors. The fixed-effects and random-effects models were used to measure the pooled estimates. The test of heterogeneity was performed using the Q statistic. Ten studies were included in this meta-analysis. Retreatment incidence was significantly increased for anti-VEGF (OR 2.52; 95% CI 1.37 to 4.66; P = 0.003) compared to the laser treatment, while the incidences of eye complications (OR 0.29; 95% CI 0.10 to 0.82; P = 0.02) and myopia were significantly decreased with anti-VEGF compared to the laser treatment. However, there was no difference in the recurrence incidence (OR 1.86; 95% CI 0.37 to 9.40; P = 0.45) and time between treatment and retreatment (WMD 7.54 weeks; 95% CI 2.00 to 17.08; P = 0.12). This meta-analysis indicates that laser treatment may be more efficacious than anti-VEGF treatment. However, the results of this meta-analysis also suggest that laser treatment may cause more eye complications and increase myopia. Large-scale prospective RCTs should be performed to assess the efficacy and safety of anti-VEGF versus laser treatment in the future.


Unique Techniques or Approaches in Microvascular and Microlymphatic Surgery.
Several methods can be used for identifying tissues for transfer in donor-site-depleted patients. A fillet flap can be temporarily stored in other parts of the body and transferred back to the site of tissue defect, including covering the amputated stump of the lower extremity. Human arm transplant is rare and has some unique concerns for the surgery and postsurgical treatment. Cosmetics of the narrow neck of transferred second toes can be improved with insertion of a flap. Lymphedema of the breast after cancer treatment can be diagnosed with several currently available imaging techniques and treated surgically with lymphaticovenous anastomosis.


Too much data, and still not enough information.
This analysis of the National Inpatient Sample Database found that Medicare and Medicaid patients with peripheral arterial disease had higher rates of amputation and in-hospital mortality as compared to private pay and Health Maintenance Organization (HMO) patients. Raising awareness of disparities of outcomes among vulnerable populations should lead all healthcare providers to examine gaps in care. Administrative databases are necessarily limited. Prospective registries should be developed to demonstrate that early detection of PAD with simple, cost effective tests like the ankle brachial index can improve outcomes.


Observing the Growth of Pb3O4 Nanocrystals by in Situ Liquid Cell Transmission Electron Microscopy.
Understanding the growth behaviors of nanomaterials during liquid-phase synthesis will be beneficial in designing and applying many functional nanodevices. However, the growth pathways regarding the nanocrystal facet development remain largely unknown as direct observation is lacking. Herein, the in situ study of Pb3O4 nanocrystals' growth is reported by using the liquid cell transmission electron microscopy with high spatial and temporal resolution. The findings indicate that Pb3O4 nanocrystals' growth follows distinct trajectories with shape evolution when the growth pathways are varied. Three growth pathways are observed, including the monomer growth of Pb3O4 nanocrystals, the coalescence growth of four stationary Pb3O4 nanocrystals, and the oriented attachment growth of Pb3O4 nanocrystal pairs and multiple randomly dispersed Pb3O4 nanocrystals. It is the first observation that Pb3O4 nanocrystals with a regular quadrilateral shape are formed, in which nanocrystal facets preferentially grow along the [002] direction of Pb3O4. Theoretical analysis confirms in this study that the surface energy and physical driving force play key roles in the growth of nanocrystals in a liquid. Such understanding of the growth pathways and quantification of formation kinetics are important for the design of hierarchical nanomaterials and the control of nanocrystal self-assembly for functional devices.


[Enhancement for anaerobic digestion of sewage sludge pretreated by microwave and its combined processes ].
To improve anaerobic digestion and dewatering of sludge, impacts of sludge pretreated by microwave (MW) and its combined processes on sludge anaerobic digestion and dewatering were investigated. The results showed that microwave and its combined processes could effectively enhance anaerobic sludge digestion. Not only the cumulative methane production in the test of the MW-H2O2-alkaline (0. 2) was increased by 13. 34% compared with the control, but also its methane production rate was much higher than that of the control. Compared with the single MW process, the addition of both H2O2 and alkaline enhanced the solubilization of particle COD( >0. 45 micron) , indicating that synergistically generated soluble organics were faster to biodegrade which resulted in the enhancement of anaerobic digestion. The MW-acid process was effective in improving sludge dewaterability, e. g. , Capillary Suction Time (CST) at only 9. 85 s. The improvement of sludge dewatering was significantly correlated with sludge physical properties such as zeta potential, surface charge density and particle size. Under different sludge pretreatment conditions, the sludge dewatering after anaerobic digestion was similar, though the difference of sludge dewatering to some degrees was observed for pretreated sludge.


Experimental and analytical efforts to characterize cutting fluid mist formation and behavior in machining.
The use of cutting fluids in machining operations is being carefully scrutinized by industry for several reasons, including its overall cost in the manufacturing process and its impact on worker health. Given the concerns associated with the use of cutting fluids, a number of experimental and analytical research efforts are being conducted to gain an understanding of the role of these fluids in various machining processes. The knowledge gained by this research will aid in the development and implementation of strategies to reduce or eliminate the negative effects of cutting fluids, while maintaining their beneficial role. This article presents the results of designed experiments focused on determining the significant variables that influence air quality during turning operations, as well as characterize the aerosol emissions associated with wet and dry turning. Air quality is characterized by measuring the mass concentration and particle size distribution of the dust and mist created during a set of machining experiments. The relative importance of vaporization/condensation and atomization as mist-generating mechanisms is also explored. The experiments revealed that spindle speed has a dominating effect on both mist mass concentration and aerodynamic particle size. Analytical models are presented that predict the average droplet size of the mist generated by atomization and are used to investigate droplet size trends for various cutting fluids and machining parameters. The results predicted by the models are consistent with the expected trends.


[Design and Implementation of a Mobile Operating Room Information Management System Based on Electronic Medical Record].
A mobile operating room information management system with electronic medical record (EMR) is designed to improve work efficiency and to enhance the patient information sharing. In the operating room, this system acquires the information from various medical devices through the Client/Server (C/S) pattern, and automatically generates XML-based EMR. Outside the operating room, this system provides information access service by using the Browser/Server (B/S) pattern. Software test shows that this system can correctly collect medical information from equipment and clearly display the real-time waveform. By achieving surgery records with higher quality and sharing the information among mobile medical units, this system can effectively reduce doctors' workload and promote the information construction of the field hospital.


Yohimbine prevents the retrograde flow of spermatozoa into the urinary bladder of dogs induced by xylazine.
This study was carried out to determine whether yohimbine antagonizes the retrograde flow of spermatozoa into the urinary bladder of dogs caused by xylazine. Adult dogs were assigned to one of four groups of six dogs each and treated as follows: saline control, xylazine (2.2 mg/kg, i.m.), yohimbine (0.2 mg/kg, i.m.), yohimbine/xylazine (yohimbine, 0.2 mg/kg, i.m., followed 10 min later by xylazine, 2.2 mg/kg, i.m.). Pre- and post-treatment urine were collected by cystocentesis from all dogs. The mean (+/- SD) adjusted total number of spermatozoa in the post-treatment urine of xylazine-treated dogs (141.02 +/- 136.75 x 10(6)) was 15 times higher (P < 0.05) than the number in the post-treatment urine of control dogs (9.16 +/- 20.26 x 10(6), 1763 times higher (P < 0.05) than the number in the urine of yohimbine-treated dogs (0.08 +/- 0.20 x 10(6), and 56 times higher (P < 0.05) than the total number in the post-treatment urine of yohimbine/xylazine-treated dogs (2.54 +/- 4.54 x 10(6)). These results confirm that xylazine induces a significant (P = 0.007) displacement of spermatozoa into the urinary bladder of dogs and demonstrate that pre-treatment with yohimbine prevents this effect.


Quercetin in association with moderate exercise training attenuates injuries induced by experimental diabetes in sciatic nerves.
Diabetic neuropathy (DN) is a frequent, serious and debilitating chronic complication of diabetes mellitus (DM). Hyperglycemia, oxidative and nitrosative stress are involved in causing nerve damage in several animals, humans and experimental models of diabetes. This study was designed to investigate the synergistic cumulative neuroprotective effect of quercetin administration and moderate exercise training on sciatic nerves injuries in streptozotocin (STZ)-diabetic rats. DM was induced in Wistar rats by intraperitoneal administration of STZ (60 mg/kg). The diabetic rats received quercetin (30 mg/kg body weight/day) and performed an exercise training program (30 minutes/day, 5 days/week) for 5 weeks. Various biochemical parameters of oxidative and nitrosative stress were determined and histopathological evaluations were performed from sciatic nerves. Diabetic rats showed significantly increased oxidative and nitrosative stress parameter levels in the sciatic nerves. Diabetic trained rats treated with quercetin exhibited a significantly reduced hyperglycemia and its metabolic abnormalities induced by intraperitoneal administration of STZ. Histological alterations of the sciatic nerves induced after STZ administration were restored by administration of quercetin. Quercetin administration in association with moderate exercise training not only attenuated the diabetic condition but also restored sciatic nerves injuries by controlling hyperglycemia to down-regulate the generation of free radicals, as well as the elevation of antioxidant enzymes.


Quantifying Changes in the Language Used Around Mental Health on Twitter Over 10 Years: Observational Study.
Mental health challenges are thought to affect approximately 10% of the global population each year, with many of those affected going untreated because of the stigma and limited access to services. As social media lowers the barrier for joining difficult conversations and finding supportive groups, Twitter is an open source of language data describing the changing experience of a stigmatized group. By measuring changes in the conversation around mental health on Twitter, we aim to quantify the hypothesized increase in discussions and awareness of the topic as well as the corresponding reduction in stigma around mental health. We explored trends in words and phrases related to mental health through a collection of 1-, 2-, and 3-grams parsed from a data stream of approximately 10% of all English tweets from 2010 to 2021. We examined temporal dynamics of mental health language and measured levels of positivity of the messages. Finally, we used the ratio of original tweets to retweets to quantify the fraction of appearances of mental health language that was due to social amplification. We found that the popularity of the phrase mental health increased by nearly two orders of magnitude between 2012 and 2018. We observed that mentions of mental health spiked annually and reliably because of mental health awareness campaigns as well as unpredictably in response to mass shootings, celebrities dying by suicide, and popular fictional television stories portraying suicide. We found that the level of positivity of messages containing mental health, while stable through the growth period, has declined recently. Finally, we observed that since 2015, mentions of mental health have become increasingly due to retweets, suggesting that the stigma associated with the discussion of mental health on Twitter has diminished with time. These results provide useful texture regarding the growing conversation around mental health on Twitter and suggest that more awareness and acceptance has been brought to the topic compared with past years.


Omnidirectional Measurements of Angle-Resolved Heat Capacity for Complete Detection of Superconducting Gap Structure in the Heavy-Fermion Antiferromagnet UPd_{2}Al_{3}.
Quasiparticle excitations in UPd_{2}Al_{3} were studied by means of heat-capacity (C) measurements under rotating magnetic fields using a high-quality single crystal. The field dependence shows C(H)∝H^{1/2}-like behavior at low temperatures for both two hexagonal crystal axes, i.e., H∥[0001] (c axis) and H∥[112[over ¯]0] (a axis), suggesting the presence of nodal quasiparticle excitations from heavy bands. At low temperatures, the polar-angle (θ) dependence of C exhibits a maximum along H∥[0001] with a twofold symmetric oscillation below 0.5 T, and an unusual shoulder or hump anomaly has been found around 30°-60° from the c axis in C(θ) at intermediate fields (1≲μ_{0}H≲2 T). These behaviors in UPd_{2}Al_{3} purely come from the superconducting nodal quasiparticle excitations, and can be successfully reproduced by theoretical calculations assuming the gap symmetry with a horizontal linear line node. We demonstrate the whole angle-resolved heat-capacity measurements done here as a novel spectroscopic method for nodal gap determination, which can be applied to other exotic superconductors.


[Accurate establishment of the retinotopic topography of area 17 in cats by intrinsic signal optical imaging].
The retinotopic topography of area 17 in cats was measured by optical imaging based on intrinsic signals. When stimulated with two neighboring gratings oriented orthogonally each other, which were positioned respectively in the upper and lower visual fields, one piece of cortex that had the retinal projection corresponding to the area around the border of the two stimulus gratings became blurred in the resultant function orientation map, because the neurons in this site received excitatory signals from both the horizontal and the vertical gratings via indirect ways. This functional map of the same cortex was compared with that elicited only by a horizontal or vertical grating stimulation in the whole visual field. Accordingly, the accurate position of the retinotopic eccentricity of the cortex in visual field can be demarcated by calculating the cross correlation coefficient of the two functional maps. Furthermore, compared with the electrophysiological measure of receptive fields of single cortical neurons, the retinotopic eccentricities revealed by optical imaging were identical. This experiment provides a fast and relatively accurate method to calculate the retinotopic eccentricities in a large cortical area of the visual cortex.


A case of hypertrophic osteoarthropathy associated with nasopharyngeal carcinoma in a child.
Hypertrophic osteoarthropathy is characterized by clubbing of the digital tips and periosteal reaction of long bones. Most of the cases are associated with malignancy or other conditions such as congenital heart disease, liver cirrhosis, pulmonary fibrosis, biliary atresia, and gastrointestinal polyps. Hypertrophic osteoarthropathy associated with malignancy is rare in children. A few cases of hypertrophic osteoarthropathy in children with nasopharyngeal carcinoma have been reported, however, there has been no report of such case in Korea. We present a case of hypertrophic osteoarthropathy associated with nasopharyngeal carcinoma with lung metastasis in a 14-yr-old boy. In this case, hypertrophic osteoarthropathy regressed after intensive chemotherapy, but subsequently the patient died of progressive lung metastasis.


Using mouse genomics to understand idiopathic interstitial fibrosis.
Idiopathic interstitial pneumonia represents a broad category of lung disorders characterized by scarring or fibrosis of the lung accompanied by varying degrees of inflammation. A number of important hypotheses based on clinical observations have substantially contributed to our understanding of the pathogenesis of the most insidious and devastating of the idiopathic interstitial pneumonias, idiopathic interstitial fibrosis (IIF). Patients with IIF usually present late in the course of their illness; thus, animal models of the early, preclinical stage of these diseases are needed. Although no model faithfully recapitulates the clinical course of disease or the histopathology observed in humans, all result in scarring of the lung and may therefore be used to understand the biological processes that contribute to this scarring. The purpose of this article is to summarize the application of mouse genetic and genomic tools to these models to advance our understanding of IIF and to describe emerging agnostic approaches to identifying genes important to the fibroproliferative component of IIF.


Regional Anesthesia in Upper-Limb Surgery.
Local and regional anesthesia is associated with numerous clinical and institutional advantages relative to general anesthesia. As anesthesiologists and surgeons increasingly integrate local and regional anesthesia into their clinical practice, an understanding of the principles, evolution, and trends underpinning modern anesthetic techniques continues to be relevant. A review of the literature in databases Medline, PubMed, and EMBASE identified recent developments, ongoing trends, and historical milestones in upper-limb regional anesthesia. Advances in regional anesthetic techniques in the last century have led to reduced postoperative pain, improved safety, and improved outcomes in upper-limb surgery. The development of ultrasound-guided techniques, as well as pharmacological advances in local anesthetic drugs and adjuncts, has further advanced the role of regional anesthesia. Wide-awake local anesthesia with no tourniquet has allowed certain procedures to be performed on select patients in outpatient and low-resource settings. This review provides an overview of local and regional anesthesia in the upper-limb from its historical origins to its contemporary applications in upper-limb surgery, particularly during the COVID-19 pandemic.


Does radiographic arthrosis correlate with cartilage pathology in Labrador Retrievers affected by medial coronoid process disease?
To compare radiographic elbow arthrosis with arthroscopic cartilage pathology in Labrador retrievers with elbow osteoarthritis secondary to medial coronoid process (MCP) disease. Retrospective epidemiological study. Labrador retrievers (n = 317; 592 elbow joints). Data were collected retrospectively (June 2007-June 2011) to identify Labrador retrievers with thoracic limb lameness and elbow pain, a complete set of elbow radiographs, and a comprehensive arthroscopic surgery report. Each radiograph was scored for osteophytosis on the anconeal process and ulnar subtrochlear sclerosis using a modification of the International Elbow Working Group (IEWG) scoring system. Elbows affected by traumatic MCP fracture, humeral condylar osteochondrosis, or ununited anconeal process were excluded. The arthroscopic report was used to generate a composite cartilage score (CCS; 0 = normal, 1 = mild, 2 = moderate, 3 = severe) for each elbow joint. Ordinal regression analysis was performed to test the relationship between radiographic arthrosis score and CCS. There was a significant relationship between radiographic elbow arthrosis and CCS (P < .001). Elbows with a higher radiographic score were significantly more likely to have a higher CCS than elbows with a lower radiographic score. For every month increase in age, the odds of having a higher CCS increased by 0.016 (1.6%). Radiographic arthrosis can be used to predict the severity of arthroscopic cartilage pathology in Labrador retrievers affected by MCP disease.


[Serratus-Intercostal Plane Block for Brest Surgery].
Serratus-intercostal plane block (SIPB) is a novel ultrasound-guided thoracic wall nerve block reported recently. We performed SIPB for perioperative analgesia together with general anesthesia in patients undergoing partial mastectomy. We chose the patients with breast cancer of upper to lower lateral quadrant or subareolar region. The patients received general anesthesia followed by ultrasound-guided SIPB. The needle was introduced in the midaxillary line at the level of the fourth or fifth rib. Under continuous ultrasound guidance, we injected 30 ml of ropivacaine 0.375-0.5% between the serratus anterior and the external intercostal muscles. After the partial mastectomy, the area of sensory loss obtained by skin prick was extended from five to six as the number of intercostal spaces. Analgesic effect was obtained for 12 to 24 hours. The cephalad dermatomal paresthesia was T2. More than 20 patients received SIPB, and no one acquired the sensory loss at T1 of dermatomal distribution. SIPB provides effective analgesia for breast surgery of upper to lower lateral quadrant and/or subareolar region. However, it should be administered with other additional analgesic agents when axillary dissection is performed, because sensory loss of T1 is difficult to achieve.


"Resultant bond moment" as a newly developed electronic parameter in the design of antibacterial, antiprotozoal nitroimidazole derivatives.
Nineteen nitroimidazole derivatives have been reported to be effective antibacterial against one strain each of Bacteroides fragilis and Clostridium perfringens. The negative logarithms of minimum inhibitory concentrations (MICs) of these nitroimidazoles were fitted by a biostatistical relation involving a newly designed structural descriptor, the Resultant Bond Moment (RBM). RBM was developed on the basis of the chemical attribute of bond moments of heteroatoms. RBM reflects the electronic characteristic of the molecule. Apart from this, steric, electronic, and hydrophobic parameters were also utilised in the search of a best fit regression equation. On the basis of these equations new investigative nitroimidazole derivatives have been predicted concerning their antibacterial and antiprotozoal efficacy.


Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1,452 patients and development of a prognostic model.
To determine the utility of hepatic resection (HR) in the treatment of patients with noncolorectal nonendocrine liver metastases (NCNELM). The place of HR in the treatment of NCNELM remains controversial, primarily due to the limitations of previously published reports and the heterogeneity of primary tumor sites and histologies. A multivariate risk model was developed by analyzing prognostic factors and long-term outcomes in 1452 patients with NCNELM treated with HR at 41 centers from 1983 to 2004. Hepatic metastases were solitary in 56% and unilateral in 71% (mean diameter, 50.5 mm). Extrahepatic metastases were present in 22%. The most common primary sites were breast (32%), gastrointestinal (16%), and urologic (14%). The most common histologies were adenocarcinoma (60%), GIST/sarcoma (13.5%), and melanoma (13%). R0 resection was achieved in 83% of patients with a 60-day mortality rate of 2.3% and a major complication rate of 21.5%. Tumor recurred in 67% of patients (liver, 24%; extrahepatic, 18%; both, 25%). Overall and disease-free survivals at 5 years were 36% and 21% and at 10 years were 23% and 15%, respectively. In multivariate analysis, factors associated with poor prognosis were patient age >60 years, nonbreast origin, melanoma or squamous histology, disease-free interval <12 months, extrahepatic metastases, R2 resection, and major hepatectomy (all P < or = 0.02). A prognostic model based on these factors effectively stratified patients into low-risk (0-3 points, 46% 5-year survival), mid-risk (4-6 points, 33% 5-year survival), and high-risk (>6 points, <10% 5-year survival) groups (P = 0.0001). HR for NCNELM is safe and effective, with outcomes mainly dependent on primary tumor site and histology. For individual patients, a statistical model based on key prognostic factors could validate the indication for hepatic resection by predicting long-term survivals.


Synthesis of the dioleoyl derivative of iododeoxyuridine and its incorporation into reconstituted high density lipoprotein particles.
We investigated the potential use of reconstituted HDL particles (NeoHDL) as a carrier for lipophilic (pro)drugs. The antiviral drug iododeoxyuridine (IDU) was used as model compound. [3H]-IDU was derivatized with two oleoyl residues to dioleoyl[3H]iododeoxyuridine ([3H]IDU-Ol2), and the lipophilic prodrug was incorporated into NeoHDL by cosonication of [3H]IDU-Ol2 with lipids and HDL apoproteins. NeoHDL particles with the same density, size, and electrophoretic mobility as native HDL were obtained, which contained 7.3 +/- 0.8% (w/w) [3H]IDU-Ol2 (about 30 molecules of prodrug per particle). NeoHDL-associated [3H]IDU-Ol2 was stable during 2 h of incubation with human plasma; the prodrug was not appreciably hydrolyzed, nor exchanged with LDL. After intravenous injection of [3H]-IDU-Ol2-loaded 125I-NeoHDL into rats, [3H]IDU-Ol2 disappeared more rapidly from the circulation than the 125I-apoproteins (78.0 +/- 8.0% vs 30.1 +/- 4.5% of the dose cleared from plasma in 60 min, respectively). The hepatic association of the prodrug was higher than that of the apoproteins (21.6 +/- 0.5 vs 5.2 +/- 1.0% of the dose at 10 min after injection, respectively). As selective clearance and uptake of lipid esters is also observed with native HDL, this suggests that, in vivo, prodrug-loaded NeoHDL may be subject to physiological HDL-specific processing. Lactosylated [3H]IDU-Ol2-loaded 125I-NeoHDL, which contains galactose residues that can be recognized by galactose receptors on parenchymal liver cells, was rapidly cleared from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)


MUTUAL MATE CHOICE AND SEX DIFFERENCES IN CHOOSINESS.
Sexual competition is associated closely with parental care because the sex providing less care has a higher potential rate of reproduction, and hence more to gain from competing for multiple mates. Sex differences in choosiness are not easily explained, however. The lower-caring sex (often males) has both higher costs of choice, because it is more difficult to find replacement mates, and higher direct benefits, because the sex providing more care (usually females) is likely to exhibit more variation in the quality of contributions to the young. Because both the costs and direct benefits of mate choice increase with increasing parental care by the opposite sex, general predictions about sex difference in choosiness are difficult. Furthermore, the level of choosiness of one sex will be influenced by the choosiness of the other. Here, we present an ESS model of mutual mate choice, which explicitly incorporates differences between males and females in life history traits that determine the costs and benefits of choice, and we illustrate our results with data from species with contrasting forms of parental care. The model demonstrates that sex differences in costs of choice are likely to have a much stronger effect on choosiness than are differences in quality variation, so that the less competitive sex will commonly be more choosy. However, when levels of male and female care are similar, differences in quality variation may lead to higher levels of both choice and competition in the same sex.


How far has robot-assisted partial nephrectomy reached?
Nephron-sparing surgery is the standard treatment for small renal mass (SRM). Nephron-sparing surgery has evolved from an open to a minimally invasive technique. Robot-assisted partial nephrectomy (RAPN) is the latest technique in this field and is reported to be safe and feasible, showing oncologically and functionally superior or compatible results compared with open and laparoscopic partial nephrectomy for SRM. This is not limited to only SRM but also applies to large and complex renal masses and other challenging situations. RAPN showed good oncological and functional outcomes for ≥clinical T2 renal tumors, complex renal masses (PADUA score ≥10, RENAL score ≥10), hilar renal tumors, and multiple renal tumors. In addition, the outcomes of RAPN in these challenging cases were not inferior to those in conventional cases. RAPN could also be applied to a number of challenging cases in which the open technique was considered first. RAPN showed good results in patients with a solitary kidney, horseshoe kidney, and in repeat surgeries. Furthermore, RAPN could be safely performed on obese, elderly, and pediatric patients. Finally, this review evaluates efficiency and utility of RAPN based on the results of challenging cases of renal masses and to project the future of RAPN.


Incidence of intussusception as studied from a hospital-based retrospective survey over a 10-year period (2001-2010) in Akita Prefecture, Japan.
One concern about rotavirus vaccines is its possible association with intussusception. Thus, it is necessary to determine the baseline incidence for intussusception in the first year of life in places where rotavirus vaccines are introduced. However, few safety data exist for the period at which the first dose of Rotarix and RotaTeq are allowed to administer in Japan. The first dose of Rotarix is scheduled to administer at 6-20 weeks of age and that of RotaTeq is scheduled to administer at 6-24 weeks of age; the upper limits for these vaccines is later than the upper limit recommended by the World Health Organization by 5 and 9 weeks, respectively. We performed a retrospective cross-sectional study by reviewing medical charts of all hospitals that provided pediatric beds in Akita Prefecture, Japan, and identifying the cases of intussusception that met the Brighton criteria level 1 in these hospitals between January 2001 and December 2010. During this 10-year period, 122 children younger than 1 year of age were diagnosed with intussusception. The incidence of intussusception was estimated at 158 per 100,000 person-years among children younger than 1 year (95% confidence interval, 131-188), 10 per 100,000 person-years for children aged 0-2 months, 165 for children aged 3-5 months, and 300 for children aged 6-8 months. This rapid and substantial increase in the incidence of intussusception during the first year of life should be considered when formulating the immunization schedule for administering rotavirus vaccines in Japan.


Excitation-Power-Dependent Upconversion Luminescence Competition in Single β-NaYbF4:Er Microcrystal Pumped at 808 nm.
Controlling the upconversion luminescence (UCL) intensity ratio, especially pumped at 808 nm, is of fundamental importance in biological applications due to the water molecules exhibiting low absorption at this excitation wavelength. In this work, a series of β-NaYbF4:Er microrods were synthesized by a simple one-pot hydrothermal method and their intense green (545 nm) and red (650 nm) UCL were experimentally investigated based on the single-particle level under the excitation of 808 nm continuous-wave (CW) laser. Interestingly, the competition between the green and red UCL can be observed in highly Yb3+-doped microcrystals as the excitation intensity gradually increases, which leads to the UCL color changing from green to orange. However, the microcrystals doped with low Yb3+ concentration keep green color which is independent of the excitation power. Further investigations demonstrate that the cross-relaxation (CR) processes between Yb3+ and Er3+ ions result in the UCL competition.


[Case of anterior ischemic optic neuropathy accompanied by Churg-Strauss syndrome].
Churg-Strauss syndrome (CSS) is a vasculitis which includes the three signs of bronchial asthma, hypereosinophilia, and vasculitis syndrome. We report a case in whom anterior ischemic optic neuropathy (AION) accompanied CSS. Such a case has not been reported previously in Japan. A 66-year-old woman with a history of bronchial asthma and eosinophilic pneumonia was hospitalized for fever, unusual feelings in both plantae and in a finger of her left hand, disturbance of visual acuity and visual field in the right eye, and skin rashes; a diagnosis of CSS was made. At the time of the first ophthalmological examination, AION was observed. Steroid therapy was started, but the treatment was not effective, despite an improvement in choroidal circulation confirmed by fluorescein angiography and indocyanine green angiography. In the unaffected eye, soft exudates appeared when the steroid dose was lowered and disappeared when the steroid dose was raised. Anterior ischemic optic neuropathy accompanied with Churg-Strauss syndrome resisted medical treatment and the prognosis was poor.


The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A-PBX1: A 10-year retrospective study.
The clinical outcomes and genomic features of E2A-PBX1 (TCF3-PBX1)-positive B-cell acute lymphoblastic leukemia (B-ALL) patients remain unclear. A total of 137 patients carrying E2A-PBX1 among 3164 B-ALL patients between 2009 and 2019 were retrospectively analyzed. The 5-year overall survival (OS) and disease-free survival (DFS) rates of the whole cohort were 68.6% and 61.0%, respectively. Age [DFS, p = 0.037; cumulative incidence of relapse (CIR), p = 0.005] and the level of minimal residual disease (MRD) after induction chemotherapy (OS, p = 0.020; DFS, p = 0.002; CIR, p = 0.006) were independent risk factors. In adolescents/adults, allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) significantly improved the 5-year prognosis (OS, p < 0.001; DFS, p < 0.001; CIR, p < 0.001). Haploidentical HSCT decreased the CIR compared with human leukocyte antigen-matched HSCT in adolescents/adults (p = 0.017). Mutations in PBX1, PAX5, CTCF and SETD2, amplification of AKT3, and deletion of CDKN2A/B were common in the total cohort, while transcriptome differences were found in the cell cycle, nerve growth factor (NGF) signaling pathway and transcriptional regulation by TP53 between adolescents/adults and children. Patients with multiple subclones at diagnosis tended to have unfavorable 3-year prognoses (DFS, p = 0.010; CIR, p = 0.021). Leukemia clones with DNA repair gene mutations showed aggressive and treatment-refractory phenotypes in this subtype of ALL. Our study indicated that age, the level of MRD and DNA repair gene mutations were associated with E2A-PBX1-positive B-ALL outcomes. Allo-HSCT, especially haploidentical HSCT, could improve the prognosis of adolescent/adult patients.


Mammary Analogue Secretory Carcinoma Arising in the Parotid Gland of Child.
Mammary analogue secretory carcinoma (MASC) of salivary glands is a newly recognized tumor entity. We report a child who was initially diagnosed with lymphangioma and referred to our institute for sclerotherapy, only to find out that the tumor was in fact MASC after excision. This case of MASC is in a 7-year-old boy, the youngest case so far reported. He referred to his primary care physician with a infra-auricular swelling, and it was diagnosed as lymphatic malformation he was referred to our institution for sclerotherapy. For Doppler and ultrasound magnetic resonance imaging, there was a distinct cystic lesion with a heterogeneous solid lesion inside. Minimally invasive treatment such as sclerotherapy was thought to be more desirable due to a pediatric case, the risk of postoperative facial paralysis and scar. However, even the successful treatment of cystic lesion with sclerotherapy, solid lesion of the tumor could be remained without pathological findings. Otolaryngologist also thought the importance of pathological diagnosis, and we finally chose surgical excision. The tumor was ultimately diagnosed as MASC considering histological and genetic findings. For child case, we tend to treat patient less invasively, and it might bring a risk of MASC being incorrectly treated nonsurgically such as with sclerotherapy. This could lead to tumor progression and wider radical excision at last. We believe that histological diagnosis should become the priority in similar cases of mixed solid and cystic tumors to avoid incorrect treatment, and we need to choose surgical excision by understanding the character of salivary gland tumor occurring in childhood.


A review of the literature related to trunk muscle performance.
In the past, there has been no comprehensive review of the literature pertaining to different methods of assessing trunk muscle strength. This review describes the different studies that have been performed, and determines the hierarchy of strength values and agonist/antagonist strength ratios for the trunk musculature. In general, the strength hierarchy consists of, from strongest to weakest: extension, flexion, side bending, and rotation. The agonist/antagonist ratio for extension/flexion is 1.30 and for rotation and side bending, motion to the right approximately equals motion to the left. Changes in the relative strengths of the different trunk muscle groups is affected by spinal pathology, and this is discussed. Possible clinical implications and direction for future research are delineated based on the findings of this review.


[Fate of matrix-bound phosphine during acidification with anaerobic bacteria].
Matrix-bound phosphine of anaerobic granular sludge was studied during methanogenic and acidogenic stage of anaerobic reactors. Results showed that at methanogenic stage, the concentration of matrix-bound phosphine of anaerobic sludge decreased as the height of reactor increased. But during acidogenic stage, matrix-bound phosphine disappeared when pH of the solution declined to 4-5. Further anaerobic static experiments showed that increased acidification and lower pH value promoted the decrease of matrix-bound phosphine. After cultivation with 2 000 mg x L(-1) glucose synthetic wastewater for two days, the matrix-bound phosphine fell from 1.76 ng x kg(-1) to 0.09 ng x kg(-1); At the same time, the highest disappearing rate of phosphine was reached 0.84 ng x (kg x d)(-1). While the glucose synthetic wastewater was 400 mg x L(-1), the disappearing rate of phosphine was only 0.27 ng x (kg x d)(-1). With further cultivation under acidogenic stage, the phosphine decreasing rate slowed down.


The analysis of natural killer cell activity by flow cytometry.
A flow cytometric assay was used to detect the lytic and binding capacities of both fresh peripheral blood lymphocytes and purified Leu-19+ natural killer cells against head and neck cancer cell lines. Results demonstrated that natural killer cell-mediated cytotoxicity and effector-target conjugate formation evaluated by flow cytometry was significantly correlated with the standard chromium 51 release assay and the single-cell microscopic assay, respectively. The sorted Leu-19+ natural killer cells demonstrated higher lytic capacity with a corresponding higher binding rate compared with the unsorted peripheral blood lymphocytes and sorted Leu-19- cells. Flow cytometric analysis of natural killer cell activity (a rapid, simple, and quantifiable procedure) is an alternative to the standard chromium 51 release assay.


P waves in acute myocardial infarction.
Relationships between P wave abnormalities in lead II and V1 and clinical as well as hemodynamic findings and the prognosis of 27 attacks of AMI were evaluated. 1) Patients with clinical left ventricular failure showed large negative deflections in lead V1 compared to patients without. 2) There was a significant correlation between the magnitude of PTF-V1 and PCW (r=-0.75, p less than 0.01). 3) In 20 of the 27 attacks (74%), PTF-V1 correctly identified whether or not PCW was normal on admission. 4) Patients with frequent premature beats and any of the bundle branch blocks had a large negative deflection in V1 compared to patients without. 5) There was a significant correlation between the magnitude of PTF-V1 and Peel's prognostic index (r=-0.74, p less than 0.01). Moreover, 70% of the patients with abnormal PTF-V1 (less than -0.03 mm-sec) and elevated Peel's prognostic index (more than 12) died during hospitalization. 6) The patients who died during hospitalization had a large negative deflection in lead V1 compared to those patients who survived. 7) Patients with past history of old myocardial infarction had a larger negative deflection in lead V1 compared to the patients without past history of old myocardial infarction. 8) There is no correlation between the duration and amplitude of P wave in lead II and PCW. 9) Thus, it is concluded that in patients with AMI, the magnitude of PTF-V1 reflects the level of PCW and is useful as a parameter for therapy and prognosis evaluation.


Human pluripotent stem cell-derived products: advances towards robust, scalable and cost-effective manufacturing strategies.
The ability to develop cost-effective, scalable and robust bioprocesses for human pluripotent stem cells (hPSCs) will be key to their commercial success as cell therapies and tools for use in drug screening and disease modelling studies. This review outlines key process economic drivers for hPSCs and progress made on improving the economic and operational feasibility of hPSC bioprocesses. Factors influencing key cost metrics, namely capital investment and cost of goods, for hPSCs are discussed. Step efficiencies particularly for differentiation, media requirements and technology choice are amongst the key process economic drivers identified for hPSCs. Progress made to address these cost drivers in hPSC bioprocessing strategies is discussed. These include improving expansion and differentiation yields in planar and bioreactor technologies, the development of xeno-free media and microcarrier coatings, identification of optimal bioprocess operating conditions to control cell fate and the development of directed differentiation protocols that reduce reliance on expensive morphogens such as growth factors and small molecules. These approaches offer methods to further optimise hPSC bioprocessing in terms of its commercial feasibility.


Imipramine and its metabolites: relationship to cerebral catecholamines in rats in vivo.
The relationship between blood and brain levels of imipramine (IMI) and its demethylated and hydroxylated metabolites was studied in rats after chronic administration of IMI. It was found that the combined concentration of IMI and its metabolites was about 10-fold higher in brain than in plasma and this ratio was independent of the dose or the time of sacrifice. However, the brain-to-plasma ratio for the individual compounds varied with the time of sacrifice after the last IMI dose. The metabolite, didesmethylimipramine, was found in significant quantities in plasma and brain tissue with a distribution similar to that of desmethylimipramine. The hydroxylated metabolites constituted less than 6% of the combined concentration of IMI and its metabolites in plasma. Small amounts of 2-OH-desmethylimipramine were found in brain but 2-OH-IMI was rarely detected in cerebral tissue. With the exception of the hypothalamus, there were no significant differences in the distribution of IMI or its metabolites among various brain regions. The relationship between the concentrations of IMI or its active metabolites in plasma or brain and the extracellular availability of cerebral norepinephrine was also studied and found to be nonlinear: the concentration of norepinephrine in the cerebroventricular fluid approached a maximal value when the combined concentration of IMI and its metabolites was 10 micrograms/g in the brain or 1.5 micrograms/ml in plasma. Cerebroventricular application of IMI or each of its metabolites resulted in an increased concentration of both norepinephrine and dopamine in the cerebroventricular fluid whereas the concentrations of catecholamine metabolites remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)


Equilibrium solubility measurement of compounds with low dissolution rate by Higuchi's Facilitated Dissolution Method. A validation study.
Incubation time plays a critical role in the accurate measurement of equilibrium solubility of compounds. Substances which dissolve very slowly generally need long incubation times (days or weeks) to reach equilibrium. However, long times may pose several problems, such as decomposition of solute, molding of buffer, and drifting of pH. Higuchi in 1979 proposed the Facilitated Dissolution Method (FDM) to dramatically reduce incubation time. It employs a small volume of water-immiscible organic solvent to partly solubilize the sample and thereby increase the surface area available for dissolution. The method has been used only rarely. In this study we performed a systematic validation of FDM using progesterone as model compound. The reference solubility value, 7.95±0.21μg/mL (p<0.05, n=5), was determined in Britton-Robinson buffer solution (pH7.4) at 25.0°C by the standardized protocol of Saturation Shake-Flask (SSF) method. Also, the solubility was measured by the FDM approach under varied experimental conditions (e.g., type and volume of organic solvent, time of agitation, and amount of solid excess), and compared to the reference value. It was demonstrated that the small amount of organic solvent used in the FDM does not impact the measured solubility, compared to the reference value. Additionally, four compounds of low dissolution rate (dexamethasone, digoxin, haloperidol and cosalane) were used to demonstrate that FDM can reduce the long equilibration time to the standardized 24h (6h stirring and 18h sedimentation). The time dependence of solubility equilibrium was measured by SSF, and the results were compared with those obtained by FDM. Our study, based on >200 solubility experiments, supports the validity of Higuchi's method. In this study we propose a standardized protocol for the FDM, where 1% v/v of organic solvent is used. Octane (or isooctane) was found to be suitable for highly hydrophobic compounds. Alternatively, octanol or 1,2-dichloroethane can be used for less lipophilic compounds.


The effect of preoperative instruction on state anxiety.
State anxiety was measured in 81 patients scheduled for back and neck surgery before and after preoperative instruction. Anxiety levels were significantly reduced after instruction was given. In 12 patients, anxiety level increased after instruction, possibly because of the removal of denial as a coping mechanism or because these patients were generally more anxious. There was no difference in hospital stay or number of analgesics received postoperatively between the group whose scores decreased and the group whose scores increased. The Increased Score Group, however, displayed more behavioral manifestations of anxiety after instruction and postoperatively. This study provides further evidence of the psychological benefit of preoperative instruction. Instruction should be provided on a consistent basis utilizing a structured format and including the patient's family.


An mHealth Pain Coping Skills Training Intervention for Hematopoietic Stem Cell Transplantation Patients: Development and Pilot Randomized Controlled Trial.
Pain is a challenge for patients following hematopoietic stem cell transplantation (HCT). This study aimed to develop and test the feasibility, acceptability, and initial efficacy of a Web-based mobile pain coping skills training (mPCST) protocol designed to address the needs of HCT patients. Participants had undergone HCT and reported pain following transplant (N=68). To guide intervention development, qualitative data were collected from focus group participants (n=25) and participants who completed user testing (n=7). After their input was integrated into the mPCST intervention, a pilot randomized controlled trial (RCT, n=36) was conducted to examine the feasibility, acceptability, and initial efficacy of the intervention. Measures of acceptability, pain severity, pain disability, pain self-efficacy, fatigue, and physical disability (self-report and 2-min walk test [2MWT]) were collected. Participants in the focus groups and user testing provided qualitative data that were used to iteratively refine the mPCST protocol. Focus group qualitative data included participants' experiences with pain following transplant, perspectives on ways to cope with pain, and suggestions for pain management for other HCT patients. User testing participants provided feedback on the HCT protocol and information on the use of videoconferencing. The final version of the mPCST intervention was designed to bridge the intensive outpatient (1 in-person session) and home settings (5 videoconferencing sessions). A key component of the intervention was a website that provided personalized messages based on daily assessments of pain and activity. The website also provided intervention materials (ie, electronic handouts, short videos, and audio files). The intervention content included pain coping advice from other transplant patients and instructions on how to apply pain coping skills while engaging in meaningful and leisure activities. In the RCT phase of this research, HCT patients (n=36) were randomized to receive the mPCST intervention or to proceed with the treatment as usual. Results revealed that the mPCST participants completed an average of 5 out of 6 sessions. The participants reported that the intervention was highly acceptable (mean 3/4), and they found the sessions to be helpful (mean 8/10) and easy to understand (mean 7/7). The mPCST participants demonstrated significant improvements in pre- to post-treatment pain, self-efficacy (P=.03, d=0.61), and on the 2MWT (P=.03, d=0.66), whereas the patients in the treatment-as-usual group did not report any such improvements. Significant changes in pain disability and fatigue were found in both groups (multiple P<.02); the magnitudes of the effect sizes were larger for the mPCST group than for the control group (pain disability: d=0.79 vs 0.69; fatigue: d=0.94 vs 0.81). There were no significant changes in pain severity in either group. Using focus groups and user testing, we developed an mPCST protocol that was feasible, acceptable, and beneficial for HCT patients with pain. ClinicalTrials.gov NCT01984671; https://clinicaltrials.gov/ct2/show/NCT01984671 (Archived by WebCite at http://www.webcitation.org/6xbpx3clZ).


Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent.
This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the β-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol.


Drug information services on a subscription basis.
A hospital-based drug information service (DIS) which provides services to five hospitals and a local pharmaceutical association on a subscription basis is described. The two methods of subscription are (1) a monthly fee based on hospital bed size, and (2) a fee per question. The fee based on hospital bed size allows unlimited DIS use and provides a guaranteed income. The fee per question is suitable for private practitioners and those hospitals requiring less frequent DIS use. The pharmaceutical association is billed a flat monthly rate which is paid out of membership dues. The DIS staffing, work load, reference sources, budget and mode of operation are discussed.