Radiofrequency-assisted liver resection: Technique and results.
Radiofrequency (RF)-assisted liver resection allows non-anatomical liver resection with reduced blood loss and offers the opportunity for a combination of resection and ablation. However, there are still concerns with regard to postoperative complications related to this technique. In the present study, we discuss the technical aspects of RF-assisted liver resections and analyse the rate of perioperative complications, focusing on post-hepatectomy liver failure (PLF), bile leak and abscess, and mortality. Between 2001 and 2015, 857 consecutive open and laparoscopic elective RF-assisted liver resections for benign and malignant liver tumours were reviewed retrospectively to assess perioperative outcomes. Median intraoperative blood loss was 130 mL, with 9.8% of patients requiring blood transfusion. Intra-abdominal collections requiring percutaneous drainage developed in 8.7% of all patients, while bile leak at resection margin developed in 2.8% of the cases. Major liver resection was performed in 34% of patients and the incidence of PLF was 1.5% with one directly related mortality (0.1%). RF-assisted liver resection has evolved into a feasible and safe technique of liver resection with an acceptable incidence of perioperative morbidity and a low incidence of PLF and related mortality.


[In vitro susceptibility of isolates of Scytalidium spp. from superficial lesions against posaconazole].
Scytalidium spp. is a dematiaceous fungi that has been frequently reported from tropical to semi subtropical regions. We distinguish two pathogenic species: S. dimidiatum and S. hyalinum which is an homologous non-pigmented mutant of S. dimidiatum. This keratinophilic mold may produce superficial disease (skin, nails) indistinguishable from dermatophytes. In Martinique, this pseudodermatophyte could represent more than 50 % of onychomycosis. Contrary to dermatophytes, the clinical response of Scytalidium spp. are typically very poor and topical treatment or systemic agents ineffective. To evaluate the potential efficacy of the new antifungal agent posaconazole, we tested in vitro 12 clinical isolates of Scytalidium spp. (seven S. dimidiatum and five S. hyalinum) against posaconazole by Etest method. For the totality of the isolates, the minimum inhibitory concentrations (MICs) were low: MICs less or equal to 0.25 microg/ml (maximum MICs of 0.25 microg/ml for S. dimidiatum and 0.032 microg/ml for S. hyalinum). These in vitro efficacy suggest that the new agent posaconazole may be a future alternative treatment.


Spontaneous regeneration of the corticospinal tract after transection in young rats: collagen type IV deposition and astrocytic scar in the lesion site are not the cause but the effect of failure of regeneration.
In young rats the corticospinal tract regenerated after a single transection of the spinal cord with a sharp blade, but regeneration failed if the transection was repeated to make a more traumatic injury. To identify cells and associated molecules that promote or impede regeneration, we compared expression of collagen type IV, glial fibrillary acidic protein (GFAP), and vimentin immunoreactivity (IR) at the lesion sites in combination with anterograde axonal tracing between animals with two types of transection. Axonal regeneration occurred as early as 18 hours after transection; regenerating axons penetrated vessel-like structures with collagen type IV-IR at the lesion site, while reactive astrocytes coexpressing GFAP- and vimentin-IR appeared in the lesioned white matter. In contrast, when regeneration failed astrocytes were absent near the lesion. By 7 days sheet-like structures with collagen type IV-IR and astrocytic scar appeared in the lesioned white matter and persisted until the end of the observation period (31 days). On the basis of their spatiotemporal appearance, collagen type IV-IR sheet-like structures and the astrocytic scar follow, rather than cause, the failure of regeneration. The major sign, and perhaps cause, of failure of axonal regeneration is likely the prolonged disappearance of astrocytes around the lesion site in the early postinjury period.


A High-Density Raman Photometry for Tracking and Quantifying of AchE Activity in The Brain of Freely Moving Animals with Network.
A high-density Raman photometry based on a dual-recognition strategy is created for accurately quantifying acetylcholinesterase (AchE) activity in 24 brain regions of free-moving animals with network. A series of 5-ethynyl-1,2,3,3-tetramethyl-based molecules with different conjugated structures and substitute groups are designed and synthesized for specific recognition of AchE by Raman spectroscopy. After systematically evaluating the recognition ability toward AchE, 2-(4-((4-(dimethylamino)benzoyl)oxy)styryl)-5-ethynyl-1,3,3-trimethyl-3H-indol-1-ium (ET-5) is finally optimized for AchE determination, which shows the highest selectivity, the greatest sensitivity, and the fastest response time among the investigated seven molecules. More interestingly, using the developed probe for AchE with high accuracy and sensitivity, the optimized AchE regulated by nitric oxide (NO) is discovered for promoting the neurogenesis of neural stem cells (NSCs). Benefiting from the high-density photometry, it is found that the activity and distribution of AchE varied in 24 brain regions, and the levels of AchE activity in 24 brain regions of Alzheimer's mice (AD) are lower than those of normal mice. It is the first time that a functional network of AchE in 24 brain regions is established. It is also found that the loss of AchE functional network in AD mice is restored and reconstructed by the controlled release of AchE regulated by NO.


Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis.
Matrix metalloproteinase (MMP) is critical to the progression of atherosclerosis and neointima hyperplasia after vascular injury. We investigated the effects of carvedilol, a pharmacological antioxidant with alpha- and beta-adrenergic blocking activity, on MMP-2 and MMP-9 expression. Vascular injury was induced with the balloon catheters on abdominal aortas of high-cholesterol-fed rabbits. On Day 21, there was significant aortic neointima formation with increased oxidative DNA damage by immunostaining with 8-hydroxy-2'-deoxyguanosine and enhanced MMP-2 and MMP-9 expressions by Western blotting, which were significantly reduced by oral administration of carvedilol (20 mg/kg/day) or probucol (100 mg/kg/day). Vascular expression (by Western blot), activity (by gelatin zymography), and mRNA levels of MMP-2 and MMP-9 were also reduced by carvedilol or probucol. Besides, pretreatment with carvedilol or probucol but not propranolol, a beta-blocker, or prazocin, an alpha-blocker, inhibited tumor necrosis factor-alpha-stimulated expressions and activities of MMP-2 and MMP-9 in human aortic smooth muscle cells. On electrophoretic mobility-shift assay, carvedilol inhibited the binding activities of activator protein-1 and specific protein-1, two major transcription factors for MMP promoter regions. Accordingly, carvedilol, a pharmacological antioxidant, inhibited in vivo and in vitro expression of MMP-2 and MMP-9 properly by modulating the redox-related pathways, suggesting its potential clinical implications.


Mast cells and complement activating immune reactions.
A rosetting of isolated rat mast cells with complement coated zymosan does not induce a histamine release. However, this procedure potentiated the release induced by ATP. Treatment of rats with prednisolone diminishes the number of the rosette forming mast cells.


Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain.
Introduced in 1997, the combination of hydrocodone and ibuprofen is the only fixed-dose combination analgesic containing an opioid and ibuprofen that has been approved by the US Food and Drug Administration. This study compared the efficacy and tolerability of combination hydrocodone 7.5 mg and ibuprofen 200 mg (HC/IB) with those of combination oxycodone 5 mg and acetaminophen 325 mg (OX/AC) in the treatment of moderate or severe acute low back pain. This was a multicenter, randomized, double-blind, parallel-group, repeat-dose study lasting up to 8 days. The recommended dosing of the study medications was 1 tablet every 4 to 6 hours, not to exceed 5 tablets per day. If adequate pain relief was not obtained, patients were permitted to take up to 4 doses per day of supplemental analgesic medication-the nonopioid component of the assigned study medication (ibuprofen 200 mg or acetaminophen 325 mg). Measures of efficacy included mean daily pain relief scores (0 = no relief, 1 = slight relief, 2 = moderate relief, 3 = good relief, and 4 = complete relief), mean daily number of tablets and doses of study medication, mean daily number of tablets and doses of supplemental analgesic medication, global evaluation (poor, fair, good, very good, or excellent), and results on the modified 36-item Short-Form Health Survey (SF-36). All efficacy measures were analyzed on an intent-to-treat basis. Tolerability was evaluated based on adverse events reported spontaneously or elicited by the in vestigators using nonsuggestive questioning, as well as on the number of patients discontinuing treatment because of adverse events. The study enrolled 147 patients (75 HC/IB, 72 OX/AC). The most common cause of low back pain was muscular/ligamentous injury (97/147; 66.0%), followed by degenerative disk disease (27/147; 18.4%). At baseline, 80 patients (54.4%) reported experiencing moderate pain, and 67 patients (45.6%) reported experiencing severe pain. There were no significant differences between HC/IB and OX/AC with regard to mean ( +/- SD) daily pain relief scores (2.40 +/- 1.06 vs 2.50 +/- 1.01, respectively), mean daily number of tablets of study medication (1.80 +/- 1.70 vs 2.20 +/- 1.60), mean daily number of doses of study medication (1.80 +/- 1.65 vs 2.10 +/- 1.58), mean daily number of tablets of supplemental analgesic medication (0.60 +/- 1.13 vs 0.50 +/- 0.99), mean daily number of doses of supplemental analgesic medication (0.60 +/- 1.07 vs 0.50 +/- 0.90), global evaluations, or mean scores on the modified SF-36. In addition, there were no significant differences in the proportion of patients experiencing adverse events with HC/IB (47; 62.7%) and OX/AC (45; 62.5%). Adverse events were consistent with those generally associated with the component analgesics and predominantly involved the central nervous system and gastrointestinal system. The results of this study suggest that HC/IB and OX/AC are similarly effective and tolerable in relieving moderate or severe acute low back pain. Additional controlled longitudinal trials are necessary to evaluate the clinical utility of HC/IB in treating acute low back pain.


Determination of propafenone in biological fluids by fused-silica capillary gas chromatography using electron-capture detection.
A gas-liquid chromatographic method with electron-capture detection using a capillary column with the inlet in the splitless injection mode is reported for the assay of propafenone. A 25 m X 0.31 mm cross-linked, 5% phenylmethylsilicone-coated fused-silica capillary column was employed for all analyses. The present method provides improved selectivity and sensitivity over other existing gas chromatographic and high-performance liquid chromatographic (HPLC) methods. Linearity was observed in the ranges 2.5-50 and 10-100 ng/ml. The coefficient of variation was found to be less than 10% over the concentration ranges studied. Application of the developed method is demonstrated by measuring serum propafenone concentrations over 24 h in a normal healthy volunteer after a single oral dose of propafenone and by measuring trough plasma propafenone concentrations at steady state in patients receiving this new antiarrhythmic drug. Validity of the present method is further demonstrated by comparison of analytical results obtained from measurement of patient samples using a modified published HPLC method.


[Current technologies for blood loss prevention during abdominal hysterectomy].
The paper deals with the development and use of original adequate transfusion-infusion programs to compensate for blood loss in abdominal hysterectomies for uterine myomas of varying sizes, by applying the current blood-supplying technologies that permit avoidance of transfusion of donor blood components. Four blood loss-replenishing programs in abdominal hysterectomy for large-sized myomas were studied for impact on the basic functions in premenopasal women. These included: (1) preoperative blood storage of blood autocomponents; (2) normovolemic hemodilution with hydroxyethyl starch (HES) solution being used as a dilutant; (3) administration of HES solutions as an independent solution compensating for blood loss, and (4) intraoperative reinfusion of autoerythrocytes. The proposed transfusion-infusion programs in abdominal hysterectomy for large-sized myomas by applying blood-preserving methods are effective in avoiding the use of donor blood components and accordingly in reducing the frequency of complications associated with transfusions of donor blood components, and improving the postoperative period.


Development and initial validation of the Drunkorexia Motives and Behaviors scales.
Drunkorexia, or restricting calorie intake on days when alcohol consumption is planned, is a trend among college students. The purpose of the present study is to develop a measure of motivations for drunkorexia before, during, and after alcohol consumption. College students (n=349, Mage=20.71years) completed an online survey including the Drinking Motives Questionnaire-Revised, the Eating Attitudes Test-26, and various drunkorexia items. A multidimensional measure of drunkorexia motives was developed through an iterative measurement development process. The first scale assesses drunkorexia motivations and behaviors through two subscales: Drunkorexia Motives and Drunkorexia Behaviors. The second scale assesses behaviors when drunkorexia is planned, but for various reasons, the individual did not restrict calories prior to alcohol consumption. The third measure examines restrictive drinking behaviors during an alcohol consumption event. The final scale measures compensatory behaviors after an alcohol consumption event. The newly developed measures relate to other established eating disorder and alcohol measures. Specifically, drunkorexia motives seem to be derived from conformity drinking motives. Male students report higher levels of drunkorexia motives and consuming alcohol when drunkorexia fails. The newly developed measures provide an additional perspective on the drunkorexia literature.


Enhancement of water intake by captopril (SQ14225), an angiotensin I-converting enzyme inhibitor, in the goldfish, Carassius auratus.
Single intraperitoneal (ip) injections of angiotension II (ANG II) stimulated water intake for 60 min in a dose-related manner in the goldfish, Carassius auratus. Single ip injections of captopril (SQ14225), an angiotension I-converting enzyme (ACE) inhibitor, at lower doses (0.4 and 4.0 micrograms/fish), stimulated water intake for 60 min. This stimulation cannot be ascribed to an increase in levels of plasma ANG I, since ANG I (2.2 micrograms/fish) did not stimulate drinking in the presence of SQ14225 (two injections of 9.9 micrograms/fish). It is suggested that the elevated plasma ANG I concentration achieved after blockade of ACE was converted into ANG II approximately 50 min after SQ14225 injections (4.0 g/fish), when the injected SQ14225 was effectively metabolized. Thus, the newly elevated level of ANG II may have been responsible for the vigorous drinking. Higher doses of SQ14225 (40 and 200 microgram/fish) did not affect the water intake for 60 min, indicating that the rate of basal water intake is independent of the renin-angiotensin system in the goldfish.


Optimization of a new method for extraction of cyanidin chloride and pelargonidin chloride anthocyanins with magnetic solid phase extraction and determination in fruit samples by HPLC with central composite design.
Here, we are reporting a sensitive, simple and rapid method for the analysis of cyanidin chloride and pelargonidin chloride anthocyanins in cherry, sour cherry, pomegranate and barberry produced in Iran. The analytes were extracted with acetonitrile-hydrochloric acid (1% v/v) mixture under optimized pretreatment conditions. Clean-up of the extract from fruits was conducted by magnetic solid phase extraction using salicylic acid functionalized silica-coated magnetite nanoparticles (SCMNPs) as the adsorbent. The optimized conditions searched with central composite design. Working under optimum conditions specified as: SCMNPs modified with salicylic acid, sorbent contact time and sample 10min, mechanical stirring time 57.3min. HPLC with UV-detection was used for determination of the analytes. The limit of detection, LOD, obtained for the two anthocyanins were 0.02 and 0.03μgg-1, respectively. The ranges of the spiked recoveries were 80.0-97.6 and 72.9-97.2%, with the relative standard deviations (RSD) of 2.1 and 2.5%, respectively.


Age-dependent decline in EGF-induced signaling is independent of intracellular thiols.
Loss of proliferative capacity is common in many tissue types during aging. We have shown that mitogenic signaling through the epidermal growth factor (EGF) receptor declines in hepatocytes from old rats. Specifically, we showed that in old hepatocytes there is a decrease in autophosphorylation of EGF receptor at Tyr-1173. This results in loss of recruitment of the adapter protein Shc to the membrane and decreased ERK MAP kinase pathway activation. Because EGF receptor signaling also requires intracellular generation of H202, we next questioned whether altering the intracellular GSH/thiol concentration may also affect the age-dependent decline in EGF receptor signaling. Surprisingly, decreased intracellular GSH had no effect on EGF receptor signaling in hepatocytes from either young or old animals. However, increasing the thiol concentration dramatically attenuated EGF receptor signaling in hepatocytes from both young and old animals. Unexpectedly, loss of EGF receptor signaling was due to a specific decrease in EGF receptor number, but not in other components of the EGF receptor signaling pathway such as ERK MAP kinase. These results suggest that age-dependent mechanisms of alteration in EGF receptor signaling are independent of thiol regulation of EGF receptor signaling.


Perioperative infliximab application has marginal effects on ischemia-reperfusion injury in experimental small bowel transplantation in rats.
Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia-reperfusion injury in isogenic transplantation. Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five groups were defined: non-transplanted animals with no treatment (group 1), isogenic transplanted animals with vehicle treatment (groups 2/3) or with infliximab treatment (5 mg/kg body weight intravenously, directly after reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4) or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL staining, real-time RT-PCR, and contractility measurements in a standard organ bath were used for determination of ischemia-reperfusion injury. All transplanted animals showed reduced smooth muscle function, while no significant advantage of infliximab treatment was observed. Reduced infiltration of neutrophils was noted in the early phase in animals treated with infliximab. The structural integrity of the bowel and infiltration of ED1-positive monocytes and macrophages did not improve with infliximab treatment. At 3 h after reperfusion, mRNA expression of interleukin (IL)-6, TNF-α, IL-10, and iNOS and MCP-1 displayed increased activation in the infliximab group. The protective effects of infliximab in the early phase after experimental small bowel transplantation seem to be unrelated to ischemia-reperfusion injury. The promising effects in allogenic transplantation indicate the need for further experiments with infliximab as complementary treatment under standard immunosuppressive therapy. Further experiments should focus on additional infliximab treatment in the setting of acute rejection.


Interactions of liposomes with the reticuloendothelial system. II: Nonspecific and receptor-mediated uptake of liposomes by mouse peritoneal macrophages.
Liposomes are taken up as intact vesicles by mouse peritoneal macrophages in a process which is temperature sensitive and is affected by inhibitors of glycolytic metabolism and of microfilament activity. Macrophages take up negatively charge vesicles more readily than positively charged vesicles (2-fold) or neutral vesicles (4-fold). Macrophages take up similar amounts of multilamellar liposomes, reversed phase liposomes and small unilamellar liposomes in terms of lipids, however this corresponds to vastly different numbers of particles and amounts of trapped volume. Coating the liposomes with macromolecular ligands capable of interacting with macrophage surface receptors can markedly promote liposome uptake. Thus, formation of an IgG-antigen complex on the liposome surface results in a 10(2)-fold enhancement of liposome uptake, while coating the vesicles with fibronectin results in a 10-fold augmentation of uptake. Uptake via IgG-mediated and fibronectin-mediated processes seem to be independent since excess unlabelled, IgG-coated liposomes will inhibit the uptake of radioactively-labelled IgG-coated liposomes much more effectively than the uptake of radioactively-labelled fibronectin-coated liposomes. Cell-bound liposomes can readily be visualized on and inside of the macrophages using fluorescence microscopy techniques.


Structural reassignment of the mono- and bis-addition products from the addition reactions of N-(Diphenylmethylene)glycinate esters to [60]fullerene under Bingel conditions.
The addition of N-(diphenylmethylene)glycinate esters (Ph2C=NCH2CO2R) to [60]fullerene under Bingel conditions gives [60]fullerenyldihydropyrroles and not methano[60]fullerenyl iminoesters [C60C(CO2R)(N=CPh2)] as previously reported. Unequivocal evidence for the structure of C60C(CO2Et)(N=CPh2) was provided by INADEQUATE NMR studies on 13C enriched material. New mechanistic details are proposed to account for the formation of [60]fullerenyldihydropyrroles and their reductive ring-opening reactions.


Prognostic impact of Ki-67 overexpression in subgroups categorized according to St. Gallen with early stage breast cancer.
Ki-67 overexpression has been reported to be related to a poor prognosis for early stage breast cancer. We analyzed whether Ki-67 has a prognostic impact on risk subgroups based on the recommendations at St. Gallen in 2007. To determine the impact of Ki-67 on each risk group, a retrospective analysis was performed in patients with breast cancer who underwent curative surgery. Ki-67 was examined by immunohistochemistry with a predefined cutoff level of 10%. A total of 1,166 patients were eligible for this analysis. During the follow-up period, distant metastasis was observed in 164 patients (14.1%), and 80 patients (6.9%) died. Ki-67 overexpression (Ki-67 ≥ 10%) was identified as an independent prognostic factor for distant-metastatic-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis. In the intermediate-risk group, the difference between Ki-67 overexpression and no overexpression was statistically significant in 5-year DFS (90.9 vs. 83.4%, p = 0.002) and OS (98.1 vs. 95.8%, p = 0.002). However, in both the low- and high-risk groups, Ki-67 overexpression was not an independent prognostic factor for either 5-year DFS or OS. Ki-67 overexpression indicates an unfavorable prognostic impact for DFS and OS. However, this impact is restricted only to those patients classified at intermediate risk.


Disordered sodium metabolism: sodium retention states.
Sodium retention frequently occurs in the critically ill patient. Sodium retention states include cardiac failure, liver failure, nephrotic syndrome, and hypoalbuminemic states. A clear understanding of the pathophysiology and the mechanism of sodium retention are essential for the proper care of these patients.


Polarization-dependent interfacial coupling modulation of ferroelectric photovoltaic effect in PZT-ZnO heterostructures.
Recently, ferroelectric perovskite oxides have drawn much attention due to potential applications in the field of solar energy conversion. However, the power conversion efficiency of ferroelectric photovoltaic effect currently reported is far below the expectable value. One of the crucial problems lies in the two back-to-back Schottky barriers, which are formed at the ferroelectric-electrode interfaces and blocking most of photo-generated carriers to reach the outside circuit. Herein, we develop a new approach to enhance the ferroelectric photovoltaic effect by introducing the polarization-dependent interfacial coupling effect. Through inserting a semiconductor ZnO layer with spontaneous polarization into the ferroelectric ITO/PZT/Au film, a p-n junction with strong polarization-dependent interfacial coupling effect is formed. The power conversion efficiency of the heterostructure is improved by nearly two orders of magnitude and the polarization modulation ratio is increased about four times. It is demonstrated that the polarization-dependent interfacial coupling effect can give rise to a great change in band structure of the heterostructure, not only producing an aligned internal electric field but also tuning both depletion layer width and potential barrier height at PZT-ZnO interface. This work provides an efficient way in developing highly efficient ferroelectric-based solar cells and novel optoelectronic memory devices.


Use of DNA fingerprinting in an epidemiologic study of outbreak-specific and non-specific strains of group C Neisseria meningitidis.
DNA fingerprints of nine group C isolates of Neisseria meningitidis were obtained by digestion with three restriction endonucleases, BamHI, EcoRI, and HindIII. Identical restriction profiles were displayed by five strains isolated from two patients and three contacts during a localized outbreak of meningococcal disease in the area served by our laboratory. A slight difference, appreciable only in the fingerprints obtained with EcoRI, was observed between these isolates and a sixth one isolated from a clinical case occurring in the same area one year later. In contrast, three additional strains, recently isolated from patients in separate areas in Italy, gave restriction profiles differing strikingly from one another and from those produced by the strains isolated in our area.


Emphysematous pyelonephritis. A report of two cases.
Emphysematous pyelonephritis is a suppurative infection of the renal parenchyma characterized by the production of gas by bacteria through fermentation. Although seemingly rare, this condition occurred in two diabetic patients on general medical wards over a two year period. Diagnosis, in an appropriate clinical setting, is confirmed roetgenologically. Escherichia coli is the most common etiologic organism. Despite appropriate medical and surgical intervention, this severe form of renal parenchymal infection carries a high mortality.


Design, Synthesis and Biological Evaluation of New Piperazin-4-yl-(acetyl-thiazolidine-2,4-dione) Norfloxacin Analogues as Antimicrobial Agents.
 In an effort to improve the antimicrobial activity of norfloxacin, a series of hybrid norfloxacin-thiazolidinedione molecules were synthesized and screened for their direct antimicrobial activity and their anti-biofilm properties. The new hybrids were intended to have a new binding mode to DNA gyrase, that will allow for a more potent antibacterial effect, and for activity against current quinolone-resistant bacterial strains. Moreover, the thiazolidinedione moiety aimed to include additional anti-pathogenicity by preventing biofilm formation. The resulting compounds showed promising direct activity against Gram-negative strains, and anti-biofilm activity against Gram-positive strains. Docking studies and ADMET were also used in order to explain the biological properties and revealed some potential advantages over the parent molecule norfloxacin.


Longitudinal medical needs for periviable NICU survivors.
To evaluate the technologies required, medications needed, and early intervention services utilized from discharge to 12 months post-discharge for periviable infants (22 0/7 to 24 6/7 weeks gestational age) followed in a comprehensive NICU follow-up clinic. Information regarding medication use, technology requirement, and early intervention services was collected prospectively at one, six, and twelve months after discharge. Neurodevelopmental assessment was completed at 12 months corrected age. 69 periviable infants were actively treated and survived to discharge during the study period. 54 infants were enrolled and followed in the comprehensive NICU follow-up clinic. Use of technology and prescribed medications decreased with a 46% reduction of infants requiring ≥1 technology device (74.1% vs. 40.4%, p < 0.01) and 64% reduction in infants requiring ≥1 medication (88.9% vs 31.9%, p < 0.01) 12 months post discharge. There was an increase in early intervention services with 83% of infants receiving services by 12 months post discharge. Technology and medication requirements were high at discharge but notably decreased in the first year after discharge concurrent with increased enrollment in early interventional services. Many periviable infants survive without severe short-term developmental delays.


Circular RNA circ_0074027 indicates a poor prognosis for NSCLC patients and modulates cell proliferation, apoptosis, and invasion via miR-185-3p mediated BRD4/MADD activation.
Circular RNAs play an imperative role in cancer development and metastasis by regulating oncogenic and tumor-suppressive pathways. However, the role and mechanism of circ_0074027 in non-small-cell lung cancer (NSCLC) have not been elucidated. The expression levels of circ_0074027 were detected by qRT-PCR. The link between circ_0074027 expression and clinicopathologic parameters was analyzed by Fisher's exact test. The prognostic role of circ_0074027 was investigated by Kaplan-Meier and Cox regression analysis. Cell counting kit-8 and flow cytometric assays were utilized to evaluate NSCLC cell proliferation and apoptosis, respectively. Wound scratch and Transwell tests were applied to detect cell migratory and invasive capacities. The interaction potential of circ_0074027 and miR-185-3p was analyzed by the circBank database, and verified by dual-luciferase reporter assay. The downstream gene of miR-185-3p was also investigated. Circ_0074027 was elevated in NSCLC specimens and cell lines. Overexpressed circ_0074027 was related to more advanced TNM stages, poorer differentiation grade, and worse overall survival. Upregulated circ_0074027 increased the proliferation of H1299 cells by inhibiting cell apoptosis. Cell migration and invasion were enhanced after circ_0074027 overexpression. Silenced circ_0074027 caused the opposite effects in the A549 cell line. For mechanism investigation, circ_0074027 directly sponges miR-185-3p to enhance bromodomain-containing protein 4 (BRD4) and MAPK-activating death domain-containing protein (MADD) expression levels at the posttranscriptional level. Furthermore, we found the oncogenic function of circ_0074027 is attributed to its modulation of BRD4 and MADD. Collectively, upregulated circ_0074027 in NSCLC accelerates cell progression via miR-185-3p/BRD4/MADD pathway as a competing endogenous RNA.


Correlation between beta 2-glycoprotein antibodies and antiphospholipid antibodies in patients with reproductive failure.
Antiphospholipid antibodies (APAs) are important in the etiology of reproductive failure. Studies have shown that binding proteins are necessary for the detection of APAs. One of these, beta 2-glycoprotein, has been shown to be necessary for detection of anticardiolipin antibodies. It is felt that some APAs may be directed to the binding protein itself, or to a combination of the binding protein and phospholipid. In this study, a comparison of APAs vs. anti beta 2-glycoprotein antibodies was performed on the sera of 123 women younger than 40 years of age with a history of reproductive failure. Antibodies to six phospholipid epitopes, cardiolipin, phosphatidyle-thanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylglycerol, and phosphatidylserine, were measured. Of the 123 women tested, 33 had one or more positive immunoglobulin (Ig)G antibodies to phospholipids, of which 9 were to cardiolipin. However, only 1 of 123 women had IgG antibodies to beta 2-glycoprotein and she was APA negative. Thirty-eight of 123 women had one or more IgM antibodies to phospholipids, with none directed to cardiolipin IgM. In contrast, only 8 of the 123 women had IgM antibodies to beta 2-glycoprotein. Five of the eight patients had IgM APA; 4 of 5 had IgM antibodies to PE, 1 to PI. There is no correlation between beta 2-glycoprotein antibodies and APA status in this population. To date, our most sensitive test for detecting phospholipid autoimmune-mediated in vitro fertilization failure still appears to be the ELISA assay for APA.


Total body composition by DXA of 241 HIV-negative men and 162 HIV-infected men: proposal of reference values for defining lipodystrophy.
The aim of this study was to define standard values for fat mass distribution by dual-energy X-ray absorptiometry in human immunodeficiency virus (HIV)-negative men and to analyze factors associated with lipodystrophy in HIV-infected men. Total-body composition was analyzed in 241 HIV-negative men (controls) and 162 HIV-infected men. We created a fat mass ratio (FMR) as the ratio of the percentage of the trunk fat mass to the percentage of the lower limbs fat mass. We defined the FMR standard values as the mean value+/-standard deviation. We compared body mass index (BMI), fat mass percentage (%FM), lean mass (LM), bone mineral density (BMD), and FMR between the control group and HIV-infected men, by age range, according to prescription of treatment and presence of clinical lipodystrophy. The FMR standard value is equal to 1.3+/-0.2. The FMR was higher in treated HIV-infected men with or without clinical lipodystrophy. The FMR was similar for naïve HIV-infected men and controls. It was positively correlated with age, cumulative time on treatment, zidovudine, stavudine, or indinavir. BMD and fat mass were lower for treated and naïve HIV-infected men than for HIV-negative men. The FMR seems to be a valuable index for measuring fat mass distribution. We defined FMR standard values from the largest group of HIV-negative men to our knowledge. Applying FMR to HIV patients could help physicians to diagnose lipodystrophy earlier.


Correction of Abeditehrani, H., Dijk, C., Sahragard Toghchi, M., & Arntz, A. (2020). Integrating Cognitive Behavioral Group Therapy and Psychodrama for Social Anxiety Disorder: An Intervention Description and an Uncontrolled Pilot Trial.
[This corrects the article e2693 in vol. 2.][This corrects the article e2693 in vol. 2.].


Iron Deficiency without Anemia: A Common Yet Under-Recognized Diagnosis in Young Women with Heavy Menstrual Bleeding.
To assess the proportion of iron deficiency that is not detected with a screening hemoglobin or complete blood count (CBC) alone in young women with heavy menstrual bleeding. Retrospective review of electronic medical records. Nationwide Children's Hospital in Columbus, Ohio. One hundred fourteen young women aged 9-19 years consecutively referred to a young women's hematology clinic with a complaint of heavy menstrual bleeding. Fifty-eight (50.9%) of all patients had ferritin <20 ng/mL indicating iron deficiency. Of the 58 patients with iron deficiency, only 24 (41.4%) were anemic and 25 (46.3%) were microcytic. The sensitivity of hemoglobin alone and CBC alone for identifying women with ferritin <20 ng/mL was 41.4% (95% confidence interval [CI], 28.7-54.1) and 46.3% (95% CI, 33.0-59.6), respectively. Both tests had reasonable specificity at 91.1% (95% CI, 83.6-98.5) for hemoglobin and 83.9% for CBC (95% CI, 74.3-93.6). Patients had significantly higher odds of having iron deficiency if they were overweight or obese (odds ratio, 2.81; 95% CI, 1.25-6.29) compared with patients with normal body mass index. Age at presentation for heavy menstrual bleeding, presence of an underlying bleeding disorder, and median household income were not significantly associated with iron deficiency. In adolescents with heavy menstrual bleeding, fewer than half of iron deficiency cases are detected when screening is performed with hemoglobin or blood count alone. Measuring ferritin levels in at-risk patients might allow for earlier implementation of iron therapy and improvement in symptoms.


Ketamine enhances phase I and phase II neuromuscular block of succinylcholine.
The effect of intravenous injection of ketamine 2, 5 and 10 mg.kg-1 on the neuromuscular blocking action of succinylcholine was studied on the indirectly stimulated adductor pollicis muscle twitch of monkeys anaesthetized with 0.5-1.0 per cent halothane in oxygen. Neuromuscular block was quantified by single twitches evoked at 0.1 Hz. The changing nature of neuromuscular block from Phase I to Phase II was monitored periodically by train-of-four fade. In the absence of succinylcholine, ketamine had no consistent neuromuscular effect of its own. In the presence of succinylcholine, ketamine in a dose-dependent manner potentiated both the Phase I and the Phase II neuromuscular blocking effect of succinylcholine. In Phase I, 2 mg.kg-1 of ketamine reduced the ED50 of succinylcholine from 0.46 +/- 0.07 mg.kg-1 to 0.33 +/- 0.06 mg.kg-1 (P less than 0.01), and increased its 25-75 per cent recovery index from 4.0 +/- 0.4 min to 5.3 +/- 0.1 min (P less than 0.01). In Phase II, ketamine in the same dose deepened a steady neuromuscular block maintained by succinylcholine infusion from 48 +/- 3 per cent block to 71 +/- 2 per cent block (P less than 0.01). We concluded that ketamine potentiates the Phase I and the Phase II neuromuscular blocks of succinylcholine.


Three-dimensional ultrasound (3D US) methods in the evaluation of calcular and non-calcular ureteric obstructive uropathy.
To prospectively assess ureteric obstructive uropathy using three-dimensional ultrasound (3D US) methods when the etiology of ureteral obstruction was proved difficult to evaluate with two-dimensional ultrasound (2D US) and plain radiography. The study had the local Ethics Committee approval. All patients gave informed consent. 318 patients: 219 men and 99 women (including 16 pregnant women) were selected within a 3-year period for 3D US based on clinical presentation, two dimensional ultrasound (2D US) results and preliminary plain radiography except for pregnant women. 3D US was performed on all patients. 301 patients had further excretory urogram before intervention decisions. The study showed a high accuracy of detection of different levels of ureteric calcular obstruction; 99.1% in men and 96.7% in women. 3D XI technology proved more efficient in stone count (88.9%) than sectional planes and rendering method altogether (55.6%). The success rate of identifying obstructive uropathy due to inflammatory variants showed a perfect diagnostic value of 100%. Similar percentages could be obtained in cases secondary to neoplastic infiltration or permeation of the ureters. Cases compared with excretory urography revealed close correlation with 3D US and superiority of the latter when renal function physiologically altered in some cases of calcular obstructive uropathy. The 3D US methods in case of obstructive uropathy have proved to be useful as an easy, mobile and non-invasive diagnostic tool, improving 2D US diagnostic utility.


[Laser irradiation as a factor of primary prophylaxis of postradiation disorders of spermatogenesis in rats and their progeny].
Experiments on male rats have established that preventive use of low-intensive impulse laser radiation (200-400 Hz) on the adrenals prevented and limited development of postradiation disorders of spermatogenesis in irradiated male rats and their progeny.


Glycine disrupts myelin, glutamatergic neurotransmission, and redox homeostasis in a neonatal model for non ketotic hyperglycinemia.
Non ketotic hyperglycinemia (NKH) is an inborn error of glycine metabolism caused by mutations in the genes encoding glycine cleavage system proteins. Classic NKH has a neonatal onset, and patients present with severe neurodegeneration. Although glycine accumulation has been implicated in NKH pathophysiology, the exact mechanisms underlying the neurological damage and white matter alterations remain unclear. We investigated the effects of glycine in the brain of neonatal rats and MO3.13 oligodendroglial cells. Glycine decreased myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) in the corpus callosum and striatum of rats on post-natal day (PND) 15. Glycine also reduced neuroglycan 2 (NG2) and N-methyl-d-aspartate receptor subunit 1 (NR1) in the cerebral cortex and striatum on PND15. Moreover, glycine reduced striatal glutamate aspartate transporter 1 (GLAST) content and neuronal nucleus (NeuN), and increased glial fibrillary acidic protein (GFAP) on PND15. Glycine also increased DCFH oxidation and malondialdehyde levels and decreased GSH concentrations in the cerebral cortex and striatum on PND6, but not on PND15. Glycine further reduced viability but did not alter DCFH oxidation and GSH levels in MO3.13 cells after 48- and 72-h incubation. These data indicate that impairment of myelin structure and glutamatergic system and induction of oxidative stress are involved in the neuropathophysiology of NKH.


Role of magnesium-doped calcium sulfate and β-tricalcium phosphate composite ceramics in macrophage polarization and osteo-induction.
In the current study, we explored the role of Mg2+-doped CaSO4/β-TCP composite biopolymer in regulating macrophage polarization and its relation with enhanced osteogenic differentiation of periodontal ligament stem cells. Furthermore, mechanism underling the regulation of macrophage polarization by CaSO4/β-TCP was evaluated. Mg2+-doped CaSO4/β-TCP composite was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Macrophage polarization was characterized using flow cytometry analysis. Macrophage morphometric analysis was conducted by FITC phalloidin staining. Western blot and qRT-PCR assays were used to assess gene expression levels and miRNAs, respectively. SEM morphology of CaSO4/β-TCP ceramic revealed a particle size of 10-50 μm, and XRD spectrum showed that characteristic peak of samples was consistent with that of CaSO4 and β-TCP. Results from flow cytometry evidenced significant upregulation of M2 macrophage markers after adding ceramic biopolymer, indicating the induction of inactivated M0 macrophage polarization to M2 macrophage. Macrophage morphometric analysis revealed development of lamellar pseudopodia on day 7 in CaSO4/β-TCP group. Furthermore, flow cytometry revealed high positivity rate of 90.34% (CD44) and 89.36% (CD146). qRT-PCR results showed that the level of miR-21-5p was significantly decreased in M2 macrophages. Moreover, western blot analysis revealed upregulated expression levels of RUNX2, osterix (Osx), and osteopontin (OPN), and ELISA exhibited increase in cytokine levels (IL-1β, IL-10, TGF-β1, and BMP-2) in the presence of macrophages, indicating the osteogenic differentiation ability of periodontal ligament stem cells. The study evidenced the regulation of macrophage polarization by Mg2+-doped CaSO4/β-TCP composite ceramic and its mediation through lncRNA PVT1/miR-21-5p/smad2 molecular axis.


Role of Salivary Immune Parameters in Patients With Primary Sjögren's Syndrome.
Several factors, including clinical manifestations and laboratory data, have been used to evaluate the disease activity of Sjögren's syndrome (SS). We investigated saliva indicators of disease activity in primary SS patients. We enrolled 138 Taiwanese patients with primary SS and 100 Taiwanese normal controls. Interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha (TNF-α), and rheumatoid factor (RF)-IgA levels in saliva samples were measured using ELISA or fluorescent enzyme-linked immunoassay. Serum IgG, IgA, and IgM levels were measured by nephelometry. Erythrocyte sedimentation rate (ESR) was measured with an automatic ESR analyzer. The t-test and Pearson correlation test were used. IL-6 level was higher in primary SS patients than in normal controls (14.23±14.77 vs 9.87±7.32, P=0.012), but there were no significant differences in IL-17A, TNF-α, and RF-IgA levels. In primary SS patients, IL-6 level correlated weakly with ESR and IgG levels (r=0.252, P=0.015, and r=0.248, P=0.017, respectively), and TNF-α level correlated weakly with IgG level (r=0.231, P=0.024). IL-6 may play a role in SS pathogenesis. Saliva IL-6 might be an indicator of disease activity in primary SS patients.


Aflatoxins levels in vegetable oils in Khartoum State, Sudan.
Vegetable oil (n = 81) for human consumption from Khartoum State in Sudan were analyzed for aflatoxins (AFs), using high-performance liquid chromatography (HPLC) with fluorescence detection following extraction with methanol:water (80:20) and clean-up using petroleum ether. Sampling included sesame oil (n = 14), peanut oil (n = 21), and sunflower oil (n = 19) purchased from retail shops, and mixed oil produced by two local manufacturers (factory A, n = 15; factory B, n = 12). AF contamination was found in 80/81 (98.8%) samples, with total AF levels [Formula: see text] of 0.43-339.9 µg/kg and mean level of 57.5 µg/kg. All sesame oils had total AF levels that were much higher than the United States Food and Drug Administration acceptable limit of 20 µg/kg. The percentage of samples with total AF values <20 µg/kg in other oils varied and was 57.14% in peanut oil, 36.8% in sunflower oil, 66.7% (mixed oil from factory A), and 91.7% (mixed oil from factory B). In conclusion, the levels of total AFs in edible oil as available in Khartoum State are quite alarming. To reduce the health hazards for the consumers, an intervention strategy to manage AFs in food commodities from Sudan is urgently required.


Termination of pregnancy following diagnosis of fetal malformation: the need for improved follow-up services.
Eighty parents were offered an emotional support and counseling service following termination of pregnancy for fetal abnormality detected by second trimester ultrasound examination. Twenty couples took up the invitation to talk about their experiences. It was found that these women and their partners were profoundly affected by their decision to terminate the pregnancy. The lack of organized follow-up by existing agencies and the availability of professional support for these parents is a serious deficiency in our prenatal diagnostic services.


Influence of natural organic matter on the transformation of metal and metal oxide nanoparticles and their ecotoxic potency in vitro.
Increased use and production of engineered nanoparticles (NPs) lead to an elevated risk of their diffuse dispersion into the aquatic environment and increased concern on unknown effects induced by their release into the aquatic ecosystem. An improved understanding of the environmental transformation processes of NPs of various surface characteristics is hence imperative for risk assessment and management. This study presents results on effects of natural organic matter (NOM) on the environmental transformation and dissolution of metal and metal oxide NPs of different surface and solubility properties in synthetic freshwater (FW) with and without NOM. Adsorption of NOM was evident on most of the studied NPs, except Sb and Sb2O3, which resulted in the formation of negatively charged colloids of higher stability and smaller size distribution compared with the same NPs in FW only. The dissolution rate of the NPs in the presence of NOM correlated with the strength of interactions between the carboxylate group of NOM and the particle surface, and resulted in either no (Mn, Sb, ZnO NPs), increased (Co, Sn NPs) and decreased (Ni, NiO, Sb2O3, Y2O3 NPs) levels of dissolution. One type of metal NP from each group (Mn, Ni, Sn) were investigated to assess whether observed differences in adsorption of NOM and dissolution would influence their ecotoxic potency. The results showed Mn, Ni, and Sn NPs to generate intracellular reactive oxygen species (ROS) in a time and dose-dependent manner. The extent of ROS generation in FW was similar for both Mn and Ni NPs but higher for Sn NPs. These findings are possibly related to interactions and infiltration of the NPs with the cells, which lead to redox imbalances which could induce oxidative stress and cell damage. At the same time, the presence of NOM generally reduced the intracellular ROS generation by 20-40% for the investigated NPs and also reduced cytotoxicity of Sn NPs, which can be attributed to the stronger interaction of carboxylate groups of NOM with the surface of the NPs.


Bleeding complications associated with warfarin treatment in ischemic stroke patients with atrial fibrillation: a population-based cohort study.
Bleeding events are the major obstacle to the widespread use of warfarin for secondary stroke prevention. Previous studies have not examined the use of risk stratification scores to estimate lifetime bleeding risk associated with warfarin treatment in a population-based setting. The purpose of this study is to determine the lifetime risk of bleeding events in ischemic stroke patients with atrial fibrillation (AF) undergoing warfarin treatment in a population-based cohort and to evaluate the use of bleeding risk scores to identify patients at high risk for lifetime bleeding events. The resources of the Rochester Epidemiology Project Medical Linkage System were used to identify acute ischemic stroke patients with AF undergoing warfarin treatment for secondary stroke prevention from 1980 to 1994. Medical information for patients seen at Mayo Clinic and at Olmsted Medical Center was used to retrospectively risk-stratify stroke patients according to bleeding risk scores (including the HAS-BLED and HEMORR2HAGES scores) before warfarin initiation. These scores were reassessed 1 and 5 years later and compared with lifetime bleeding events. One hundred patients (mean age, 79.3 years; 68% women) were studied. Ninety-nine patients were observed until death. Major bleeding events occurred in 41 patients at a median of 19 months after warfarin initiation. Patients with a history of hemorrhage before warfarin treatment were more likely to develop major hemorrhage (15% versus 3%, P = .04). Patients with baseline HAS-BLED scores of 2 or more had a higher lifetime risk of major bleeding events compared with those with scores of 1 or less (53% versus 7%, P < .01), whereas those with HEMORR2HAGES scores of 2 or more had a higher lifetime risk of major bleeding events compared with those with scores of 1 or less (52% versus 16%, P = .03). Patients with an increase in the HAS-BLED and HEMORR2HAGES scores during follow-up had a higher remaining lifetime risk of major bleeding events compared with those with no change. Our findings indicate high lifetime bleeding risk associated with warfarin treatment for patients with ischemic stroke. Risk stratification scores are useful to identify patients at high risk of developing bleeding complications and should be recalculated at regular intervals to evaluate the bleeding risk in anticoagulated patients with ischemic stroke.


Experimental evaluation of rigor mortis. IV. Change in strength and evolution of rigor mortis in the case of physical exercise preceding death.
Evolution of rigor mortis in rats exercised before death shows the following characteristics with respect to controls: (1) Its intensity is increased in the initial phase. (2) It reaches its maximum development at the same time. (3) Higher maximum values are reached (in our experiments 1.39 times the maximum values for controls). (4) Higher values are maintained from 100 minutes to 16 hours with statistically significant differences. (5) It attains resolution at the same time.


[Severe irradiation injury due to insufficient diagnostics (chronic osteomyelitis--Ewing-sarcoma) (author's transl)].
The differential diagnosis between Ewing-sarcoma and chronic osteomyelitis can only be established by scintigraphy, angiography and histological specimen. Treating such a case by irradiation only under suspicion of an Ewing-sarcoma is hazardous and will be followed by severe damage of the body.


Differentiation of chronic mass-forming pancreatitis from pancreatic ductal adenocarcinoma using contrast-enhanced computed tomography.
Both chronic mass-forming pancreatitis (CMFP) and pancreatic ductal adenocarcinoma (PDAC) are focal pancreatic lesions and share very similar clinical symptoms and imaging performance. There is great clinical value in preoperative differentiation of those two lesions. The purpose of this study was to investigate the value of computed tomography (CT) features in discriminating CMFP from PDAC. Forty-seven patients with pathologically confirmed PDAC and 21 patients with CMFP were included in this study. Demographic and CT features, including tumor location, size, margin, pancreatic or bile duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, and tumor contrast enhancement, were retrospectively analyzed and compared. Multivariate logistic regression analyses were adopted to identify relevant CT imaging features to discriminate CMFP from PDAC. There were significant differences between CMFP and PDAC with respect to main pancreatic duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, and tumor contrast enhancement. Delayed contrast enhancement (>70.5 Hounsfield units) showed high sensitivity and specificity of 84.2% and 84.7%. The areas under the curve (AUCs) of the predicting models based on qualitative and quantitative variables were 0.770 (95% CI: 0.660-0.880) and 0.943 (95% CI: 0.888-0.999), respectively. When all significant variables were used in combination to build a predicting model, the AUC was 0.969 (95% CI: 0.930-1.000) with 84.2% sensitivity and 94.7% specificity. Main pancreatic duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, tumor size, and tumor contrast enhancement were shown to be useful CT imaging features in discriminating CMFP from PDAC.


Motor unit firing behavior during prolonged 50% MVC dorsiflexion contractions in young and older adults.
The purpose of this study was to investigate changes in motor unit firing behavior during prolonged contractions in young and older adults. Motor unit activity was recorded from the tibialis anterior of 16 subjects (8 young and 8 older), while they performed isometric dorsiflexion at 50% MVC until task failure. Mean motor unit firing rate, the standard deviation (SD), and coefficient of variation (CV) of the interspike intervals, and number of doublet discharges were calculated for a total of 52 motor units, tracked for an average of 92.9+/-68.6s. There was no age-related difference in the time to task failure. A modest decline in firing rate was observed in 71% of the motor units, with no significant age-related difference. The SD and CV of the interspike interval had a positive slope in 65% and 69% of the motor units, respectively, with no significant age-related differences. The number of doublet discharges remained stable throughout the contraction. Both groups exhibited motor unit dropout (discharge cessation) during the contraction. Thus, a fatiguing task producing modest changes in firing rate in young and older adults is accompanied by an appreciable increase in firing rate variability. The incidence of doublet discharges is not increased during fatiguing contractions.


One-year prospective study on the effect of workplace bullying on long-term sickness absence.
To examine the effect of workplace bullying on long-term sickness absence using a prospective design. Although bullying has been identified as a serious problem in the health care sector, little attention has been given to the possible effect of workplace bullying on long-term sickness absence and its implications. The sample consisted of 9949 employees (78.1% response rate) working in the elderly-care sector in 36 Danish municipalities. Long-term sickness absence was measured by linking a survey on work and health to the national register on social transfer payments. Among the 1171 employees that were bullied at work in the past 12 months, 1.8% were frequently bullied and 7.3% were occasionally bullied. The risk of long-term sickness absence was higher for those frequently bullied even after adjusting for psychosocial work characteristics [rate ratio (RR) = 1.92, confidence interval (CI): 1.29-2.84; P < 0.05]. This is the first prospective study that explored the effect of both frequent and occasional bullying on long-term sickness absence among health care employees. The effect of frequent bullying on long-term sickness absence was independent of the psychosocial work characteristics. Workplace bullying might impact negatively the quality of care and patients safety.


CMIP6 models informed summer human thermal discomfort conditions in Indian regional hotspot.
The frequency and intensity of extreme thermal stress conditions during summer are expected to increase due to climate change. This study examines sixteen models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) that have been bias-adjusted using the quantile delta mapping method. These models provide Universal Thermal Climate Index (UTCI) for summer seasons between 1979 and 2010, which are regridded to a similar spatial grid as ERA5-HEAT (available at 0.25° × 0.25° spatial resolution) using bilinear interpolation. The evaluation compares the summertime climatology and trends of the CMIP6 multi-model ensemble (MME) mean UTCI with ERA5 data, focusing on a regional hotspot in northwest India (NWI). The Pattern Correlation Coefficient (between CMIP6 models and ERA5) values exceeding 0.9 were employed to derive the MME mean of UTCI, which was subsequently used to analyze the climatology and trends of UTCI in the CMIP6 models.The spatial climatological mean of CMIP6 MME UTCI demonstrates significant thermal stress over the NWI region, similar to ERA5. Both ERA5 and CMIP6 MME UTCI show a rising trend in thermal stress conditions over NWI. The temporal variation analysis reveals that NWI experiences higher thermal stress during the summer compared to the rest of India. The number of thermal stress days is also increasing in NWI and major Indian cities according to ERA5 and CMIP6 MME. Future climate projections under different scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5) indicate an increasing trend in thermal discomfort conditions throughout the twenty-first century. The projected rates of increase are approximately 0.09 °C per decade, 0.26 °C per decade, and 0.56 °C per decade, respectively. Assessing the near (2022-2059) and far (2060-2100) future, all three scenarios suggest a rise in intense heat stress days (UTCI > 38 °C) in NWI. Notably, the CMIP6 models predict that NWI could reach deadly levels of heat stress under the high-emission (SSP5-8.5) scenario. The findings underscore the urgency of addressing climate change and its potential impacts on human well-being and socio-economic sectors.


Cigarette smoking, leukemia, and multiple myeloma.
To evaluate previously reported associations with cigarette smoking, the incidence of leukemia and multiple myeloma was determined with follow-up of up to 24 years of 57,224 never-smokers, 20,928 former smokers, and 64,839 current cigarette smokers who received multiphasic health checkups. Cigarette smoking was associated with the development of acute nonlymphocytic leukemia in men only (relative risk, 2.8; 95% confidence interval, 1.2 to 6.4). Chronic myeloid leukemia showed an association with smoking of borderline significance in men only. Chronic lymphocytic leukemia and multiple myeloma were not related to cigarette smoking. In the men with acute nonlymphocytic leukemia there was a suggestion of a dose-response relation but it was not statistically significant. The association of cigarette smoking with acute nonlymphocytic leukemia was not explained by alcohol or coffee consumption or exposure to occupational hazards. This study adds to the growing body of evidence that cigarette smoking predisposes to acute nonlymphocytic leukemia in men.


Escherichia coli glucuronylsynthase: an engineered enzyme for the synthesis of beta-glucuronides.
The glycosynthase derived from E. coli beta-glucuronidase catalyzes the glucuronylation of a range of primary, secondary, and aryl alcohols with moderate to excellent yields. The procedure provides an efficient, stereoselective, and scalable single-step synthesis of beta-glucuronides under mild conditions.


Psychological issues in genetic counselling.
In the case of prenatal diagnosis and its possible consequences, there is discussion on the limits of freedom of decision. Nevertheless, there is considerable agreement that the individual family should be helped to make its own decisions and to live with these decisions. To attain these goals psychological issues are necessarily of importance. This paper presents concepts on these psychological issues and how they have to be taken into account in counselling. The character of mutuality in providing information is emphasized as well as cognitive and affective processes determining the understanding and outcome of genetic counselling. The role of prior knowledge, expectations, experience, and meaning attached to the disease and its consequences are discussed. Tasks for the counselling staff ranging from preparation for genetic counselling to follow-ups, counselling skills, and methods facilitating the counselling process are specified.


New insights into the effects of self-association of the cation [Au[C(NHMe)(2)](2)](+) on its solid state structure and luminescence.
Colorless [Au[C(NHMe)(2)](2)]X.H(2)O (X = Cl or Br) crystallize as dimers with Au.Au separations of 3.1231(3) A (Cl salt) and 3.1297(4) A (Br salt) between the linear, two-coordinate cations, and there is no direct interaction of Au(I) with the halide ions which are hydrogen bonded to ligand N-H groups and the water molecules. The luminescence of these dimers occurs at higher energy than that observed in extended chains of the same cation in the corresponding (PF(6))(-) and (BF(4))(-) salts and shows the important effects of aggregation on the observed luminescence.


Highly stable and efficient Cr(VI) immobilization from water by adsorption with the La-substituted ferrihydrite as a naturally-occurring geosorbent in soils.
Ferrihydrite (Fh) is a vital geosorbent in the natural environment. Here, Fh materials with lanthanum (La) substituted in varied La/La + Fe ratios were synthesized, and these La-Fh materials were investigated in-depth via adsorption kinetic and isothermal experiments to explore their adsorption performance for chromate [Cr(VI)] in soils. Material properties of La-Fh were further characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectrometer (FTIR), and X-ray photoelectron spectroscopy (XPS). The results clearly indicate that La3+ can be integrated into the Fh lattice, but the increase in La amount substituted into Fh is slowed down when the La/La + Fe ratio reaches to a larger value. Those La3+ cations that fail to become integrated may either get adsorbed or form a phase of La(OH)3 on La-Fh surfaces. We also find that La substitution reduces the specific surface area (SSA) of La-Fh samples but raises their pHpzc, which hampers La-Fh conversion to hematite and thus increases the chemical stability. These changes are related to the La-Fh structure and surface aspects, but they do not negatively affect the Cr(VI) adsorption efficacy, which can be promoted over a wide pH range to an alkaline pH. For instance, the maximum adsorption amount of Cr(VI) by 20%La-Fh is 30.2 mg/g at a near-neutral pH. However, the entire chromate adsorption processes are affected by H2PO4- and humic acid due to their strong affinities for Cr(VI), but almost not influenced by NO3- and Cl-. All the Cr(VI)-Fh reactions are well described by the fitted adsorption Freundlich model and conform to the pseudo-second-order reaction kinetic equation. The mechanisms which enhance La-Fh's adsorption ability for Cr(VI) are governed by chemical interactions, because La substitution can increase the hydroxyl density on Fh surfaces and thus improve the reactivity of La-Fh towards Cr(VI), leading to an evidently enhanced Cr(VI) immobilization onto La-Fh.


Retroperitoneal fibrosis: case series of five patients and review of the literature.
Chronic periaortitis (CP) is an umbrella term used to describe a group of nosologically allied conditions that include idiopathic retroperitoneal fibrosis (Ormond's disease), inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis. Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighboring structures-ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Here we describe a 5 years follow-up (2006-2011) of 5 patients admitted to our hospital with symptoms, laboratory, imaging and pathologic finding compatible with retroperitoneal fibrosis. We review our clinical course of our patient with respect to the literature.


From funny current to HCN channels: 20 years of excitation.
The "funny" (pacemaker) current has unusual characteristics, including activation on hyperpolarization, permeability to K(+) and Na(+), modulation by internal cAMP, and a tiny, single-channel conductance. In cardiac cells and neurons, pacemaker channels control repetitive activity and excitability. The recent cloning of HCN subunits provides new insight into the molecular basis for the funny channel properties.


Would doctors dream of electric blood bankers? Large language model-based artificial intelligence performs well in many aspects of transfusion medicine.
Large language models (LLMs) excel at answering knowledge-based questions. Many aspects of blood banking and transfusion medicine involve no direct patient care and require only knowledge and judgment. We hypothesized that public LLMs could perform such tasks with accuracy and precision. We presented three sets of tasks to three publicly-available LLMs (Bard, GPT-3.5, and GPT-4). The first was to review short case presentations and then decide if a red blood cell transfusion was indicated. The second task was to answer a set of consultation questions common in clinical transfusion practice. The third task was to take a multiple-choice test experimentally validated to assess internal medicine postgraduate knowledge of transfusion practice (the BEST-TEST). In the first task, the area under the receiver operating characteristic curve for correct transfusion decisions was 0.65, 0.90, and 0.92, respectively for Bard, GPT-3.5 and GPT-4. All three models had a modest rate of acceptable responses to the consultation questions. Average scores on the BEST-TEST were 55%, 40%, and 87%, respectively. When presented with transfusion medicine tasks in natural language, publicly available LLMs demonstrated a range of ability, but GPT-4 consistently scored very well in all tasks. Research is needed to assess the utility of LLMs in transfusion medicine practice. Transfusion Medicine physicians should consider their role alongside such technologies, and how they might be used for the benefit and safety of patients.


Dermatoses associated with travel to Burkina Faso and diagnosed by means of teledermatology.
The pattern of dermatoses occurring in travellers to tropical areas is poorly documented. To diagnose skin diseases in travellers to Burkina Faso by means of teledermatology; to assess the educational value of teledermatology for the local general practitioner (GP). Patients (Westerners and Burkinabese nationals) were included in the study if they presented with a cutaneous disease to the GP based in Ouagadougou, Burkina Faso. Images of the skin lesions were acquired with a point-and-shoot digital camera and sent via the Internet, together with the clinical history. Diagnostic concordance between dermatologists in France and the GP in Ouagadougou was analysed as a simple proportion of agreement and 95% confidence interval. One hundred and twenty-four patients (M/F ratio 1.17; 80.6% Westerners) were included in the study. One hundred and thirty dermatoses were identified: 73 (56%) were of infectious origin, and 19 (15%) were related to eczematous dermatitis. The skin infections were mainly due to bacteria (18%), fungi (14%) or arthropods (13%). Parasitic dermatoses were observed only in Burkinabese nationals. Among Westerners, fungal dermatoses were observed only in long-term residents. The diagnostic agreement between the local GP and the remote dermatologists was 49% overall (95% confidence interval 41-58). Agreement between the GP and the dermatologists on the dermatological category improved significantly over time (P<0.05). Telemedecine can improve the management of cutaneous diseases among Western travellers. Most dermatoses observed in Western travellers to Burkina Faso are of infectious origin. Teledermatology has educational value for local GPs.


The effect of ribose and purine modified adenosine analogues on the secretion of histamine from rat mast cells induced by ionophore A23187.
The purine nucleosides adenosine and 2',5'-dideoxyadenosine (2',5'ddAdo) enhance and inhibit respectively the anti-IgE-induced secretion of histamine and transient rise in cellular levels of cyclic AMP in rat mast cells. These findings have provided evidence for a role for cyclic AMP in the activation of mast cell secretion. It has been generally accepted that the nucleosides mediate their effects on mast cells by altering adenylate cyclase activity. We have investigated the effect of various purine and ribose modified analogues of adenosine on secretion of histamine from rat mast cells induced by ionophore A23187 for which there is no associated elevation in cyclic AMP and no evidence for the activation of adenylate cyclase in its mechanism of action. Adenosine and N6, phenylisopropyladenosine (0.01-1000 microM) (activators of adenylate cyclase in many tissues) enhanced the secretion of histamine induced by ionophore A23187 and anti-IgE. Two inhibitors of adenylate cyclase had differential effects on secretion. 2',5'ddAdo (100-1000 microM) inhibited both A23187-and anti-IgE-mediated secretion; whilst 9-beta-D-arabinofuranosyladenine had no effect on secretion. These results suggest that the ability of these nucleosides to modulate histamine secretion is unrelated to their effects on adenylate cyclase.


The effect of Clinical Practice Guidelines on prescribing practice in mental health: A systematic review.
Clinical Practice Guidelines are succinct evidence-based recommendations and in psychiatry, exist to advise on psychotropic prescribing to effectively treat mental health conditions whilst minimising medication adverse effects. Implementation of psychiatric guidelines have, in the past, demonstrated little and transient impact on clinical practice. How effective prescribing guidelines are in aligning practice with evidence currently is unknown and this systematic review aimed to investigate said efficacy. Literature searches were performed on MEDLINE, EMBASE, and CINAHL up to September 2019 and articles were selected by two reviewers independently with discrepancies resolved by a third reviewer. The review identified 18 eligible articles pertaining to the following conditions: depressive disorders, psychotic disorders, post-traumatic stress disorder, anxiety disorders, bipolar affective disorder, attention deficit/hyperactivity disorder, borderline personality disorder, and opiate addiction with depression guidelines being the most frequently evaluated. Seven studies revealed guidelines effected no change in psychotropic prescribing. The remaining studies illustrated that even when practice was changed, the effect was generally small, emphasising the need to change guideline development and implementation, taking into account obstacles or opportunities specific to psychotropic pharmacotherapy.


Streptozotocin-induced diabetes in rats causes neuronal deficits in tyrosine hydroxylase and 5-hydroxytryptamine specific to mesenteric perivascular sympathetic nerves and without loss of nerve fibers.
The aim of this study was to investigate the possibility that inadequate venous return to the heart in diabetes is the result of a neuropathy which affects autonomic nerves supplying the splanchnic vasculature. Mesenteric veins from rats with streptozotocin-induced diabetes were markedly dilated in vivo compared to veins from control animals. Dilation appeared to be the result of loss of muscle tone rather than hypertrophy or hyperplasia of the vessel wall. Using quantification by image analysis and double-labeling immunohistochemistry on mesenteric veins, significant reductions in the density of nerve plexuses staining for 5-hydroxytryptamine (5-HT) and tyrosine hydroxylase (TH) were shown in vessels from diabetic rats compared to controls. No reductions were observed in the density of nerve plexuses stained for the neuronal marker, PGP 9.5, or for substance P (SP), a marker for afferent nerve fibers. These results indicate neurochemical deficits in experimentally induced diabetes which are specific to perivascular noradrenergic nerves and which, within the time-scale of our experiments, do not involve loss of nerve fibers. These deficits may contribute to an increase in venous pooling of blood in the splanchnic vasculature of diabetic rats and thus to inadequate venous return to the heart.


Therapeutic effect of oligomeric proanthocyanidin in cuprizone-induced demyelination.
What is the central question of this study? Oligomeric proanthocyanidin has the capacity to alleviate abnormalities in neurological functioning. However, whether oligomeric proanthocyanidin can reduce the progression of demyelination or promote remyelination in demyelinating diseases remains unknown. What is the main finding and its importance? Oligomeric proanthocyanidin can improve cuprizone-induced demyelination by inhibiting immune cell infiltration, reversing overactivated microglia, decreasing the inflammatory cytokines secreted by inflammatory cells and decreasing the production of myelin oligodendrocyte glycoprotein35-55 -specific antibody in the brain. Demyelinating diseases of the CNS, including multiple sclerosis, neuromyelitis optica and acute disseminated encephalomylitis, are characterized by recurrent primary demyelination-remyelination and progressive neurodegeneration. In the present study, we investigated the therapeutic effect of oligomeric proanthocyanidin (OPC), the most effective component of grape seed extract, in cuprizone-fed C57BL/6 mice, a classic demyelination-remyelination model. Our results showed that OPC attenuated abnormal behaviour, reduced demyelination and increased expression of myelin basic protein and expression of O4+ oligodendrocytes in the corpus callosum. Oligomeric proanthocyanidin also reduced the numbers of B and T cells, activated microglia in the corpus callosum and inhibited secretion of inflammatory factors. Furthermore, concentrations of myelin oligodendrocyte glycoprotein-specific antibodies were significantly reduced in serum and brain homogenates after OPC treatment. Together, these results demonstrate a potent therapeutic effect for OPC in cuprizone-mediated demyelination and clearly highlight multiple effects of this natural product in attenuating myelin-specific autoantibodies and the inflammatory microenvironment in the brain.


Longitudinal study of tissue- and subunit-specific obesity-induced regulation of the pyruvate dehydrogenase complex.
The tissue-specific expression of the mitochondrial pyruvate dehydrogenase complex (PDHc) has been studied in an animal model of obesity with hyperinsulinemia, the obese (fa/fa) Zucker rat. Liver and heart were obtained from 4 and 8 week-old obese rats and age-matched lean animals, and in each tissue the following parameters were analyzed: (1) total activity of the mitochondrial PDHc; (2) abundance of the mitochondrial PDHc subunits on Western blots; and (3) abundance of the E1alpha and E1beta subunit mRNAs on Northern blots and semi-quantitative RT-PCR. Regardless of age, obese rats showed an increase in liver total PDHc activity and a coordinate increase in liver E1alpha and E1beta PDHc subunit abundance. At 4 weeks, obese rats also showed an increase in liver PDH E1alpha mRNA level, but regardless of age E1beta mRNA level was unchanged. In contrast, neither total PDHc activity nor the concentration of its protein subunits were increased in heart of obese rats. Thus, obese Zucker rats display a liver-specific early increase in PDHc which results from a selective up-regulation of the E1alpha gene expression.


Congenital mesoblastic nephroma associated with polyhydramnios and hypercalcemia.
Congenital mesoblastic nephroma (CMN) can present with atypical clinical and imaging findings. A premature male neonate was born to an 18-year-old woman after 33 weeks' gestation, which was complicated by polyhydramnios and placenta abruptio. A right abdominal mass was diagnosed antenatally. From the 1st day of life, the newborn had hypercalcemia with initially normal parathormone levels and polyuria for the first hours of life and normal urine output afterwards. Ultrasonographic study and magnetic resonance imaging of the abdomen showed at the upper pole of the right kidney a heterogeneous, solid, poorly defined mass, partially surrounded by a subcapsular fluid collection mimicking malignant rhabdoid tumor of the kidney. Surgical resection revealed a CMN of mixed, classic, and in areas, cellular type. One year after the resection, the patient is asymptomatic and normocalcemic. In conclusion, CMN may present with atypical clinical and imaging findings, necessitating an extensive work-up in order to exclude highly malignant renal tumors of the neonatal period.


Potential of magnetic resonance spectroscopic imaging in predicting absence of prostate cancer in men with serum prostate-specific antigen between 4 and 10 ng/ml: a follow-up study.
Screening for prostate cancer using serum prostate-specific antigen (PSA) determination has a positive predictive value of only 30% to 42% for a PSA level between 4 and 10 ng/mL. Magnetic resonance spectroscopic imaging (MRSI), which identifies cancer on the basis of changes in cellular metabolite levels, might be able to identify patients with noncancerous PSA elevation and help avoid unnecessary biopsies. We tested this hypothesis by evaluating the incidence of prostate cancer in men with a PSA level of 4 to 10 ng/mL and a negative MRSI study. A total of 155 men underwent a three-dimensional proton MRSI of the prostate before transrectal ultrasound-guided biopsy for clinical indications. MRSI was performed using an endorectal coil on a 1.5-T magnetic resonance scanner. Patients with no voxels positive for malignancy underwent standard sextant biopsy, and additional MRSI-targeted biopsies were obtained in men with suspicious or malignant voxels. Patients with a biopsy negative for cancer underwent repeat serum PSA estimation every 6 months for a minimum of 18 months. Of the 155 men, 36 (mean PSA level of 6.47 ng/mL, range 4.25 to 9.9) had no malignant voxels on MRSI. None of them were positive for cancer on biopsy. Of these 36 men, 26 completed at least 18 months (mean 26.9, range 18 to 44) of follow-up. Four patients required repeat biopsies and one, with a persistently elevated PSA level was diagnosed with prostate cancer 29 months after the initial MRSI. The results of our study have shown that prostate biopsy can be deferred in patients with an increased serum PSA of 4 to 10 ng/mL if their MRSI does not show any malignant voxels.


Alternative sources of valine and isoleucine for prompt reduction of plasma leucine in maple syrup urine disease patients: A case series.
In maple syrup urine disease (MSUD), leucine (Leu) accumulation, and its metabolites cause brain toxicity, and at diagnosis rapid plasma Leu reduction is essential. Valine (Val) and isoleucine (Iso) supplements are necessary to promote anabolism and enable prompt reduction of plasma Leu. Val/Iso supplements are unavailable in Iran, so an alternative source was necessary. An emergency protocol was developed using an unconventional source of Val and Iso to prompt reduction of high plasma Leu levels during an acute metabolic crisis to prevent brain encephalopathy and neurological sequelae. Five children with classical MSUD were referred aged 1-25 months, with a prolonged high plasma Leu of more than 1500 μmol/L and acute symptoms (irritability, poor feeding, and hypotonia). Initially, breast milk/regular infant formula was stopped. Val and Iso were given in calculated amounts from a Leu-free formula containing Iso/Val (Xleu Maxamaid, Nutricia Ltd.) to promote anabolism. It was prescribed for a controlled and limited time with a branched chain amino acid (BCAA) free formula. Frequent amino acid monitoring was conducted. Natural protein was re-added after normalizing plasma Leu. Plasma Leu declined by a median (range) of 1677 (1501-1852) μmol/L within 3-4 days of intervention. The median follow-up time was 24 months (range: 14-32) and patients showed improvement in motor and cognitive skills after normalizing plasma Leu (75-200 μmol/L). Most had improvement in their head circumference (n = 4). Due to the unavailability of individual Val/Iso supplements, a Leu-free formula rapidly lowered plasma Leu concentrations during acute crisis, to prevent cerebral edema and brain damage in MSUD.


The Edinburgh Dental Dispensary 1860 to 1879.
The Edinburgh Dental Dispensary began in 1860 as a private charity to provide free treatment for the poor and to teach students. In 1862 the dispensary became a public charity in new premises with a committee of managers. Dental students were admitted in 1864. By 1867 the annual number of patient attendances was about 4,000 and the mainstay of treatment was extraction. Housekeepers were the only support staff. The dispensary was constantly impecunious; in 1869 the managers considered discontinuing the service. In February 1879, following the 1878 Dentists Act, the dispensary was merged into the new Edinburgh Dental Hospital and School.


A reassessment of the effects of luminal [Ca2+] on inositol 1,4,5-trisphosphate-induced Ca2+ release from internal stores.
Inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release from intracellular stores displays complex kinetic behavior. While it well established that cytosolic [Ca2+] can modulate release by acting on the InsP3 receptor directly, the role of the filling state of internal Ca2+stores in modulating Ca2+ release remains unclear. Here we have reevaluated this topic using a technique that permits rapid and reversible changes in free [Ca2+] in internal stores of living intact cells without altering cytoplasmic [Ca2+], InsP3 receptors, or sarcoendoplasmic reticulum Ca2+ ATPases (SERCAs). N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylene diamine (TPEN), a membrane-permeant, low affinity Ca2+ chelator was used to manipulate [Ca2+] in intracellular stores, while [Ca2+] changes within the store were monitored directly with the low-affinity Ca2+ indicator, mag-fura-2, in intact BHK-21 cells. 200 microM TPEN caused a rapid drop in luminal free [Ca2+] and significantly reduced the extent of the response to stimulation with 100 nm bradykinin, a calcium-mobilizing agonist. The same effect was observed when intact cells were pretreated with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid(acetoxymethyl ester) (BAPTA-AM) to buffer cytoplasmic [Ca2+] changes. Although inhibition of Ca2+ uptake using the SERCA inhibitor tBHQ permitted significantly larger release of Ca2+ from stores, TPEN still attenuated the release in the presence of tBHQ in BAPTA-AM-loaded cells. These results demonstrate that the filling state of stores modulates the magnitude of InsP3-induced Ca2+release by additional mechanism(s) that are independent of regulation by cytoplasmic [Ca2+] or effects on SERCA pumps.


Females Are More Likely Than Males to Fill an Opioid Prescription in the Year After Anterior Cruciate Ligament Reconstruction.
To report rates of preoperative and postoperative opioid use between male and female patients and to identify risk factors for extended opioid use following anterior cruciate ligament reconstruction (ACLR). Patients undergoing ACLR between 2011 and 2018 were identified from the PearlDiver database. The opioid refill rates for males vs females were compared at monthly intervals for 1 year after ACLR. Patients who filled an opioid prescription <3 months before surgery were classified as opioid users, while those who had never filled one were classified as nonopioid users. Of 106,995 ACLR patients, 37,890 (35.4%) were opioid users <3 months before surgery, and 37,554 (35.1%) had never filled an opioid prescription. Of the preoperative opioid users, 20,413 (53.9%) were female and 17,477 (46.1%) were male (P < .001). Postoperatively, females were at higher risk of filling an opioid prescription at each monthly interval, except for the first month after surgery. The refill rate for opioid users was also higher than that for nonopioid users at each monthly interval after ACLR. In addition to patient sex, a preoperative diagnosis of anxiety/depression, low back pain, myalgia, a history of drug dependence, alcohol abuse, and tobacco use increased a patient's risk of filling an opioid prescription postoperatively. This study demonstrated that females are significantly more likely to be opioid users than males prior to ACLR and are more likely to continue to refill an opioid prescription in the year following surgery. Multiple risk factors were associated with prolonged postoperative opioid utilization, including female sex, anxiety/depression, low back pain, myalgia, a history of drug dependence, alcohol abuse, and tobacco use. Level III, retrospective cohort study.


Platelet-rich plasma in periodontal defect treatment after extraction of impacted mandibular third molars: Retraction.
[This retracts the article on p. 139 in vol. 3, PMID: 23833487.].


6-Gingerol suppresses tumor cell metastasis by increasing YAPser127 phosphorylation in renal cell carcinoma.
According to the World Health Organization, the incidence and mortality rates of renal cell carcinoma (RCC) are rapidly increasing worldwide. Serious side effects caused by immune therapy and resistance to targeted drug therapy are urgent clinical problems facing kidney treatment. There is increasing global interest in developing natural products with a reduced number of side effects as adjunctive therapeutic options for RCC. Ginger is a spice and herbal remedy used worldwide, and 6-gingerol is a major pharmacologically active ingredient in ginger. In our study, we found that 6-gingerol suppressed RCC cell migration and metastasis in vitro and in vivo. Moreover, reduction in MMP2, Slug, and Vimentin protein levels was observed following 6-gingerol treatment of 786-O and ACHN cells. Furthermore, we revealed the mechanisms underlying the ability of 6-gingerol to inhibit RCC cell migration and metastasis. 6-Gingerol increased yes-associated protein (YAP)ser127 phosphorylation and reduced YAP levels in cell nuclei. We also used a series of loss-of-function and gain-of-function experiments to support our results. Western blot results showed that MMP2, Slug, and Vimentin protein expression was downregulated in YAP-silenced cells and upregulated in YAP-overexpressing cells. Transwell data demonstrated that YAP suppressed RCC migration ability. Immunofluorescence images showed that 6-gingerol decreased YAP levels, leading to disordered F-actin and a reduction in cell lamellipodia. Overall, our results indicated that 6-gingerol is a potential antimetastatic compound for use in kidney therapy.


A 3 kDa peptide is involved in the chemoattraction in vitro of the male Schistosoma mansoni to the female.
In vitro experiments on adult Schistosoma mansoni worms have shown the existence of mutual attraction between males and females mediated by factor(s) released by both sexes. Males were attracted to female-released factor(s), which was found in <30 kDa fractions. A combination of bioassays, size fractionations, chromatographic and chemical and enzymatic treatments were used to identify female-released factor(s) that attracted males. Boiling reduced the attraction of males towards female incubate. Male-attractant factor(s) was not in the female vomitus, and TLC showed the absence of lipids and carbohydrates in the female incubate. Male-attractant factor(s) was found to be sensitive to proteases and to be hydrophilic in nature. Using RP-HPLC, a 3260 Da peptide released by S. mansoni adult females that plays a role in attracting the males was identified, purified and partially characterized. A partial amino acid sequence <QVHHQK> of that peptide was obtained using MALDI peptide-MS and MALDI-TOF/TOF.


Left Ventricular Outflow Obstruction From Mechanical Circulatory Support in Critical Aortic Stenosis: A Cautionary Tale.
We submit a cautionary tale of a patient with critical aortic stenosis presenting with acute myocardial infarction and cardiogenic shock, who underwent balloon aortic valvuloplasty, insertion of a transvalvular left percutaneous ventricular assist device and high-risk percutaneous coronary intervention, with a post-operative course complicated by outflow obstruction from the device itself. (Level of Difficulty: Intermediate.).


Spinal cord missile injuries during the Lebanese civil war.
Spinal cord injuries due to penetrating wounds are not uncommon. The management of these injuries remains controversial especially with regard to the effect of laminectomy on the neurological outcome. Between 1980 and 1989, 64 patients injured by bullets and shell fragments to the spinal cord were reviewed. There were 58 males and 6 females: 24 injuries (37.5%) involved the cervical spine, 37 (57.8%) the dorsal spine, and 3 (4.7%) the lumbar spine. One group (group I) consisted of 47 patients (73.4%) who had immediate and complete sensorimotor loss of function. Another group (group II) contained 13 patients (20.3%) who presented with incomplete and non-progressive spinal cord deficit. One patient (1.6%) (group III) had progressive spinal cord deficit. Three patients (4.7%) (group IV) had injuries to the cauda equina. The results were analyzed using a chi-squared test when possible. In group I, 20 patients (42.5%) underwent laminectomy with no recovery, and 27 (57.5%) were treated conservatively, with 1 patient (3.7%) achieving marked improvement (p > 0.05). In group II, 3 patients (23.1%) underwent laminectomy with the 3 (100%) improved, and 10 patients (76.9%) were treated conservatively, with 8 (80%) recovering (p > 0.05). Our data in groups I and II agree with previously published literature that shows no significant advantage of performing laminectomies following penetrating spinal cord injuries. Moreover, group I patients had a poor prognosis whether laminectomy was done or not, and group II patients had a good prognosis whether laminectomy was done or not.


Phosphodiesterase-5 Inhibitory Activity of Canthin-6-One Alkaloids and the Roots of Eurycoma longifolia and Eurycoma harmandiana.
Eurycoma longifolia (EL) and Eurycoma harmandiana (EH) are natural medicinal plants belonging to the Simaroubaceae family, and are well-known for their ability to enhance male sexual performance. The present study investigated the phosphodiesterase-5 (PDE-5) inhibitory activity of intact roots of EL and EH. Additionally, canthin-6-one alkaloids, β-carboline alkaloids, and quassinoids were also screened for PDE-5 inhibitory activity. We developed in vitro root and callus cultures of EL and EH to determine their PDE-5 inhibitory activity. Our results indicated that canthin-6-one alkaloids, which include canthin-6-one-9-O-β-D-glucopyranoside, 9-methoxycanthin-6-one, canthin-6-one, and 9-hydroxycanthin-6-one, exhibited PDE-5 enzymatic inhibitory activity, with IC50 values of 2.86±0.23, 3.30±1.03, 4.31±0.52, and 4.66±1.13 μM, respectively. The ethanolic extract of the intact roots of EL and EH, and the in vitro root culture of EH had large amounts of canthin-6-one alkaloids (1.50±0.04, 2.12±0.03, and 3.48±0.08 mg/g dry weight, respectively), and showed potent PDE-5 inhibition. Our findings indicate that in vitro root cultures of EH may be used to replace intact plants, and canthin-6-one-9-O-β-D-glucopyranoside should be further investigated for development as a health supplement.


[Idiopathic congenital dilatation of the common bile duct and pregnancy. Report of one case, reflexions and comments (author's transl)].
Congenital idiopathic dilatation of the common bile duct, called commonly and incorrectly congenital cyst of the common bile duct, is sometimes diagnosed during pregnancy. The latter may be the source of severe complications. The disease should thus be treated rapidly, even if the pregnancy is at a late stage. In a case of this type we carried out surgical treatment in two stages: firstly simple external drainage of the common bile duct and of the gall bladder and only after labour has been brought to term by Caesarian section, for breech presentation, was a cystojejunostomy carried out on a Y shaped jejunal loop.


Stereo-controlled synthesis of functionalized tetrahydropyridines based on the cyanomethylation of 1,6-dihydropyridines and generation of anti-hepatitis C virus agents.
Densely functionalized tetrahydropyridines were stereoselectively synthesized from 1,6-dihydropyridines. Exploiting a carbonyl group installed at the C3 position of the 1,6-dihydropyridine system, we devised a strategy for cyanomethylation at C2/C6 and subsequent divergent installation of an allyl group at C3/C5 in a highly regio- and stereo-controlled manner. This versatile protocol for programmable functionalization of the 1,6-dihydropyridine system allows the divergent and streamlined synthesis of multiply-substituted tetrahydropyridines as an important class of biologically and medicinally relevant scaffolds. Two of the N-heterocyclic compounds bearing an alkyl nitrile group showed anti-hepatitis C virus (HCV) activity.


The effects of strengthening and high-impact exercises on bone metabolism and quality of life in postmenopausal women: a randomized controlled trial.
The aim of this prospective, randomized controlled 6-month interventional trial was to investigate the effects of strengthening and high-impact exercise training on bone mineral density (BMD), bone turnover markers and health-related quality of life (HRQoL) in postmenopausal women. Forty-two eligible postmenopausal women with osteopenia who referred to our outpatient clinics were included in the study and allocated equally to three groups receiving strengthening exercise, high-impact exercise or no exercise (control). The supervised training program consisted of a one-hour exercise session three times a week for six months. BMD at the L1-L4 and femoral neck, serum bone turnover markers (osteocalcin, OC; N-telopeptides of type I collagen, NTx) and HRQoL were measured at the beginning and sixth months. There was a significant increase in the BMD at the lumbar spine (p=0.017) and femoral neck (p=0.013) in the high-impact group compared to the strengthening and control groups. Serum OC (p=0.033) increased, and NTx (p=0.034) decreased significantly only in the high-impact group. HRQoL improved significantly in both training groups (p< 0.001). Our data suggest that 6-month supervised high-impact exercise training can be effective in prevention of bone loss at lumbar spine and femoral neck. These data also indicate that both supervised training programs improve HRQoL in postmenopausal women.


In vivo isolated liver perfusion technique in a rat hepatic metastasis model: 5-fluorouracil concentrations in tumor tissue.
An in vivo method of isolated rat liver perfusion was developed with true vascular isolation and recirculating perfusate. This new surgical technique to temporarily isolate the liver vascularly, and the perfusion procedure are described in depth. Twelve inbred WAG/RIJ rats were subjected to 25 min of normothermic liver perfusion without chemotherapy, and all rats survived the procedure. Hepatic functional and histological integrity were not significantly altered during perfusion. To determine the role of isolated liver perfusion (ILP) as a means of improved targeting of antitumor agents, 5-fluorouracil (5-FU) concentrations were monitored in hepatic tumor and liver tissues and in systemic plasma using high-performance liquid chromatography. Fifty-one rats with hepatic tumors of colonic origin were randomly assigned to one of three dosage groups (20, 40, or 80 mg/kg) receiving 5-FU by ILP, hepatic artery infusion (HAI), or jugular vein infusion (JVI). ILP resulted in significantly increased 5-FU concentrations in liver tissue. However, no significant differences were found in tumor tissue concentrations of 5-FU between the three treatment modalities. 5-FU concentrations in tumor tissue increased as a function of the dose with ILP, HAI, and JVI. ILP was associated with the lowest systemic drug concentrations. The low systemic 5-FU concentrations with ILP suggest a higher maximum tolerable dose. This mode of treatment deserves to be studied further in our model before conclusions can be drawn regarding its therapeutic potential.