Early Intervention with a Compression Sleeve in Mild Breast Cancer-Related Arm Lymphedema: A 12-Month Prospective Observational Study.
In our previous randomized controlled trial (RCT), the progression/no progression of mild breast cancer-related arm lymphedema (BCRL) was examined among women randomized to a compression group (CG) with a compression sleeve (compression class (ccl) 1) or not (NCG) for 6 months. In the present prospective study, BCRL in the CG and NCG was followed for 12 months. At the end of the RCT, 33 women with mild BCRL were eligible in the CG and 37 in the NCG. The proportional differences in no progression/progression of BCRL were defined as a >2% increase from start of RCT or exceeding 10% in the lymphedema relative volume as measured by the water displacement method. In addition, changes in the lymphedema relative volume and tissue dielectric constant ratio, which measures local tissue water, were examined. At the end of the RCT (i.e., after 6 months), a one-month break of the compression treatment was made in the CG. If the lymphedema relative volume progressed by definition, the compression treatment was resumed and continued, with follow-up of all women at 9 and 12 months. A larger proportion of women in the NCG showed progression (57%, 61%, 67%) compared to the CG (16%, 22%, 31%) at 6, 9, and 12 months (p < 0.001, 0.005, 0.012), respectively. Twelve (33%) women in the NCG did not progress at all. No changes of the lymphedema relative volume and local tissue water were found over time at any follow-ups, but were stable on a low level. To avoid the progression of mild BCRL into a chronic issue in the long-term, compression sleeve ccl 1 may be applied immediately after early diagnosis of mild BCRL.


Stress increases gene expression of phenylethanolamine N-methyltransferase in spleen of rats via pituitary-adrenocortical mechanism.
Gene expression of phenylethanolamine N-methyltransferase (PNMT), the enzyme catalyzing conversion of norepinephrine to epinephrine, has been detected in rat spleen using the reverse transcription polymerase chain reaction. PNMT identity was subsequently verified by Southern blots. Localization of the spleen cells responsible for the PNMT gene expression was investigated by the in situ hybridization and PNMT mRNA was found to be present in the white pulp. The hypothesis that stress may produce an increase in PNMT gene expression in rat spleen was tested and a robust rise in the relative abundance of PNMT mRNA levels was observed after a single or repeated immobilization (about 80%). Adrenalectomy or hypophysectomy completely prevented the immobilization-induced increase in spleen PNMT mRNA levels, suggesting that stress-induced PNMT gene expression in the spleen is regulated predominantly via pituitary-adrenocortical axis. In control animals, however, spleen PNMT was not significantly affected by the ectomies and therefore basal PNMT gene expression might be regulated by different mechanism(s).Thus, PNMT gene expression in the rat spleen is exaggerated by stress stimuli, suggesting its role in physiological regulations.


Approximant-based orientation determination of quasicrystals using electron backscatter diffraction.
Orientation mapping of quasicrystalline materials is demonstrated using crystalline approximant structures in the technique of electron backscatter diffraction (EBSD). The approximant-based orientations are symmetrised according to the rotational point group of the quasicrystal, including the visualization of orientation maps using proper colour keys for quasicrystal symmetries. Alternatively, approximant-based orientation data can also be treated using pseudosymmetry post-processing options in the EBSD system software, which enables basic grain size estimations. Approximant-based orientation analyses are demonstrated for icosahedral and decagonal quasicrystals.


Somato-visceral convergence in cat dorsal root ganglion neurones demonstrated by double-labelling with fluorescent tracers.
We have investigated the possibility of somato-visceral convergence in thoracic sensory dorsal root ganglia (DRG) of cats, using the technique of double-labelling with fluorescent tracers. Combinations of propidium iodide (PI) and Fast Blue (FB) or bisbenzimide (Bb) were found to be the most appropriate. FB or Bb were injected into the splanchnic nerve, and PI into the intercostal nerves. The 9th-11th thoracic cord segments and ganglia were removed after perfusal and frozen sections cut. Single- and double-labelled neurones were observed in the DRG and single-labelled neurones only in the ventral horn (PI) and lateral horn (FB, Bb) of the thoracic spinal cord. The double-labelled neurones accounted for approximately 1% of all labelled neurones, although this may be an underestimate due to the techniques used to prevent migration of the tracer from labelled cells. The double-labelled neurones provide evidence for somato-visceral convergence and indicate that the pre-spinal convergence hypothesis could explain the phenomenon of referred pain.


Electrocardiographic infarct size assessment after thrombolysis: insights from the Acute Myocardial Infarction STudy ADenosine (AMISTAD) trial.
Noninvasive methods are needed to evaluate reperfusion success in patients with acute myocardial infarction (MI). The AMISTAD trial was analyzed to compare MI size and myocardial salvage determined by electrocardiogram (ECG) with technetium Tc 99m sestamibi single-photon emission computerized tomography (SPECT) imaging. Of 236 patients enrolled in AMISTAD, 166 (70 %) with no ECG confounding factors and no prior MI were included in this analysis. Of these, group 1 (126 patients, 53%) had final infarct size (FIS) available by both ECG and SPECT. Group 2 (56 patients, 24%) had myocardium at risk, FIS, and salvage index (SI) assessed by both SPECT and ECG techniques. Aldrich/Clemmensen scores for myocardium at risk and the Selvester QRS score for final MI size were used. Salvage index was calculated as follows: SI = (myocardium at risk-FIS)/(myocardium at risk). In group 1, FIS was 15% (6, 24) as measured by ECG and 11% (2, 27) as measured by SPECT. In the adenosine group, FIS was 12% (6, 21) and 11% (2, 22). In the placebo group, FIS was 16.5% (7.5, 24) and 11.5% (3.0, 38.5) by ECG and SPECT, respectively. The overall correlation between SPECT and ECG for FIS was 0.58 (P = .0001): 0.60 in the placebo group (P = .0001) and 0.54 (P = .0001) in the adenosine group. In group 2, myocardium at risk was 23% (17, 30) and 26% (10, 50) with ECG and SPECT, respectively (P = .0066). Final infarct size was 17% (6, 21) and 12% (1, 24) (P < .0001). The SI was 29% (-7, 57) and 46% (15, 79) with ECG and SPECT, respectively (P = .0510). The ECG measurement of infarct size has a moderate relationship with SPECT infarct size measurements in the population with available assessments. This ECG algorithm must further be validated on clinical outcomes.


Exogenous hydrogen peroxide as a possible messenger for the stimulation effect of magnetized physiological solution on heart contractility.
The dual effect of magnetized physiological solution (MPS) on snail heart muscle contractility (muscle relaxation and stimulation of heartbeat) was shown previously. The MPS-induced relaxation of the heart muscle has been explained by activation of cGMP-dependent Ca(2+) effluxes from the muscle; however, the mechanism of the stimulating effect of MPS on heartbeat remains unclear. As in the presence of paramagnetic oxygen molecules, magnetic fields could generate the exogenous reactive oxygen species such as hydrogen peroxide (H(2)O(2)), we hypothesize that H(2)O(2) may play a role as the possible messengers through which the activation effect of MPS on heartbeat is realized. To test this hypothesis, the dose-dependent effects of exogenous H(2)O(2) on heart muscle contractility and (45)Ca uptake were studied. Here we compared the obtained data with the previous results of the effects of MPS on heart muscle contractility and (45)Ca uptake. We found that exogenous H(2)O(2) and MPS have similar effects on Na(+)-K(+) pump-induced transient inhibition of muscle contractility and (45)Ca uptake. The Na(+)-K(+) pump-induced depression of H(2)O(2)-sensitivity of muscle contractility is determined by activation of Ca(2+) efflux from the cell. On the basis of these data we suggest the exogenous H(2)O(2) as a possible messenger through which the stimulation effect of MPS on heart muscle is realized.


Cholinesterases as markers of the inflammatory process associated oxidative stress in cattle infected by Babesia bigemina.
The objective of this study was to assess the influence of an asymptomatic experimental infection by Babesia bigemina on cholinesterase's as markers of the inflammatory process and biomarkers of oxidative imbalance. For this purpose, eight naive animals were used, as follows: four as controls or uninfected; and four infected with an attenuated strain of B. bigemina. Blood samples were collected on days 0, 7 and 11 post-inoculation (PI). Parasitemia was determined by blood smear evaluation, showing that the infection by B. bigemina resulted in mean 0.725 and 0.025% on day 7 and 11 PI, respectively, as well as mild anemia. The activities of acetylcholinesterase, butyrylcholinesterase and catalase were lower, while levels of thiobarbituric acid reactive substances and superoxide dismutase activity were higher in infected animals, when compared with the control group. This attenuated strain of B. bigemina induced an oxidative stress condition, as well as it reduces the cholinesterasés activity in infected and asymptomatic cattle. Therefore, this decrease of cholinesterase in infection by B. bigemina purpose is to inhibit inflammation, for thereby increasing acetylcholine levels, potent anti-inflammatory molecules.


Lithium: long-term effects on the kidney. III. Prospective study.
Renal function in 32 patients treated with lithium for an average period of 10 years was reexamined 2 years after the first examination. A markedly influenced tubular function leading to increased urine volume (average 3 litres/24 h) and decreased renal concentrating capacity was still found, whereas glomerular function remained unimpaired in nearly all of the patients. No statistically significant changes in renal functions were observed at the follow-up examination. The results were compared with the same renal functional tests obtained from a control group consisting of 53 patients with affective disorders never treated with lithium. The control group had a significantly lower urine output (average 2 litres/24 h), but lithium-treated patients on a one-dose schedule had an average urine volume of only 500 ml/24 h more than the controls. In conclusion, this prospective study found no evidence of a progressive impairment of glomerular or tubular function in lithium-treated patients reexamined after 2 years. Patients with affective disorders never treated with lithium had normal renal concentrating capacity.


Significance of binding to Na,K-ATPase in the tissue distribution of ouabain in guinea pigs.
Ouabain binds specifically to Na,K-ATPase on the plasma membrane and therefore serves to measure the tissue concentration of Na,K-ATPase. We examined the role of ouabain binding to Na,K-ATPase in its overall tissue distribution. The tissue-to-plasma concentration ratio (Kp,vivo) was defined in each tissue after intravenous administration of 3H-ouabain in guinea pigs, and specific binding of ouabain to Na,K-ATPase was measured in tissue homogenate to obtain the dissociation constant and binding capacity in each tissue. A predicted tissue-to-plasma concentration ratio (Kp,vitro) was calculated using the obtained binding parameters and the volume of extracellular space in each tissue. The absolute values of Kp,vitro were comparable to those of Kp,vivo, except in brain. Regression analysis showed that the specific binding capacity of Na,K-ATPase in each tissue is the main factor in the tissue variation of Kp,vivo. Therefore, the binding of ouabain to Na,K-ATPase plays a significant role in the tissue distribution of ouabain.


Comparison of methods used for pre-concentrating small volumes of organic volatile solutions.
Eight pre-concentration techniques were compared for their capacity to retain volatile and semi-volatile solutes during evaporation of solvent (dichloromethane). The 2-ml test-samples containing 0.2 ppm or 2 ppm (v/v) of volatile and semi-volatile solutes were concentrated to a final volume of 1 ml, 200 microl and 50 microl, respectively. When pre-concentrating to 50 microl, the highest recoveries for both the diluted (0.2 ppm) and concentrated (2 ppm) solutions were found by passive evaporation in a test tube at 22 degrees C. The pre-concentration time from 2 ml to 50 microl by this method was 19-20 h. Heating the test tube to 47 degrees C yielded lower recoveries in dilute samples, but the recoveries of concentrated samples were only slightly lower than the recoveries obtained by passive evaporation. The evaporation time was decreased to 1-2 h. The recoveries and the reproducibility of these methods were superior to the other pre-concentration methods tested. Loss of solute was apparently mainly caused by the fast vapour streams created when speeding up the process of evaporation by heating or by introducing a gas stream into the tube. This increased co-evaporation and thereby solute loss. The capacity of the methods to trap the escaping vapours and create a reflux determined the capacity of the methods to recover the solutes. The experiments demonstrated that more solute is lost during the pre-concentration of dilute samples compared to more concentrated solutions.


Granulocyte-macrophage colony stimulating factor potentiates human polymorphonuclear leukocyte aggregation responses to formyl-methionyl-leucyl-phenylalanine.
Polymorphonuclear leukocytes (PMN) are known to be activated by several lymphokines and can be induced to release lysosomal enzymes, prostaglandins (PG), thromboxanes (TX) and lipoxygenase products that may be involved in PMN aggregation responses during inflammatory reactions. Granulocyte-macrophage colony stimulating factor (GM-CSF), a glycoprotein cytokine released by immunocompetent cells, has been found to prime neutrophil responses, such as increased cell aggregation after exposure to various biological stimulants. In this study, we examined the effects of the cytokine GM-CSF on human neutrophilic aggregation stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and its influence on the production of various arachidonic acid metabolites. Neutrophil aggregation of purified PMNs was measured by the percent change in light transmission in a standard aggregometer, and the arachidonic acid products leukotriene B4 (LTB4) and thromboxane A2 (TXA2) were quantified by radioimmunoassay. We found that GM-CSF and other cytokines, used alone, did not cause any significant increase in aggregation of the PMN. However, prior exposure of PMN to GM-CSF markedly increased the aggregation induced by FMLP as opposed to that detected with PMN stimulated with only FMLP. This priming effect was not observed with PMN preincubated with interleukin-1 (IL-1), tumor necrosis factor (TNF) or interleukin-6 (IL-6). In addition, GM-CSF and IL-6 both failed to stimulate the production of LTB4 and TXA2, products which are known to induce PMN aggregation. These findings provide new evidence suggesting that GM-CSF facilitates the action of FMLP on the adhesion dependent cellular functions of the inflammatory response, serving as an important co-factor in neutrophil aggregation.


microRNA-211-mediated targeting of the INHBA-TGF-β axis suppresses prostate tumor formation and growth.
Prostate cancer (PCa) stem cells increase the sustainability of tumor growth, resulting in high relapse rates in patients with PCa. This goal of the present study was to elucidate the function of microRNA (miR)-211 in PCa stem cell activities. Based on the initial findings from the GSE26910 dataset, inhibin-β A (INHBA) was used for subsequent experiments, and miR-211 was then predicted as a candidate regulatory miR. Subsequently, INHBA and miR-211 were observed to be highly and poorly expressed in PCa tissues, respectively, and miR-211 negatively target INHBA. CD44+CD133+ cells were isolated, and both miR-211 and INHBA expression was altered in these cells to assess functional role of miR-211 and INHBA in PCa stem cells. Overexpression of miR-211 decreased expression of TGF-β1, TGF-β2, smad2, smad3, phosphorylated smad2 and smad3, and stem cell markers. miR-211 upregulation or INHBA knockdown resulted in reductions in the proliferation, invasion, colony-forming ability, sphere-forming ability, and stemness of PCa stem cells but enhanced their apoptosis in vitro. Furthermore, miR-211 upregulation or INHBA silencing decreased tumor growth and cell apoptosis in vivo. Taken together, these results indicate that upregulation of miR-211 has tumor-suppressive properties by inhibiting TGF-β pathway activation via INHBA in PCa stem cells.


Combining capecitabine and bevacizumab in metastatic breast cancer: a comprehensive review.
Both capecitabine and bevacizumab are established agents in the treatment of metastatic breast cancer, but until recently clinical data supporting their use in combination were limited. We review available data on the capecitabine-bevacizumab combination in breast cancer, particularly results from the RIBBON-1 trial in the first-line setting, and we discuss these findings in light of previous studies. We also examine ongoing trials investigating capecitabine-bevacizumab combination therapy.


ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5-fluorouracil combination chemotherapy in patients with advanced colorectal cancer.
The aim of our study was to assess whether the polymorphism of the nucleotide excision repair enzyme, excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1), had an effect on the tumor response in patients treated with standard chemotherapy regimens for a metastatic colorectal cancer. We have studied the synonymous polymorphism that causes a single nucleotide change C to T at codon 118 converting a codon of common usage (AAC) to a less used codon (AAT), both coding asparagine. This change results in a decreased ERCC1 gene expression, which impairs repair activity. Ninety-one patients with a median age of 55.1 years treated for a metastatic colorectal cancer were included in our retrospective study. The ERCC1 polymorphism was analyzed in the normal tissue of all patients. Twenty (22%) were homozygous for AAC codon (C/C genotype), 30 were (33%) homozygous for AAT codon (T/T genotype), and 41 (45%) were heterozygous (C/T genotype). The objective response rate to oxaliplatin in combination with 5-fluorouracil (5-FU) was significantly higher in the T/T genotype group compared with the C/T and the C/C genotype groups (61.9%, 42.3%, and 21.4%, respectively; P = 0.018). By contrast, no significant difference was observed when patients were treated with either 5-FU alone (45%, 29.2%, and 33.3%, respectively; P = 0.407) or in combination with irinotecan (46.1%, 25.0%, and 27.3%, respectively; P = 0.305). Our observations allowed us to define the first useful predictive criterion for oxaliplatin/5-FU response in patients with metastatic colorectal cancer.


Analysis of intraoperative laboratory measurements and imaging techniques such as Tc-99 m-MIBI SPECT/CT, 18F-fluorocholine PET/CT and ultrasound in patients operated with prediagnosis of parathyroid adenoma.
The aim of this study is to determine accurately the localization of the adenoma with the imaging methods in the patients, who are planned to be operated on with prediagnosis of parathyroid adenoma. In our study, the files of the patients who were considered to have parathyroid adenoma and underwent operation between 2012 and 2020 with the methods such as Tc99m-MIBI SPECT/CT, 18F-fluorocholine PET/CT, and ultrasound, and biochemical examinations were examined retrospectively. In this study, 31 (18.2%) male and 139 (81.8%) female adult patients were included. The sensitivities of localization methods were 82.6% for ultrasound and 78.4% for scintigraphy. Adenoma was localised in the right place in 14 of 15 (93.3%) patients with the 18F-fluorocholine PET/CT method. A statistically significant correlation was found between the sensitivity of scintigraphy, the gland weights (p: 0.002), and phosphor values (p: 0.039). A statistically significant improvement was observed in the intact PTH value (p: 0.001) 15 min after the removal of adenoma. A statistically significant improvement was observed in the serum PTH value (p: 0.001), the serum phosphorus value (p: 0.001), and the serum calcium (p: 0.001) in the first 3 months after the operation. Determining localization accurately for the patients enables performing operations with minimally invasive surgery successfully in a shorter time. Also, fewer complications and faster recovery are seen in the patients. It was concluded that studying intraoperative intact PTH and using 18F-fluorocholine PET/CT method for localization give more accurate results for localization and allow having more successful operation outcomes.


Linking Immuno-Epidemiology Principles to Violence.
Societies have always struggled with violence, but recently there has been a push to understand violence as a public health issue. This idea has unified professionals in medicine, epidemiological, and psychology with a goal to end violence and heal those exposed to it. Recently, analogies have been made between community-level infectious disease epidemiology and how violence spreads within a community. Experts in public health and medicine suggest an epidemiological framework could be used to study violence. Building upon results from community organizations which implement public health-like techniques to stop violence spread, we look to formalize the analogies between violence and infectious diseases. Then expanding on these ideas and using mathematical epidemiological principals, we formulate a susceptible-exposed-infected model to capture violence spread. Further, we ran example numerical simulations to show how a mathematical model can provide insight on prevention strategies. The preliminary simulations show negative effects of violence exposure have a greater impact than positive effects of preventative measures. For example, our simulation shows that when the impact of violence exposure is reduced by half, the amount of violence in a community drastically decreases in the long-term; but to reach this same outcome through an increase in the amount of after exposure support, it must be approximately fivefold. Further, we note that our simulations qualitatively agree with empirical studies. Having a mathematical model can give insights on the effectiveness of different strategies for violence prevention. Based on our example simulations, the most effective use of community funding is investing in protective factors, instead of support after violence exposure, but of course these results do not stand in isolation and will need to be contextualized with the rest of the research in the field.


Cognitive impairment of vascular origin: neuropathology of cognitive impairment of vascular origin.
The term cognitive impairment of vascular origin is used to designate global cognitive deficits as well as focal neurological deficits such as aphasia, apraxia and agnosia of vascular/circulatory origin. It has been useful for identifying early clinical and neuroradiological alterations that might permit therapeutic strategies geared to curbing the progression of cerebrovascular disease. Multi-infarct encephalopathy, infarcts in strategic areas, lacunae and lacunar status, Binswanger's encephalopathy, hippocampal sclerosis, cortical granular atrophy and watershed infarcts are common lesions. Hypertension and vascular diseases such as arteriosclerosis, small blood vessel disease, inflammatory diseases of the blood vessels, Sneddon syndrome, cerebral amyloid angiopathies, cerebral autosomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Maeda's syndrome are causative of cognitive impairment of vascular origin. Other less common causes are hereditary endotheliopathy with retinopathy, neuropathy and strokes (HERNS), cerebro-retinian vasculopathy (CRV), hereditary vascular retinopathy (HVR) (all three linked to 3p21.1-p21.3), hereditary infantile hemiparesis with arteriolar retinopathy and leukoencephalopathy (HIHRATL) (not linked to 3p21), fibromuscular dysplasia, and moya-moya disease. Lack of uniformity of clinical manifestations, the variety of vascular diseases and circulatory factors, the diverse, but often convergent, neuropathological substrates, and the common association with unrelated neurodegenerative diseases in the elderly, make it hard to assume a single clinical approach in the diagnosis and treatment of cognitive impairment of vascular origin. Rather, environmental and genetic risk factors, underlying vascular diseases, associated systemic, metabolic and neurodegenerative diseases and identification of extent and distribution of lesions with morphological and functional neuroimaging methods should be applied in every individual patient.


Bioavailability of mifepristone in capsule versus tablet form in healthy nonpregnant women.
The study was conducted to assess the bioavailability of two formulations of mifepristone in capsule and tablet forms at a single dose of 75 mg (half the registered dose in China). A randomized two-way crossover study was conducted in 18 healthy nonpregnant women. Each subject was orally given a single dose of mifepristone at 75 mg in capsule or tablet form on an alternate basis. Serial blood samples were collected over a period of 96 h and assayed for the plasma concentration of mifepristone by high-performance liquid chromatography. Paired t tests were used to compare the capsule and tablet forms in terms of maximum concentration (C(max)), time to maximum concentration (T(max)) and area under the curve over 96 h (AUC(0-96 h)). Relative bioavailability (capsule/tablet) was derived from AUC(0-96 h). Bioequivalability was analyzed by two one-sided t tests. The major pharmacokinetic parameters were as follows: C(max) values were 1.26+/-0.38 and 1.25+/-0.40 mcg/mL, T(max) values were 0.94+/-0.34 and 0.89+/-0.47 h, T(1/2Ke) values were 36.2+/-21.0 and 33.4+/-12.3 h and AUC((0-96 h)) values were 19.7+/-6.4 and 19.6+/-9.9 mcg.h/mL for mifepristone in capsule and tablet forms, respectively. No significant difference was observed among these parameters. The relative bioavailability was 109.4+/-34.8%. This study suggests that the two formulations of mifepristone are bioequivalent, which provides pharmacokinetic evidence for further reducing the dosage of mifepristone in clinical use.


Depression and anxiety in women during pregnancy and neonatal outcome: data from the EDEN mother-child cohort.
According to the World Health Organization, mental health disorders are the leading causes of disease burden in women from 15 to 44 years. These conditions in pregnant women may affect the offspring. To analyze the relation between depression and anxiety of pregnant women and neonatal outcomes including gestational age and birthweight. Observational cohort study. 2002 women recruited before the 20th gestational week. Gestational age at delivery in completed weeks of amenorrhea and preterm delivery defined as birth before 37 completed weeks of gestation. Spontaneous preterm birth (PB) defined as either spontaneous preterm labor or preterm premature rupture of the membranes. Medically indicated preterm delivery defined as delivery that begins by induction or cesarean section. Birthweight as a continuous variable and centiles of the customized fetal weight norms for the French population. From the 1719 women included in the study, 7.9% (n=135) were classified as "anxious", 11.8% (n=203) as "depressed", 13.2% (n=227) as "depressed and anxious". After adjusting for potential confounders, depression combined with anxiety during pregnancy increased the risk of spontaneous PB (Odds Ratio: 2.46 [1.22-4.94]), but did not influence medically indicated PB nor birthweight. In this study, comorbidity of depressive and anxiety symptoms was the worst condition during pregnancy. Further studies are needed to investigate depression and anxiety together to improve the comprehension of the biological modifications involved.


Soman-induced convulsions: the neuropathology revisited.
The organophosphorus compound soman, an irreversible inhibitor of cholinesterases, produces seizure activity and related brain damage. Studies using various biochemical markers of programmed cell death (PCD) suggested that soman-induced cell damage in the brain was apoptotic rather than necrotic. However, it has recently become clear that not all PCD is apoptotic, and the unequivocal demonstration of apoptosis requires ultrastructural examination. Therefore, the present study was undertaken to reinvestigate the damage produced in the brains of mice sacrificed at various times within the first 24 h or at 7 days after a convulsive dose of soman. Classical histology and ultrastructural examination were performed. The immunohistochemical expression of proteins (p53, Bax) involved in PCD, DNA fragmentation (TUNEL method at light and electron microscopy levels) and the glial reaction were also explored. Our study confirms that the severity of lesions depended on the duration of convulsions and shows that cerebral changes were still occurring as late as 7 days after the onset of long-lasting convulsions. Our observations also establish that there was a large variety of ultrastructurally distinct types of cell damage, including hybrid forms between apoptosis and necrosis, but that pure apoptosis was very rare. A prominent expression of p53 and Bax proteins was detected indicating that PCD mechanisms were certainly involved in the morphologically diverse forms of cell death. Since purely apoptotic cells were very rare, these protein expressions were presumably involved either in nonapoptotic cell death mechanisms or in apoptotic mechanisms occurring in parallel with nonapoptotic ones. Moreover, evidence for DNA fragmentation by the TUNEL method was found in apoptotic but also in numerous other morphotypes of cell damage. Therefore, TUNEL-positivity and the expression of PCD-related proteins, in the absence of ultrastructural confirmation, were here shown not to provide proof of apoptosis. In soman poisoning as well as in other cerebral pathologies, premature conclusions on this question can potentially be misleading and might even lead to detrimental therapies.


Dissociation between biochemical and behavioral recovery in MPTP-treated mice.
Injection of a low dose of haloperidol, that has no obvious behavioral effects in normal mice, produces akinesia, catalepsy, and somatosensory neglect in MPTP-treated mice. These neuroleptic-induced sensorimotor impairments are exhibited soon after MPTP treatments and coincide with a decrease in both striatal DA and DOPAC levels. DA and DOPAC content gradually return to near-control levels over a 3-5 month period. Interestingly, while the haloperidol-induced somatosensory deficits declined in parallel with the rise in DA and DOPAC levels, the motor deficits persisted for up to 5 months after MPTP administration. These data suggest subtle differences in the neurochemical mediation of these behaviors and that the persistence of neuronal impairments may not necessarily be revealed by near-normal transmitter levels.


Analysis of the quality of remote working experience: a speech-based approach.
The current pandemic situation has led to an extraordinary increase in remote working activities all over the world. In this paper, we conducted a research study with the aim to investigate the Quality of Remote Working Experience (QRWE) of workers when conducting remote working activities and to analyse its correlation with implicit emotion responses estimated from the speech of video-calls or discussions with people in the same room. We implemented a system that captures the audio when the worker is talking and extracts and stores several speech features. A subjective assessment has been conducted, using this tool, which involved 12 people that were asked to provide feedback on the QRWE and assess their sentiment polarity during their daily remote working hours. ANOVA results suggest that speech features may be potentially observed to infer the QRWE and the sentiment polarity of the speaker. Indeed, we have also found that the perceived QRWE and polarity are strongly related.


A randomized comparison of ultrathin and standard colonoscope in cecal intubation rate and patient tolerance.
Complete colonoscopy examination cannot be performed in as many as 10% of cases. The new 9.2-mm ultrathin colonoscope (UTC) with an extra bending section may improve procedure tolerance and allow improvement in colonoscopy completion rate compared with a 12.9-mm standard colonoscope (SC). To compare the performance of the 9.2-mm UTC with that of the 12.9-mm SC. Prospective, randomized, controlled trial. Academic endoscopic unit. Subjects 18 years and older undergoing their first colonoscopy. Subjects were randomized to either the UTC or SC group. First and rescue successful cecal intubation rates, subject satisfaction scores, and sedation requirements were compared. A total of 1121 patients (56% women, mean age 53.6 years) were randomized to the UTC group (n = 551) or the SC group (n = 570). There was no statistically significant difference in the first successful cecal intubation rate between the UTC and SC groups (98.9% vs 97.4%, P = .057). The mean (standard deviation) dose of midazolam and pethidine used was significantly lower in the UTC group (2.65 [0.65] mg vs 2.82 [0.85] mg, P < .001 and 27.6 [7.4] mg vs 29.7 [9.6] mg, P < .001, respectively). The mean (standard deviation) patient satisfaction score was similar between groups (6.99 [2.89] vs 7.04 [3.06], P = .762). Of the 21 patients (1.9%) with an incomplete initial colonoscopy (6 in the UTC group and 15 in the SC group), all 6 in the UTC group had their procedure completed with an SC. Eleven of 15 patients in the SC group had their procedures completed with a UTC in the same session. Low failure rate may mask any difference between the 2 colonoscopes as a rescue instrument. The 9.2-mm UTC has performance characteristics similar to those of an SC in Chinese subjects undergoing their first colonoscopy performed by experienced and trainee endoscopists. ( NCT01142167.).


A novel grass hybrid to reduce flood generation in temperate regions.
We report on the evaluation of a novel grass hybrid that provides efficient forage production and could help mitigate flooding. Perennial ryegrass (Lolium perenne) is the grass species of choice for most farmers, but lacks resilience against extremes of climate. We hybridised L. perenne onto a closely related and more stress-resistant grass species, meadow fescue Festuca pratensis. We demonstrate that the L. perenne × F. pratensis cultivar can reduce runoff during the events by 51% compared to a leading UK nationally recommended L. perenne cultivar and by 43% compared to F. pratensis over a two year field experiment. We present evidence that the reduced runoff from this Festulolium cultivar was due to intense initial root growth followed by rapid senescence, especially at depth. Hybrid grasses of this type show potential for reducing the likelihood of flooding, whilst providing food production under conditions of changing climate.


Differences in health behavior and nutrient intake status between diabetes-aware and unaware Korean adults based on the Korea national health and nutrition examination survey 2016-18 data: A cross-sectional study.
The aim of this study was to investigate the nutritional intakes and treatment regimens of Korean patients with type 2 diabetes who were aware of their condition. Participants (n = 16582) aged ≥ 19 years from the 2016-18 National Health and Nutrition Survey were divided into diabetes-aware and unaware groups and the variables were compared. Among 1,906 (11.5%) diabetic adults, 1,433 (75.2%) were aware of their condition; 130 (9.1%) had nutrition education, and 1,340 (93.5%) were in the diabetes-aware treatment group. The diabetes-aware group had higher average age (P < 0.0001) and lower average BMI (P = 0.0015) than the unaware group. Intake of total fat (P = 0.0034), saturated fatty acids (P = 0.0021), riboflavin (P = 0.0035) and niacin (P = 0.0228) was significantly higher in the unaware group than in the diabetes-aware group, after adjusting energy intake for age and sex. Current smoking (P = 0.0046) and heavy drinking (P < 0.0001) rates were higher in the unaware group, whereas fiber intake (P = 0.0054) was lower in the unaware group. Higher levels of glycated hemoglobin were found in the group treated for diabetes (7.2%) than in the no-treatment (6.8%) group (P = 0.0048). Diabetes control was significantly better in the high income group. There is a need to strengthen nutritional education to prevent diabetes and improve the health status of diabetic patients in Korea.


Estimation of the burden of flu-association influenza-like illness visits on total clinic visits through the sentinel influenza monitoring system in Senegal during the 2013-2015 influenza seasons.
Knowing the burden of influenza is helpful for policy decisions. Here we estimated the contribution of influenza-like illness (ILI) visits associated with laboratory-confirmed influenza among all clinic visits in a Senegal sentinel network. ILI data from ten sentinel sites were collected from January 2013 to December 2015. ILI was defined as an axillary measured fever of more than 37.5 °C with a cough or a sore throat. Collected nasopharyngeal swabs were tested for influenza viruses by rRT-PCR. Influenza-associated ILI was defined as ILI with laboratory-confirmed influenza. For the influenza disease burden estimation, we used all-case outpatient visits during the study period who sought care at selected sites. Of 4030 ILI outpatients tested, 1022 were influenza positive. The estimated proportional contribution of influenza-associated ILI was, per 100 outpatients, 1.2 (95% CI 1.1-1.3), 0.32 (95% CI 0.28-0.35), 1.11 (95% CI 1.05-1.16) during 2013, 2014, 2015, respectively. The age-specific outpatient visits proportions of influenza-associated ILI were higher among children under 5 years (0.68%, 95% CI: 0.62-0.70). The predominant virus during years 2013 and 2015 was influenza B while A/H3N2 subtype was predominant during 2014. Influenza viruses cause a substantial burden of outpatient visits particularly among children under 5 of age in Senegal and highlight the need of vaccination in risk groups.


The association between undiagnosed diabetes and cognitive function: findings from the China health and retirement longitudinal study.
The cognitive function of people with diabetes has gained an increasing interest in recent years, and this study focuses on exploring the relationship between undiagnosed diabetes and cognitive function among the middle-aged and elderly people in China. The data came from the China Health and Retirement Longitudinal Study (CHARLS) which was conducted between July and October 2015. 9855 subjects were enrolled in the study. Executive function and episodic memory were used to assess cognitive function. The subjects were divided into three groups: no diabetes, diagnosed diabetes, and undiagnosed diabetes, and weighted multiple linear regression models were established to evaluate the association of undiagnosed diabetes with cognitive function. After controlling for covariates, undiagnosed diabetes was statistically associated with executive function (β = -0.215, P < 0.01). In the age group of ≥65 years, undiagnosed diabetes was statistically associated with executive function (β = -0.358, P < 0.01) and episodic memory (β = -0.356, P < 0.01). When adjusting for confounders, no statistically significant associations were found between diagnosed diabetes and cognitive function except in 45-54 age group (β = 0.374, P < 0.05). The cross-sectional study suggested that undiagnosed diabetes was linked to poor cognitive function, especially in the elderly population. Timely diagnosis and active treatment of diabetes are important to reduce the occurrence of cognitive impairment. Further prospective cohort studies are required to articulate the association between undiagnosed diabetes and cognitive function.


Initiation of the Virtual Interview: A 5-Y Evaluation of General Surgery Residency Match Results.
The virtual residency application season posed numerous challenges for the 2021 residency match process. Many residency programs are exploring relationships between this novel format and the match process. The purpose of this study was to compare one of the largest general surgery residency program's applications and match data from preCOVID years to the 2021 virtual cycle. A retrospective review was performed of applicants to a single general surgery residency program from 2017 to 2021. The primary outcome was the number of locally matched applicants. The secondary outcomes were the total number of applications, change in applicant demographics, and variability of the geographic spread during this study period. Chi-square tests of independence, Fisher's exact tests, and negative binomial regression were performed. 6819 applicants were included in the study. In 2021, an increase in applications was observed. The distribution of 2021 applications was statistically different from previous years regarding gender and race (P < 0.0001). The 2021 application cycle had a greater proportion of applicants from the United States (P < 0.0001) and southern US medical schools (P = 0.008). While the 2021 cycle had significantly more interviews (P = 0.013), there were no significant differences in the demographic composition of interviewees. During the 2021 application year, all 11 matches were from southern medical schools and there was a trend to more matched female applicants compared to previous years. During the 2021 COVID-19 virtual match cycle, an increase in both the number of applications and number of interviews for general surgery residency was identified. The characteristics of applicants who interviewed and matched were not different when compared to previous years. As virtual interviews may become more commonplace, it is important to assess all factors that may be involved in the dynamic residency application process.


Pathogen-produced catalase affects immune priming: A potential pathogen strategy.
Immune priming in invertebrates occurs when the first contact with a pathogen/parasite enhances resistance after a second encounter with the same strain or species. Although the mechanisms are not well understood, there is evidence that priming the immune response of some hosts leads to greater pro-oxidant production. Parasites, in turn, might counteract the host attack with antioxidants. Virulent pathogen strains may therefore mask invertebrate immune priming. For example, different parasite species overexpress catalase as a virulence factor to resist host pro-oxidants, possibly impairing the immune priming response. The aim of this study was firstly to evaluate the specificity of immune priming in Tenebrio molitor when facing homologous and heterologous challenges. Secondly, homologous challenges were carried out with two Metarhizium anisopliae strains (Ma10 and CAT). The more virulent strain (CAT) overexpresses catalase, an antioxidant that perhaps impairs a host immune response mediated by reactive oxygen species (ROS). Indeed, T. molitor larvae exhibited better immune priming (survival) in response to the Ma10 than CAT homologous challenge. Moreover, the administration of paraquat, an ROS-promoting agent, favoured survival of the host upon exposure to each fungal strain. We propose that some pathogens likely overcome pro-oxidant-mediated immune priming defences by producing antioxidants such as catalase.


Prevention of induction of unresponsiveness to class I antigens by veto activity of donor marrow in cylophosphamide-treated mice.
The survival of skin grafts from B6.C-H-2bm1 (bm1; Kbm1,IAb,IE-,Db) mice was prolonged when C57BL/6 CrSlc (B6; H-2b) mice were inoculated intravenously with 9 x 10(7) spleen cells (SC) plus 3 x 10(7) bone marrow cells from bm1 mice 14 days prior to skin grafting. When B6 mice were inoculated i.v. with bm1 cells and treated intraperitoneally with 200 mg/kg cyclophosphamide (CP) 2 days later, the survival of bm1 skin grafts was not prolonged at all, suggesting antagonism between the veto cell-mediated enhancement by donor cells and CP-induced enhancement. In order to deplete the veto cells from the tolerogen, SC plus BMC were treated with anti-Thy1.2 mAb+C' or CP. The survival of the bm1 skin grafts was not prolonged at all in B6 mice inoculated with Thy1.2-treated bm1 or bm1 cells from CP-treated donors. When B6 mice were inoculated with Thy1.2-treated or CP-treated bm1 cells and followed by CP treatment, however, the survival of bm1 skin grafts was prolonged moderately. These results strongly suggested that the unresponsiveness induced with donor-derived veto cells prevents the tolerance induction to class I alloantigens (H-2Kbm1) by our protocol of CP-induced tolerance. Furthermore, in B6 mice injected with anti-Thy1.2 mAb on day -1 and bm1 cells on day 0, the survival of bm1 skin grafts was not prolonged at all. However, skin graft tolerance to bm1 antigens was induced when B6 mice were injected with anti-Thy1.2 mAb on day -1 and bm1 cells on day 0 followed by CP on day 2. These results may also be explained by the depletion of donor-derived veto cells in the recipient mice.


Gastrointestinal complications of oncologic therapy.
Gastrointestinal complications are common in patients undergoing various forms of cancer treatment, including chemotherapy, radiation therapy, and molecular-targeted therapies. Many of these complications are life-threatening and require prompt diagnosis and treatment. Complications of oncologic therapy can occur in the esophagus (esophagitis, strictures, bacterial, viral and fungal infections), upper gastrointestinal tract (mucositis, bleeding, nausea and vomiting), colon (diarrhea, graft-versus-host disease, colitis and constipation), liver (drug hepatotoxicity and graft-versus-host disease), and pancreas (pancreatitis). Treatment of the different gastrointestinal complications should be tailored to the individual patient and based on the underlying pathophysiology of the complication.


Getting lost in translation? Workplace based assessments in surgical training.
Workplace based assessments (WBA) are integral to the competence-based surgical training curriculum that currently exists in the UK. The GMC emphasise the value of WBA's as assessments for learning (formative), rather than as assessments of learning (summative). Current implementation of WBA's in the workplace though, is at odds with their intended use, with the formative functions often being overlooked in favour of the summative, as exemplified by the recent announcement that trainees are required to complete a minimum of 40 WBA's a year, an increase from 24. Even before this increase, trainees viewed WBA's as tick-box exercises that negatively impact upon training opportunities. As a result, the tools are commonly misused, often because both trainees and trainers lack understanding of the benefits of full engagement with the formative learning opportunities afforded by WBA's. To aid the transition in mind-set of trainees and trainers to the purpose of assessment in the workplace, the GMC propose the introduction of 'supervised learning events' and 'assessments of performance' to supersede 'WBA's'. The impact of this change and how these will be integrated into surgical training is yet to be seen, but is likely to be a step in the right direction.


Circulating Galectin-1 and 90K/Mac-2BP Correlated with the Tumor Stages of Patients with Colorectal Cancer.
The simultaneous correlation of serum galectin-1, galectin-3, and 90K/Mac-2BP levels with clinical stages of patients with colorectal cancer has not yet been clarified. We plan to measure the serum levels of galectin-1, galectin-3, and 90K/Mac-2BP of patients at different stages of colorectal cancer and analyze the correlation of these galectins with stages of colorectal cancers. 198 colorectal cancer patients (62 ± 13 (range 31-85) years old, 43.6% female) were recruited for this study. Subjects' blood samples were checked for serum galectin-1, galectin-3, 90K/Mac-2BP, and carcinoembryonic antigen by sandwich enzyme-linked immunosorbent assay. We determined the correlation between plasma concentrations with clinical tumor stages. Colorectal cancer patients with larger cancer sizes (stages T3, T4 rather than T1, T2) have higher serum 90K/Mac-2BP (P = 0.014) and patients with lymph node metastasis have higher serum galectin-1 (P = 0.002) but there was not a significant correlation between galectin-3 and tumor staging of colon cancer. In colorectal cancer patients even with normal carcinoembryonic antigen, serum galectin-1 could predict more lymph node metastasis. We found 90K/Mac-2BP correlated with the size of colorectal cancer. Galectin-1 but not galectin-3 was associated with lymph node metastasis. Galectin-1 could predict more lymph node metastasis in colorectal cancer patients with normal serum carcinoembryonic antigen.


Design and synthesis of an orally active GPIIb/IIIa antagonist based on a phenylpiperazine scaffold.
The design and synthesis of an orally active LMW non-peptide GPIIb/IIIa antagonist, based on a N,N'-bisphenylpiperazine scaffold, is described. The optimal compound showed a high in vitro binding potency (pIC50 = 8.7) in combination with potent oral antithrombotic activity (30-40% inhibition of thrombus growth at 0.3-3 mg/kg) with a duration of action of > 90 min. in a hamster cheek pouch model.


Modelling Electricity Consumption During the COVID19 Pandemic: Datasets, Models, Results and a Research Agenda.
The COVID19 pandemic has impacted the global economy, social activities, and Electricity Consumption (EC), affecting the performance of historical data-based Electricity Load Forecasting (ELF) algorithms. This study thoroughly analyses the pandemic's impact on these models and develop a hybrid model with better prediction accuracy using COVID19 data. Existing datasets are reviewed, and their limited generalization potential for the COVID19 period is highlighted. A dataset of 96 residential customers, comprising 36 and six months before and after the pandemic, is collected, posing significant challenges for current models. The proposed model employs convolutional layers for feature extraction, gated recurrent nets for temporal feature learning, and a self-attention module for feature selection, leading to better generalization for predicting EC patterns. Our proposed model outperforms existing models, as demonstrated by a detailed ablation study using our dataset. For instance, it achieves an average reduction of 0.56% & 3.46% in MSE, 1.5% & 5.07% in RMSE, and 11.81% & 13.19% in MAPE over the pre- and post-pandemic data, respectively. However, further research is required to address the varied nature of the data. These findings have significant implications for improving ELF algorithms during pandemics and other significant events that disrupt historical data patterns.


Pediatric neurodegenerative white matter processes: leukodystrophies and beyond.
Pediatric neurodegenerative white matter processes are complex, numerous and result from a vast array of causes ranging from white matter injury or inflammation to congenital metabolic disorders. When faced with a neurodegenerative white matter process on neuroimaging, the first step for the radiologist is to determine whether the findings represent a congenital metabolic leukodystrophy or one of various other white matter processes. In this review we first describe a general approach to neurodegenerative white matter disorders. We will briefly describe a few white matter diseases that mimic metabolic leukodystrophies. In the second half of the review we discuss an approach to distinguishing and classifying white matter leukodystrophies.


Exploring the relationship between posttraumatic stress disorder symptoms and momentary heart rate variability.
Exposure to trauma-related cues has been associated with a prolonged decrease in heart rate variability (HRV) under laboratory conditions, however the relationship between PTSD symptoms and HRV has not been evaluated during everyday life. The present study sought to determine whether Posttraumatic Stress Disorder (PTSD) symptoms reported during everyday life were related to reduced HRV. Eighty-three young adults with PTSD underwent 24-hour Holter monitoring, during which PTSD symptoms were measured using ecological momentary assessment (EMA). Multilevel modeling was used to examine the association between PTSD symptom severity and low frequency (LF) and high frequency (HF) HRV. PTSD symptoms were associated with reductions in LF HRV, independently of age and activity level. There was no significant association between PTSD symptom levels and HF HRV. These results indicate that an association between momentary PTSD symptom severity and reduced LF HRV is significant and observable in young adults with PTSD. Findings highlight the need for cardiovascular screening in young adults with PTSD and early interventions that target physiological reactivity in PTSD.


A novel 55-basepair deletion of hydroxymethylbilane synthase gene found in a Chinese patient with acute intermittent porphyria and her family: A case report.
Acute intermittent porphyria (AIP) is caused by hydroxymethylbilane synthase (HMBS) gene mutation. A Chinese female patient with very typical AIP symptoms of severe abdominal pain, seizures, hypertension, and tachycardia, accompanied with hyponatremia, anemia, and hyperbilirubinemia. She was diagnosed as AIP based on positive result of urine porphobilinogen and her clinical syndrome. The proband was treated with intravenous glucose (at least 250 g per day) for 4 days. HMBS mutation was investigated in this family by Sanger sequencing. A heterozygous mutation of the HMBS gene was identified in the proband and 7 other family members. Genetic sequencing showed a deletion of 55 basepairs (C.1078_1132delGCCCATTAACTGGTTTGTGGGGCACAGATGCCTGGGTTGCTGCTGTCCAGTGCCT) including the stop codon position, leading to frameshift mutation. The mutation has not been documented in current gene databases. Further prediction of mutated protein structure suggests that the mutation is likely to produce prolonged peptide with structural change and less stability. Physicians should pay attention to AIP attack in patients with suspected symptoms and make use of genetic testing to increase identification of mutated HMBS gene carriers for further preventive strategy.


Gram stain in Legionnaires' disease.
A case of Legionnaires' disease is presented in which gram staining of impression smears from lung biopsy specimens showed Legionella pneumophila while other laboratory findings remained negative. This case illustrates the usefulness of gram staining in this disease and in the management of therapy.


Infective endocarditis associated with cell wall-deficient bacteria. Electron microscopic findings in four cases.
Although cell wall-deficient bacteria have been isolated in vitro from cases of endocarditis, no pathogenic role has been established for these forms in human disease. One criterion difficult to satisfy is the demonstration of these variants in human tissue, and electron microscopic documentation has not been reported. Cardiac valvular vegetations from four cases of endocarditis were examined by electron microscopy because of unusual histologic features of minimal inflammation and organization and small organisms that stained poorly by Gram stain. Although cell wall-complete bacteria were identified in the specimens, each showed the presence of cell wall-deficient forms within the vegetations; these variants predominated in three cases. Since manifestations of infective endocarditis were present in three cases and conventional cultures were negative, the evidence indirectly suggests a pathogenic role for these aberrant bacteria in human disease.


Cerebrospinal fluid shunt infections. Report of 41 cases and a critical review of the literature.
All shunt procedures performed at our institution from July 1982 to December 1987 were analyzed for factors possibly related to shunt infection. There were 41 infections detected in 31 patients for an overall rate of 6.9%. Only intraventricular hemorrhage (IVH) as an etiology of the hydrocephalus and internalization of an external ventricular drain (EVD) were found to correlate with septic risk. An extensive review of all the English language literature concerning shunt infections over the last 15 years was undertaken. Little consensus could be found among the 35 publications in regard to factors predisposing to shunt sepsis. Even the issue of antibiotic prophylaxis remains clouded as all papers examined exhibited methodologic flaws.


First insights into region-specific lipidome alterations of prefrontal cortex and hippocampus of mice exposed chronically to microcystins.
Microcystins (MCs), a group of most widespread freshwater cyanotoxins that possess strong neurotoxicity, can adversely affect brain structures and functions and are linked to neurodegenerative diseases. Despite the essential role of lipids in brain structures and functions, the brain lipidome profile of mammals exposed to MCs remains unexplored, hindering a clear understanding of the neurotoxic effects of MCs and underlying mechanisms. In this study, we performed untargeted lipidomic profiling using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) on the prefrontal cortex and hippocampus of mice orally exposed to 30 and 300 μg/kg body mass/day of microcystin-leucine arginine (MC-LR) for 180 days to evaluate the impacts of MC-LR on the brain lipidome profile and functions. Our results show that MC-LR resulted in a decline in cognitive parameters, as assessed by the Morris water maze test. Interestingly, apparent neurodegenerative changes were observed in the prefrontal cortex, but not in the hippocampus. Comprehensive lipidomic analyses uncovered profound, region-specific changes in the phospholipid and sphingolipid profile at the levels of lipid subclasses, lipid species, and fatty acyl composition. These changes showed overall decrease trends of lipid content in the prefrontal cortex yet increasing trends in the hippocampus. We identified distinct transcriptional regulations of lipid metabolism and apoptosis by MC-LR in the two regions, which appeared to underlie the neurodegenerative changes. Collectively, this study uncovers region-specific changes in the brain lipidome profile and functions induced by MCs, shedding light on the role of lipid dysfunction in neurotoxicity mechanism of MCs.


Delayed Complications After Transsphenoidal Surgery for Pituitary Adenomas.
Perioperative complications after transsphenoidal surgery for pituitary adenomas have been well documented in the literature; however, some complications can occur in a delayed fashion postoperatively, and reports are sparse about their occurrence, management, and outcome. Here, we describe delayed complications after transsphenoidal surgery and discuss the incidence, temporality from the surgery, and management of these complications based on the findings of studies that reported delayed postoperative epistaxis, delayed postoperative cavernous carotid pseudoaneurysm formation and rupture, vasospasm, delayed symptomatic hyponatremia, hypopituitarism, hydrocephalus, and sinonasal complications. Our findings from this review revealed an incidence of 0.6%-3.3% for delayed postoperative epistaxis at 1-3 weeks postoperatively, 18 reported cases of delayed carotid artery pseudoaneurysm formation at 2 days to 10 years postoperatively, 30 reported cases of postoperative vasospasm occurring 8 days postoperatively, a 3.6%-19.8% rate of delayed symptomatic hyponatremia at 4-7 days postoperatively, a 3.1% rate of new-onset hypopituitarism at 2 months postoperatively, and a 0.4%-5.8% rate of hydrocephalus within 2.2 months postoperatively. Sinonasal complications are commonly reported after transsphenoidal surgery, but spontaneous resolutions within 3-12 months have been reported. Although the incidence of some of these complications is low, providing preoperative counseling to patients with pituitary tumors regarding these delayed complications and proper postoperative follow-up planning is an important part of treatment planning.


In-depth characterization of the aggregation state of cellulose nanocrystals through analysis of transmission electron microscopy images.
Dispersion of cellulose nanocrystals (CNCs) is of utmost importance to guarantee their reliable application. Nevertheless, there is still no consensual method to characterize CNC aggregation. The hypothesis of this paper is that dispersion could be quantified through the classification of aggregates detected in transmission electron microscopy images. k-Means was used to classify image particulate elements of five CNC samples into groups according to their geometric features. Particles were classified into five groups according to their maximum Feret diameter, elongation, circularity and area. Two groups encompassed the most application-critical aggregates: one integrated aggregates of high complexity and low compactness while the other included elongated aggregates. In addition, the characterization of CNC dispersion after different levels of sonication was achieved by assessing the change in the number of elements belonging to each cluster after sonication. This approach could be used as a standard for the characterization of the aggregation state of CNCs.


Serotherapy of cancer: cellular changes in primary rat mammary carcinomas after infusion of syngeneic sera absorbed with protein A-Sepharose.
Serotherapy and plasma therapy have proved to be effective in the treatment of diverse neoplasms. The mechanisms of the tumoricidal or growth-inhibitory effects are unknown. We previously reported that activation of the alternative pathway of complement in absorbed sera correlated with the presence of anti-tumor activity. Complement components generated during absorption may serve as the initial mediators of cytotoxicity; for example, C5a may function in its role as a chemo-attractant. To further investigate the anti-tumor mechanisms, we undertook a series of sequential histological studies of in vivo changes in tumors following i.v. serotherapy. We found diffuse inflammatory cellular infiltrates in the interstitial compartments of primary mammary carcinomas of rats within 3-4 hr of administration of protein A-Sepharose absorbed syngeneic serum. The number of inflammatory cells was significantly higher in tumors from treated rats: total infiltrating cells (p = 0.002), eosinophils (p = 0.001), neutrophils (p = 0.001), macrophages (p = 0.001), lymphocytes (p = 0.004) and plasma cells (p = 0.001). Also, the mitotic index of tumor cells was significantly lower 4 hr after serotherapy when compared with that of untreated rat tumor cells. C3 in tumor tissue was decreased at 4 hr following serotherapy. Fibrosis was present in tumor nodules with retarded growth 5 weeks after the start of serotherapy. Localization of the infiltrating cells to tumor interstitial compartments prevents direct contact between inflammatory cells and neoplastic cells, making it unlikely that direct cell-cell killing occurs. Indirect cell killing within the tumor bed apparently occurs through several mechanisms involving interactions between serotherapy-initiated humoral mediators and inflammatory cells. The resulting anti-tumor effects include microvascular injury leading to localized ischemia, tumor infarction, and fibroblastic reactions obstructing tumor invasion and growth.


Decreasing effects of protein kinase inhibitors on the expression of NOS2 and inflammatory cytokines and on phagocytosis in rat peritoneal macrophages is partly related to repolarization.
The JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) pathway plays a pivotal role in macrophage polarization, but other signaling routes may also be involved. The aim of this study was to reveal the relationship of activation between rat peritoneal macrophages and their polarization, to detect the signaling routes involved, and find selective protein kinase inhibitors decreasing the production of inflammatory proteins in activated peritoneal macrophages. Rat macrophages were elicited with i.p. casein injection. CD80 and CD206 markers, NOS2 (Nitric oxide synthase 2), arginase, cytokines and phagocytosis were investigated by ELISA (Enzyme Linked Immunosorbent Assay), Western Blot, fluorescent microscopic and flow cytometry. Statistical methods were ANOVA (Analysis Of Variance) and Student t-tests. Resident and elicited cells expressed both CD80 and CD206 polarization markers. The involvement of MAPK (mitogen-activated protein kinases) and JAK/STAT pathways in the polarization was evidenced by a phosphorylation array, supported by Western blotting, by cytokine markers and by the inhibitory effects of kinase inhibitors. The expression of NOS2 and inflammatory cytokines was higher in elicited cells suggesting their M1 polarization. This effect was reduced by the inhibitors of MAPK and JAK/STAT pathways. Phagocytosis was also higher in elicited macrophages and decreased by these inhibitors. Nevertheless, they cannot change macrophage polarization unambiguously, as levels of CD80 and CD206 markers were not changed. For comparison, human blood macrophages were also studied. Similar effects and several differences were observed between the two types of macrophages, suggesting the role of the previous differentiation in defining their characteristics. Selected anti-cancer protein kinase inhibitors of p38, MAPK and JAK/STAT pathways are possible candidates for the therapy of inflammatory diseases.


Fatal deep venous thrombosis and pulmonary embolism secondary to melioidosis in China: case report and literature review.
Burkholderia pseudomallei is a gram-negative bacterium and the causative pathogen of melioidosis, which manifests a variety ranges of infection symptoms. However, deep venous thrombosis (DVT) and pulmonary embolism (PE) secondary to bacteremic melioidosis are rarely documented in the literature. Herein, we reported a fatal case of melioidosis combined with DVT and PE. A 54-year-old male construction worker and farmer with a history of diabetes was febrile, painful in left thigh, swelling in left lower limb, with chest tightness and shortness of breath for 4 days. He was later diagnosed as DVT of left lower extremity and PE. The culture of his blood, sputum and bone marrow samples grew B. pseudomallei. The subject was administrated with antibiotics (levofloxacin, cefoperazone/tazobactam, and imipenem) according to antimicrobial susceptibility testing and low molecular heparin for venous thrombosis. However, even after appropriate treatment, the patient deteriorated rapidly, and died 2 weeks after admission. This study enhanced awareness of the risk of B. pseudomallei bloodstream infection in those with diabetes. If a patient has predisposing factors of melioidosis, when DVT is suspected, active investigation and multiple therapeutic interventions should be implemented immediately to reduce mortality rate.


The effect of dexamethasone administration on rat intestinal permeability: the role of bacterial adherence.
Previous studies have shown that dexamethasone administration to rats results in diminution of biliary secretory immunoglobulin A concentration and alters intestinal barrier function to bacteria. The aims of this study were to examine and characterize the effect of dexamethasone on intestinal permeability and to determine the possible influence of bacterial adherence to the mucosa in this process. Groups of adult Fisher rats were studied, and the effects of dexamethasone administration and bowel decontamination on bacterial adherence and intestinal permeability were determined in various bowel segments. Dexamethasone administration was associated with a significant increase in bacterial adherence to the mucosa, which was most pronounced in the cecum (4.33 +/- 0.2 colony forming units (cfu) (log10) per gram of mucosa for control vs. 6.23 +/- 0.2 for dexamethasone). This was accompanied by significant alterations in intestinal permeability as measured by a decrease in transepithelial electrical resistance (49.5 +/- 4.1 omega.cm2 for control vs. 25.4 +/- 2.5 omega.cm2 for dexamethasone). Dual sodium-mannitol flux analysis showed this defect to be predominantly paracellular. Antibiotic decontamination of the intestine completely abrogated the intestinal permeability defect observed in this model. Bacterial-mucosal cell interactions may be responsible for alterations in intestinal permeability after dexamethasone administration.


Lecithin : cholesterol acyl transfer (LACT) and fatty acid composition of lecithin and cholesterol esters in young male myocardial infarction survivors.
Lecithin : cholesterol acyl transfer (LCAT) and relative fatty acid composition of serum lecithin and cholesterol esters were studied in 20 young male survivors of myocardial infarction (MI). Comparisons were made with controls matched for serum cholesterol. There was no difference in LCAT rate between MI patients and controls. The relative content of arachidonic acid in cholesterol esters was higher in MI patients. The fatty acid composition of lecithin and cholesterol esters suggests an equal transfer of linoleic and oleic acids from lecithin to cholesterol. Furthermore negative correlations were found between LCAT and linoleic acid content of lecithin (r = --0.43, P less than 0.01) and cholesterol esters (r = --0.45, P less than 0.01). This inverse relationship does not seem to be linked to substrate specificity, but rather to be mediated by influences in common on serum lipid content and turnover.


Professionals in 'alliance' achieve more effective discharge planning.
A general hospital's discharge planning program shows how patients' needs can be met more effectively when various health care professionals work in "alliance" rather than in more rigid modes, such as "the team." In alliance, professionals can perform nontraditional roles, compromise, and shift dominance and partnerships in order torespond to patients' needs with more flexibility and common sense.


Multi-phase distribution and comprehensive ecological risk assessment of heavy metal pollutants in a river affected by acid mine drainage.
To date, there is a lack of a comprehensive research on heavy metals detection and ecological risk assessment in river water, sediments, pore water (PW) and suspended solids (SS). Here, the concentrations of heavy metals, including Cu, Zn, Mn, Cd, Pb and As, and their distribution between the four phases was studied. Samples for analysis were taken from twelve sites of the Hengshi River, Guangdong Province, China, during the rainy and dry seasons. A new comprehensive ecological risk index (CERI) based on considering metal contents, pollution indices, toxicity coefficients and water categories is offered for prediction of potential risk on aquatic organisms. The results of comprehensive analysis showed that the highest concentrations of Cu, Zn and Mn of 6.42, 87.17 and 98.74mg/L, respectively, in PW were comparable with those in water, while concentrations of Cd, Pb and As of 609.5, 2757 and 96.38μg/L, respectively, were 2-5 times higher. The sum of the exchangeable and carbonate fractions of target metals in sediments followed the order of Cd > Mn > Zn > Pb > Cu > As. The distribution of heavy metals in phases followed the order of sediment > SS > water > PW, having the sum content in water and PW lower than 2% of total. The elevated ecological risk for a single metal and the phase were 34,585 for Cd and 1160 for water, respectively, implied Cd as a priority pollutant in the considered area. According to the CERI, the maximum risk value of 769.3 was smaller than 1160 in water, but higher than those in other phases. Out of considering the water categories and contribution coefficients, the CERI was proved to be more reliable for assessing the pollution of rivers with heavy metals. These results imply that the CERI has a potential of adequate assessment of multi-phase composite metals pollution.


Upregulation of Runt related transcription factor 1 (RUNX1) contributes to tendon-bone healing after anterior cruciate ligament reconstruction using bone mesenchymal stem cells.
Anterior cruciate ligament (ACL) injury could lead to functional impairment along with disabilities. ACL reconstruction often fails owing to the regeneration failure of tendon-bone interface. Herein, we aimed to investigate the effects of Runt related transcription factor 1 (RUNX1) on tendon-bone healing after ACL reconstruction using bone mesenchymal stem cells (BMSCs). BMSCs were isolated from the marrow cavity of rat femur, followed by the modification of RUNX1 with lentiviral system. Then, an ACL reconstruction model of rats was established with autografts. Results of flow cytometry exhibited positive-antigen CD44 and CD90, as well as negative-antigen CD34 and CD45 of the BMSCs. Then, we found that RUNX1-upregulated BMSCs elevated the decreased biomechanical strength of the tendon grafts after ACL reconstruction. Moreover, based on the histological observation, upregulation of RUNX1 was linked with better recovery around the bone tunnel, a tighter tendon-bone interface, and more collagen fibers compared to the group of BMSCs infected with LV-NC. Next, RUNX1-upregulated BMSCs promoted osteogenesis after ACL reconstruction, as evidenced by the mitigation of severe loss and erosion of the cartilage and bone in the tibial and femur area, as well as the increased number of osteoblasts identified by the upregulation of alkaline phosphatase, osteocalcin, and osteopontin in the tendon-bone interface. Elevated expression of RUNX1 contributed to tendon-bone healing after ACL reconstruction using BMSCs.


High-Frequency Occurrence of Surfactin Monomethyl Isoforms in the Ferment Broth of a Bacillus subtilis Strain Revealed by Ion Trap Mass Spectrometry.
Surfactins are cyclic lipopeptides consisting of a β-hydroxy fatty acid of various chain length and a peptide ring of seven amino acids linked together by a lactone bridge, forming the cyclic structure of the peptide chain. These compounds are produced mainly by Bacillus species and possess numerous biological effects such as antimicrobial (antiviral, antibacterial, and antifungal) activities. A mixture of surfactins extracted from Bacillus subtilis strain SZMC 6179J was examined by HPLC-ESI-IT-MS technique, enhancing their separation to reveal novel lipopeptide varieties with higher masses and to characterize their structures. During the MS² spectra analyses of their sodiated molecular ions [M + Na]⁺, a previously rarely encountered group of surfactins was detected and two novel types of the group were discovered containing methyl esterified aspartic acid residue in their fifth amino acid position. The relative amounts of these monomethyl isoforms exceeded 35% of the produced surfactin in total. In the m/z value of 1114, all the detected isoforms possessed aspartic acid 4-methyl ester residue in their fifth amino acid position (C17-[Lxx4, AME5], C18-[AME5]), offering an opportunity to separate a pure fraction of the compound and to study its biological activities in the future.


An interaction between thyroid hormone and nerve growth factor in the regulation of choline acetyltransferase activity in neuronal cultures, derived from the septal-diagonal band region of the embryonic rat brain.
Culture conditions have been established for growing neurons from the medial frontal part of the forebrain, containing the septum and the diagonal band of Broca, of 17-day-old rat embryos in a chemically defined medium. At 10 days in vitro, the cultures contained more than 96% nerve cells of which about 18% were cholinergic neurons, while the proportion of astrocytes was less than 1%. The majority of the cells that stained for acetylcholinesterase were bipolar but with different sizes and shapes. During development both the specific activity of choline acetyltransferase (ChAT) and the amount of protein increased markedly in the cholinergic cultures, ChAT activity rising much more than the protein content. Exposure of the cultures to nerve growth factor (NGF) or 3,3',5-triiodo-L-thyronine (T3) enhanced the expression of ChAT activity in a dose-dependent manner. The elevation of ChAT activity was due to an increase in the amount of enzyme per cholinergic cell, since, during the experimental period studied, neither treatment with NGF nor with T3 had significant effects on the total protein content of the cultures or on the number of cells, including the cholinergic neurons. When cultures were supplemented with both agents at maximal effective concentrations, the stimulation in ChAT activity was much greater than the sum of the individual effects. The observations indicate that subcortical cholinergic neurons, which are affected in Alzheimer's disease and in Down's syndrome, are subject to regulation by an interaction between thyroid hormone and local humoral factors such as NGF.


Boys Do Cry: Age and Gender Differences in Psycho-Physiological Distress during the COVID-19 Pandemic in Italy.
This article contributes to the quality of life literature by investigating gender and age gaps in psycho-physiological distress during the COVID-19 pandemic in Italy. Specifically, we investigate whether women experienced higher levels of distress than men, and if such gap can be explained by a greater negative reaction of women in the experience of a negative COVID-19 related event, such as the illness or death of a relative. Moreover, we explore whether age moderated or amplified the effect of a negative event on distress among women and men. To do so we rely on an ad hoc survey carried out between April 2020 and June 2021 in Italy, the first European country to be hit by the pandemic. Our results indicate that subjects who experienced the hospitalization or, more so, the death of a family member during the pandemic were more exposed to psycho-psychological distress compared to subjects who were not directly touched by COVID-19. Moreover, our results show that while women were on average more likely to express feelings of distress than men in absence of evident stressors, this gap disappeared among subjects who experience the death of a relative. Furthermore, our results indicate that experiencing a negative COVID-19 related event led to an increase in distress among all respondents except older men, who appeared to be the most resilient to the manifestation of any sign of distress. These results speak to important age and gender differences in the feelings and externalization of grief in the Italian context.


Augmented mechanical response of muscular thin-fiber receptors in aged rats recorded in vitro.
Musculoskeletal pain deteriorates quality of life by disrupting daily activities and is a considerable economic burden to many countries because of the large number of patients. Little is known about the peripheral neural mechanisms of muscular nociception in the aged, although structural and functional changes in the muscle are apparent as a function of age. The aim of the present study was to investigate the activities of aged muscle nociceptors systematically to mechanical, chemical and thermal stimuli, and to compare with the data from young animals. Activities of single C-fibers were recorded from in vitro preparations of extensor digitorum longus muscle-nerve excised from hind legs of aged rats (125-133 weeks). Mechanical threshold measured by a ramp mechanical stimulus in the aged muscle (median; 45.2 mN (IQR; 38.1-59.1 mN), n=29) was significantly lower than that in the younger muscle (median; 65.4 mN (IQR; 46.6-122.0 mN), n=33, p<0.01, Mann-Whitney U-test) reported in our previous study (Taguchi et al., 2005). In addition, the magnitude of the mechanical response during the first 5s of the 10s stimulus was significantly greater in the aged muscle (11.0 spikes (IQR; 6.5-20.5 spikes)) than in the young (7.0 spikes (IQR; 4.0-11.5 spikes), p<0.05, Mann-Whitney U-test). In contrast, the numbers of discharges induced by chemical (pH 5.5, ATP and bradykinin) and thermal (cold and heat) stimuli were not different with the different ages. These results showed an augmented mechanical response in muscle C-afferents in the aged rats.


In vitro antiproliferative effect of a water-soluble Laminaria japonica polysaccharide on human melanoma cell line A375.
A water-soluble polysaccharide WPS-2-1, purified from Laminaria japonica, has been found to have antitumor activity. In this study, WPS-2-1 exhibited high anti-proliferative activity on A375 cells in a dosedependent manner. Further investigation indicated that WPS-2-1 induced A375 cells apoptosis. Moreover, WPS-2-1-induced apoptosis was associated with the alteration in expressions of Bcl-2 family proteins. Mitochonadrial apoptotic pathway was involved in WPS-2-1-induced apoptosis, which included the loss of mitochondrial membrane and activation of caspase-3/9. The results in this study suggested that WPS-2-1 could effectively inhibit proliferation of A375 cells in vitro and induce apoptosis via mitochondrial apoptotic pathway. It might serve as a potential antitumor agent.


Electronic alerts for triage protocol compliance among emergency department triage nurses: a randomized controlled trial.
Alerts embedded in electronic health records (EHRs) are designed to improve processes at the point of care. The aim of this study was to determine if an EHR alert-at emergency department (ED) triage-increases the ED triage nurse's utilization of triage protocols. ED triage nurses were randomized to receive either a passive EHR alert or no intervention for patients with the following complaints: minor trauma with extremity injuries or female patients with abdominal pain. The EHR alert notified the nurse that the patient was eligible for diagnostic testing: radiographs for patients with injured extremities or urinalysis for female patients with abdominal pain. Twenty-eight nurses triaged 20,410 patients in the 6 months before the intervention and 19,157 in the 6 months after the intervention. Before the intervention, the urinalysis protocol was implemented in 101/624 (16.2%) patients triaged by the intervention group and 116/711 (16.3%) triaged by the control group. After the intervention, the urinalysis protocol was implemented in 146/530 (27.6%) patients triaged by the intervention group and 174/679 (25.6%) triaged by the control group. Before the intervention, the radiograph protocol was implemented in 58/774 (7.5%) patients triaged by the intervention group and 45/684 (6.6%) triaged by the control group. After the intervention, the radiograph protocol was implemented in 78/614 (12.7%) patients triaged by the intervention group and 79/609 (13.0%) triaged by the control group. The use of a passive EHR alert to promote ED triage protocols showed little benefit. Before the widespread implementation of EHR alerts for patient care, rigorous studies are required to determine the best alert methods and the impacts of such interventions.


Public and professional education on urgent therapy for acute ischemic stroke: a community-based intervention in Changsha.
Excessive delay of presentation for stroke in China is reported. In this study, an intervention trial was conducted to promote urgent therapy for acute ischemic stroke. Two communities in Changsha were selected as either intervention or control community from November 2007 to December 2011. Public and professional education was regularly implemented in the intervention community. Publics' knowledge about early identification and urgent therapy of ischemic stroke was surveyed before and after intervention in the two communities. During the intervention period, first-ever ischemic stroke cases occurring in the intervention community (intervention group) and that in the control community (control group) were collected and followed for 90 days. After intervention, the publics' knowledge levels in the intervention community improved significantly. Intervention group' average presentation time was shorter than control group (8.3 ± 5.8 vs. 10.5 ± 6.5 h, P = 0.018). Percentage of presentation time within 3 h (48.0 %), the rate of ambulance use (59.0 %), and thrombolytic therapy (9.3 %) in the intervention group was all obviously higher than that in the control group (21.5, 41.3, and 4.5, respectively). When admitted, the intervention group had lower mean systolic blood pressure (160.8 ± 26.7 vs. 164.7 ± 26.8 mmHg, P = 0.000) than control group. Survivors in the intervention group were more likely to be in higher Barthel index scoring groups than that in the control group at day 90 [(75, 50-100) vs. (65, 35-90), P = 0.035]. Public and professional education may promote prompt presentation and urgent therapy for ischemic stroke, which may be helpful for patients' prognosis.


Potentiometric titration behavior of polyaspartic acid prepared by thermal polycondensation.
The dissociation behavior of polyaspartic acid prepared by thermal polycondensation was studied by potentiometric titrations at various ionic strengths. From the analysis of the titration curves, the ratio of alpha- and beta-linkaged aspartyl residues was estimated at about 7:3 and the intrinsic dissociation constants of alpha- and beta-carboxyl groups are 3.25 and 4.35, respectively.


Combating Obesity in Head Start: Outdoor Play and Change in Children's Body Mass Index.
To determine whether increased outdoor play time at Head Start was associated with greater changes in body mass index (BMI) over the course of a preschool year. The authors used data from 2810 children from the Family and Child Experiences Survey 2006 cohort. With children's spring BMI as the outcome (both continuously measured and dichotomized to measure the risk of obesity), the authors conducted weighted regression analyses, controlling for child-level, family-level, and school-level covariates, including preschool entry BMI. Children played outdoors at school for roughly 37 minutes per day, with little variation across half-day and full-day programs. The more children played outdoors, the more their BMI decreased over the preschool year (β = -.05, 95% confidence interval (CI) [-0.08 to -0.01]) and the less likely they were to be obese (odds ratio = 0.99, 95% CI [0.98-0.99]). The difference between high levels and low levels of outdoor play corresponded to 0.18 BMI points and a 42% reduction in children's risk of obesity. Sixty minutes was the "tipping point" for the association between outdoor play time and improvements in children's BMI. These associations were also stronger among children who were obese at the start of the year, less active at home, and living in unsafe neighborhoods. Outdoor play time at Head Start is associated with decreases in children's BMI scores and, thus, may serve as an important means of preventing obesity. Head Start programs should consider establishing clear guidelines encouraging more outdoor time.


Impact of intrauterine balloon tamponade on emergency peripartum hysterectomy following vaginal delivery.
To assess the impact of intrauterine balloon tamponade as a second-line technique before resorting to emergency peripartum hysterectomy in cases with severe postpartum hemorrhage and uterotonic treatment failure following vaginal delivery. A retrospective, monocentric study evaluating cases of uterotonic treatment failure with severe postpartum hemorrhage following vaginal delivery between January 2005 and June 2018. Cases of cesarean section, amniotic embolism, uterine rupture, placenta accreta, and postpartum hemorrhage by vaginal laceration were excluded. The primary study outcome was incidence of emergency peripartum hysterectomy before and after use of intrauterine balloon tamponade was initiated. Among the 55,776 women who gave birth vaginally at our site during the study period, 161 (0.3 %) had severe postpartum hemorrhage with medical treatment failure (78 during the period prior to intrauterine balloon tamponade use, and 83 after intrauterine balloon tamponade use was initiated). The intrauterine balloon tamponade failure rate was 21.9 % (n = 18). Emergency peripartum hysterectomy was performed in 7 cases prior to intrauterine balloon tamponade use and 2 cases during use of intrauterine balloon tamponade. Thus, we observed a nonsignificant decrease in emergency peripartum hysterectomy after use of intrauterine balloon tamponade was implemented (9.0 % vs. 2.4 %, p = 0.09). However, the decrease was significant among patients who underwent conservative surgical treatment before intrauterine balloon tamponade use (53.8 % vs. 12.5 %, p = 0.041). Though we did not find a significant overall reduction in emergency peripartum hysterectomy following implementation of intrauterine balloon tamponade, there was a decrease in these cases when conservative surgical treatment was followed by intrauterine balloon tamponade.


Reference data for distal blood pressure in healthy elderly and middle-aged individuals measured with the strain gauge technique. Part I: resting distal blood pressure.
Most patients referred to our department for distal blood pressure (DBP) determination on suspicion of arterial peripheral vascular disease (apvd) are more than 60 years of age, whereas the only available reference data for resting pressure are based on data from healthy individuals aged between 43 and 57 years. Our aim was to investigate whether newly collected reference data for DBP measured using the strain-gauge technique in healthy subjects older than 60 years and in others between 45 and 58 years were significantly different from the old reference data used in daily practice. . Group I comprised 31 healthy persons aged between 61 and 87 years and group II 14 healthy middle-aged hospital staff members aged between 45 and 58 years. Strict rules of inclusion were followed. For group I, significantly greater gradients (DBP(toe) - systolic arm blood pressure and DBP(toe) - DBP(ankle)) were found in the new reference data compared to the old. No significant difference between the mean values of the gradient (DBP(ankle) - systolic arm blood pressure) was found between the old and new reference data, although the variation was significantly wider in the new reference data; the lower level of normality was therefore -15 mmHg compared to 0 mmHg in the old reference data. For group II, no significant differences between the gradients were found comparing the new and old reference data. These new data indicate that reference data gathered from middle-aged subjects should be changed when DBP measurements are used in patients older than 60 years of age.


The hemisoleus rotational flap provides a novel superior autograft reconstructive option for the treatment of chronic extensor mechanism disruption.
Chronic disruption of the extensor mechanism is a devastating problem after total knee arthroplasty. Quadriceps tendon ruptures occur at an estimated 0.1% prevalence in the setting of total knee arthroplasty. Complete tears of the quadriceps tendon generally have poor results and high rates of rerupture. We present a case of a quadriceps tendon rupture after total knee arthroplasty which reruptured after initial direct repair. The patient presented to us with a chronically retracted rerupture and was subsequently reconstructed successfully with a novel extended medial gastrocnemius-soleus-calcaneus local rotational pedicle flap.


Outcome measures in rheumatology applied in self-management interventions targeting people with inflammatory Arthritis A systematic review of outcome domains and measurement instruments.
Evaluating the effect of self-management interventions targeting people with inflammatory arthritis (IA) is a challenge because self-management interventions are complex and consensus on important outcomes is lacking. The aim is to identify, and map applied outcome domains and outcome measurement instruments from previous trials measuring the effect of self-management interventions targeting people with IA. We performed an informative systematic literature review following guidance from the 'Outcome Measures in Rheumatology' (OMERACT) and 'Core Outcome Measures in Effectiveness Trials' (COMET) initiatives. Trials describing their experimental intervention as "self-management" applied in people diagnosed with any IA were included. Information on outcome domains and the corresponding measurement instruments were extracted, sorted, and categorized in domains and sub-domains. From a total of 2,502 records, we included 38 trials published between 1988 and 2021. We identified 12 different outcome domains, covering 39 subdomains, collected with 119 different measurement instruments. The most frequently applied outcome domains were self-efficacy, pain, physical functioning/disability, anxiety and depression, quality of life, fatigue, global assessment/disease activity and coping. The applied measurement instruments varied within each outcome domain and were predominantly patient-reported outcomes. The outcome domains and measurement instruments used in self-management trials were widely diverse and differ from the current general OMERACT Core Outcome Sets (COS) for IA conditions. Further steps towards the establishment of a COS to be reported in all self-management intervention trials will enhance the relevance and the subsequent impact on the body of evidence from these trials.


Synthesis of higher alcohols over highly dispersed Cu-Fe based catalysts derived from layered double hydroxides.
Highly dispersed Cu-Fe based catalysts with Fe/Cu molar ratios ranging from 0.2 to 1 were prepared via thermal decomposition of layered double hydroxides (LDHs) precursors and tested for higher alcohol synthesis (HAS) via CO hydrogenation. The catalysts were characterized using different techniques such as XRD, TEM, XPS, and H2-TPR. It was demonstrated that the Cu and Fe ions were highly dispersed in the brucite-like layers of the LDHs. With increased Fe/Cu atomic ratio, the tetrahedrally coordinated Cu ion content, Cu reduction temperatures, and the spacing of layers initially increase until the Fe/Cu ratio reaches 0.5 and then decrease. In addition to the catalytic evaluation for CO hydrogenation and catalyst characterization, the relationships between the physical-chemical properties of the catalysts and their catalytic performances were also investigated. It was also found that the alcohols/hydrocarbons ratios correlate linearly with the tetrahedrally coordinated Cu ion content. Moreover, higher reduction temperatures of Cu species as well as larger spacing between the layers in the catalyst are favorable for the synthesis of alcohols. The incorporation of a suitable amount of Fe is beneficial for the production of higher alcohols, with the best catalytic performance (alcohol selectivity of 20.77% and C2+ alcohol selectivity of 48.06%) obtained from a Fe/Cu atomic ratio of 0.5.


Impact of irinotecan and oxaliplatin on overall survival in patients with metastatic colorectal cancer: a population-based study.
A look at the temporal impact of advancements in therapeutic options in the last 10 years-from fluorouracil to irinotecan and oxaliplatin-on overall survival in a population-based cohort.


Fundamentals of laparoscopic surgery: a surgical skills assessment tool in gynecology.
To describe our experience with the Fundamentals of Laparoscopic Surgery (FLS) program as a teaching and assessment tool for basic laparoscopic competency among gynecology residents. A prospective observational study was conducted at a single academic institution. Before the FLS program was introduced, baseline FLS testing was offered to residents and gynecology division directors. Test scores were analyzed by training level and self-reported surgical experience. After implementing a minimally invasive gynecologic surgical curriculum, third-year residents were retested. The pass rates for baseline FLS skills testing were 0% for first-year residents, 50% for second-year residents, and 75% for third- and fourth-year residents. The pass rates for baseline cognitive testing were 60% for first- and second-year residents, 67% for third-year residents, and 40% for fourth-year residents. When comparing junior and senior residents, there was a significant difference in pass rates for the skills test (P=.007) but not the cognitive test (P=.068). Self-reported surgical experience strongly correlated with skills scores (r-value=0.97, P=.0048), but not cognitive scores (r-value=0.20, P=.6265). After implementing a curriculum, 100% of the third-year residents passed the skills test, and 92% passed the cognitive examination. The FLS skills test may be a valuable assessment tool for gynecology residents. The cognitive test may need further adaptation for applicability to gynecologists.


Human fortilin is a molecular target of dihydroartemisinin.
Dehydroartemisinin (DHA) is an effective anti-malaria agent. Fortilin is an anti-apoptotic molecule overexpressed in many human cancers. Here, we show that DHA binds human fortilin, increases the ubiquitination of fortilin, shortens fortilin's half-life in a proteasome-dependent fashion, and reduces cellular levels of fortilin in varieties of cells. DHA induced DNA fragmentation in U2OS cells in a fortilin-dependent manner. The fortilin-knocked-down cells were less susceptible--and fortilin-overexpressing cells more susceptible--to DHA than were wild-type cells, suggesting that apoptotic effects of DHA are-at least partly-conferred through fortilin. Together, these data suggest that fortilin is a molecular target of DHA. DHA and its derivative may prove to be viable anti-cancer agents in fortilin-overexpressing cancers.