Hearts and minds: suicide among United States combat troops in Vietnam, 1957-1973.
The literature on suicides among military personnel in a combat zone remains anecdotal. Although one finds literary and journalistic accounts of the problem, it has not been systematically analyzed. This paper will examine suicides among American combat troops during their tour of duty in Vietnam. Utilizing statistical data from the Southeast Asia Combat Area Casualties Database (SACACD), the authors will survey its epidemiology among U.S. ground troops in Vietnam from 1957 to 1973. The results suggest that certain types of combat troops were significantly more likely than others to commit suicide. These findings not only provide important predictors for military health professionals in the assessment of suicide risk, they also raise disturbing questions about the nature of organized armed conflict.


Long-term outcome of lupus nephritis in Asian Indians.
There are sparse data on outcome of lupus nephritis from developing countries. This study looks at outcome in Asian Indians. This retrospective study included patients at a single center over 20 years. Patients were treated as per standard protocols. The primary outcome measure was chronic renal failure or death; the secondary outcome was end-stage renal disease or death. The worst-case scenario was also calculated, considering those lost to followup in the first year as events. Kaplan-Meier survival curves and the log rank test were used for survival analysis. Data are shown as the mean ± SD. We included 188 patients with lupus nephritis, with a female:male ratio of 11:1, a mean ± SD age at onset of 23.6 ± 10.5 years, and a median followup time of 6 years (interquartile range 3-9 years). Of 136 patients with a biopsy sample, the distribution was as follows: class II in 22, class III in 36, class IV in 61, class V in 16, and class VI in 1. Survival with normal renal function was 84%, 69%, and 57% at 5, 10, and 15 years, respectively; in the worst-case scenario, survival was 77%, 63%, and 51%, respectively. There was no difference in survival by histologic class; however, nonbiopsied patients had lower survival. Renal survival was 91%, 81%, and 76% at 5, 10, and 15 years, respectively; in the worst-case scenario, survival was 79%, 70%, and 66%, respectively. Risk factors for poor outcome were low C3, hematuria, hypertension, creatinine, lack of remission, and occurrence of major infection. There was a high rate of major infections of 42.3%, with tuberculosis at 11.5%. Infections caused one-half of all deaths. The outcome of lupus nephritis in Asian Indians with standard immunosuppressive regimens is reasonable, but immunosuppression is associated with a high rate of infection.


Overexpression of Sphk2 is associated with gefitinib resistance in non-small cell lung cancer.
Lung cancer is the major cause of cancer-related death worldwide, and 80 % of them are non-small cell lung cancer (NSCLC) cases. Recent studies have shown that sphingosine kinase 2 (SphK2) could promote tumor progression; however, whether SphK2 could affect the chemoresistance of NSCLC to chemotherapy remains unclear. To determine whether SphK2 serves as a potential therapeutic target of NSCLC, we utilized small interference RNA (siRNA) to knock down SphK2 expression in human NSCLC cells and analyzed their phenotypic changes. The data demonstrated that knockdown of SphK2 led to decreased proliferation and enhanced chemosensitivity and apoptosis to gefitinib in NSCLC cells. In this study, we describe the findings that overexpression of SphK2 promotes chemoresistance in NSCLC cells. Inhibition of SphK2 might be considered as a strategy in NSCLC treatment with gefitinib.


Morphofunctional characteristics of the right ventricle in Chagas' dilated cardiomyopathy.
Right ventricular involvement is a typical characteristic of Chagas' disease, and it has been described especially in the early stages of the disease. However, the role of right ventricular dysfunction in cardiac failure due to Chagas' cardiomyopathy has not been well established. Seventy-four patients with positive serology tests for Trypanosoma cruzi and Chagas' dilated cardiomyopathy characterized by left ventricular dilatation and systolic dysfunction were studied. Clinical history, physical exam, ECG, chest X-ray and Doppler echocardiogram with color flow mapping were obtained in all. Mean age was 47.5+/-12.9 and 51 were males (69%). Sixty-five patients (88%) were in NYHA functional classes I and II. Mild systolic dysfunction was present in 35 (47%) while in 18 (24%), dysfunction was moderate and in 21 (28%) it was severe. In 43 patients (58%), only the left ventricle was involved by echocardiographic criteria; the remaining 31 patients (42%) showed biventricular involvement. No patient had isolated involvement of the right ventricle. Greater dilation of the right ventricle was associated with larger diastolic (p<0.002) and systolic (p<0.001) diameters of the left ventricle. Systolic pulmonary artery pressure was obtained non-invasively in 54 patients. Pulmonary hypertension was associated with right ventricular dilation (p<0.005) and with systolic dysfunction of the left ventricle (p<0.001). In this group of patients with Chagas' dilated cardiomyopathy, right ventricular dysfunction was present when there was associated and significant involvement of the left ventricle and with higher levels of pulmonary pressure.


Is polycystic ovary syndrome associated with elevated muscle sympathetic nerve activity?
Polycystic ovary syndrome (PCOS) is a complex disorder characterized by reproductive abnormalities, cardiometabolic disturbances and a heightened risk of cardiovascular disease. A small but compelling body of research demonstrates that females with PCOS present with elevated muscle sympathetic nerve activity (MSNA) at rest. Heightened MSNA is present in lean, overweight and obese females with PCOS, but limited evidence suggests that androgens may be more strongly linked to elevated MSNA in lean females with PCOS than in obese females with PCOS. Although the specific mechanisms underlying elevated MSNA in PCOS remain elusive, sympathetic activation is implicated in the progression of several cardiovascular diseases and may contribute to the cardiovascular pathophysiology of PCOS. Encouragingly, MSNA appears responsive to non-pharmacological intervention, making the sympathetic nervous system a promising therapeutic target to mitigate cardiovascular risk in PCOS. This brief review summarizes the existing evidence regarding elevated MSNA, cardiovascular risk profile and vascular function, as well as the potential for clinical intervention and future research directions in females with PCOS. NEW FINDINGS: What is the topic of this review? The presence of elevated muscle sympathetic nerve activity in females with polycystic ovary syndrome and the implications for cardiovascular health. What advance does it highlight? The sympathetic nervous system likely contributes to elevated cardiovascular disease risk in females with polycystic ovary syndrome. Moreover, it presents as a promising therapeutic target for mitigating cardiovascular disease and merits further investigation.


Reactive oxygen species activate human peripheral blood dendritic cells.
This study investigates the effects of hydrogen peroxide, a potent oxygen free radical donor, on the phenotype and function of dendritic cells differentiated from peripheral blood precursors. We report that hydrogen peroxide induces an up-regulation of several dendritic cell surface markers involved in interaction with T cells, including MHC Class II molecules (DQ and DR) and the co-stimulatory molecules CD40 and CD86. Moreover we have observed that H2O2-treated dendritic cells are more efficient in promoting T cell proliferation than normal dendritic cells and that this enhancement can be blocked using the free radical scavenger agent N-acetylcysteine. Oxygen free radicals are a common by-product of inflammation, and our results suggest they may play an important role in activation of sentinel dendritic cells, linking tissue damage to the initiation of an adaptive immune response.


Antioxidant defence system during exponential and stationary growth phases of Phycomyces blakesleeanus: response to oxidative stress by hydrogen peroxide.
An analysis of the components of the antioxidant defence system in exponential and stationary growth phases of filamentous fungus Phycomyces blakesleeanus and the response to the oxidative stress hydrogen peroxide were performed. There is a strong positive correlation between mycelial antioxidant capacity and the contents of gallic acid, d-erythroascorbate (d-EAA) or d-erythroascorbate monoglucoside (d-EAAG). These secondary metabolites are specifically synthesized by this fungus and reach maximal values in the stationary growth phase, suggesting that they can play some role in the antioxidant defence system of this fungus. There is a differential expression of the two more notable antioxidant activities, catalase (CAT) and superoxide dismutase (SOD), depending of the growth stage of P. blakesleeanus, CAT being expressed in the exponential and SOD in the stationary phase. Phycomyces blakesleeanus showed a high resistance to the oxidative stress caused by H2O2 (50 and 200 mM) which was higher in exponential phase. This higher resistance can be explained by the presence of CAT, glutathione peroxidase (GPx), and the probable contribution of glutathione-S-transferase (GST) and high levels of reduced form of glutathione (GSH). The transition to stationary phase was accompanied with a higher physiological oxidative damage illustrated by the higher protein carbonylation. In this growth stage the resistance of the fungus to the oxidative stress caused by H2O2 could be explained by the presence of SOD, GPx, and the probable contribution of GST as well as of secondary metabolites, mainly d-EAA and d-EAAG. These results highlight a specific response to oxidative stress by H2O2 depending on the growth phase of P. blakesleeanus.


Quantitative gated blood pool SPECT for the assessment of coronary artery disease at rest.
Planar gated blood pool imaging (GBPI) has long proven to be useful for the noninvasive assessment of ventricular function. From a practical viewpoint, gated blood pool single photon emission computed tomography (GBPS) acquisition can be accomplished in the same time as a three-view planar series, with the benefit of a tomographic perspective that avoids chamber overlap. Quantitative gated blood pool SPECT was applied to 10 patients who underwent coronary arteriography, contrast ventriculography, and planar gated blood pool imaging. For each patient, the mid-short axis oblique slice was divided into 4 discrete segments using 4 different reference models and 2 forms of segmentation. A center of mass (counts) fixed in the end-diastolic frame and segmentation that bisected the ventricular septum proved to have the highest sensitivity and specificity for determining regional wall motion abnormalities at rest in myocardium supplied by severely diseased coronary arteries (>75 %). GBPS correctly identified 19 of 21 abnormal segments (90%), with good specificity (95%), whereas ventriculography identified 12 (57%) and planar GBPI identified 9 (43%) of the segments supplied by diseased coronaries. Quantitative GBPS appears to be a sensitive method for assessing coronary artery disease at rest in myocardium perfused by severely diseased coronary arteries.


Increased mast cell numbers in the conjunctiva of glaucoma patients: a possible indicator of preoperative glaucoma surgery inflammation.
Inflammation is a risk factor for scarring after trabeculectomy surgery. Mast cells are important mediators of inflammation and scarring in allergic eye disease. This exploratory project investigated the presence of mast cells in the conjunctiva of glaucoma patients having trabeculectomy surgery. Conjunctival biopsies from glaucoma patients belonging to specific groups: medically treated glaucoma (M, n=6), repeat glaucoma surgery (S, n=8), and uveitic glaucoma (U, n=7). The control group (C, n=8) was retinal detachment patients undergoing repair surgery for the first time. Immunohistochemistry techniques stained for the presence of the intracellular mast cell enzyme tryptase. The median mast cell tryptase-positive counts for all glaucoma groups (M, S, and U) ranged from 0.102-0.113 cells/mm2 compared to 0.064 cells/mm2 for group C. This was statistically significant comparing group S to group C (P=0.0063), but not when comparing groups U or M to group C. The mast cell tryptase-positive counts did not significantly differ among the groups. Mast cell numbers were significantly increased in glaucoma patients who have previously undergone surgery (group S). Mast cell activity may contribute to the scarring process and the increased risk of excessive conjunctival scarring after trabeculectomy surgery. Further investigation needs to be performed to evaluate this potential role.


Determinants of underweight among 6-59 months old children in Berahle, Afar, North East Ethiopia: a case control study 2016.
The objective of this study was to identify determinants of underweight among 6-59 months old children in Berahle Woreda, Afar, North East Ethiopia, in 2016. The median age (IQR) of cases and controls were 24 (34) and 18 (23) months respectively and 51.6% of the children were not exclusively breast-fed but 64.8% controls were exclusively breastfed. Age group of 48-59 months (AOR = 11.93; 95% CI 3.88-36.67), illiterate mothers (AOR = 2.32; 95% CI 1.19-4.55), low dietary diversity (AOR = 4.57; 95% CI 2.40-8.69), diarrhea in the past of 2 weeks (AOR = 2.93; 95% CI 1.46-5.85), birth interval (AOR = 5.17; 95% CI 2.37-11.26) and unprotected source of water (AOR = 2.62; 95% CI 1.42-4.85) were determinant factors of underweight.


Long-term effects of transient chemically induced colitis on the visceromotor response to mechanical colorectal distension.
Acute gastrointestinal infections with transient mucosal inflammation frequently precede the onset of functional GI disorders with altered visceral sensory function. We hypothesized that an acute inflammation of the mucosa is linked to long-lasting alterations of afferent visceral pathways. Utilizing abdominal wall electromyography, we tested the visceromotor response to tonic rectal distension (60 mm Hg/3 min) in fasted, conscious, male Lewis rats (n = 40) with a barostat device before and 2, 4, 15, and 17 weeks after rectal instillation of saline or trinitrobenzenesulfonic acid plus ethanol. Tissue samples from paired controls were obtained to assess histologic tissue alterations. Inflammatory changes were present up to 2 weeks after acid/ethanol instillation but not after saline instillation. Compared to baseline measurements, the visceromotor response to colorectal distension increased significantly and reached a maximum 17 weeks (P < 0.001) after induction of colitis, while it decreased in control experiments (P < 0.05). In conclusion, these data suggest that an acute inflammation has long-term effects on somatosensory functioning.


Comparison of total versus partial revision of primary ventriculoperitoneal shunt failures.
Optimal surgical management of patients presenting with primary shunt failure in the era of neuroendoscopy remains complex. The value of replacing the entire shunt system as opposed to a single shunt component has not been assessed extensively. In a retrospective study, the records of all patients who underwent their first shunt revision due to mechanical obstruction between September 2007 and December 2011 were reviewed. Shunt revisions were classified as total (entire shunt replaced) or partial (only malfunctioning component replaced). Patients having a minimum follow-up of 1 year after primary shunt revision were included in the study. Kaplan-Meier (shunt survival curves) and log-rank analysis were used to compare failure rates between partially and totally revised shunts. Records of 62 patients in whom cause of primary shunt failure was obstruction (P roximal or distal) were analyzed retrospectively. At the end of follow-up period, 26 out of 28 partial revision group and 22 out of 34 total revision group had shunt failure. The median survival of the shunt in the partial revision and total revision groups was 60 and 270 days, respectively. The method (partial/total revision) related difference in shunt survival duration was statistically significant as shown by log-rank analysis (log-rank test value = 5.94 and P < 0.05). Partial revision of shunt predisposes to accelerated shunt failure as compared with total revision in cases of obstructed ventriculoperitoneal shunt.


Restricted coronary flow reserve in patients with mitral regurgitation improves after mitral reconstructive surgery.
The purpose of this study was to assess coronary flow characteristics in patients with chronic mitral regurgitation (MR). Coronary flow reserve (CFR) has been reported to be restricted in cases with left ventricular (LV) volume overload caused by aortic regurgitation and increased LV preload. The study populations consisted of 31 patients with nonrheumatic chronic MR. Eleven with chest pain and normal coronary arteries served as control subjects. Phasic coronary flow velocities were obtained in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg/min adenosine infusion intravenously) using a 0.014-in. (0.036 cm), 15-MHz Doppler guide wire. Coronary flow reserve was obtained from the ratio of hyperemic/baseline time-averaged peak velocity (APV). Thirteen cases who underwent mitral valve reconstructive surgery were also studied 1 month after surgery. Compared with control subjects, CFR was significantly reduced in cases with MR (2.1+/-0.5 vs. 33+/-0.6, respectively, p < 0.01) because baseline APV was significantly greater (28+/-8 vs. 19+/-6 cm/s, respectively, p < 0.01), although maximal hyperemic APV was not significantly different (56+/-14 vs. 61+/-16 cm/s, respectively, p = NS). Significant correlations were obtained between CFR and LV end-diastolic pressure (LVEDP) (r = 0.70, p < 0.01), LV mass index (r = 0.42, p < 0.01), LV end-diastolic volume (r = 038, p = 0.04) and MR volume (r = 0.39, p = 0.03), and stepwise regression analysis showed LVEDP was the most important determinant of CFR in MR (r2 = 0.49, p < 0.0001). This restricted CFR improved significantly after mitral valve reconstructive surgery (2.1+/-0.5 vs. 3.1+/-0.6, respectively, p < 0.01) because of reduction of baseline APV (28+/-8 vs. 21+/-8 cm/s, respectively, p < 0.01). Coronary flow reserve is limited in cases with MR because of elevation of baseline resting flow velocity. This reduction of CFR correlates well with increase in LV preload, mass and volume overload, especially with increase in LV preload, and this restricted CFR improves after mitral valve surgery.


Small-Animal Imaging Using Diffuse Fluorescence Tomography.
Diffuse fluorescence tomography (DFT) has been developed to image the spatial distribution of fluorescence-tagged tracers in living tissue. This capability facilitates the recovery of any number of functional parameters, including enzymatic activity, receptor density, blood flow, and gene expression. However, deploying DFT effectively is complex and often requires years of know-how, especially for newer mutlimodal systems that combine DFT with conventional imaging systems. In this chapter, we step through the process of using MRI-DFT imaging of a receptor-targeted tracer in small animals.


Adenoviral transduction of mesenchymal stem cells.
Intact or genetically manipulated mesnechymal stem cells (MSCs) are being considered an important cell source for developing human cell-based therapeutic approaches. For applications in which transient, high-level expression of the transgene is necessary, adenovirus vectors have become increasingly popular gene-transfer vehicles. However, host range and cell-type tropism restrict the use of specific adenovectors, sometimes necessitating the lengthy development of vectors with appropriate cell specificity. Here, we present a versatile and inexpensive porcine MSC transduction procedure that can also be used on other cell types from various species, including human that are otherwise refractory to adenovirus infection.


Prospective validation of Sophia observation withdrawal symptoms: A paediatric delirium scale in critically ill children in Denmark.
Paediatric delirium (PD) is increasingly recognised as a common disorder in critically ill children with a reported prevalence ranging from 9% to 66%. We validated the PD component of the Sophia Observation withdrawal Symptoms-Paediatric Delirium (SOS-PD) scale in a Danish setting to provide increased awareness and reliable identification of this critical condition, thereby paving the way for improved pathways to targeted delirium care. The objectives of this study were to criterion validate the PD component of the SOS-PD screening tool by comparing blinded psychiatric and nurse assessments and to estimate the prevalence of delirium in critically ill children in a Danish context. A prospective observational study was performed on critically ill children aged between 3 m and 18 y, admitted to an intensive care unit, with a hospital stay of 48 h or more. Assessments took place on a fixed weekday over an 18-month period. To test accuracy and criterion validity, bedside nurses' SOS-PD assessments were compared to the reference standard, a diagnostic assessment performed by a child psychiatrist according to the Diagnostic and Statistical Manual-V criteria by use of the Vanderbilt Assessment of Delirium in Infants and Children. We included 141 children in the study, 30 (21%) of whom were diagnosed with delirium by the child psychiatrist. The accuracy of the delirium diagnosis was 93.6% (95% confidence interval [CI]: 88.3-97.1) among the nurses' SOS-PD assessments compared to the reference standard. The SOS-PD demonstrated a high sensitivity of 83.3% (95% CI: 65.3-94.4) and a high specificity of 96.4% (95% CI: 91.0-99.0) with five false-negative and four false-positive cases. The PD component of the SOS-PD tool has good accuracy and validity for assessments performed by nurses compared to a child psychiatrist's diagnosis in critically ill children in a Danish setting. We recommend the use of the SOS-PD instrument in clinical practice.


Bifidobacteria in disease: from head to toe.
Bifidobacteria as a strictly anaerobic gram-positive bacteria, is widely distributed in the intestine, vagina and oral cavity, and is one of the first gut flora to colonize the early stages of life. Intestinal flora is closely related to health, and dysbiosis of intestinal flora, especially Bifidobacteria, has been found in a variety of diseases. Numerous studies have shown that in addition to maintaining intestinal homeostasis, Bifidobacteria may be involved in diseases covering all parts of the body, including the nervous system, respiratory system, genitourinary system and so on. This review collects evidence for the variation of Bifidobacteria in typical diseases among various systems, provides mild and effective therapeutic options for those diseases that are difficult to cure, and moves Bifidobacteria from basic research to further clinical applications.


The 1,25-dihydroxyvitamin D3 (VD) analogues MC903, EB1089 and KH1060 activate the VD receptor: homodimers show higher ligand sensitivity than heterodimers with retinoid X receptors.
The nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), VDR, belongs to the nuclear receptor superfamily. This ligand-inducible transcription factor mediates the genomic VD signalling pathways by binding to specific response elements in the promoter region of VD regulated genes. Two types of natural VD response elements are used as models for the VDR-mediated transcriptional activation: one is bound by VDR-homodimers and is found in the human osteocalcin gene promoter, and the other is bound by heterodimers of VDR with retinoid X receptors (RXRs) as in the mouse osteopontin promoter. Here, we demonstrate that the VD analogues MC903, EB1089 and KH1060, previously shown to be potent regulators of proliferation and differentiation, are able to act as ligands for VDR and replace VD as a ligand in both nuclear signalling pathways. We found that they have different potency and sensitivity in their ability to stimulate the hormone-dependent promoter element. MC903 and EB1089 provide about 20% higher induction of gene activity than VD in a gene reporter system, whereas KH1060 was more sensitive, inducing transcription at about 100-fold lower doses than VD. Interestingly, VD and its analogues induce VDR homodimer-mediated gene activity at a 3- to 4-fold lower concentration than that of VDR-RXR heterodimers. This suggests that the ligand concentration is an additional regulatory level in the discrimination between signalling pathways involving homo- and heterodimeric hormone receptors.


The Adsorption Behavior of Gas Molecules on Co/N Co-Doped Graphene.
Herein, we have used density functional theory (DFT) to investigate the adsorption behavior of gas molecules on Co/N3 co-doped graphene (Co/N3-gra). We have investigated the geometric stability, electric properties, and magnetic properties comprehensively upon the interaction between Co/N3-gra and gas molecules. The binding energy of Co is -5.13 eV, which is big enough for application in gas adsorption. For the adsorption of C2H4, CO, NO2, and SO2 on Co/N-gra, the molecules may act as donors or acceptors of electrons, which can lead to charge transfer (range from 0.38 to 0.7 e) and eventually change the conductivity of Co/N-gra. The CO adsorbed Co/N3-gra complex exhibits a semiconductor property and the NO2/SO2 adsorption can regulate the magnetic properties of Co/N3-gra. Moreover, the Co/N3-gra system can be applied as a gas sensor of CO and SO2 with high stability. Thus, we assume that our results can pave the way for the further study of gas sensor and spintronic devices.


Cardiac cycle-dependent alternating flow in vertebral arteries with subclavian artery stenoses.
Continuous-wave Doppler sonography is a reliable method for detecting severe subclavian stenosis and occlusion as well as subclavian steal. Intermediate stages leading to subclavian steal can also be detected. These are characterized by a cardiac-phase-dependent alternating flow direction in the vertebral artery. Some cases of proximal subclavian or proximal vertebral artery stenosis produce a systolic deceleration of flow in the vertebral artery. Stenosis and occlusion of the subclavian artery as well as stenosis of the subclavian and vertebral arteries can be distinguished. The pulse curve changes described can be reversed by a vascular by-pass. Alternating flow direction or systolic deceleration of flow in the radial artery could also be observed or induced in a iatrogenic model using Cimino's a-v fistula in the arm in patients on dialysis. The results in beginning subclavian steal situations can be applied in principle to other collateral circulations, and in particular to the hemodynamics in the region of watersheds.


On the behavior of electrokinetic streaming potential during protein filtration with fully and partially retentive nanopores.
An experimental investigation of the electrokinetic streaming potentials of both fully and partially retentive nanopores as compared with the filtration progress of dilute globular protein solution under different surface charge conditions was performed using hollow fibers. The streaming potential is generated by the electrokinetic flow effect within the electric double layer of the charged surface. Depending on the solution pH, both the protein and the pore wall can be either repulsive or attractive due to the long-range electrostatic interaction. The repulsive electrostatic interaction allows the protein particles to stay in a suspended state above the outer surface of hollow fibers instead of being deposited. The apparent streaming potential value at partially retentive pores is larger than that at fully retentive pores for the oppositely charged case; however, the opposite behavior is shown for the same-charged case. The axial-position-dependent streaming potential was also observed in order to explore the development of a concentration polarization layer during the cross-flow filtration. The time evolution of the streaming potential during the filtration of protein particles is related to the filtrate flux, from which it can be found to provide useful real-time information on particle deposition onto the outer surfaces of hollow fibers.


Proteins of fast axonal transport in regenerating rat sciatic sensory axons: a conditioning lesion does not amplify the characteristic response to axotomy.
The regeneration rate of axons following injury can be influenced by the past history of the neuron: if an axon received a "conditioning" lesion its regeneration rate from a subsequent "test" lesion is increased. Because regeneration is associated with the increased synthesis and fast axonal transport of growth-associated proteins of unknown functions, we investigated whether the increased regeneration rate (to 81%) seen in conditioned rat sciatic sensory axons following a test lesion was associated with an amplification of the increase in growth-associated protein expression. The test lesion did not produce any amplification of the increase in growth-associated protein expression resulting from the preceding conditioning lesion. We conclude that this aspect of the cell body reaction to axotomy is not involved in the conditioning lesion effect on regeneration rate, and, as a corollary, it appears that fast-transported proteins whose expression alters after axotomy are not involved in the regulation of the regeneration rate.


Efficacy of Systemically Administered Retargeted Oncolytic Herpes Simplex Viruses-Clearance and Biodistribution in Naïve and HSV-Preimmune Mice.
We investigated the anticancer efficacy, blood clearance, and tissue biodistribution of systemically administered retargeted oncolytic herpes simplex viruses (ReHVs) in HSV-naïve and HSV-preimmunized (HSV-IMM) mice. Efficacy was tested against lung tumors formed upon intravenous administration of cancer cells, a model of metastatic disease, and against subcutaneous distant tumors. In naïve mice, HER2- and hPSMA-retargeted viruses, both armed with mIL-12, were highly effective, even when administered to mice with well-developed tumors. Efficacy was higher for combination regimens with immune checkpoint inhibitors. A significant amount of infectious virus persisted in the blood for at least 1 h. Viral genomes, or fragments thereof, persisted in the blood and tissues for days. Remarkably, the only sites of viral replication were the lungs of tumor-positive mice and the subcutaneous tumors. No replication was detected in other tissues, strengthening the evidence of the high cancer specificity of ReHVs, a property that renders ReHVs suitable for systemic administration. In HSV-IMM mice, ReHVs administered at late times failed to exert anticancer efficacy, and the circulating virus was rapidly inactivated. Serum stability and in vivo whole blood stability assays highlighted neutralizing antibodies as the main factor in virus inactivation. Efforts to deplete mice of the neutralizing antibodies are ongoing.


Electron microscopic localization of acetylcholinesterase in the dentate gyrus of young and adult rats.
Acetylcholinesterase (AChE) histochemical staining occurred in neurons of the dentate gyrus at the day of birth and steadily increased in intensity and distribution during the first 3 postnatal weeks until the adult pattern was reached. Granule cells failed to display AChE staining; however, the somata of most non-principal cells in these regions showed AChE activity. It is interesting that most hilar neurons in the dentate gyrus were AChE-positive, but molecular layer local circuit neurons and pyramidal basket cells associated with the granule cell layer did not display AChE staining. AChE reaction product was localized to the nuclear envelope and cisternae of the granular endoplasmic reticulum in the labeled neuronal somata. In addition, the neuropil in the dentate gyrus displayed AChE staining associated with membranes. The possible cholinoceptive role of the AChE somata in the hilus is discussed.


Viral Vector-Based Modeling of Neurodegenerative Disorders: Parkinson's Disease.
Gene therapy methods are increasingly used to model Parkinson's disease (PD) in animals in an effort to test experimental therapeutics within a more relevant context to disease pathophysiology and neuropathology. We have detailed several criteria that are critical or advantageous to accurately modeling PD in a murine model or in a nonhuman primate. Using these criteria, we then evaluate approaches made to model PD using viral vectors to date, including both adeno-associated viruses and lentiviruses. Lastly, we comment on the consideration of aging as a critical factor for modeling PD.


Purification of plasmid DNA vectors by aqueous two-phase extraction and hydrophobic interaction chromatography.
The current study explores the possibility of using a polyethyleneglycol(PEG)-ammonium sulphate aqueous two-phase system (ATPS) as an early step in a process for the purification of a model 6.1 kbp plasmid DNA (pDNA) vector. Neutralised alkaline lysates were fed directly to ATPS. Conditions were selected to direct pDNA towards the salt-rich bottom phase, so that this stream could be subsequently processed by hydrophobic interaction chromatography (HIC). Screening of the best conditions for ATPS extraction was performed using three PEG molecular weights (300, 400 and 600) and varying the tie-line length, phase volume ratio and lysate load. For a 20% (w/w) lysate load, the best results were obtained with PEG 600 using the shortest tie-line (38.16%, w/w). By further manipulating the system composition along this tie-line in order to obtain a top/bottom phase volume ratio of 9.3 (35%, w/w PEG 600, 6%, w/w NH4)2 SO4), it was possible to recover 100% of pDNA in the bottom phase with a three-fold increase in concentration. Further increase in the lysate load up to 40% (w/w) with this system resulted in a eight-fold increase in pDNA concentration, but with a yield loss of 15%. The ATPS extraction was integrated with HIC and the overall process compared with a previously defined process that uses sequential precipitations with iso-propanol and ammonium sulphate prior to HIC. Although the final yield is lower in the ATPS-based process the purity grade of the final pDNA product is higher. This shows that it is possible to substitute the time-consuming two-step precipitation procedure by a simple ATPS extraction.


The lncRNA UNC5B-AS1 promotes proliferation, migration, and invasion in papillary thyroid cancer cell lines.
The incidence of thyroid cancer detection is continually improving worldwide with the spread of diagnostic imaging and surveillance. Although we have made great progress, there are still unknown mechanisms of papillary thyroid cancer. We found that UNC5B-AS1 is a potential oncogene in thyroid cancer. Therefore, our study aimed to investigate the biological functions of the lncRNA UNC5B-AS1 in papillary thyroid cancer. As a result, RNA-seq data on primary papillary thyroid cancer (PTC) in the TCGA database were obtained. RT-qPCR was performed to evaluate the expression levels in thyroid tissue. We then analysed the expression level of UNC5B-AS1 and its association with clinicopathologic characteristics in the TCGA database. We downregulated UNC5B-AS1 using small interfering RNA and carried out assays of cell proliferation, colony formation, migration and invasion to explore the function of UNC5B-AS1 in PTC cell lines (TPC1 and BCPAP). These results suggested that the lncRNA UNC5B-AS1 was significantly upregulated in both the TCGA cohort and our tissue cohort. Upregulated UNC5B-AS1 correlated with lymph node metastasis (P < 0.001), tumor size (P = 0.002) and histological type (P = 0.013). We also achieved an area under the ROC curve (AUC) of 93.2% for our validated cohort, which was consistent with the AUC of 94.5% for the TCGA cohort, for differentiating between PTC tissues and normal tissues. Downregulating UNC5B-AS1 expression at the RNA level significantly inhibited cell proliferation, colony formation, migration, and invasion in PTC cell lines (TPC1 and BCPAP). This study demonstrated that the lncRNA UNC5B-AS1 plays an important role in tumourigenesis and metastasis of PTC and may be a potential therapeutic target for PTC.


[Avoidance of ventricular pacing in patients with sinus node disease or intermittent AV block].
In patients with frequent right ventricular stimulation, worsening of heart failure and atrial fibrillation may occur. Avoidance of unnecessary right ventricular pacing is a major requirement for pacemaker selection and programming in patients with sinus node disease or intermittent AV block. In dual chamber pacemakers this goal can be achieved by programming a long AV delay or an AV delay hysteresis. Algorithms that allow AAI pacing in a dual chamber pacing mode and change to DDD mode in case of high degree AV block are a new attempt to avoid unnecessary right ventricular pacing. The article describes various strategies to avoid unnecessary ventricular pacing and discusses their advantages and disadvantages.


Non-invasive estimation of cardiac output in mechanically ventilated patients: a prolonged expiration method.
A non-invasive method for the estimation of cardiac output in mechanically ventilated patients is described. The method is based on prolonged expiration, and relies on measurement of gas concentrations and flow rate. A pneumatic system, with an ad hoc designed orifice resistance, has been made and experimentally characterized to adapt the breathing circuit to this application. Cardiac output is calculated using two algorithms and the results are compared with the ones obtained by thermodilution. To this purpose, we prospectively enrolled twenty mechanically ventilated patients, who had undergone cardiac surgery, and both algorithms show good correlation with thermodilution (R > 0.8). The application of the first algorithm gave mean cardiac output values slightly lower than those obtained by thermodilution (-6%), while the application of the second algorithm gave higher values (+30%). Difference standard deviations between paired measurements is 0.72 L min(-1) for the first algorithm and 1.07 L min(-1) for the second one. Standard deviation obtained by the application of the first algorithm is slightly lower than those relative to other minimally invasive techniques. Through prolonged expiration, and standardization and automation of the procedure on mechanically ventilated patients, the proposed system allows to obtain a non-invasive estimation of cardiac output.


Optical detection of organophosphorus compounds based on Mn-doped ZnSe d-dot enzymatic catalytic sensor.
In this paper, we report a sensitive and selective method for detection of organophosphorus compounds (OPs) based on Mn:ZnSe d-dots-enzyme-hydrogen peroxide (H(2)O(2)) fluorescence quenching system. Acetylcholine esterase (AChE) can hydrolyze acetylcholine (ACh) to choline. Subsequently, choline oxidase (ChOx) oxidizes choline to generate H(2)O(2). The enzyme-generated H(2)O(2) can quench the fluorescence of Mn:ZnSe d-dots. When paraoxon are introduced in solution, it can interact with the active centers of AChE and decrease the enzyme activity. This leads to the decrease of the H(2)O(2) production and then the fluorescence quenching rate of Mn:ZnSe d-dots. Experimental results showed that the enzyme inhibition percentage of Mn:ZnSe d-dots-ChOx-AChE-ACh system was proportional to the logarithm of paraoxon in the range 4.84×10(-11) to 4.84×10(-6) mol/L with the detection limit (S/N=3) of 1.31×10(-11) mol/L. The proposed biosensor has been employed for quick determination of paraoxon in tap water and milk samples with satisfactory reproducibility and accuracy. This nano-biosensor was proved to be sensitive, rapid, simple and tolerance of most interfering substances.


Mid- and low-rectal cancer: laparoscopic vs open treatment-short- and long-term results. Meta-analysis of randomized controlled trials.
The laparoscopic approach in the treatment of mid- or low-rectal cancer is still controversial. Compared with open surgery, laparoscopic resection of extraperitoneal cancer is associated with improved short-time non-oncological outcomes, although high-level evidence showing similar short- and long-term oncological outcomes is scarce. The aim of our paper is to study the oncological and non-oncological outcomes of laparoscopic versus open surgery for extraperitoneal rectal cancer. A systematic review of MedLine, EMBASE, and CENTRAL from January 1990 to October 2020 was performed by combining various key words. Only randomized controlled trials (RCTs) comparing laparoscopic versus open surgery for extraperitoneal rectal cancer were included. The quality of RCTs was assessed using the Cochrane reviewer's handbook. This meta-analysis was based on the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. This study analyzes laparoscopic versus open surgery for extraperitoneal rectal cancer. Primary outcomes were oncological parameters. Fifteen RCTs comprising 4,411 patients matched the selection criteria. Meta-analysis showed a significant difference between laparoscopic and open surgery in short-time non-oncological outcomes. Although laparoscopic approach increased operation time, it decreases significantly the blood loss and length of hospital stay. No significant difference was noted regarding short- and long-term oncological outcomes, but 4 and 5 years disease-free survival were statistically higher in the open group. There are still questions about the long-term oncological outcomes of laparoscopic surgery for extraperitoneal rectal cancer being comparable to the open technique. Considering that all surgical resections have been performed in high volume centers by expert surgeons, the minimally invasive surgery in patients with extraperitoneal cancer could still be not considered equivalent to open surgery in terms of oncological radicality.


In vitro intrathymic differentiation kinetics of human fetal liver CD34+CD38- progenitors reveals a phenotypically defined dendritic/T-NK precursor split.
Human CD34+CD38- hematopoietic precursor cells from fetal liver are able to develop into T, NK, and dendritic cells in a hybrid human/mouse fetal thymic organ culture (FTOC). In this report, we pay particular attention to the early events in differentiation of these precursor cells. We show that the CD34+CD38- precursor cells, which are CD4-CD7-cyCD3-HLA-DR-/++ (cy, cytoplasmatic), differentiate into a CD4+ population that remained CD7-cyCD3-HLA-DR++ and a CD4- population that expressed CD7 and cyCD3. The CD4+CD7-cyCD3- cells differentiate into phenotypically and functionally mature dendritic cells, but do not differentiate into T or NK cells. The CD4-CD7+cyCD3+ population later differentiates into a CD4+CD7+cyCD3+HLA-DR- population, which has no potential to differentiate into dendritic cells but is able to differentiate into NK cells and gammadelta and alphabeta T lymphocytes. These findings support the notion that the T/NK split occurs downstream of the NK/dendritic split.


Effect of Tianshu capsule in treatment of migraine: a meta-analysis of randomized control trials.
To review the efficacy of Tianshu capsule in the treatment of migraine. Retrieving papers from Pubmed, cochrane central register of controlled trials (CENTRAL), Weipu database (VIP), China biology medicine (CBM), China national knowledge infrastructure (CNKI), and Wanfang Data. Two reviewers retrieved and extracted the information independently. Retrieval time scale is up to August 2012. Software Review Manager 5.1 was used for analysis. A total of 10 studies including 937 migraine patients. The merged data shows Tianshu capsule had a higher effective rate in treating migraine, and there is no significant heterogeneity between Tianshu capsule group and control group (Chi2 = 6.33, df = 9, P = 0.71, I2 = 0%), OR = 4.18 [95% CI (2.93,5.95)]. Tianshu capsule alone compared to conventional therapy also showed advantages, and there was low heterogeneity (chi2 = 4.53, df = 3, P = 0.21, I2 = 34%), OR = 3.95 [95% CI (2.32, 6.72)]. Meta-analysis results show that clinical efficacy of Tianshu capsule was better than that of the control group in the treatment of migraine and there was a significant difference (P < 0.000 01). Tianshu capsule had better efficacy in the treatment of migraine with fewer adverse effects.


Porcine thyroid cytosolic, latent, alkaline, ribonuclease: does an acidification step during purification alter the enzyme's properties?
The effect of an acidic step in the purification of porcine thyroid, latent, alkaline ribonuclease was studied using highly purified acid-treated and non-acid-treated enzymes. The enzymes differed by affinity and CM-cellulose chromatography, specific activity, in distribution among multiple forms, in response to some mono- and divalent salts, in degree of inhibition by p-chloromercuriphenylsulfonate and ribonuclease inhibitor, in activity toward poly (U). The acid-treated enzyme was very heterogeneous as shown by chromatography on affinity and ion-exchange columns and electrophoresis. The enzymes had similar molecular weights, pH optima, ionic strength effects, general specificity and products.


Photoelectrochemical Polymerization for Solid-State Dye-Sensitized Solar Cells.
Dye-sensitized solar cells represent promising alternative photovoltaic (PV) technologies with the advantages of low material cost, ease of production, and high performance for indoor applications. Solid-state DSCs (ssDSCs) have been developed to greatly diminish the problems of electrolyte leakage and electrode corrosion. However, the power conversion efficiency of ssDSCs generally is much lower than traditional liquid DSCs, resulting in low conductivity and poor pore infiltration of solid HTMs in mesoporous structures. To overcome these problems, in situ photoelectrochemical polymerization (PEP) approach is developed to synthesize polymer HTMs in the porous electrodes, enabling enhancement of pore infiltration fraction and conductivity. The PEP method offers great opportunities for engineering the HTM interfaces, tuning the charge dynamics, and improving the PV performance of ssDSCs. Here the authors aim to present a coherent review of the recent development of material engineering and interfacial optimization for ssDSCs. The recent advances in the PEP are also summarized, with special emphasis on how the influencing factors control the PEP kinetics, the polymer properties as well as the device performance. This review provides a deep understanding of the mechanism of photopolymerization across different conditions, which serves as a guidebook for further optimization of the PEP process for ssDSCs.


Chromium(VI) interaction with plant and animal mitochondrial bioenergetics: a comparative study.
The mechanism of Cr(VI)-induced toxicity in plants and animals has been assessed for mitochondrial bioenergetics and membrane damage in turnip root and rat liver mitochondria. By using succinate as the respiratory substrate, ADP/O and respiratory control ratio (RCR) were depressed as a function of Cr(VI) concentration. State 3 and uncoupled respiration were also depressed by Cr(VI). Rat mitochondria revealed a higher sensitivity to Cr(VI), as compared to turnip mitochondria. Rat mitochondrial state 4 respiration rate triplicated in contrast to negligible stimulation of turnip state 4 respiration. Chromium(VI) inhibited the activity of the NADH-ubiquinone oxidoreductase (complex I) from rat liver mitochondria and succinate-dehydrogenases (complex II) from plant and animal mitochondria. In rat liver mitochondria, complex I was more sensitive to Cr(VI) than complex II. The activity of cytochrome c oxidase (complex IV) was not sensitive to Cr(VI). Unique for plant mitochondria, exogenous NADH uncoupled respiration was unaffected by Cr(VI), indicating that the NADH dehydrogenase of the outer leaflet of the plant inner membrane, in addition to complexes III and IV, were insensitive to Cr(VI). The ATPase activity (complex V) was stimulated in rat liver mitochondria, but inhibited in turnip root mitochondria. In both, turnip and rat mitochondria, Cr(VI) depressed mitochondrial succinate-dependent transmembrane potential (Deltapsi) and phosphorylation efficiency, but it neither affected mitochondrial membrane permeabilization to protons (H+) nor induced membrane lipid peroxidation. However, Cr(VI) induced mitochondrial membrane permeabilization to K+, an effect that was more pronounced in turnip root than in rat liver mitochondria. In conclusion, Cr(VI)-induced perturbations of mitochondrial bioenergetics compromises energy-dependent biochemical processes and, therefore, may contribute to the basal mechanism underlying its toxic effects in plant and animal cells.


Manipulating electron redistribution induced by asymmetric coordination for electrocatalytic water oxidation at a high current density.
Electronic structure manipulation with regard to active site coordination is an effective strategy to improve the electrocatalytic oxygen evolution reaction (OER) activity. Herein, we present the structure-activity relationship between oxygen-atom-mediated electron rearrangement and active site coordination asymmetry. Ni2+ ions are introduced to FeWO4 on Ni foam (NF) via self-substitution to break the symmetry of the FeO6 octahedron and regulate d-electron structure of Fe sites. Structural regulation optimizes the adsorption energy of hydroxyl on the Fe sites and promotes the partial formation of hydroxyl oxide with high OER activity on the tungstate surface. Fe0.53Ni0.47WO4/NF with the asymmetric FeO6 octahedron of Fe sites can achieve an ultralow overpotential of 170 mV at 10 mA cm-2 and 240 mV at 1000 mA cm-2 with robust stability for 500 h at high current density under alkaline conditions. This research develops novel electrocatalysts with impressive OER performance and provides new insights into the design of highly active catalytic systems.


Lack of effect of tacrine administration on the anticoagulant activity of warfarin.
The effect of tacrine administration on prothrombin time was studied in 13 patients receiving prolonged warfarin therapy. After a 3-week baseline period and 5 days of placebo administration, patients received 20 mg tacrine four times daily for 5 days. Prothrombin times were determined during baseline, daily before the morning doses of placebo and tacrine, and 14 days after the last tacrine dose (closeout). Mean (+/- SD) prothrombin times were 16.2 +/- 2.8 seconds at baseline, 15.1 +/- 2.6 seconds during the placebo phase, 15.8 +/- 3.6 seconds during the tacrine phase, and 15.3 +/- 3.6 seconds at closeout, indicating that tacrine has no effect on the anticoagulant activity of warfarin. Alteration of warfarin dosage should not be required in patients receiving concurrent tacrine therapy.


Platycodin D inhibits HFD/STZ-induced diabetic nephropathy via inflammatory and apoptotic signaling pathways in C57BL/6 mice.
The dried root of Platycodon grandiflorum (Jacq.) A.DC. (PG) is a traditional herb used in Asian countries and is widely used in formulas for the treatment of diabetes. Platycodin D (PD) is one of the most important components of PG. This study aimed to investigate the improvement effects and regulatory mechanisms of PD on kidney injury in a high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic nephropathy (DN). Model mice were treated with oral gavage of the PD (2.5, 5 mg/kg) for 8 weeks. Determination of serum lipid and renal function-related indexes creatinine (CRE), and blood urea nitrogen (BUN) levels in mice, and histopathological section analysis of kidney. Molecular docking and molecular dynamics were utilized to study the binding ability of PD to target NF-κB and apoptosis signaling pathway-related proteins. Moreover, Western blot was used to test the expressions of NF-κB and apoptosis-related proteins. Vitro experiments were performed to validate the related mechanisms using RAW264.7 cells and HK2 cells cultured by high glucose. In vivo experiments, the administration of PD (2.5 and 5.0 mg/kg) reduced fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR) levels in DN mice, while lipid levels and renal function were significantly improved. Furthermore, PD significantly inhibited the development of DN in the model mice by regulating NF-κB and apoptotic signaling pathways, reduced the abnormal elevation of serum inflammatory factors TNF-α and IL-1β, and repaired renal cell apoptosis. In vitro experiments, NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (PDTC) was used to confirm that PD can alleviate high glucose-induced inflammation in RAW264.7 cells and inhibit the release of inflammatory factors. And in HK2 cell experiments, it was verified that PD can inhibit ROS generation, reduce the loss of JC-1 and suppress HK2 cell injury by regulating NF-κB and apoptotic pathways. These data suggested that PD has the potential to prevent and treat DN and is a promising natural nephroprotective agent.


Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration.
Lung cancer maintains high morbidity and mortality rate globally despite significant advancements in diagnosis and treatment in the era of precision medicine. Pathological analysis of tumor tissue, the current gold standard for lung cancer diagnosis, is intrusive and intrinsically confined to evaluating the limited amount of tissues that could be physically extracted. However, tissue biopsy has several limitations, including the invasiveness of the procedure and difficulty in obtaining samples for patients at advanced stages., there Additionally,has been no major breakthrough in tumor biomarkers with high specificity and sensitivity, particularly for early-stage lung cancer. Liquid biopsy has been considered a feasible auxiliary tool for tearly dianosis, evaluating treatment responses and monitoring prognosis of lung cancer. Circulating tumor DNA (ctDNA), an ideal biomarker of liquid biopsy, has emerged as one of the most reliable tools for monitoring tumor processes at molecular levels. Herein, this review focuses on tumor heterogeneity to elucidate the superiority of liquid biopsy and retrospectively discussdeciphersolution. We systematically elaborate ctDNA biological characteristics, introduce methods for ctDNA detection, and discuss the current role of plasma ctDNA in lung cancer management. Finally, we summarize the drawbacks of ctDNA analysis and highlight its potential clinical application in lung cancer.


Evidence on incest based on homozygosity. The use of multiple hypervariable probes for the probable detection or exclusion of incest.
An opinion is sometimes requested on the future health of a child who is up for adoption when parental incest is a realistic possibility and it is impossible or inexpedient to acquire blood from both parents. In such circumstances evidence of incest may be obtained by an analysis of blood from the child alone.


Improved thermal conductivity of polyurethane (PU)-/SiC composite fabricated via solution casting method and its mechanical model for prediction and comparison.
Polymer composites having high thermal conductivity (TC) gained great interest, including the advancement of electronic devices to become more functionalized, scaled, and integrated. In view of these, herein, highly thermal conductive polyurethane (PU)-/SiC composites are fabricated via the solution casting method. Silicon carbide is used as the filler in both flexible and rigid-polyurethane matrices to enhance the value of TC for electronic applications. A novel model has also been developed based on the Coran-Patel model for analysis and comparison of TC of as-synthesized composites. Calculated thermal conductivities by the model are found to be consistent with the experimental results. The highest measured TC for flexible as well as rigid-PU composites is 0.521 and 0.542 Wm-1K-1 representing improvements of 106% and 87% over their pure equivalents, respectively. SEM and DSC techniques are employed to analyze the samples' morphology, and other thermal properties, respectively.


Relationship of bone density to estradiol and cortisol in anorexia nervosa and bulimia.
Dual photon absorptiometry was used to assess the risk of developing osteoporosis in patients with anorexia nervosa and patients of normal weight with bulimia nervosa. Anorectic patients had significantly lower vertebral bone mineral densities compared with healthy controls. Bulimic patients had values similar to those of controls, and the differences between bulimics and anorectics narrowly missed significance. No significant difference was found between patient groups in measurements of serum estradiol, but anorectics, compared with bulimics, had significantly higher values of 24-hour urinary free cortisol. Hypercortisolemia, by diminishing bone formation and increasing bone resorption, is likely to contribute to the development of osteoporosis in patients with eating disorders.


Development of topical patches releasing allicin using garlic extract.
Treating hair loss of Alopecia areata is a quite challenge. The treatment not only needs to be effective but must meet specific requirements in terms of accurate dose, sustain release, comfortable application with aesthetic appearance. Thus, the study was designed to develop sustained release topical patches releasing allicin using different sources, including the extract from fresh and aged garlic, and commercially pure one. Patches were formulated by solvent casting method using ethylene-vinyl acetate as backing layer and Carbopol® 971P NF (CP) as mucoadhesive polymer. Physicochemical properties were evaluated including weight, thickness, drug content, surface pH, moisture content, folding endurance, and swelling. In addition to in vitro diffusion study across the cellulose and Strat-M® membranes. Patches showed good physicochemical properties. No significant difference (p > 0.05) was obvious in the percentage of allicin diffused across cellulose membrane between patch A (loaded with commercial allicin), patch B1 (loaded with fresh garlic extract), and patch C (loaded with aged garlic extract). However, ethanol enhanced the diffusion of allicin. The percentage of allicin diffused across cellulose membrane over 20 h from patch E (45 mg CP, 2 mL fresh garlic extract-equivalent to 60 mg allicin-and 1 mL of ethanol) was 79.94%. The flux and permeability coefficients were 2.62 mg/cm2 /h and 0.52 cm/h, respectively, with an enhancement ratio of 2.60 times the reference patch M (mashed garlic). Promising development of topical patches of allicin using garlic extract as natural source with lower cost than the commercial pure allicin and higher aesthetic acceptance than the used mashed garlic.


Current Landscape of Ancillary Diagnostic Testing in Chronic Lymphocytic Leukemia.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is a heterogeneous disease with variable patient outcomes. A multidisciplinary technical evaluation, including flow cytometry, immunohistochemistry, molecular and cytogenetic analyses, can comprehensively characterize a patient's leukemia at diagnosis, identify important prognostic biomarkers, and track measurable residual disease; all of which can impact patient management. This review highlights the key concepts, clinical significance, and main biomarkers detectable with each of these technical approaches; the contents are a helpful resource for medical practitioners involved in the workup and management of patients with CLL.


Botulinum toxin in post-stroke patients: stiffness modifications and clinical implications.
To objectively quantify stiffness and clinical changes in the upper limb of poststroke patients following botulinum toxin (BT) injection. Eighteen consecutive chronic post-stroke spastic patients were injected Botulinum toxin A in the forearm flexor spastic muscles. Spasticity was clinically evaluated with the Ashworth scale. Stiffness was measured with indices (passive stiffness index (ISI) and total stiffness index (TSI) obtained by mechanical wrist displacements induced by a torque motor,which could also provide the stretch reflex threshold speed (SRTS) from flexor muscles. Functional status was measured with the Barthel index and a specific hand ability scale, pain with a visual analogue scale (VAS). The ranges of voluntary wrist extension (EROM) and flexion (FROM) and wrist isometric extension and flexion (IE-IF) strength were also calculated. IE and EROM significantly increased, being respectively p < 0.01 and p < 0.05; also SRTS was augmented (p < 0.001),while TSI showed lower values (p < 0.001); the Ashworth score decreased at least one point. Hand function for selected tasks improved in 50% of patients, the Barthel index only in 4 (22 %), forearm pain was completely relieved in 3 patients (17 %). BT can be considered a valid therapeutic tool in all spastic patients, because of immediate advantages: reduction of muscle hypertonia, pain relief, improvement in selected motor performances.


The Evolution (and Future) of Stereotactic Body Radiotherapy in the Treatment of Oligometastatic Disease.
This review outlines the history of the oligometastatic state from its first proposal to the current formulation. The article discusses the accumulating evidence for the biology of oligometastases, including clinical parameters, such as number and rate of progression, as well as ongoing molecular profiling efforts. The authors then discuss the current state of prospective clinical trials. They review the early site-specific as well as subsite agnostic studies using stereotactic body radiation therapy. Moreover, the article makes the case for why phase II trials should not be practice changing, and highlights the pivotal importance of accruing to phase III clinical trials.


Identifying gaps in the treatment of hepatitis C in patients co-infected with HIV in Edmonton, Alberta.
With the availability of direct-acting antivirals, Hepatitis C (HCV) is now considered a treatable disease. Patients who are co-infected with human immunodeficiency virus (HIV) and HCV represent an ideal patient population to treat for HCV, as (1) patients are routinely taking medication for HIV, and therefore would be able to complete HCV drug regimens, and (2) HIV infection has been shown to increase HCV disease progression. We sought to determine the occurrence of HCV co-infection among HIV patients in our provincial cohort, determine whether they received treatment for HCV, and identify currently viremic patients who can be linked to care. HCV laboratory testing data (HCV antibody and HCV RNA) and HCV medication dispensation data was collected for all HIV positive patients. Current and previous HCV infection and treatment was assessed. Chart reviews were conducted for HCV viremic patients to assess their HIV care and social determinants. Of the 2417 HIV positive patients, 392 (16.2%) were identified as being co-infected with HCV. 198 (50.5%) of the HIV-HCV co-infected patients received HCV treatment and 232 (59.2%) were not viremic on the most recent HCV RNA test. 99 (69.2%) had a suppressed HIV infection suggesting they are active in their HIV care and good candidates for HCV treatment. Despite the availability of direct-acting antivirals, many patients who are co-infected with HIV and HCV are not being treated for HCV. Routine surveillance of HIV-HCV co-infected patients could improve HCV treatment rates in a high-risk population.


Mucosa-Associated Lymphoid Tissue Lymphoma of the Ascending Colon Successfully Removed With Endoscopic Submucosal Dissection.
Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of non-Hodgkin lymphoma with characteristic histopathological features and can occur in various extranodal sites, including the gastrointestinal tract. While gastric MALT lymphoma has been extensively researched, primary lymphoma presentation in the colorectal mucosa is rare and lacks any association with Helicobacter pylori infection. Furthermore, there are currently no standardized treatment guidelines for this condition. This report presents a rare case of primary MALT lymphoma that manifested as a broad-based polyp. The diagnosis was confirmed through histopathological and immunohistochemical examination, and the polyp was resected endoscopically with the endoscopic submucosal dissection technique.


Electrocardiographic Markers and the Left Ventricular Ejection Fraction have Cumulative Effects on Risk of Sudden Cardiac Death.
To assess potential improvement in SCD risk prediction by adding selected risk markers from the 12-lead ECG to measurement of the left ventricular ejection fraction (LVEF). Novel strategies to improve risk stratification for sudden cardiac death (SCD) are needed. Given the modest odds associated with most individual risk markers, combining multiple markers may be a useful approach. From the ongoing Oregon Sudden Unexpected Death Study, SCD cases with pre-event LVEF available were compared to matched control subjects with coronary artery disease. Resting heart rate, QRS duration (QRSD), and JTc intervals were measured from archived ECGs prior and unrelated to the SCD event. Independent odds of SCD for individual and combined ECG markers were calculated. SCD cases (n= 317; 67.9 ± 12.9 years) were more likely than controls (n=317; 67.9 ± 12.8 years) to have LVEF ≤ 35% (26% vs. 11%). Mean heart rate, QRSD, and JTc were significantly higher in cases (all p<0.0001). In adjusted analyses, higher heart rate [OR 2.6 (1.8 - 3.7)], QRSD [OR 1.5 (1.0 - 2.5)] and JTc [OR 2.3 (1.6 - 3.4)] were independently associated with SCD. When ECG markers were combined, SCD odds progressively increased with one [OR 3.4 (2.1 - 5.4)] and ≥ 2 elevated markers [OR 6.3 (3.3 - 12.1)]. Addition of ECG markers to an adjusted model with LVEF improved discrimination (C statistic 0.724 vs. 0.642) and net reclassification (by 22.7%) (p<0.0001). Combining selected 12-lead ECG markers with LVEF improves SCD risk prediction, and warrants further investigation in prospective studies.


African American Patients Experience Worse Outcomes than Hispanic Patients Following Bariatric Surgery: an Analysis Using the MBSAQIP Data Registry.
Obesity rates in Hispanics and African Americans (AAs) are higher than in Caucasians in the USA, yet the rate of metabolic and bariatric surgery (MBS) for weight loss remains lower for both Hispanics and AAs. Patient demographics and outcomes of adult AA and Hispanic patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedures were analyzed using the MBSAQIP dataset [2015-2018] using unmatched and propensity-matched data. In total, 173,157 patients were included, of whom 98,185 were AA [56.7%] [21,163-RYGB; 77,022-SG] and 74,972 were Hispanic [43.3%] [20,282-RYGB; 54,690-SG]). Preoperatively, the AA cohort was older, had more females, and higher BMIs with higher rates of all tracked obesity-related medical conditions except for diabetes, venous stasis, and prior foregut surgery. Intra- and postoperatively, AAs were more likely to experience major complications including unplanned ICU admission, 30-day readmission/reintervention, and mortality. After propensity matching, the differences in ED visits, treatment for dehydration, 30-day readmission, 30-day intervention, and pulmonary embolism remained for both SG and RYGB cohorts. Progressive renal insufficiency and ventilator use lost statistical significance in both cohorts. Conversely, 30-day reoperation, postoperative ventilator requirement, unplanned intubation, unplanned ICU admission, and mortality lost significance in the RYGB cohort, but not SG patients. Outcomes for AA patients were worse than for Hispanic patients, even after propensity matching. After matching, differences in major complications and mortality lost significance for RYGB, but not SG. These data suggest that outcomes for RYGB may be driven by the presence and severity of pre-existing patient-related factors.


Spontaneous Subarachnoid Hemorrhage with Negative Angiography Managed in a Stroke Unit: Clinical and Prognostic Characteristics.
Perimesencephalic subarachnoid hemorrhage (p-SAH) is linked to a benign prognosis compared with aneurysmal SAH. However, the outcome in nonperimesencephalic angiographically negative SAH (np-SAH) is not well established. We reviewed our experience and evaluated the clinical and prognostic differences between patients with p-SAH and np-SAH. Retrospective observational study based on data collected prospectively from all patients admitted to our hospital with SAH during the past 11 years. After selecting patients with normal angiography, we categorized them as either p-SAH or np-SAH according to the Rinkel criteria. Demographic, clinical, radiologic, and prognostic features were recorded. We collected a total of 41 (12.53%) angiographically negative SAH: 17 p-SAH (41.46%) and 24 np-SAH (58%-53%). The np-SAH group included the 6 patients with Glasgow Coma Scale (GCS) less than 15 (P = .083), and all 5 patients with Hunt & Hess (H&H) scores more than II (P = .045), being the GCS = 15 and H&H less than II in the rest of np-SAH and in all of the p-SAH patients. The average hospital stay in days was longer in the np-SAH group (24 ± 7.08) than in the p-SAH group (17 ± 5.11; P = .55). Hydrocephalus requiring external ventricular drainage (EVD) was only recorded in the np-SAH group (29.16%, P = .029). On discharge, all patients had H&H grade less than II and modified Rankin Scale measured 3 months later was less than 2 in both groups. Our results agree with other studies showing a low complication rate for SAH patients with a normal angiography, especially in the p-SAH group. The prognosis appears to be less favorable in terms of a more frequent need for EVD, so a more cautious approach is recommended in this subgroup.


The effect of 1,2,4-thiotriazolyl 5-mercaptoacetic acid new derivatives on lipid peroxidation in the heart from adult and old rats during stress.
The effect of 3-(4-pyridyl)-1,2,4-thiotriazolyl 5-mercaptoacetic acid kalium salt (Rumosol) and 3-(4-pyridyl)-1,2,4-thiotriazolyl 5-mercaptoacetic acid morpholinium salt (drug 2) on the concentration of Schiff base in myocardium of adult (10-12 months) and old (22-25 months) Wistar rats during immobilized stress were investigated. Here we show that the accumulation of Schiff base in the heart from both age groups was inhibited after injection of derivatives of 1,2,4-thiotriazolyl 5-mercaptoacetic acid prior to immobilization. Drug 2 possessed a two-fold higher pronounced capacity against Rumosol to inhibit the accumulation of Schiff base in the heart during stress. In myocardium from old rats, drug 2 decreased more effectively the stress-induced stimulation of lipid peroxidation as compared to dimethyl sulfoxide.


Posterior extrapleural intervertebral space release combined with wedge osteotomy for the treatment of severe rigid scoliosis.
Retrospective clinical case series. To report the technique and results of posterior extrapleural intervertebral space release (PEISR) combined with wedge osteotomy (WO) for the treatment of severe rigid scoliosis. Conventional surgical correction techniques for severe rigid scoliosis include anterior release combined with posterior instrumentation and fusion and vertebral column resection. Between 2004 and 2009, 18 patients underwent PEISR and WO at a single institution. The indications were scoliosis with coronal Cobb's angle greater than 90° and curve flexibility less than 25%. The median age at surgery was 18.1 years (range, 13-26 yr). Nine patients had a preoperative forced vital capacity that was less than 40% of predicted. All patients had a minimum 2-year radiographical and clinical follow-up (range, 2.0-5.7 yr). A mean of 4.2 discs were excised per patient (range, 2-6 discs) along with a mean of 1.2 vertebrae removed in the osteotomy. Mean number of vertebrae fused was 13.8 (range, 10-16 vertebrae). Mean operating time was 8.8 hours (range, 6.2-12.6 hr), with a mean blood loss of 3990 mL (range, 2600-6100 mL). The mean preoperative Cobb angle of 108.5° (range, 92°-136°) was corrected to 30° at the most recent follow-up (72.4% correction rate). Preoperative thoracic kyphosis of 52° (range, 5°-115°) was corrected to 26° (range, 17°-52°). The mean preoperative coronal imbalance of 3.5 cm was corrected to 0.6 cm (83.8% correction) and the sagittal imbalance of 2.8 cm was corrected to 0.3 cm (90.3% correction). There were no neurological complications. There were no instances of infection or muscle necrosis. Hemopneumothorax occurred in 2 patients. PEISR, combined with WO, through a single posterior approach is a technically challenging but safe and effective procedure for severe rigid scoliosis. This posterior-only approach allows for dramatic radiographical correction that surpasses that reported for posterior VCR.


Acid and alkaline phosphatase activity in Trypanosoma cruzi epimastigotes.
Phosphatase activity in intact Trypanosoma cruzi epimastigotes has been demonstrated. After subcellular fractionation three activities were characterized: (a) a membrane-bound microsomal acid activity with an optimum pH of 4.0 and a Km of 1.2 mM, strongly inhibited by tartrate and fluoride; (b) a soluble cytosolic acid activity with an optimum pH of 5.5 and a Km of 0.95 mM, strongly inhibited by p-hydroxymercuribenzoate, EDTA and copper ions and activated by cyanide, manganese and magnesium ions; and (c) a soluble cytosolic alkaline activity with an optimum pH of 8.0 and a Km of 3.8 mM, inhibited by p-hydroxymercuribenzoate, fluoride, EDTA, and copper, calcium and zinc ions. This activity was increased by magnesium and manganese ions.


Temporal analysis of N-acetylglucosamine extension of N-glycans in the middle silk gland of silkworm Bombyx mori.
N-glycosylation of proteins is an important post-translational modification in eukaryotic cells. One of the key modifications in protein N-glycosylation is N-acetylglucosamine (GlcNAc) extension mediated by N-acetylglucosaminyltransferase I (GNTI), which triggers N-glycan maturation from high-mannose-type to hybrid- and complex-type structures in Golgi. However, the temporal contributions of GNTI to GlcNAc extension and the resultant N-glycan structures in insects have not been analyzed. Here, focusing on GlcNAc extension of N-glycan in the silkworm Bombyx mori, we analyzed the temporal N-glycan alterations in the middle silk gland (MSG) and characterized the property of key enzyme for complex-type N-glycan biosynthesis, B. mori GNTI (BmGNTI). N-glycan analysis of N-glycoproteins in the MSG demonstrated that BmGNTI identified and characterized in this study consistently contributed to GlcNAc extension of N-glycans, which led to the accumulation of GlcNAc-extended N-glycans as predominant structures throughout the MSG development. The expression profile of GlcNAc extension-related genes revealed that the enzymes contributing to the hydrolysis of GlcNAc showed stage-specific expressions, thereby resulting in accumulations of the end product N-glycans of the enzyme. These results lead to the speculation that not BmGNTI but rather glycosylhydrolases critically influenced the structural formations and the changes in the ratio of N-glycans with GlcNAc residue(s) in MSG.


Cancer therapy based on extracellular vesicles as drug delivery vehicles.
Extracellular vesicles (EVs) are lipid bilayer vesicles of nanometric size secreted by cells to communicate with other cells, either nearby or remotely. Their physicochemical properties make them a promising nanomedicine for drug transport and release in cancer therapy. In this review, we present the different types and biogenesis of EVs and highlight the importance of adequately selecting the cell of origin in cancer therapy. Furthermore, the main methodologies followed for the isolation of EVs and drug loading, as well as the modification and functionalization of these vesicles to generate EV-based nanocarriers are discussed. Finally, we review some of the main studies using drug-loaded exosomes in tumor therapy both in in vitro and in vivo models (even in resistant tumors). These investigations show promising results, achieving significant improvement in the antitumor effect of drugs in most cases. However, the number of clinical trials and patents based on these nanoformulations is still low, thus further research is still warranted in this area.


Cholinergic receptor binding and autoradiography in brains of non-neurological and senile dementia of Alzheimer-type patients.
Muscarinic and nicotinic cholinergic receptor distribution was studied by dry-mount autoradiography in brains obtained postmortem from patients with senile dementia of Alzheimer-type (SDAT) and non-neurological controls. Sections were incubated with either [N-methyl-3H]scopolamine, ([3H]NMS) or [125I]alpha-bungarotoxin, ([125I]alpha-BTX). No significant difference in the affinity and number of muscarinic and nicotinic receptors was found in hippocampus, frontal, temporal and cingulate cortex between SDAT patients and non-neurological controls. However, some SDAT cases showed diffuse instead of laminar [3H]NMS labeling in cortical regions. The labeling pattern was not affected by the presence of neuritic plaques and neurofibrillary tangles.


[Potentials of infusion therapy in enhancing the detoxification effect of hemosorption in patients suffering from suppurative-septic complications of mechanical injury].
Under study was the application of microvasoplegia as a method of preoperative management in fulfilling hemosorption in patients with pyo-septic complications of a severe mechanical trauma. The method of infusion and medicamentous therapy used before hemosorption is described. Laboratory examinations of the enzyme toxemia level have shown pathogenetic grounds of the complex method of treatment. Positive clinical results were obtained.


Lessons learned from a pilot study on the health status of children from itinerant populations.
The pilot study is used to guide development of a research design or to test an already developed plan; however, results of pilot work often are not reported. Pilot work can yield many valuable lessons and provide investigative training to the principal investigator and as well as evidence to funding agencies that the research is feasible and worthwhile. The pilot study described here is preliminary work on health disparities in two itinerant populations: carnival and migrant farmworker children. This pilot study had three aims: (a) identify the most productive methods to recruit subjects from these two "invisible" populations; (b) test feasibility of the research protocol; and (c) collect preliminary data on the children's health status for future research proposals.


Effect of long-term adjuvant temozolomide chemotherapy on primary glioblastoma patient survival.
Glioblastoma multiforme (GBM) is the most common primary malignant central nervous system (CNS) tumor. The Stupp regimen is the standard treatment, although the optimal number of temozolomide (TMZ) treatment cycles remains controversial. We compared the effects of standard 6 cycles versus > 6 cycles of TMZ chemotherapy post-surgery with concurrent chemoradiotherapy on primary GBM patient survival. We performed a single center retrospective study of GBM patients that underwent total resection, concurrent chemoradiotherapy, and at least 6 cycles of adjuvant TMZ chemotherapy from June 2011 to August 2018. Patients were divided into 2 groups based on adjuvant TMZ treatment plan: Group A(n = 27): standard 6-cycle adjuvant TMZ therapy and Group B(n = 26): > 6 cycles of adjuvant TMZ therapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Continuous variables were analyzed by ANOVA, and the Kaplan-Meier method was used to evaluate PFS and OS. Univariate and multivariate COX analyses determined correlation between survival rates and covariates. We used The Mini Mental State Examination (MMSE) and Karnofsky Performance Status (KPS) to assess patients' neurocognitive function and quality of life. After follow-up, median PFS was 15 months in in Group A (95%CI 9.5-20.5) and 20.1 months in Group B (95%CI 15.9-24.4). Group A median OS was 19.4 months (95%CI 15.5-23.2), compared to 25.6 months in Group B (95%CI 20.4-30.8). The 2-year survival rate of Groups A and B was 36% was 66%, respectively (P = 0.02). and 5-year survival was 7% in both. Multivariate COX regression analysis showed association between patient PFS and long-period adjuvant chemotherapy, but not OS. There were no significant difference in disability or quality of life during treatment with Stupp protocol, but differences in MMSE and KPS were in favour of the Groups B after year 1 of the treatment (P < 0.05). Long-term adjuvant TMZ chemotherapy was beneficial for PFS and 2-year survival rate in GBM patients, and improved their quality of life contemporarily. But OS was not significantly improved.


Quinolone derivatives containing strained spirocycle as orally active glycogen synthase kinase 3β (GSK-3β) inhibitors for type 2 diabetics.
The design, synthesis, and evaluation of 6-6-7 tricyclic quinolones containing the strained spirocycle moiety aiming at the GSK-3β inhibitor were described. Among the synthesized compounds, 44, having a cyclobutane ring on a spirocycle, showed excellent GSK-3β inhibitory activity in both cell-free and cell-based assays (IC(50) = 36nM, EC(50) = 3.2μM, respectively). Additionally, 44 decreased the plasma glucose concentration dose-dependently after an oral glucose tolerance test in mice.


Rapid start-up of partial nitrification reactor by exogenous AHLs and Vanillin combined with intermittent aeration.
Quorum sensing (QS) and quorum quenching (QQ) are common phenomena in microbial systems and play an important role in the nitrification process. However, rapidly start up partial nitrification regulated by N-acyl-homoserine lactones (AHLs)-mediated QS or QQ has not been reported. Hence, we chose N-butyryl homoserine lactone (C4-HSL) and N-hexanoyl homoserine lactone (C6-HSL) as the representative AHLs, and Vanillin as the representative quorum sensing inhibitor (QSI) combined intermittent aeration to investigate their effects on the start-up process of partial nitrification. The start-up speed in the group with C4-HSL or C6-HSL addition was 1.42 or 1.26 times faster than that without addition, respectively. Meanwhile, the ammonium removal efficiency with C4-HSL or C6-HSL addition was increased by 13.87 % and 17.30 % than that of the control group, respectively. And, partial nitrification could maintain for a certain period without AHLs further addition. The increase of Nitrosomonas abundance and ammonia monooxygenase (AMO) activity, and the decrease of Nitrobacter abundance and nitrite oxidoreductase (NXR) activity were the reasons for the rapid start-up of partial nitrification in the AHLs groups. Vanillin addition reduced AMO and hydroxylamine oxidoreductase (HAO) activity, and increased Nitrobacter abundance and NXR activity, thus these were not conducive to achieving partial nitrification. Denitrifying bacteria (Hydrogenophaga, Thauera and Aquimonas) abundance increased in the Vanillin group. QS-related bacteria and gene abundance were elevated in the AHLs group, and reduced in the Vanillin group. Function prediction demonstrated that AHLs promoted the nitrogen cycle while Vanillin enhanced the carbon cycle. This exploration might provide a new technical insight into the rapid start-up of partial nitrification based on QS control.


Gastric emptying of barium sulphate suspension compared with that of water.
Test meals consisting of water or a suspension of barium sulphate were given to two normal subjects. The rates of decrease of the volume of the gastric contents were indistinguishable for the two meals.


Effects of dietary saturated and polyunsaturated fat on lipoprotein lipase and hepatic triglyceride lipase activity.
The effects of saturated and polyunsaturated dietary fat on the lipolytic activity of post-heparin plasma, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were studied in the rat. The lipolytic activity was studied from 0 to 60 min using labelled chylomicrons as the substrate. Triacylglycerol hydrolysis rate was higher for the plasma of rats fed high fat diets (14% fat by weight). Chylomicrons of rats fed saturated or unsaturated fats were hydrolyzed at the same rate within the first 15 min but afterwards hydrolysis of chylomicrons of rats fed saturated fat was slower. The activities of LPL and HTGL were increased by high fat diets. Unsaturated fat increased more LPL activity than saturated fat conversely, HTGL activity was enhanced more by saturated fat than by unsaturated fat.


Dietary kaempferol suppresses inflammation of dextran sulfate sodium-induced colitis in mice.
In ulcerative colitis (UC), reduction of inflammation may represent a key mechanism in UC therapy, and anti-inflammatory agents would be good candidates for preventing UC. Kaempferol, a natural flavonoid, is believed to have anti-inflammatory activities and has been shown to be potentially immune-modulatory. The aim of this study was to determine whether kaempferol alleviates the inflammatory responses of dextran sulfate sodium (DSS)-induced colitis in mice. Female C57BL/6J mice were divided into six groups: a negative control group, a DSS control group, and DSS + 0.1% or 0.3% kaempferol pre- or post-fed groups. At the end of the experimental period, clinical and biochemical markers were evaluated. Plasma levels of NO and PGE(2) were significantly decreased in both the 0.3% kaempferol pre- and post-fed groups. The plasma LTB(4) level was profoundly decreased in all animals fed kaempferol. Colonic mucosa MPO activity was also suppressed in both the 0.3% kaempferol pre- or post-fed groups. TFF3 mRNA, a marker for goblet cell function, was up-regulated in kaempferol pre-fed animals. These results indicate that kaempferol is an effective anti-inflammatory agent that protects colonic mucosa from DSS-induced UC. Dietary kaempferol fed prior to colitis induction was more effective to suppress some of the colitis-associated markers.


The transport of lipoprotein cholesterol into bile: a reassessment of kinetic studies in the experimental animal.
Studies were undertaken to assess the contribution of lipoprotein cholesterol to bile and to determine whether already-existent hepatic free cholesterol and the free cholesterol which is newly generated from the hydrolysis of hepatic cholesteryl esters are equally available for secretion into bile or constitute metabolically separate pools. Rats with a bile fistula were injected with an intravenous bolus of high-density lipoprotein recombinants containing free [14C]cholesterol and [3H]cholesteryl esters. Results showed (1) that bile free [14C]cholesterol secretion was a constant and linear proportion of the whole liver free [14C]cholesterol pool, (2) that secretion into bile of free [3H]cholesterol was in direct proportion to the rate of hydrolysis of hepatic [3H]cholesteryl esters, and (3) that rates of biliary cholesterol secretion were very similar when secretion was calculated using the specific activity of free [14C]cholesterol and free [3H]cholesterol in the entire liver to 'label' the precursor free cholesterol pool. Furthermore, rates of secretion that were calculated using either isotope closely approximated the mass of free cholesterol that was directly measured in bile. Results thus indicate that because of equilibration and extensive dilution by the large pool of already-existent free cholesterol, the transport of isotopic cholesterol from lipoproteins cannot be used to directly assess the contribution of lipoprotein cholesterol to the cholesterol that is secreted in bile. These studies further suggest that the totality of preformed free cholesterol in the liver is in metabolic equilibrium in one single kinetic pool and that all hepatic free cholesterol is potentially available for secretion into bile.


Isolation and characterization of snRNA and scRNA gene candidates from a human genomic library.
A simple procedure for the isolation and preparative gel electrophoresis of snRNA and scRNA is described. These small RNA species were used to select DNA sequences from a human genomic library which are able to protect hybridized snRNA or scRNA against T1-ribonuclease attack. The snRNA clones obtained contain only sequences for one snRNA species and only one copy of the respective gene. In contrast, more than one 7S RNA gene is present within the scRNA clones.


Effectiveness of Structured Education in Reduction of Postpartum Depression Scores: A Quasi-Experimental Study.
The aim of this study was to evaluate effectiveness of structured education in reduction of postpartum depression scores among women. This was a quasi-experimental study with a pre-post tests and a control group. Non-random sampling was used and the study included a total of 103 Turkish women, 52 of whom were in the intervention group and 51 were in the control group. The women in the intervention group were offered structured education for postpartum depression and given structured education material. Effectiveness of the education given was evaluated by comparing scores for Edinburg Postpartum Depression Scale obtained before and after delivery between the intervention and the control groups. Before education, median score (8.0±4.8) for Edinburg Postpartum Depression Scale of the intervention group were significantly higher the than the control group (6.0±6.0, p=0.010), but the groups were statistically similar in terms of having depression (intervention: 17.3%, control: 11.8%, p=0.425). After education, the median score for Edinburg Postpartum Depression Scale and the ratio of the women having depression in the intervention group were significantly lower than in the control group (respectively intervention: 4.0±3.0, control: 10.0±4.0, p=0.000; intervention: 7.7%, control: 25.5%, p=0.015). Besides, the median score (8.0±4.8) of the intervention group before education were significantly higher than the score (4.0±3.0) obtained after education (p=0.000), while the median score (6.0±6.0) of the control group before education were lower than the score (10.0±4.0) obtained after education (p=0.000). This study revealed that structured education offered to women by nurses was effective in reducing the postpartum depression scores and the numbers of women having depression.


Dose-response of intravenous calcium in the surgical intensive care unit.
Background Hypocalcemia is common in patients admitted to the surgical intensive care unit and is associated with increased morbidity and mortality. Current dosing strategies do not always achieve ionized calcium (iCa) normalization, especially in patients with severe hypocalcemia. Objective The purpose of this study was to explore the association between intravenous (IV) calcium dose and change in ionized calcium. Setting Patients admitted to the surgical intensive care unit with concomitant hypocalcemia at a large academic hospital in the United States. Method This single center, retrospective cohort study evaluated the association between IV calcium dose and subsequent change in ionized calcium level in adult surgical intensive care unit patients with hypocalcemia. The primary outcome of this study was to develop a model exploring the association between IV calcium dose and change in iCa levels. Secondary outcomes included describing the average IV calcium dose required to normalize iCa levels, average time to normalization of iCa levels, and assessing the safety of IV calcium replacement. Main outcome measure Change in iCa. Results One hundred and ninety-four patients met study criteria. In the final model initial iCa level, total calcium dose, the interaction between initial iCa level and total calcium dose, age, and pancreatitis remained. The model (R2 = 0.625) is expressed by the following equation: Change in iCa level = 0.462 - 0.011 × [Ca dose] - 0.0007 × [Age] - 0.259 × [Initial iCa] + 0.076 × [initial iCa × Ca dose] - 0.076 × [Pancreatitis]. Removing two patients that received > 10 grams of total calcium improved the R2 to 0.769. Lastly, a simplified model removing age and pancreatitis found a similar R2 of 0.756. Conclusion We observed that change in iCa level after initial calcium dose depended on the baseline iCa. Our full and simplified model excluding two outliers predicted 76.9% and 75.6% of the variation in iCa response, respectively. If validated in other settings this model could be utilized to provide more accurate calcium dosing.


Evolutional insights into the interaction between Rab7 and RILP in lysosome motility.
Lysosome motility is critical for the cellular function. However, Rab7-related transport elements showed genetic differences between vertebrates and invertebrates, making the mechanism of lysosomal motility mysterious. We suggested that Rab7 interacted with RILP as a feature of highly evolved organisms since they could interact with each other in Spodoptera frugiperda but not in Drosophila melanogaster. The N-terminus of Sf-RILP was identified to be necessary for their interaction, and Glu61 was supposed to be the key point for the stability of the interaction. A GC-rich domain on the C-terminal parts of Sf-RILP hampered the expression of Sf-RILP and its interaction with Sf-Rab7. Although the corresponding vital amino acids in the mammalian model at the C-terminus of Sf-RILP turned to be neutral, the C-terminus would also help with the homologous interactions between RILP fragments in insects. The significantly different interactions in invertebrates shed light on the biodiversity and complexity of lysosomal motility.


Analysis of 5S rDNA Genomic Organization Through the RepeatExplorer2 Pipeline: A Simplified Protocol.
The ribosomal RNA genes (rDNA) are universal genome components with a housekeeping function, given the crucial role of ribosomal RNA in the synthesis of ribosomes and thus for life-on-Earth. Therefore, their genomic organization is of considerable interest for biologists, in general. Ribosomal RNA genes have also been largely used to establish phylogenetic relationships, and to identify allopolyploid or homoploid hybridization.Here, we demonstrate how high-throughput sequencing data, through graph clustering implemented in RepeatExplorer2 pipeline ( https://repeatexplorer-elixir.cerit-sc.cz/galaxy/ ), can be helpful to decipher the genomic organization of 5S rRNA genes. We show that the linear shapes of cluster graphs are reminiscent to the linked organization of 5S and 35S rDNA (L-type arrangement) while the circular graphs correspond to their separate arrangement (S-type). We further present a simplified protocol based on the paper by (Garcia et al., Front Plant Sci 11:41, 2020) about the use of graph clustering of 5S rDNA homoeologs (S-type) to identify hybridization events in the species history. We found that the graph complexity (i.e., graph circularity in this case) is related to ploidy and genome complexity, with diploids typically showing circular-shaped graphs while allopolyploids and other interspecific hybrids display more complex graphs, with usually two or more interconnected loops representing intergenic spacers. When a three-genomic comparative clustering analysis from a given hybrid (homoploid/allopolyploid) and its putative progenitor species (diploids) is performed, it is possible to identify the corresponding homoeologous 5S rRNA gene families, and to elucidate the contribution of each putative parental genome to the 5S rDNA pool of the hybrid. Thus, the analysis of 5S rDNA cluster graphs by RepeatExplorer, together with information coming from other sources (e.g., morphology, cytogenetics) is a complementary approach for the determination of allopolyploid or homoploid hybridization and even ancient introgression events.


Cells carrying C5b-9 complement complexes in human atherosclerotic wall.
Fibrous plaques and intimal thickenings of 5 femoral and 5 iliac human arteries obtained at surgery were processed for indirect and double-labeling immunoelectron microscopy using an affinity purified rabbit IgG anti-C5b-9 neoantigen and the EBM 11 monoclonal antibody anti-human macrophages. The C5b-9 complexes were localized in intact cells, disintegrated cells and cell debris enmeshed in the connective tissue matrix. Some of the cell debris bearing C5b-9 deposits was found to be of macrophage origin. Endocyted or exocyted pieces of membrane with pore-forming C5b-9 complexes were also identified. Damage of cells by complement in atherosclerotic lesions may contribute to atherogenesis.


Cost-effectiveness analysis of intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy for anal cancer.
To compare the cost-effectiveness of intensity modulated radiation therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal cancer and determine disease, patient, and treatment parameters that influence the result. A Markov decision model was designed with the various disease states for the base case of a 65-year-old patient with anal cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health states accounting for rates of local failure, colostomy failure, treatment breaks, patient prognosis, acute and late toxicities, and the utility of toxicities were informed by existing literature and analyzed with deterministic and probabilistic sensitivity analysis. In the base case, mean costs and quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291 (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost-effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per QALY, respectively. In our base model, IMRT was a cost-ineffective strategy despite the reduced acute treatment toxicities and their associated costs of management. The model outcome was sensitive to variations in local and colostomy failure rates, as well as patient-reported utilities relating to acute toxicities.