Incongruent pattern of neurokinin B expression in rat and mouse brains.
The expression patterns of Tac2 and NK3 mRNA and of pep2, the neurokinin B (NKB) precursor protein, were compared in rats and mice. Pep2 immunoreactivity was observed in fibers, terminals, and perikarya in the brains of both species, but the number of NKB-immunoreactive cells was generally smaller in mice than in the corresponding nuclei in rats. Congruent distribution patterns of Tac2 mRNA and NKB were found in many nuclei of the thalamus and hypothalamus (habenula, anterodorsal nucleus, preoptic area, arcuate nucleus, paraventricular nucleus). However, mice expressed Tac2 mRNA neither in the hippocampus nor in the nucleus of the lateral olfactory tract, in contrast to rats. Accordingly, mice showed no NKB in the projection areas of these nuclei, such as the olfactory tubercle, whereas a clear NKB signal was present in rat tissues. Surprisingly, we found nearly identical NK3 mRNA expression patterns in both species, despite the species differences in NKB expression. Thus, although the expression patterns of Tac2 and NKB are similar in rats and mice, noteworthy differences exist. Our results have important implications for the interpretation of behavioral results concerning the NKB/NK3 system in these species.


Oxidative Stress and Mitochondrial Dysfunction in Human Diseases: Pathophysiology, Predictive Biomarkers, Therapeutic.
Mitochondria are important sites for a variety of cellular processes, including amino acid and fatty acid metabolism, the citric acid cycle, nitrogen metabolism, and oxidative phosphorylation to produce ATP [...].


Is the site of thrombus formation in the left atrial appendage associated with the risk of cerebral embolism?
Atrial fibrillation (AF) is a risk factor for cerebral embolism, with the left atrial appendage (LAA) being considered as the source of emboli. However, the relationship between the histologic properties of LAA thrombi and the occurrence of cerebral embolism is not known. Seventy-six hearts from patients who died within 1 month after cerebral embolism were studied at autopsy. Patients were grouped according to the presence of AF and the presence of valvular disease (VD). We determined whether the LAA thrombi adhered to the trabecular region or the remainder of the LAA. LAA thrombi were grouped into three stages: a fresh stage in which thrombi consisted of fibrin and platelets, an organizing stage in which angiogenesis was observed in the thrombi, and an organized stage in which endothelial cells covered the surface of the thrombi. The AF+/VD- group included 19 patients (25.0%), the AF+/VD+ group 8 (10.5%), the AF-/ VD- group 37 (48.7%), and the AF-/VD+ group included 12 patients (15.8%). LAA thrombi were observed in 15 patients (78.9%) in the AF+/VD- group, and all of the thrombi adhered to the trabecular region. Thrombi in the fresh and the organizing stages were observed in 10 patients (66.7%). Patients in the AF+/VD- group accounted for about 25% of the cases of cerebral embolism. All of these thrombi were attached to the trabecular region, and about 70% of them could represent an embolic source.


HAX1 enhances the survival and metastasis of non-small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway.
HS-1-associated protein-1 (HAX1) has been reported to be overexpressed in non-small cell lung cancer (NSCLC) tissues. However, the underlying mechanism of HAX1 in NSCLC has not previously been demonstrated. The present study investigated the role and underlying mechanism of HAX1 in NSCLC. The HAX1 expression were confirmed in NSCLC tissues through TCGA database and qRT-PCR. Moreover, we performed qRT-PCR, Western blotting, Transwell assays, TUNEL assays and so on to evaluate the role of HAX1 in A549 and H1299 cell lines. mRNA expression of HAX1 was overexpressed in NSCLC tissues compared to adjacent normal tissues according to The Cancer Genome Atlas (TCGA) database. QRT-PCR assays showed that HAX1 mRNA expression was upregulated in NSCLC tissues. The high HAX1 mRNA levels were found to be positively associated with tumor size, TNM stage and lymphatic metastasis. Silencing of HAX1 promoted apoptosis and reduced invasion of A549 and H1299 cells by inhibiting the AKT/mTOR and MDM2/P53 signal pathway. AKT agonist SC79 could inhibit apoptosis and promote proliferation, migration and invasion of A549 and H1299 cells transfected with si-HAX1. The present study provided a better understanding of HAX1 mechanism in NSCLC and potential therapeutic target for NSCLC.


Screening performances of an 8-item UPSIT Italian version in the diagnosis of Parkinson's disease.
Hyposmia is a common finding in Parkinson's disease (PD) and is usually tested through the University of Pennsylvania Smell Identification Test (UPSIT). The aim of our study is to provide a briefer version of the Italian-adapted UPSIT test, able to discriminate between PD patients and healthy subjects (HS). By means of several univariate and multivariate (machine-learning-based) statistical approaches, we selected 8 items by which we trained a partial-least-square discriminant analysis (PLS-DA) and a decision tree (DT) model: class predictions of both models performed better with the 8-item version when compared to the 40-item version. An area under the receiver operating characteristic (AUC-ROC) curve built with the selected 8 odors showed the best performance (sensitivity 86.8%, specificity 82%) in predicting the PD condition at a cut-off point of ≤ 6. These performances were higher than those previously calculated for the 40-item UPSIT test (sensitivity 82% and specificity 88.2 % with a cut-off point of ≤ 21). Qualitatively, our selection contains one odor (i.e., apple) which is Italian-specific, supporting the need for cultural adaptation of smell testing; on the other hand, some of the selected best discriminating odors are in common with existing brief smell test versions validated on PD patients of other cultures, supporting the view that disease-specific odor patterns may exist and deserve a further evaluation.


A case of monoclonal immunoglobulin G1-lambda deposition associated with membranous feature in a patient with hepatitis C viral infection.
A 63-year-old man with hepatitis C virus infection was admitted to our hospital for nephrotic syndrome. Light microscopic analysis of a percutaneous renal biopsy showed thickening of the glomerular capillary walls and spike formation. Immunofluorescence revealed granular deposition of monoclonal immunoglobulin G1-lambda and C3 complement along the glomerular basement membrane. Urinary protein excretion decreased slightly after combined treatment with steroid and an immunosuppressive agent. Monoclonal immunoglobulin deposition disease with membranous feature is rare. Additional reports of such cases are needed to elucidate the mechanisms and optimal therapy for this rare entity.


Research in patients with heart failure: challenges in recruitment.
Published studies of patients with heart failure may not include details about the challenges in the recruitment process. To describe the recruitment process during the first 18 months of a study being conducted to evaluate cognitive deficits in patients with chronic heart failure. Details of the recruitment process are described for 2 clinic sites. A total of 4,027 echocardiograms were screened at site 1 to evaluate eligibility. Of the 161 patients eligible, 61 (38%) were invited to participate, and 29 of the 61 (48%) completed the study. At site 2, four hundred thirty-seven medical records of patients were screened, resulting in 163 eligible patients (37%). The staff invited 70 of the 163 patients (43%) to participate, and 52 of the 70 (74%) completed the study. The refusal rate was 23% at site 1 and 21% at site 2. Successful recruitment in studies involving patients with heart failure often requires screening of a large group of patients.


Inhaled nitric oxide in neonatal and paediatric transport.
Since the first reports of the use of inhaled nitric oxide in the early 1990s its applications have been refined to a number of specific conditions. Pre-term and term neonates benefit significantly in the improvement of oxygenation in conditions such as hypoxic respiratory failure and persistent pulmonary hypertension of the neonate and the reduction in referral rates to extra corporeal membrane oxygenation. Many neonatal units still do not have the ability to administer inhaled nitric oxide though an increasing number of neonatal units have acquired the capability to deliver inhaled nitric oxide in recent years with commercially available delivering devices. In either case if the neonate needs transfer for further management or extra corporeal membrane oxygenation the journey can be improved if inhaled nitric oxide is introduced during transport or could deteriorate if inhaled nitric oxide was discontinued during transport. Delivery of inhaled nitric oxide during transport can be technically challenging and the consequences of increased or interrupted delivery can be dangerous. The different modes of transport either by road or air can influence the method of delivery. We describe our method of delivering inhaled nitric oxide during the retrievals we undertake and how this changes depending upon the type of journey performed. We also suggest guidelines for its use during transport and outline the precautions we take to ensure safety of patient and carers during transport.


New graduate nurse transitioning: necessary or nice?
This study investigated the influence of personal factors, orientation, continuing education, and staffing shortage on the satisfaction, intent to leave their job, and intent to leave the profession of a random sample of new graduate nurses from varied facilities and geographic locations. It further examined the influence of personal factors and orientation on turnover rates among new graduate nurses. The findings indicate that orientation programs are essential to the retention and satisfaction of new graduate nurses. Given current economic constraints, this study supports nurse executives' ability to advocate for and receive funding for transition-to-work programs as well as the placement of new graduate nurses in well-staffed units.


An alternative surgical approach to facilitate minimally invasive mitral valve surgery.
An alternative approach to minimally invasive mitral valve surgery is described that permits direct great vessel cannulation and direct aortic clamp occlusion through a 6- to 8-cm incision. This approach reduces the complexity of the procedure, and hopefully, will contribute to more widespread adoption of less invasive techniques in mitral valve surgery.


Hospital mortality associated with day and time of admission to intensive care units.
To investigate whether hospital mortality of patients was associated with the day of the week or time of admission to intensive care units (ICUs). Cohort study. One hundred two adult, general (mixed medical/surgical) ICUs in England, Wales and Northern Ireland. A total of 56,250 admissions from 1995 to 2000 that fit the inclusion criteria for calculation of the APACHE II probability of hospital mortality. None. Crude and case mix adjusted hospital mortality were examined by day of the week and time of day of admission to ICU. Patients admitted on Saturday and Sunday had higher crude hospital mortality compared with admissions on Wednesday [Saturday crude odds ratio (OR) 1.41, 95% CI 1.32-1.52; Sunday OR 1.56, 1.45-1.68]. The association was still significant after adjustment using the UK APACHE II model (Saturday OR 1.16, 1.1.07-1.26; Sunday OR 1.24, 1.14-1.35) but not after adjustment using individual components of the APACHE II model (Saturday OR 1.03, 0.95-1.12; Sunday OR 1.09, 1.00-1.19). Night admissions were also associated with higher mortality compared with day both before and after adjustment for case mix using the UK APACHE II model (crude OR 1.43, 1.37-1.51; adjusted OR 1.16, 1.10-1.23) but not after adjustment using components of the APACHE II model (OR 1.02, 95% CI 0.96-1.09). After appropriate adjustment for case mix, day of the week and time of day of admission of patients to ICU were not associated with significant differences in hospital mortality.


[Secretion of radioactively labeled amino acids into the digestive tract. 4. 14C label and 14C-leucine in the digestive tract following subcutaneous injection of 14C-leucine in rats after ligation of the pancreas].
Secretion into the Gastro-Intestinal Tract of Amino Acids Labelled with Radioactive Isotopes. (4) 14C-Labelling and 14C-Leucine in the Gastro-Intestinal Tract after Subcutaneous Injection of 14C-Leucine to Rats with Tied-off Pancreatic Gland.


TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction.
Diabetic cardiovascular complications are characterised by oxidative stress-induced endothelial dysfunction. Uncoupling protein 2 (UCP2) is a regulator of mitochondrial reactive oxygen species (ROS) generation and can antagonise oxidative stress, but approaches that enhance the activity of UCP2 to inhibit ROS are scarce. Our previous studies show that activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin can prevent cardiometabolic disorders. In this study, we conducted experiments in vitro and in vivo to investigate the effect of capsaicin treatment on endothelial UCP2 and oxidative stress. We hypothesised that TRPV1 activation by capsaicin attenuates hyperglycemia-induced endothelial dysfunction through a UCP2-mediated antioxidant effect. TRPV1(-/-), UCP2(-/-) and db/db mice, as well as matched wild type (WT) control mice, were included in this study. Some mice were subjected to dietary capsaicin for 14 weeks. Arteries isolated from mice and endothelial cells were cultured. Endothelial function was examined, and immunohistological and molecular analyses were performed. Under high-glucose conditions, TRPV1 expression and protein kinase A (PKA) phosphorylation were found to be decreased in the cultured endothelial cells, and the effects of high-glucose on these molecules were reversed by the administration of capsaicin. Furthermore, high-glucose exposure increased ROS production and reduced nitric oxide (NO) levels both in endothelial cells and in arteries that were evaluated respectively by dihydroethidium (DHE) and DAF-2 DA fluorescence. Capsaicin administration decreased the production of ROS, restored high-glucose-induced endothelial dysfunction through the activation of TRPV1 and acted in a UCP2-dependent manner in vivo. Administration of dietary capsaicin for 14 weeks increased the levels of PKA phosphorylation and UCP2 expression, ameliorated the vascular oxidative stress and increased NO levels observed in diabetic mice. Prolonged dietary administration of capsaicin promoted endothelium-dependent relaxation in diabetic mice. However, the beneficial effect of capsaicin on vasorelaxation was absent in the aortas of UCP2(-/-) mice exposed to high-glucose levels. TRPV1 activation by capsaicin might protect against hyperglycemia-induced endothelial dysfunction through a mechanism involving the PKA/UCP2 pathway.


Motor cortex involvement during verbal versus non-verbal lip and tongue movements.
We evaluated left and right motor cortex involvement during verbal and non-verbal lip and tongue movements in seven healthy subjects using whole-head magnetoencephalography. The movements were paced by tone pips. The non-verbal tasks included a kissing movement and touching the teeth with the tongue. The verbal tasks comprised silent articulation of the Finnish vowel /o/, which requires mouth movement similar to that in the kissing task, pronouncing the same self-selected word repeatedly, and producing a new word for every tone pip. Motor cortex involvement was quantified by task-related suppression and subsequent rebound of the 20-Hz activity. The modulation concentrated to two sites along the central sulcus, identified as the motor face and hand representations. The 20-Hz suppression in the face area was relatively similar during all tasks. The post-movement rebound, however, was significantly left-lateralized during word production. In the non-verbal tasks, hand areas showed pronounced suppression of 20-Hz activity that was significantly diminished for the verbal tasks. The latencies of the 20-Hz suppression in the left and right face representations were correlated across subjects during verbal mouth movements. Increasing linguistic content of lip and tongue movements was thus manifested in spatially more focal motor cortex involvement, left-hemisphere lateralization of face area activation, and correlated timing across hemispheres.


A case of malignant lymphoma with diastolic heart failure.
In patients with malignant lymphoma, the first signs and symptoms are frequently noncardiac and clinical manifestations of cardiac involvement are often nonspecific. This case report presents a patient with malignant lymphoma whose first manifestation was characteristic of heart failure, mainly due to diastolic dysfunction, and whose postmortem examination revealed massive myocardial invasion.


Vascular peroxidase 1 is independently associated with worse kidney function in patients with peripheral artery disease.
Oxidative stress is involved in cardiovascular disease such as peripheral artery disease (PAD). Vascular Peroxidase 1 (VPO1), a novel heme-containing peroxidase mainly expressed in the cardiovascular system, aggravates oxidative stress. Evidence in humans is limited. Current work aims to measure VPO1 in patients suffering from PAD, and to evaluate the association of VPO1 with conventional markers of cardiovascular risk factors (CVRF), including the estimated glomerular filtration rate (eGFR) and albuminuria categories. This study is part of a longitudinal observational study. At baseline, 236 PAD-patients were included. VPO1 plasma levels (ng/mL) were measured by commercially available ELISA kits. A two-sided p level of < 0.05 was considered statistically significant. In the cross-sectional analysis (n = 236), VPO1 associated with ageing (p = 0.035) as well as with eGFR and albuminuria category, the markers of chronic kidney disease (CKD)-progression (p = 0.042). The longitudinal 18-months follow-up analysis (n = 152) demonstrated that baseline VPO1 predicts rapid kidney function decline (RKFD) (n = 49), defined as more than - 3 mL/min/1.73m2 eGFR loss per year, (OR per one SD VPO1 1.60 (1.11-2.30); p = 0.009). This association between VPO1 and kidney function withstood the multivariable adjustment for traditional CVRF including baseline eGFR and urine albumin-to-creatinine ratio (UACR), (adjOR per one SD VPO1 1.73 (1.14-2.61); p = 0.046). This study is first to reveal that VPO1 is independently associated with declining kidney function in patients with PAD. VPO1 shows a tighter association to kidney function than to other CVRF. This finding points to VPO1 as a potential target protein to assess CKD-progression.


An approach to use an unusual adenosine transporter to selectively deliver polyamine analogues to trypanosomes.
In this paper we describe an approach to selectively deliver compounds to trypanosomes using an adenosine transporter which is unique to the trypanosome. Various polyamine analogues have been attached to known substrates of this adenosine transporter. The compounds prepared interact specifically with the adenosine transporter, some with a similar efficiency to berenil, a known substrate.


Is anterolateral ligament rupture a reason for persistent rotational instability after anterior cruciate ligament reconstruction?
The aim of the present study was to evaluate the clinical role of anterolateral ligament (ALL) rupture and its impact on rotational stability by comparing the clinical results and rotational stability between reconstructed anterior cruciate ligament (ACL) with intact ALL knees and reconstructed ACL with ALL injured knees. A total of 69 patients who had undergone surgery for ACL reconstruction and had received a minimum of two years of follow-up were included. Patients were divided into two groups with respect to the presence of ALL rupture on knee magnetic resonance imaging. Patients were assessed preoperatively and at final follow-up with physical examination findings and functional outcomes. Rotational stability was measured by a non-invasive rotameter-like device at the final follow-up at different torque values of 5 Nm (newton metres), 10 Nm and 15 Nm, and compared between the two groups. The ALL was considered to be ruptured in 45 cases, named Group I (65.2%). The ALL was considered to be intact in 24 cases, named Group II (34.8%). No significant difference was found between the groups regarding the improvement of the clinical scores and physical examination findings (P > 0.05). Group I showed significantly higher internal rotation difference compared with Group II in all torque values (P < 0.05). The difference found on rotational measurement is possibly under the value of minimal clinical important difference and does not have a clinical effect, therefore ALL reconstruction is not recommended as a standard treatment in all patients.


Comparative Analysis of Outcomes in Patients Undergoing Femoral Endarterectomy plus Endovascular (Hybrid) or Bypass for Femoropopliteal Occlusive Disease.
The gold-standard for management of combined common femoral artery (CFA) and superficial femoral artery (SFA) atherosclerotic occlusive disease has traditionally been open femoral endarterectomy and femoral-popliteal bypass. Hybrid approaches involving an open and endovascular component are increasingly common. The aim of this study was to compare perioperative outcomes in patients who underwent an open versus hybrid revascularization. NSQIP data, years 2012-2017, were queried for patients who underwent nonemergent CFA endarterectomy with either SFA transluminal intervention or bypass. The primary outcome of interest was a composite of cardiovascular, pulmonary, and renal complications (systemic) and mortality. Two propensity-weight adjusted analyses were performed: 1) comparing hybrid and prosthetic bypass 2) comparing hybrid and vein bypass. There were 4,478 patients included (1,537 hybrid, 1,408 prosthetic, 1,533 vein); 64.8% were men, and the mean age was 67.8 ± 9.7 years; 29.9% had claudication, 38.8% had tissue loss, and 31.3 were unspecified. In the propensity-weighted analysis comparing hybrid to prosthetic bypass, there was no difference in systemic complications (OR = 1.29 for prosthetic vs. hybrid; 95% CI: 0.95-1.76; P = 0.107) or mortality (OR = 1.54; 95% CI: 0.71-3.33; P = 0.275). Prosthetic bypass was associated with more deep surgical-site infections (OR = 2.02; 95% CI: 1.19-3.45; P = 0.010), postoperative sepsis (OR = 2.07; 95% CI: 1.13-3.76; P = 0.018), unplanned 30-day readmission (OR = 1.28; 95% CI: 1.04-1.58; P = 0.021), and the composite of any complication (OR = 1.38; 95% CI: 1.18-1.61; P < 0.001). In the propensity-weighted analysis comparing hybrid to vein bypass, there was no difference in systemic complications (OR = 1.10 for vein vs. hybrid; 95% CI: 0.81-1.49; P = 0.552) or mortality (OR = 0.91; 95% CI: 0.42-2.00; P = 0.819). Vein bypass was associated with more superficial surgical-site infections (OR = 1.45; 95% CI: 1.04-2.02; P = 0.028), and the composite of any complication (OR = 1.32; 95% CI: 1.13-1.54; P = 0.001). Overall mortality was significantly higher patients with systemic complications (13.9% vs 0.1%; P < 0.001). Systemic complications were less common in patients with claudication undergoing hybrid revascularization than vein or prosthetic bypass. Claudicants undergoing bypass experienced more systemic complications than those undergoing hybrid procedures, but there appears to be no increased risk of systemic complications or mortality with open reconstruction when compared to hybrid procedures for other indications. Other complications, such as infection, postoperative transfusion, and readmission, were more common in the bypass groups.


Synthesis of some new diaryl and triaryl hydrazone derivatives as possible estrogen receptor modulators.
1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and 1-naphthyl-1-(4-substituted phenyl)-methanone (2,4-dinitrophenyl)hydrazones have been synthesized and evaluated for their anti-implantation, uterotrophic, antiuterotrophic, anticancer and antimicrobial activities. Diphenolic hydrazone (compound 6) showed maximum uterotrophic inhibition of 70%, whereas compound 20 exhibited cytotoxicity in the range of 50-70% against MCF-7 and ZR-75-1 human malignant breast cell lines.


Histopathological Correlates of Lobar Microbleeds in False-Positive Cerebral Amyloid Angiopathy Cases.
A definite diagnosis of cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid β in walls of cerebral small vessels, can only be obtained through pathological examination. A diagnosis of probable CAA during life relies on the presence of hemorrhagic markers, including lobar cerebral microbleeds (CMBs). The aim of this project was to study the histopathological correlates of lobar CMBs in false-positive CAA cases. In 3 patients who met criteria for probable CAA during life, but showed no CAA upon neuropathological examination, lobar CMBs were counted on ex vivo 3T magnetic resonance imaging (MRI) and on ex vivo 7T MRI. Areas with lobar CMBs were next sampled and cut into serial sections, on which the CMBs were then identified. Collectively, there were 25 lobar CMBs on in vivo MRI and 22 on ex vivo 3T MRI of the analyzed hemispheres. On ex vivo MRI, we targeted 12 CMBs for sampling, and definite histopathological correlates were retrieved for 9 of them, of which 7 were true CMBs. No CAA was found on any of the serial sections. The "culprit vessels" associated with the true CMBs instead showed moderate to severe arteriolosclerosis. Furthermore, CMBs in false-positive CAA cases tended to be located more often in the juxtacortical or subcortical white matter than in the cortical ribbon. These findings suggest that arteriolosclerosis can generate lobar CMBs and that more detailed investigations into the exact localization of CMBs with respect to the cortical ribbon could potentially aid the diagnosis of CAA during life. ANN NEUROL 2023;94:856-870.


Prospective randomized comparison of oxybutynin, functional electrostimulation, and pelvic floor training for treatment of detrusor overactivity in women.
The purpose of this study is to compare the effectiveness of oxybutynin, functional electrostimulation (FES), and pelvic floor training (PFT) for treatment of women with detrusor overactivity. Sixty-four subjects were randomized to oxybutynin (n=22), FES (n=21), or PFT (n=21). Women were evaluated before and after completion of 12 weeks of treatment by subjective response, voiding diary, and urodynamic test. There was subjective symptomatic improvement in 77% of the women treated with oxybutynin, 52% with FES, and 76% with PFT. Urgency resolved in 64% of women treated with oxybutynin, 52% with FES, and in 57% with PFT. Urodynamic evaluation was normal in 36% treated with oxybutynin, 57% with FES, and 52% with PFT. Maximum detrusor involuntary contraction pressure decreased in all groups (p<0.05). All treatments were equally effective. Subjective reduction of urge-incontinence episodes was associated with symptomatic improvement.


MR imaging of the shoulder after surgery.
This review article describes postoperative MR findings relating to surgery in shoulder impingement syndrome, including rotator cuff lesions, shoulder instability, and arthroplasty. Potentially misleading postoperative findings are emphasized. Because standard MR imaging may not always be the method of choice for post operative imaging, alternative imaging techniques have been included (MR arthrography, CT arthrography, and sonography).


How human capital and energy prices play their role to enhance renewable energy: defining the role of innovations and trade openness in G-11 countries.
It is crucial to switch from nonrenewable energy to renewable energy sources to improve environmental quality. For this reason, innovations play a crucial part, yet the use of renewable energy is insufficient. This work contributes to the literature by Using both aggregate and disaggregated data, this study investigates the relationship between energy consumption, trade openness, human capital (HCA), and innovations in G11 nations. This study analyzed yearly data from 1990 to 2020 using empirical methods of augmented mean group (AMG) and cross-sectional autoregressive distributed lag (CS-ARDL) techniques. The findings highlight the significance of human capital, energy pricing, and innovations in fostering the growth of renewable energy in G-11 nations. A 1% increase in GDP and trade openness will enhance total energy consumption by 0.47% and 0.07%. GDP and trade are also increasing non and renewable energy consumption. A 1% increase in human capital and eco-innovations are increasing renewable energy by reducing non-renewable energy consumption. In addition, the G-11's rising commerce and GDP have increased their reliance on energy sources that rely on fossil fuels. The authors of this study suggest raising HCA as a means of encouraging the G-11 to use cleaner forms of energy. The need to bolster renewable energy to achieve a cleaner environment in the G-11 countries.


Videoendoscopic diagnosis of esophageal motility disorders.
Esophageal motility disorders are usually diagnosed by manometry. We evaluated videoendoscopy as a diagnostic test. In this study, 20 patients with achalasia, 13 with scleroderma, and 33 control subjects had a standard endoscopic examination followed by protocol videotaping of swallows to observe contractions in the esophagus and in the lower esophageal sphincter. Tapes were later reviewed by 2 blinded observers who recorded their motility findings and diagnoses. In the mid esophagus at 25 cm, lumen-occluding peristaltic contractions were identified in 26 of 33 control subjects versus 1 of 20 achalasia (p < 0.001) and 3 of 13 scleroderma patients (p < 0.005). As viewed in the lower esophagus, the lower esophageal sphincter opened normally in 31 of 33 control subjects versus 1 of 20 achalasia (p < 0.001). In scleroderma, the sphincter never closed in 12 of 13 patients (p < 0. 001 versus control subjects). A diagnostic sequence of sphincter opening followed by contraction in the esophageal body and subsequent sphincter closing was seen in 33 of 33 control subjects, 2 of 20 achalasia, and 1 of 13 scleroderma patients (both, p < 0. 001). The observers made the correct diagnosis in 96% of cases. Achalasia and esophageal scleroderma can be identified by endoscopic observation of motility. This procedure may represent an adjunctive diagnostic test to manometry.


Tick communities of cattle in smallholder rural livestock production systems in sub-Saharan Africa.
The majority of the African population lives in rural areas and depends on agriculture for their livelihoods. To increase the productivity and sustainability of their farms, they need access to affordable yield-enhancing inputs of which parasite control is of paramount importance. We therefore determined the status of current tick species with the highest economic impact on cattle by sampling representative numbers of animals in each of seven sub-Saharan countries. Data included tick species' half-body counts from approximately 120 cattle at each of two districts per country, collected four times in approximately 1 year (to include seasonality). Study sites were chosen in each country to include high cattle density and tick burden. East Africa (Ethiopia, Uganda and Tanzania) showed overall a higher diversity and prevalence in tick infestations compared to West African countries (Benin, Burkina Faso, Ghana and Nigeria). In East Africa, Amblyomma variegatum (vector of Ehrlichia ruminantium), Rhipicephalus microplus (Babesia bovis, B. bigemina, Anaplasma marginale), R. evertsi evertsi (A. marginale) and R. appendiculatus (Theileria parva) were the most prevalent tick species of economic importance. While the latter species was absent in West Africa, here both A. variegatum and R. microplus occurred in high numbers. Rhipicephalus microplus had spread to Uganda, infesting half of the cattle sampled. Rhipicephalus appendiculatus is known for its invasive behaviour and displacement of other blue tick species, as observed in other East and West African countries. Individual cattle with higher body weights, as well as males, were more likely to be infested. For six tick species, we found reduced infestation levels when hosts were treated with anti-parasiticides. These baseline data allow the determination of possible changes in presence and prevalence of ticks in each of the countries targeted, which is of importance in the light of human-caused climate and habitat alterations or anthropogenic activities. As many of the ticks in this study are vectors of important pathogens, but also, as cattle may act as end hosts for ticks of importance to human health, our study will help a wide range of stakeholders to provide recommendations for tick infestation surveillance and prevention.


Mid-term results after endovascular stent-graft placement due to penetrating atherosclerotic ulcers of the thoracic aorta.
To determine mid-term durability of endovascular stent-graft placement in patients with penetrating atherosclerotic ulcers (PAU) involving the thoracic aorta and to identify risk factors for death as well as early and late cardiovascular events. From 1997 to 2006, 27 patients (mean age 66 yrs) presented with PAU (rupture n=7). Mean numeric EuroScore was 11 and mean logistic EuroScore was 35. Median follow-up was 42 (10-86) months, being complete in all patients. Outcome variables included death and occurrence of early and late cardiovascular events. In-hospital mortality was 11%. Primary success rate was 100%. Actuarial survival rates at 1, 3 and 5 years were 93%, 78% and 70%, respectively. Hemodynamic instability (HR 2.5, 2.1-3.9; p=0.034) as well as logistic EuroScore (HR 2.8, 2.4-4.3; p=0.019) was identified as independent predictor of early and late cardiovascular events. Endovascular stent-graft placement in patients with PAU is an effective palliation for a life-threatening sign of a severe systemic process. Hemodynamic instability at referral and a high preoperative risk score predict adverse outcome. During mid-term follow-up, patients are mainly limited by sequelae of their underlying disease.


Synthesis and biological analysis of novel glycoside derivatives of l-AEP, as targeted antibacterial agents.
To develop targeted methods for treating bacterial infections, the feasibility of using glycoside derivatives of the antibacterial compound l-R-aminoethylphosphonic acid (l-AEP) has been investigated. These derivatives are hypothesized to be taken up by bacterial cells via carbohydrate uptake mechanisms, and then hydrolyzed in situ by bacterial borne glycosidase enzymes, to selectively afford l-AEP. Therefore the synthesis and analysis of ten glycoside derivatives of l-AEP, for selective targeting of specific bacteria, is reported. The ability of these derivatives to inhibit the growth of a panel of Gram-negative bacteria in two different media is discussed. β-Glycosides (12a) and (12b) that contained l-AEP linked to glucose or galactose via a carbamate linkage inhibited growth of a range of organisms with the best MICs being <0.75mg/ml; for most species the inhibition was closely related to the hydrolysis of the equivalent chromogenic glycosides. This suggests that for (12a) and (12b), release of l-AEP was indeed dependent upon the presence of the respective glycosidase enzyme.


Roles of catalytic ozonation by bimetallic Fe/Ce loading sludge-derived biochar in amelioration of sludge dewaterability: Performance and implementation mechanisms.
In this study, an environmentally friendly alternative was developed using catalytic ozonation by sludge-derived biochar loaded with bimetallic Fe/Ce (O3/SBC-FeCe) for enhanced sludge dewatering. The results indicated that the lowest capillary suction time (CST) of 20.9 s and water content of dewatered sludge cake (Wc) of 64.09% were achieved under the dosage of 40 mg O3/g dry solids (DS) and 0.4 g SBC-FeCe/g DS which were considered as the optimum condition. In view of excellent electron exchanging capacity of SBC-FeCe with rich Lewis acid sites and conversions of valence sates of Fe and Ce, more O3 were decomposed into reactive oxygen species under the catalytic action of SBC-FeCe, which strengthened oxidizing capacity. Enhanced oxidation rendered sludge cells inactivation and compact network structure rupture releasing intracellular water and organic substances. Subsequently, hydrophilic organic matters were attacked and eliminated lessening sludge viscosity and colloidal forces and intensifying hydrophobicity and flowability. In addition, changes of sludge morphology suggested that sludge roughness was alleviated, structural strength and compressibility were raised and porous and retiform structure was constructed providing channels for water outflow by adding skeleton builder of SBC-FeCe. Overall, the synergistic interaction of strengthened oxidation and skeleton construction improved sludge dewaterability.


Distinguishing analgesic drugs from non-analgesic drugs based on brain activation in macaques with oxaliplatin-induced neuropathic pain.
The antineoplastic agent oxaliplatin is a first-line treatment for colorectal cancer. However, neuropathic pain, characterized by hypersensitivity to cold, emerges soon after treatment. In severe instances, dose reduction or curtailing treatment may be necessary. While a number of potential treatments for oxaliplatin-induced neuropathic pain have been proposed based on preclinical findings, few have demonstrated efficacy in randomized, placebo-controlled clinical studies. This failure could be related, in part, to the use of rodents as the primary preclinical species, as there are a number of distinctions in pain-related mechanisms between rodents and humans. Also, an indicator of preclinical pharmacological efficacy less subjective than behavioral endpoints that is translatable to clinical usage is lacking. Three days after oxaliplatin treatment in Macaca fascicularis, a significantly reduced response latency to cold (10 °C) water was observed, indicating cold hypersensitivity. Cold-evoked bilateral activation of the secondary somatosensory (SII) and insular (Ins) cortex was observed with functional magnetic resonance imaging. Duloxetine alleviated cold hypersensitivity and significantly attenuated activation in both SII and Ins. By contrast, neither clinically used analgesics pregabalin nor tramadol affected cold hypersensitivity and cold-evoked activation of SII and Ins. The current findings suggest that suppressing SII and Ins activation leads to antinociception, and, therefore, could be used as a non-behavioral indicator of analgesic efficacy in patients with oxaliplatin-induced neuropathic pain.


Safety assessment of graphene oxide and microcystin-LR complex: a toxicological scenario beyond physical mixture.
Nanomaterials have been widely used in electrochemistry, sensors, medicine among others applications, causing its inevitable environmental exposure. A raising question is the "carrier" effect due to unique surface properties of nanomaterials, which may collectively impact the bioavailability, toxicokinetic, distribution and biological effects of classic toxicants. Noteworthy, this aspect of information remains largely unexplored. Here, we deliberately selected two entities to mimic this scenario. One is graphene oxide (GO), which is made in ton quantity with huge surface-area that provides hydrophilicity and π-π interaction to certain chemicals of unique structures. The other is Microcystin-LR (MCLR), a representative double-bond rich liver-toxic endotoxin widely distributed in aquatic-system. Firstly, the adsorption of GO and MCLR after meeting under environmental conditions was explored, and then we focused on the toxicological effect and related mechanism of GO-MCLR complex on human skin cutin forming cells (HaCaT cells) and normal liver cells (L02 cells). Abiotically, our study demonstrated that GO could effectively adsorb MCLR through hydrogen bonding and π-π interaction, the oxidation degree of GO-MCLR decreased significantly and surface defect level raised. Compared to GO or MCLR, GO-MCLR was found to induce more remarkable apoptosis and ferroptosis in both HaCaT and L02 cells. The underlying mechanism was that GO-MCLR induced stronger intracellular reactive oxygen species (ROS) and mtROS generation, followed by Fe2+ accumulation, mitochondrial dysfunction and cytoskeletal damage. These results suggest that the GO-MCLR complex formed by GO adsorption of MCLR may exhibit more toxic effects than the single material, which demonstrates the necessity for assessing nano-toxicant complexity. Our discovery may serve as a new toxicological paradigm in which nanomaterial mediated surface adsorption effects could impact the degree of cytotoxicity and toxicological mechanisms of classic toxins.


The use of intracellular dialysis to study signal transduction coupling in the squid giant axon.
The squid giant axon has proved a useful model in the study of ionic channel gating, intracellular homeostasis and receptor-mediated signal transduction leading to generation of intracellular second messengers. In the latter category, previous studies on activation of adenylate or guanylate cyclase have used intact and intracellularly perfused axons to investigate the effects of extra- and intracellular agents on the transduction processes. However, the perfusion of the axon interior washes out many factors which may be important in the processes under study. We introduce here the use of porous cellulose dialysis tubing as a means to circumvent these problems. We find that this dialysis technique is a simple procedure to set-up, and the serotonin/G-protein/adenylate cyclase system can readily be studied in the dialysed axon. This approach should allow investigation under conditions which retain asymmetric transmembrane conditions.


CDK12 phosphorylates 4E-BP1 to enable mTORC1-dependent translation and mitotic genome stability.
The RNA polymerase II (RNAPII) C-terminal domain kinase, CDK12, regulates genome stability, expression of DNA repair genes, and cancer cell resistance to chemotherapy and immunotherapy. In addition to its role in mRNA biosynthesis of DNA repair genes, we show here that CDK12 phosphorylates the mRNA 5' cap-binding repressor, 4E-BP1, to promote translation of mTORC1-dependent mRNAs. In particular, we found that phosphorylation of 4E-BP1 by mTORC1 (T37 and T46) facilitates subsequent CDK12 phosphorylation at two Ser-Pro sites (S65 and T70) that control the exchange of 4E-BP1 with eIF4G at the 5' cap of CHK1 and other target mRNAs. RNA immunoprecipitation coupled with deep sequencing (RIP-seq) revealed that CDK12 regulates release of 4E-BP1, and binding of eIF4G, to many mTORC1 target mRNAs, including those needed for MYC transformation. Genome-wide ribosome profiling (Ribo-seq) further identified specific CDK12 "translation-only" target mRNAs, including many mTORC1 target mRNAs as well as many subunits of mitotic and centromere/centrosome complexes. Accordingly, confocal imaging analyses revealed severe chromosome misalignment, bridging, and segregation defects in cells deprived of CDK12 or CCNK. We conclude that the nuclear RNAPII-CTD kinase CDK12 cooperates with mTORC1, and controls a specialized translation network that is essential for mitotic chromosome stability.


Protozoa lectins and their role in host-pathogen interactions.
Lectins are proteins/glycoproteins of non-immune origin that agglutinate red blood cells, lymphocytes, fibroblasts, etc., and bind reversibly to carbohydrates present on the apposing cells. They have at least two carbohydrate binding sites and their binding can be inhibited by one or more carbohydrates. Owing to carbohydrate binding specificity of lectins, they mediate cell-cell interactions and play role in protozoan adhesion and host cell cytotoxicity, thus are central to the pathogenic property of the parasite. Several parasitic protozoa possess lectins which mediate parasite adherence to host cells based on their carbohydrate specificities. These interactions could be exploited for development of novel therapeutics, targeting the adherence and thus helpful in eradicating wide spread of protozoan diseases. The current review highlights the present state knowledge with regard to protozoal lectins with an emphasis on their haemagglutination activity, carbohydrate specificity, characteristics and also their role in pathogenesis notably as adhesion molecules, thereby aiding the pathogen in disease establishment.


Video-assisted thoracoscopic surgery for pulmonary sequestration in children.
The purpose of this report is to describe our experience with video-assisted thoracoscopic surgery for pulmonary sequestration in children. From May 2001 to June 2004, video-assisted thoracoscopic surgery was attempted for antenatally diagnosed pulmonary sequestration in 8 consecutive infants. Mean age at the time of surgery was 10 months (range, 4 to 44 months). Six lesions were located in the left lower lobe and two in the right lower lobe. Endovascular embolization was attempted before video-assisted thoracoscopic surgery in only 1 patient. All procedures were performed in the lateral decubitus position, and single-lung ventilation was used in all cases. Conversion to open surgery was necessary in two cases. Video-assisted thoracoscopic surgery was successful in 6 patients. After being identified and isolated, the aberrant artery was controlled by endoscopic ligation, and lobectomy, wedge resection, or sequestration was performed depending on the type of lesion. Mean operative time was 155 minutes. Average hospital stay was 3.5 days. There were no postoperative complications. Follow-up ranged from 4 to 50 months. Video-assisted thoracoscopic surgery is technically feasible for pulmonary sequestration. Early resection obviates the risk of infection. Elective ligation of the aberrant artery is a safe alternative to the use of stapling devices or clips. Cosmetic results are excellent.


Sexual Activity and Related Factors of Older Women in Hunan, China: A Cross-Sectional Study.
Sexuality has an important impact on people's physical and mental health, but current research on the sexual activity of older Chinese women has many limitations and more detailed studies are needed. The objective was to determine the prevalence of sexual activity and related factors in women aged 55 to 85 years in Hunan, China. Based on the data from the Hunan Provincial Women Health Needs Survey in 2018, we conducted a secondary analysis of 2,401 older women aged 55 and above. The dependent variable was sexual activity, and independent variables included sociodemographic characteristics, health behaviors, reproductive and chronic medical history, and psychological characteristics. All statistical analyses were performed using SPSS 26.0. Chi-square test was used to assess the association between categorical variables, and binary logistic regression was used to examine factors related to sexual activity. Sexual activity and related factors. The prevalence of sexual activity among older women was 12.5% (301/2401) in the past month. Having a partner (OR = 1.484; 95% CI, 1.048-2.101; P = .026), jogging (OR = 2.061; 95% CI, 1.391-3.054; P < .001), dancing (OR = 1.477; 95% CI, 1.106-1.974; P = .008), vegetarian-based diet (OR = 2.197; 95% CI, 1.334-3.618; P = .002), meat-based diet (OR = 2.196; 95% CI, 1.144-4.216; P = .018) were positively associated with being sexually active. Whereas, aging (OR = 0.781; 95% CI, 0.647-0.942; P = .010), living in the urban (OR = 0.628; 95% CI, 0.488-0.808; P < .001), hypertension (OR = 0.702; 95% CI, 0.520-0.949; P = .021), and anxiety (OR = 0.680; 95% CI, 0.475-0.972; P = .034) were negatively associated with being sexually active. Health care workers need to be aware that older women still have sexual activity and understand the needs of older women for sex education, take the initiative to discuss safe sex with them, and solve their sexual problems. This is one of the largest studies to determine the prevalence of sexual activity among older women in China and its related factors. In addition, new factors such as exercise types and eating habits related to sexual activity were discovered. The limitation of this study is that it did not use a specific questionnaire to assess the sexual activity and did not consider physical tenderness other than sexual intercourse. Some older women still have had sexual activity in the past month and factors such as lifestyles that can be changed and chronic diseases that can be self-managed were found to predict sexual activity. Li T, LuoY, Meng Y, et al. Sexual Activity and Related Factors of Older Women in Hunan, China: A Cross-Sectional Study. J Sex Med 2022;19:302-310.


Evaluation and application of a new scintillator-based heat-resistant back-scattered electron detector during heat treatment in the scanning electron microscope.
A new high-temperature detector dedicated to the collection of backscattered electrons is used in combination with heating stages up to 1050°C, in high-vacuum and low-vacuum modes in order to evaluate its possibilities through signal-to-noise ration measurements and different applications. Four examples of material transformations occurring at high temperature are herein reported: grain growth during annealing of a rolled platinum foil, recrystallisation of a multiphased alloy, oxidation of a Ni-based alloy and complex phase transformations occurring during the annealing of an Al-Si coated boron steel. The detector could be potentially adapted to any type of SEM and it offers good opportunities to perform high-temperature experiments in various atmospheres.


Molecular importance of prawn large heat shock proteins 60, 70 and 90.
Considering the importance of heat shock proteins (HSPs) in the innate immune system of prawn, a comparative molecular approach was proposed to study the crustacean large HSPs 60, 70 and 90. Three different large HSPs were identified from freshwater prawn Macrobrachium rosenbergii (Mr) cDNA library during screening. The structural and functional characteristic features of HSPs were studied using various bioinformatics tools. Also, their gene expression and mRNA regulation upon various pathogenic infections was studied by relative quantification using 2(-ΔΔCT) method. MrHSP60 contains a long chaperonin 60 domain at 46-547 which carries a chaperonin 60 signature motif between 427 and 438, whereas MrHSP70 contains a long HSP70 domain at 21-624 and MrHSP90 carries a HSP90 domain at 188-719. The two dimensional analysis showed that MrHSP60 contains more amino acids (52%) in helices, whereas MrHSP70 (40.6%) and MrHSP90 (51.8%) carried more residues in coils. Gene expression results showed significant (P < 0.05) expression of MrHSP60, 70 and 90 in haemocyte, gill and hepatopancreas, respectively. Further, the expression level was up-regulated upon bacterial (Aeromonas hydrophilla and Vibrio harveyi) and viral [white spot syndrome virus (WSSV) and M. rosenbergii nodo virus (MrNV)] infections during various time periods. The gene expression results exhibited the potential involvement of these three HSPs in the immune system of prawn. The study indicated the potentiality of these molecules, thereby protecting cells against pathogens as well as severe cellular and environmental stresses in crustaceans.


Maternal 11-Ketoandrostenedione Rises Through Normal Pregnancy and Is the Dominant 11-Oxygenated Androgen in Cord Blood.
Adrenal-derived 11-oxygenated androgens (11oAs) are known important contributors to human physiology and disease but have not been studied in pregnancy. We characterize 11oAs in normal human pregnancy and neonatal period and assess the ratios between 11oAs and compare with ratios of other steroids that undergo placental metabolism. Prospective cohort study, 2010-2018. Academic institution. Pairs of pregnant women and newborns (n = 120) were studied. Inclusion criteria were maternal age between 18 and 42 years old, spontaneous singleton pregnancies, and intention to deliver at University of Michigan. Maternal venous blood was collected during first trimester and at term. Neonatal cord blood was collected following delivery. Steroids were measured via liquid chromatography-tandem mass spectrometry. Levels of 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone, and 11-ketotestoterone (11KT) in maternal first trimester, maternal term, and neonatal cord blood were compared. 11OHA4-to-11KA4 ratios were correlated with cortisol-to-cortisone ratios. Dominant 11oAs in pregnancy and the cord blood are 11OHA4 and 11KA4, compared to 11OHA4 and 11KT in adult men and nonpregnant women. We found a rise in 11oA concentrations, particularly 11KA4, from first to third trimester. In cord blood, the concentration of 11KA4 exceeded those of both 11OHA4 and 11KT, reflecting placental 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) and 17β-hydroxysteroid dehydrogenase (17βHSD2) activities, respectively. 11OHA4-to-11KA4 ratios are concordant with cortisol-to-cortisone ratios across all maternal and fetal compartments, reflecting placental 11βHSD2 activity. Placental 17βHSD2 activity defends the fetus against the androgen 11KT. Our normative values may be used in future studies of 11oAs in complicated pregnancies.


Targeting PKCι-PAK1 in EGFR-mutation positive non-small cell lung cancer.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) induce significant responses in EGFR-mutation positive non-small cell lung cancer (NSCLC). However, universal progression is observed. The effect of the anti-rheumatoid agent, auranofin, a selective inhibitor of oncogenic protein kinase C iota (PKCι) signaling and IPA-3, a non-ATP competitive p21-activated kinase 1 (PAK1) inhibitor in treatment-naïve and EGFR TKI-resistant EGFR-mutation positive NSCLC cell lines was investigated. PC9 and HCC827 cells were used. The four EGFR-TKI resistant cell lines were established from PC9. Cell viability assays, drug combination studies, and western blotting were performed. The combination index, and RTK or non-RTK expression were performed. The combination of IPA-3 and auranofin was highly synergistic in all 6 cell lines (combination indexes ranged from 0.37-0.62). The activities on EGFR, CDCP1, AXL, MET, and downstream effector pathways, including PAK1, PKCι, ERK, AKT, STAT3, Src, and YAP1 were abrogated. The combination of auranofin with IPA-3 could be a potential therapy for EGFR-mutation positive NSCLC resistant to EGFR TKIs. Auranofin with IPA-3 could become a therapeutic solution for EGFR-mutation positive NSCLC patients resistant to EGFR TKIs.


Detection of Coxiella burnetii DNA and anti-Coxiella burnetii IgG antibodies in precolostral blood samples of stillborn calves in an endemically infected Holstein dairy herd.
Coxiella burnetii (C. burnetii), an intracellular zoonotic bacterium causing Q fever, occurs widely in cattle herds. After invasion of the pregnant uterus and initial localization in the placenta, active C. burnetii infections may spread to the fetus hematogenously or by the amniotic-oral route and thus may cause abortion, premature delivery, stillbirth, and weak offspring (APSW) complex. In a case-control study, we investigated precolostral blood samples of 56 stillborn calves and 30 live births from a dairy herd endemically infected with C. burnetii "C-cluster" strains and an increased stillbirth rate in primiparous cows. Within the group of the stillborn calves, four precolostral blood samples (7.1%) were tested positive for C. burnetii DNA by PCR and one serum sample (1.8%) positive for anti-C. burnetii IgG antibodies by a commercial ELISA test, respectively. Neither C. burnetii DNA nor anti-C. burnetii IgG antibodies were detected in the samples of calves being born alive. In conclusion, we demonstrated that coxiellaemia and precolostral seroconversion occurred sporadically in stillborn calves from this endemically infected herd. Due to the low detection rates, C. burnetii could not be confirmed to be the cause of the increased stillbirth rate.


Neuronal activity of medial wall of frontal cerebral cortex of rats at various stages of learning.
The activity of neurons of the medial wall of the frontal cortex of the brain of rabbits was investigated during their performance of a task of delayed spatial choice. The recording of neuronal activity was carried out in two groups of animals which were at different stages of training. Different types of spatially selective neurons were found. The possible association of the character of the neuronal reorganizations with the level of learning of the animal is discussed.


Effect of hydrocortisone on arginase activity in ICRC mouse mammary tumours in vitro.
Three fold increase of arginase activity was observed in hydrocortisone treated mammary tumour tissue when compared to the untreated tissue in vitro. No change in succinic dehydrogenase activity was observed. It is likely that arginase present in mammary tumour is due to the presence of mammary tumour virus and it is tempting to speculate that the increase in arginase activity by hydrocortisone may be due to sustained viral production in the presence of hydrocortisone.


[Comparison of the effect between procaine and 5-aza-dc on wnt inhibitory factor 1 promoter methylation of HepG2].
To observe the CpG island methylation status, mRNA and protein expression of the Wnt inhibitory factor-1 (Wif-1) gene with procaine or 5'-Aza-2'-deoxycycytidine (5-aza-dc) on HepG2. And to explore the comparison of the demethylation with 5-aza-dc or procaine. HepG2 cells were treated with 5-aza-dc or procaine. Wif-1 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). Wif-1 protein expression was detected by Western blot. The promoter methylation status of Wif-1 gene on treatment or not were detected by methylation-specific PCR (MSP). (1) RT-PCR and Western blot exhibited that both Wif-1 mRNA and Wif-1 protein expression were positive in groups treated with procaine and 5-aza-dc and highly positive in the L0 cells group, but weakly even negative in the HepG2 cells without any treatment, the difference were statistically significant (P < 0.05) (procaine experimental group was higher than that of 5-aza-dc experimental group, P < 0.05). (2) The positive rates of the promoter hypermethylated in procaine and 5-aza-de groups were (14.41 +/- 3.37)% and (29.29 +/- 1.84)%. Both of the two groups showed a part of the de-methylation status (P < 0.05). Both of procaine and 5-aza-dc can reverse the abnormal methylation of Wif-1 gene. Procaine can be more effective than conventional used 5-aza-dc and could be a new demethylation drug.


Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma.
Cholangiocarcinomas are highly lethal tumours of the intrahepatic or extrahepatic biliary tract. The aetiology is largely unknown, and the potential roles of gallstones and gall bladder removal (cholecystectomy) need to be addressed in a large study with a long follow-up. A population-based nationwide Swedish cohort study was carried out, in which patients hospitalised for gallstone diagnosis with or without gallbladder removal (cholecystectomy) between 1965 and 2008 were identified in the Swedish Patient Registry. The cohort was followed up for cancer in the Swedish Cancer Registry. The observed numbers of intra- and extrahepatic cholangiocarcinomas that developed after one year of follow-up were compared with the expected numbers, calculated from the corresponding background population, and the relative risks were estimated by standardised incidence ratios (SIRs) and 95% confidence intervals (CIs). Among the 192,960 non-cholecystectomised individuals with gallstones, there was a more than two-fold overall increased risk of both intra- and extra- hepatic cholangiocarcinomas, which remained stable over the follow-up period (SIR 2.77, 95% CI 2.17-3.49, and SIR 2.58, 95% CI 2.21-3.00, respectively). In the cholecystectomy cohort, including 345,251 people and 4,854,969 person-years, 325 incident cholangiocarcinomas were identified, of which 98 (30%) were intrahepatic and 227 (70%) were extrahepatic. Initially (1-4 years after surgery), the risk was increased for both intrahepatic cholangiocarcinoma (SIR 1.80, 95% CI 1.19-2.62) and extrahepatic cholangiocarcinoma (SIR 2.29, 95% CI 1.83-2.82), but no increase remained after 10 years of follow-up or more (SIR 1.10, 95% CI 0.79-1.48, and SIR 0.87, 95% CI 0.70-1.07, respectively). Gallstones seem to increase the risk of both intra- and extrahepatic cholangiocarcinoma. However, this risk seems to decline to the level of the background population with time after cholecystectomy.


Influence of Measurement Depth and Acquisition Parameters on Shear Wave Speed and Shear Wave Dispersion in Certified Phantoms Using a Canon Aplio Clinical Ultrasound Scanner.
The aim of the work described here was to investigate the relative contribution of confounding factors on liver shear wave speed (SWS) and shear wave dispersion slope (SWDS) measurements in three certified phantoms using a Canon Aplio clinical ultrasound scanner. A Canon Aplio i800 i-series ultrasound system (Canon Medical Systems Corporation, Otawara, Tochigi, Japan) with i8CX1 convex array (center frequency = 4 MHz) was used to examine dependencies caused by the depth, width and height of the acquisition box (AQB), the depth and size of the region of interest (ROI), the AQB angle and the pressure of the ultrasound probe on the surface of the phantom. Results revealed that depth is the most significant confounder in both SWS and SWDS measurements. AQB angle, height and width and ROI size exhibited minimal confounding effects on measurements. For SWS, the most consistent measurement depth is when the top of the AQB is placed between 2 and 4 cm, and the ROI is located between 3 and 7 cm deep. For SWDS, results indicate that measurement values significantly decrease with depth from the surface of the phantom until approximately 7 cm deep, and consequently no stable area of AQB placement or ROI depth exists. In contrast to SWS, the same ideal acquisition depth range cannot necessarily be applied to SWDS measurements because of a significant depth dependency.


Haematological and renal toxicity of radiation therapy in neuroblastoma paediatric patients.
The objective of this study was to evaluate the renal and hematologic toxicity in paediatric patients with adrenal high-risk neuroblastoma who have received radiation therapy (RT) as part of radical treatment. Pediatric patients diagnosed with high-risk adrenal neuroblastoma who received RT as part of the definitive treatment between January 2004 and May 2020 in a single institution were selected. Complete blood counts (CBC) and creatinine clearance (CrCl) pre-RT and post-RT were compared through the Wilcoxon signed-rank test and correlated with survival analysis by Cox regression. Forty-two children with a median age of 3 years at diagnosis and 2.8 years of follow-up were selected. A significant and acute decrease in lymphocytes was found (p = 0.002) 1 month from RT. Patients with a drop higher than 50% of the previous value experimented a significant reduction in overall survival (55 vs 10%; p = 0.031). At the end of the follow-up, a significant increase in all blood counts was observed. With respect to renal function, an acute and significant decrease in CrCl was observed tin patients younger than 4 years who received RT (p = 0.013). However, it was not clinically relevant. Our data suggest that acute lymphopenia occurs after RT and could be associated with a poorer prognosis. Other blood counts are reduced after RT and all of them are in physiological range at the end of follow-up. Our cohort presented excellent renal outcomes without any case of chronic renal dysfunction.


Quadriparesis following cervical epidural steroid injections: case report and review of the literature.
Cervical epidural steroid injections are frequently used in the conservative management of neck pain, cervical radiculitis, and cervical radiculopathy. Between 64-76% of patients who receive injections report subjective pain improvement. Injections are usually well-tolerated with only mild, transient side effects, although a few case reports of patients with adverse effects do appear in the literature. Some clinicians have expressed concerns about epidural injections above the C7-T1 level, and in the use of methylprednisolone epidurally; as yet, neither is a consensus viewpoint. This case report describes severe adverse effects (quadriplegia and respiratory arrest) associated with an epidural injection into the C6-C7 space. Although the patient's symptoms improved somewhat with supportive care, quadriparesis appears irreversible. No reports of quadriparesis after cervical epidural injection were found in the literature, although other adverse effects have been reported. The patient was injected by a fellowship-trained pain management specialist in an outpatient surgicenter using C-arm fluoroscopic guidance. Immediately he experienced respiratory arrest with quadriplegia. He was intubated and transferred to the hospital, then transferred again to Christiana Health Care Services. The patient was hospitalized, treated with steroid protocol within 8 hours, and followed clinically for 6 months. Magnetic resonance imaging within 6 hours of the injury and 6 months later showed no significant findings aside from lordosis (40 degrees angle) of the cervical spine at the C6-C7 level. Although evidence is not conclusive, this patient may have suffered a vascular event from a cervical epidural injection.


Towards therapeutic application of ocular stem cells.
The first example of cell therapy using cultured stem cells dates back to 1981, when it was demonstrated that human epidermis could be grown in the laboratory and transplanted onto burnt patients to reconstitute a functional epidermis [Green H, Kehinde O, Thomas J. Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc Natl Acad Sci USA 1979;76(11):5665-8; Banks-Schlegel S, Kehinde O, Green H. Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Lancet 1981;1:75-8; Gallico 3rd GG, O'Connor NEMJ, Compton CC, Kehinde O, Green H. Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med 1984;311(7):448-51]. This was the onset of regenerative medicine, which is now being developed also in many other fields including ophthalmology. Emerging cell therapies for the restoration of sight have focused on two areas of the eye that are critical for visual function, the cornea and the retina. The relatively easy access of the cornea, the homogeneity of the cells forming the different layers of the corneal epithelium and the improvement of cell culture protocols are leading to considerable success in corneal epithelium restoration. Rebuilding the entire cornea is however still far from reality. The restoration of the retina has recently been achieved in different animal models of retinal degeneration using immature photoreceptors, and two other promising strategies have been demonstrated: transplantation of endothelial precursors to rescue retinal vessels and neurons, and transplantation of retinal pigmented epithelial cells to preserve vision over the long term. The relevance of these approaches will be discussed in function of the disease targeted.


In vivo enhancement of angiogenesis by adenoviral transfer of HIF-1alpha-modified endothelial progenitor cells (Ad-HIF-1alpha-modified EPC for angiogenesis).
Hypoxia inducible factor (HIF)-1alpha over-expression may have beneficial effects in cell therapy of hypoxia-induced pathophysiological processes, such as ischemic disease. Our previous study showed the feasibility of ex vivo modification of endothelial progenitor cells (EPCs) by HIF-1alpha transfection. In this study, we sought to determine if such ex vivo modified EPCs facilitated functional therapeutic neovascularization. Ad-HIF-1alpha was transduced in human EPC in vitro. HIF-1alpha-transduced EPCs were administered to nude mice with hindlimb ischemia. BrdU-labeling of these EPCs showed that they enhanced neovascularization in vivo. Limb and toe necrosis was significantly reduced in HIF-1alpha-EPC group compared to GFP-EPC group and medium control group at 14 days after transplantation (both P<0.05). A statistically significant difference was still observed in the HIF-1alpha group until 1 and 2 months of follow-up. Neovascularization was improved by both histological and physiological assessments. Exogenous EPC homing was observed. HIF-1alpha over-expression enhanced its mRNA and protein expression in the ischemia zone. The expression of genes downstream of HIF-1alpha was examined to explore the possible mechanism of EPC homing. In conclusion, HIF-1alpha-EPC gene transfer augments impaired neovascularization in experimentally induced mouse hindlimb ischemia in vivo.


Adaptable antibody Nanoworms designed for non-Hodgkin lymphoma.
Despite advancements in antibody-based therapies for non-Hodgkin lymphoma (NHL), at least two major therapeutic needs remain unmet: i) heterogenous activation of host immunity towards B cell NHL; and ii) lack of antibody-based therapeutics for T cell NHL. This study explores the molecular characteristics of an adaptable modality called antibody Nanoworms and demonstrates their receptor clustering activity as a means to overcome and address abovementioned needs. To test this, four selected therapeutic receptors of B cell (CD19, CD20, HLA-DR10) and T cell (CD3) NHL were targeted by Nanoworms. Regardless of the target or the cell type, Nanoworms inherently clustered bound receptors on the cell-surface through their multivalency and activated intracellular signaling without any secondary crosslinker. As a sole agent, Nanoworms induced apoptosis by clustering CD20 or HLA-DR10, and arrested the cell cycle upon CD19 clustering. Interestingly, CD3 clustering was particularly advantageous in inducing activation-induced cell death (AICD) in an aggressive form of T cell NHL named Sézary syndrome that is fatal, limited in antibody-based therapeutics, and has poor outcomes to traditional chemotherapy. As Nanoworms can be easily designed to target any receptor for which a scFv is available, they may provide solutions and add therapeutic novelty to underserved diseases.


Subcellular fractionation of rat cerebellum: separation of synaptosomal populations and heterogeneity of mitochondria.
A crude mitochondrial fraction (M) derived from manually disrupted cerebellar tissue and enriched in choline acetyltransferase (ChAT) activity was fractionated by centrifugation in discontinuous and continuous sucrose gradients. Further purification of 'cholinergic' synaptosomes was achieved (relative specific activity (RSA) of ChAT greater than 3), but the overlap with other synaptosomal populations was still considerable. Hand-homogenized cerebella processed through the full fractionation procedure described here and in previous papers yielded preparations enriched in certain neuronal structures and a fraction in which 'heavy' free mitochondria was concentrated. To characterize these preparations the activities of two transmitter enzymes (CHAT and glutamate decarboxylase, GAD) and 6 mitochondrial enzymes (succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), monoamine oxidase, citrate synthase, fumarase and GABA-aminotransferase) were determined. The distribution of the transmitter enzymes was clearly different in the preparations containing various neuronal structures. The GAD:ChAT RSA ratio was 2.4 for the glomerulus particles, 1.3 for the molecular layer fragments, 0.6 for the myelinated axon segments, and 0.2 for the 'cholinergic' synaptosomes. The mitochondrial enzyme profile of the preparations comprising mainly neuronal structures differed markedly from that of the 'free' mitochondrial fraction. Notably the latter was greatly enriched in GDH (RSA 5.6), whereas the SDH:GDH RSA ratio was relatively high in the former preparations. Nevertheless there were notable differences in the enzyme profile of the fractions of predominantly neuronal origin indicating that the enzyme composition of mitochondria of neuronal processes is not uniform.


Medical Prognosis of Infectious Diseases in Nursing Homes by Applying Machine Learning on Clinical Data Collected in Cloud Microservices.
treating infectious diseases in elderly individuals is difficult; patient referral to emergency services often occurs, since the elderly tend to arrive at consultations with advanced, serious symptoms. it was hypothesized that anticipating an infectious disease diagnosis by a few days could significantly improve a patient's well-being and reduce the burden on emergency health system services. vital signs from residents were taken daily and transferred to a database in the cloud. Classifiers were used to recognize patterns in the spatial domain process of the collected data. Doctors reported their diagnoses when any disease presented. A flexible microservice architecture provided access and functionality to the system. combining two different domains, health and technology, is not easy, but the results are encouraging. The classifiers reported good results; the system has been well accepted by medical personnel and is proving to be cost-effective and a good solution to service disadvantaged areas. In this context, this research found the importance of certain clinical variables in the identification of infectious diseases. this work explores how to apply mobile communications, cloud services, and machine learning technology, in order to provide efficient tools for medical staff in nursing homes. The scalable architecture can be extended to big data applications that may extract valuable knowledge patterns for medical research.


Trout (Salmo gairdneri R.) liver 5-aminolevulinate synthetase: subcellular distribution and properties.
The subcellular distribution of trout liver 5-aminolevulinate synthetase has been studied. A cytosolic form of the enzyme has been found. Its activity was a 30% of the mitochondrial enzyme. The cytosolic form has a molecular weight of 110,000, larger than the mitochondrial enzyme (70,000). The two enzyme forms showed a pH optimum of 7.5. The kinetic characteristic of both forms suggest that the cytosolic form is a precursor of the mitochondrial ALA-synthetase.


Treatment of sinus tachycardia with heart-rate feedback.
A 23-year-old male with a history of sinus tachycardia was treated with heart-rate feedback in eight sessions. From a pretreatment average of 103 beats per minute (BPM) as recorded in two separate baseline sessions, the heart rate dropped to 66 BPM in the last treatment session. At follow-up the heart rate seemed stabilized within the normal range, averaging 68 BPM after 1 month and 73 BPM after 12 months. Simultaneous EMG recordings of m. frontalis suggest a generalized effect of this treatment. Results are discussed in terms of somatic and respiratory mediation.


Host defense mechanisms and compromises in the trauma patient.
Infection in multiple trauma patients remains the number one complication and the second leading cause of death in this population. Because each type of injury has its own intrinsic infection risks and the treatment of the injury necessitates the use of invasive therapy, the prevention of infection may not be possible. The most effective infection control measures may be continual nursing assessment of the patient, including observing for subtle changes that would indicate the presence of an infection. It is the early distinction of infection as the underlying mechanism of inflammatory responses and fever that best facilitates an expedient and appropriate course of therapy. Classic recommendations of infection control practices such as hand washing and meticulous aseptic technique during all procedures, plus an awareness of the many ways that microorganisms can contaminate and innoculate the patient are the best strategies for nursing care. Nursing actions must be guided by a clear understanding of the patient's host defense mechanisms and how they are jeopardized by both the injury and the therapy. This understanding facilitates the implementation of specific nursing care measures to promote the restoration of normal host defense mechanisms and to prevent further compromise of the trauma patient while in the ICU.


Risk factors for procedure-related fetal losses after mid-trimester genetic amniocentesis.
The objective of this study was to determine the institutional pregnancy loss rate following second-trimester genetic amniocentesis and to ascertain whether factors exist which would identify pregnancies at increased risk of having a procedure-related fetal loss. University Teaching Hospital Details of the procedure and pregnancy outcome of all patients who had amniocentesis planned or performed between 15-22 gestational weeks between January 1997 and June 2004 were extracted from our clinical audit database. The procedure-related fetal loss rate, defined as all unintended abortions, stillbirths and neonatal deaths without major fetal abnormalities or obvious obstetric causes, was determined and compared to a presumed background fetal loss rate of 0.8% based on a cohort of women who did not undergo the procedure. A total of 3468 consecutive amniocentesis were performed in 3440 patients with 3498 fetuses. The mean gestational age at amniocentesis was 17.6 +/- 1.2 weeks. The majority (98.6%) required only one puncture and a transplacental procedure was required in 2.7% cases. A total of 3465 chromosomal studies were performed. Sixty six cases (1.9%) of major chromosomal abnormalities were detected. Pregnancy outcome was ascertained in all except 26 singleton pregnancies (0.74%). There were 3285 (93.9%) livebirths, 103 (2.9%) termination of pregnancies (TOP), 6 (0.17%) fetal demises before the procedure, and 20 (0.61%) unintended fetal losses due to significant fetal abnormalities or obstetric complications. The remaining 58 fetal losses (1.66%) were classified as potentially procedure-related, which could be either background fetal losses or procedure-related. The procedure-related fetal loss rate after correcting for the background loss rate was 0.86%.Potentially procedure-related fetal losses were found to be significantly associated with a procedure at 18 weeks or beyond (odds ratio OR = 1.97), a procedure performed for abnormal second-trimester biochemical screening test (OR = 3.08), a bloody tap (OR = 6.48), and a female fetus (OR = 2.39); but not to the number of punctures (p = 0.66) nor transplacental amniocentesis (p = 0.104). Mid-trimester amniocentesis is associated with a small but significant risk of fetal loss of 0.86%.


Resveratrol binds and activates RKIP protein in colorectal cancer.
Raf-1 kinase inhibitory protein (RKIP) acts as a tumor cell metastasis suppressor and prognostic indicator for survival in various cancers. Its use is predicted to improve therapy for various malignancies, including colorectal cancer (CRC). RKIP, frequently denoted as phosphatidylethanolamine-binding protein 1, is expressed in all normal mammalian tissues. RKIP functions as an inhibitor of the Raf-1, PI-3K, and MAP kinase (MAPK) pathways. In this study, we found that resveratrol induced the expression of RKIP at protein levels. To elucidate the structural basis of the interaction between resveratrol and RKIP, we performed computational studies that explore the binding affinity and ligand efficacy of resveratrol against RKIP. This study reveals the prognostic significance of RKIP metastasis suppressor activity against CRC and its structural arrangements during drug-target interactions.


Frederick Sanger, Erwin Chargaff, and the metamorphosis of specificity.
That a transformation of ruling ideas in genetics and biochemistry took place at the dawn of molecular biology, in the late 1940s, is a commonplace; but the nature and components of that transformation are widely misunderstood. The change is often identified with the importation into biology of new styles of thought and new rigor by the many scientists trained in physics or chemistry who came into the nascent field--notably, Max Delbrück, Max Perutz, Francis Crick, John Kendrew, Maurice Wilkins, Rosalind Franklin. Most generally, the change is supposed to be the realization that genes are made not of protein but of nucleic acid--and this change was initiated, of course, by the work of Oswald Avery and his colleagues. These changes are not mutually exclusive, and both were surely important to the genesis of molecular biology. But logically prior to them, more fundamental, was another transformation in ruling preconceptions, one that has been neglected: the revolution in understanding of the chemical structures--the sequences of subunits--of proteins and of nucleic acids which was wrought by the work of Frederick Sanger and of Erwin Chargaff. This was a metamorphosis in the understanding of biochemical specificity, and while it astonished many biochemists it set free the small groups of those who were beginning to call themselves molecular biologists, enabling them to think of the relationship between genes and proteins in entirely new ways.


Regulation of glucocorticoid receptors in the kidney of immature and mature male rats.
1. Specific binding of [3H]dexamethasone to cytosol and the activation of bound hormone-receptor complexes were studied in the kidney of immature (3-week) and mature (26-week) Long-Evans male rats. 2. The concentration of specific binding sites was significantly higher (25%) in the kidney of immature rats as compared with mature, while dissociation constants (Kd) remain unaltered at both ages. 3. Heat activation (25 degrees C for 45 min) significantly enhanced the binding of [3H]dexamethasone-receptor complexes to DNA-cellulose and purified nuclei at both ages to the same extent. Cross-mixing experiments (i.e. binding of activated cytosol from mature rats to nuclei of immature and vice versa) gave similar results to the non-mixed groups. 4. Ca2+ activation (0 degree C for 45 min with 20 mM Ca2+) also enhanced the nuclear and DNA-cellulose binding at both ages but to a greater magnitude in immature rats. 5. Differences in the number of specific binding sites and some of the physicochemical properties of kidney glucocorticoid receptors presented here between immature and mature rats may underlie the functional changes in tissue response with age.


Genetic dissection of puberty in mice.
Determining the neural mechanisms controlling gonadotrophin-releasing hormone (GnRH) release is of pivotal importance in understanding central control of reproductive physiology in vertebrates. Targeted genetic manipulation of kisspeptin and GPR54 neurons has provided new insights into the mechanisms modulating GnRH release and thereby regulating hypothalamic-pituitary-gonadal axis activity during reproductive maturation. While conditional ablation of the oestrogen receptor α gene in kisspeptin neurons results in a dramatic advancement of the onset of puberty in female mice, subsequent pubertal maturation is arrested in these animals, as they fail to acquire normal ovulatory cyclicity. These data suggest that two oestrogen receptor α-dependent mechanisms, one a 'brake' and the other an 'accelerator', are sequentially operated in kisspeptin neurons during pubertal development of female mice to gate and then to activate GnRH release. In a different experimental approach, we removed entire kisspeptin neurons from the mouse brain and thus from the neural circuits controlling reproduction. Surprisingly, the onset of puberty in females was unaffected by kisspeptin neuron ablation. Furthermore, the animals attained regular ovulatory cyclicity and were fertile. Consistent with this, female mice lacking neurons that express the kisspeptin receptor GPR54 were also fertile, suggesting female reproductive maturation in the absence of kisspeptin/GPR54 signalling. However, acute kisspeptin neuron ablation in adult mice inhibited fertility, indicating that there is developmental compensation for the loss of kisspeptin neurons during reproductive neural circuit formation. Finally, we showed that kisspeptin neurons become an indispensable part of reproductive neural circuitry in the mouse brain before postnatal day 20.


Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: a type of hypoxic (energy deficient) brain damage.
The clinical signs and morphological brain lesions associated with histotoxic hypoxia induced by subcutaneous injection of 3-nitropropionic acid (NPA) in rats are described, and compared to hypoxic brain damage from other causes including ischemia and hypoglycemia. The brains were perfusion-fixed with paraformaldehyde/glutaraldehyde fixative, and examined by light and electron microscopy. Intoxicated rats developed severe neurological disease characterized by somnolence, uncoordinated gait with stereotypical paddling movements, and ventral or lateral recumbency. Recumbent rats had a selective, bilaterally symmetrical pattern of severe morphological injury in the caudate-putamen, hippocampus, and thalamus. Recumbency was a consistent indicator of the development of morphological brain lesions. In contrast to reports describing rat models of ischemia and hypoglycemia, morphological injury was not seen in the cerebral and cerebellar cortices of NPA-intoxicated rats. Ultrastructurally, neuronal alterations ranged from chromatin clumping with increased cytoplasmic lucency to severe cellular shrinkage or swelling with marked mitochondrial swelling (high amplitude swelling). White matter alterations included axonal swelling and adaxonal splitting of myelin lamellae. Vascular changes included perivascular deposits of proteinaceous material presumably from leakage of serum proteins, variable electron lucency of endothelial cell cytoplasm, an apparent increase in pinocytotic vesicles, rare platelet thrombosis of capillaries, and rare intravascular blebs of luminal plasma membrane. As a model of brain damage following energy deficiency, NPA intoxication has the advantages of producing morphological brain injury in a highly predictable anatomical pattern, and at a time paralleling the onset of clinical recumbency.


Efficient removal of levofloxacin by a magnetic NiFe-LDH/N-MWCNTs nanocomposite: Characterization, response surface methodology, and mechanism.
Antibiotic pollutants in water bodies, was studied to remove using an oxidized, nitrogen-doped, and Fe3O4 and NiFe-LDH decorated MWCNT (magnetic NiFe-LDH/N-MWCNTs) nanocomposite (NC). The novel, engineered NC was characterized by different techniques of SEM, XRD, TEM, EDX, and XPS and then examined under different main effective parameters of NC dose, levofloxacin (LVX) concentration, pH, time, and temprature. The experimentally obtained data then evaluated using the modeling approaches of RSM, GRNN, and ANFIS. The as prepared adsorbent showed an excellent adsorption performance (removal efficiency = 95.28% and adsorption capacity = 344.83-454.55 mg/g) under the respective values of the mentioned parameters of 0.152 g, 23.01 mg/L, 12.00 min, and 37.5 °C, respectively. The comparison of the models showed that although all of them accurately predicted the removal efficiency, ANFIS presented the best capability with R2, RMSE, MSE, MAE, as well as AAD of 0.9998, 0.0082, -0.0004, 0.0069, 0.1322, respectively. The adsorption by the NC followed Freundlich isotherm (R2 = 0.9993) and PSO kinetic (>0.998) models, confirming a heterogenous chemisorption process. The thermodynamic parameters showed an endothermic and spontaneous nature for LVX removal by magnetic NiFe-LDH/N-MWCNTs NC. A high-performance efficiency, appropriate reusability (five times without loss of efficiency), as well as easy separation due to magnetic properties, makes the NC to a promising option in removing LVX from water.


Pediatric chordoid glioma with chondroid metaplasia.
Chordoid gliomas are uncommon primary brain tumors that arise in the region of the third ventricle. Reports of this entity to date have been limited to adults. We present a case of a chordoid glioma arising in the hypothalamic/third ventricle region of a 12-year-old male who presented with visual symptoms. The neoplasm consisted of cords and clusters of well-differentiated, spindled-to-rounded cells containing abundant eosinophilic cytoplasm within a prominent mucinous matrix. Unlike other chordoid gliomas, this lesion contained islands and sheets showing cartilaginous differentiation intermixed with the glial component. A graded transition between neoplastic glial and chondroid regions was evident, and cells in both regions were strongly immunoreactive for GFAP and S-100. Cartilaginous metaplasia is infrequent in gliomas, but occurs most often in pediatric neoplasms of the midline such as this chordoid glioma. Thus, chondroid metaplasia represents an unusual histopathologic feature of chordoid glioma-in this case, presenting in a child.


Ethanolic extract of Dalbergia sissoo promotes rapid regeneration of cortical bone in drill-hole defect model of rat.
Leaves of Dalbergia sissoo is known to have protective actions against postmenopausal bone loss in rat. In this study, we have evaluated the fracture healing properties of ethanolic extract (EE) of Dalbergia sissoo leaves. To observe the fracture healing property in the drill-hole injury model, we randomly divided total 32 adult female Sprague Dawley rats (180±200g) into 4 groups: (i) Control operated group; (ii) EE (250mg/kg/day); (iii) EE (500mg/kg/day) and (iv) EE (1000mg/kg/day). The right femora were fractured at the mid-diaphysis region and each group of rats received their respective treatment for 15days. Ethanol extract dose dependently induced bone regeneration at the fracture site assessed by fluorochrome labeling. All of three doses, 250mg/kg/day dose significantly increased bone volume fraction, trabecular thickness, trabecular number, and connectivity density and decreased trabecular separation in bone. Furthermore, the extract induced the expression of osteogenic genes including BMP-2, BMP-4, RunX-2 and COL-1 compared to the control group. The EE improved fracture healing much earlier (day 15) than the normal healing process, as assessed by the increased callus volumes and mineralized nodule formation. This extract is found beneficial in fracture healing of rat.


[Value of electroretinography and early echography in severe eye injuries].
We tested Dawson-Trick-Litzlkow (DTL) fiber electrode as the active electrode in electroretinogram associated with an B echography in important ocular trauma. The advantages are its atraumatic characteristic and the good quality of the electroretinogram.


Lazarus sign and extensor posturing in a brain-dead patient. Case report.
A man was declared brain dead after having sustained a gunshot wound to the head. All clinical criteria for the diagnosis of brain death were met. The electroencephalogram was isoelectric, and four-vessel angiography demonstrated the absence of cerebral blood flow. However, stereotypic spontaneous movements were observed which persisted for several hours. The possible mechanism is discussed and a short review of the literature is given.


INSIGHT FLU005: An Anti-Influenza Virus Hyperimmune Intravenous Immunoglobulin Pilot Study.
Hemagglutination inhibition (HAI) antibody responses to anti-influenza virus hyperimmune intravenous immunoglobulin (hIVIG) were characterized. Thirty-one patients with influenza during the 2013-2014 season were randomly assigned to receive 0.25 g/kg of hIVIG (n = 16) or placebo (n = 15). For hIVIG recipients, the ratio of geometric mean titers (1 hour after infusion/before infusion) was 4.00 (95% confidence interval [CI], 2.61-6.13) for 2009 pandemic influenza A(H1N1) and 1.76 (95% CI, 1.33-2.32) for influenza A(H3N2) and influenza B. Among patients with 2009 pandemic influenza A(H1N1), ratios for hIVIG (n = 9) versus placebo (n = 8) were higher 1 hour after infusion (3.9 [95% CI, 2.3-6.7]) and sustained through day 3 (2.0 [95% CI, 1.0-4.0]). hIVIG administration significantly increases HAI titer levels among patients with influenza, supporting the need to perform a clinical outcomes study. NCT02008578.


Matching methods in precision oncology: An introduction and illustrative example.
Randomized controlled trials (RCTs) are uncommon in precision oncology. We provide an introduction and illustrative example of matching methods for evaluating precision oncology in the absence of RCTs. We focus on British Columbia's Personalized OncoGenomics (POG) program, which applies whole-genome and transcriptome analysis (WGTA) to inform advanced cancer care. Our cohort comprises 230 POG patients enrolled between 2014 and 2015 and matched POG-naive controls. We generated our matched cohort using 1:1 propensity score matching (PSM) and genetic matching prior to exploring survival differences. We find that genetic matching outperformed PSM when balancing covariates. In all cohorts, overall survival did not significantly differ across POG and POG-naive patients (p > 0.05). Stratification by WGTA-informed treatment indicated unmatched survival differences. Patients whose WGTA information led to treatment change were at a reduced hazard of death compared to POG-naive controls in all cohorts, with estimated hazard ratios ranging from 0.33 (95% CI: 0.13, 0.81) to 0.41 (95% CI: 0.17, 0.98). These results signal that clinical effectiveness of precision oncology approaches will depend on rates of genomics-informed treatment change. Our study will guide future evaluations of precision oncology and support reliable effect estimation when RCT data are unavailable.


Protocol of a multicenter, single-blind, randomised, parallel controlled feeding trial evaluating the effect of a Chinese Healthy Heart (CHH) diet in lowering blood pressure and other cardiovascular risk factors.
Unhealthy diet has been identified as the number one attributor of total mortality in China, accounting for more than 20% of total deaths. Although the Dietary Approach to Stop Hypertension (DASH) and Mediterranean diets have been proven beneficial in managing cardiovascular risk factors in Western countries, whether healthy diets with similar cardiovascular benefits can be developed that are consistent with Chinese food culture remains unknown. The Diet, ExerCIse and CarDiovascular hEalth (DECIDE)-Diet trial is a multicentre, single-blind, randomised controlled feeding trial to evaluate the effect of the Chinese Healthy Heart (CHH) diet, in comparison with the Chinese usual diet, in lowering cardiovascular risk factors among community residents with the increased cardiovascular risk. A total of 360 adults aged between 25 and 75 years old and with systolic blood pressure between 130 and 159 mm Hg will be recruited from four centres located in four areas representing four major Chinese cuisines: Beijing, Shanghai, Guangzhou and Chengdu. After 1 week of run-in period with local usual diet, the compliant participants will be randomised to the intervention group with the CHH diet or the control group with the usual local diet, on a 1:1 ratio, for 4 weeks. Body weight of study participants will be maintained during the entire study period. The primary outcome is the change in SBP from the baseline to the end of the study. DECIDE-Diet trial will be the first randomised controlled feeding trial to evaluate the effect of a CHH diet in lowering cardiovascular risk factors. This trial will provide compelling evidence on the CHH diet in effect of improving cardiovascular health among Chinese food consumers all around the world. This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Peking University Institutional Review Board (approval number: IRB00001052-18094). The results will be disseminated through academic conferences and publications in international peer-reviewed journals. ClinicalTrials.gov Registry (NCT03882645); Pre-results.


Thioredoxin-interacting protein regulates insulin transcription through microRNA-204.
Beta-cell dysfunction and impaired insulin production are hallmarks of diabetes, but despite the growing diabetes epidemic, the molecular mechanisms underlying this disease have remained unclear. We identified thioredoxin-interacting protein (TXNIP), a cellular redox regulator, as a crucial factor in beta-cell biology and show that beta-cell TXNIP is upregulated in diabetes, whereas TXNIP deficiency protects against diabetes by preventing beta-cell apoptosis. Here we show that TXNIP and diabetes induce beta-cell expression of a specific microRNA, miR-204, which in turn blocks insulin production by directly targeting and downregulating MAFA, a known insulin transcription factor. In particular, we first discovered the regulation of miR-204 by TXNIP by microarray analysis, followed by validation studies in INS-1 beta cells, islets of Txnip-deficient mice, diabetic mouse models and primary human islets. We then further found that TXNIP induces miR-204 by inhibiting the activity of signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in miR-204 regulation. We also identified MAFA as a target that is downregulated by miR-204. Taken together, our results demonstrate that TXNIP controls microRNA expression and insulin production and that miR-204 is involved in beta-cell function. The newly identified TXNIP-miR-204-MAFA-insulin pathway may contribute to diabetes progression and provides new insight into TXNIP function and microRNA biology in health and disease.