Food group contributions to nutrient intake in whites, blacks, and Mexican Americans in Texas.
The existence of three different ethnic groups, living within a defined geographic area in Texas and maintaining fairly distinct life-styles, provided an excellent opportunity to compare their dietary behaviors. Information about food consumption was obtained by 24-hour dietary recall from a group of 431 whites, blacks, and Mexican Americans residing in two counties in southeast Texas. Food group and subgroup contributions to 11 nutrients were calculated. The intake patterns of Mexican Americans demonstrated both an adherence to traditional or familiar Mexican food items, such as beans and tortillas, and a preference for foods not previously reported to be commonly consumed by that ethnic group, specifically beef. The current study provides a base of information necessary to implement dietary changes acceptable within the context of a particular culture's world view. Results revealed differences in food intake patterns that would be helpful in designing practical nutrition education programs specifically targeted toward these ethnic groups. For example, inadequate sources of nutrients were identified, as were sources of excess fat.


Angiotensin protects cortical neurons from hypoxic-induced apoptosis via the angiotensin type 2 receptor.
The effects of angiotensin on mouse cortical neuronal cultures exposed to chemical-induced hypoxia was investigated. Cultures exposed to 10 mM sodium azide for 5 min showed a 17% increase in apoptosis when assayed 24 h postinsult. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocked sodium azide-induced cell death suggesting that the NMDA receptor contributes to the mediated cell death. Pretreatment of cultured neurons with angiotensin decreased sodium azide-induced apoptosis by 94%. When the AT(1) receptor was blocked by its receptor antagonist, losartan, angiotensin activation of the AT(2) receptor completely inhibited sodium azide-induced apoptosis. Pretreatment of neurons with the AT(2) receptor antagonist PD123319 resulted in angiotensin reducing sodium azide-induced apoptosis by 48%. These results demonstrate that angiotensin can significantly attenuate sodium azide-induced apoptosis primarily through activation of the AT(2) receptor and suggests that angiotensin may have a protective role in neurons undergoing ischemic injury.


Understanding the underlying metabolic abnormalities of polycystic ovary syndrome and their implications.
Women with polycystic ovary syndrome have an increased rate of obesity, with a propensity toward abdominal deposition of body fat. Independent of obesity, at least half of affected women have insulin resistance. To understand the mechanisms of insulin resistance in polycystic ovary syndrome, it is necessary to understand normal insulin signaling. Women with polycystic ovary syndrome have normal binding of insulin to its receptor but have decreased activation of events downstream of the receptor. This insulin resistance occurs mostly in the peripheral tissues (muscle and fat cells), and results in increased pancreatic insulin secretion to maintain normal glucose levels. Obese women with polycystic ovary syndrome have a relative defect in insulin secretion. At least 20% of obese patients with polycystic ovary syndrome have glucose intolerance or diabetes, versus about 5% of the healthy age-matched population. Obesity and insulin resistance probably increase the risk of cardiovascular disease in women with polycystic ovary syndrome. The metabolic features of polycystic ovary syndrome are important health risk factors and need to be considered seriously, even if the patient seeks treatment for other concerns.


Facility-Level Variation in Use of Locoregional Therapy for Metastatic Prostate Cancer.
We sought to understand patient- and institution-level factors associated with use of locoregional therapy for newly diagnosed metastatic prostate cancer in the era before the availability of evidence supporting its efficacy. We queried the National Cancer Database to identify patients diagnosed with metastatic prostate adenocarcinoma (stage M1) between 2004 and 2017. We assessed patient factors associated with definitive local therapy with radiotherapy or radical prostatectomy using multilevel logistic regression accounting for clustering within institutions. We further characterized trends in facility-level use and examined institutional factors associated with utilization. We identified 35,933 patients with M1 prostate cancer at 1,188 facilities. A total of 4,146 patients (11.5%) received local therapy for M1 disease (radiation therapy in 3,378 and radical prostatectomy in 768). Use of local treatment was concentrated among a smaller number of facilities: 50% of all local therapy was delivered at 161 facilities (14% of total). At the patient level, uninsured status (OR 0.62, 95% CI 0.49-0.79, p <0.01) and high comorbidity (Charlson-Deyo score, OR 0.39, 95% CI 0.26-0.6, p <0.01) were associated with lower odds of local therapy. High-utilizing facilities (top quartile) were more commonly community centers (OR 1.76, 95% CI 10.7-2.95, p <0.01) and differed by geographic region (South Atlantic vs West South Central region: OR 0.48, 95% CI 0.25-0.88, p=0.02). In the period before locoregional therapy was supported by clinical practice guidelines, locoregional therapy use varied significantly at the facility level and was driven by a smaller number of high-utilizing facilities. These findings can contextualize expected increase in the use of local therapy for metastatic prostate cancer.


The effect of phenylglyoxal on the translocation of pyruvate in rat-heart mitochondria.
The effect of phenylglyoxal, an arginine-specific reagent, on the translocation of pyruvate and on the binding of alpha-cyanocinnamate by rat-heart mitochondria has been studied. It has been found that both the uptake and the oxidation of pyruvate by mitochondria are inhibited by phenylglyoxal. The inhibitory potency increases with the increasing of the pH of the medium. Phenylglyoxal does not affect the transmembrane delta pH. Phenylglyoxal also inhibits the binding of alpha-cyanocinnamate to mitochondria. Substrates of the carrier, such as pyruvate itself and monochloroacetate, partially prevent the inhibition of alpha-cyanocinnamate binding by phenylglyoxal, whilst acetate has no effect in this respect. Phenylglyoxal affects only the affinity of the alpha-cyanocinnamate binding site(s), without changing their total number. The results obtained indicate that arginine residues are involved in the mechanism of pyruvate translocation and of alpha-cyanocinnamate binding in rat-heart mitochondria.


Tuberculous meningitis and HIV.
To identify factors associated with HIV-infected status in children admitted with tuberculous meningitis (TBM), and to find out whether HIV co-infection affects in-hospital outcome. This prospective hospital-based study was conducted from May 2000 to August 2003. All consecutive children, aged 1 month to 12 years of age, admitted with a diagnosis of TBM were enrolled. Relationship between 35 features viz., two demographic factors, nine clinical features, 13 neurological features, five laboratory (including cerebrospinal fluid) parameters, six radiological (including computed tomography scan brain) features, and the two outcomes (disabled survivor or death); with HIV-infected status was assessed. Of a total 123 TBM cases enrolled, eight (6.5%) were HIV-infected. There was no significant difference between the two groups, except that more children in the HIV-infected group had Hb < 8 gm/dl: both on bivariate analysis, (OR, 12.0; 95% CI, 2.6-55.9; P = 0.001) and on multivariate analysis (OR, 12.30; 95% CI, 1.9-79.6; P = 0.008). Outcome was similar in both the groups. Only presence of Hb < 8 gm/dl was associated with HIV-infected status. HIV co-infection did not affect the outcome.


Rebooting a sports pharmacy advanced pharmacy practice experience: Utilizing medicinal chemistry as a foundational approach to get pharmacists back in the game.
To implement a sports pharmacy advanced pharmacy practice experience (SP-APPE) utilizing medicinal chemistry as a foundational approach. A student-pharmacist and medicinal chemistry faculty member collaborated to reboot a SP-APPE. Approached from a medicinal chemistry perspective and tailored to the infrastructure of the university, three fourth-year student-pharmacists piloted the SP-APPE (fall 2017 to fall 2018). Various performance enhancing drugs (PEDs) and supplements were investigated. Student-pharmacists evaluated general knowledge of PEDs along with the perceived value of pharmacists in sports among student-athletes, athletic personnel, and pre-APPE students. By demonstrating how legitimate medications were chemically similar to substances banned by sports governing agencies, comparing chemical structures/pharmacophores of PEDs to those of various prescription drugs, and comprehending athletes' misuse of PEDs, student-pharmacists educated student-athletes and athletic personnel on pertinent topics spanning pharmacy and sports (e.g., marijuana, medication sharing, deciphering supplement labels). Laboratory analytical methods that detect PEDs and educational points regarding potential adverse health risks posed by PED usage were also reviewed. Survey participants (approximately 75%, n = 134) perceived pharmacists as valuable to student-athletes and athletic personnel. Student-pharmacists indicated that medicinal chemistry knowledge was strengthened by completing the APPE and relevant to their pharmacy careers. Based on medicinal chemistry principles, the SP-APPE provided a venue for student-pharmacists to interact with athletics, assist with drug information education, and identify drugs or supplements as chemically related to those banned by sports governing agencies. Confident in medicinal chemistry concepts, student-pharmacists translated their expertise to benefit the patient/student-athlete.


iTRAQ-Based Proteomics Suggests Ephb6 as a Potential Regulator of the ERK Pathway in the Prefrontal Cortex of Chronic Social Defeat Stress Model Mice.
Major depressive disorder (MDD) is a worldwide concern and devastating psychiatric disease. The World Health Organization claims that MDD leads to at least 11.9% of the global burden of disease. However, the underlying pathophysiology mechanisms of MDD remain largely unknown. Herein, we proteomic-based strategy is used to compare the prefrontal cortex (PFC) in chronic social defeat stress (CSDS) model mice with a control group. Based on pooled samples, differential proteins are identified in the PFC proteome using iTRAQ coupled with LC-MS/MS. Ingenuity Pathway Analysis (IPA) is then followed to predict relevant pathways, with the ephrin receptor signaling pathway selected for further research. Additionally, as the selected key proteins of the ephrin receptor signaling pathway, ephrin type-B receptor 6 (EphB6) and the ERK pathway are validated by Western blotting. Altogether, increased understanding of the ephrin receptor signaling pathway in MDD is provided, which implicates further investigation of PFC dysfunction induced by CSDS treatment.


Determinants of long-term health-related quality of life in adult patients with mild traumatic brain injury.
Mild traumatic brain injury (mTBI) usually leads to the appearance of post-concussion symptoms (PCS) which may resolve after a short time. In this study, the mental and physical aspects of quality of life (QoL) were evaluated 6 months after mTBI, and the association of demographic and injury-related factors, post-injury primary executive function and PCS types with the long-term QoL status was investigated. 123 eligible mTBI patients of initial sampling participated in follow-up phase of this longitudinal study. The demographic, clinical, and para-clinical data of patients were recorded. Paraclinical data comprised brain lesion volume, type and location determined by CT scan. The executive function and primary PCS were examined during the discharge using the verbal fluency task and a checklist, respectively. QoL was measured via SF-36 questionnaire. The collected data were entered into SPSS 22, and analyzed using appropriate statistical tests. Youngers aged between 18 and 35 years and women had a lower QoL score than others. Primary somatic and cognitive PCS together were associated with poor QoL. There was no significant difference in QoL and executive function scores between the normal and abnormal brain CT groups. However, among people with abnormal CT, those having multifocal lesions including at least an intracranial hemorrhage type such as intra parenchymal hemorrhage or extra-axial bleeding together with other intracranial lesions or skull fracture demonstrated less QoL score in SF-36. A significant correlation was discovered between the scores of the executive function and QoL in mental dimensions of SF-36. This study emphasizes on the clinical significance of early executive function and PCS examination in mTBI population, as well as optimal management of the victims regardless of the initial brain CT findings, especially in high-risk populations.


Patient safety and quality improvement in rehabilitation medicine.
Patient safety in medical settings has become a major concern. As more and more individuals seek rehabilitative care for their medical conditions or are referred to rehabilitation specialists with increasingly complex medical conditions, the issue of patient safety in the rehabilitation setting takes on added importance. This article introduces the concepts of patient safety, cognitive biases, systems thinking, and quality improvement as they apply to the rehabilitation medicine.


Quercetin relieves chronic lead exposure-induced impairment of synaptic plasticity in rat dentate gyrus in vivo.
Increasing evidence suggests that lead (Pb) produces impairments partly through oxidative stress. Though many researchers have investigated protective effect of some antioxidant nutrients against Pb toxicity, little information is available about the effect of antioxidants on Pb-induced impairment of synaptic plasticity. Quercetin, a strong antioxidant and radical scavenger, is the representative natural flavonoid molecule abundant in fruits and vegetables. Previous studies have found that quercetin was neuroprotective in many cases. This study was designed to evaluate the effect of quercetin on chronic Pb exposure-induced impairment of synaptic plasticity in adult rat dentate gyrus (DG) area in vivo. The input/output (I/O) functions, paired-pulse reactions (PPR), excitatory postsynaptic potential (EPSP), and population spike (PS) amplitude were measured in the DG area of different groups of rats in response to stimulation applied to the lateral perforant path. The results showed that the depressed I/O, PPR, and long-term potentiation (LTP) of Pb-exposed group were significantly increased by quercetin treatment. In addition, hippocampal Pb concentration was partially reduced after quercetin treatment. These findings suggest that quercetin treatment could relieve chronic Pb exposure-induced impairment of synaptic plasticity and might be a potential therapeutic intervention to cure cognitive deficits induced by Pb.


Assay of interferon-mediated protein kinase activity from plasma and tissue extracts.
Interferon-treated mouse and human cells show enhanced levels of a protein kinase activity which is manifested by the phosphorylation of endogenous 67,000 and 72,000 Mr proteins, respectively. Enhanced levels of such kinase activity are also detectable in the plasma of patients treated with interferon and in the plasma and tissues of interferon-treated mice. A rapid and efficient method of assay for these protein kinase activities is described. The samples are first incubated with heparin (100 units/ml), which results in the inhibition of different protein kinase activities, but not the one mediated by interferon. The latter one is then assayed after partial purification on poly(rI):(rC)-Sepharose or poly(rG)-Sepharose. The protein kinase from human and mouse cells in culture and from the different tissues of mice binds specifically to poly(rI):(rC)-Sepharose. On the other hand, the protein kinase activity from both mouse and human plasma shows a higher affinity toward poly(rG)-Sepharose. These methods are successfully applied for the determination of the interferon-mediated protein kinase activity from tissue extracts and plasma.


Ubiquitin-dependent regulation of COPII coat size and function.
Packaging of proteins from the endoplasmic reticulum into COPII vesicles is essential for secretion. In cells, most COPII vesicles are approximately 60-80 nm in diameter, yet some must increase their size to accommodate 300-400 nm procollagen fibres or chylomicrons. Impaired COPII function results in collagen deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII coats have remained elusive. Here, we identified the ubiquitin ligase CUL3-KLHL12 as a regulator of COPII coat formation. CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats. As a result, ubiquitylation by CUL3-KLHL12 is essential for collagen export, yet less important for the transport of small cargo. We conclude that monoubiquitylation controls the size and function of a vesicle coat.


Explaining the increased arrest rate among mental patients: the changing clientele of state hospitals.
The arrest rates of nearly 2,000 psychiatric patients released from psychiatric centers in 1968 and those of nearly 2,000 patients released in 1975 were compared with the arrest rates of a group of 5,000 patients studied 25 years earlier. In general, arrest rates among the two recent samples were considerably higher than general population rates, primarily because of the large proportion of patients previously arrested. Other characteristics related to subsequent arrest were age and admitting diagnosis. One additional finding was that the number of patients with prior arrests had increased markedly over the years.


Efficacy of clinically relevant temozolomide dosing schemes in glioblastoma cancer stem cell lines.
The effectiveness of temozolomide (TMZ) dosing schemes and the "rechallenge" of recurrent glioblastoma (GBM) with TMZ are controversial. We therefore compared the efficacy of different TMZ dosing schemes against GBM cancer stem cell (CSC) lines in vitro. In O(6)-methyl-guanidine-methyl-transferase (MGMT)-negative CSC lines, all schedules (1 day on/27 days off, 5 days on/23 days off, 7 days on/7 days off, 21 days on/7 days off, continuous low-dose TMZ) depleted clonogenic cells. In TMZ-resistant CSC lines, the 7 days on/7 days off scheme showed higher toxicity as compared with the other schemes. However, clinically feasible concentrations remained ineffective in highly resistant CSC lines. In addition, none of the schedules induced long-term depletion of clonogenic cells even at the highest concentrations (up to 250 μM). After sublethal TMZ treatment for 5 days, TMZ rechallenge of recovering CSC lines remained effective. Our data advocate CSC lines as in vitro model to address clinical questions. Using this model, our data suggest the effectiveness of TMZ in MGMT-negative CSC lines and support the concept of TMZ rechallenge. The 7 days on/7 days off scheme consistently showed the best activity of all schedules in TMZ-resistant CSC lines.


Dental functional status with and without tooth replacement in a Chinese adult population.
The objective of this study is to investigate the prevalence of missing teeth and prosthodontic replacements in a Chinese adult population using a hierarchical dental functional classification system. A total of 1,462 dentate subjects over 40 years from Shandong Province, China were included and categorized in the functional classification system with and without tooth replacements. Depending on replacements, subjects could be reclassified (promoted) to categories reflecting higher functionality. "Promotions" were considered indicators for prosthodontic effectiveness. Homogeneities after dichotomization into functional categories appeared to be moderate to good. In the "≥10 teeth in each jaw" branch, mean number of teeth and posterior occluding pairs were 27.93 ± 2.74 and 7.10 ± 1.94, respectively. In the branch "<10 teeth in each jaw," these figures were 16.17 ± 5.54 and 1.49 ± 1.45. Fixed dental prostheses (FDPs) added on average 3.5 artificial teeth; 46% of subjects with FDP promoted to a higher functional level. For removable dental prostheses (RDPs), these numbers were 8.5% and 79%, respectively. Promotion value per tooth added was significantly higher for FDPs. The classification system was able to quantify the effectiveness of teeth replacements. It was shown that RDPs were more effective when higher numbers of teeth were replaced, while FDPs were more effective per artificial tooth added.


Estimating the risk of mortality attributable to recent late HIV diagnosis following admission to the intensive care unit: A single-centre observational cohort study.
Despite improvements in survival of people with HIV admitted to the intensive care unit (ICU), late diagnosis continues to contribute to in-ICU mortality. We quantify the population attributable fraction (PAF) of in-ICU mortality for recent late diagnosis among people with HIV admitted to a London ICU. Index ICU admissions among people with HIV were considered from 2000 to 2019. Recent late diagnosis was a CD4 T-cell count < 350 cells/μL and/or AIDS-defining illness at/within 6 months prior to ICU admission. Univariate comparisons were conducted using Wilcoxon rank-sum/Cochran-Armitage/χ2 /Fisher's exact tests. We used Poisson regression (robust standard errors) to estimate unadjusted/adjusted (age, sex, calendar year of ICU admission) risk ratios (RRs) and regression standardization to estimate the PAF. In all, 207 index admissions were included [median (interquartile range) age: 46 (38-53) years; 72% male]; 58 (28%) had a recent late diagnosis, all of whom had a CD4 count < 350 cells/μL, and 95% had advanced HIV (CD4 count < 200 cells/μL and/or AIDS at admission) as compared with 57% of those who did not have a recent late diagnosis (p < 0.001). In-ICU mortality was 27% (55/207); 38% versus 22% in those who did and did not have a recent late diagnosis, respectively (p = 0.02). Recent late diagnosis was independently associated with increased in-ICU mortality risk (adjusted RR = 1.75) (95% confidence interval: 1.05-2.91), with 17.08% (16.04-18.12%) of deaths being attributable to this. There is a need for improved public health efforts focused on HIV testing and reporting of late diagnosis to better understand potentially missed opportunities for earlier HIV diagnosis in healthcare services.


Incidence of aflatoxin, zearalenone, and deoxynivalenol on corn in Argentina.
The study of the incidence of aflatoxins, zearalenone, and deoxynivalenol was the aim of this work. This investigation was carried out upon recently harvested corn samples collected in the Departamento of Rio Cuarto, Province of Córdoba, Argentina. 150 samples of corn were analized to investigate aflatoxins B1, G1, and zearalenone contamination. Out of these 150 samples 58 were selected and deoxynivalenol was examined.The incidence value for aflatoxin B1 was of 3.3% (5 samples), aflatoxin G1 1.3 % (2 samples), and zearalenone 6 % (9 samples).The analysis of the 58 samples showed that 24% of them were contaminated with deoxynivalenol.


[Effect of the duration of the previous ischemia and of the mass of ischemic tissue on the state of the coagulating and anticoagulating blood systems in tourniquet shock].
In the experiments on 80 rabbits it was shown that the inclusion of the previously ischemized extremities into circulation is accompanied by elevation of coagulating potential of the blood and inhibition of fibrinolysis shortly after the tourniquet removal followed by hypocoagulation and fibrinolysis activation. These changes depend on the duration and mass of previously ischemized tissues. It is suggested that in tourniquet shock these disorders lead either to the danger of intravascular thrombosis or to hypocoagulation with secondary fibrinolysis.


Late gadolinium enhancement of the right ventricular myocardium: is it really different from the left ?
It has been suggested that, in late gadolinium enhancement, the signal of right ventricular myocardium is nulled at a shorter inversion time than the left. While we initially made the same observation, we believe that the difference is not real, but results from artifacts. We present 7 cases as well as computer simulations to describe the nature of these artifacts and explain how they can create the impression of different inversion times for the right and left ventricle. At inversion times that are shorter than ideal for the myocardium a black rim can be seen at the border of the myocardium with blood on the inside and with fat on the outside. This is most likely a partial volume effect. The thin myocardium of the right ventricle is sandwiched between these black rims and, at a low spatial resolution, is no longer visible. In this case, the adjacent black rims may then be misinterpreted as myocardium. While black rims also occur on the left side, the myocardium is thicker and remains discernable as a separate layer. As a consequence, the optimal inversion time for the right ventricle only appears different from that for the left. In fact, in the presence of hypertrophy of the right ventricle or during systolic wall thickening we did not find a difference in inversion times between the left and right ventricle. We conclude that sufficient spatial resolution is important for adequate late gadolinium enhancement of the right ventricle.


Synthetic approaches to the 2010 new drugs.
New drugs are introduced to the market every year and each represents a privileged structure for its biological target. These new chemical entities (NCEs) provide insights into molecular recognition and also serve as leads for designing future new drugs. This review covers the synthesis of 15 NCEs that were launched anywhere in the world in 2010.


Exploring the Potential of Chat GPT in Personalized Obesity Treatment.
Obesity has become a serious global health problem. For some patients who cannot be treated with traditional methods, artificial intelligence technologies are a new source of hope. Chat GPT is a language model that has become popular in recent times and has many applications in natural language processing. This article focuses on the potential use of Chat GPT in obesity treatment. Chat GPT can provide personalized recommendations on topics, such as nutrition plans, exercise programs, and psychological support. In this way, a personalized treatment plan can be created based on the individual needs of patients and a more effective approach to obesity treatment can be achieved. However, some ethical and security concerns should also be considered regarding the use of this technology. In conclusion, the potential of Chat GPT in obesity treatment is promising, and with the effective use of this technology, better results can be achieved in obesity treatment.


MDR-like ABC transporter AtPGP4 is involved in auxin-mediated lateral root and root hair development.
Previous data have suggested an involvement of MDR/PGP-like ABC transporters in transport of the plant hormone auxin and, recently, AtPGP1 has been demonstrated to catalyze the primary active export of auxin. Here we show that related isoform AtPGP4 is expressed predominantly during early root development. AtPGP4 loss-of-function plants reveal enhanced lateral root initiation and root hair lengths both known to be under the control of auxin. Further, atpgp4 plants show altered sensitivities toward auxin and the auxin transport inhibitor, NPA. Finally, mutant roots reveal elevated free auxin levels and reduced auxin transport capacities. These results together with yeast growth assays suggest a direct involvement of AtPGP4 in auxin transport processes controlling lateral root and root hair development.


Maternal reproductive history and premenopausal risk of hypertension and cardiovascular disease: a Danish cohort study.
The metabolic changes of pregnancy resemble a cardiovascular risk profile and may persist postpartum, with body mass index (BMI) as a potential modifier. We examined the association between the number of live-birth pregnancies and maternal premenopausal risks of hypertension and cardiovascular disease (CVD), accounting for pre-pregnancy BMI as well as abortions and stillbirths. A prospective cohort study. Mothers from the Danish National Birth Cohort (1996 to 2002). For each of these women, registry data on all pregnancies from 1973 to 2011 were obtained, as were self-reported pre-pregnancy weight and height. A total of 44 552 first-time mothers in the Danish National Birth Cohort. Risks of hypertension and CVD during and between live-birth pregnancies separately and combined as live-birth cycles. After adjustment for abortions, stillbirths, pre-pregnancy BMI and other covariates, a higher risk of hypertension was observed in the first (HR 1.53, 95% CI: 1.37 to 1.72) and fourth and subsequent live-birth cycles (HR 1.72, 95% CI: 1.15 to 2.58), compared with the second. However, as number of live-birth pregnancies increased, risk of hypertension decreased during live-birth pregnancies and increased between live-birth pregnancies (tests for trend, p<0.01). For CVD, we found an overall J-shaped but non-significant association with number of live-birth pregnancies. No interaction with pre-pregnancy BMI (<25 versus ≥25 kg/m2) was observed. Premenopausal women had the highest risk of hypertension and CVD during their first live-birth pregnancy and after their fourth live-birth pregnancy. All risks were independent of BMI before the first live-birth pregnancy and of number of abortions and stillbirths.


Postcentral Gyrus High-Grade Glioma: Maximal Safe Anatomic Resection Guided by Augmented Reality with Fiber Tractography and Fluorescein.
Intraaxial tumors of the central lobe are challenging lesions to deal with because of the high eloquence of this anatomic area.1,2 Diffusion tensor imaging magnetic resonance imaging and fluorescein (F) have proven to be useful in the planning and execution, respectively of glioma surgery.3-9 Nevertheless, the advantages of intraoperative use of augmented reality (AR) with diffusion tensor imaging-based high-definition fiber tractography (HDFT) are still underestimated. In the AR HDFT-F technique reported by our group, the integration of AR into the microscope comes through the BrainLAB Curve navigation platform (BrainLAB AG, Munich Germany), Smartbrush software (BrainLAB AG), KINEVO 900 surgical microscope (Carl Zeiss, Oberkochen, Germany), and YELLOW 560 filter (Carl Zeiss).9 The microscope establishes a wired autodetection of the navigation platform, and the eyepiece functions as a "see-through display" of the AR images, which are overlapped onto the surgical field. Video 1 shows the technical key aspects of the intraoperative use of the AR HDFT-F technique in the maximal safe anatomic resection of a postcentral gyrus high-grade glioma.


Measurement of Antibody-Mediated Reduction of Plasmodium yoelii Liver Burden by Bioluminescent Imaging.
Antibodies against the infectious sporozoite stage of malaria have been shown to be effective in preventing infection of the liver and in mitigating the ensuing blood stage. However, only a handful of antibody targets have been vetted and shown to be successful in mediating in vivo protection. Even more limited are the means with which to measure how effectively antibodies can reduce the number of parasites establishing infection in the liver. Traditionally, only qPCR of infected mouse livers could accurately measure liver parasite burden. However, this procedure requires sacrifice of the animal and precludes monitoring of the ensuing blood stage infection. Herein we describe a method of accurately assessing antibody-mediated reduction of parasite liver burden by combining passive or active immunization of mice and mosquito bite challenge with luciferase-expressing transgenic P. yoelii parasites. This method is rapid, reliable and allows for observation of blood stage disease in the same animal. This model will prove integral in screening the efficacy of novel antibody targets as the search for a more effective malaria vaccine continues.


Optimal Temperature for Radiofrequency Ablation of Lumbar Medial Branches for Treatment of Facet-Mediated Back Pain.
Radiofrequency ablation (RFA) of the medial branch nerves that innervate the facet joints is a well-established treatment modality; however, studies to determine the optimal radiofrequency ablation temperature are lacking. A wide range (70 to 90°C) has been used. This study aimed to compare outcomes with two set temperatures for the lumbar facet medial branch ablation, 90 and 80°C. This retrospective study compared the degree of patient self-reported functional improvement relief, postoperative opioid dose changes, as well as duration among lumbar facet medial branch (RFA) patients who had the procedures performed at 80 or 90°C. Patients who underwent the procedure at 90°C had 3.1 (95% CI 1.7, 6.5) times the odds (P = 0.0004) of reporting functional improvement of at least 50% when compared to those who underwent neurotomy at 80°C. For self-reported functional improvement greater or equal to 75%, the results were sustained with an odds ratio of 2.8 (95% CI 1.2, 5.7) favoring those with 90°C temperature neurotomy (P = 0.002). There seems to be significant functional improvement associated with temp of 90°C compared to 80°C, with no added risk of complications. Randomized controlled studies are warranted.


Quantification of soluble E-receptor in the serum of patients with various diseases and its accompanying in vitro immunosuppression in neoplasia.
Evidence in the literature indicates that soluble E-receptor in the serum may modulate T-dependent immune response. We have developed a solid-phase radioimmunoassay to measure the soluble form of E-receptor from various sources. The assay detects solubilized antigens derived from E-receptor-bearing T lymphocytes and not with non-E-receptor-bearing B lymphocytes. The sensitivity limit of the assay is 0.1 ng/ml of purified E-receptor antigen. Using this assay, one can show that the T-cell mitogen phytohaemagglutinin stimulated both lymphocytes and cells of the resting human T-cell lymphoma cell line Jurkat to shed or secrete E-receptor into the culture medium. Results of the radioimmunoassay performed on human sera indicated that some patients with Hodgkin's disease, melanoma, sarcoma, or acute or chronic lymphocytic leukaemia had elevated levels of this antigen in their serum, whereas normal human sera registered lower levels. Elevated levels of the soluble form of E-receptor in the serum were suggestive of an in vitro assessment of their immunosuppressive activity. These results indicate that activation of T-cell immunity in vivo may result in humoral immunosuppression.


Neutrophil-derived azurocidin alarms the immune system.
Azurocidin (heparin-binding protein/cationic antimicrobial protein of 37 kD) is a protein that is mobilized rapidly from emigrating polymorphonuclear leukocytes (PMN). Initially, this inactive serine protease was recognized for its antimicrobial effects. However, it soon became apparent that azurocidin may act to alarm the immune system in different ways and thus serve as an important mediator during the initiation of the immune response. Azurocidin, released from PMN secretory vesicles or primary granules, acts as a chemoattractant and activator of monocyte and macrophages. The functional consequence is enhancement of cytokine release and bacterial phagocytosis, allowing for a more efficient bacterial clearance. Leukocyte activation by azurocidin is mediated via beta(2)-integrins, and azurocidin-induced chemotaxis is dependent on formyl-peptide receptors. In addition, azurocidin activates endothelial cells leading to vascular leakage and edema formation. For these reasons, targeting azurocidin release and its actions may have therapeutic potential in inflammatory disease conditions.


Anti-Sm: its predictive value in systemic lupus erythematosus.
The clinical manifestations of 131 rheumatic disease patients with anti-Sm antibody were studied. A variety of standard tests was utilized in the study, namely, the FANA test with mouse kidney as substrate for the assay of ANA, the Crithidia test for anti-double stranded DNA (anti-dsDNA) and double immunodiffusion for detecting antibodies to extractable nuclear antigens. The patients were grouped according to the presence of anti-Sm alone, or anti-Sm with some other antibodies. There were 17 with anti-Sm alone; 55 with anti-Sm+anti-RNP; 15 with anti-Sm+anti-dsDNA; and 44 with anti-Sm+anti-RNP. The result of our study showed that although anti-Sm could be found in other diseases, it was exclusively detected in SLE only if anti-dsDNA was also present. Further, the SLE patients with anti-Sm alone had more frequent central nervous system manifestations than other groups of patients. The renal manifestation was observed more frequently in the group of SLE patients with anti-Sm+anti-dsDNA (92.9%). Among other major manifestations, haematologic involvement had a tendency to be less common in the group of patients with anti-Sm alone. The study concludes that the presence of anti-Sm antibody may be of some value to predict the clinical outcome.


Resident Involvement in Hip Arthroscopy Procedures Does Not Affect Short-Term Surgical Outcomes.
To evaluate whether the presence of residents in hip arthroscopy (HA) procedures affects short-term surgical outcomes. The American College of Surgeons National Surgical Quality Improvement Program Database was used to identify patients who underwent HA from 2006 to 2012. Demographic and 30-day outcome variables were compared between cohorts of patients with and without residents. Multivariate logistic regression was used to identify whether resident involvement was an independent risk factor for adverse outcomes. Propensity score matching was performed to control for all demographic and intraoperative variables. A total of 869 patients (59.7% female) were included in this study, 626 of which reported data on resident involvement. Patients were mostly White (73.4% of cases without a resident, 51.8% with a resident, P < .05). Those with residents were younger (P = .016), had lower modified 5-item frailty index (mFI-5) scores (P = .028), and had fewer cardiac comorbidities (P = .008). There was no difference in diabetic status, dyspnea symptoms, history of chronic obstructive pulmonary disease, renal comorbidity, neurologic comorbidity, cumulative comorbidities, history of bleeding disorders, inpatient vs. outpatient treatment, preoperative functional status, smoking history, and steroid use for chronic conditions. There was no difference in all complications, operative time, length of stay, reoperation, readmission, wound complication, venous thromboembolism, blood transfusions, or sepsis. Propensity score match for demographic and intraoperative differences found no association between resident involvement and increased complications. Resident involvement was not an independent risk factor for all complications studied. Resident involvement in HA procedures was not a risk factor for 30-day complications between 2006 and 2012. Resident involvement did not increase the risk of adverse outcomes, readmission, reoperation, or length of stay, nor did it significantly increase operative times.


Superficial siderosis of the central nervous system.
There have been 87 cases of superficial siderosis of the CNS reported in the world literature and 63 cases had developed the clinical syndrome with sufficient details to be reviewed. It is a distinct clinical syndrome characterized by sensorineural deafness (95%), cerebellar ataxia (88%) and pyramidal signs (76%). Other features include dementia (24%), bladder disturbance (24%), anosmia (at least 17%), aniscoria (at least 10%) and sensory signs (13%). Less frequent features are extra-ocular motor palsies, neck or backache, bilateral sciatica and lower motor neuron signs (5-10% each). Males are more often affected than females (3:1). The age of onset ranged from 14 to 77 years, age at death from 29 to 78 years and duration until death from 1 to 38 years excluding premature death due to the underlying cause or as a result of surgery. Up to 27% become bed bound at 1-37 years from the first symptom due to either cerebellar ataxia, a myelopathic syndrome or both. Symptomatic subarachnoid haemorrhage occurred in 37% and the CSF was haemorrhagic and/or xanthochromic in 75%. It is now accepted that superficial siderosis is due to chronic subarachnoid haemorrhage and a source of bleeding has been reported in 54% of cases; it was either due to dural pathology (47%) including a CSF cavity lesion or cervical root lesion, a vascular tumour (35%) or a vascular abnormality (18%). Arguments are presented that the remaining cases were also due to chronic haemorrhage and that there is no evidence for a non-haemorrhagic form of superficial siderosis. There have been 14 incidental cases diagnosed by MRI or at post-mortem with no symptoms attributable to superficial siderosis during life, supporting the notion of a pre-symptomatic phase to the illness. In 22 patients who had developed the syndrome, the duration of this pre-symptomatic phase could be calculated and ranged from 4 months to 30 years with an average of 15 years. At present the most promising treatment for superficial siderosis is surgical ablation of the bleeding sources.


Focus group data as a tool in assessing effectiveness of a hand hygiene campaign.
Routine handwashing has been proven to decrease incidence of health care-associated infections, including methicillin-resistant Staphylococcus aureus (MRSA), spawning numerous attempts to "advertise" its importance. However, most control measures fail to evaluate systematically the efficacy of handwashing initiatives. The purpose of this study was to implement a hand hygiene program in an academic medical center, utilizing visual cues developed with periodic input from hospital personnel. After estimation of baseline compliance (20%), visual cues in the form of 11'' x 17'' posters were developed in a sequential fashion, based on suggestions from participants. The stepwise approach was supported by data collected via focus groups. These data were used to design target-specific messages and to understand better the benefits of utilizing participant input. Postexposure compliance rates indicated a modest improvement over baseline, increasing to 37% during the 12-month study. In addition, the stepwise design proved to be highly useful in guiding the intervention process. Analysis of qualitative data also elucidated numerous routes through which effective hand hygiene campaigns could be implemented. Through diligent observation and participant feedback, the research team was able to develop and market educational cues to meet service demands of health care professionals in a unified effort to control health care-associated infections. Future interventions should employ incremental evaluation designs supported by participant input to develop effective hand hygiene initiatives.


[Systematic review of health-related utilities in Spain: the case of mental health].
Currently, there is no registry of utility values for the Spanish population that could potentially be used in economic evaluations. Consequently, a systematic review of utilities or preferences for health states in the Spanish population was conducted. The results related to mental health are reported. A systematic review of the literature was conducted. The main databases searched were MEDLINE, CRD, Embase, PsycINFO, CINAHL, and Cochrane. The search strategy combined terms related to utilities and Spain. The inclusion criteria comprised the resident population in Spain, whether affected by any disease or not; the reported utilities had to be evaluated through a tool validated in Spain (i.e., EQ-5D, HUI, SF-6D) and/or following accepted techniques (e.g., time trade-off, standard gamble, or the visual analog scale). A narrative synthesis of articles was undertaken and the results related to mental health summarized. A total of 103 articles were finally included, from which 742 utility values were extracted. Sixty-nine utility values related to mental health and behavioral disorders were extracted from 12 studies. The most widely used tool was the E5-QD questionnaire. Most of the excluded articles evaluated quality of life but did not provide an estimation of utilities. This review adds value to research on utilities in Spain by gathering values to be included in economic evaluations, as well as by identifying research gaps in this field. The utility values related to mental health identified in this study are similar to those reported in international publications.


Endoscopic detection of esophageal low-grade squamous dysplasia: How to predict pathologic upgrades before treatment?
In this study we aimed to predict the risk factors related to histopathologic upgrade after endoscopic submucosal dissection (ESD) in patients with pre-ESD esophageal squamous low-grade intraepithelial neoplasm (LGIN). A training cohort of 201 patients with biopsy-confirmed esophageal squamous LGIN and underwent ESD at a tertiary medical center between January 2017 and July 2019 were included. Risk factors for histological upgrade were identified using the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then established. Internal validation was evaluated by discrimination, calibration plot, and decision-curve analysis. Another cohort of 48 patients were prospectively collected from July 2019 to June 2021 for external validation of the nomogram. The rate of histological upgrade was 34.8% (70/201) and 27.1% (13/48) in the training and validation sets, respectively. LASSO regression identified that tumor area (mm2 ) per biopsy, Lugol's staining pattern, background coloration, and the circumferential range of the lesion were significantly associated with histological upgrade. The final nomogram attained favorable prediction efficacy in the training cohort (area under the receiver operating curve [AUROC] 0.96, 95% confidence interval [CI] 0.94-0.98) and validation cohort (AUROC 0.92, 95% CI 0.79 -0.99). This model generated well-fitted calibration and clinical-decision curves in both cohorts. The nomogram may better guide clinical decision on whether performing EDS or follow-up for suspicious lesions in patients with biopsy-confirmed esophageal squamous LGIN.


Atomistic insights into the selective therapeutic activity of 6-(2,4-difluorophenoxy)-5-((ethylmethyl)pyridine-3-yl)-8-methylpyrrolo[1,2-a]pyrazin-1(2H)-one towards bromodomain-containing proteins.
Cross-target effect has been one of the major mechanisms of drug toxicity, this has necessitated the design of inhibitors that are specifically tailored to target particular biomolecules. 6-(2,4-difluorophenoxy)-5-((ethylmethyl)pyridine-3-yl)-8-methylpyrrolo[1,2-a] pyrazin-1(2H)-one (Cpd38) is an inhibitor possessing high inhibition rate and tailored specificity towards bromodomain-containing protein 4 (BRD4). In this research, we used an array of computational techniques to provide insight at the atomistic level the specific targeting of BRD4 by Cpd38 relative to the binding of Cpd38 with E1A binding protein P300 (EP300); another bromodomain-containing protein (BCP). Comparatively, binding of Cpd38 improved the conformational stability and compactness of BRD4 protein when compared to the Cpd38 bound EP300. Also, Cpd38 induced a conformational change in the active site of BRD4 that facilitated a complementary pose between Cpd38 and BRD4 suitable for effective atomistic interactions. Expectedly, thermodynamic calculations revealed that the Cpd38-BRD4 system had higher binding energy (-36.11 Kcal/mol) than the Cpd38-EP300 system with a free binding energy of -15.86 Kcal/mol. Noteworthy is the opposing role Trp81 (acting as hydrogen bond acceptor) and Pro1074 (acting as hydrogen bond donor) found on the WPF and LPF loops respectively play in maintaining Cpd38 stability. Furthermore, the hydrogen bond acceptor/donator ratio was approximately 4:1 in Cpd38-BRD4 system compared with 2:1 in Cpd38-EP300 system. Taken together, atomistic insights and structural perspectives detailed in this report supplements the experimental report supporting the improved selectivity of Cpd38 for BRD4 ahead of other BCPs while providing leeway for the future design of BET selective agents with better pharmacological profile.


Amelioration of endothelial dysfunction by sodium glucose co-transporter 2 inhibitors: pieces of the puzzle explaining their cardiovascular protection.
Sodium glucose co-transporter 2 inhibitors (SGLT-2is) improve cardiovascular outcomes in both diabetic and non-diabetic patients. Preclinical studies suggest that SGLT-2is directly affect endothelial function in a glucose-independent manner. The effects of SGLT-2is include decreased oxidative stress and inflammatory reactions in endothelial cells. Furthermore, SGLT2is restore endothelium-related vasodilation and regulate angiogenesis. The favourable cardiovascular effects of SGLT-2is could be mediated via a number of pathways: (1) inhibition of the overactive sodium-hydrogen exchanger; (2) decreased expression of nicotinamide adenine dinucleotide phosphate oxidases; (3) alleviation of mitochondrial injury; (4) suppression of inflammation-related signalling pathways (e.g., by affecting NF-κB); (5) modulation of glycolysis; and (6) recovery of impaired NO bioavailability. This review focuses on the most recent progress and existing gaps in preclinical investigations concerning the direct effects of SGLT-2is on endothelial dysfunction and the mechanisms underlying such effects.


Alteration of cyclic nucleotide levels in brain following intracranial self-stimulation in the rat.
In a first experiment, 14 rats were implanted with an electrode in the ventral tegmental area and trained to self-stimulate. On the experimental day only half of the rats were allowed to self-stimulate for about one hour. All rats were then sacrificed by immersion in liquid nitrogen. Seven brain regions were dissected and assayed for the endogenous concentration of cyclic nucleotides. Self-stimulation induced significant changes in striatum and hippocampus. However, a subsequent experiment showed that the same pattern of changes in the striatum can be produced by motor activity. On the other hand, changes in the hippocampus were specific to the self-stimulation group suggesting that this structure is associated with the brain reward system.


Overexpression of the Escherichia coli sugE gene confers resistance to a narrow range of quaternary ammonium compounds.
SugE of Escherichia coli, first identified as a suppressor of groEL mutations but a member of the small multidrug resistance family, has not previously been shown to confer a drug resistance phenotype. We show that high-level expression of sugE leads to resistance to a subset of toxic quaternary ammonium compounds.


Necrosis of choroidal melanoma: in ciliary artery involvement with temporal arteritis.
A choroidal melanoma was clinically suspected in one eye of an 84-year-old farmer. At the time of the first examination the patient refused the studies necessary for a certain diagnosis as well as any treatment. Later, when the eye suddenly became blind and painful, it was enucleated. Pathological study revealed necrosis of all ocular contents, but the presence of a choroidal melanoma could still be verified histologically. The ciliary artery supplying the region of the melanoma was involved with giant cell arteritis. General examination of the patient gave support to a diagnosis of temporal arteritis, and steroid treatment resulted in general improvement.


[Mechanisms of T-cell-mediated hypersensitivity in mice infected with the intestinal helminth Trichinella spiralis].
Intestinal hypersensitivity reactions during parasitic helminth infections are T-cell-dependent. Little is known about the characteristics of T-cells that initiate and regulate intestinal inflammation or about how they do this. In this paper data are presented that indicate that during Trichinella spiralis infections in mice T-cells regulate intestinal inflammation in the same way that they regulate delayed-type hypersensitivity reactions in the skin and cellular immune responses against tumors.


Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation.
Neuroprotective strategies for prevention of the neuropathological sequelae of traumatic brain injury (TBI) have largely failed in translation to clinical treatment. Thus, there is a substantial need for further understanding the molecular mechanisms and pathways which lead to secondary neuronal cell death in the injured brain. The intracerebral activation of the complement cascade was shown to mediate inflammation and tissue destruction after TBI. However, the exact pathways of complement activation involved in the induction of posttraumatic neurodegeneration have not yet been assessed. In the present study, we investigated the role of the alternative complement activation pathway in contributing to neuronal cell death, based on a standardized TBI model in mice with targeted deletion of the factor B gene (fB-/-), a "key" component required for activation of the alternative complement pathway. After experimental TBI in wild-type (fB+/+) mice, there was a massive time-dependent systemic complement activation, as determined by enhanced C5a serum levels for up to 7 days. In contrast, the extent of systemic complement activation was significantly attenuated in fB-/- mice (P < 0.05,fB-/- vs. fB+/+; t = 4 h, 24 h, and 7 days after TBI). TUNEL histochemistry experiments revealed that posttraumatic neuronal cell death was clearly reduced for up to 7 days in the injured brain hemispheres of fB-/- mice, compared to fB+/+ littermates. Furthermore, a strong upregulation of the anti-apoptotic mediator Bcl-2 and downregulation of the pro-apoptotic Fas receptor was detected in brain homogenates of head-injured fB-/- vs. fB+/+ mice by Western blot analysis. The alternative pathway of complement activation appears to play a more crucial role in the pathophysiology of TBI than previously appreciated. This notion is based on the findings of (a) the significant attenuation of overall complement activation in head-injured fB-/- mice, as determined by a reduction of serum C5a concentrations to constitutive levels in normal mice, and (b) by a dramatic reduction of TUNEL-positive neurons in conjunction with an upregulation of Bcl-2 and downregulation of the Fas receptor in head-injured fB-/- mice, compared to fB+/+ littermates. Pharmacological targeting of the alternative complement pathway during the "time-window of opportunity" after TBI may represent a promising new strategy to be pursued in future studies.


The planning of orthopaedic reconstructive surgery using computer-aided simulation and design.
Three-dimensional reconstructions from computed tomographic (CT) images are currently being used clinically in a wide variety of orthopaedic surgical applications. The computer may be used to select the optimum standard artificial joint replacement or to design a custom artificial joint replacement for a particular patient. Where large bony defects exist, the computer may be used to design bone allografts for joint reconstruction and to manufacture models of the bones for use in planning the surgery. In cases where osteotomies are performed to improve the mechanics of the joint, each proposed osteotomy may be simulated on the computer to identify the surgical plan that will optimally normalize the diseased joint.


Purification of unique alpha subunits of GTP-binding regulatory proteins (G proteins) by affinity chromatography with immobilized beta gamma subunits.
Novel G protein alpha subunits were purified from rat brain by an affinity matrix containing immobilized beta gamma subunits (Pang, I.-H., and Sternweis, P. C. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 7814-7818). They were unique based on the following criteria. These alpha subunits migrated differently through polyacrylamide gels with an apparent molecular mass of 42 kDa. They did not behave similarly to the other brain G proteins by conventional chromatographic techniques. Antisera raised against a common region of known alpha subunits failed to recognize these 42-kDa polypeptides. Finally, primary sequences of tryptic fragments of these proteins contain regions homologous to, yet unique from, the other alpha subunits. Sequences are identical with one or more members of a new family of alpha subunits recently identified by molecular genetic techniques (Strathmann, M., Wilke, T. M., and Simon, M. I. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 7407-7409); most of the primary sequence identifies an alpha subunit labeled alpha q. These polypeptides were not substrates for ADP-ribosylation catalyzed by pertussis toxin. They bound GTP gamma S only with slow rates and low stoichiometry. Antisera to peptides based on primary sequence were specific for the new alpha subunits and indicate that they are widely distributed at low levels in different tissues but more concentrated in brain and lung. This procedure provides a means of preparing native G proteins that have a potential role as modulators of pertussis toxin-insensitive regulatory pathways.


Ocular and cervical vestibular evoked myogenic potentials elicited by air-conducted, low-frequency sound.
Sound is not only detected by the cochlea, but also, at high intensities, by the vestibular system. Acoustic activation of the vestibular system can manifest itself in vestibular evoked myogenic potentials (VEMPs). In a clinical setting, VEMPs are usually evoked with rather high-frequency sound (500 Hz and higher), despite the fact that only a fraction of saccular and utricular hair cells in the striolar region is available for high-frequency stimulation. As a growing proportion of the population complains about low-frequency environmental noise, including reports on vestibular symptoms, the activation of the vestibular system by low-frequency sound deserves better understanding. We recorded growth functions of oVEMPs and cVEMPs evoked with air-conducted sound at 120 Hz and below. We estimated VEMP thresholds and tested whether phase changes of the stimulus carrier result in changes of VEMP amplitude and latency. The VEMP response of the otholith organs to low-frequency sound is uniform and not tuned when corrected for middle ear attenuation by A-weighting the stimulus level. Different stimulus carrier phases result in phase-correlated changes of cVEMP latencies and amplitudes. VEMPs can be evoked with rather low-frequency sound, but high thresholds suggest that they are unlikely to be triggered by environmental sounds.


Linkage of the NKG2 and CD94 receptor genes to D12S77 in the human natural killer gene complex.
The human natural killer (NK) gene complex is located on the short arm of chromosome 12 and contains a number of genes encoding C-type lectin receptors important for natural killer cell function. Among these are CD94 and the five NKG2 genes. The CD94 protein associates with different NKG2 isoforms to heterodimeric receptors which function to inhibit or trigger cytotoxicity of NK cells depending on the NKG2 isoform. We selected two yeast artificial chromosome clones comprising approximately 1.5 Mb of the NK gene complex and established a contig of underlying P1-derived artificial chromosome clones containing all NKG2 and the CD94 genes. A detailed analysis shows that all six genes are found within a region of 100 to 200 kilobases proximal of the marker D12S77. The gene order established is D12S77 - CD94 - NKG2D - NKG2F - NKG2E - NKG2C - NKG2A. The NKG2 genes are of identical transcriptional orientation, whereas the CD94 gene is placed in opposite orientation. The tight genomic linkage of these genes and the identical orientation of the NKG2 genes suggest coordinate regulation of expression during the differentiation of natural killer cells.


Recognition of the HLA-DRB1*14:119 allele in a Singaporean bone marrow donor.
Nucleotide substitutions in exon 2 of DRB1*14:54:01:01 result in the novel DRB1*14:119 allele.


[Periodic local approximation for the model free description of measurement courses of biorhythmic processes--demonstration example for the selection of smoothness parameters].
Measured time series with known basic periodicity may be modelfreely evaluated by procedures of local adjusted approximation. Examples of motility time series recorded in chronobiological experiments in the seasonal course of a year demonstrate aspects of choosing values of the smoothing parameter and the resulting effects for the quantitative description of the measured variations as well as for their interpretation.


Exosomal LncRNAs and hepatocellular Carcinoma: From basic research to clinical practice.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis. The incidences of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Long noncoding RNAs (lncRNAs) wrapped in exosomes can change the expression of their target genes in recipient cells, thereby regulating the behavior of recipient cells. Increasing evidence has demonstrated that there is a correlation between the activation of exosomal lncRNAs and the development of HCC. In this review article, we highlighted the functions of exosomal lncRNAs in the development of HCC, showing that exosomal lncRNAs play a vital role in the growth and progression of HCC and are targets for HCC.


Ultrasensitive and Selective Detection of SARS-CoV-2 Using Thermotropic Liquid Crystals and Image-Based Machine Learning.
Rapid, robust virus-detection techniques with ultrahigh sensitivity and selectivity are required for the outbreak of the pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Here, we report that the femtomolar concentrations of single-stranded ribonucleic acid (ssRNA) of SARS-CoV-2 trigger ordering transitions in liquid crystal (LC) films decorated with cationic surfactant and complementary 15-mer single-stranded deoxyribonucleic acid (ssDNA) probe. More importantly, the sensitivity of the LC to the SARS ssRNA, with a 3-bp mismatch compared to the SARS-CoV-2 ssRNA, is measured to decrease by seven orders of magnitude, suggesting that the LC ordering transitions depend strongly on the targeted oligonucleotide sequence. Finally, we design a LC-based diagnostic kit and a smartphone-based application (app) to enable automatic detection of SARS-CoV-2 ssRNA, which could be used for reliable self-test of SARS-CoV-2 at home without the need for complex equipment or procedures.


[Cardiac tamponade as first manifestation of multiple myeloma : A case report with literature review].
Multiple myeloma is a hematologic malignancy characterized by clonal proliferation of plasma cells, mainly in bone marrow. Extramedullary disease is reported in many cases and may occur at diagnosis, at progression, or during relapse phase. Pericardial involvement is a rare condition that usually occurs with advanced-stage disease. We report a rare case of 76-year-old women with plasma cell-based pericardial effusion with cardiac tamponade as a form of presentation of multiple myeloma and discuss it in the light of literature. Diagnosis was established by pericardial fluid cytology. The patient received systemic chemotherapy, according to MPT protocol.


PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells.
Oncogenic transformation is believed to impact the vascular phenotype and microenvironment in cancer, at least in part, through mechanisms involving extracellular vesicles (EVs). We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). We report that NB4 cells produce considerable numbers of EVs, which are readily taken up by cultured endothelial cells triggering their increased survival. NB4 EVs contain PML-RARa transcript, but no detectable protein, which is also absent in endothelial cells upon the vesicle uptake, thereby precluding an active intercellular trafficking of this oncogene in this setting. ATRA treatment changes the emission profile of NB4-related EVs resulting in preponderance of smaller vesicles, an effect that occurs in parallel with the onset of cellular differentiation. ATRA also increases IL-8 mRNA and protein content in NB4 cells and their EVs, while decreasing the levels of VEGF and tissue factor (TF). Endothelial cell uptake of NB4-derived EVs renders these cells more TF-positive and procoagulant, and this effect is diminished by pre-treatment of EV donor cells with ATRA. Profiling angiogenesis-related transcripts in intact and ATRA-treated APL cells and their EVs reveals multiple differences attributable to cellular responses and EV molecular packaging. These observations point to the potential significance of changes in the angiogenic signature and activity associated with EVs released from tumor cells subjected to targeted therapy.


Effects of polarized and non-polarized red-light irradiation on proliferation of human Wharton's jelly-derived mesenchymal cells.
Light emitting diode (LED) irradiation has recently been introduced as an encouraging strategy for promotion of cell proliferation. Human umbilical cord Wharton's jelly-derived mesenchymal (hUCM) cells are among the most available mesenchymal cells with a promising application in regenerative medicine. The aim of the present study was to examine the effect of polarized (PL) and non-polarized (NPL) red-light emitted by LED on various proliferation properties of hUCM cells. Cell proliferation was assessed 48 h after irradiation of hUCM cells by different energy densities. Cell density increased to a significant level both in PL and NPL irradiation at 0.954 J/cm2 following WST-1 assay. Staining of irradiated and non-irradiated cells with Hoechst after 3 and 6 days revealed an increased proliferation rate in irradiated cells, but the non-irradiated cells proliferated more than irradiated cells at day 9 of cultivation. Similar results were obtained in trypan blue assay. Scratch repair test for 18 h with an interval of 6 h did not reveal a significant difference between irradiated and non-irradiated cells. In addition, CFU-F assay in PL irradiated cells was higher than control when 500 cells/plate was cultivated. Totally, this study revealed that hUCM cells could be induced to achieve higher number of cells by PL and NPL red-light irradiation after 48 h.


Activation of brain somatostatin 2 receptors stimulates feeding in mice: analysis of food intake microstructure.
We recently reported that the oligosomatostatin receptor agonist, ODT8-SST increases food intake in rats via the somatostatin 2 receptor (sst(2)). We characterized ingestive behavior following intracerebroventricular (icv) injection of a selective sst(2) agonist in freely fed mice during the light phase. The sst(2) agonist (0.01, 0.03, 0.1, 0.3 or 1μg/mouse) injected icv under short inhalation anesthesia dose-dependently increased cumulative light phase food intake over 4h compared to vehicle with a 3.1-times increase at 1μg/mouse (p<0.05). Likewise, the sst(2,3,5) agonist octreotide (0.3 or 1μg/mouse) dose-dependently increased 4-h food intake, whereas selective sst(1) or sst(4) agonists at 1μg/mouse did not. In vehicle-treated mice, high fat diet increased caloric intake/4h by 2.8-times compared to regular diet (p<0.05) and values were further increased 1.4-times/4h by the sst(2) agonist. Automated continuous assessment of food intake established a 6.6-times higher food intake during the dark phase due to increased number of meals, meal size, meal duration and rate of ingestion compared to non-treated mice during the light phase. During the first 4h post icv sst(2) agonist injection, mice had a 57% increase in number of meals with a 60% higher rate of ingestion, and a 61% reduction in inter-meal intervals, whereas meal sizes were not altered compared to vehicle. These data indicate that the activation of brain sst(2) receptors potently stimulates the light phase ingestive behavior under basal or high fat diet-stimulated conditions in mice. The shortened inter-meal interval suggests an inhibitory effect of the sst(2) agonist on "satiety", whereas "satiation" is not altered as indicated by normal meal size.


QM Automata: A New Class of Restricted Quantum Membrane Automata.
The term "Unconventional Computing" describes the use of non-standard methods and models in computing. It is a recently established field, with many interesting and promising results. In this work we combine notions from quantum computing with aspects of membrane computing to define what we call QM automata. Specifically, we introduce a variant of quantum membrane automata that operate in accordance with the principles of quantum computing. We explore the functionality and capabilities of the QM automata through indicative examples. Finally we suggest future directions for research on QM automata.


[The trans depathologization perspective: a contribution to public health approaches and clinical practices in mental health? SESPAS Report 2020].
Over the last decade, the academic-activist trans depathologization perspective has contributed to a change in the conceptualization of gender transition processes. Observing an interrelation between psychiatrization and transphobic violence, trans depathologization activist groups and allies demand the removal of the diagnostic classification of transexuality as a mental disorder. Furthermore, they have developed trans health care models and legal gender recognition processes based on depathologization and human rights perspectives. They propose changing the role of mental health professionals in trans health care, substituting the psychiatric assessment role by accompaniment and psychological support tasks. The trans depathologization perspective can be related to various approaches and topics relevant in public health and mental health, among them sociology of diagnosis, human rights based approaches to health, human rights protection in mental health, universal health coverage, review of diagnostic classifications, intersectionality perspectives, reflections on bioethical principles, models of integrated people-centered health services and approaches to research ethics. Over the last few years, informed decision-making models have been developed for trans health care in several countries and world regions. Health professionals, including mental health professionals, as well as professionals from the educational and judicial-administrative sector, can have an important role in addressing situations of discrimination and transphobic violence, contributing to the construction of a society that respects, recognizes and celebrates gender diversity.


[Diagnostic image (149). A woman with a mass at the base of the tongue. Lingual thyroid].
A 48-year-old woman had a lump in her throat and dysphagia. On examination an oropharyngeal mass was seen which was diagnosed as a lingual thyroid.


Dermoscopy for the Diagnosis of Conjunctival Lesions.
This article describes the present literature on dermoscopy of conjunctiva and shows the results of a dermoscopy study of 147 conjunctival tumors. Melanomas were characterized by a heavy pigmentation, irregular dots, and a higher prevalence of gray color compared with nevi. Squamous cell carcinomas had peculiar hairpin and glomerular vessels. Primary acquired melanoses were characterized by regularly distributed light brown dots. A large part of nevi had small cysts.


Comparative clinical evaluation of ketotifen and montelukast sodium in asthmatic Iraqi patients.
Asthma is a common and chronic inflammatory condition of the airways whose cause is not completely understood. Although many classes of drugs are used for management of asthma, the response is variable due to multifactor reasons. This study was designed to evaluate the outcome of using ketotifen or montelukast sodium in Iraqi asthmatic patients. Single blinded randomized clinical trial was utilized, in which 100 asthmatic patients were recruited from Al-Karama hospital and randomized into two groups; 1st group (50 patients, treated with ketotifen for 4 weeks) and 2nd group (50 patients treated with montelukast sodium for 4 weeks). Asthma symptom score and wheezing were recorded at the beginning (first visit) and at the end of the study (after one month). Pulmonary function tests (PFTs) were performed by spirometry, and the patients' use of asthma drugs and their symptoms were evaluated at each visit. The result showed that asthma symptom, chest wheezing, and PFT values were significantly improved in the two groups at the end of the study compared to first visit (p < 0.05). All symptoms were significantly lower and PFT values were higher in the 2nd group compared to 1st group (p < 0.05). In conclusion, both ketotifen and montelukast sodium showed significant changes in asthma symptoms and PFT after one month of treatment, but the changes were more significant with montelukast group (2nd group) compared with ketotifen group (1st group) and this indicate that montelukast was more effective than ketotifen in treatment of asthmatic patients.


Biochemical characterisation of elsamicin and other coumarin-related antitumour agents as potent inhibitors of human topoisomerase II.
Elsamicin (EM) is a recently discovered antitumour agent that is structurally related to several other compounds displaying anticancer activities, including chartreusin (CT), chrysomycin V (CV) and M (CM), gilvocarcin V (GV) and ravidomycin (RM). The biochemical events resulting in cytotoxicity for most of these compounds have not been clearly elucidated. There is some evidence that GV and CT bind to DNA and that GV is photosensitive, causing DNA damage. Therefore, we investigated the effects of these chemicals on DNA in cells and on pBR322 plasmid DNA. Using alkaline elution techniques, we found that all these compounds induced, to a different extent, DNA breakage in the human lung adenocarcinoma A549 cell line. In addition, all either bound to or intercalated into DNA, as indicated by their ability to alter the electrophoretic migration of DNA in agarose gels. Using the P4 unknotting assay, EM, CT, CV, CM, GV and RM were found to be potent inhibitors of the catalytic activity of topoisomerase II (topo II). Their potencies were compared with the known topo II inhibitors teniposide (VM-26) and doxorubicin (DX). EM was the most potent, with an IC50 of 0.4 mumol/l followed in order by CV, GV, and CT. VM-26 was the least potent with an IC50 of 15 mumol/l. It was concluded from these results that EM, GV, CV, CM and CT are capable of inhibiting topo II and that EM is the most potent inhibitor of topo II yet discovered.


Hemodynamic, hepatorenal, and postoperative effects of desflurane-fentanyl and midazolam-fentanyl anesthesia in coronary artery bypass surgery.
The purpose of this study was to compare the hemodynamic, hepatorenal, and postoperative effects of desflurane-fentanyl and midazolam-fentanyl anesthesia during coronary artery bypass surgery. Prospective study. University hospital. Sixty patients undergoing elective coronary artery bypass grafting surgery with ejection fraction more than 45%. Anesthesia was induced with etomidate, 0.2 mg/kg, and fentanyl, 5 microg/kg, in group D (n = 30) and with midazolam, 0.1 to 0.3 mg/kg, and fentanyl, 5 microg/kg, in group M (n = 30). Anesthesia was maintained with desflurane, 2% to 6%, and fentanyl, 15 to 25 microg/kg, in group D and midazolam infusion, 0.1 to 0.5 mg/kg/h, and fentanyl, 15 to 25 microg/kg, in group M. Hemodynamic monitoring included a 5-lead electrocardiogram, a radial artery catheter, and a pulmonary artery catheter. Data were obtained before induction of anesthesia (t0), after induction of anesthesia (t1), after intubation (t2), after surgical incision (t3), after sternotomy (t4), before cardiopulmonary bypass (t5), after protamine infusion (t6), and at the end of the surgery (t7). Blood samples were obtained to measure total bilirubin, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase, creatinine, and blood urea nitrogen just before induction of anesthesia and at the first, fourth, and 14th days postoperatively. Intraoperative hemodynamic responses were similar in both groups, and transient hepatic and renal dysfunctions were observed in the postoperative period in both groups. The extubation and intensive care unit discharge times were found to be shorter in the desflurane-fentanyl group.


Ectopic meningioma of the orbit.
Ectopic meningiomas within the orbit are very rare. Most of the previously reported cases were located along the medial wall. Here we report on three cases of ectopic meningiomas presenting as superomedial orbital masses along with their radiological and histopathological features. All three patients underwent surgical excision of the tumor via anterior orbitotomy.


Expression pattern of the Hedgehog signaling pathway in pituitary adenomas.
Several studies have demonstrated the role of Wnt and Notch signaling in the pathogenesis of pituitary adenomas, but data are scarce regarding the role of Hedgehog signaling. In this study we investigated the differential expression of gene targets of the Hedgehog signaling pathway. Formalin-fixed, paraffin-embedded specimens from adult patients who underwent transphenoidal resection and normal human pituitary tissues that were obtained from autopsies were used. Clinical information and data from pre-operative MRI scan (extracellular tumor extension, tumor size, displacement of the optic chiasm) were retrieved from the Hospital's database. We used a customized RT(2) Profiler PCR Array, to investigate the expression of genes related to Notch and Hedgehog signaling pathways (PTCH1, PTCH2, GLI1, GLI3, NOTCH3, JAG1, HES1, and HIP). A total of 52 pituitary adenomas (32 non-functioning adenomas, 15 somatotropinomas and 5 prolactinomas) were used in the final analysis. In non-functioning pituitary adenomas there was a significant decrease (approximately 75%) in expression of all Hedgehog related genes that were tested, while Notch3 and Jagged-1 expression was found significantly increased, compared with normal pituitary tissue controls. In contrast, somatotropinomas demonstrated a significant increase in expression of all Hedgehog related genes and a decrease in the expression of Notch3 and Jagged-1. There was no significant difference in the expression of Hedgehog and Notch related genes between prolactinomas and healthy pituitary tissues. Hedgehog signalling appears to be activated in somatotropinomas but not in non-functioning pituitary adenomas in contrast to the expression pattern of Notch signalling pathway.


Peripheral Insertion of Pediatric Central Venous Catheters in Adults with Difficult I.V. Access.
Difficult intravenous access is a frequent occurrence in critical care and emergency medicine. Prior intravenous access, chemotherapy use, and obesity are a few factors associated with difficult access. Alternatives to peripheral access are often contraindicated, not feasible, or not readily available. To describe the feasibility and safety of peripheral insertion of peripherally inserted pediatric central venous catheters (PIPCVC) in a cohort of adult critical care patients with difficult intravenous access. Prospective observational study of adult patients with difficult intravenous access who underwent peripheral insertion of pediatric PIPCVCs at a large university hospital. During a 1-year period, 46 patients were evaluated for PIPCVC; 40 catheters were placed successfully. The median age of the patients was 59 years (range 19-95 years) and 20 (50%) were female. The median body mass index was 27.2 (range 17.1-41.8). The basilic vein was accessed in 25/40 (63%) patients, the cephalic in 10/40 (25%), and the accessed vessel was missing in 5/40 (13%) cases. The PIPCVCs were in place for a median of 8 days (range 1-32). One superficial thrombosis and one deep occurred; pulmonary embolism did not occur. PIPCVC placement seems to be a feasible option in patients in whom peripheral intravenous access is difficult. The safety of this technique needs to be evaluated in prospective studies.


Methyl purple, an exceptionally sensitive monitor of chloroplast photosystem I turnover: physical properties and synthesis.
Methyl purple is a recently introduced quinone-imide redox dye that has been shown to be an exceptionally sensitive monitor of photosystem I activity in chloroplasts. This compound has a wide range of potential applications for studies of photosynthetic electron transfer and photosynthetic bioenergetics, but the physical properties of the compound must first be established rigorously. The specific molar absorption coefficients of both the anionic and protonated forms of methyl purple have been determined. The oxidation-reduction midpoint potential of methyl purple over the pH range 3 to 12 was also determined by polarographic methods, and the effect of pH on the visible absorption spectrum is reported. A detailed procedure for the synthesis of methyl purple is given.


Assessment of biomarkers in type 2 diabetic subjects without any complications.
Type 2-diabetes (T2D), is a public health problem which has reached epidemic proportions due to the rapidly increasing rates of this disease worldwide. It is known that adipose tissue can synthesize and release pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1, adiponectin and leptin that are associated with body fat mass. Hence comparing the biomarkers with individuals without hyperglycemia would help us to understand the level of increase in their values though the vascular complications have not begun. This was a cross sectional study comprising 229 diabetic persons and 205 healthy individuals. High sensitivity reactive protein (hs-CRP) was estimated using nephelometry technique. Inflammatory markers and adiponectin were measured using ELISA instrument. Tumor necrosis factor α (TNF-α) (40.56%) and Leptin (45.43%) were significantly increased in the diabetic group when compared with normal study population. Adiponectin was significantly decreased in diabetic study population (11.94%). This was supported by a significant correlation between the glycemic index HbA1c and TNF-α (r=0.376, p=0.01), adiponectin (r=-0.381, p=0.01) and leptin (r=0.269, p=0.01) in diabetic population, but the significance was lost among the normal healthy individuals. The most promising biomarkers of diabetes such as TNF-α, adiponectin, leptin has shown a marked difference in this diabetic population. This study proves the assessment of these biomarkers as future predictors of type 2 diabetes.


Position-specific incorporation of dansylated non-natural amino acids into streptavidin by using a four-base codon.
Novel non-natural amino acids carrying a dansyl fluorescent group were designed, synthesized, and incorporated into various positions of streptavidin by using a CGGG four-base codon in an Escherichia coli in vitro translation system. 2,6-Dansyl-aminophenylalanine (2,6-dnsAF) was found to be incorporated into the protein more efficiently than 1,5-dansyl-lysine, 2,6-dansyl-lysine, and 1,5-dansyl-aminophenylalanine. Fluorescence measurements indicate that the position-specific incorporation of the 2,6-dnsAF is a useful technique to probe protein structures. These results also indicate that well-designed non-natural amino acids carrying relatively large side chains can be accepted as substrates of the translation system.


Adjunctive Therapies for Ventricular Arrhythmia Management: Autonomic Neuromodulation-Established and Emerging Therapies.
The autonomic nervous system plays an integral role in the pathophysiology of ventricular arrhythmias. In the modern era, several therapeutic interventions are available to the clinician for bedside and procedural/surgical management, and there are many ways in which modulation of the autonomic nervous system can provide life-saving benefit. This review discusses some of the current treatment options, the supporting evidence, and also introduce some of the emerging therapies in this expanding field of electrophysiology.


Mosquito cells (C6/36) fail to support the complete replication of Penaeus merguiensis hepandensovirus.
Mosquito cell lines (C6/36) were reported in the literature to support the propagation of Penaeus monodon hepandensovirus (PmoHDV). We aim to evaluate the susceptibility and viral propagation of P. merguiensis hepandensovirus (PmeHDV) which is ∼22% different to PmoHDV in Aedes albopictus cell line (C6/36). Cellular changes in the infected cell culture were detected. Vacuole formation was seen in both infected and uninfected cell cultures. The average number of disrupted cellular membranes in the infected cells (presumptive dead cells) was significantly higher than that of uninfected cells at passage two (F=9.749, d.f. 1, 22, p<0.05). Using a proliferation assay, light absorption of infected cells peaked at 2weeks post-infection (O.D.=0.27) but was significantly lower than that of the uninfected groups (O.D.=0.37) (F=6.879, d.f. 1, 94, p<0.05) suggesting hindered cell growth. PCR of the serial passages of the infected cell cultures indicated weak positive results for PmeHDV infection and TaqMan quantitative PCR confirmed that the average number of viral copies declined from 3.8×105 to 5.69×102 copies per μL and the mean of cycle times increased from 19.26 to 27.63. These results are interpreted to mean C6/36 allows the initial stage of PmeHDV replication, but the virus was incapable of using C6/36 for patent replication of its' virions.


Does Leptinotarsa decemlineata larval survival after pesticide treatment depend on microbiome composition?
The microbiomes of some arthropods are believed to eliminate pesticides by chemical degradation or stimulation of the host immune system. The Colorado potato beetle (CPB; Leptinotarsa decemlineata) is an important agricultural pest with known resistance to used pesticides. We sought to analyze microbiome composition in CPB larvae from different sites and to identify the effect of pesticides on the microbiome of surviving and dead larvae after chlorpyrifos treatment in laboratory. Changes in the Lactococcus lactis community in larvae treated with chlorpyrifos and fed by potato leaves with L. lactis cover were studied by manipulative experiment. The microbiome was characterized by sequencing the 16S RNA gene. The microbiome of L. decemlineata larvae is composed of a few operational taxonomic units (OTUs) (Enterobacteriaceae, Pseudocitrobacter, Acinetobacter, Pseudomonas, L. lactis, Enterococcus, Burkholderia and Spiroplasma leptinotarsae). The microbiome varied among the samples from eight sites and showed differences in profiles between surviving and dead larvae. The survival of larvae after chlorpyrifos treatment was correlated with a higher proportion of L. lactis sequences in the microbiome. The S. leptinotarsa profile also increased in the surviving larvae, but this OTU was not present in all sampling sites. In manipulative experiments, larvae treated with L. lactis had five-fold lower mortality rates than untreated larvae. These results indicate that the microbiome of larvae is formed from a few bacterial taxa depending on the sampling site. A member of the gut microbiome, L. lactis, is believed to help overcome the toxic effects of chlorpyrifos in the larval gut. © 2023 Society of Chemical Industry.


Impact of technological innovation and renewable energy on ecological footprint in G20 countries: The moderating role of institutional quality.
The connection between ecological footprint and economic complexity has significant implications for environmental sustainability regarding the policy. Additionally, institutional quality is crucial in ensuring environmental sustainability and moderating the link between economic complexity and ecological footprint. The task of achieving sustainable environmental development and preventing further degradation of the environment poses a formidable challenge to policymakers. This study delves into the significance of technology innovation and renewable energy in creating a more sustainable environment. Recognizing the need for a more critical review, this research establishes the dynamic linkage between ecological footprint, renewable energy consumption, and technological innovation, especially in conjunction with a moderating component, particularly institutional quality, in G20 countries from 1990 to 2021. We employ advanced panel approaches to address panel data analysis concerns, such as cross-sectional dependence, slope heterogeneity, unit root, cointegration test and CS-ARDL. The long-term estimator indicates that renewable energy and technological innovation negatively but significantly impact the ecological footprint. Whilst economic growth, FDI, and urbanization have shown a positive and significant impact on ecological footprint; institutional quality negatively moderates the relationship between ecological footprint, renewable energy, and technological innovation in the G20 countries. Further evidence from the Dumitrescu-Hurlin Granger causality test shows that efforts to expand access to renewable energy, technological advancements, and economic growth will significantly affect environmental impacts. Based on our results, it is imperative to introduce more favorable legislation and encourage technological advancements in the field of renewable energy if we want to achieve our sustainable development objectives.


Wnt and Wnt inhibitors in bone metastasis.
Bone metastasis is a clinically devastating development of progressive cancers including prostate carcinoma, breast carcinoma and multiple myeloma. Bone metastases are typically painful, lead to adverse skeletal-related events, such as fracture, and are highly resistant to therapy. A major contribution to the ability of cancers to successfully establish bone metastases is their ability to exploit mechanisms of normal bone remodeling. Wnts are a large family of morphogenic proteins that are critical for bone development and contribute to maintaining bone mass in the mature organism. Wnt function is balanced by the presence of a variety of endogenous inhibitors, such as the dickkopf family members, secreted frizzled related proteins and sclerostin. Together, these factors contribute to normal bone homeostasis, allowing for dynamic changes in bone to withstand alterations in physical forces and physiological needs. In this review, we describe the role that Wnts and their inhibitors have in normal bone biology and cancer-related bone pathology. An overview of Wnt signaling pathways is discussed and key bone microenvironment cellular players, as they pertain to Wnt biology, are examined. Finally, we describe clinical trials of several Wnt inhibitor antagonists for patients with tumor-related bone disease. As few options currently exist for the treatment of bone-metastatic disease, Wnt proteins and their inhibitors offer promise for the development of novel therapeutics.


The effect of pre-incubation and direct procedure for the alanine transaminase assay in two kits compared.
The kinetic measurement of serum alanine transaminase was carried out on two enzyme kits (Roche and Calbiochem), done as a direct method and a pre-incubation method. Variable results from commercial control sera and patient sera by these four procedures were obtained. Pre-incubation enzyme values were generally lower than the direct values (mean difference 10%), but there were marked differences between the results from the two kits. This finding has important significance especially for laboratories participating in external QC Programmes. Frequent precision checks of the method and a local reference range are therefore necessary.


The MVM ventilator and 3D π PET scanner development arising from basic science work.
During the COVID-19 pandemic, members of the DarkSide-20k (DS) Dark Matter international experimental collaboration together with engineers, scientists and manufacturers in Italy, Canada, the USA and eight other countries diverted their research efforts to develop MVM, a new readily manufactured, relatively low-cost ventilator tailored to the most severe intubated patients. Using expertise developed for DS, they produced and received authorization for 7300 units delivered to the Canadian government for its stockpile, now being considered for donation to other countries in urgent need. Other members of DS are using photo-electronics innovation to develop 3D π a more sensitive positron emission tomography (PET) scanner that can provide better resolution and reduce doses, of particular value for providing access for pediatric patients.


Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting duct.
Nephronophthisis is characterised by renal fibrosis, tubular basement membrane disruption and corticomedullary cyst formation leading to end stage renal failure. Mutations in NPHP1 account for the underlying genetic defect in 25% of patients with nephronophthisis. Loss of urine concentration ability may be an early feature of nephronophthisis. Using yeast-2-library screening with the SH3 domain of nephrocystin-1 as bait, we identify Ack1 as a novel interaction partner. This interaction is confirmed using exogenous over-expression followed by co-immunoprecipitation. Ack1 is an activated Cdc42-associated kinase, and like nephrocystin-1, is a known interactor of p130Cas. Nephrocystin-1 partially colocalises with Ack1 at cell-cell contacts in IMCD3 cells. In human kidney, nephrocystin-1 expression is limited to cell-cell junctions in renal collecting duct cells. These data define Ack1 as a novel interaction partner of nephrocystin-1 and implicate cell-cell junctions and the renal collecting duct in the pathology of nephronophthisis.


Editorial Commentary: Preoperative Patient-Reported Outcomes Measurement Information System Scores Vary Over Time.
Patient-Reported Outcomes Measurement Information System (PROMIS) scores have considerable potential to both streamline the collection of outcome data and provide a common set of metrics to compare and benchmark patient-reported outcomes after orthopaedic procedures. An analysis of PROMIS scores collected at the preoperative clinical visit and the day of surgery found considerable changes in upper- and lower-extremity physical function, pain interference, and depression. These findings suggest that health status may vary between the day of operative consent and the day of surgery. Given the importance of patient-reported outcomes in clinical research, quality assurance, and value-based health care, the potential for large changes in scores leading up to the procedure warrants attention toward the timing of PROMIS administration to ensure that the health status of the patient-and its variation-is accurately captured.


Genetic causes and treatment of isolated growth hormone deficiency-an update.
Isolated growth hormone deficiency is the most common pituitary hormone deficiency and can result from congenital or acquired causes, although the majority of cases are idiopathic with no identifiable etiology. Known genes involved in the genetic etiology of isolated growth hormone deficiency include those that encode growth hormone (GH1), growth-hormone-releasing hormone receptor (GHRHR) and transcription factor SOX3. However, mutations are identified in a relatively small percentage of patients, which suggests that other, yet unidentified, genetic factors are involved. Among the known factors, heterozygous mutations in GH1 remain the most frequent cause of isolated growth hormone deficiency. The identification of mutations has clinical implications for the management of patients with this condition, as individuals with heterozygous GH1 mutations vary in phenotype and can, in some cases, develop additional pituitary hormone deficiencies. Lifelong follow-up of these patients is, therefore, recommended. Further studies in the genetic etiology of isolated growth hormone deficiency will help to elucidate mechanisms implicated in the control of growth and may influence future treatment options. Advances in pharmacogenomics will also optimize the treatment of isolated growth hormone deficiency and other conditions associated with short stature, for which recombinant human growth hormone is a licensed therapy.


Mortality from diabetic nephropathy in the United Kingdom.
Deaths in diabetic subjects dying under 50 years of age in the United Kingdom during 1979 have been analysed with special reference to diabetic nephropathy. Fifteen percent of 447 deaths were from nephropathy. Uraemic deaths from nephropathy were particularly common in those whose diabetes was diagnosed under 31 years old, and responsible for over one-quarter of deaths in this age group. Most deaths from nephropathy occur before 30 years' duration of diabetes and are rare in those of longer duration, suggesting that some diabetic patients are more and others less prone to this complication. There were more men than women in a ratio of approximately 1.3:1. Severe retinopathy is usually present in end-stage renal failure causing blindness in one out of three cases, and impaired vision in a further one out of three. Blind patients were not otherwise more severely affected by diabetic complications than others. It is estimated that approximately three-quarters of the diabetic subjects who develop end-stage renal failure from nephropathy may be suitable for dialysis or transplantation.