Strength of public preferences for endovascular or open aortic aneurysm repair.
This study evaluated public preferences for the treatment processes for abdominal aortic aneurysm repair in order to allow them to be incorporated into a cost-effectiveness analysis. This was a telephone survey using a trade-off method in UK resident adults (aged at least 18 years) with no previous diagnosis of a vascular condition. Some 167 of 209 participants (79·9 per cent) stated that they would prefer endovascular aneurysm repair (EVAR), 40 (19·1 per cent) preferred open surgery and two (1·0 per cent) stated no preference. Participants preferred EVAR because of the less invasive nature of the intervention and quicker recovery. Participants preferring open surgery cited reasons such as having a single follow-up appointment, and a procedure that felt more permanent. When participants were asked to make a sacrifice in order to have their preferred treatment, 122 (58·4 per cent) favoured EVAR, 18 (8·6 per cent) favoured open surgery and 69 (33·0 per cent) had no preference. Those preferring EVAR were willing to give up a mean of 0·135 expected quality-adjusted life-years (QALYs) to have EVAR, compared with a willingness to give up 0·033 expected QALYs among those preferring open repair. These results indicate a clear preference for EVAR over open surgery for aortic aneurysm.


Learning the language of abstinence in addiction treatment: some similarities between relapse-prevention with disulfiram, naltrexone, and other pharmacological antagonists and intensive "immersion" methods of foreign language teaching.
Relapse-prevention (RP) is an educational process. Learning to abstain from alcohol or opiates after years of dependence involves selectively suppressing old, maladaptive habits of thought and behavior and establishing new, adaptive ones. This process resembles foreign language (FL) learning. Effective FL teaching techniques are relevant to RP. "Immersion," the most effective FL teaching method, discourages students from using their first language ab initio, requiring them to use the FL instead, however inexpertly. It resembles exposure and response-prevention for phobic or compulsive disorders. Supervised disulfiram aids RP by discouraging alcoholics from responding to real-life drinking cues in the "language" of excessive drinking, requiring them, ab initio, to practice new, alcohol-free responses. Supervised or depot naltrexone acts similarly in opiate dependence. We discuss the concept of antagonist-assisted abstinence.


Discovery of two novel ALKBH5 selective inhibitors that exhibit uncompetitive or competitive type and suppress the growth activity of glioblastoma multiforme.
A group of RNA methylation enzymes is currently of interest as a new target for cancer therapy. Alpha-ketoglutarate-dependent dioxygenase B (AlkB) homolog 5 (ALKBH5) is an N6 -methyladenosine (m6 A) demethylation enzyme, and by high-throughput screening from pure small molecule compounds, we identified two novel inhibitors, Ena15 and Ena21, against it. Each compound showed either uncompetitive or competitive inhibition for 2-oxoglutarate (2OG). In addition, Ena21 had little inhibitory activity for fat mass and obesity-associated protein (FTO), which is another N6 -methyladenosine demethylation enzyme, while Ena15 enhanced the demethylase activity of FTO. The predicted binding poses of both compounds with the crystal structure of ALKBH5 (PDB ID: 4NRO) were comparable with these observations pertaining to the interaction of the 2OG catalytic site in this enzyme kinetics. Furthermore, either knockdown of ALKBH5 or inhibition with Ena15 or Ena21 inhibited cell proliferation of glioblastoma multiforme-derived cell lines, decreased cell population in the synthesis phase of the cell cycle, increased m6 A RNA level, and stabilized FOXM1 mRNA. Based on these results, Ena15 and Ena21 were found to be potential candidates that might help in further research into the biological function of ALKBH5.


Coincidence of a myeloproliferative and a lymphoproliferative disorder--a random event?
A patient with coinciding polycythemia vera and chronic lymphocytic leukemia is reported. Based on a literature review and vital statistics it is concluded that the coincidence is probably fortuitous.


Exposure to airborne polychlorinated biphenyls and type 2 diabetes in a Danish cohort.
Previous research indicates an association between higher-chlorinated polychlorinated biphenyls (PCBs) and type 2 diabetes (T2D). However, less is known about the extent to which PCB exposure in indoor air, composed primarily of lower-chlorinated PCBs, affects T2D risk. We assessed the association between indoor air exposure to PCBs in residential buildings and T2D incidence. The register-based 'Health Effects of PCBs in Indoor Air' (HESPAIR) cohort comprises 51,921 Danish residents of two residential areas with apartments built with and without PCB-containing materials (reference apartments). We assessed exposure status by combining register-based information on relocation history with extrapolated values of exposure based on PCB-measurements in indoor air from subsets of the apartments. T2D cases were identified in the Danish registers during 1977-2018. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression analyses with time-varying exposure. We identified 2737 incident T2D cases during the follow-up. Exposure to ≥3300 ng/m3 PCB × year (3rd tertile of PCByear) was associated with higher risk of T2D (HR 1.15, 95% CI 1.02-1.30) compared with exposure to <300 ng/m3 PCB × year (reference). However, among individuals with lower cumulated PCByear, the risk was similar to residents with exposure <300 ng/m3 PCB × year (300-899 ng/m3 PCB × year: HR 0.98, 95% CI 0.87-1.11; 900-3299 ng/m3 PCB × year: HR 0.96, 95% CI 0.83-1.10). We observed a marginally higher risk of T2D, but there was no evidence of an exposure-response relationship. The results should be interpreted with caution until confirmed in other independent studies of PCB exposure in indoor air.


The suppression of heterotopic ossifications: radiation versus NSAID therapy--a prospective study.
This prospective, randomized study compares the effect of postoperative irradiation and nonsteroidal anti-inflammatory drug (NSAID) therapy on the prevention of heterotopic ossifications after the implantation of a total hip endoprosthesis. A total of 154 operations were performed; one group of patients underwent radiation treatment of 3 x 3.3 Gy, and the other group took 3 x 50 mg of diclofenac per day over a period of 3 weeks. Average age, sex, preoperative diagnosis, and risk factors were similar in both groups. Postoperative radiation began on average 2.9 days after operation, and the radiation therapy was finished on average within 3.8 days. NSAID prophylaxis was begun on the first postoperative day. Heterotopic ossifications occurred in two of the patients who had undergone postoperative prophylaxis by radiation. In both cases, the ossification was Brooker I, and there was no functional impairment. There were no ossifications of Brooker II-IV in this group. One patient had a Staphylococcus epidermidis infection, and fistula revision had to be carried out; the prosthesis could be left in place. In the group treated with NSAID, 16 heterotopic ossifications stage Brooker I and 2 stage Brooker II could be detected. Eleven patients stopped the treatment because of gastrointestinal problems. Both postoperative radiation and NSAID therapy have proved to be effective prophylactic methods. In direct comparison, radiation prophylaxis by 3 x 3.3 Gy proved to be slightly more successful than NSAID prophylaxis.


Stable physical activity patterns predominate in a longitudinal study of physical activity among young adults in Canada from before to during the COVID-19 pandemic.
We examined change in walking, moderate-to-vigorous physical activity (MVPA) and meeting MVPA guidelines from before to during the COVID-19 pandemic, and identified factors associated with newly meeting and no longer meeting MVPA guidelines during the pandemic. Complete data were available for 614 young adults participating in the ongoing Nicotine Dependence in Teens (NDIT) study pre-pandemically in 2010-12 and 2017-20, and during the pandemic in 2020-21. Change in physical activity was examined in four sub-groups (i.e., stable inactive, newly met MVPA guidelines, no longer met MVPA guidelines, stable active). Factors associated with newly and no longer met MVPA guidelines were identified in multivariable logistic regression. While walking and MVPA changed little from 2010-2 to 2017-20, both declined during the pandemic (median for both = -30 min/week). 63.3% of participants reported no change in meeting MVPA guidelines during the pandemic, 11.4% newly met MVPA guidelines and 25.2% no longer met MVPA guidelines. Male sex, not university-educated, amotivated to engage in physical activity reported pre-pandemic, and endorsing physical activity as a COVID-19 coping strategy were associated with newly met MVPA guidelines. Male sex, not university-educated, higher problem-focused coping scores and endorsing physical activity as a COVID-19 coping strategy were protective of no longer met MVPA guidelines. Increased understanding of why some participants increased or decreased MVPA during the pandemic is needed to inform physical activity-related policy during pandemics.


Fear of missing out predicts repeated measurements of greater negative affect using experience sampling methodology.
Fear of missing out (FOMO) has been increasingly researched recently, especially in relation to negative affectivity constructs. Our aim was to examine relations between FOMO and repeated measurements of negative affect over one week. We investigated associations between FOMO and prospectively-measured negative affect over one week in an experience sampling study of 93 undergraduate students. Participants completed an initial web survey assessing depression, anxiety and FOMO. Over the week, participants responded to daily text messages, assessing negative affect from earlier in the day. On a bivariate basis, FOMO, depression and anxiety severity were related to daily negative affect assessments. Using multivariate growth modeling, higher initial negative affect was related to decreasing negative affect over the week. Female sex and higher anxiety related to higher initial negative affect ratings. Higher FOMO levels related to increasing negative affect over the week. Findings were based on self-report methodology, using university students and only one week of measurement. Results suggest that women and more anxious individuals had higher initial negative affect, while FOMO predicted increasing negative affect over the week. Results advance understanding of FOMO in relation to psychopathology, and are discussed in the context of Self-Determination Theory.


Theoretical study of formate, tartrate, tartronate, and glycolate production from 6-carbon trioxylate intermediate in the citric acid cycle.
Reaction pathways of side products (formate, glycolate, and tartronate) from dihydroxyfumarate (DHF) were theoretically investigated as DHF is an intermediate in the process of producing tartrates and oxalate from glyoxylate of the citric acid cycle. The proposed pathways for each reaction were mapped by density functional theory (DFT) calculations. The transitions states were confirmed by analyzing the vibrational frequency and the intrinsic reaction coordinate (IRC) theory. The corresponding reaction activation energy, enthalpy change, Gibb's free energy change, and rate of reactions were calculated to get a clear picture of the whole reaction pathway. In the whole process, the decarboxylation reaction showed the highest energy barrier of 20-23 kcal/mol. Proton transfer and hydroxylation reactions were almost barrierless. As most of these reactions have very low energy barrier, our findings elucidate the high probability of those reactions under experimental conditions.


Influenza vaccination in 18 developed countries, 1980-1992.
Influenza continues to be an important cause of preventable morbidity and mortality. Although influenza vaccine is widely recommended for older high-risk individuals, no studies have compared its use in different countries. We gathered information on influenza vaccine distribution in 18 developed countries for the period 1980-1992. During the 1980s there was a > or = 10-fold difference in annual per capita vaccine distribution among these countries, and in 1992 the difference was still more than 7-fold. Several countries demonstrated large increases in vaccine use over the study period, some showing substantial increases in specific years. Thirteen of the 18 countries recommend influenza vaccination for all elderly persons and 11 countries provide reimbursement for vaccination through national or social health insurance. These countries tend to have higher levels of vaccine use. Historical, economic and political factors also affect vaccination practices and policies, but their relationships to differences in vaccine use between countries are not known. A better understanding of why the use of influenza vaccine varies among countries will be important if its protective benefits are to be fully realized.


Cholesterol heterogeneity in bovine rod outer segment disk membranes.
Rod outer segment disk membranes have been used to study visual transduction events. Numerous studies have also focused on protein-lipid interactions in these membranes. The possible heterogeneity of the disk membrane composition has not been addressed in such studies. Freeze fracture studies (Andrews, L. D., and Cohn, A. I. (1979) J. Cell Biol. 81, 215-220; Caldwell, R., and McLaughlin, B. (1985) J. Comp. Neurol. 236, 523-537) suggest a difference in cholesterol content between newly formed and old disks. This potential heterogeneity in disk membrane composition was investigated using digitonin. Osmotically intact bovine rod outer segment disk membranes prepared by Ficoll flotation were separated based on the cholesterol content of the disks. The addition of digitonin to disk membrane suspensions in a one-to-one molar ratio with respect to cholesterol produced an increase in the density of the membranes in proportion to the amount of cholesterol present. The digitonin-treated disks were separated into subpopulations using a sucrose density gradient. Disks were shown to vary in cholesterol to phospholipid ratio from 0.30 to 0.05. The ratio of phospholipid to protein remained constant in all disk subpopulations at approximately 65 phospholipids per protein. No significant change in the fatty acid composition of the disks was observed as a function of change in cholesterol content. This work demonstrates compositional heterogeneity in disk membranes which may ultimately affect function.


Transferrin receptor 1 overexpression is associated with tumour de-differentiation and acts as a potential prognostic indicator of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. An excess of iron in liver tissue causes oxidative stress, leading to hepatocellular carcinogenesis. Iron metabolism, which is regulated by a complex mechanism, is important for cancer cell survival. The aim of this study is to clarify the role of iron regulatory protein in the progression of HCC and in patient outcome. We first investigated the mRNA level of iron metabolism-related genes, including hepcidin, ferroportin 1 (FPN-1) and transferrin receptor (TFR)-1/2. TFR-1/2 protein expression was then evaluated in surgical specimens from 210 cases using immunohistochemistry, and we compared clinicopathological factors with TFR-1/2 expression. The mRNA expression levels of TFR-1 were significantly increased in HCC tissues compared with adjacent non-cancerous tissues (P = 0.0013), but there were no differences in other genes. High expression of TFR-1 in HCC was associated with the absence of alcohol abuse (P = 0.0467), liver cirrhosis (P < 0.0001), higher alpha-fetoprotein (AFP; P < 0.0001), smaller tumour size (P = 0.0022), poor histological differentiation (P < 0.0001) and morphological features (P < 0.0001). In contrast, high expression of TFR-2 in HCC was associated with lower AFP (P < 0.0001), well-differentiated histological grade (P < 0.0001) and morphological features (P = 0.0010). Multivariate analysis for both overall survival and recurrence-free survival indicated that high TFR-1 expression was a significant prognostic factor for poor outcome. We found an inverse correlation of TFR-1 and TFR-2 expression in AFP and tumour differentiation. TFR-1 overexpression suggests a higher risk of recurrence and death in HCC patients following liver resection.


Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-alpha-induced VCAM-1 expression.
Novel chalcone derivatives have been discovered as potent inhibitors of TNF-alpha-induced VCAM-1 expression. Thienyl or benzothienyl substitution at the meta-position of ring B helps boost potency while large substitution at the para-position on ring B is detrimental. Various substitutions are tolerated on ring A. A lipophilicity-potency relationship has been observed in several sub-series of compounds.


Ethical challenges in tracheostomy-assisted ventilation in amyotrophic lateral sclerosis.
The special nature of amyotrophic lateral sclerosis (ALS) and tracheostomy with invasive ventilation (TIV) leads to challenges that can be difficult in two senses: not only to handle well, but also to discuss with patients and other involved stakeholders. Because of the delicate nature of interpersonal relations and communication in ALS, some of the downsides to TIV may almost take on a nature of taboo, making them difficult to raise for open discussion. Yet these ethical challenges are important to be aware of, not only for health professionals and managers but, arguably, also for patients and next of kin. They are important also for a wider professional and societal debate about whether and to whom TIV should be offered. In this paper we highlight and examine ethical challenges in TIV for ALS, with a special emphasis on those that are hard to discuss openly and that therefore might fail to be addressed. The analysis is structured by the four core principles of healthcare ethics: beneficence, nonmaleficence, respect for patient autonomy, and justice.


Functional role of lipid metabolism in activated T-lymphocytes.
Exogenous long-chain fatty acids are readily taken up by unstimulated lymphocytes derived from the thymus of calves or rabbits and esterified to complex lipids, primarily phospholipids and triacylglycerols. Compared to saturated fatty acids, unsaturated fatty acids are incorporated preferentially. Furthermore, unsaturated fatty acids are transferred from triacylglycerols to phospholipids. The transfer cannot be observed with palmitic acid. With regard to individual phospholipid species, oleic acid and linoleic acid are found primarily in phosphatidylcholine. Arachidonic acid, however, is transferred to phosphatidylethanolamine and phosphatidylinositol as well. This suggests an arachidonic-specific transfer between individual phospholipids. Stimulation of the cells with the mitogen concanavalin A results in an enhanced incorporation of the fatty acids and an enhanced transfer from triacylglycerols to phospholipids. Triacylglycerols may thus be regarded as a labile intracellular storage pool that may be activated upon mitogenic stimulation.


Novel findings of an old algorithm: PVC response "Atrial Pace'' initiates atrial arrhythmias in Abbott ICD and CRT-D devices.
Many algorithms have been developed to ensure the safety and accuracy of cardiac implantable electric devices (CIED). A specific algorithm designed to prevent pacemaker induced tachycardia (PMT) after a premature ventricular complex (PVC response) is available in all Abbott (former St. Jude Medical) CIED. However, a few case reports suggest that this algorithm may be proarrhythmic when programmed to Atrial Pace (A-Pace on PVC). We analyzed the data of all (n = 333) Abbot implantable cardioverter defibrillator (ICD) and cardiac resynchronization defibrillator (CRT-D) devices followed remote using the Merlin.net Patient Care Network in our institute in 2020. Status of the PVC response algorithm A-Pace on PVC or Off was collected, and all atrial mode switch (AMS) episodes longer than 30 s were thoroughly evaluated. Data on clinical characteristics of the patients was collect from the electronic patient records. A total of 173 patients had A-Pace on PVC and twenty-five of them (14%) had at least one atrial high rate episode (AHRE) >30 s (AHRE) triggered by the action of this algorithm. The median PVC count was higher in patients who had algorithm triggered AHRE than in those with no algorithm-triggered AHRE (1.7% [IQR 0-3.2] vs. 0% [IQR 0-1.1], p < .0001). The major clinical characteristics were comparable in the two groups. The A-Pace on PVC setting was frequently used in our patients. Our study shows that a considerable number of patients had at least one AHRE triggered by the algorithm. The use of this algorithm should be carefully reconsidered.


Modeling of chitosan modified PLGA atorvastatin-curcumin conjugate (AT-CU) nanoparticles, overcoming the barriers associated with PLGA: An approach for better management of atherosclerosis.
Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Atorvastatin (AT) is the first line of treatment for coronary atherosclerosis; however its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin (CU) is evidenced in several crucial signaling pathways linked to lipid regulation and inflammation. To enhance the therapeutic efficacy and physical properties of AT and CU, a new conjugate derivative (AT-CU) was synthesized and assessed by in silico, in vitro characterizations, and in vivo efficacy through mice model. Although the biocompatibility and biodegradability of Polylactic-co-Glycolic Acid (PLGA) in nanoparticles are well documented, burst release is a common issue with this polymer. Hence the current work used chitosan as a drug release modifier to the PLGA nanoparticles. The chitosan-modified PLGA AT-CU nanoparticles were prepaid by single emulsion and solvent evaporation technique. With raising the concentration of chitosan the particle size grew from 139.2 nm to 197.7 nm, the zeta potential rose from -20.57 mV to 28.32 mV, and the drug encapsulation efficiency improved from 71.81% to 90.57%. At 18 h, the burst release of AT-CU from PLGA nanoparticles was seen, hitting abruptly 70.8%. For chitosan-modified PLGA nanoparticles, the burst release pattern was significantly reduced which could be due to the adsorption of the drug on the surface of chitosan. The efficiency of the ideal formulation i.e F4 (chitosan/PLGA = 0.4) in treating atherosclerosis was further strongly evidenced by in vivo investigation.


Transient global amnesia associated with accidental high-frequency stimulation of the right hippocampus in deep brain stimulation for segmental dystonia.
We report on a 66-year-old woman with segmental dystonia treated with chronic bilateral deep brain stimulation of the globus pallidus internus, in whom accidental high-voltage, high-frequency stimulation induced an episode of transient global amnesia (TGA) via an electrode contact which was misplaced in the right hippocampus. A possible mechanism underlying this TGA episode may have been the inhibition of local neuronal activity or fiber activation by high current density via direct electrical stimulation of hippocampal structures. While a unifying etiology of TGA has not been proven so far, our case demonstrates a possible link between focal electrical stimulation of hippocampal structures and the full clinical picture of the syndrome.


CORRELATION OF CHOROIDAL THICKNESS AND BODY MASS INDEX.
To evaluate the possible changes in the microvascular structure of the choroid by measuring choroidal thickness (CT) in four different body mass index (BMI) groups of healthy individuals. One hundred and sixty eyes of 160 healthy individuals (70 females and 90 males) were included in this cross-sectional study. Healthy individuals were divided into 4 groups according to their BMIs. Cases with BMI ≤ 18.50 formed Group 1, cases with BMI between 18.50 and 24.99 formed Group 2, cases with BMI between 25.00 and 29.99 formed Group 3, and cases with BMI between 30.00 and 34.99 formed Group 4. The CT was measured by the enhanced depth imaging technique of the spectral domain optical coherence tomography. The CT was measured at subfoveal area and at 500-μm intervals to the nasal and temporal to the fovea up to 2,000 μm. The measurements were then statistically compared among the four groups. The mean ages were 26.5 ± 6.9 years (range: 18-39 years) in Group 1, 27.2 ± 5.0 (range: 21-38 years) in Group 2, 28.5 ± 5.9 (range: 20-40 years) in Group 3, and 29.25 ± 5.6 (range: 20-40 years) in Group 4. The mean subfoveal CT (in micrometers) was 378 ± 86 (range: 189-563) in Group 1, 384 ± 102 (range: 225-643) in Group 2, 314 ± 66 (range: 160-455) in Group 3, and 317 ± 63 (range: 220-411) in Group 4. There was a statistically significant difference among the 4 groups in regard to CT in all locations (P < 0.05). We have demonstrated that BMI may have an influence on the CT of healthy persons. Individuals in both Group 3 and Group 4 have thinner choroids than the individuals in both Group 1 and Group 2.


Bovine oviductal epithelial cells: their cell culture and applications in studies for reproductive biology.
Epithelial cells of the mammalian oviduct play an important role in reproductive and developmental events that occur there. Oviductal epithelial cells from several mammalian species can be isolated and cultured in serum or serum-free medium in vitro and cell culture of bovine oviductal epithelial cells (BOEC) has been described by many investigators. Cultured BOEC show a wide variety of secretory activities and these secretory factors may influence early embryonic development or sperm function. Monolayer cultures of BOEC have been widely used for in vitro co-culture of bovine preimplantation embryos. The use of BOEC co-culture systems has improved embryonic development in nearly all the studies conducted. In addition, interaction of bovine spermatozoa with BOEC, in a similar manner to that observed for spermatozoa in vivo, induced specific changes in sperm capacitation and consequently improved the fertilizing capacity of bovine spermatozoa in vitro. Thus co-culture systems with BOEC may not only offer an excellent model for studying the mechanisms of capacitation and acrosome reaction of bovine spermatozoa but also provide a useful tool for the improvement of embryo development in vitro.


Recurrence of primary hyperparathyroidism following spontaneous remission with intracapsular hemorrhage of a parathyroid adenoma.
A few patients with primary hyperparathyroidism (PHPT) have a chance of spontaneous remission by either infarction of or hemorrhage into or around the parathyroid adenoma. In most cases, biochemical derangements associated with PHPT are permanently improved after spontaneous remission. Here we report a case with a recurrence of PHPT 4 months after spontaneous remission with acute intracapsular hemorrhage of parathyroid adenoma. In the literature, only two cases have been reported to have experienced a recurrence of clinical features of PHPT after infarction but not hemorrhage of parathyroid adenomas. Thus, the spontaneous remission of biological derangements in PHPT upon hemorrhage or infarction of parathyroid adenoma could be temporary. One should carefully observe such patients thereafter.


Development and early diagnosis of critical illness myopathy in COVID-19 associated acute respiratory distress syndrome.
The COVID-19 pandemic has greatly increased the incidence and clinical importance of critical illness myopathy (CIM), because it is one of the most common complications of modern intensive care medicine. Current diagnostic criteria only allow diagnosis of CIM at an advanced stage, so that patients are at risk of being overlooked, especially in early stages. To determine the frequency of CIM and to assess a recently proposed tool for early diagnosis, we have followed a cohort of COVID-19 patients with acute respiratory distress syndrome and compared the time course of muscle excitability measurements with the definite diagnosis of CIM. Adult COVID-19 patients admitted to the Intensive Care Unit of the University Hospital Bern, Switzerland requiring mechanical ventilation were recruited and examined on Days 1, 2, 5, and 10 post-intubation. Clinical examination, muscle excitability measurements, medication record, and laboratory analyses were performed on all study visits, and additionally nerve conduction studies, electromyography and muscle biopsy on Day 10. Muscle excitability data were compared with a cohort of 31 age-matched healthy subjects. Diagnosis of definite CIM was made according to the current guidelines and was based on patient history, results of clinical and electrophysiological examinations as well as muscle biopsy. Complete data were available in 31 out of 44 recruited patients (mean [SD] age, 62.4 [9.8] years). Of these, 17 (55%) developed CIM. Muscle excitability measurements on Day 10 discriminated between patients who developed CIM and those who did not, with a diagnostic precision of 90% (AUC 0.908; 95% CI 0.799-1.000; sensitivity 1.000; specificity 0.714). On Days 1 and 2, muscle excitability parameters also discriminated between the two groups with 73% (AUC 0.734; 95% CI 0.550-0.919; sensitivity 0.562; specificity 0.857) and 82% (AUC 0.820; CI 0.652-0.903; sensitivity 0.750; specificity 0.923) diagnostic precision, respectively. All critically ill COVID-19 patients showed signs of muscle membrane depolarization compared with healthy subjects, but in patients who developed CIM muscle membrane depolarization on Days 1, 2 and 10 was more pronounced than in patients who did not develop CIM. This study reports a 55% prevalence of definite CIM in critically ill COVID-19 patients. Furthermore, the results confirm that muscle excitability measurements may serve as an alternative method for CIM diagnosis and support its use as a tool for early diagnosis and monitoring the development of CIM.


Tongqiao Huoxue Decoction ameliorates traumatic brain injury-induced gastrointestinal dysfunction by regulating CD36/15-LO/NR4A1 signaling, which fails when CD36 and CX3CR1 are deficient.
Gastrointestinal (GI) dysfunction, as a common peripheral-organ complication after traumatic brain injury (TBI), is primarily characterized by gut inflammation and damage to the intestinal mucosal barrier (IMB). Previous studies have confirmed that TongQiao HuoXue Decoction (TQHXD) has strong anti-inflammatory properties and protects against gut injury. However, few have reported on the therapeutic effects of TQHXD in a TBI-induced GI dysfunction model. We aimed to explore the effects of TQHXD on TBI-induced GI dysfunction and the underlying mechanism thereof. We assessed the protective effects and possible mechanism of TQHXD in treating TBI-induced GI dysfunction via gene engineering, histological staining, immunofluorescence (IF), 16S ribosomal ribonucleic acid (rRNA) sequencing, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and flow cytometry (FCM). TQHXD administration ameliorated TBI-induced GI dysfunction by modulating the abundance and structure of bacteria; reconstructing the destroyed epithelial and chemical barriers of the IMB; and improving M1/M2 macrophage, T-regulatory cell (Treg)/T helper 1 cell (Th1 ), as well as Th17 /Treg ratios to preserve homeostasis of the intestinal immune barrier. Notably, Cluster of Differentiation 36 (CD36)/15-lipoxygenase (15-LO)/nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling was markedly stimulated in colonic tissue of TQHXD-treated mice. However, insufficiency of both CD36 and (C-X3-C motif) chemokine receptor 1 (CX3CR1) worsened GI dysfunction induced by TBI, which could not be rescued by TQHXD. TQHXD exerted therapeutic effects on TBI-induced GI dysfunction by regulating the intestinal biological, chemical, epithelial, and immune barriers of the IMB, and this effect resulted from the stimulation of CD36/NR4A1/15-LO signaling; however, it could not do so when CX3CR1 and CD36 were deficient. TQHXD might therefore be a potential drug candidate for treating TBI-induced GI dysfunction.


Visible characteristics and structural modifications relating to enlarged facial pores.
Many factors relate to enlargement and visibility of facial pores. However, how enlargement relates to modification of the skin structure is still poorly analysed. Therefore, our aim was to characterise the visible features and the micro-environment of facial pores. We recruited 160 women, half of them with normal-size facial pores, the other half presenting enlarged pores. We analysed their right cheek using standardised photography, in vivo reflectance microscopy and optical coherence tomography. If the area of pores is indeed the most differentiating visible characteristic, enlarged facial pores are also denser and more contrasted. At the structural level, enlarged facial pores present a more regular organisation of keratinocytes, an irregular dermo-epidermal junction and a higher attenuation of collagen between the surface and deeper layers. Still, the most relevant alterations of enlarged facial pores are the presence of bright tubular structures surrounding hair follicles and enlarged hair shafts. These observations suggest that alterations of the stroma could result in altered skin tensions, leading to the dilation of the infundibulum and enlarged hair shaft. The modified tension would also explain the more regular organisation of the keratinocytes and the irregular dermo-epidermal junction.


Incidence of arrhythmias after thoracic surgery: thoracotomy versus video-assisted thoracoscopy.
Atrial arrhythmias, especially supraventricular tachycardia (SVT) and atrial fibrillation, are common after thoracotomy and lung surgery. There are few existing data on the incidence of postoperative arrhythmias after video-assisted thoracoscopy (VAT). The purpose of the present investigation was to retrospectively determine the incidence of postoperative arrhythmias in patients who underwent VAT compared with those who underwent thoracotomy, and which factors are associated with an increased risk for arrhythmias in both groups. A retrospective investigation. A metropolitan university hospital. The medical records of 124 patients who underwent thoracotomy and 81 patients who underwent VAT over a 2-year period were reviewed. There was a 17% incidence of atrial arrhythmias after thoracotomy and 10% after VAT, but the difference was not statistically significant. In both groups, atrial fibrillation was the most common atrial arrhythmia. Patients receiving digoxin were at higher risk for postoperative arrhythmias. Patients older than 65 years were at risk for arrhythmias after thoracotomy and patients older than 80 years were at risk for arrhythmias after VAT. Patients who had postoperative arrhythmias had prolonged hospital stays compared with patients who did not have arrhythmias.


Novel effects of edaravone on human brain microvascular endothelial cells revealed by a proteomic approach.
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger used for acute ischemic stroke. However, it is not known whether edaravone works only as a free radical scavenger or possess other pharmacological actions. Therefore, we elucidated the effects of edaravone on human brain microvascular endothelial cells (HBMECs) by 2 dimensional fluorescence difference gel electrophoresis (2D-DIGE). We found 38 protein spots the intensity of which was significantly altered 1.3 fold on average (p< 0.05) by the edaravone treatment and successfully identified 17 proteins of those. Four of those 17 proteins were cytoskeleton proteins or cytoskeleton-regulating proteins. Therefore, we subsequently investigated the change of size and shape of the cells, the actin network, and the tight junction of HBMEC by immunocytochemistry. As a result, most edaravone-treated HBMECs became larger and rounder compared with those that were not treated. Furthermore, edaravone-treated HBMECs formed gathering zona occludens (ZO)-1, a tight junction protein, along the junction of the cells. In addition, we found that edaravone suppressed interleukin (IL)-1β-induced secretion of monocyte chemoattractant protein-1 (MCP-1), which was reported to increase cell permeability. We found a novel function of edaravone is the promotion of tight junction formations of vascular endothelial cells partly via the down-regulation of MCP-1 secretion. These data provide fundamental and useful information in the clinical use of edaravone in patients with cerebral vascular diseases.


Nonenzymatic all-solid-state coated wire electrode for acetylcholine determination in vitro.
A nonenzymatic all-solid-state coated wire acetylcholine electrode was investigated. Poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT/PSS) as conducting polymer was coated on one end of a gold wire (0.5mm in diameter). The acetylcholine selective membrane containing heptakis(2,3,6-tri-Ο-methyl)-β-cyclodextrin as an ionophore covered the conducting polymer layer. The electrode could work stably in a pH range of 6.5-8.5 and a temperature range of 15-40°C. It covered an acetylcholine concentration range of 10(-5)-10(-1)M with a slope of 54.04±1.70mV/decade, while detection limit was 5.69±1.06µM. The selectivity, dynamic response, reproducibility and stability were evaluated. The electrode could work properly in the rat brain homogenate to detect different concentrations of acetylcholine.


Fracture toughness enhancement of h-BN monolayers via hydrogen passivation of a crack edge.
Molecular dynamics-based simulations were performed in conjunction with reactive force-field potential parameters to investigate the effect of crack-edge passivation via hydrogenation on the fracture properties of h-BN nanosheets. In semi-hydrogenated (H is attached to either B or N) and fully hydrogenated (H is attached to both B and N) crack-edge atoms, three hybridisation states-sp2, sp3 and sp2 + sp3-were considered in the simulations. Significant improvement in the fracture toughness of h-BN nanosheets was predicted with semi- and fully hydrogenated crack-edge atoms. An overall improvement in fracture toughness of h-BN in the range of 16%-23% was estimated with the sp3 or sp2 + sp3 hybridisation state of crack-edge atoms. This significant shift in the fracture toughness of h-BN nanosheets was attributed to lowered crack-edge energy, a stress-relieving mechanism and blunting of the crack tip. Semi-hydrogenated crack-edge atoms with hydrogen attached only to N atoms have shown a negative response in terms of fracture toughness.


Facile synthesis and electrochemical properties of a novel Ni-B/TiC composite coating via ultrasonic-assisted electrodeposition.
A novel Ni-B/TiC composite coating was synthesized by ultrasonic-assisted direct current electrodeposition. Ultrasonic technology was adopted to prevent the agglomeration of nanoparticle, improve the structure and corrosion resistance, using an ultrasonic bath at frequency 40 KHz and acoustic power 300 W. The influences of current density and deposition time on its structure and electrochemical behaviors were studied. Under ultrasonic dispersion, the composite coatings are smooth, compact with protrusion structure sparsely distributed on it. The average roughness (Sa) was about 13.6-26.1 nm. The crystallite size is 10-21 nm. The preferred orientation is Ni (1 1 1) texture. EIS results indicated that the corrosion resistance was greatly improved by ultrasonic-assisted method. The corrosion mechanism is consistent with one-time constant EEC model of Rs(CPEdlRct). With the increase of immersion time, the Rct of the composite coating often first increased and then decreased. Under ultrasonic, current density 2 A dm-2 and deposition time 20 min were the appropriate parameters for the optimal corrosion resistance and excellent long-term electrochemical stability in 3.5 wt% NaCl corrosive solution. This coating shows good application prospect for corrosion protection in aggressive environment.


Increased Expression of Laminin Subunit Alpha 1 Chain by dCas9-VP160.
Laminin-111 protein complex links the extracellular matrix to integrin α7β1 in sarcolemma, thus replacing in dystrophic muscles links normally insured by the dystrophin complex. Laminin-111 injection in mdx mouse stabilized sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscles from exercised-induced damages. These results suggested that increased laminin-111 is a potential therapy for DMD. Laminin subunit beta 1 and laminin subunit gamma 1 are expressed in adult human muscle, but laminin subunit alpha 1 (LAMA1) gene is expressed only during embryogenesis. We thus developed an alternative method to laminin-111 protein repeated administration by inducing expression of the endogenous mouse Lama1 gene. This was done with the CRSPR/Cas9 system, i.e., by targeting the Lama1 promoter with one or several gRNAs and a dCas9 coupled with the VP160 transcription activation domain. Lama1 mRNA (qRT-PCR) and proteins (immunohistochemistry and western blot) were not detected in the control C2C12 myoblasts and in control muscles. However, significant expression was observed in cells transfected and in mouse muscles electroporated with plasmids coding for dCas9-VP160 and a gRNA. Larger synergic increases were observed by using two or three gRNAs. The increased Lama1 expression did not modify the expression of the α7 and β1 integrins. Increased expression of Lama1 by the CRISPR/Cas9 system will have to be further investigated by systemic delivery of the CRISPR/Cas9 components to verify whether this could be a treatment for several myopathies.


The subcellular distribution of myeloid-related protein 8 (MRP8) and MRP14 in human neutrophils.
Myeloid-related protein 8 (MRP8) and MRP14 are S100 family calcium binding proteins that form a heterodimer known as calprotectin or MRP8/14 that is present in the cytosol of neutrophils and monocytes. MRP8/14 becomes associated with endothelium at sites of monocyte and neutrophil adhesion and transmigration and induces a thrombogenic and inflammatory response by increasing the endothelial transcription of proinflammatory chemokines and adhesion molecules. The distribution of MRP8/MRP14 among neutrophil granules and plasma membranes is unclear and was investigated to better understand the role of this molecule in acute inflammation. Three monoclonal antibodies specific for MRP8 and MRP14 were characterized and used in immunoblotting assays of neutrophil whole cell extracts, and isolated plasma membranes, primary granules, secondary granules and cytosol. MRP8 and MRP14 were detected in neutrophil cytosol, plasma membrane, primary granule and secondary granule fractions. MRP8/14 demonstrated a calcium-dependent adherence to plasma membranes and primary granules and could be removed by washing with EGTA in a high ionic strength buffer. In contrast, MRP8/14 was found within the contents of the secondary granules. Activated neutrophils released secondary granules and MRP8/14. MRP8/14 is located in neutrophil cytosol and secondary granule fractions and is loosely associated with plasma membranes. MRP8/14 released with secondary granules by activated neutrophils likely binds to endothelium and plays an important role in acute inflammation.


Electroencephalographic and radionuclide studies in dialysis dementia.
Six maintenance hemodialysis patients with dialysis dementia (severe mental deterioration, speech disturbances, apraxia, facial grimacing, and myoclonus) were studied. They were matched with respect to age, duration of dialysis, and underlying renal disease with six patients who had no dementia and who acted as controls for the electroencephalographic (EEC) studies. The dementia patients had marked slowing of the EEG rhythm to 5--7 Hz with high voltage biphasic or triphasic spikes, and were clearly separated by frequency distribution analysis from the controls. Radio-iodinated serum albumin (RISA) cisternography in dementia patients demonstrated ventricular reflux, prolonged stasis, late appearance of the parasagittal strip, and persistence of RISA for up to 72--96 hr, which suggest an alteration in cerebrospinal fluid (CSF) dynamics.


Real-World Evidence of Improved Glycemic Control in People with Diabetes Using a Bluetooth-Connected Blood Glucose Meter with a Mobile Diabetes Management App.
Background: The OneTouch Verio Reflect (OTVR) meter provides ColorSure Dynamic Range Indicator (DCRI) and Blood Sugar Mentor (BSM) features that are complemented by the OneTouch Reveal (OTR) mobile app. We sought to provide real-world evidence that these products support improved glycemic control. Methods: Anonymised glucose and app analytics were extracted from the LifeScan server for 4154 people with type 1 diabetes (PwT1D) and 13,623 people with type 2 diabetes (PwT2D). Data from their first 14 days were compared with the 14 days before the 90-day time point using paired within-subject differences. Results: Percentage glucose readings in range (RIR) 70-180 mg/dL improved by +8.1% (from 58% to 66.1%) in PwT1D and by +11.2% (from 72.4% to 83.6%) in PwT2D. Hyperglycemic readings (>180 mg/dL) reduced by -8.5% (from 37.1% to 28.6%) in PwT1D and by -11.3% (from 26.4% to 15.1%) in PwT2D. Mean glucose reduced on average by -14.5 mg/dL (from 174.8 to 160.2 mg/dL) in PwT1D and -18.2 mg/dL (from 157.8 to 139.6 mg/dL) in PwT2D. Glycemic improvement was strongly associated with OTR app engagement. Two to three sessions or 11 to 20 min/week in the app improved readings in range in PwT1D by +7.0% or +8.4%, respectively. Similar engagement trends for glycemic improvement were observed in PwT2D. Proportions of subjects achieving a 5% or 10% improvement in RIR were 46.9%/36.6% for PwT1D and 48.7%/37.7% for PwT2D. Conclusions: Real-world data from over 17,000 people with diabetes (PWDs) demonstrated significantly improved readings in range and reduced the burden of hyperglycemia in PWDs using the OTVR meter and OTR app.


Estradiol measurement after GnRH-stimulation as a method to diagnose the presence of ovaries in the female domestic cat.
There is currently no method to reliably diagnose the presence of ovarian tissue in inactive intact female cats except laparatomy which is an invasive procedure. All available tests require that the queen is in estrus. Obvious overt symptoms of estrus are, however, not always observed and some queens may have only 2 estrus periods/year. Therefore this study was designed to evaluate if it is possible to diagnose the presence of ovarian tissue by measurement of estradiol before and/or after stimulation with a GnRH-analogue. Twenty-two female cats were divided into two groups; 11 females that were known to have been ovariectomized and 11 females that were known to be intact. From each cat a heparinised blood sample was collected from the cephalic vein for resting estradiol and progesterone measurements. All cats were treated with a GnRH-analogue buserelin (Receptal, 0.4microg/kg im). Two hours later a second blood sample was collected. Median estradiol increased after stimulation with buserelin in intact but not in ovariectomized females (11 range 5-21 vs. 20 range 12-41, P=0.004 and 6 range 4-9 vs. 6 range 5-9 P=0.8) and did not overlap between the two groups. The highest estradiol concentration post-GnRH in the ovariectomized group was 9pmol/L while the lowest in the intact group was 12pmol/L. Progesterone was basal in all cats except one both before and after GnRH-stimulation. In conclusion this study demonstrates that measurement of estradiol concentration in plasma 2h after stimulation with a GnRH-analogue seems to be a reliable method to diagnose the presence of ovarian tissue in the female cat.


Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome.
Fragile X syndrome (FXS) is a leading cause of inherited mental retardation. In the vast majority of cases, this X-linked disorder is due to a CGG expansion in the 5' untranslated region of the fmr-1 gene and the resulting decreased expression of its associated protein, FMRP. FXS is characterized by a number of cognitive, behavioral, anatomical, and biological abnormalities. FXS provides a unique opportunity to study the consequence of mutation in a single gene on the development and proper functioning of the CNS. The current focus on the role of FMRP in neuronal maturation makes it timely to assemble the extant information on how reduced expression of the fmr-1 gene leads to neuronal dysmorphology. The purpose of this review is to summarize recent genetic, neuroanatomical, and behavioral studies of fragile X syndrome and to offer potential mechanisms to account for the pleiotropic phenotype of this disorder.


Evaluating publication bias for clinical trials supporting new dermatologic drug approvals from 2003 to 2018.
The degree of publication bias and impact of the Food and Drug Administration Amendments Act (FDAAA) of 2007, which aimed to improve clinical trial transparency, has yet to be examined for recent dermatologic drugs. The objective of our study was to estimate the degree of publication bias for clinical trials supporting FDA approval of new dermatologic drugs. This retrospective cohort study examined all phase II and III efficacy trials supporting approval of new dermatologic drugs from 2003 to 2018. FDA drug approval documents were reviewed for supportive clinical trial information, and publications were matched using PubMed and Google Scholar searches. Ratios of relative risks (RRR) comparing positive versus non-positive trials before and after FDAAA enactment served to estimate publication bias. We found that the likelihood of publishing positive versus non-positive drug trials in dermatology was unchanged before and after FDAAA enactment (RRR 0.87, 95% CI 0.37-2.08), as was the likelihood of publishing without misleading interpretation (RRR 1.51, 95% CI 0.22-10.50). There was no measurable publication bias for efficacy trials supporting new drug approvals in dermatology over the past 15 years. Fewer pre-FDAAA trials (n = 21) compared to post-FDAAA trials (n = 106) met inclusion criteria. Though not analyzed in this study, safety and secondary efficacy results are other potential sources for publication bias.


Human-Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons and Glia for the Elucidation of Pathogenic Mechanisms in Alzheimer's Disease.
Alzheimer's disease (AD) is a common neurodegenerative disorder and a mechanistically complex disease. For the last decade, human models of AD using induced pluripotent stem cells (iPSCs) have emerged as a powerful way to understand disease pathogenesis in relevant human cell types. In this review, we summarize the state of the field and how this technology can apply to studies of both familial and sporadic studies of AD. We discuss patient-derived iPSCs, genome editing, differentiation of neural cell types, and three-dimensional organoids, and speculate on the future of this type of work for increasing our understanding of, and improving therapeutic development for, this devastating disease.


Vitamin D and Other Risk Factors among Stroke Patients.
Stroke is common neurological problems in Nepal. The common risk factors for stroke are age, hypertension, diabetes, dyslipidemia and atrial fibrillation. Vitamin D is an emerging risk factors for cardio-cerebrovascular disease. This study is to find out Vitamin D and risk factors in stroke patient in Nepalese population. We reviewed the record of 281 stroke patients, admitted to Neurology ward of College of Medical Sciences, Bharatpur, Nepal from 1st January to 31st December 2013. The records were analyzed on the basis of age, sex, hypertension (HTN), body mass index (BMI), smoking habits, hemoglobin(Hb), diabetes mellitus(DM), Lipid profile, Atrial fibrillation(AF) and vascular territory with clinical and radiological evidences. The vitamin D analysis was done all stroke patients. Total patient were 281, with male 161 and age range from 18 - 87. Ischemic stroke was noted in 86.8% and hemorrhagic stroke was noted in 13.2% of patients. Middle cerebral artery (MCA) ischemia was noted in 51.5% of patients and anterior cerebral artery (ACA) ischemia was noted in 3% of patients. Multiple infarcts were noted in 12.90% of patients. About half of them were smoker, hypertension 47.40%, Diabetes mellitus 24.20% and 14.1% had atrial fibrillation. 174 (61.92%) of the stroke had less than sufficient Vitamin D. The common risk factors for stroke patients like smoking, hypertension, diabetes mellitus and atrial fibrillations are present in Nepalese population. The level of vitamin D was also low in stroke patients.


Persistence of FoxJ1+ Pax6+ Sox2+ ependymal cells throughout life in the human spinal cord.
Ependymal cells lining the central canal of the spinal cord play a crucial role in providing a physical barrier and in the circulation of cerebrospinal fluid. These cells express the FOXJ1 and SOX2 transcription factors in mice and are derived from various neural tube populations, including embryonic roof and floor plate cells. They exhibit a dorsal-ventral expression pattern of spinal cord developmental transcription factors (such as MSX1, PAX6, ARX, and FOXA2), resembling an embryonic-like organization. Although this ependymal region is present in young humans, it appears to be lost with age. To re-examine this issue, we collected 17 fresh spinal cords from organ donors aged 37-83 years and performed immunohistochemistry on lightly fixed tissues. We observed cells expressing FOXJ1 in the central region in all cases, which co-expressed SOX2 and PAX6 as well as RFX2 and ARL13B, two proteins involved in ciliogenesis and cilia-mediated sonic hedgehog signaling, respectively. Half of the cases exhibited a lumen and some presented portions of the spinal cord with closed and open central canals. Co-staining of FOXJ1 with other neurodevelopmental transcription factors (ARX, FOXA2, MSX1) and NESTIN revealed heterogeneity of the ependymal cells. Interestingly, three donors aged > 75 years exhibited a fetal-like regionalization of neurodevelopmental transcription factors, with dorsal and ventral ependymal cells expressing MSX1, ARX, and FOXA2. These results provide new evidence for the persistence of ependymal cells expressing neurodevelopmental genes throughout human life and highlight the importance of further investigation of these cells.


Patients with mental illness as victims of homicide: a national consecutive case series.
The media attention received by homicides committed by patients with mental illness is thought to increase stigma. However, people with mental illness can also be victims of violence. We aimed to assess how often victims of homicide are current mental health patients and their relationship to the perpetrators. In a national consecutive case-series study, we obtained data for victims and perpetrators of all confirmed homicides between Jan 1, 2003, and Dec 31, 2005, in England and Wales. We requested information about contact with mental health services in the 12 months before the homicide for all victims and perpetrators. For victims and perpetrators who had contact with mental health services in the 12 months before homicide, we sent questionnaires to the clinician responsible for the patient's care. 1496 victims of confirmed homicide died between Jan 1, 2003, and Dec 31, 2005, in England and Wales. Patients with mental illness were more likely to die by homicide than were people in the general population (incidence rate ratio 2·6, 95% CI 1·9-3·4). 90 homicide victims (6%) had contact with mental health services in the 12 months before their death. 213 patients with mental illness were convicted of homicide in the same 3 year period. 29 of 90 patient victims were killed by another patient with mental illness. In 23 of these 29 cases, the victim and perpetrator were known to each other, and in 21 of these cases, the victims and perpetrators were undergoing treatment at the same National Health Service Trust. In these 29 cases in which patient victims were killed by another patient with mental illness, alcohol and drug misuse (19 victims [66%], 27 perpetrators [93%]) and previous violence (7 victims [24%], 7 perpetrators [24%]) were common in both victims and, particularly, perpetrators. In seven of the 29 cases in which the victim was killed by another patient with mental illness, both victim and perpetrator were diagnosed with schizophrenia. The high risk of patients with mental illness being victims of homicide is an important antistigma message, although this risk partly comes from other patients with mental illness; overall, the risk of patients committing homicide is greater than the risk of being a victim of homicide. Identification and safeguarding of patients at risk of violence should be prominent in clinical risk assessment. Healthcare Quality Improvement Partnership.


Stress peptide PACAP stimulates and stabilizes neonatal breathing through distinct mechanisms.
Pituitary adenylate cyclase-activating peptide (PACAP) is an important mediator of the stress response and is crucial in maintaining breathing in neonates. Here we investigate the role of exogenously applied PACAP in neonatal breathing using the neonatal rat in situ working heart-brainstem preparation. A 1-min bolus of 250 nM PACAP-38 caused an increased in respiratory frequency that was rapid and transient, but had no effect on neural tidal volume or neural minute ventilation. Denervation of the carotid body abolished this effect. PACAP had a persistent effect on breathing stability in both carotid body-intact and -denervated preparations, as shown by decreases in respiratory variability 5 min following application. These data suggest that PACAP released during stress acts via carotid body dependent and independent mechanisms to stimulate and stabilize breathing. These mechanisms may account for PACAP's critical role in defending neonatal breathing against environmental stress.


Activation of Lyt-2+ T cells by antibodies towards brain-associated antigens. II. Antibody-dependent induction of "nonspecific" cell-mediated cytotoxicity.
Purified IgG from a rabbit anti-mouse brain antiserum (RaMB), previously shown to activate most Lyt-2+ T cells, was probed for lectin-like effects on cell-mediated cytolysis (CML) and found to induce "nonspecific" killing of syngeneic B cell targets by allospecific cytotoxic T lymphocytes (CTL) as effectively as concanavalin A, and at levels comparable to antigen-specific cytolysis of target cells. Interestingly, RaMB-mediated "nonspecific" CML of syngeneic targets, by polyclonally or specifically activated CTL, was restricted to B cell targets and cold target inhibition experiments indicated that syngeneic target cell blasts do not functionally interact with effector CTL in the presence of RaMB. The role of target cell Fc receptors was demonstrated by the competitive inhibition of RaMB-dependent CML by normal rabbit IgG. We conclude that RaMB both activates and bridges the effector CTL to target cells, RaMB-mediated "nonspecific" CML being a similar phenomenon to lectin-facilitated "nonspecific" cytolysis, and the mirror image of classical ADCC. These observations allowed us to interpret the effects of RaMB on allo-major histocompatibility complex-specific CML. Since RaMB stimulates specific CML of B cell targets while selectively blocking that of T cell targets, we conclude that RaMB antibodies interact with structures associated with the CTL antigen receptor, explaining the contradictory effects previously reported with monoclonal antibodies against the CTL receptor complex, which can both stimulate and inhibit T cell functions.


Report of the incidence of implant insert fracture and repair of Core-Vent dental implants.
This is a report of the fracture of Core-Vent 2.0-mm-O.D. cementable abutments. A technique for removal and replacement of these inserts is described, which enables the clinician to retain the original mesostructure bar.


The animal specimens of terrestrial and limnetic ecosystems in the environmental specimen banking programme of Germany.
In the terrestrial and limnetic sampling areas of the Environmental Specimen Banking Programme of Germany five animal species were collected. The goal of this paper is to show first the concept and criteria of the specimen selection for Environmental Specimen Banking with regard to the function of the specimens in the concept of ESB which refers to the role of the species in the trophic levels of the different ecosystems. Secondly, the substantial parts of the sampling operation procedures like the sampling design and the procedure of sampling are shown for five animal specimens.


Effect of ovary preservation period on recovery rate and categories of dromedary camel oocytes.
The aim of this study was to evaluate the effect of different periods of ovary preservation at 25-30 °C for 5, 6, 7, 9, 12 and 24 h on recovery rate and oocyte categories of dromedary camel oocytes. Camel ovaries were collected from El-Bassatein slaughterhouse, Cairo. The collected ovaries were placed immediately after slaughtering into thermos in saline solution (0.9% NaCl) supplemented with antibiotics (100 IU penicillin and 100 μg streptomycin/ml) at 25-30 °C and transported to the laboratory within 4-5 h. Ovaries were washed three times with warmed (30 °C) phosphate buffer solution (PBS) and one time with ethanol (70%). All visible follicles on the ovarian surface (2-8 mm in diameter) were counted. Oocytes were aspirated using a 20-gauge hypodermic needle. Oocyte yield was recorded and the number of oocytes/ovary was calculated. Oocytes were classified into five categories (compact, partial denuded, denuded, shrunken and cleaved oocytes). Results show that average number of follicles on each ovary was not significantly affected by preservation period, although tended to reduce only after 5 h of ovary preservation. However, this number was insignificantly reduced by increasing period of ovary preservation more than 5 up to 24 h. Average number of oocytes on each ovary was significantly (P < 0.05) reduced only between 5 and 6 h of ovary preservation. Average number of oocytes showed higher reduction rate between 5 and 6 h from 12.4 to 9.3/ovary as well as between 9 and 12 h. Oocyte recovery rate showed insignificant decrease from 88.1% at 5 h to 78.6% at 9 h of preservation. However, it showed significant (P < 0.05) reduction to 62.0% between 9 and 12 h, then insignificantly decreased to 58.6 at 24 h of preservation of the ovaries. Frequency distribution and recovery rate of each category was the highest for compact oocytes and the lowest for cleaved oocytes at all periods of preservation. Increasing preservation period significantly (P < 0.05) decreased frequency distribution of compact and cleaved oocytes, while increased frequency distribution of partial denuded, denude and shrunken oocytes. It might be concluded from the present results that the preservation of dromedary camel ovaries at 25-30 °C for 5-6 h was effective for maintaining the oocytes quality and recovery rate compared with the other preservation periods.


Exploring the key communicator role of exosomes in cancer microenvironment through proteomics.
There have been many attempts to fully understand the mechanism of cancer behavior. Yet, how cancers develop and metastasize still remain elusive. Emerging concepts of cancer biology in recent years have focused on the communication of cancer with its microenvironment, since cancer cannot grow and live alone. Cancer needs to communicate with other cells for survival, and thus they secrete various messengers, including exosomes that contain many proteins, miRNAs, mRNAs, etc., for construction of the tumor microenvironment. Moreover, these intercellular communications between cancer and its microenvironment, including stromal cells or distant cells, can promote tumor growth, metastasis, and escape from immune surveillance. In this review, we summarized the role of proteins in the exosome as communicators between cancer and its microenvironment. Consequently, we present cancer specific exosome proteins and their unique roles in the interaction between cancer and its microenvironment. Clinically, these exosomes might provide useful biomarkers for cancer diagnosis and therapeutic tools for cancer treatment.


Advances in cancer tissue microarray technology: Towards improved understanding and diagnostics.
Over the past few years, tissue microarray (TMA) technology has been established as a standard method for assessing the expression of proteins or genes across large sets of tissue specimens. It is being adopted increasingly among leading research institutions around the world and utilized in cancer research in parallel with the cDNA microarray technology. This article summarizes various aspects of cancer understanding and diagnostics in which TMA has had great impact. Although tremendous advances continue to be made to facilitate imaging and archiving of TMA specimens, automatic evaluation and quantitative analysis of TMA still remains an important challenge for modern investigators.


The historical context in conversation: Lexical differentiation and memory for the discourse history.
When designing a definite referring expression, speakers take into account both the local context and certain aspects of the historical context, including whether similar referents have been mentioned in the past. When a similar item has been mentioned previously, speakers tend to elaborate their referring expression in order to differentiate the two items, a phenomenon called lexical differentiation. The present research examines the locus of the lexical differentiation effect and its relationship with memory for the discourse. In three experiments, we demonstrate that speakers differentiate to distinguish current from past referents; there was no evidence that speakers differentiate in order to avoid giving two items the same label. Post-task memory tests also revealed a high level of memory for the discourse history, a finding that is inconsistent with the view that failures of memory underlie low differentiation rates. Instead, memory for the discourse history, while necessary, is not sufficient for speakers to design language with respect to the historical context. Speakers must additionally view the discourse history as relevant to design language with respect to this broader context. Finally, measures of memory for past referents point to asymmetries between speakers and listeners in their memory for the discourse, with speakers typically remembering the discourse history better.


A Critical Appraisal of Educational Theory to Examine HBCU and Black Students' Professional Identity Formation.
This article explores educational theories and existing literature that describe the impact of Historically Black College or University (HBCU) educational environments on Black students' personal and professional development. Literature on professional identity formation (PIF) in pharmacy education is also examined to describe the influence of HBCU pharmacy education on Black pharmacy students' PIF. Tinto's theory of student retention, Arroyo and Gasman's HBCU educational framework, and Bank's theory of multicultural education are described, as key elements of HBCU education that foster PIF in minoritized student populations. Each of the 3 models addresses professional identity traits associated with pharmacists and pharmacy students, and this review examines the role of HBCU education in Black Doctor of Pharmacy students' development of academic competence, leadership, professional communication, and advocacy. Existing educational frameworks and models of student retention can be applied to promote student growth, psychological safety, and feelings of belonging in minoritized student populations. By engaging these models, pharmacy training environments can support Black students and other minoritized student populations as they develop their own professional identities in the pursuit of fulfilling careers.


Anaesthetic and surgical technique for bilateral adrenalectomy in stress sensitive pigs.
A technique for anaesthesia of Pietrain pigs using thiopentone or ketamine, ventilation with nitrous oxide and oxygen and muscle relaxation with pancuronium, is described. Bilateral adrenalectomy was carried out by a mid line laparotomy and details of the surgical technique are illustrated. Four of the 10 animals died 7--13 hours after surgery with a hyperthermic response.


Design of adaptive structures through energy minimization: extension to tensegrity.
This paper gives a new formulation to design adaptive structures through total energy optimization (TEO). This methodology enables the design of truss as well as tensegrity configurations that are equipped with linear actuators to counteract the effect of loading through active control. The design criterion is whole-life energy minimization which comprises an embodied part in the material and an operational part for structural adaptation during service. The embodied energy is minimized through simultaneous optimization of element sizing and actuator placement, which is formulated as a mixed-integer nonlinear programming problem. Optimization variables include element cross-sectional areas, actuator positions, element forces, and node displacements. For tensegrity configurations, the actuators are not only employed to counteract the effect of loading but also to apply appropriate prestress which is included in the optimization variables. Actuator commands during service are obtained through minimization of the operational energy that is required to control the state of the structure within required limits, which is formulated as a nonlinear programming problem. Embodied and operational energy minimization problems are nested within a univariate optimization process that minimizes the structure's whole-life energy (embodied + operational). TEO has been applied to design a roof and a high-rise adaptive tensegrity structure. The adaptive tensegrity solutions are benchmarked with equivalent passive tensegrity as well as adaptive truss solutions, which are also designed through TEO. Results have shown that since cables can be kept in tension through active control, adaptive tensegrity structures require low prestress, which in turn reduces mass, embodied energy, and construction costs compared to passive tensegrity structures. However, while adaptive truss solutions achieve significant mass and energy savings compared to passive solutions, adaptive tensegrity solutions are not efficient configurations in whole-life energy cost terms. Since cable elements must be kept in tension, significant operational energy is required to maintain stable equilibrium for adaptation to loading. Generally, adaptive tensegrity solutions are not as efficient as their equivalent adaptive truss configurations in mass and energy cost terms.


Creating designer laccases.
High redox potential laccases from white-rot fungi are recalcitrant to engineering. Maté et al. (2010) employed directed evolution to improve the activity and expression level of the fungal laccase from basidiomycete PM1, followed by rational design to restore thermostability lost during evolution, resulting in a highly active and stable enzyme.


Expedient Route to the functionalized calyciphylline A-type skeleton via a Michael addition-RCM strategy.
An efficient, robust, and scalable strategy to access the functionalized core of calyciphylline A-type alkaloids has been developed starting from commercially available 3-methylanisole. Key features of this approach are an intramolecular Michael addition/allylation sequence and a ring-closing metathesis step.


Synthesis and in vitro biological evaluation of 3-ethyl-1,5-naphthyridin-2(1H)-one derivatives as potent PARP-1 selective inhibitors and PARP-1 DNA trappers.
Inhibition of poly (ADP-ribose) polymerase (PARP) has been applied with great success in the clinical treatment of homologous recombination-deficient malignancy. Recent study demonstrated that not only PARP-1 inhibition but also DNA trapping contributes to the efficacy in BRCA mutant tumors and the toxicities results from the poor selectivity of PARP-1 over PARP-2 as well as their DNA trapping. Herein, a series of 3-ethyl-1,5-naphthyridin-2(1H)-one derivatives (7a-7l, 8a-8n) were synthesized and identified as PARP-1 selective inhibitors and PARP-1 DNA trappers. Among them, compound 8m was found to be highly potent and selective. It inhibited PARP-1 activity and BRCA mutant DLD-1 cell activity with IC50 values of 0.49 nM and 4.82 nM, and the in vitro DNA trapping efficacy of compound 8m was 1.85 nM. Compared with AZD5305, compound 8m significantly improved the selectivity of PARP-1 over PARP-2 as well. Compound 8m was>1000-fold selective for PARP-1 DNA trapping over PARP-2.


Isolation of a cDNA clone for murine catalase and analysis of an acatalasemic mutant.
We have investigated the genetic control of murine catalase expression by analyzing catalase transcription and translation products from the tissues of control (Csa) and acatalasemic (Csb) mouse strains. Csb animals possess nearly normal catalase enzyme activity levels in liver, while displaying approximately 20 and 1% of normal activity levels in kidney and red blood cells, respectively. Immunoblot analyses of catalase in these tissues have revealed reduced levels of immunologically reactive catalase protein in Csb kidney and red blood cells, paralleling the reduction of catalase enzyme activity in these tissues. In order to determine the molecular basis for Csb acatalasemia, we have isolated a cDNA clone for murine catalase and have used this probe to analyze Csa and Csb genomic DNA and catalase mRNA. These studies have revealed: 1) no restriction fragment length polymorphisms between Csa and Csb genomic DNAs; 2) no differences in the levels of Csa and Csb catalase mRNA within a single tissue; and 3) no differences in the sizes of Csa and Csb catalase mRNAs. These observations suggest that the genetic defect that produces the tissue-specific reduction of catalase expression in Csb mice is not due to a marked rearrangement of DNA within the Csb catalase structural gene. Furthermore, the Csb mutation does not act at the level of gene transcription or mRNA stability, but rather at the level of mRNA translation and/or catalase protein turnover.


Safety of antiplatelet therapy prior to intravenous thrombolysis in acute ischemic stroke.
There is some uncertainty whether prior use of antiplatelet (AP) drugs increases the risk of symptomatic intracerebral hemorrhage (SICH) and influences functional outcome in patients with ischemic stroke treated with intravenous thrombolysis. To assess whether prior use of AP drugs is related to outcome following intravenous tissue plasminogen activator therapy in patients with ischemic stroke. A single-center prospective observational cohort study of the relation between prior AP therapy, occurrence of SICH, and functional outcome of consecutive patients with ischemic stroke undergoing intravenous thrombolysis with tissue plasminogen activator in a university hospital between April 1, 2002, and November 30, 2006. The occurrence of SICH and favorable outcome reflecting independence defined as a modified Rankin Scale score of 2 or lower at 3 months. Of the 301 patients who received intravenous tissue plasminogen activator, 89 used AP drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 12 patients (13.5%; 95% confidence interval, 7.8%-22.3%) who had received AP drugs and in 6 patients (2.8%; 95% confidence interval, 1.2%-6.2%) without prior AP therapy (P = .001). Multivariate analysis revealed that prior AP therapy was an independent predictor of SICH (odds ratio, 6.0; 95% confidence interval, 2.0-17.1). Nonetheless, prior AP therapy was independently associated with a favorable outcome (odds ratio, 2.0; 95% confidence interval, 1.0-4.3). Despite a higher incidence of SICH, the net benefit of intravenous tissue plasminogen activator therapy for acute ischemic stroke was greater in patients using AP drugs.


Molecular detection of bovine and porcine Torque teno virus in plasma and feces.
Torque teno virus (TTV) is frequently detected in humans, livestock and some companion animals. Very little is known about presence of TTV in Canadian livestock and the goal of this study was to evaluate the presence of TTV in swine and cattle using molecular tools. TTV DNA was detected and confirmed by sequencing in the plasma of 90.5% and in the feces of 60.3% of the animals tested in a single swine herd as well as 80.9% and 1.1% in the plasma of individuals from general Quebec swine and cattle populations, respectively. The impact of the TTV presence in livestock population for the agri-food chain should be further investigated.


Anti-malarial activities of acylated bruceolide derivatives.
Several O-acylated derivatives of bruceolide (2) were synthesized and their anti-malarial activities together with selective toxicities were examined. It was found that 3,15-di-O-acetyl-(3c), 3,15-di-O-propionyl-(3d) and 15-O-propionylbruceolide (3b), as well as bruceine B (3a), exhibited potent anti-malarial activities with high selective toxicities.


In vitro and ex vivo effects of indobufen on red blood cell deformability.
We have studied the effect of indobufen, a cyclo-oxygenase blocking agent which has proved useful in patients with obstructive vascular disease, on red blood cell (RBC) filterability in vitro and in a pilot study ex vivo. The addition of indobufen in vitro to blood samples from 10 healthy volunteers did not significantly modify RBC deformability. We evaluated the ex vivo effect of indobufen (200 mg bd) in 14 patients with obstructive vascular disease. A significant improvement in RBC deformability was noted on the 5th, 14th, and 28th days of treatment, 2 h after the morning dose. Acetylsalicylic acid given to 6 similar patients had no effect suggesting that the positive haemorheological effect of indobufen is probably not linked to its cyclooxygenase blocking effect.


Correction to: Hepatocellular Carcinoma with Bone Metastases: Incidence, Prognostic Significance, and Management-Single-Center Experience.
The original version of this article unfortunately contained a mistake in the Author group section. Author first names and family names were interchanged.


Level of sustainability reporting of Malaysian IPO companies.
This paper aims to determine the level of sustainability reporting (SR) among Malaysian initial public offering (IPO) companies. Due to a lack of awareness about SR and its dimensions, these aspects have not been receiving the necessary push from the public domain. This study is exploratory in nature. Secondary data were used by conducting content analysis of the annual reports of 139 sampled IPO companies listed on Bursa Malaysia from 2007 to 2017. Data were analysed using descriptive statistics, with extent and quality being used as measures of SR. The results demonstrated gradual improvements of the extent and quality of SR among Malaysian IPO companies. The overall extent of SR was 20.70%, with employee disclosure scoring the highest (34.87%), followed by society disclosure (32.77%), environmental disclosure (22.48%), and finally product disclosure (9.88%). The overall quality of SR was 32.04%, with society disclosure scoring the highest (36.09%), followed by employee disclosure (34.13%), environmental disclosure (20.28%), and finally product disclosure (9.50%). SR dimensions, namely society, environmental, employee, and product received little interest from most of the IPO companies. This study proposes that additional studies can be conducted to investigate SR among IPO companies.


Synthetic metabolism for biohalogenation.
The pressing need for novel bioproduction approaches faces a limitation in the number and type of molecules accessed through synthetic biology. Halogenation is widely used for tuning physicochemical properties of molecules and polymers, but traditional halogenation chemistry often lacks specificity and generates harmful by-products. Here, we pose that deploying synthetic metabolism tailored for biohalogenation represents an unique opportunity towards economically attractive and environmentally friendly organohalide production. On this background, we discuss growth-coupled selection of functional metabolic modules that harness the rich repertoire of biosynthetic and biodegradation capabilities of environmental bacteria for in vivo biohalogenation. By rationally combining these approaches, the chemical landscape of living cells can accommodate bioproduction of added-value organohalides which, as of today, are obtained by traditional chemistry.


Alcohol ADME in primates studied with positron emission tomography.
The sensitivity to the intoxicating effects of alcohol as well as its adverse medical consequences differ markedly among individuals, which reflects in part differences in alcohol's absorption, distribution, metabolism, and elimination (ADME) properties. The ADME of alcohol in the body and its relationship with alcohol's brain bioavailability, however, is not well understood. The ADME of C-11 labeled alcohol, CH(3) (11)CH(2)OH, 1 and C-11 and deuterium dual labeled alcohol, CH(3) (11)CD(2)OH, 2 in baboons was compared based on the principle that C-D bond is stronger than C-H bond, thus the reaction is slower if C-D bond breaking occurs in a rate-determining metabolic step. The following ADME parameters in peripheral organs and brain were derived from time activity curve (TAC) of positron emission tomography (PET) scans: peak uptake (C(max)); peak uptake time (T(max)), half-life of peak uptake (T(1/2)), the area under the curve (AUC(60 min)), and the residue uptake (C(60 min)). For 1 the highest uptake occurred in the kidney whereas for 2 it occurred in the liver. A deuterium isotope effect was observed in the kidneys in both animals studied and in the liver of one animal but not the other. The highest uptake for 1 and 2 in the brain was in striatum and cerebellum but 2 had higher uptake than 1 in all brain regions most evidently in thalamus and cingulate. Alcohol's brain uptake was significantly higher when given intravenously than when given orally and also when the animal was pretreated with a pharmacological dose of alcohol. The study shows that alcohol metabolism in peripheral organs had a large effect on alcohol's brain bioavailability. This study sets the stage for clinical investigation on how genetics, gender and alcohol abuse affect alcohol's ADME and its relationship to intoxication and medical consequences.


Activation of p38 and p42/44 MAP kinase in neuropathic pain: involvement of VPAC2 and NK2 receptors and mediation by spinal glia.
Activation of intracellular signaling pathways involving p38 and p42/44 MAP kinases may contribute importantly to synaptic plasticity underlying spinal neuronal sensitization. Inhibitors of p38 or p42/44 pathways moderately attenuated responses of dorsal horn neurons evoked by mustard oil but not brush and alleviated the behavioral reflex sensitization seen following nerve injury. Activation of p38 and p42/44 MAP kinases in spinal cord ipsilateral to constriction injury was reduced by antagonists of NMDA, VPAC2 and NK2 (but not related) receptors, the glial inhibitor propentofylline and inhibitors of TNF-alpha. A VPAC2 receptor agonist enhanced p38 phosphorylation and caused behavioral reflex sensitization in naïve animals that could be blocked by co-administration of p38 inhibitor. Conversely, an NK2 receptor agonist activated p42/44 and caused behavioral sensitization that could be prevented by co-administration of p42/44 inhibitor. Thus, spinal p38 and p42/44 MAP kinases are activated in neuropathic pain states by mechanisms involving VPAC2, NK2, NMDA receptors and glial cytokine production.


Esophageal achalasia: laparoscopic versus conventional open Heller-Dor operation.
The laparoscopic treatment of esophageal achalasia has recently been introduced, and the occasional reports in the literature seem to indicate considerable advantages for patients in terms of surgical trauma, postoperative discomfort, and appearance. As yet, however, no studies have directly analyzed the benefits and shortcomings of the new surgical technique by comparison with the conventional open procedure. The objective of our study was to review recent experience with the laparoscopic Heller-Dor operation (LAP-HD) at the Department of Surgery of Padua University and compare it with the traditional open Heller-Dor procedure (OPEN-HD) to assess early effectiveness in patients with primary esophageal achalasia. The records of 17 patients who had LAP-HD and a matched group of 17 patients who had OPEN-HD were retrospectively reviewed. The duration of procedures, morbidity, several aspects of the postoperative course, and hospital costs were recorded and compared. Results of clinical follow-up and of manometric and pH-monitoring studies performed 6 months postoperatively were also evaluated in both patient groups. LAP-HD took longer than OPEN-HD (mean 178 versus 125 minutes). There was no mortality or major morbidity in either group. Postoperative pain and ileus and need for IV nutrition lasted a shorter time for LAP-HD patients (P < 0.0001). Consequently, the median postoperative hospital stay and the median interval before returning to normal activity were also shorter (4 and 14 days for the LAP-HD group versus 10 and 30 days for the OPEN-HD group, P < 0.0001). During follow-up, dysphagia recurred in 1 patient of the LAP-HD group and gastroesophageal reflux was registered in 1 patient of the OPEN-HD group. Lower esophageal sphincter pressure decreased significantly after both procedures. Laparoscopic management of achalasia leads to short-term results comparable to those of the well-established open technique. In view of the less severe surgical trauma and lower hospital cost, the laparoscopic approach is preferable, but long-term studies are needed.


Molecular detection of hepatitis B virus genotype E with immune escape mutations in chronic hepatitis B patients on long-term antiviral therapy in Jos, Nigeria.
Previous studies in Nigeria have reported the presence of hepatitis B virus (HBV) genotype E and the availability of immune escape mutants. There is a paucity of data on chronic patients on long-term antiviral therapy for HBV infection. This study assessed HBV genotypes and drug resistance variants among patients with chronic HBV infection receiving tenofovir in Jos, Nigeria. This cross-sectional study consecutively enrolled 101 patients (51 with HIV/HBV co-infection and 50 with HBV infection only) on antiviral therapy from February 2018 to May 2019 at four hospitals in Jos, Nigeria. DNA quantification of HBV was performed on all samples; 30 samples with detectable viral load were selected for genotyping using Sanger sequencing by targeting the full-length sequences of reverse transcriptase gene of the HBV genome. Phylogenetic analysis was performed with reference sequences from GenBank. Escape mutant and drug resistance analysis were performed using HBV drug resistance interpretation and Geno2pheno. Only 30 (29.7%) of the 101 study participants had detectable HBV DNA. Of these, six (20.0%) isolates were successfully amplified and sequenced. The identified genotype was E, including escape mutations L127R (16.7%) and G145A (16.7%). This study revealed exclusive dominance of genotype E in Nigeria. The S gene mutations G145A and L271R are known to be associated with modified antigenicity and impaired serologic assays, which may cause false negatives in the detection of anti-HBV surface antigen. The presence of mutants that are associated with vaccine immune escape may also have diagnostic and vaccine immune response implications.


Transurethral resection of the prostate after radiotherapy for prostate cancer: impact on quality of life.
To evaluate the impact of transurethral resection of the prostate on quality of life after radiotherapy for prostate cancer. A group of 49 consecutive patients with and 487 without prior transurethral resection of the prostate responded to the Expanded Prostate Cancer Index Composite questionnaire before, on the last day, and a median time of 2 months and 16 months after external beam radiotherapy (70-78 Gy). A matched-pair analysis was used to avoid the influence of treatment-associated confounding factors, including dose, treatment volume and hormonal therapy. Significantly smaller acute urinary score changes relative to baseline levels resulted with versus without prior transurethral resection of the prostate (mean function/bother score decrease of 3/6 vs 18/21 points at the end of radiotherapy; P < 0.01), affecting urinary incontinence (pads to control urinary leakage in 4% vs 24%; P = 0.03) and irritative/obstructive symptoms (big/moderate problem with weak urinary stream in 11% vs 37%; P = 0.02). As opposed to acute changes, transurethral resection of the prostate was a significant predisposing factor for a long-term urinary function score decrease >10 points (20% vs 6% of patients with vs without prior resection; P = 0.04). Urinary incontinence risk was higher for patients with a longer time from resection to radiotherapy. Transurethral resection of the prostate significantly affects acute (considerably fewer symptoms) and long-term (relevant toxicity in some cases) urinary quality of life after radiotherapy for prostate cancer.


Effects of a chemotactic factor, N-formylmethionyl peptide, on adherence, superoxide anion generation, phagocytosis, and microtubule assembly of human polymorphonuclear leukocytes.
FMLP promoted microtubule assembly in PMNs at concentrations which were chemotactic for the cells. At higher concentrations than those required for chemotaxis, FMLP enhanced the adherence of PMNs to nylon glass fibers. With colchicine, PMN adherence was inhibited, but upon exposure to FMLP, PMN adherence could be restored. The effect of FMLP on PMN adherence was transitory and was no longer evident by 5 min. At concentrations similar to those employed in the adherence studies. FMLP induced the cells to briefly generate O-2, since ferricytochrome C reduction was no longer evident by 5 min. Pretreatment of the PMNs with cytochalasin B enhanced the release of O-2 by PMNs exposed to FMLP. On the other hand, there was no effect of FMLP on phagocytosis of C3-coated particles. These results suggest that FMLP induces responsive cells to develop a hyperadherent plasma membrane which is largely independent on microtubule control. Since oligopeptides similar of AMLP are formed in bacteria, it is likely that the action of N-formylated peptides is important in regulating the inflammatory response.


Needs of Patients with Schizophrenia Among an Ethnic Minority Group in Latin America.
The aim of the study is to describe the need profile of outpatients with schizophrenia belonging to an Aymara ethnic group in Latin-America and to compare that profile to non-Aymara patients. A sample of 253 patients were evaluated with the Two-Way Communication Checklist (2-COM Checklist) measuring the needs and satisfaction of the patient; Positive and Negative Syndrome scale for Schizophrenia (PANSS) and Attitude to the Drugs (DAI-10). No significant differences were found between Aymara and non-Aymara, either in the total number of needs or in the subscales of satisfaction or in the types of needs. After adjustment for socio-demographic and clinical factors, patients with higher severity (PANSS) had higher number of needs and lower level of satisfaction. Higher score on DAI-10 is related to a higher total number of needs and better satisfaction with medication. Age, sex, ethnicity and employment were also associated with specific needs. The profile of the needs of schizophrenic Aymara patients does not differ from that of non-Aymara patients, and that in both groups it is necessary that the treatment primarily address symptom management and the subjective aspects of quality of life.


A systematic review with meta-analysis on balance, fatigue, and motor function following aquatic therapy in patients with multiple sclerosis.
In this systematic review and meta-analysis, we aimed to evaluate the impact of long-term aquatic exercise training on balance, fatigue, and motor function. Scopus, PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Ovid Medline, EBSCO Cumulative Index to Nursing, and Allied Health Literature were searched on April 19, 2021. The search included randomized and non-randomized controlled trials, case-control studies, case series, and case reports. Two independent reviewers reviewed titles and abstracts to determine which studies satisfied the eligibility criteria. Two reviewers independently surveyed the full texts and conducted the study selection, data extraction, and quality assessment. Data synthesis was applied to summarize information from included studies. Meta-analysis was performed using RevMan 5. From 170 studies that were identified in the initial search, 16 trials (794 participants) satisfied the eligibility criteria. Aquatic therapy had a positive effect on fatigue compared to control group based on Modified Fatigue Impact Scale (MFIS) in physical (SMD, -1.29; 95% CI, [(-1.65) - (-0.93)]; I2=88%) cognitive (SMD, -0.75; 95% CI, [(-1.08)-(- 0.43)]; I2=78%), and psychological (SMD, -1.25; 95% CI, [(-1.59) - (-0.90)]; I2=79%) domains, and Fatigue Severity Scale (FSS) (SMD, -0.53; 95% CI, [(-0.86) - (-0.20)]; I2=57%). In addition, aquatic therapy improved balance based on the Berg Balance Scale (BBS) compared to the control group (SMD, 1.19; 95% CI, [(0.62)-(1.76)]; I2=11%) CONCLUSIONS: Aquatic therapy has positive effects on fatigue and balance. Further research is needed to confirm the clinical utility of aquatic therapy for multiple sclerosis patients in the long term.


Uniform manganese hexacyanoferrate hydrate nanocubes featuring superior performance for low-cost supercapacitors and nonenzymatic electrochemical sensors.
Uniform manganese hexacyanoferrate hydrate nanocubes are prepared via a simple chemical precipitation method at room temperature. Due to both micro/mesopores of the Prussian blue analogue and nanocubic structures, the manganese hexacyanoferrate hydrate nanocubes allow the efficient charge transfer and mass transport for electrolyte solution and chemical species. Thus, the manganese hexacyanoferrate hydrate nanocube electrode shows a good rate capability and cycling stability for electrochemical capacitors. Furthermore, electrodes modified with manganese hexacyanoferrate hydrate nanocubes demonstrate a sensitive electrochemical response to hydrogen peroxide (H2O2) in buffer solutions with a high selectivity.


Effect of insulin secretagogues on major cardiovascular events and all-cause mortality: A meta-analysis of randomized controlled trials.
In 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs) and all-cause mortality as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin secretagogues (sulfonylureas and glinides) with this respect. A MEDLINE database search was performed to identify all RCTs, up to January 1st, 2020, with duration≥52 weeks, in which insulin secretagogues (glibenclamide, gliclazide, glimepiride, glipizide, chlorpropamide, repaglinide, nateglinide) were compared with either placebo or active comparators. The principal endpoints were MACE (restricted for RCT reporting MACEs within their outcomes) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered. Fourteen RCTs were included in the analysis for MACEs (919 in insulin secretagogues and 1,087 in control group). Insulin secretagogues were not significantly associated with an increased risk of MACEs in comparison with controls (MH-OR 1.08 [95% CI 0.96, 1.22], p = 0.20). When considering the 48 RCTs fulfilling criteria for inclusion in the analysis on all-cause mortality, insulin secretagogues were associated with a significantly increased risk of all-cause mortality (MH-OR 1.11 [1.00, 1.23], p = 0.04). This meta-analysis suggests that insulin secretagogues are associated with an increased risk of all-cause mortality when compared with placebo or other anti-hyperglycaemic drugs.


Cycles in nonlinear age-structured models. I. Renewal equations.
A variety of density-dependent population models can be described by nonlinear renewal equations. This paper develops analytical tools for such models to study the sustained population cycles which arise by bifurcation. The results obtained describe explicitly the direction of bifurcation, and the period, form, and dynamic stability of sustained cycles. The results are illustrated by application to a cohort-controlled model of human populations which has been proposed as a formalization of the Easterlin effect.