Executive Functions, Episodic Autobiographical Memory, Problem-Solving Capacity, and Depression Proposal for a Structural Equations Model.
The executive functions play an important role in storing and recovering autobiographical memories, especially episodic memories. These types of memories provide information about solutions and experiences from the past that can be utilized as examples in the present when seeking solutions to any problem. In addition, a close relationship between depression and the executive functions has been widely recognized. This study aims to elaborate a structural equations model that empirically supports the relationships among the executive functions, episodic autobiographical memory, and the adaptive capacity to solve problems, taking into account the depressed mood state. In all, 32 healthy elderly people, 32 patients with Parkinson disease, 32 with amnestic mild cognitive impairment, and 32 with Alzheimer disease were evaluated. Structural equation models were estimated to test the effects among the constructs. The final model shows adequate fit indexes, thus revealing that an individual's problem-solving capacity will depend on the capacity to access the episodic autobiographical memory, which in turn will depend on the maintenance of executive functioning. In a parallel way, the mood state, and specifically depression, will play a modulator role because when there is depressive symptomatology, some capacities that depend on executive control can be diminished.


Characterization of ocular receptors for pituitary adenylate cyclase activating polypeptide (PACAP) and their coupling to adenylate cyclase.
Pituitary adenylate cyclase activating polypeptide (PACAP), a recently discovered neuropeptide, has large structural homology with vasoactive intestinal polypeptide (VIP). Two molecular forms exist, one with 27 (PACAP-27) and one with 38 (PACAP-38) amino acids. PACAP-27 is identical to the N-terminal of PACAP-38. Two major types of PACAP receptors have been identified; selective PACAP receptors, which bind PACAP with a much higher affinity than VIP, and non-selective VIP/PACAP receptors, which bind PACAP and VIP with equally high affinity. In the present investigation, PACAP receptors in different parts of the albino rabbit eye, and their coupling to adenylate cyclase were characterized. Crude tissue homogenates from iris, ciliary body, retina and choroid were used. Competition binding curves were established for VIP, PACAP-27 and PACAP-38, with [125I]VIP or [125I-Acetyl-His1]PACAP-27 as tracer. The effects on adenylate cyclase activity were determined by plotting dose-response curves (10(-10)-10(-6) M) for VIP, PACAP-27 and PACAP-38. The anterior uvea had mainly (approximately 80%) non-selective VIP/PACAP receptors, but a small amount of selective PACAP receptors was detected. In the retina, the selective PACAP receptor predominated (approximately 85%), while the choroid (including the retinal pigment epithelium) had approximately 60% selective PACAP receptors. PACAP-27 and PACAP-38 stimulated the formation of cAMP with the same efficacy: 6.9-fold in the ciliary body, 3.6-fold in the iris, 5.1-fold in the retina and 2.3-fold in the choroid.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacological characterization of positive inotropic derivatives of 4-amino-7-methyl-1,8-naphthyridine-3-carboxylic acid.
The positive inotropic effect of a series of 4-amino-7-methyl-1,8-naphthyridine-3-carboxylic acid derivatives was compared with the effects of known inotropic agents (ouabain, dihydroouabain, isoproterenol, adrenaline, histamine and isobutylmethylxanthine) in guinea-pig atrial and ventricular myocardial preparations. With respect to their functional effects, the 1,8-naphthyridine compounds are clearly different from drugs acting on the cAMP system, whereas several similarities with cardiac glycoside effects were found. Their ability to inhibit [3H]ouabain binding in guinea-pig cardiac membranes correlates well with their effects on myocardial contractile force. However, the latter effect was exerted by tenfold lower concentrations. The dissimilarities found between the 1,8-naphthyridines and digitalis may be due to a different type of interaction with the binding site on the (Na(+) + K+)-ATPase.


Probing the catalytic triad of an archaeal RNA splicing endonuclease.
Among the four known mechanisms of intron removal, three are reputedly catalyzed by RNA molecules. In the fourth mechanism, a protein endonuclease removes introns from nuclear tRNA and all archaeal RNAs. Three strictly conserved residues of the splicing endonuclease, a histidine, a lysine, and a tyrosine, were predicted to catalyze the intron cleavage reaction in a manner similar to that of the catalytic triad of ribonuclease A. Single-turnover kinetic parameters were obtained for the wild-type enzyme and two triad mutants. Mutation of histidine to alanine produced an at least approximately 28-fold reduction; mutation of tyrosine to phenylalanine produced an at least approximately 7-fold reduction in activity, while a histidine and tyrosine double mutation abolished cleavage. The single mutation of lysine to glutamic acid abolished RNA cleavage activity in the absence of a divalent metal but maintained a substantial level of activity in the presence of specific divalent metals. These data support important functional roles already proposed for the catalytic triad and suggest an intriguing hypothesis in which the splicing endonuclease is an intermediate in the transition from the RNA to the RNP world.


Assessing Histology Structures by Ex Vivo MR Microscopy and Exploring the Link Between MRM-Derived Radiomic Features and Histopathology in Ovarian Cancer.
The value of MR radiomic features at a microscopic scale has not been explored in ovarian cancer. The objective of this study was to probe the associations of MR microscopy (MRM) images and MRM-derived radiomic maps with histopathology in high-grade serous ovarian cancer (HGSOC). Nine peritoneal implants from 9 patients with HGSOC were imaged ex vivo with MRM using a 9.4-T MR scanner. All MRM images and computed pixel-wise radiomics maps were correlated with the slice-matched stroma and tumor proportion maps derived from whole histopathologic slide images (WHSI) of corresponding peritoneal implants. Automated MRM-derived segmentation maps of tumor and stroma were constructed using holdout test data and validated against the histopathologic gold standard. Excellent correlation between MRM images and WHSI was observed (Dice index = 0.77). Entropy, correlation, difference entropy, and sum entropy radiomic features were positively associated with high stromal proportion (r = 0.97,0.88, 0.81, and 0.96 respectively, p < 0.05). MR signal intensity, energy, homogeneity, auto correlation, difference variance, and sum average were negatively associated with low stromal proportion (r = -0.91, -0.93, -0.94, -0.9, -0.89, -0.89, respectively, p < 0.05). Using the automated model, MRM predicted stromal proportion with an accuracy ranging from 61.4% to 71.9%. In this hypothesis-generating study, we showed that it is feasible to resolve histologic structures in HGSOC using ex vivo MRM at 9.4 T and radiomics.


The risk stratification and prognostic evaluation of soluble programmed death-1 on patients with sepsis in emergency department.
To evaluate the efficacy of soluble programmed death-1 (sPD-1) for risk stratification and prediction of 28-day mortality in patients with sepsis, we compared serum sPD-1 with procalcitonin (PCT), C-reactive protein (CRP), and the Mortality in Emergency Department Sepsis (MEDS) score. A total of 60 healthy volunteers and 595 emergency department (ED) patients were recruited for this prospective cohort study. According to the severity of their condition on ED arrival, the patients were allocated to the systemic inflammatory response syndrome group (130 cases), sepsis group (276 cases), severe sepsis group (121 cases), and septic shock group (68 cases). In addition, all patients with sepsis were also divided into the survivor group (349 cases) and nonsurvivor group (116 cases) according to the 28-day outcomes. When the severity of sepsis increased, the levels of sPD-1 gradually increased. The levels of sPD-1, PCT, CRP and the MEDS score were also higher in the nonsurvivor group compared to the survivor group. Logistic regression suggested that sPD-1, PCT, and the MEDS score were independent risk factors for 28-day mortality of patients with sepsis. Area under the curve (AUC) of sPD-1, PCT and the MEDS score for 28-day mortality was 0.725, 0.693, and 0.767, respectively, and the AUC was improved when all 3 factors were combined (0.843). Serum sPD-1 is positively correlated with the severity of sepsis, and it is valuable for risk stratification of patients and prediction of 28-day mortality. Combining sPD-1 with PCT and the MEDS score improves the prognostic evaluation.


Botulinum neurotoxin: the neuromuscular junction revisited.
Botulinum neurotoxin is the neuromuscular poison that is responsible for the fatal disease botulism. This toxin is also a valued therapeutic agent in the treatment of an increasing number of neuromuscular disorders. Unfortunately, in the wrong hands, botulinum neurotoxin is also a deadly biological "weapon. The diverse health consequences of botulinum neurotoxin combined with the increased threat of bioterrorism underscore the profound importance of understanding exactly how this toxin exerts its effects on the clinically relevant mammalian target site, the neuromuscular junction. Despite the fact that a great deal has been learned about the cellular actions of botulinum neurotoxin during the past three decades, questions still remain. For example, what protein or proteins mediate transport of the toxin into the cholinergic nerve terminal? What factors control the duration of toxin action in the nerve terminal? Until recently, scholarly pursuit of such questions was technically challenging in neuromuscular tissues. Recent advancements in biotechnology have now made it feasible to pursue these important issues at the neuromuscular junction and to correlate biochemical studies in nontarget tissues with clinically relevant functional outcomes. This narrative reviews our current understanding of the actions of botulinum neurotoxin at the neuromuscular junction, presents recent findings from our own work in neuromuscular tissues, and encourages future studies regarding botulinum neurotoxin at its target site.


A fatal case of mercuric cyanide poisoning.
A 57-year-old pharmacist was found dead 11 days after his disappearance. At the autopsy, samples of blood, urine, gastric content were obtained. Presence of ethanol, cyanide and mercury were detected in some samples. Cyanide and mercury were identified and quantified using high-performance liquid chromatography with diode array detector (HPLC) in fluorescence mode and ICP with mass selective detector (ICP-MS) respectively. Whole blood concentrations of ethanol was 1.72 g/L. Cyanide and mercury concentrations in whole blood were respectively 0.16 and 3.8 mg/L. Concentrations of cyanide (27 mg/L) and mercury (150 mg/L) in gastric contents prove a massive oral ingestion of mercuric cyanide or mercuric oxycyanide occurred. In this case report, the death was attributed to the combined toxicity of cyanide and mercury.


On the origin of the yolk protein ferritin in snails.
The iron storage protein, ferritin, is the major yolk protein in freshwater snails. In this report we show by in vitro labelling experiments that yolk ferritin of the snails Lymnaea stagnalis L. and Planorbarius corneus L. is an exogenous protein synthesized in the midgut gland and secreted into the hemolymph. Gonad and mantle tissue are inactive in the synthesis of yolk ferritin, but, together with the midgut gland, they synthesize another ferritin type (soma ferritin) which is not released into the hemolymph and which may be a housekeeping ferritin. Soma ferritin and yolk ferritin are not in a precursor/product relationship since subunits of both ferritins are synthesized as primary translation products in rabbit reticulocyte lysate programmed with poly (A)+ RNA from midgut gland and gonad. Results suggest that both ferritins are synthesized on different mRNAs (and possibly on different genes) so they may be regulated in a different way.


[Rational diagnosis and therapy of irritable colon].
The irritable bowel syndrome is a common motility disorder of the gut characterized by constipation, diarrhea and abdominal pain. Symptoms are markedly influenced by psychological factors. The diagnosis is based on typical symptoms and exclusion of organic diseases. Psychological support by the physician is an important part of the patients' treatment. High fiber diets and bulking agents may be prescribed in addition. Antispasmodic and antidiarrheal drugs should be given only the shortest time possible, while psychotropic drugs are seldom necessary.


Prediction of Coronary Artery Calcium and Cardiovascular Risk on Chest Radiographs Using Deep Learning.
To assess the ability of deep convolutional neural networks (DCNNs) to predict coronary artery calcium (CAC) and cardiovascular risk on chest radiographs. In this retrospective study, 1689 radiographs in patients who underwent cardiac CT and chest radiography within the same year, between 2013 and 2018, were included (mean age, 56 years ± 11 [standard deviation]; 969 radiographs in women). Agatston scores were used as ground truth labels for DCNN training on radiographs. DCNNs were trained for binary classification of (a) nonzero or zero total calcium scores, (b) presence or absence of calcium in each coronary artery, and (c) total calcium scores above or below varying thresholds. Results from classification of test images were compared with established 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores in each cohort. Classifier performance was measured using area under the receiver operating characteristic curve (AUC) with attention maps to highlight areas of decision-making. Binary classification between zero and nonzero total calcium scores reached an AUC of 0.73 on frontal radiographs, with similar performance on laterals (AUC, 0.70; P = .56). Performance was similar for binary classification of absolute total calcium score above or below 100 (AUC, 0.74). Frontal radiographs that tested positive for a predicted nonzero CAC score correlated with a higher 10-year ASCVD risk of 17.2% ± 10.9 compared with 11.9% ± 10.2 for a negative test, indicating predicted CAC score of zero (P < .001). Multivariate logistic regression demonstrated the algorithm could predict a nonzero calcium score independent of traditional cardiovascular risk factors. Performance was reduced for individual coronary arteries. Heat maps primarily localized to the cardiac silhouette and occasionally other cardiovascular findings. DCNNs trained on chest radiographs had modest accuracy for predicting the presence of CAC correlating with cardiovascular risk.Keywords: Coronary Arteries, Cardiac, Calcifications/Calculi, Neural NetworksSee also the commentary by Gupta and Blankstein in this issue.©RSNA, 2021.


Acquisition and clearance of perianal human papillomavirus infection in relation to HIV-positivity in men who have sex with men in the Netherlands.
This study was performed to establish the prevalence of perianal human papillomavirus (HPV) infection in relation to HIV-positivity in a group of men who have sex with men (MSM), and to correlate follow-up data with regard to acquisition and clearance of HPV infection. Data with regard to HPV prevalence and HIV serostatus during two visits were compared. At both visits participants underwent a routine venereological examination and swabs were taken from the perianal region for HPV DNA testing. During both visits HPV types 16, 18, 31, 33 and 52 were significantly more often detected in HIV-positive individuals. Persistence of HPV type 31 at the perianal region was significantly more often seen in HIV-positive MSM (p=0.036) while the incidence of type 16 may be associated with HIV positivity (p=0.059). In HIV-positive MSM significantly more high-risk HPV types were detected at the perianal region.


Transcriptome-Wide Identification and Characterization of Circular RNAs in Leaves of Chinese Cabbage (Brassica rapa L. ssp. pekinensis) in Response to Calcium Deficiency-Induced Tip-burn.
Circular RNA (circRNA) is a newly discovered non-coding RNA, which play significant roles in the function and transcriptional regulation of microRNA. To date, in Chinese cabbage, the functional characteristic of circRNAs in response to calcium deficiency-induced tip-burn have not been reported. In this study, 730 circRNAs were isolated from Chinese cabbage leaves, of which 23 and 22 were differentially expressed in different calcium deficiency stages compared with the control. Forty-six host genes of the differentially expressed circRNAs were identified, and one circRNA was found to act as miRNAs sponges. Based on the functional analysis of host genes and target mRNAs of the corresponding miRNAs, the identified circRNAs might participated in response to stimulus, electron carrier activity, ATPase activity, cell wall metabolism, transcription factors and plant hormone signal transduction. ABF2, a positive regulator of the abiotic stress response in the abscisic acid (ABA) pathway, may play a role in calcium deficiency tolerance through a circRNA regulatory pathway. Correspondingly, the concentration of ABA is also increased during the Ca2+ deficiency stress. Our results suggest that circRNAs participate in a broad range of biological processes and physiological functions in the response to calcium deficiency-induced tip-burn and provide a basis for further studies of the biological roles that circRNAs play in the plant stress response.


[Surgical treatment of eloquent brain area tumors using neurophysiological mapping of the speech and motor areas and conduction tracts].
To evaluate the efficacy of intraoperative neurophysiological mapping in removing eloquent brain area tumors (EBATs). Sixty five EBAT patients underwent surgical treatment using intraoperative neurophysiological mapping at the Pirogov National Medical and Surgical Center in the period from 2014 to 2015. On primary neurological examination, 46 (71%) patients were detected with motor deficits of varying severity. Speech disorders were diagnosed in 17 (26%) patients. Sixteen patients with concomitant or isolated lesions of the speech centers underwent awake surgery using the asleep-awake-asleep protocol. Standard neurophysiological monitoring included transcranial stimulation as well as motor and, if necessary, speech mapping. The motor and speech areas were mapped with allowance for the preoperative planning data (obtained with a navigation station) synchronized with functional MRI. In this case, a broader representation of the motor and speech centers was revealed in 12 (19%) patients. During speech mapping, no speech disorders were detected in 7 patients; in 9 patients, stimulation of the cerebral cortex in the intended surgical area induced motor (3 patients), sensory (4), and amnesic (2) aphasia. In the total group, we identified 11 patients in whom the tumor was located near the internal capsule. Upon mapping of the conduction tracts in the internal capsule area, the stimulus strength during tumor resection was gradually decreased from 10 mA to 5 mA. Tumor resection was stopped when responses retained at a stimulus strength of 5 mA, which, when compared to the navigation data, corresponded to a distance of about 5 mm to the internal capsule. Completeness of tumor resection was evaluated (contrast-enhanced MRI) in all patients on the first postoperative day. According to the control MRI data, the tumor was resected totally in 60% of patients, subtotally in 24% of patients, and partially in 16% of patients. In the early postoperative period, the development or aggravation of a motor neurological deficit was detected in 18 patients: worsening of paresis was observed in 11 patients, and worsening of speech disorders occurred in 7 patients. After 4 months, motor and speech disorders regressed in 10 patients. Therefore, a persistent neurological deficit developed after surgery in 8 (12%) patients (motor deficit in 5 cases; speech deficit in 3 cases). Resection of eloquent brain area tumors using intraoperative neurophysiological monitoring enables complete resection of the tumor at a low risk of persistent neurological deficits, which ultimately improves the patient's life prognosis.


Aldehydes as Alkylating Agents for Ketones.
Common and non-toxic aldehydes are proposed as reagents for alkylation of ketones instead of carcinogenic alkyl halides. The developed reductive alkylation reaction proceeds in the presence of the commercially available ruthenium catalyst [(cymene)RuCl2 ]2 (as low as 250 ppm) and carbon monoxide as the reducing agent. The reaction works well for a broad substrate scope, including aromatic and aliphatic aldehydes and ketones. It can be carried out without a solvent and often gives nearly quantitative yields of the products. This straightforward and cost-effective method is promising not only for laboratory application but also for industry, which produces carbon monoxide as a large-scale waste product.


A mutual regulation between cell-cell adhesion and N-glycosylation: implication of the bisecting GlcNAc for biological functions.
Changes in oligosaccharide structures are associated with numerous physiological and pathological events. E-cadherin-mediated cell-cell adhesion is believed to be both temporally and spatially regulated during development, and represents a key step in the acquisition of the invasive phenotype for many tumors. Here, we focus mainly on a mutual regulation between E-cadherin-mediated cell-cell adhesion and N-acetylglucosaminyltransferase III (GnT-III) expression, and discuss its implications for biological functions.


Self-induced correction of the genetic defect in tyrosinemia type I.
A mosaic pattern of immunoreactive fumarylacetoacetase (FAH) protein was found in liver tissue in 15 of 18 tyrosinemia type I patients of various ethnic origins. One additional patient had variable levels of FAH enzyme activity in liver tissue. In four patients exhibiting mosaicism of FAH protein, analysis for the tyrosinemia-causing mutations was performed in immunonegative and immunopositive areas of liver tissue by restriction digestion analysis and direct DNA sequencing. In all four patients the immunonegative liver tissue contained the FAH mutations demonstrated in fibroblasts of the patients. In the immunopositive nodules of regenerating liver tissue one of the mutated alleles apparently had reverted to the normal genotype. This genetic correction was observed for three different tyrosinemia-causing mutations. In each case a mutant AT nucleotide pair was reverted to a normal GC pair.


Mendelian neurodegenerative disease genes involved in autophagy.
The lysosomal degradation pathway of macroautophagy (herein referred to as autophagy) plays a crucial role in cellular physiology by regulating the removal of unwanted cargoes such as protein aggregates and damaged organelles. Over the last five decades, significant progress has been made in understanding the molecular mechanisms that regulate autophagy and its roles in human physiology and diseases. These advances, together with discoveries in human genetics linking autophagy-related gene mutations to specific diseases, provide a better understanding of the mechanisms by which autophagy-dependent pathways can be potentially targeted for treating human diseases. Here, we review mutations that have been identified in genes involved in autophagy and their associations with neurodegenerative diseases.


Transcatheter Tricuspid Valve Replacement in Orthotopic Heart Transplant.
A patient with history of orthotopic heart transplant (OHT) followed by tricuspid valve replacement and two subsequent balloon valvuloplasties was offered transcatheter tricuspid valve replacement (TTVR) to avoid what would have been his fourth sternotomy. TTVR in patients with OHT can be a valuable approach to prevent further open-heart surgeries, which carry added morbidity and mortality.


TRPV2 enhances axon outgrowth through its activation by membrane stretch in developing sensory and motor neurons.
Thermosensitive TRP (thermo TRP) channels are well recognized for their contributions to sensory transduction, responding to a wide variety of stimuli including temperature, nociceptive stimuli, touch, and osmolarity. However, the precise roles for the thermo TRP channels during development have not been determined. To explore the functional importance of thermo TRP channels during neural development, the temporal expression was determined in embryonic mice. Interestingly, TRPV2 expression was detected in spinal motor neurons in addition to the dorsal root ganglia from embryonic day 10.5 and was localized in axon shafts and growth cones, suggesting that the channel is important for axon outgrowth regulation. We revealed that endogenous TRPV2 was activated in a membrane stretch-dependent manner in developing neurons by knocking down the TRPV2 function with dominant-negative TRPV2 and TRPV2-specific shRNA and significantly promoted axon outgrowth. Thus, for the first time we revealed that TRPV2 is an important regulator for axon outgrowth through its activation by membrane stretch during development.


Expression of the G72/G30 gene in transgenic mice induces behavioral changes.
The G72/G30 gene complex is a candidate gene for schizophrenia and bipolar disorder. However, G72 and G30 mRNAs are expressed at very low levels in human brain, with only rare splicing forms observed. We report here G72/G30 expression profiles and behavioral changes in a G72/G30 transgenic mouse model. A human BAC clone containing the G72/G30 genomic region was used to establish the transgenic mouse model, on which gene expression studies, western blot and behavioral tests were performed. Relative to their minimal expression in humans, G72 and G30 mRNAs were highly expressed in the transgenic mice, and had a more complex splicing pattern. The highest G72 transcript levels were found in testis, followed by cerebral cortex, with very low or undetectable levels in other tissues. No LG72 (the long putative isoform of G72) protein was detected in the transgenic mice. Whole-genome expression profiling identified 361 genes differentially expressed in transgenic mice compared with wild-type, including genes previously implicated in neurological and psychological disorders. Relative to wild-type mice, the transgenic mice exhibited fewer stereotypic movements in the open field test, higher baseline startle responses in the course of the prepulse inhibition test, and lower hedonic responses in the sucrose preference test. The transcriptome profile changes and multiple mouse behavioral effects suggest that the G72 gene may play a role in modulating behaviors relevant to psychiatric disorders.


Base-compositional biases and the bat problem. I. DNA-hybridization melting curves based on AT- and GC-enriched tracers.
We explored the interordinal relationships of mammals using DNA-DNA hybridization, with particular reference to the much-debated problem of whether the megabats and microbats are more closely related to each other than the megabats are to primates. To try to improve resolution when taxa are distantly related and the melting points of hybrids are low and difficult to distinguish, we increased the GC content of DNA by a fractionation method that used the same melting-point apparatus used in the hybridization studies. When we used GC-rich DNA as the tracer to make hybrids, the melting point of the self-hybrid shifted to a higher temperature as expected, but the behaviour of heterologous hybrids varied with the taxa being compared. When the melting point of the heterologous hybrid also shifted to a higher temperature so that the two compared taxa maintained the same or proportional distance, we called this 'following behaviour', because the heterologous hybrid made with GC-rich tracer 'followed' the GC-rich self-hybrid to higher temperatures. We also commonly saw anomalous behaviour, where the melting point of the heterologous hybrid shifted to a lower temperature when compared with an AT-rich hybrid. In these anomalous cases, the distance measured between the taxa increased markedly as a result of GC-enrichment, indicating that an underestimate of distance may have resulted from AT bias in DNA. This inference was supported by the finding that it was rare to observe a decrease in measured distance between taxa using GC-rich DNA, but very common to find an increase as would be expected from the generally higher AT contents of eutherian DNAs. Moreover, the most extreme cases, where distances changed most using GC-rich DNA, were usually those involving comparisons between taxa known to have the most extreme AT-biases among mammals, such as the megabats and rhinolophoid (including megadermatid) microbats. Our results show consistent underestimates of measured differences between eutherian taxa with extreme AT-biases.


Use of commercially available oral rehydration solutions in Lima, Peru.
Caregivers' practices concerning oral rehydration of young children during diarrheal illness were investigated in a periurban community of low socioeconomic level in Lima, Peru. Data of 330 caregivers of children aged 6-36 months were analyzed; 72.7% of all caregivers would give commercially available oral rehydration solutions (ORSs). However, only 58.6% of those caregivers with children that had experienced diarrhea during the previous week stated that they had used commercially available ORSs, a significantly lower percentage. The main reason for not using commercially available ORSs was that caregivers did not know about them. Of all recipes caregivers provided for homemade ORS, none contained the recommended concentrations of sugar and salt. Educating caregivers about availability, benefits, and use of commercially available ORSs as well as correct preparation of homemade ORS is urgently needed.


An Overview of Chitosan Nanofibers and their Applications in the Drug Delivery Process.
Chitosan is a polycationic natural polymer which is abundant in nature. Chitosan has gained much attention as natural polymer in the biomedical field. The up to date drug delivery as well as the nanotechnology in controlled release of drugs from chitosan nanofibers are focused in this review. Electrospinning is one of the most established and widely used techniques for preparing nanofibers. This method is versatile and efficient for the production of continuous nanofibers. The chitosan-based nanofibers are emerging materials in the arena of biomaterials. Recent studies revealed that various drugs such as antibiotics, chemotherapeutic agents, proteins and anti-inflammatory analgesic drugs were successfully loaded onto electrospun nanofibers. Chitosan nanofibers have several outstanding properties for different significant pharmaceutical applications such as wound dressing, tissue engineering, enzyme immobilization, and drug delivery systems. This review highlights different issues of chitosan nanofibers in drug delivery applications, starting from the preparation of chitosan nanofibers, followed by giving an idea about the biocompatibility and degradation of chitosan nanofibers, then describing how to load the drug into the nanofibers. Finally, the major applications of chitosan nanofibers in drug delivery systems.


Comparison of Multisegmental Foot and Ankle Motion Between Total Ankle Replacement and Ankle Arthrodesis in Adults.
Total ankle replacement (TAR) and ankle arthrodesis (AA) are usually performed for severe ankle arthritis. We compared postoperative foot segmental motion during gait in patients treated with TAR and AA. Gait analysis was performed in 17 and 7 patients undergoing TAR and AA, respectively. Subjects were evaluated using a 3-dimensional multisegmental foot model with 15 markers. Temporal gait parameters were calculated. The maximum and minimum values and the differences in hallux, forefoot, hindfoot, and arch in 3 planes (sagittal, coronal, transverse) were compared between the 2 groups. One hundred healthy adults were evaluated as a control. Gait speed was faster in the TAR ( P = .028). On analysis of foot and ankle segmental motion, the range of hindfoot sagittal motion was significantly greater in the TAR (15.1 vs 10.2 degrees in AA; P = .004). The main component of motion increase was hindfoot dorsiflexion (12.3 and 8.6 degrees). The range of forefoot sagittal motion was greater in the TAR (9.3 vs 5.8 degrees in AA; P = .004). Maximum ankle power in the TAR (1.16) was significantly higher than 0.32 in AA; P = .008). However, the range of hindfoot and forefoot sagittal motion was decreased in both TAR and AA compared with the control group ( P = .000). Although biomechanical results of TAR and AA were not similar to those in the normal controls, joint motions in the TAR more closely matched normal values. Treatment decision making should involve considerations of the effect of surgery on the adjacent joints. Level III, case-control study.


Dynamic Monte Carlo simulations of the three-dimensional random-bond Potts model.
The effect of random bonds on the phase transitions of the three-dimensional three-state Potts model is investigated with extensive dynamic Monte Carlo simulations. In the weakly disordered regime, the phase diagram is obtained with a recently suggested nonequilibrium reweighting method. The tricritical point separating the first- and second-order transitions is determined, and the critical exponents of the continuous phase transition induced by quenched randomness are estimated.


Lateral preference in Williams-Beuren syndrome is associated with cognition and language.
Williams-Beuren syndrome (WBS) is a genetically defined neurodevelopmental disorder presenting with intellectual disability associated with a specific neurocognitive profile characterized by anxiety, hypersociability, poor visuospatial skills and relatively preserved language. We have defined the lateral preference in 69 individuals (40 males and 29 females, age range 5-47 years) with WBS confirmed by molecular testing, and explored its correlation with cognition, behavior problems, the main aspects of the behavioral phenotype, and specific molecular variants (parental origin and size of the 7q11.23 deletion). Lateral preference (hand, foot, eye and ear) and neurobehavioral features [intelligence quotient (IQ), sociability, visuospatial construction, narrative skills and behavior] were assessed by a battery of tests and parental interviews. A large proportion of WBS individuals showed either left or mixed handedness (26 and 19%, respectively). Hand, foot and ear lateral preference showed significant association with IQ, with individuals with mixed lateral preference presenting lower general IQ, especially verbal IQ, with respect to subjects with well-defined laterality. Approachability, visuospatial ability, behavior problems or molecular variants were not associated with lateral preference. Our results indicate that, as in other neurodevelopmental disorders, laterality is poorly defined in a significant proportion of WBS individuals, and reinforces the idea that a correct definition of lateral preference is important for cognition and language.


Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.
Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system.


Illusion and reality: practical pitfalls in interpreting clinical trials.
This paper has attempted to review for the reader some of the common problem areas in the interpretation of results of cancer treatment. The intention has been to point out potential pitfalls in interpretation so that the reader can comprehend the literature with more insight and criticalness . The plethora of journals and ongoing investigations indicates a greater need for critical understanding on the part of readers. This understanding stretches from the definitions of success and failure used in generating survival curves, to the accumulation and analysis of data and presentation of the results. We hope this paper will help the reader to achieve a greater degree of that understanding.


Economic evaluation of micafungin versus caspofungin for the treatment of candidaemia and invasive candidiasis.
Micafungin demonstrated non-inferiority to caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in a major randomised clinical trial. The aim of this study was to investigate if micafungin is a cost-saving option compared with caspofungin for treating candidaemia and IC. A decision analytical model was constructed to capture downstream consequences of using either agent as initial therapy for candidaemia and IC. The main outcomes were treatment success and treatment failure (i.e. death, mycological persistence, emergent infection, clinical failure but microbiological success). Outcome probabilities and treatment pathways were derived from the literature. Cost inputs were from the latest Australian resources, and resource use was estimated by expert panel. The analysis was from the Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted. Micafungin (AU$52 816) was associated with a lower total cost than caspofungin (AU$52 976), with a net cost-saving of $160 per patient. This was primarily due to the lower cost associated with alternative antifungal treatment in the micafungin arm. Hospitalisation was the main cost-driver for both arms. The model outcome was most sensitive to the proportion of treatment success in the micafungin arm. Uncertainty analysis demonstrated that micafungin had a 58% chance of being cost-saving compared with caspofungin. Micafungin was cost-equivalent to caspofungin in treating candidaemia and IC, with variation in drug acquisition cost the critical factor.


Maintenance of self-imposed delay of gratification by four chimpanzees (Pan troglodytes) and an orangutan (Pongo pygmaeus).
Delay maintenance, which is the continuance over time of the choice to forgo an immediate, less preferred reward for a future, more preferred reward, was examined in 4 chimpanzees (Pan troglodytes) and 1 orangutan (Pongo pygmaeus). In the 1st experiment, the apes were presented with 20 chocolate pieces that were placed, one at a time, into a bowl that was within their reach. The apes could consume the available chocolate pieces at any time during a trial, but no additional pieces would be given. The total length of time taken to place the 20 items into the bowl ranged from 60 s to 180 s. All 5 apes delayed gratification on a majority of trials until all 20 chocolate pieces were presented. Unlike in most experiments with human children using this test situation, attention by the apes to the reward was not detrimental to delay maintenance. In a 2nd experiment with the chimpanzees only, 4 foods of differing incentive value were presented in different trials in the same manner as in Experiment 1. The chimpanzees were highly successful in obtaining all food pieces, and there was no difference in performance as a function of food type.


Seizure in a nonpredisposed individual induced by single-pulse transcranial magnetic stimulation.
Seizure induction is a rare, but serious adverse effect of the otherwise very safe method of transcranial magnetic stimulation (TMS). There are only very few single case reports concerning seizure in single-pulse TMS. All of these reports describe individuals with neurological disorders or epileptogenic medication. To our knowledge, we are the first to describe a healthy subject who developed symptoms of a seizure after single-pulse TMS during motor threshold estimation. This case report provides evidence that single-pulse TMS may provoke a seizure even in the absence of neurological risk factors. Differential diagnoses of a classic neurological seizure, that is, convulsive syncope and psychogenic seizure, are discussed. Neurogenic seizure after TMS and convulsive syncope are the most probable hypotheses, although clear specification of this singular incident remains impossible. Therefore, to minimize the risk for such rare adverse effects, existing and new suggestions are combined to provide reasonable precautions to be taken before and during TMS application.


Serum Levels of Visfatin and Interleukin-6 in Non-Obese Versus Obese Men with Coronary Artery Disease.
To evaluate and compare the serum levels of visfatin, interleukin-6 and lipid profile in non-obese and obese male patients with coronary artery disease. Observational, comparative study. Punjab Institute of Cardiology and Lahore General Hospital, Lahore, from July to December 2013. The participants included 20 non-obese group I with coronary artery disease (CAD) and 20 obese males group II with coronary artery disease (angiographically confirmed). All the participants were in the age group of 35 - 55 years being non-smokers and non-diabetic. Serum visfatin and interleukin-6 levels were analysed by Enzyme Linked Immunosorbent Assay (ELISA). Lipid profile was also evaluated. Results were compared with T-test and Mann Whitney U test. The values were considered significant at 0.05 level of significance. Serum visfatin 9.05 versus 3.9 ng/ml and interleukin-6 12.80 versus 0.60 pg/ml levels were significantly (p-value < 0.001 of both) raised in the obese CAD group as compared to non-obese with CAD. Lipid profile also showed raised levels of total serum cholesterol, low density lipoproteins, triglycerides, very low density lipoproteins and low levels of high density lipoproteins in obese group. Significantly raised levels of serum visfatin and interleukin-6 indicate adipose tissue as an imperative source of these adipocytokines involved in inflammation in CAD. Altered lipid profile also seen in obese patients with CAD.


Combat exposure and mental health outcomes: The incremental impact of nonsexual harassment on women veterans.
Objective: This study investigated the impact of combat exposure and nonsexual harassment (verbal and nonverbal behaviors that convey negative and harmful attitudes on the basis of minority status) on mental health functioning in female veterans who were deployed Afghanistan and Iraq. Method: Participants (N = 134) completed measures of combat exposure, nonsexual harassment, PTSD, depression, and alcohol use. Results: Binary logistic regression models indicated nonsexual harassment was significantly associated with later symptoms of PTSD and depression, but not problem drinking; combat exposure was significantly associated with symptoms of PTSD and alcohol use, but not depression. Relative risk ratios indicated that for women with even minimal exposure to combat, experiencing nonsexual harassment significantly increased the likelihood of manifesting PTSD, depression, and problem drinking symptoms that met at least minimum threshold for clinical diagnoses. The impact of nonsexual harassment resulted in an almost 4 times greater risk for PTSD symptoms and problem drinking and up to 6 times greater risk for depression when experienced concurrently with combat exposure. Conclusions: Although nonsexual harassment does not pose the same physical threat as assault from enemy fire, findings suggest that it does pose an invisible threat to mental health and contribute to understanding and contextualizing the impact of nonsexual harassment on female veterans' psychological well-being. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Course evaluation in post-basic education.
Course evaluation is defined 'as the collection and use of information in order to make decisions about an educational programme' (Cronbach 1963). The study described in this paper was undertaken by members of the professional and research staff of the Joint Board of Clinical Nursing Studies, London. The paper describes how the need for work on course evaluation arose and how a package was developed and piloted in 15 course centres with a total of 205 students. The ways in which the package is being used by schools of nursing and colleges of higher and further education is also described. The philosophy that evaluation has an important part to play in developing dynamic and sound educational systems is emphasized. Evaluation should be an integral part of every course and planned at the outset with other parts of the detailed course programme, involving both students and teachers in measuring the effectiveness of the course.


Microfilaria in pleural fluid cytology: A rare finding.
Lymphatic filariasis is endemic in India and Southeast Asia. Detection of microfilaria is infrequently reported during cytological evaluation of various lesions or body cavity fluids. Presence of microfilaria in pleural fluid cytology is very rare finding even in endemic areas. Few cases of accidental finding of microfilaria have been reported in association with malignant pleural effusion. But pleural effusion of filarial origin is extremely rare manifestation. Here we report a classical case of microfilaria in pleural fluid cytology.


Species-specific peptide ligands for the detection of Bacillus anthracis spores.
Currently available detectors for spores of Bacillus anthracis, the causative agent of anthrax, are inadequate for frontline use and general monitoring. There is a critical need for simple, rugged, and inexpensive detectors capable of accurate and direct identification of B. anthracis spores. Necessary components in such detectors are stable ligands that bind tightly and specifically to target spores. By screening a phage display peptide library, we identified a family of peptides, with the consensus sequence TYPXPXR, that bind selectively to B. anthracis spores. We extended this work by identifying a peptide variant, ATYPLPIR, with enhanced ability to bind to B. anthracis spores and an additional peptide, SLLPGLP, that preferentially binds to spores of species phylogenetically similar to, but distinct from, B. anthracis. These two peptides were used in tandem in simple assays to rapidly and unambiguously identify B. anthracis spores. We envision that these peptides can be used as sensors in economical and portable B. anthracis spore detectors that are essentially free of false-positive signals due to other environmental Bacillus spores.


Congenital right ventricular diverticulum associated with a ventricular septal defect: a rare echocardiographic finding.
A neonate presented on the first day of life with tachypnea and poor feeding. The infant's initial echocardiogram demonstrated outpouching of the lateral wall of the right ventricle (RV) associated with a large ventricular septal defect (VSD). At 9 days of age he was diagnosed with osteogenesis imperfecta (OI). Despite treatment with digoxin, diuretics, and captopril he required hospitalization twice during his first 2 months of life for congestive heart failure (CHF). The VSD was closed at three and one-half months of age without resection of the diverticulum and CHF symptoms resolved. At 26 months of age he is doing well despite the residual RV diverticulum. Congenital cardiac diverticula are rare forms of cardiac malformations and their echo-Doppler features are herein discussed.


Laryngeal papillomatosis: immunologic and viral basis for therapy.
The distressing nature of laryngeal papillomatosis and lack of clinical progress in its treatment are reviewed. Presently accepted and investigative methods of therapy are reviewed with special attention being given to immune therapy. Support for the concept of a viral etiology is discussed and other etiologic agents considered. Known and possibly significant roles of wart virus antibodies are discussed and the importance of complex interplay between maternal and fetal immune systems explored as a possible explanation for some puzzling aspects of laryngeal papillomatosis. Finally, a proposed experimental design is outlined, the purpose of which is to provide a useful animal model to investigate immune changes in laryngeal papillomatosis, as well as effects of surgical or medical therapy.


Universal mRNA Translation Enhancement with Gold Nanoparticles Conjugated to Oligonucleotides with a Poly(T) Sequence.
DNA-conjugated gold nanoparticles (AuNPs) have been shown to enhance the translation of mRNA. However, the specific sequence on the DNA dictates the specific mRNA to be enhanced. This study describes poly(thymine)-functionalized AuNPs (AuNP-p(T)DNA) capable of enhancing the translation of any mRNA template that is incorporated into pcDNA6 vector with bovine growth hormone (BGH) polyadenylation signal (P(A)). We demonstrated this by incorporating four genes: green fluorescence protein (GFP), general control nonderepressible 5 (GCN5), cAMP-responsive element binding protein 1 (CREB1), and X-box-binding protein 1-spliced (XBP-1S) separately into pcDNA6 vector with BGH P(A) before their expression in HeLa lysate. The addition of AuNP-p(T)DNA to HeLa lysate containing GFP, GCN5, CREB1, and XBP-1S mRNA increased protein synthesis 1.80, 1.99, 1.95, and 2.20 times, respectively. Similar translation enhancement was also observed in a multiplex reaction containing the mRNA of three genes together in the lysate. Complementary p(T)DNA hybridization to the poly(A) tail of the mRNA was critical as the removal of either p(T)DNA or BGH P(A) in XBP-1S mRNA or the replacement of p(T)DNA with p(A)DNA reduced the translation back to baseline level. Finally, an optimum length of 25 nucleotides for the DNA oligomer and a AuNP-p(T)DNA:mRNA ratio of 0.658 achieved a 3.08-fold translation enhancement. The AuNP-p(T)DNA nanoconstruct could be incorporated into commercial cell-free protein synthesis kits as a universal translation enhancer.


Pneumonia in South-East Asia Region: public health perspective.
Globally, pneumonia is the leading cause of death in young children and burden of disease is disproportionately high in South-East Asia Region of WHO. This review article presents the current status of pneumonia disease burden, risk factors and the ability of health infrastructure to deal with the situation. Literature survey was done for the last 20 years and data from country offices were also collected. The estimated incidence of pneumonia in under five children is 0.36 episodes per child, per year. Risk factors are malnutrition (40% in India), Indoor air pollution, non-breast feeding, chronic obstructive pulmonary disease, etc. Strengthening of health care delivery system for early detection and treatment and as well as minimization of preventable risk factors can avert a large proportion of death due to pneumonia.


Haemophagocytic lymphohistiocytosis associated with fulminant hepatitis and multiorgan failure following primary Epstein-Barr virus and herpes simplex virus type 1 infection.
We present a case of severe fatal hepatitis in a young patient presumably triggered by two ubiquitous viral diseases which occurred in close succession. This case is unusual because of the exceptional chronological sequence of primary Epstein-Barr virus and herpes simplex virus type 1 infection causing systemic immune dysregulation associated with rapidly developing liver failure and consecutive multiorgan failure. Clinical, laboratory and histopathological findings indicated the development of secondary haemophagocytic lymphohistiocytosis triggered by these closely succeeding viral primary infections.


A diversity of cancer incidence and mortality in West Asian populations.
Western Asia comprises a large proportion of the world population with different ethnicities and religions inhabiting areas of diverse geographic features. The countries of this region have experienced rapid economic growth over the latter half of the 20th century, which continues to this day, resulting in major changes in lifestyle of the population. The aim of this study was to compare the incidence and mortality of cancer in West Asia using the estimates reported by the International Agency for Research on Cancer (IARC) in Globocan-2012. Countries with high-quality data or national data (based on the definition of the Globocan-2012) were included in the analysis. These included Bahrain, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, and Turkey. We also found high-quality cancer data from regional cancer registries in 3 Iranian and 3 Turkish provinces. Data on cancer incidence and mortality were collected and described in tables and graphs. Spearman's correlation test was used to assess the correlation between geographic coordinates and the incidence age-standardized rate (ASR; per 100,000 person-years) of cancers. Nine countries and 6 regional registries were included. Cancers of the lung (ASR, 33.3), prostate (24.9), bladder (19.1), stomach (16.5), and colorectal (15.9) were the most common malignancies in men. The most common cancers in women were those of the breast (35.4), colorectal (12.1), thyroid (10.3), stomach (9.2), and lung (6.7). The incidence rates of upper gastrointestinal and lung cancers were considerably higher in the northern part of this region, including Turkey and northern Iran compared with southern countries. High incidences of breast, colorectal, prostate, and bladder cancers were found in countries located in the northwest including Jordan, Lebanon, and Turkey. The most common cancers differed by country. Consequently, cancer control programs must be tailored to the most common types of cancers in each country. Lack of high-quality data for some West Asian countries was the major limitation of this study. Therefore, as the first step of cancer control programs, it is recommended that well-structured population-based cancer registries be established in all of these countries.


Global research evidence on nomophobia during 2008-2022: a bibliometric analysis and review.
Nomophobia, often known as a 21st-century disorder, is a recent condition that has received considerable attention, with numerous studies conducted to better understand it since it was first introduced in 2008. To better understand the present research status and prospects to assist practitioners, policymakers, and funding agencies in protecting the population from nomophobia-related harm, a bibliometric study of nomophobia-related publications was conducted. We used Scopus and dimensions.ai to perform a search between 2008 and 2022. The HistCite, R software, and VOSviewer were used to analyze the data and extract relevant keywords indexed in medical databases using mesh heading phrases. Between January 2008 and April 2022, 1,781 papers, 30 datasets, two grants, six patents, four clinical trials, and five policy documents were identified. The bulk of the articles included in this review were published after 2017 with the majority written in English. Most of the research focuses on determining the prevalence of nomophobia in various populational groups, such as students, clinical samples, and the general adult population. Several studies examined the possible association between nomophobia symptoms and other psychiatric or physical health issues, such as changes in sleep, learning and attention, academic performance, coping strategies, etc. The current body of research knowledge of nomophobia in the main includes epidemiologic and diagnostic effort that has provided mixed results regarding its assessment and prevalence rates, and appreciable data on its treatment and prevention are lacking.


[Failure of platelet spreading in thrombasthenia due to changes of high molecular weight membrane glycopeptides (author's transl)].
Rabbit and thrombastheinic platelet membranes were examined by SDS polyacrylamide gel electrophoresis. Both rabbit and thrombasthenic platelets failed to spread on siliconized glass surfaces and revealed platelet membrane glycoprotein patterns quite different from those of normal human platelet membranes. Typical for normal platelet membranes are four high molecular weight glycoprotein bands. The platelet membranes from rabbits and from one thrombasthenic patient showed only the first major glycopolypeptide with an apparent molecular weight of 135000 and 120000 D respectively. Other platelet membrane glycopeptides (both the carbohydrate and polypeptide moiety) were completely absent in thrombasthenia. The rabbit platelet membrane yet contains two strong polypeptides in this high molecular weight region, however, without corresponding carbohydrate moieties. Therefore, we support the view that the carbohydrate chains from two high molecular weight glycoproteins are of importance for platelet spreading on glass surfaces.


Limited prescribing powers for newly qualified nurses?
New graduate nurses will be given limited prescribing powers, according to the Nursing and Midwifery Council's (NMC) draft education plans as seen by Nursing Standard. The unpublished plans, called Standards for Registered Nurse Education, are under consideration by the regulator in its 'radical' overhaul of nursing education.


Improving hospital discharge arrangements for people who are homeless: A realist synthesis of the intermediate care literature.
This review presents a realist synthesis of "what works and why" in intermediate care for people who are homeless. The overall aim was to update an earlier synthesis of intermediate care by capturing new evidence from a recent UK government funding initiative (the "Homeless Hospital Discharge Fund"). The initiative made resources available to the charitable sector to enable partnership working with the National Health Service (NHS) in order to improve hospital discharge arrangements for people who are homeless. The synthesis adopted the RAMESES guidelines and reporting standards. Electronic searches were carried out for peer-reviewed articles published in English from 2000 to 2016. Local evaluations and the grey literature were also included. The inclusion criteria was that articles and reports should describe "interventions" that encompassed most of the key characteristics of intermediate care as previously defined in the academic literature. Searches yielded 47 articles and reports. Most of these originated in the UK or the USA and fell within the realist quality rating of "thick description". The synthesis involved using this new evidence to interrogate the utility of earlier programme theories. Overall, the results confirmed the importance of (i) collaborative care planning, (ii) reablement and (iii) integrated working as key to effective intermediate care delivery. However, the additional evidence drawn from the field of homelessness highlighted the potential for some theory refinements. First, that "psychologically informed" approaches to relationship building may be necessary to ensure that service users are meaningfully engaged in collaborative care planning and second, that integrated working could be managed differently so that people are not "handed over" at the point at which the intermediate care episode ends. This was theorised as key to ensuring that ongoing care arrangements do not break down and that gains are not lost to the person or the system vis-à-vis the prevention of readmission to hospital.


Modification of TNF-alpha pharmacokinetics in SA-1 tumor-bearing mice.
Fibrosarcoma-SA-I-tumor-bearing mice were treated s.c. in the vicinity of tumors (peri-tumorally) or intravenously, with recombinant human TNF-alpha lacking 1 to 3 amino acids from N-terminal part (TNF-alpha Nv3). Tumor growth delay, observed after both routes of TNF-alpha Nv3 application, was statistically significant, though a better anti-tumor effect was achieved after peri-tumoral application. TNF-alpha Nv3 serum levels were determined in these animals and compared with TNF-alpha Nv3 serum levels in healthy animals, which were treated with TNF-alpha Nv3 either s.c. or i.v. The peak serum levels of TNF-alpha Nv3 applied peri-tumorally/s.c. were significantly higher in tumor-bearing than in healthy mice, whereas smaller differences in peak serum levels were found after i.v. application, which might correlate with anti-tumor activity. Whatever the route of application, TNF-alpha Nv3 elimination from the serum of tumor-bearing mice was slower than that in healthy animals. Also, comparison of TNF-alpha Nv3 pharmacokinetic parameters for tumor-free and sarcoma- or melanoma-bearing mice has demonstrated that the pharmacokinetics of TNF-alpha Nv3 are modified in tumor-bearing animals.


A randomized controlled trial of a 2% minocycline gel as an adjunct to non-surgical periodontal treatment, using a design with multiple matching criteria.
Topical locally delivered minocycline is an adjunctive to non-surgical periodontal treatment, but there are few reported trials. Previous trials have reported differences between changes in probing depth in treatment and control groups, but no differences in probing attachment level. In the present study, 30 subjects were paired according to gender, age, ethnic group, smoking habits, and probing depths. Both groups received intensive oral hygiene education and root planing with local anaesthesia. Active or placebo gel was placed subgingivally at planed sites in each subject according to a double-blind protocol, immediately after instrumentation, and 2 and 4 weeks later. A periodontal examination was made with a constant force probe before instrumentation, and 6 and 12 weeks later, 2 subjects failed to complete the study, and their pairs were therefore not included in the analysis. Results were tested with analysis of covariance. Differences between groups in mean probing depth did not reach statistical significance at any visit (baseline: test (T) = 5.93 mm, control (C) = 5.74 mm; 6 weeks: T = 3.53 mm, C = 3.63 mm; 12 weeks: T = 3.29 mm, C = 3.44 mm), but mean probing attachment levels were different (p < 0.05) at both reassessments (baseline: T = 6.86 mm, C = 6.83 mm; 6 weeks: T = 4.93 mm, C = 5.30 mm; 12 weeks T = 4.91 mm, C = 5.27 mm). There was also a difference in the number of sites with bleeding on deep probing at 12 weeks (p < 0.05). This trial showed that adjunctive minocycline gel provided a more advantageous outcome for nonsurgical periodontal treatment in terms of probing attachment level and bleeding on deep probing. This trial was a good example of experimental, as opposed to community, design, and used limited resources to show a clear result.


Molecular Targeting of ERKs/RSK2 Signaling in Cancers.
Accumulating studies have provided concrete evidence that p90 ribosomal S6 kinase 2 (RSK2) is a key signaling molecule involved in cell proliferation, transformation, and cancer development. RSK2 is known to be an etiological gene of Coffin-Lowry Syndrome (CLS). Recently, signaling analysis and molecular biological approaches have provided concrete evidence that RSK2 plays an essential role in human cancers. Here, we will extensively discuss signaling pathways regulating RSK2 activity, the role of RSK2 in human cancer development, inhibitors suppressing RSK2 activity, and why RSK2 is an important target to develop drugs for human cancers.


A case of bisphosphonate-related osteonecrosis of the maxilla with orbital cellulitis.
Bisphosphonates are used for the treatment of bone metastases of cancer and prevention of osteoporosis. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has unclear mechanisms, but its elucidation, prevention, and treatment are essential to improve patient outcomes.An 88-year-old woman who was taking oral bisphosphonates for 4 years presented with a 5-day history of gradual orbital pain. Computed tomography (CT) revealed bilateral maxillary sinusitis and bony destruction at the base of the right maxillary sinus and inferior orbital wall. We diagnosed her with bisphosphonate-related osteonecrosis of the maxilla. In addition to intravenous antibiotic treatment, an endoscopic sinus surgery was performed. The patient's postoperative course was uneventful.To the best of our knowledge, this is the first case report of BRONJ with orbital cellulitis. This condition should be considered among patients taking bisphosphonates, who manifest with symptoms of orbital cellulitis and bone destruction on imaging.


Histone acetyltransferase 1 is required for DNA replication fork function and stability.
The replisome is a protein complex on the DNA replication fork and functions in a dynamic environment at the intersection of parental and nascent chromatin. Parental nucleosomes are disrupted in front of the replication fork. The daughter DNA duplexes are packaged with an equal amount of parental and newly synthesized histones in the wake of the replication fork through the activity of the replication-coupled chromatin assembly pathway. Histone acetyltransferase 1 (HAT1) is responsible for the cytosolic diacetylation of newly synthesized histone H4 on lysines 5 and 12, which accompanies replication-coupled chromatin assembly. Here, using proximity ligation assay-based chromatin assembly assays and DNA fiber analysis, we analyzed the role of murine HAT1 in replication-coupled chromatin assembly. We demonstrate that HAT1 physically associates with chromatin near DNA replication sites. We found that the association of HAT1 with newly replicated DNA is transient, but can be stabilized by replication fork stalling. The association of HAT1 with nascent chromatin may be functionally relevant, as HAT1 loss decreased replication fork progression and increased replication fork stalling. Moreover, in the absence of HAT1, stalled replication forks were unstable, and newly synthesized DNA became susceptible to MRE11-dependent degradation. These results suggest that HAT1 links replication fork function to the proper processing and assembly of newly synthesized histones.


Fas-mediated apoptosis of the hematopoietic progenitor cells in mice infected with murine cytomegalovirus.
The effects of cytomegalovirus (CMV) infection on hematopoietic progenitor cells in vivo were investigated to elucidate the pathogenesis of CMV-induced myelosuppression. BALB/c mice were inoculated with 0.2LD50 of murine CMV (MCMV). Lineage marker negative, c-kit positive (Lin-c-kit+) and Lin-CD34+ cells, which are both phenotypically defined as hematopoietic progenitor cells, showed a significant reduction in number on day 3 postinfection (pi). Moreover, the reduction in the number of day-14 colony-forming units-spleen (CFU-S), another indicator to identify hematopoietic progenitor cells, was noted on day 3 pi. To clarify the mechanism of such depletion, we examined the cells undergoing apoptosis in the Lin- populations and found a 15-fold increase in the apoptosis-induction of these cells. Furthermore, an increase in the expression level of Fas, which mediates apoptosis, was observed in such Lin-c-kit+ and Lin-Sca-1+ cells on day 3 pi. In vitro treatment with the anti-Fas antibody accelerated the apoptosis in Lin- cells, but not in the uninfected control cells, thus indicating that the upregulated Fas on Lin- cells is directly related to the acceleration of apoptosis found in these cells in vivo. These results suggest that MCMV infection reduces the number of hematopoietic progenitor cells in bone marrow at least in part due to Fas-mediated apoptosis, and this phenomenon is thus considered to contribute to CMV-induced myelosuppression.


A novel host factor for human respiratory syncytial virus.
Human respiratory syncytial virus (RSV) is the leading viral cause of severe lower respiratory disease in young children worldwide. As part of a genome-wide siRNA screen, we recently discovered that actin-related protein 2 (ARP2) is a host factor in the RSV replication cycle. ARP2 is a major constituent of the ARP2/3 complex, which catalyzes actin polymerization involved in cell morphology and motility. In the course of investigating this finding, we also found that RSV infection of human lung epithelial A459 cells induced filopodia formation and stimulated cell motility. The increase in filopodia formation was due, at least in part, to the expression of the RSV fusion F protein. Filopodia formation and increased cell motility appeared to shuttle RSV particles to nearby uninfected cells, facilitating virus cell-to-cell spread. ARP2 depletion did not reduce RSV entry or gene expression early in infection, but reduced subsequent virus production, filopodia formation, cell motility, and viral spread. Thus, the RSV F protein, ARP2-mediated actin nucleation, filopodia formation, and cell mobility all contribute to previously unrecognized mechanisms for RSV cell-to-cell spread that may promote RSV pathogenesis.


[FORCE-FEEDING OR LIFE-SAVING? - DEALING WITH HUNGER STRIKES IN ISRAEL].
Force feeding of fasting hunger-striking prisoners is the subject of considerable controversy in Israel and elsewhere, posing a direct conflict between two basic ethical values: that of human life and respect for autonomy. The Israel Medical Association, as well as the World Medical Association, has taken the position that force feeding of such prisoners is an act of torture and is therefore unethical. However this paper presents an opposing view, which recently became the law in Israel, that, whereas the rights of prisoners to decree a hunger strike as a form of protest should be respected, if the prolongation of the strike reaches a stage of clear and present danger to the life and health of a prisoner, the saving of the prisoner's life must take precedence over considerations of autonomy. The paper present the steps that should be taken, including extensive and empathic efforts to persuade the prisoner to end his/her fast; gaining the approval of a hospital's ethics committee; and gaining the approval of a district court judge; the feeding is to be carried out in the most humane and sensitive manner as befitting a lifesaving procedure for any patient. This position is consistent with Israel's Basic Law: Human Dignity and Liberty, Israel's Patient Rights Law, Israel's "Do not stand idly by your fellow man's blood" Law, with several Israeli court decisions and in keeping with the dominant Israeli culture. Finally, instructions for physicians who object to such measures are discussed, ascertaining the freedom of conscience as well as preserving the life of the hunger-strikers.


Salvianolic acid B inhibits mitochondrial dysfunction by up-regulating mortalin.
Salvianolic acid B is an antioxidative ingredient derived from Radix Salviae miltiorrhizae that has been widely used to treat liver diseases. However, the therapeutic mechanism underlying Salvianolic acid B has remained largely unknown. Our studies verified that Salvianolic acid B efficiently blocked mitochondrial deformation and dysfunction induced by H2O2 in the human hepatocyte cell line HL7702. Mortalin, a mitochondrial molecular chaperone, maintains mitochondrial morphology stabilization and function integrity. Previous results showed that mortalin overexpression has been observed in hematoma carcinoma cells and that mortalin maintains mitochondrial homeostasis and antagonizes oxidative stress damage. We found that Salvianolic acid B significantly up-regulated mortalin protein expression levels. In addition, Salvianolic acid B lost the function of preventing mitochondrial deformation and dysfunction induced by oxidative stress under mortalin knockdown conditions. We further found that mortalin overexpression increases the mRNA expression of mitofusin-related factor Mfn1 and mitofission-related factor hFis1. In conclusion, Salvianolic acid B maintains the mitochondrial structure stabilization and functional integrity by up-regulating mortalin, which may be associated with increased mitofusin factor Mfn1 and reduced mitofission factor hFis1.


Prevalence of Physical Violence Against Brazilian Women: Systematic Review and Meta-Analysis.
Violence against women is a major problem in Brazil, but data on its prevalence are scarce. We aimed to estimate the prevalence of physical violence against women in Brazil. We conducted a systematic review and meta-analysis of the prevalence of physical violence against women. Population-based researches that assessed physical violence in Brazilian women were searched on MEDLINE, Embase, Scopus, and VHL/BIREME. The last search update was carried out in March 2020. Two researchers selected the studies, extracted the data, and assessed the quality of the eligible studies. Summary of prevalence and 95% confidence interval (CI) was calculated using Freeman-Tukey double arccosine transformation, weighted by the official local population size. Heterogeneity was estimated by I 2 and investigated by meta-regression analyses. Of 3,408 reports, 13 studies carried out from 1999 to 2016 (n = 25,781 women) were included. Most studies had limitations on sample size (5/13) and response rate (7/13). The prevalence of physical violence was 22.4% in lifetime (95% CI [21.6, 23.2%]; I 2 = 99.0%), and 11.5% in previous year (95% CI [11.1, 11.9%]; I 2 = 99.5%). Assuring privacy during interview significantly increased the prevalence (p = .028; residual I 2 = 80.0%). Higher prevalence was also observed in studies with adequate sample source, validated questionnaire, and privacy (in both recall periods), potentially due to lower risk of nonresponse bias. Over two in 10 Brazilian women suffered physical violence during their lives, and over one tenth, in the previous year. Measurement of outcome affected the prevalence; privacy should be assured for the interviewee for future reliable estimates in the country.


The Medical Humanities at the Northeastern Ohio Universities College of Medicine: historical, theoretical, and curricular perspectives.
The Human Values in Medicine Program (HVM) at the Northeastern Ohio Universities College of Medicine is composed of 120 required hours in medical humanities, social sciences, and behavioral sciences. In addition to a required HVM month in the fourth year when the bulk of the course work is completed, students can also choose from lectures, seminars, and short courses during the first, second, and third years. The broad goal of the HVM program as originally conceived was for students to use the content and skills of the humanities disciplines to reflect on their own and others' values, and to appraise their role in the patient-physician relationship, both in the community and in the larger culture. During the past several years, a cultural studies orientation has also been included, particularly the practice of critical analysis aimed at identifying the inequities and injustices within the doctor-patient relationship, in medical training, and in health care access and delivery in the U.S. and beyond. Current program development includes standardizing a bioethics curriculum for all students and developing a required fourth-year course that all students take during their HVM elective month.


Theoretical and experimental analyses of a legged piezoelectric bending actuator with shoe soles made of polyimide composites.
Friction materials form a critical component of piezoelectric actuators, and wear of the material affects output and service life of the actuator. This paper examines the influence of polyimide (PI) composites when used as a friction material on the performance of a legged piezoelectric bending actuator. We design and manufacture demountable shoe soles, made of a novel PI-based friction material, for an actuator. A Coulomb friction model is also established to determine the behavior resulting from contact-induced friction between the surface and the actuator. Reciprocating wear tests involving an insulation rubber pad against phosphor bronze and PI composites as friction materials yielded average friction coefficients of 0.21 and 0.28, respectively. We also found that PI composites have higher wear resistance than phosphor bronze, with a specific wear rate of 1.36 × 10-4 mm3/N m. The results of experiments and simulations indicate that the shoe soles made of PI composites reduced the actuator's driving frequency and vibrational amplitude, but they did not affect the principle of locomotion of the actuator. Furthermore, the operational stability of the actuator improved by 46.8% by using the demountable shoe soles made of PI composites, albeit at the cost of its velocity and load capacity. This work has guiding significance for the design and selection of friction materials for piezoelectric actuators.


LOX-induced lipid peroxidation mechanism responsible for the detrimental effect of marine diatoms on zooplankton grazers.
Some marine diatoms negatively affect the reproduction of dominant zooplankton grazers such as copepods, thus compromising the transfer of energy through the marine food chains. In this paper, the metabolic mechanism that leads to diatom-induced toxicity is investigated in three bloom-forming microalgae. We show that copepod dysfunctions can be induced by highly reactive oxygen species (hROS) and a blended mixture of diatom products, including fatty acid hydroperoxides (FAHs); these compounds display teratogenic and proapoptotic properties. The process is triggered by the early onset of lipoxygenase activities that elicit the synthesis of species-specific products, the basic structures of which were established (1-20); these compounds boost oxidative stress by massive lipid peroxidation. Our study might explain past laboratory and field results showing how diatoms damage zooplankton grazers even in the absence of polyunsaturated aldehydes, a class of molecules that has been formerly implicated in mediating the toxic activity of diatoms on copepods.


Quipazine increases renin release by a peripheral hemodynamic mechanism.
Systemically administered serotonin (5-HT) agonists have been suggested to act centrally to increase plasma renin activity (PRA) and arterial pressure (AP). To test this hypothesis, hemodynamic responses were determined in conscious male rats after intracerebroventricular (i.c.v.) or intravenous (i.v.) administration of the direct 5-HT agonist quipazine. When administered i.v., quipazine increased AP and PRA, and decreased renal blood flow (RBF); doses of quipazine i.c.v. that increased AP to a similar degree failed to increase PRA. The increase in PRA elicited by i.v. quipazine was not blocked by propranolol, suggesting non-neural mechanisms. The increase in AP and decrease in RBF elicited by i.v. quipazine were not eliminated by prazosin, enalapril, or a V1-vasopressin antagonist administered alone or in combination. LY 53857, a 5-HT2 antagonist that enters the central nervous system (CNS), blocked all responses to i.v. quipazine. In contrast, the peripheral 5-HT2 antagonist xylamidine blocked the renin and RBF responses, but only attenuated the pressor response to quipazine. These data suggest that quipazine can act in the CNS to increase AP, but when administered systemically quipazine also activates vascular 5-HT2 receptors to increase AP further and to decrease RBF. The increase in PRA caused by i.v. quipazine is secondary to renal hemodynamics and is unrelated to CNS actions of this drug.


Study of Adsorption and Flocculation Properties of Natural Clays to Remove Prorocentrum lima.
High accumulations of phytoplankton species that produce toxins are referred to as harmful algal blooms (HABs). HABs represent one of the most important sources of contamination in marine environments, as well as a serious threat to public health, fisheries, aquaculture-based industries, and tourism. Therefore, methods effectively controlling HABs with minimal impact on marine ecology are required. Marine dinoflagellates of the genera Dinophysis and Prorocentrum are representative producers of okadaic acid (OA) and dinophysistoxins responsible for the diarrhetic shellfish poisoning (DSP) which is a human intoxication caused by the consumption of shellfish that bioaccumulate those toxins. In this work we explore the use of natural clay for removing Prorocentrum lima. We evaluate the adsorption properties of clays in seawater containing the dinoflagellates. The experimental results confirmed the cell removal through the flocculation of algal and mineral particles leading to the formation of aggregates, which rapidly settle and further entrain cells during their descent. Moreover, the microscopy images of the samples enable one to observe the clays in aggregates of two or more cells where the mineral particles were bound to the outer membranes of the dinoflagellates. Therefore, this preliminary data offers promising results to use these clays for the mitigation of HABs.


Venous air embolism during neurosurgery. A comparison of various methods of detection in man.
A comparison of the various methods available for the detection of air embolus has been carried out in patients undergoing posterior fossa exploration in the sitting position. A group of 17 patients (Group A) was comprehensively monitored by a central venous catheter, an infra-red carbon dioxide analyser and a Doppler ultrasonic flow transducer in addition to more traditional clinical methods. Group B (19 patients) was monitored by commonly used clinical methods consisting of continuous palpation of the radial pulse, intermittent blood pressure measurement, the use of an oesophageal stethoscope and the electrocardiograph. In Group A the detection of air embolus varied from 6% using an oesophageal stethoscope to 58% by the Doppler method. In Group B air embolus was diagnosed in 10% of patients. One patient in each group died from air embolus; one patient had a paradoxical embolus to the coronary arteries. It is concluded that comprehensive monitoring for air embolus, including the use of Doppler ultrasound, is an essential part of the management of these patients, for both diagnosis and treatment.


Effect of detergents on pathogenicity plasmids of escherichias.
The study dealth with effects of cationic detergents miramistin (alkylamidopropyldimethylbenzylammonium chloride), catamine AB (alkyldimethylbenzylammonium chloride) and the anionic compound sodium dodecyl sulphate (SDS) on the elimination from E. coli cells of plasmids determining the Hly, Ent and, indirectly, Col, F, and R markers of pathogenicity as well as their transfer upon conjugation. At subbacteriostatic concentrations, miramistin and catamine AB were found to suppress the transfer of Hly, Ent, F, and R plasmids during conjugation when applied to the donor, recipient or added to the conjugation medium without, however, eliminating plasmids. This is due to the disruption by detergents of F, J pili and other surface cell structures resulting in diminished ability to conjugate. Anionic SDS eliminated F and R plasmids without affecting Hly, Ent and Col.


Tissue engineering of ligaments: a comparison of bone marrow stromal cells, anterior cruciate ligament, and skin fibroblasts as cell source.
Anterior cruciate ligament (ACL) reconstruction surgery still has important problems to overcome, such as "donor site morbidity" and the limited choice of grafts in revision surgery. Tissue engineering of ligaments may provide a solution for these problems. Little is known about the optimal cell source for tissue engineering of ligaments. The aim of this study is to determine the optimal cell source for tissue engineering of the anterior cruciate ligament. Bone marrow stromal cells (BMSCs), ACL, and skin fibroblasts were seeded onto a resorbable suture material [poly(L-lactide/glycolide) multifilaments] at five different seeding densities, and cultured for up to 12 days. All cell types tested attached to the suture material, proliferated, and synthesized extracellular matrix rich in collagen type I. On day 12 the scaffolds seeded with BMSCs showed the highest DNA content (p < 0.01) and the highest collagen production (p < 0.05 for the two highest seeding densities). Scaffolds seeded with ACL fibroblasts showed the lowest DNA content and collagen production. Accordingly, BMSCs appear to be the most suitable cells for further study and development of tissue-engineered ligament.


Preconcentration of trace arsenite and arsenate with titanium dioxide nanoparticles and subsequent determination by silver diethyldithiocarbamate spectrophotometric method.
A novel method of preconcentration of trace arsenite and arsenate by using titanium dioxide nanoparticles as adsorbent was described. The concentrations of preconcentrated arsenite and arsenate were determined by a silver diethyldithiocarbamate spectrophotometric method without desorption. Batch adsorption experiments were carried out as a function of the pH, contact time, amount of titanium dioxide nanoparticles, and solution volume. In the pH range 5 to 6, adsorption rates of arsenite and arsenate were higher than 98%. The calibration coefficient was 0.9991, and the linear range was 0 to 100 microg/L. The developed method was precise, with the relative standard deviation <5% at concentration level of 10 microg/L, with a detection limit (3sigma, n=6) of 0.44 microg/L. The accuracy of the method for total arsenic was validated by standard reference materials (SRM 3103a) (National Institute of Standards and Technology, Gaithersburg, Maryland). The method was also applied to the analysis of arsenite and arsenate in natural water samples to verify the accuracy. The recovery values remained in a narrow range, from 95 to 103%.


Viscoelastic behaviour of deformed spines under correction with halo pelvic distraction.
The applied tensile tractive force between skull and pelvis of the Halo Pelvic Distraction appliance has been measured using a simple compression spring device. Details of these external force measurements with daily distraction and correction of spinal deformity are illustrated for 10 patients which include tuberculous kyphoses, paralytic scolioses, and congenital and idiopathic scolioses. The relationships between applied load, time, amount of distraction, and extent of spinal curvature were studied in terms of the biomechanical proerties of elasticity and plasticity. A linear relationship exists between the total distraction distance and the reduction in the angle of the spinal deformity. For this correction procedure the rates of distraction, the total distraction amount, the total duration of the distractional period, and the maximum load depend on each individual spinal deformity with its particular peculiarities.


Effect of different levels of feed restriction and fish oil fatty acid supplementation on fat deposition by using different techniques, plasma levels and mRNA expression of several adipokines in broiler breeder hens.
Reproductive hens are subjected to a restricted diet to limit the decline in fertility associated with change in body mass. However, endocrine and tissue responses to diet restriction need to be documented. We evaluated the effect of different levels of feed restriction, with or without fish oil supplementation, on metabolic parameters and adipokine levels in plasma and metabolic tissues of reproductive hens. We designed an in vivo protocol involving 4 groups of hens; RNS: restricted (Rt) unsupplemented, ANS: ad libitum (Ad, receiving an amount of feed 1.7 times greater than animals on the restricted diet) unsupplemented, RS: Rt supplemented, and AS: Ad supplemented. The fish oil supplement was used at 1% of the total diet composition. Hens fed with the Rt diet had a significantly (P < 0.0001) lower growth than Ad hens, while the fish oil supplementation had no effect on these parameters. Furthermore, the bioelectrical impedance analysis (BIA) and the fat ultrasonographic examinations produced similar results to the other methods that required animals to be killed (carcass analysis and weight of adipose tissue). In addition, the Rt diet significantly (P < 0.05) decreased plasma levels of triglycerides, phospholipids, glucose and ADIPOQ, and fish oil supplementation decreased plasma levels of RARRES2. We also showed a positive correlation between insulin values and ADIPOQ or NAMPT or RARRES2 values, and a negative correlation of fat percentage to RARRES2 values. Moreover, the effects of the Rt diet and fish oil supplementation on the mRNA expression depended on the factors tested and the hen age. Rt diet and fish oil supplementation are able to modulate metabolic parameters and the expression of adipokines and their receptors in metabolic tissue.


Ultrasound-Induced Prenatal Stress: New Possibilities for Modeling Mental Disorders.
The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress. The use of variable frequency ultrasound in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of prenatal stress induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment.


Band gap narrowing of titanium oxide semiconductors by noncompensated anion-cation codoping for enhanced visible-light photoactivity.
"Noncompensated n-p codoping" is established as an enabling concept for enhancing the visible-light photoactivity of TiO2 by narrowing its band gap. The concept embodies two crucial ingredients: the electrostatic attraction within the n-p dopant pair enhances both the thermodynamic and kinetic solubilities, and the noncompensated nature ensures the creation of tunable intermediate bands that effectively narrow the band gap. The concept is demonstrated using first-principles calculations, and is validated by direct measurements of band gap narrowing using scanning tunneling spectroscopy, dramatically redshifted optical absorbance, and enhanced photoactivity manifested by efficient electron-hole separation in the visible-light region. This concept is broadly applicable to the synthesis of other advanced functional materials that demand optimal dopant control.


Low-temperature rapid-scan detection of reactive intermediates in epoxidation reactions catalyzed by a new enzyme mimic of cytochrome p450.
The use of synthetic iron(III) porphyrins as models for heme-type catalysts in biomimetic cytochrome P450 research has provided valuable information on the nature and reactivity of intermediates produced in the "peroxide shunt" pathway. This article reports spectroscopic detection of reactive intermediates formed in the epoxidation reaction of cis-stilbene with m-chloroperoxybenzoic acid catalyzed by a new mimic of cytochrome P450 with a substituted RSO3- group (1). The application of low-temperature rapid-scan stopped-flow techniques enabled the determination of equilibrium and rate constants for the formation and decay of all intermediates in the catalytic cycle of 1, including the rate constant for the formation (1*+)FeIV=O and for oxygen transfer to the substrate. Noteworthy, the reaction of (1*+)FeIV=O with cis-stilbene leads to an almost complete re-formation (95%) of the starting complex 1. The results show that complex 1 is a valuable catalyst with promising properties for further applications in a biomimetic approach toward mimicking oxygenation reactions of cytochrome P450.


[Restless legs syndrome in patients diagnosed with attention deficit hyperactivity disorder].
Restless legs syndrome (RLS) is a common neurological disease. RLS has been linked to various psychiatric disorders, especially with attention deficit hyperactivity disorder (ADHD). The main objective was to describe the frequency of RLS in pediatric patients diagnosed with ADHD. Secondary objectives of the study were describe other sleep disorders in ADHD patients. A multicentre prospective study was conducted in nine Spanish centers. We included children aged 6-18 years diagnosed with ADHD between January and June 2015. Data were collected by 13 researchers doctors through an interview with the parent/caregiver and with the child. To assess the degree of functioning of patients with ADHD we used the Children's Global Assessment Scale. The Sleep Disturbance Scale for Children was applied to screening sleep disorders in childhood. A sample of 73 patients was collected. Five patients (6.8%) met diagnostic criteria for RLS: four of them definitive and one probable. RLS is a frequent condition in adulthood but also in adolescence and childhood. ADHD patients have an increased risk of an RLS.


The Prevalence of Inflammatory Bowel Disease (IBD) in Patients with Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis.
This systematic review and meta-analysis aim to update the pooled prevalence of Inflammatory bowel disease (IBD) in patients with multiple sclerosis (MS). Two researchers independently and systematically searched PubMed, Scopus, EMBASE, Web of Science, and google scholar. They also searched for references of the included studies, and conference abstracts that were published up to September 2021. The literature search revealed 5719 articles, after deleting duplicates 3616 remained. Finally, 17 studies were included. The pooled prevalence of IBD in MS was 1% (I2 = 96.3%, P < 0.001). The pooled odds ratio of developing IBD in MS cases was 1.36 (95% CI: 1.1-1.6) (I2 = 58.3, P = 0.01). The results of this systematic review and meta-analysis show that the pooled prevalence of IBD in MS patients was 1% and the pooled odds ratio of developing IBD in MS cases was 1.36.


Arousal and the control of perception and movement.
Recent discoveries on the nature of the activity generated by the reticular activating system (RAS) suggest that arousal is much more involved in perception and movement than previously thought. The RAS is not simply an amorphous, unspecific region but rather a distinct group of nuclei with specific cell and transmitter types that control waking and modulate such processes as perception and movement. Thus, disturbances in the RAS will affect a number of neurological disorders. The discovery of gamma band activity in the RAS determined that high threshold calcium channels are responsible for generating gamma band activity in the RAS. Results showing that waking is mediated by CaMKII modulation of P/Q-type channels and REM sleep is modulated by cAMP/PK modulation of N-type channels points to different intracellular pathways influencing each state. Few studies address these important breakthroughs. Novel findings also show that the same primate RAS neurons exhibiting activity in relation to arousal are also involved in locomotion. Moreover, deep brain stimulation of this region, specifically the pedunculopontine nucleus (PPN DBS), in Parkinson's disease has salutary effects on movement, sleep, and cognition. Gamma oscillations appear to participate in sensory perception, problem solving, and memory, and coherence at these frequencies may occur at cortical or thalamocortical levels. However, rather than participating in the temporal binding of sensory events, gamma band activity generated in the RAS may help stabilize coherence related to arousal, providing a stable activation state during waking, and relay such activation to the cortex. Continuous sensory input will thus induce gamma band activity in the RAS to participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our perceptions and actions. Such a role has received little attention but promises to help understand and treat a number of neurological disorders.