Proteomic profiling of early degenerative retina of RCS rats.
To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student's t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.


Patient release criteria following radioactive iodine-131 treatment in the light of international practice: where does South Africa fit in?
The release from hospital of patients treated with radioactive iodine-131 (I) remains a controversial issue as a result of the range of guidelines implemented by national regulatory bodies responsible for radiation protection in various countries worldwide. The aim of this study was to review and analyse the literature on patient release criteria (PRC) applied internationally in an attempt to achieve a justifiable approach to setting equivalent criteria in South Africa. In 2016, the South African Department of Health, Directorate: Radiation Control added conditions (numbers 50 and 90), to licences to use radioactive nuclides. These conditions state that patients must be hospitalized when the dose rate at 1 m is above 25 μSv/h, or more than 555 MBq of iodine-131 was administered to the patient. However, these criteria do not consider patients' socioeconomic conditions. A literature survey was carried out of articles detailing PRC from high-income countries as well as those in the middle-income and lower-income groups. Socioeconomic conditions within countries were determined using the International Monetary Fund lists of gross domestic product. The results from the literature have shown that in setting PRC, several countries have considered the socioeconomic conditions prevailing in their countries to achieve harmony between public protection and cost associated with hospitalization. The South African authority conditions must be seen in the context of the approach followed by other countries. Considering the international context, a justifiable, and potentially implementable, guideline or policy for improving individualized and more caring patient management is advocated.


Use of physiological criteria for improving physical work conditions.
Physical work is still present in many countries, specially in developing ones. The physiological analysis of the work load could be conducted through two different ways, referring to his energetic cost and/or to the mechanical power of the human motor. The purpose of ergonomics is to organize any physical professional task in order to maintain the workers as much as possible inside the limits of a fatiguing activity. The process of fatigue affects differently a "general activity" and a "local work." If a worker is engaged in a general hard activity, like carrying a load or pushing a trolley, an increase of oxygen consumption or/and an acceleration of the heart rate could be observed. This latter, allowing to estimate the oxygen cost of the work, is more affected if the work is performed in a hot environment. In order to establish the ratio between the data observed at the work place and the maximal working capacity of the organism, it is possible to experiment with the physiological effects of transitory increases of the work stress, by increasing the load or/and the frequency of the repetition of the "unit" of work done. When the task could be described in terms of local work, the correct methodology is based upon the general rules established respectively for the static and the dynamic work. In both the cases, it is possible to determine the critical rate of the muscular activity, the part of the muscular capacity engaged at the work place and the probable time for local exhaustion, in order to limit the duration of each period of work. It should be remembered that 50 years ago, Lucien Brouha proposed that heart rate determinations at work be used as a criteria for a better organization of human work by a non-sophisticated method.


Kidney dysfunction in the recipients of liver transplants.
1. Pretransplant kidney function is an important predictor of posttransplant kidney function. 2. Chronic kidney disease is present in 20% of liver transplant recipients by 5 years. 3. Kidney function is impacted by pretransplant management of the consequences of the hepatorenal syndrome. 4. The use of calcineurin inhibitor (CNI)-based immunosuppression is an important factor in the development of chronic kidney disease, and the use of mycophenolic acid- or sirolimus-based immunosuppression with reduced-dose CNI may be of benefit.


Artificial Nerve Conduit for Recurrent Laryngeal Nerve Reconstruction in Thyroid Surgery.
Oncological reconstruction of the recurrent laryngeal nerve (RLN) is sometimes necessary for RLN invaded by thyroid cancer. There have been no case reports of RLN reconstruction using artificial nerve conduits, which are often used for peripheral nerves. In this study, we retrospectively evaluate the feasibility, safety, and efficacy of a collagen conduit with collagen filaments for RLN reconstruction cases at our hospital. Artificial nerve conduits were used in seven cases of RLN reconstruction. Two patients had preoperative unilateral vocal cord paralysis with severe vocal cord atrophy, and two had vocal cord paresis without atrophy. The remaining three patients had functional vocal cords before surgery that had to be resected via surgery due to thyroid cancer infiltration of the RLN. Reconstruction was performed using RENERVE®, which is a collagen conduit. Voice examination and laryngeal endoscopy were performed 1, 3, and 12 months after surgery. There was no improvement in the phonetics of the two patients with vocal cord atrophy before surgery. In the remaining five cases, three with functional vocal cords improved to preoperative values, and two with vocal cord paresis improved to greater than preoperative values. We report the first case series using an artificial nerve conduit for human RLN reconstruction. In cases of RLN resection when the patient has good voice quality pre-operatively, reconstruction of the RLN using an artificial nerve may be a favorable option in cases where direct anastomosis or ansa cervicalis to RLN anastomosis cannot be performed. 4 Laryngoscope, 133:1773-1779, 2023.


Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats.
Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, "fast" and "slow" tooth movers during orthodontic treatment.


Phase-field boundary conditions for the voxel finite cell method: Surface-free stress analysis of CT-based bone structures.
The voxel finite cell method uses unfitted finite element meshes and voxel quadrature rules to seamlessly transfer computed tomography data into patient-specific bone discretizations. The method, however, still requires the explicit parametrization of boundary surfaces to impose traction and displacement boundary conditions, which constitutes a potential roadblock to automation. We explore a phase-field-based formulation for imposing traction and displacement constraints in a diffuse sense. Its essential component is a diffuse geometry model generated from metastable phase-field solutions of the Allen-Cahn problem that assumes the imaging data as initial condition. Phase-field approximations of the boundary and its gradient are then used to transfer all boundary terms in the variational formulation into volumetric terms. We show that in the context of the voxel finite cell method, diffuse boundary conditions achieve the same accuracy as boundary conditions defined over explicit sharp surfaces, if the inherent length scales, ie, the interface width of the phase field, the voxel spacing, and the mesh size, are properly related. We demonstrate the flexibility of the new method by analyzing stresses in a human femur and a vertebral body.


Longitudinal study on occlusal force distribution in lower distal-extension removable partial dentures with conus crown telescopic system.
The purpose of this study was to examine longitudinal changes of the occlusal force distribution in lower distal-extension removable partial dentures with the conus crown telescopic system. Occlusal force applied to the denture and forces transmitted to the retainers were measured on several separate occasions from the insertion of new dentures to about 3 months after. The occlusal force distribution ratio to the retainers was calculated when a load of 20 N was applied to the denture. The results are summarized as follows: (i) The more posterior the loading point of occlusal force, the smaller was the ratio. When the occlusal force was applied to the most anterior artificial tooth, the ratio was 65-100% of the occlusal force. (ii) As the denture wearing time proceeded, the ratio was decreased. The smaller the ratio, the greater was the rate of its decrease.


Iranian Nurses' Challenges in Caring for Older Adults: A Content Analysis Study.
The current study describes Iranian nurses' challenges in caring for older adults. Participants included 22 nurses who were selected by purposeful method and underwent semi-structured, face-to-face interviews. The interviews were reviewed, and three categories and seven subcategories were noted. The category older adults-nurse interaction challenges included: specific characteristics of older adults and inappropriate interaction between nurses and older adults. The category structural problems included: shortage of nurses, inappropriateness of ward environment, and service problems. The category educational gap included: lack of training on principles of older adult ethics in nursing curriculum and shortage of personnel training on manner of relationship with older adults. The current study is the first qualitative study regarding nurses' challenges in caring for older adults in Iran, and the results reveal aspects of nurses' understanding about the said challenges in this country. There is a need for culture-based caring programs that are responsive to older adults' needs. [Res Gerontol Nurs. 2017; 10(3):115-120.].


Translational repressor activity is equivalent and is quantitatively predicted by in vitro RNA binding for two iron-responsive element-binding proteins, IRP1 and IRP2.
Iron regulatory proteins (IRPs) bind to specific RNA stem-loop structures known as iron-responsive elements (IREs) which mediate the post-transcriptional regulation of many genes of iron metabolism. Most studies have focused on the role of IRP1, which has previously been shown to bind with high affinity to IREs and mediate repression of in vitro translation of ferritin mRNAs. More recently, a second IRP has been identified that is expressed in all tissues and that binds IREs (Rouault, T. A., Haile, D. H., Downey, W. E., Philpott, C. C., Tang, C., Samaniego, F., Chin, J., Paul, I., Orloff, D., Harford, J. B., and Klausner, R. D. (1992) BioMetals 5, 131-140; Henderson, B. R., Seiser, C., and Kuhn, L. C. (1993) J. Biol. Chem. 268, 27327-27334; Guo, B., Yu, Y., and Leibold, E. A. (1994) J. Biol. Chem. 269, 24252-24260; Samaniego, F., Chin, J., Iwai, K., Rouault, T. A., and Klausner, R. D. (1994) J. Biol. Chem. 269, 30904-30910). Here we report that purified recombinant IRP2 inhibits translation of ferritin mRNAs with a molar efficacy equal to that of recombinant IRP1. There is a quantitative correlation between binding to isolated RNA target motifs, as judged by gel retardation assays, and translational repressor function as assayed in an in vitro translation system. In contrast to IRP1, IRP2 is not inactivated for RNA binding by alkylation with N-ethylmaleimide or phenylmaleimide, and as we would therefore predict, IRP2 treated with N-ethylmaleimide remains an effective repressor of ferritin translation. As IRP1 and IRP2 clearly have equal capability of mediating translational repression in vitro, the contributions of both IRPs to overall regulation must be considered in describing the pathways of iron regulated gene expression in individual cells.


The steroid benefit in treating complicated haemangioma.
The clinical study included 30 patients with complicated cutaneous haemangioma (ulceration, bleeding, obstruction of anatomical orifices, and interference with function or movement). The patients were studied regarding the age group, sex, site of lesion, size of lesion, and the percentage of regression after treatment with steroid.The age ranged from three months to six years, there were 20 female patients and 10 male patients. We used local injection of diluted triamcinolone 4 mg with 5 ml. 0.9% NACI (normal saline), injected through 23-guage syringe under local or general anaesthesia every two weeks for six to eight sessions depending on the severity of the case, followed by a local pressure dressing. We measured the size of the lesion before each session and recorded the regression of the lesion. The patients were followed up for two years. Haemangioma commonly presents in infants and children, most commonly in females, especially in the head and neck and are usually of a small size. It regresses if the treatment is started earlier.


Aberrant SKP1 Expression: Diverse Mechanisms Impacting Genome and Chromosome Stability.
The S-phase Kinase-Associated Protein 1 (SKP1) is a core component of the SKP1, Cullin 1, F-box protein (SCF) complex, an E3 ubiquitin ligase that serves to poly-ubiquitinate a vast array of protein targets as a signal for their proteasomal degradation, thereby playing a critical role in the regulation of downstream biological processes. Many of the proteins regulated by SKP1 and the SCF complex normally function within pathways that are essential for maintaining genome stability, including DNA damage repair, apoptotic signaling, and centrosome dynamics. Accordingly, aberrant SKP1 and SCF complex expression and function is expected to disrupt these essential pathways, which may have pathological implications in diseases like cancer. In this review, we summarize the central role SKP1 plays in regulating essential cellular processes; we describe functional models in which SKP1 expression is altered and the corresponding impacts on genome stability; and we discuss the prevalence of SKP1 somatic copy number alterations, mutations, and altered protein expression across different cancer types, to identify a potential link between SKP1 and SCF complex dysfunction to chromosome/genome instability and cancer pathogenesis. Ultimately, understanding the role of SKP1 in driving chromosome instability will expand upon our rudimentary understanding of the key events required for genome/chromosome stability that may aid in our understanding of cancer pathogenesis, which will be critical for future studies to establish whether SKP1 may be useful as prognostic indicator or as a therapeutic target.


Functional asplenia in childhood onset systemic lupus erythematosus.
Fatal pneumococcal sepsis due to functional asplenia in a child with systemic lupus erythematosus (SLE) and transient hyposplenism in a 2nd child during an acute flare of SLE are described. Splenic ultrasound examinations and radionuclide spleen scans in 11 other children with SLE were normal. Splenic atrophy and dysfunction is an uncommon but potentially fatal complication of SLE in childhood.


Acute heart failure: current pharmacological treatment and perspectives.
Acute heart failure (AHF) represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Symptoms and clinical signs of AHF (e.g. dyspnoea, orthopnoea, oedema, jugular vein distension, and variation of body weight) are mostly related to systemic venous congestion secondary to various mechanisms including extracellular fluids, increased ventricular filling pressures, and/or auto-transfusion of blood from the splanchnic into the pulmonary circulation. Thus, the initial management of AHF patients should be mostly based on decongestive therapies on admission followed, before discharge, by rapid implementation of guideline-directed oral medical therapies for heart failure. The therapeutic management of AHF requires the identification and rapid diagnosis of the disease, the diagnosis of the cause (or triggering factor), the evaluation of severity, the presence of comorbidities, and, finally, the initiation of a rapid treatment. The most recent guidelines from ESC and ACC/AHA/HFSA have provided updated recommendations on AHF management. Recommended pharmacological treatment for AHF includes diuretic therapy aiming to relieve congestion and achieve optimal fluid status, early and rapid initiation of oral therapies before discharge combined with a close follow-up. Non-pharmacological AHF management requires risk stratification in the emergency department and non-invasive ventilation in case of respiratory failure. Vasodilators should be considered as initial therapy in AHF precipitated by hypertension. On the background of recent large randomized clinical trials and international guidelines, this state-of-the-art review describes current pharmacological treatments and potential directions for future research in AHF.


Bacterioplankton Production in Lakes along an Altitude Gradient in the Subarctic North of Sweden.
We examined changes in bacterioplankton standing stock and production in subarctic lakes in the north of Sweden to elucidate their coupling to lake physical, chemical, and biological characteristics. Sixteen lakes situated along an altitude gradient extending from the coniferous forest to the high-alpine belt were studied during 1998 and 1999. The summer mean bacterial numbers and production varied substantially between the lakes, with a general trend toward decreasing values with increasing altitude. The results demonstrate that P probably restricted bacterial utilization of DOC in the coniferous forest lakes, while low DOC concentrations limited bacterial growth during the summer in the alpine lakes. The primary production of plankton was insufficient to support bacterial production in the lakes. High input of allochthonous DOC to the alpine lakes in spring was sufficient both to increase the bacterial production and to induce P-limitation. As a consequence, there was a tendency toward higher bacterial activity in the spring compared to the summer in the alpine lakes. The results indicate that most of the bacterial standing stock and production are supported by allochthonous DOC plus DOC from benthic production, and more or less limited by the phosphorus supply. We therefore suggest that bacteria populations in subarctic lakes may be indirectly affected by climate variations through its impact on the input of DOC and nutrients from the lake catchments.


Multichannel intraluminal impedance for the assessment of post-fundoplication dysphagia.
Dysphagia often occurs after fundoplication, although its pathophysiology is not clear. We sought to better understand postfundoplication dysphagia by measuring esophageal clearance with multichannel intraluminal impedance (MII) along with more traditional work-up (manometry, upper gastrointestinal imaging [UGI], endoscopy). We evaluated 80 consecutive patients after laparoscopic fundoplication between April 2002 and November 2004. Patients were evaluated clinically and underwent simultaneous manometry and MII, 24-hour pH monitoring, endoscopy, and UGI. For analysis, patients were divided into the following groups based on the presence of dysphagia and fundoplication anatomy (by UGI/endoscopy): (1) Dysphagia and normal anatomy; (2) Dysphagia and abnormal anatomy; (3) No dysphagia and abnormal anatomy; and (4) No dysphagia and normal anatomy. Patients with dysphagia (Groups 1 & 2) had similar peristalsis (manometry), but were more likely to have impaired clearance by MII (32 pts, 62%) than those without dysphagia (9 pts, 32%, P = 0.01). Patients with abnormal anatomy (Groups 2 & 3) were also more likely to have impaired esophageal clearance (66%vs. 38%, P = 0.01). Finally, of patients that had normal fundoplication anatomy, those with dysphagia were much more likely to have impaired clearance (12 pts, 52%) than those with dysphagia (4 pts, 21%, P = 0.03). MII after fundoplication provides objective evidence of esophageal clearance, and is commonly abnormal in patients with abnormal fundoplication anatomy and/or dysphagia. Esophageal clearance is impaired in the majority of patients with postoperative dysphagia, even with normal fundoplication anatomy and normal peristalsis. MII may detect disorders in esophageal motility not detected by manometry.


Spatial and temporal variability of carbohydrates in the northern Adriatic--a possible link to mucilage events.
Large-scale mucilage events in the northern Adriatic have become more frequent during the last few decades. Since carbohydrates (CHO) comprise one of the major constituents of the Adriatic mucilage, studying their seasonal and spatial patterns is one of the key prerequisites for the understanding of this phenomenon. This paper reports on the distribution of particulate (PTCHO) and dissolved carbohydrates (DTCHO) in the period from June 1999 to July 2002, with a special emphasis on the summer mucilage events. A particular attention was paid to the relationship between the phytoplankton crop as reflected by photosynthetic pigments and carbohydrate levels in different seasons. The concentration of PTCHO varied in a very wide range (1-72 micromol C/l). Their seasonal distribution revealed that enhanced levels of PTCHO occurred only in the surface layer (0-5 m) and were associated with major phytoplankton blooms. However, the main pool of CHO was in the dissolved fraction, comprising on average 84+/-10% of the total CHO. In contrast to PTCHO, there was no seasonal coincidence between the enhanced phytoplankton biomass and concentrations of DTCHO. In fact, the concentration of DTCHO showed regularly a marked increase during summer, when the phytoplankton biomass remained relatively low. Nevertheless, the concentration of DTCHO in the productive surface layer, influenced by the Po River discharges, was significantly higher than that in the deeper layers. The detailed vertical distribution of carbohydrates indicated that phytoplankton populations in the bottom layer possessed a rather modest potential as a source of CHO. The spatial distribution in the surface layer along the transect Rovinj-Po River mouth revealed only a moderate increase of the total CHO concentration in the more eutrophic western part of the basin. Analysis of pluriannual variability of the total CHO levels showed that probability of a mucilage event in a given year depended on the accumulation of CHO during spring, but, even more, on the prevailing circulation pattern in the basin during the stratification period.


[In vivo imaging of osteoblasts.]
Osteoblasts are bone-forming cells which produce bone matrix proteins and control calcium and mineral deposition. It is still unknown how osteoblasts work through the processes actually, because most of bone researches use static images of sections. Recently developed intravital imaging system with multiphoton microscopy can enable dynamic observation of living individual cells without making sections. This technique has so high-resolution in the Z direction that it is particularly useful for observation of deep tissues like bones. Here we introduce our data about osteoblast live cell imaging in vivo and in vitro including intravital imaging and summarize the latest reports about it.


An overview of maxillofacial trauma for nurses.
A team approach is necessary in order to maximally evaluate, treat, monitor, and rehabilitate the patient with maxillofacial injuries. An overview of the complexities of the management of patients with significant maxillofacial injuries is presented in a manner that should assist any nurse in the assessment and subsequent management of such patients.


Asymmetry of neuron numbers in the hippocampal formation of prenatally malnourished and normally nourished rats: a stereological investigation.
There is considerable evidence for lateralization of hippocampal function and hemispheric asymmetry in humans. In the rat, studies have reported asymmetries in the thicknesses of layers, the volumes of hippocampal subfields, and the density of cells at specific points along the septotemporal axis. To determine if there is an asymmetry of neuron numbers and whether prenatal malnutrition affects any asymmetries, 90-day old male Sprague-Dawley rats that were either normally nourished or malnourished prenatally were perfused with 4% paraformaldehyde and the brains cut into 30-micro m sections. One interrupted series of sections through the entire hippocampus was analyzed stereologically to estimate the total number of neurons in the hilus of the dentate gyrus, the CA3/CA2 stratum pyramidale (SP), the CA1 SP, and the SP of the prosubiculum/subiculum of both hemispheres. Significant asymmetries (P < 0.05) were found in the CA1 and CA3/CA2 subfields, with the right hemisphere containing 21 and 6% fewer neurons, respectively. Malnutrition reduced neuron numbers in the CA1 subfield by 12%, but did not alter the hemispheric asymmetry. Our findings agree with previous reports of left dominant asymmetries in the rat brain and suggest that this may result from differences in total numbers of neurons.


Anal High-risk Human Papillomavirus Infection, Squamous Intraepithelial Lesions, and Anal Cancer in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first systematic review and meta-analysis evaluating the burden of anal human papillomavirus disease in patients with UC and CD. PubMed, Web of Science, and Scopus were searched until November 2022. Meta-analyses were performed using random effects models. The protocol was recorded at PROSPERO register with the number CRD42022356728. Six studies, including 78 711 patients with UC with a total follow-up of 518 969 person-years, described the anal cancer incidence rate. For anal cancer incidence rate in CD, six studies were selected, including 56 845 patients with a total follow-up of 671 899 person-years. The incidence of anal cancer was 10.2 [95% CI 4.3 - 23.7] per 100 000 person-years in UC and 7.7 [3.5 - 17.1] per 100 000 person-years in CD. A subgroup analysis of anal cancer in perianal CD, including 7105 patients, was calculated with incidence of 19.6 [12.2 - 31.6] per 100 000 person-years [three studies included]. Few studies described prevalence of anal cytological abnormalities [four studies including 349 patients] or high-risk human papillomavirus [three studies including 210 patients], with high heterogeneity. Prevalence of cytological abnormalities or high-risk human papillomavirus was not associated with pharmacological immunosuppression in the studies included. The incidence of anal cancer is higher in UC than in CD, with the exception of perianal CD. There are limited and heterogeneous data on anal high-risk human papillomavirus infection and squamous intraepithelial lesions prevalence in this population.


Usefulness of pimobendan in the treatment of heart failure.
The effects of the benzimidazole-pyridazinone pimobendan (UD-CG 115 BS) on systemic haemodynamics, myocardial performance and the distribution of cardiac output were studied in open-chest anaesthetized pigs. After intravenous bolus injections (0.1-0.5 mg X kg-1, n = 7) increases in heart rate (up to 37%), LVdP/dtmax (up to 54%) and decreases in systemic vascular resistance (up to 33%) and left ventricular filling pressure (up to 50%) were observed, while cardiac output was unchanged. Vasodilation occurred in nearly all regional vascular beds, but was most pronounced in the adrenals (200%), followed by stomach (150%), small intestines (130%), heart (125%) and brain (110%). O2-consumption was not affected in spite of the increases in heart rate and myocardial inotropy. To evaluate the direct effects on the myocardial, pimobendan was also infused (1-5 micrograms X kg-1 X min-1, n = 7) directly into the left anterior descending coronary artery. In addition to a marked vasodilation of the coronary bed (140%), also a lowering of the left ventricular filling pressure (up to 20%) and cardiac output (15%) was observed, but no changes in regional myocardial function, LVdP/dtmax and systemic vascular resistance occurred. Immediately after intracoronary bolus injections (1 mg X kg-1, n = 4), vasodilation of the coronary vessels was apparent, but myocardial contractility was not affected. This may explain that cyclic AMP content, determined in biopsies excised 30 s after injection, was unaltered. It may be concluded that pimobendan exerts actions on the cardiovascular system which may be useful in the treatment of heart failure.


Direct assay of urinary steroid glucuronides for monitoring the approach of ovulation.
The concentrations of estrone-3-glucuronide (E(1)3G) and pregnanediol-3-glucuronide (P(2)3G) in daily samples of early morning urine (EMU) were correlated with the levels of estradiol (E2), progesterone (P) and LH in respective plasma samples. Forty-six menstrual cycles were studied, in order to determine the practical usefulness of the urine assays for detecting: a) an individualized estrogen concentration threshold value, announcing the approach of ovulation. b) an individualized signal provided by P(2)3G in urine from which it can be assumed that ovulation has already occurred. The results showed that the concentration of E2 in plasma, in any day of the cycle, can be precisely inferred from the respective concentration of E(1)3G in EMU. The estimation of the plasmatic P values from those of P(2)3G in EMU had to be based on different factors according to the phase of the cycle, fact that suggests the presence of a phase-related variation in the glucuronization of P metabolites. Considering three consecutive E(1)3G urinary assay results, it was possible to identify a threshold value termed Estrogen-Peak Initiating Rise (E-PIR), which anticipated in 3.02 +/- 0.18 days the occurrence of an LH peak. The attempts to detect the occurrence of ovulation by an individualized urinary P(2)3G signal proved disappointing. The signal was detected, either before, simultaneously or after the LH peak.


The Regulatory Role of Non-coding RNA in Autophagy in Myocardial Ischemia-Reperfusion Injury.
Following an acute myocardial infarction (AMI), thrombolysis, coronary artery bypass grafting and primary percutaneous coronary intervention (PPCI) are the best interventions to restore reperfusion and relieve the ischemic myocardium, however, the myocardial ischemia-reperfusion injury (MIRI) largely offsets the benefits of revascularization in patients. Studies have demonstrated that autophagy is one of the important mechanisms mediating the occurrence of the MIRI, while non-coding RNAs are the main regulatory factors of autophagy, which plays an important role in the autophagy-related mTOR signaling pathways and the process of autophagosome formation Therefore, non-coding RNAs may be used as novel clinical diagnostic markers and therapeutic targets in the diagnosis and treatment of the MIRI. In this review, we not only describe the effect of non-coding RNA regulation of autophagy on MIRI outcome, but also zero in on the regulation of non-coding RNA on autophagy-related mTOR signaling pathways and mitophagy. Besides, we focus on how non-coding RNAs affect the outcome of MIRI by regulating autophagy induction, formation and extension of autophagic vesicles, and the fusion of autophagosome and lysosome. In addition, we summarize all non-coding RNAs reported in MIRI that can be served as possible druggable targets, hoping to provide a new idea for the prediction and treatment of MIRI.


Syndrome of multiple pterygia, camptodactyly, facial anomalies, hypoplastic lungs and heart, cystic hygroma, and skeletal anomalies: delineation of a new entity and review of lethal forms of multiple pterygium syndrome.
Three unrelated stillborn infants (cases 1-3) are presented here with a distinct constellation of multiple anomalies: namely, multiple pterygia involving chin-to-sternum, cervical, axillary, antecubital, crural and/or popliteal areas, flexion contractures of multiple joints, small chest, hydrops, characteristic abnormal facial appearance with hypertelorism, markedly flattened nasal bridge with hypoplastic nasal alae, cleft palate, micrognathia, apparently low-set malformed ears, short neck with a cystic hygroma at the back of the neck and head, and pulmonary and cardiac hypoplasia. Radiographic studies, in addition, showed scalp edema, microbrachycephaly, flattened mandibular angle, lack of normal curvature at the cervico-thoracic junction, marked bony fusion of posterior spinous processes of older fetuses (cases 1, 2), thin crowded ribs, markedly hypoplastic scapulae, hypoplastic iliac wings, ischia and pubic bones, undermodeling of tubular bones, and radio-ulnar synostosis. Histologic studies of the skeletal system showed cartilaginous and bony fusion of the spinous processes (cases 1, 2), fusion of epiphyseal cartilages of distal humerus and proximal ulna, a poorly developed joint space, an abnormal growth plate, and weak safranin staining of the resting cartilages (cases 1, 2). To the best of our knowledge, this pattern of anomalies constitutes a previously undescribed syndrome. Prenatal diagnosis of this entity is possible by ultrasonographic studies on the basis of nonimmune fetal hydrops, a cystic hygroma at the back of the head and neck, diminished fetal activity, short and fixed limbs, and/or maternal hydramnios. Three additional cases (cases 4-6) are also presented to show a possible heterogeneity of this syndrome.


Validation of the Levenson Self-Report Psychopathy Scale in Bulgarian Substance-Dependent Individuals.
The co-occurrence of psychopathy and substance use disorders (SUDs) is associated with higher relapse rates and increased risk of violent offending. Studies on the validity of psychopathy measures in community samples and substance-dependent individuals (SDIs) are scarce. The aim of the current study was to examine the psychometric properties of the Levenson Self-Report Psychopathy Scale (LSRP) in a sample of Bulgarian SDIs and non-dependent controls. We tested 615 participants: 106 heroin users, 91 amphetamine users, 123 polysubstance users, and 295 controls. Confirmatory factor analyses replicated the tri-factor structure of the LSRP (egocentric, antisocial, callous). The scale demonstrated acceptable reliability and validity. SDIs scored significantly higher than controls on the total scale and subscales of the LSRP, indicating good discriminant validity. Overall, results indicate that the LSRP is a valid instrument for measuring psychopathy in Bulgarian community samples.


Do jumbo cups cause hip center elevation in revision THA? A computer simulation.
Acetabular revision THA with use of a large (jumbo) cup is an effective treatment for many cavitary and segmental peripheral bone defects. However, the jumbo cup may result in elevation of the hip center and protrusion through the anterior acetabular wall as a result of the oversized geometry of the jumbo cup compared with the physiologic acetabulum. The purpose of this computer simulation was to determine how much elevation of the hip center and anterior wall protrusion occurs in revision THA with use of a jumbo cup technique in which the inferior edge of the jumbo cup is placed at the inferior acetabular rim and the superior edge of the jumbo cup is placed against host bone at the superior margin of a posterosuperior bone defect. Two hundred sixty-five pelvic CT scans were analyzed by custom CT analytical software. The computer simulated oversized reaming. The vertical and anterior reamer center shifts were measured, and anterior column bone removal was determined. The computer simulation demonstrated that the hip center shifted 0.27 mm superiorly and 0.02 mm anteriorly, and anterior column bone removal increased 0.86 mm for every 1-mm increase in reamer diameter. Our results indicate that the jumbo cup technique results in hip center elevation despite placement of the cup adjacent to the inferior acetabulum. For a hypothetical increase from a 54-mm socket to a 72-mm socket, as one might see in the context of the revision of a failed THA, our model would predict an elevation of the hip center of approximately 5 mm and loss of approximately 15 mm of anterior column bone. This suggests that an increase in femoral head length may be needed to compensate for the hip center elevation caused by the use of a large jumbo cup in revision THA. A jumbo cup may also result in protrusion through the anterior wall.


[Thumb reconstruction with modified free wrap-around flap].
To evaluate the function of the reconstructed thumbs and the donor feet after thumb reconstructions with modified wrap-around flap. A total of 65 patients who accepted thumb reconstruction with the modified wrap-around flap between January 2003 and October 2007 were followed up, including 54 males and 11 females with an average age of 33 years (range 15-46 years). There were 12 cases of skin degloving injury and late class I B defect, 44 cases of class II defect and 9 cases of class III A defect. The reconstructed thumbs and donor feet were examined and evaluated. Foot function index-verbal rating scales (FFI-5pt), American Orthopaedic Foot and Ankle Society (AOFAS) for hallux metatarsophalangeal-interphalangeal score, gait analysis and dynamic pedobarography were conducted to 20 patients who were followed up recently. Sixty-five patients were followed up 6-60 months with an average of 22 months. The reconstructed thumbs had aesthetic appearance and satisfactory range of motion. The two-point discrimination was (9.7 +/- 2.8) mm, showing statistically significant difference (P < 0.05) when compared with that of the contralateral normal thumb [(4.2 +/- 1.1) mm]. Full or most length of the donor toes were preserved in 63 patients. The width of remaining plantar strip skin that covered the plantar weight-bearing area was (24.5 +/- 3.7) mm, and its two-point discrimination was (9.0 +/- 2.6) mm; showing no statistically significant difference (P > 0.05) when compared with that of contralateral normal one [(8.1 +/- 1.9) mm]. Of the 20 patients who were followed up recently, the evaluation of the FFI-5pt score showed that the pain scale score was 5.6 +/- 4.5, the disability scale score was 1.2 +/- 2.7, and the FFI-5pt total scale score was 3.2 +/- 2.9. The results of AOFAS clinical rating scale showed that the pain scale score was 34.0 +/- 5.0, the function scale score was 38.7 +/- 4.2, the alignment scale score was 15.0 +/- 0, and the total AOFAS scale score was 87.7 +/- 7.4. There was no statistically significant difference (P > 0.05) in the durations of subphases of the gait cycle between the donor foot and the contralateral normal foot, and in the peak force and force-time integral of the two whole foot. The peak force of the donor toe was significantly smaller than that of the contralateral normal toe (P < 0.05), but there was no significant difference in the peak pressure (P > 0.05); and there were no significant differences in the peak forces and peak pressures of other six anatomical sites of the two feet (P > 0.05). Using the modified wrap-around flap for thumb reconstruction, aesthetic and functional thumbs can be obtained, and most of the function of the donor feet can be preserved.


[Sediment-water flux and processes of nutrients and gaseous nitrogen release in a China River Reservoir].
The key processes and fluxes of nutrients (N and P) and gaseous N (N2 and N2O) across the sediment-water interface in a river reservoir (Xipi) of the Jiulong River watershed in southeast China were studied. Intact core sediment incubation of nutrients exchange, in-situ observation and lab incubation of excess dissolved N2 and N2O (products of nitrification, denitrification and Anammox), and determination of physiochemical and microbe parameters were carried out in 2013 for three representative sites along the lacustrine zone of the reservoir. Results showed that ammonium and phosphate were generally released from sediment to overlying water [with averaged fluxes of N (479.8 ± 675.4) mg. (m2. d)-1 and P (4. 56 ± 0.54) mg. (m2 d) -1] , while nitrate and nitrite diffused into the sediment. Flood events in the wet season could introduce a large amount of particulate organic matter that would be trapped by the dam reservoir, resulting in the high release fluxes of ammonium and phosphate observed in the following low-flow season. No clear spatial variation of sediment nutrient release was found in the lacustrine zone of the reservoir. Gaseous N release was dominated by excess dissolved N2 (98% of total), and the N2 flux from sediment was (15.8 ± 12. 5) mg (m2. d) -1. There was a longitudinal and vertical variation of excess dissolved N2, reflecting the combined results of denitrification and Anammox occurring in anoxic sediment and fluvial transport. Nitrification mainly occurred in the lower lacustrine zone, and the enrichment of N2O was likely regulated by the ratio of ammonium to DIN in water.


Evaluation of the diagnostic use of free prostate specific antigen/total prostate specific antigen ratio in detecting prostate cancer.
To assess whether Free/Total prostate specific antigen (PSA) would enhance prostate cancer detection in men with total serum PSA between 2.5 and 10 ng/ml. This case control study was conducted in the Department of Urology and Renal Transplantation, Jinnah Hospital, Lahore from January 2001 to June 2004. A total of 200 consecutive patients with symptoms of prostate disease, age 60 years or above, and serum PSA level 2.5 to 10.0 were included. Before trans-rectal biopsy of the prostate, a blood sample was taken and total and free PSA levels measured. The results were correlated with biopsy results. All patients had signs of benign prostate disease on digital rectal examination. As a second part of the study, we estimated free prostate specific antigen/total prostate specific antigen ratio (FPSA/TPSA) in 100 local age-matched population who presented to our department with diseases other than that of prostate. Of the 200 patients included in the study, 122 had free/total prostate specific antigen ratio (FPSA/TPSA) > 0.18 and 78 patients had < 0.18. Of the later 78 patients, 68 (87%) had cancer. Six of the 122 patients showed malignancy on biopsy. In regard to free/total prostate specific antigen ratio there was statistically significant difference between prostate cancer and benign prostate hyperplasia (p < 0.001). The sensitivity and specificity of the FPSA/TPSA ratio were 91.9% and 92.1% respectively with 87.2% positive predictive value. The mean total PSA for the benign prostates hyperplasia, prostate cancer and control group were 6.5, 7.2 and 5.2 respectively. FPSA/TPSA ratio in the control group was > 0.42. Free to total PSA ratio improves early detection of carcinoma of prostate and prevents the patients from unnecessary biopsy.


Genomics of apicomplexan parasites.
The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively) represent a significant global healthcare burden. Despite their significance, few treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. To lay the foundation for programs of drug discovery and vaccine development, genome sequences for many of these organisms have been generated, together with large-scale expression and proteomic datasets. Comparative analyses of these datasets are beginning to identify the molecular innovations supporting both conserved processes mediating fundamental roles in parasite survival and persistence, as well as lineage-specific adaptations associated with divergent life-cycle strategies. The challenge is how best to exploit these data to derive insights into parasite virulence and identify those genes representing the most amenable targets. In this review, we outline genomic datasets currently available for apicomplexans and discuss biological insights that have emerged as a consequence of their analysis. Of particular interest are systems-based resources, focusing on areas of metabolism and host invasion that are opening up opportunities for discovering new therapeutic targets.


Intratumoral Genetic Heterogeneity in Rectal Cancer: Are Single Biopsies representative of the entirety of the tumor?
Demonstrate intratumoral genetic heterogeneity in rectal cancer. Several clinical management decisions in rectal cancer may be influenced by pretreatment biopsy information. However, in the setting of significant intratumoral heterogeneity, biopsies may not be representative of the entirety of the tumor and limit the reliability of the information provided from them for clinical decision management. Three fragments from a single rectal adenocarcinoma were chosen for whole-exome sequencing followed by mutation detection analysis. About 25 Gb of unambiguously mapped sequences were generated for each sample resulting in a median fold-coverage of 35x. Captured sequences mapped to the reference human genome were then used for the detection of somatic point mutations. Overall, 193 unique somatic point mutations were identified. Only 53 (27%) of these were shared by all three fragments, including known genes involved in early phases of the adenoma-carcinoma sequence (such as, APC). Approximately, 115 (59%) mutations were exclusively present in only one of the fragments, including mutations in "driver" genes (DNAH12). Jaccard distances showed a median distance of 0.603 for pair-wise comparison of fragments indicating significant heterogeneity between them. Considerable intratumoral heterogeneity is present among naive rectal cancers. The majority of point mutations detected in different fragments from rectal cancers are frequently unique to a single fragment. These findings support that gene mutations found on single pretreatment biopsies will not necessarily be representative of mutations present in the entirety of the tumor and therefore may limit the utility of the biological information provided by single biopsy fragments for clinical management decisions.


Ocular Gnathostomiasis-Update of Earlier Survey.
Ocular gnathostomiasis is rather a rare food-borne zoonosis caused by infection with the larvae of several species of genus Gnathostoma and is a representative ocular larva migrans syndrome. In our previous literature survey, we found 73 cases of ocular gnathostomiasis reported up to and including 2009, though additional sporadic cases have been reported in Asia and the Americas since that report. Here, we review 10 additional cases reported since 2010, and also update current findings regarding epidemiological and clinical features in affected patients.


Mental Health Consequences of the COVID-19 Pandemic Among Ontario's Youth: A Cross-Sectional Study.
The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on the mental health and wellbeing of Ontario's youth. Our study investigated the psychological impacts of COVID-19 on the pediatric population of Ontario, using a survey derived from the Revised Children's Anxiety and Depression Scale (RCADS) system to identify children who may benefit from seeking professional help. Our cross-sectional study examined the potential risk factors that contributed to worsening mental health and wellbeing in children, including changes in sleep patterns, appetite, and physical activity levels, as well as the diagnosis of a family member with COVID-19. Our study found that 24%, 9.4%, and 15.5% of participants exhibited symptoms of depression, anxiety, and obsessive-compulsive disorder (OCD), respectively, according to the RCADS system. Furthermore, there were significant associations between the presence of symptoms and the diagnosis of a family member with COVID-19 or a frontline worker in the family. This suggests a need to create interventions to support the families of frontline workers and those directly affected by a COVID-19 diagnosis.


Kawasaki disease in adults. An otolaryngologist's perspective.
Kawasaki disease has been recognized for more than 15 years in children, but it is only recently that adult cases have been known to occur. One such case is reported herein. The cases of previously described adult patients are reviewed in depth, emphasizing the otolaryngologic findings. Diagnosis is based on clinical findings with prominent fever, oropharyngeal erythema, dermatitis, and cervical lymphadenopathy. The underlying lesion is a vasculitis and treatment is mainly supportive, although aspirin seems to have some value in the prevention of cardiac complications.


Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae.
The in vivo activities of piperacillin-tazobactam and cefepime were compared with those of ticarcillin-clavulanate, ceftazidime, cefotaxime, and imipenem in a rat model of intra-abdominal abscess with a strain of Klebsiella pneumoniae elaborating an extended-spectrum beta-lactamase (TEM-26). With the exception of ceftazidime, all of the antimicrobial agents significantly reduced bacterial counts within abscesses at the end of therapy compared with those in untreated controls. Residual viable cell counts (mean +/- standard deviation in log10 CFU/gram) were as follows: control, 8.76 +/- 0.97; ceftazidime, 8.00 +/- 0.76; piperacillin-tazobactam, 3.87 +/- 1.72; ticarcillin-clavulanate, 3.74 +/- 1.34; cefepime, 3.15 +/- 1.19; cefotaxime, 2.61 +/- 0.77; imipenem, 2.41 +/- 0.93. Imipenem was more effective than either of the inhibitor combinations (P < 0.05). Cefotaxime was unexpectedly effective given its poor in vivo activity against this organism in our earlier studies, which used a different dose and total duration of therapy (L. B. Rice, J. D. C. Yao, K. Klimm, G. M. Eliopoulos, and R. C. Moellering, Jr., Antimicrob. Agents Chemother. 35:1243-1244, 1991). These observations suggest that the effectiveness of cephalosporins in the treatment of experimental infections caused by extended-spectrum beta-lactamase-producing K. pneumoniae may be highly dependent on dosing regimens, even for a specific organism and site of infection.


Concurrent evaluation of microscopic observation of drug susceptibility assay for pulmonary and extrapulmonary tuberculosis.
Methods for detection and drug susceptibility of tuberculosis (TB) with solid media are inexpensive but slow and laborious. Rapid methods to diagnose TB and multidrug-resistant TB (MDR-TB) are a global priority for TB control. A study was performed to compare the sensitivity of detection of mycobacterial growth and time of culture positivity by microscopic observation of drug susceptibility (MODS) assay with that of Lowenstein-Jensen (LJ) culture in pulmonary and extrapulmonary TB and to evaluate the concordance of the susceptibilities to isoniazid (INH) and rifampicin (RIF) by MODS and proportion method on LJ. A prospective, laboratory-based study was conducted on a total of 300 samples from suspected cases of pulmonary and extrapulmonary TB. Samples were inoculated on LJ medium as per the standard guidelines and MODS assay was performed. Sensitivity of MODS assay was 80% and 83.3% and specificity was 92.9% and 83.3% for pulmonary and extrapulmonary samples, respectively. Difference between mean time to detection of Mycobacterium TB (MTB) by LJ medium and MODS was statistically significant, with MODS being faster. drug susceptibility testing (DST) by MODS when compared to economic variant of proportion method was 87.87% for RIF, 90.9% for INH, and 96.96% for MDR-TB detection. MODS assay provides rapid, safe, and sensitive detection of TB faster than the existing gold standard. It is extremely promising in effectively diagnosing MDR-TB.


Rituximab Monotherapy in the Management of a Rare Case of an HIV Associated Lymphoproliferative Disorder.
Background. Castleman's disease (CD), also known as angiofollicular node hyperplasia, is a rare heterogenous lymphoproliferative disorder. This disease exists as two distinct entities: a localized or unicentric CD (UCD) which has a more benign clinical course and multicentric CD (MCD) which is a systemic disease and carries a worse prognosis. MCD is often associated with human immunodeficiency virus (HIV) infection and these patients are usually coinfected with human herpes virus-8 (HHV-8). Rituximab is an anti-CD20 monoclonal antibody that has become integral to the management of this disease. It is used alone or in combination with chemotherapy to treat MCD. Case Report. We describe a case of a 58-year-old man with HIV and HHV-8 MCD and evidence of organ failure with a poor performance status that went into complete remission after four cycles of therapy with weekly rituximab. Conclusion. HIV-MCD can be challenging to diagnose and to manage. Early recognition can reduce morbidity and mortality associated with the disease. Rituximab monotherapy can be used as a safe and effective treatment option in patients with a poor performance status.


Infections due to resistant Candida species in patients with cancer who are receiving chemotherapy.
The apparent increase in the prevalence of candidal infections among patients with cancer and the changes in the spectrum of Candida pathogens infecting these patients are associated with a number of factors. Selection of less-susceptible organisms occurs because antibacterial and antifungal agents alter microbial flora, and the use of these agents can lead to mutations that confer antibiotic resistance to initially susceptible organisms. Candida organisms that are resistant to polyenes and azoles have been increasingly isolated from specimens from oncology patients, and outbreaks of infections due to these less-susceptible organisms have been reported in several centers. Antifungal resistance has largely been observed among non-albicans Candida species, especially Candida parapsilosis, Candida lusitaniae, and Candida krusei. However, there also has been an increase in the isolation of resistant Candida albicans, the more prevalent and more virulent species of Candida, from specimens from other patients. Isolation of resistant C. albicans from oncology patients has been rare, although the potential for further problems exists. These observations emphasize the importance of the selective pressure exerted by antifungal agents on the microbiological flora of patients and the influence of these agents on the prevalence and spectrum of fungal pathogens in clinical settings.


Sol-gel synthesis of low-dimensional silica within coordination nanochannels.
Sol-gel condensation of tetramethoxysilane (TMOS) inside the channels of a coordination pillared layer structure [Cu2(pzdc)2(dpe)]n (1a; pzdc = pyrazine-2,3-dicarboxylate, dpe = 1,2-di(4-pyridyl)ethylene) produced subnanosized silica dispersed within the host framework. In this system, the growth of silica is effectively constrained, and the resultant silica shows a drastic decrease of its crystallization temperature because of its minute size.


Trails of kilovolt ions created by subsurface channeling.
Using scanning tunneling microscopy, we observe the damage trails produced by keV noble-gas ions incident at glancing angles onto Pt(111). Surface vacancies and adatoms aligned along the ion trajectory constitute the ion trails. Atomistic simulations reveal that these straight trails are produced by nuclear (elastic) collisions with surface layer atoms during subsurface channeling of the projectiles. In a small energy window around 5 keV, Xe+ ions create vacancy grooves that mark the ion trajectory with atomic precision. The asymmetry of the adatom production on the two sides of the projectile path is traced back to the asymmetry of the ion's subsurface channel.


Distribution of carbon-14 and associated radiation dose in rat fetal brain and liver after maternal injection of [14C]thymidine.
Pregnant Sprague-Dawley rats were injected intravenously with [14C]thymidine on day 13.5 of gestation, and the concentrations and radiation doses of 14C in the fetal brain and liver were determined by liquid scintillation counting and autoradiography with imaging plates. The concentrations of 14C in the whole fetal brains determined by liquid scintillation counting were 1.01% of the injected dose per gram wet weight at 6 h after injection and decreased to 0.39% g-1 at 48 h after injection. A significant accumulation of 14C was observed in the fetal liver: 3.8 and 0.51% of the injected dose per gram wet weight at 6 and 48 h after injection, respectively. Autoradiography showed that, especially at earlier periods after injection, there was remarkable concentration of 14C in the ventricular zone of the brain and the central region of the liver. With increasing time after injection, the distribution of 14C became relatively uniform. The concentrations of 14C in the ventricular zone of the fetal brain, determined by autoradiography, were much higher than those in the whole brain as determined by liquid scintillation counting. Cumulative radiation doses for 6-48 h after injection were 1.27 mGy for the whole fetus and 1.45 mGy for the whole brain. In contrast, the cumulative radiation dose for the ventricular zone of the brain which was determined by autoradiography was approximately 2.2 times that for the whole brain.


Cognitive differences between anxious, normal, and ADHD children on a dichotic listening task.
To compare the performance of children with anxiety disorders with that of children with attention-deficit hyperactivity disorder (ADHD) and normal controls in the processing of emotional information. A total of 57 children ages 8 to 11 years (18 anxious, 20 ADHD, 19 normal control) were administered a dichotic listening task for the detection of words and emotions. Comparisons of overall performance, false alarms, and a sensitivity index (which took false alarms into account) were done using repeated measures analyses of variance. Anxious children made fewer false alarms for emotion targets compared to both ADHD children and normal controls, and fewer false alarms for words compared to normal controls. When controlling for false alarms, their performance exceeded that of both ADHD children and normal controls. There were no group differences in correct responses. Performance on a dichotic listening task differentiates anxious, ADHD, and normal children, particularly when listening for emotional targets. Further studies using this task may therefore elucidate differences in the processing of words and emotions between these three groups of children.


Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies.
Cariprazine, a potent dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, is Food and Drug Administration approved for treating schizophrenia and manic or mixed episodes of bipolar I disorder. A post-hoc safety/tolerability analysis of data from the four acute trials in the cariprazine schizophrenia clinical development program (NCT00404573; NCT00694707; NCT01104766; NCT01104779) was carried out using the overall safety population (all patients who received ≥1 dose of study drug) and modal daily dose subgroups (1.5-3, 4.5-6, and 9-12 mg/day). These exploratory findings were summarized using descriptive statistics. Cariprazine was generally well tolerated. The incidence of treatment-emergent adverse events versus placebo was similar for cariprazine 1.5-3 mg/day and higher for cariprazine 4.5-6 and 9-12 mg/day; a dose-response relationship was observed for akathisia, extrapyramidal symptoms, and diastolic blood pressure. The mean changes in metabolic parameters were generally similar in cariprazine-treated and placebo-treated patients. There was no prolactin level increase or QTc value greater than 500 ms; small increases in mean body weight (∼1to2 kg) versus placebo were observed. Within the Food and Drug Administration-approved dose range (1.5-6 mg/day), cariprazine was generally safe and well tolerated in patients with schizophrenia.


Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions.
Alkynyl selenides were synthesized by a straightforward one-pot and three-step methodology, without the need of diselenides as starting reagents, under an oxygen atmosphere and using PEG 200 as the solvent. This procedure involves the in situ generation of dialkyl diselenides through a K3PO4-assisted reaction of an alkyl selenocyanate obtained by a nucleophilic substitution reaction between KSeCN and alkyl halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted benzofuran and indole derivatives starting from convenient 2-substituted acetylenes.


Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.
Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-β-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-β-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.


Sperm Morphology Assessment in Captive Neotropical Primates.
The main objective of this study was to evaluate sperm morphology in four neotropical primate species to compare the sperm morphological traits and the sperm morphometric parameters as a basis for establishing normative sperm standards for each species. Data from 80 ejaculates collected from four primate species, Callithrix jacchus, Callimico goeldii, Alouatta caraya and Ateles geoffroyi, were analysed for detection of sperm morphological alterations using subjective World Health Organization (WHO-2010) standards and Sperm Deformity Index (SDI) criteria, objective computer-assisted sperm morphometry analysis (CASMA) and subpopulation sperm determination (SSD) methods. There were multiple differences (p < 0.01) observed among primate species in values obtained from WHO-2010, SDI, CASMA and SSD sperm analysis methods. In addition, multiple significant positive and negative correlations were observed between the sperm morphological traits (SDI, Sperm Deformity Index Head Defects, Sperm Deformity Index Midpiece Defects, Sperm Deformity Index Tail Defects, Normal Sperm, Head Defects, Midpiece Defects and Tail Defects) and the sperm morphometric parameters (SSD, Area (A), Perimeter (P), Length (L), Width (W), Ellipticity, Elongation and Rugosity) (p ≤ 0.046). In conclusion, our findings using different evaluation methods indicate that pronounced sperm morphological variation exists among these four neotropical primate species. Because of the strong relationship observed among morphological and morphometric parameters, these results suggest that application of objective analysis methods could substantially improve the reliability of comparative studies and help to establish valid normative sperm values for neotropical primates.


Altered cellular distribution of tuberin and glucocorticoid receptor in sporadic fundic gland polyps.
Gastric fundic gland polyps (FGPs) are considered hamartomas, and various gastrointestinal hamartomas are associated with tuberous sclerosis complex (TSC). The aim of this study was to investigate a possible link between TSC proteins (hamartin and tuberin) and sporadic FGPs. We examined 33 sporadic FGPs and 26 biopsies of normal fundic mucosa by immunohistochemistry. Nuclear immunoreactivity for tuberin was dramatically reduced or lost in most sporadic FGPs, and tuberin unexpectedly accumulated in the cytoplasm in oxyntic glands. About 18% (6/33) of FGPs were immunopositive in an average of 1.7% of oxyntic cell nuclei, compared with 77% (20/26) of controls in an average of 24.4% of oxyntic cell nuclei (P <.01). No change in hamartin was noted. We further examined the tuberin-associated proteins glucocorticoid receptor (GCR) and p27. Nuclear immunoreactivity for GCR was lost in most sporadic FGPs, but p27 distribution was normal. Sporadic FGPs had a low frequency of staining for Ki-67 except for some cells from cystic components, which is consistent with their slow growth. Our results are consistent with the hypothesis that tuberin may play an important role in pathogenesis of sporadic FGPs. First, an altered cellular localization of tuberin may lead to the deregulation of cell proliferation by interrupting its interaction with hamartin. Second, altered cellular localization of tuberin may preclude its negative regulation of gene transcription mediated by GCR.


Translation and Initial Validation of the Japanese Version of the Self-Beliefs Related to Social Anxiety Scale.
Cognitive models of social anxiety posit that there are several types of maladaptive beliefs responsible for persistent social anxiety. Although these beliefs are theoretically important, currently there is no validated measure of these beliefs in Japan. In the present study, we translated into Japanese a well-validated measure of these beliefs, the Self-Beliefs Related to Social Anxiety (SBSA) Scale. The psychometric properties of the scale were also examined in two nonclinical samples ( ns = 401 and 30). Using confirmatory factor analysis, the Japanese version of the SBSA was found to have a correlated three-factor structure that consisted of "conditional beliefs," "unconditional beliefs," and "high standard beliefs." In addition, the Japanese version of the SBSA and its subscales demonstrated good internal consistency reliability and test-retest reliability. The Japanese version of the SBSA also demonstrated good convergent and divergent validity. Future applications of the Japanese version of the SBSA are discussed.


Bio-interactive nanoarchitectonics with two-dimensional materials and environments.
Like the proposal of nanotechnology by Richard Feynman, the nanoarchitectonics concept was initially proposed by Masakazu Aono. The nanoarchitectonics strategy conceptually fuses nanotechnology with other research fields including organic chemistry, supramolecular chemistry, micro/nanofabrication, materials science, and bio-related sciences, and aims to produce functional materials from nanoscale components. In this review article, bio-interactive nanoarchitectonics and two-dimensional materials and environments are discussed as a selected topic. The account gives general examples of nanoarchitectonics of two-dimensional materials for energy storage, catalysis, and biomedical applications, followed by explanations of bio-related applications with two-dimensional materials such as two-dimensional biomimetic nanosheets, fullerene nanosheets, and two-dimensional assemblies of one-dimensional fullerene nanowhiskers (FNWs). The discussion on bio-interactive nanoarchitectonics in two-dimensional environments further extends to liquid-liquid interfaces such as fluorocarbon-medium interfaces and viscous liquid interfaces as new frontiers of two-dimensional environments for bio-related applications. Controlling differentiation of stem cells at fluidic liquid interfaces is also discussed. Finally, a conclusive section briefly summarizes features of bio-interactive nanoarchitectonics with two-dimensional materials and environments and discusses possible future perspectives.


Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells.
Mesenchymal stem cells (MSCs) have exhibited great potential in the therapy of cardiovascular disease. However, the application of MSCs is hampered by apoptosis, which reduces the number of cells in the host cardiac microenvironment. Ulinastatin (UTI), a broad‑spectrum protease inhibitor that can be purified from human urine, has attracted attention for its protective effects through its immunomodulatory and anti‑inflammatory properties. The present study aimed to evaluate the effects of UTI on serum deprivation‑induced apoptosis of MSCs and investigate its molecular mechanisms. Cell viability was determined by the MTT assay. Apoptosis was assessed by flow cytometric analysis with Annexin V/propidium iodide staining. The protein levels of cleaved caspase‑3, B‑cell lymphoma‑2 (Bcl‑2) family proteins, total‑Akt and phospho‑Akt were evaluated by western blot. The results of the present study demonstrated that UTI exhibited a protective effect in serum deprived MSCs, as indicated by increased cell viability, and a reduction in the rate of apoptosis and caspase‑3 activation. In addition, treatment with UTI significantly decreased the expression levels of Bcl‑2, Bcl‑extra large and Bcl‑associated X protein. Furthermore, activation of the Akt signaling pathway was involved in the UTI‑induced anti‑apoptotic effects. The present findings indicated that UTI is able to promote the survival of MSCs under serum deprivation conditions. The present study may be helpful in improving the therapeutic efficacy of MSC transplantation used to cure chronic ischemic heart disease.


Hypertension and cardiac arrhythmias: executive summary of a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).
Hypertension (HTN) is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease (CAD), stroke, peripheral artery disease and chronic renal failure. Hypertensive heart disease can manifest as many types of cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in HTN patients, especially in those with left ventricular hypertrophy (LVH), CAD, or HF. In addition, high doses of thiazide diuretics commonly used to treat HTN, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia), contributing further to arrhythmias, while effective blood pressure control may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between HTN and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit of comprehensively reviewing the available evidence and publishing a joint consensus document on HTN and cardiac arrhythmias, and providing up-to-date consensus recommendations for use in clinical practice. The ultimate judgment on the care of a specific patient must be made by the healthcare provider and the patient in light of all individual factors presented. This is an executive summary of the full document co-published by EHRA in EP-Europace.


The effect of statins on bone turnover biomarkers: a systematic review and meta-analysis of randomized controlled trials.
Few studies have considered the effect of statins on bone turnover biomarker levels and the results of these studies are inconsistent. Here we performed a meta-analysis of the effect of statins on bone turnover biomarker levels. We used keywords, free words, and related words that included the terms "hydroxymethylglutaryl-CoA reductase inhibitors," "statin," and "bone turnover biomarkers" to search PubMed, Cochrane Library, and Embase. The Cochrane Risk Bias Evaluation Tool was used to evaluate the risk of bias, and Review Manager 5.3 and Stata 13.0 were used for statistical analyses. Six randomized controlled trials involving a total of 382 subjects were included in the meta-analysis. The results showed that statins increased the osteocalcin (OC) [mean difference (MD) = 0.73 ng/mL, 95% CI: 0.12, 1.35, I2 = 23% and p = 0.26], and decreased cross-linked N-telopeptide (NTX) (MD = -1.14 nM BCE, 95% CI: -2.21, -0.07, I2 = 0%, p = 0.53) and C-terminal peptide of type I collagen (CTX) (MD = -0.03 ng/mL, 95% CI: -0.05, -0.01, I2 = 0% and p = 0.56). There was no effect on bone-specific alkaline phosphatase (MD = -1.37 U/L, 95% CI: -3.09, 0.34, I2 = 0% and p = 0.94) and intact parathyroid hormone (MD = -1.73 pg/mL, 95% CI: -4.35, 0.89, I2 = 0% and p = 0.77). Statins increase bone formation biomarker OC and decrease bone resorption biomarker NTX and CTX levels.


Lateralization and frequency selectivity in normal and impaired hearing.
The onset-time difference delta T required to lateralize a 30-ms bifrequency tone burst toward the leading ear was measured as a function of the frequency difference delta F between the tone in the left ear and the tone in the right ear. At center frequencies of 0.5 and 4 kHz, four normal listeners tested at 80 and 100 dB SPL had delta Ts that were relatively constant at subcritical delta Fs, but increased at delta Fs wider than a critical band. At 1 kHz, delta T increased with delta F even at subcritical delta Fs. Ten listeners with cochlear impairments were tested at 100 dB SPL. Seven had normal delta Ts at 4 kHz, despite hearing losses between 50 and 70 dB. At 0.5 and 1 kHz, mildly impaired listeners had nearly normal lateralization functions, whereas more severely imparied listeners had very large delta Ts and no frequency selectivity. These and other findings indicate that listeners even with moderate to severe hearing losses can lateralize normally on the basis of interaural differences in onset envelope, but not on the basis of temporal differences in the fine structure.


Simultaneous penile-vaginal intercourse orgasm is associated with satisfaction (sexual, life, partnership, and mental health).
Previous multivariate research found that satisfaction was associated positively with frequency of specifically penile-vaginal intercourse (PVI; as opposed to other sexual activities) as well as with vaginal orgasm. The contribution to satisfaction of simultaneous orgasm produced by PVI merited direct examination in a large representative sample. To examine the associations of aspects of satisfaction (sexual, life, own mental health, partner relationship) with consistency of simultaneous orgasm produced by PVI (as well as with PVI frequency and vaginal orgasm consistency). A representative sample of Czechs (N = 1,570) aged 35-65 years completed a survey on aspects of satisfaction, PVI frequency, vaginal orgasm consistency, and consistency of simultaneous orgasm produced by PVI (the latter being a specially timed version of vaginal orgasm for women). Analysis of variance of satisfaction components (LiSat scale items) from age and the sexual behaviors. For both sexes, all aspects of satisfaction were associated with simultaneous PVI orgasm consistency and with PVI frequency (except female life satisfaction). All aspects of satisfaction were also associated with vaginal orgasm consistency. Multivariate analyses indicated that PVI frequency and simultaneous orgasm consistency make independent contributions to the aspects of satisfaction for both sexes. For both sexes, PVI frequency and simultaneous orgasm produced by PVI (as well as vaginal orgasm for women) are associated with greater life, sexual, partnership, and mental health satisfaction. Greater support for these specific aspects of sexual activity is warranted.


Experiences of a patient-initiated self-monitoring service in inflammatory arthritis: A qualitative exploration.
The aim of the present study was to explore patients' experience of a patient-initiated self-monitoring service for people with rheumatoid or psoriatic arthritis who are on methotrexate. The study took the form of qualitative semi-structured interviews, embedded within a randomized controlled trial. Twelve participants who were randomly assigned to the intervention arm were interviewed. Interviews digitally, transcribed verbatim and analysed using inductive thematic analysis. The study received full National Health Service ethics approval from Camden and Islington Community Local Research Ethics Committee (Ref. 09/H0722/91). Analysis revealed five key themes. Participants described usual care as burdensome and an inefficient use of time, particularly those in employment. Being able to self-monitor and initiate their own care increased patients' knowledge about their illness and its treatment, and enabled them to gain a sense of control and ownership over their arthritis. They appreciated the personalized nature of the new service, which allowed them to be seen at a time and by a method more appropriate to their needs. There were, however, some concerns about fidelity to the service protocol, confusion about the lack of consistency between symptoms and laboratory results, and anxiety about self-monitoring. Overall, participants were positive about the new service, in comparison with usual care, valuing its tailored approach and empowering effects. Further work is needed to ensure adherence to the service protocol and address anxieties around self-monitoring prior to any widespread implementation of the service.


Severe psychological distress among patients with epilepsy during the COVID-19 outbreak in southwest China.
To compare the severity of psychological distress between patients with epilepsy and healthy controls during the COVID-19 outbreak in southwest China, as well as identify potential risk factors of severe psychological distress among patients with epilepsy. This cross-sectional case-control study examined a consecutive sample of patients older than 15 years treated at the epilepsy center of West China Hospital between February 1 and February 29, 2020. As controls, sex- and age-matched healthy visitors of inpatients (unrelated to the patients) were also enrolled during the same period. Data on demographics and attention paid to COVID-19 were collected by online questionnaire, data on epilepsy features were collected from electronic medical records, and psychological distress was evaluated using the 6-item Kessler Psychological Distress Scale (K-6). Potential risk factors of severe psychological distress were identified using multivariate logistic regression. The 252 patients and 252 controls in this study were similar along all demographic variables except family income. Patients with epilepsy showed significantly higher K-6 scores than healthy controls and spent significantly more time following the COVID-19 outbreak (both P < .001). Univariate analyses associated both diagnosis of drug-resistant epilepsy and time spent paying attention to COVID-19 with severe psychological distress (defined as K-6 score >12; both P ≤ .001). Multivariate logistic regression identified two independent predictors of severe psychological distress: time spent paying attention to COVID-19 (odds ratio [OR] = 1.172, 95% confidence interval [CI] = 1.073-1.280) and diagnosis of drug-resistant epilepsy (OR = 0.283, 95% CI = 0.128-0.623). During public health outbreaks, clinicians and caregivers should focus not only on seizure control but also on mental health of patients with epilepsy, especially those with drug-resistant epilepsy. K-6 scores > 12 indicate severe psychological distress. This may mean, for example, encouraging patients to engage in other activities instead of excessively following media coverage of the outbreak.


Probing the responsive behavior of polyelectrolyte brushes using electrochemical impedance spectroscopy.
Cyclic voltammetry and impedance spectroscopy were employed to probe the responsive properties of polyelectrolyte brushes. Poly[(dimethylamino)ethyl methacrylate] (PDMAEMA) brushes over 100 nm thick on gold substrates were synthesized via surface-initiated atom-transfer radical polymerization and quaternized with methane iodide to obtain cationic brushes (Q-PDMAEMA). Q-PDMAEMA brushes respond to electrolytes by exhibiting swollen and collapsed states. Swollen brushes allow good permeability of electroactive probes, while collapsed states block electron transport. Electrolytes have different impacts on the electrochemical properties of Q-PDMAEMA. Some salts (NaNO3) cause brush collapse due to charge screening, while others such as those with more hydrophobic anions (ClO4-, PF6-, and Tf2N-) induce brush collapse because of solubility changes. The collapsed brushes exhibit intrinsically different resistance as probed with impedance. Charged screened brushes retain good permeability to electroactive probes. Strongly coordinating hydrophobic anions lead to insoluble brushes, resulting in a high resistance. These results show that electrochemical impedance spectroscopy is a powerful technique to probe the properties and structure of polyelectrolyte brushes.


Significance of HLA in Graves' disease and Graves' orbitopathy in Asian and Caucasian populations - a systematic review.
Graves' disease (GD) and Graves' orbitopathy (GO) development were suspected to be HLA-related in both Asian and Caucasian populations. However, most studies were performed with application of serological methods or low resolution genetic typing, which led to inconsistent results even among the same population. The present review is intended to summarize the state-of-art knowledge on the HLA significance in GD and GO in Asians and Caucasians, as well as to find the most significant alleles for each of the populations. PubMed was searched for relevant articles using the following search terms: HLA plus thyroid-associated ophthalmopathy or Graves' disease or Graves' orbitopathy or thyroid eye disease or thyroid-associated orbitopathy. In Asian population GD was found to be associated mostly with B*46:01, DPB1*05:01, DRB1*08:02/03, DRB1*16:02, DRB1*14:03, DRB1*04:05, DQB1*05:02 and DQB1*03:03, while DRB1*07:01, DRB1*01:01, DRB1*13:02, DRB1*12:02 are potentially protective. HLA-B*38:02, DRB1*16:02, DQA1*01:02, DQB1*05:02 can be considered associated with increased risk of GO in Asians, while HLA-B*54:01 may play protective role. In Caucasians, C*07:01, DQA1*05:01, DRB1*03, DQB1*02:01 are associated with GD risk while DRB1*07:01, DQA1*02:01 may be protective. Significance of HLA in the course of GD and novel aspects of HLA amino acid variants and potential HLA-based treatment modalities were also discussed.


Current challenges of lung cancer care in an aging population.
Lung cancer is the most common cancer in the elderly with a high mortality rate. Despite the high incidence, the elderly are under-represented in clinical trials and under-treated in clinical practice. These patients have a higher prevalence of comorbid disease, higher polypharmacy interactions, and an increased risk of mortality and toxicity with cancer treatments, compared to younger patients. Often data about their treatments come from retrospective analysis including patients who do not reflect the general elderly population. However, elderly patients can often receive cancer treatment similar to younger patients and an active treatment should not be denied based on older age.


Foetal echocardiography of transposition of the great arteries and common arterial trunk.
Advances in foetal echocardiography allow detection of conotruncal anomalies such as transposition of the great arteries and common arterial trunk. Early detection of these anomalies is important for appropriate delivery planning, family counselling, and management. This manuscript will review the anatomic considerations, differential diagnosis, and foetal echocardiographic features of each of these malformations and review the importance of prenatal diagnosis and family counselling.


Burkholderia gladioli osteomyelitis in association with chronic granulomatous disease: case report and review.
We describe a case of insidious small bone osteomyelitis and soft tissue abscess with Burkholderia gladioli in a 6-year-old Caucasian boy with chronic granulomatous disease. DNA sequencing of the 16S ribosomal RNA gene confirmed the bacterial identification. Clinical cure was achieved with a combination of antimicrobial therapy and surgical debridement. A review of infections caused by Burkholderia spp., other than Burkholderia cepacia complex, in pediatric patients with chronic granulomatous disease is provided.


[Acute renal failure in severe forms of peritonitis].
Acute kidney insufficiency is exact defined organ insufficiency. It is due to the possibility of quantitative valuation of kidney's functions through some laboratory tests and research. The author tries to find direct dependence between the development of this complication and the age of the patient; and also between this and final exit of peritonitis. An object of this research are 460 patients with acute forms of peritonitis. In 379 (82 per cent) of the patients urea was under 16.7 and mortality-rate was 13 per cent, i.e. close to the total result for this disease. In 81 (18 per cent) value of urea is more than 16.7 and the death-rate in this group is 52 (64 per cent), i.e. to a large degree higher than that in total. Correlative coefficient r = 0.418 is the evidence for the correlation between this complication and the final exit of disease.


Public Stigma Toward Mental Illness in Jordan: A Cross-Sectional Survey of Family Members of Individuals With Schizophrenia, Depression, and Anxiety.
Stigma affects family members of individuals with mental illness. A survey of 640 family members of individuals with mental illness was conducted. Three factors were found to influence stigma regarding schizophrenia, depression, and anxiety: (a) preconceived stereotypes, (b) a sense of personal responsibility or blame for the condition, and (c) perceptions of the patient's inability to recover from the condition. A stronger association between negative stereotypes and inability to recover was found with schizophrenia than depression or anxiety. Conversely, depression and anxiety were found to be correlated with personal responsibility or blame for the condition. The public perception of mental health conditions (e.g., depression, anxiety, schizophrenia) has a crucial role in deriving programs for reducing stigma and raising awareness. Personalized and efficacious treatment regimens may be facilitated by understanding these perceptions and the underlying explanations for why they exist. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 36-43.].


Reduced clearance of respiratory syncytial virus infection in a preterm lamb model.
Respiratory syncytial virus (RSV) causes significant respiratory disease in children worldwide. For the study of severe RSV disease seen in preterm infants, a suitable animal model is lacking. The novel hypothesis of this study was that preterm lambs are susceptible to bovine RSV (bRSV) infection, an analogous pneumovirus with ruminant host specificity, and that there would be age-dependent differences in select RSV disease parameters. During RSV infection, preterm lambs had elevated temperatures and respiration rates with mild anorexia and cough compared to controls. Gross lesions included multifocal consolidation and atelectasis with foci of hyperinflation. Microscopic lesions included multifocal alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the RSV antigen to all layers of bronchiolar epithelium from a few basal cells to numerous sloughing epithelia. A few mononuclear cells were also immunoreactive. To assess for age-dependent differences in RSV infection, neonatal lambs were infected similarly to the preterm lambs or with a high-titer viral inoculum. Using morphometry at day 7 of infection, preterm lambs had significantly more cellular immunoreactivity for RSV antigen (P <0.05) and syncytial cell formation (P <0.05) than either group of neonatal lambs. This work suggests that perinatal RSV clearance is age-dependent, which may explain the severity of RSV infection in preterm infants. The preterm lamb model is useful for assessing age-dependent mechanisms of severe RSV infection.


Temperature and state dependence of dynamic phrenic oscillations in the decerebrate juvenile rat.
The aim of the present study was to determine characteristics of fast oscillations in the juvenile rat phrenic nerve (Ph) and to establish their temperature and state dependence. Two different age-matched decerebrate, baro- and chemodenervated rat preparations, in vivo and in situ arterially perfused models, were used to examine three systemic properties: 1) generation and dynamics of fast oscillations in Ph activity (both preparations), 2) responses to anoxia (both preparations), and 3) the effects of temperature on fast oscillations (in situ only). Both juvenile preparations generated power and coherence in two major bands analogous to adult medium- and high-frequency oscillations (HFO) at frequencies that increased with temperature but were lower than in adults. At < 28 degrees C, however, Ph oscillations were confined primarily to one low-frequency band (20-45 Hz). During sustained anoxia, both preparations produced stereotypical state changes from eupnea to hyperpnea to transition bursting (a behavior present only in vivo during incomplete ischemia) to gasping. Thus the juvenile rat produces a sequential pattern of responses to anoxia that are intermediate forms between those produced by neonates and those produced by adults. Time-frequency analysis determined that fast oscillations demonstrated dynamics over the course of the inspiratory burst and a state dependence similar to that of adults in vivo in which hyperpnea (and transition) bursts are associated with increases in HFO, while gasping contains no HFO. Our results confirm that both the fast oscillations in Ph activity and the coherence between Ph pairs produced by the juvenile rat are profoundly state- and temperature-dependent.


Trabecular Architecture Determines Impulse Propagation Through the Early Embryonic Mouse Heart.
Most embryonic ventricular cardiomyocytes are quite uniform, in contrast to the adult heart, where the specialized ventricular conduction system is molecularly and functionally distinct from the working myocardium. We thus hypothesized that the preferential conduction pathway within the embryonic ventricle could be dictated by trabecular geometry. Mouse embryonic hearts of the Nkx2.5:eGFP strain between ED9.5 and ED14.5 were cleared and imaged whole mount by confocal microscopy, and reconstructed in 3D at 3.4 μm isotropic voxel size. The local orientation of the trabeculae, responsible for the anisotropic spreading of the signal, was characterized using spatially homogenized tensors (3 × 3 matrices) calculated from the trabecular skeleton. Activation maps were simulated assuming constant speed of spreading along the trabeculae. The results were compared with experimentally obtained epicardial activation maps generated by optical mapping with a voltage-sensitive dye. Simulated impulse propagation starting from the top of interventricular septum revealed the first epicardial breakthrough at the interventricular grove, similar to experimentally obtained activation maps. Likewise, ectopic activation from the left ventricular base perpendicular to dominant trabecular orientation resulted in isotropic and slower impulse spreading on the ventricular surface in both simulated and experimental conditions. We conclude that in the embryonic pre-septation heart, the geometry of the A-V connections and trabecular network is sufficient to explain impulse propagation and ventricular activation patterns.


Race and survival after out-of-hospital cardiac arrest in a suburban community.
To determine whether race, when controlled for income, is an independent predictor of survival to hospital discharge after out-of-hospital cardiac arrest (OHCA). Prospective OHCA data were collected over 4 years (1991-1994) from a convenience sample of OHCA patients transported to nine hospitals in three suburban counties. Race was determined from hospital and vital statistics records. The average household income was identified from ZIP codes and used as a marker of socioeconomic status. Demographic data and known predictors of survival were compared between blacks and whites. A logistic regression analysis was used to assess the association between race, income, and survival. Of the 1,690 patients, 223 (13%) were blacks and 1,467 (87%) were whites. Average household income was less for blacks than for whites ($40,225 versus $46,193; P < .001), but both populations were affluent by national standards (national percentile ranks were 73% and 88%, respectively). The populations were no different in percentage of witnessed arrests (57% versus 61%; P = .465). Blacks were younger (mean +/- SD, 62 +/- 16 versus 68 +/- 15 years; P < .001); less frequently received bystander CPR (11% versus 20%; P = .002); less often had ventricular tachycardia or ventricular fibrillation (37% versus 50%; P < .001); and had a shorter advanced life support call-response interval (median, 4 versus 6 minutes; P < .001). The odds ratio for survival (white/black) was .931 (95% confidence interval, .446 to 1.945). Race was not found to predict adverse OHCA outcomes in this affluent population.