Dysfunctional parenting and emotional problems and substance misuse: Enhancing psychological flexibility in college students.
This cross-sectional study aimed to investigate the mediating role of psychological flexibility in the relationship between dysfunctional parenting (i.e., dysfunctional parent modes) and emotional problems and substance misuse among Turkish college students. Participants were 466 undergraduate students (69% female) aged between 18 and 45 years (M = 21.46, SD = 3.31) from a public university in Turkey. The majority of participants in the study reported never or infrequent use of tobacco, alcohol, and prescription drugs, with daily or almost daily use reported by less than a quarter of the sample for each substance. Results showed that higher levels of dysfunctional parent modes were associated with increased emotional problems and substance misuse. Moreover, psychological flexibility mediated the relationship between dysfunctional parent modes and emotional problems, as well as both mediated and moderated the relationship between dysfunctional parent modes and substance misuse. Results from the study also showed that people in the at-risk group for substance misuse reported higher levels of dysfunctional parent modes and emotional problems, as well as lower levels of psychological flexibility than the typical group. These results suggest that psychological flexibility may play a significant role in the link between dysfunctional parent modes and emotional problems and substance misuse among Turkish college students. Future research should investigate whether interventions targeting psychological flexibility could be effective in reducing emotional problems and substance misuse among students with dysfunctional parent modes.


[Results of immunoprophylaxis of HIV-infected patients with 13-valent conjugated pneumococcal vaccine].
To assess changes in the composition of the microflora of the upper respiratory tract and indicators of cellular immunity 1 year after the administration of 13-valent conjugated pneumococcal vaccine (PCV13) in adult HIV-infected patients. Were recruited 100 participants of both sexes (50% male and 50% female). All patients underwent microbiological and immunological (determination of the level of CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD45RO+ peripheral blood lymphocytes) examinations before vaccine administration and after 12 months. Immunization with PCV13 leads to a statistically significant decrease in the carriage of Streptococcus pneumoniae 1 year after vaccination (p=0.012). After 1 year after the administration of PCV13, the patients showed a statistically significant increase in the total number of T-lymphocytes, T-helpers, and cytotoxic T-lymphocytes in comparison with pre-vaccination levels. A statistically significant increase in the level of CD45RO+ lymphocytes was found 1 year after the administration of PCV13 (p0.0001). S. pneumoniae was found on the mucous membrane of the posterior pharyngeal wall in 16% of the participants, indicating its high prevalence in HIV-infected patients. Also, representatives of enterobacteria and Candida spp. were found in smears. (22 and 15% of participants, respectively). One year after the vaccine administration, pneumococcus was isolated from 5 participants, which is statistically significantly lower than before immunization (p=0.012). After the introduction of PCV13, there is a statistically significant increase in the total number of T-lymphocytes, T-helpers and cytotoxic T-lymphocytes 1 year after immunization. However, there is no statistically significant increase in the B-lymphocyte population. In addition, PCV13 leads to the formation of immunological memory cells in HIV-infected patients. Thus, immunoprophylaxis with PCV13 in adult HIV-infected patients leads to a decrease in the carriage of S. pneumoniae, and also promotes the stimulation of the T-cell link of the immune system and stimulates the formation of immunological memory cells.


The Pharmacokinetics of Vitamin C.
The pharmacokinetics of vitamin C (vitC) is indeed complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), the absorption and elimination are highly dose-dependent. Moreover, the tissue specific expression levels and subtypes of these SVCTs result in a compartmentalized distribution pattern with a diverse range of organ concentrations of vitC at homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. The homeostasis of vitC is influenced by several factors, including genetic polymorphisms and environmental and lifestyle factors such as smoking and diet, as well as diseases. Going from physiological to pharmacological doses, vitC pharmacokinetics change from zero to first order, rendering the precise calculation of dosing regimens in, for example, cancer and sepsis treatment possible. Unfortunately, the complex pharmacokinetics of vitC has often been overlooked in the design of intervention studies, giving rise to misinterpretations and erroneous conclusions. The present review outlines the diverse aspects of vitC pharmacokinetics and examines how they affect vitC homeostasis under a variety of conditions.


Growth hormone induced rise in glomerular filtration rate is not obliterated by angiotensin-converting enzyme inhibitors.
In 8 healthy normotensive probands with normal glomerular filtration rate, the effect of recombinant human growth hormone (rhGH) on inulin clearance (Cin) was examined in an open study with intraindividual crossover with or without enalapril pretreatment (20 mg/day). rhGH was administered by subcutaneous injection (4.5 U twice daly) for 3 days. On the following day Cin was measured with an enzymatic steady state infusion technique. Systemic hemodynamics and potential metabolic effects of rhGH, i.e., inulin-like growth factors I and II, somatomedin-binding protein, glucagon, C peptide, amino acid pattern, etc., were monitored. On controlled dietary intake of protein, the median Cin rose 72 h after start of rhGh administration from 114 (range 91-158) to 135 (108-167) ml/min/1.73 m2 without enalapril pretreatment (p less than 0.01) and from 111 (88-153) to 131 (100-173 ml/min/1.73 m2 with enalapril pretreatment (p less than 0.02). The results confirm that (1) rhGH increases Cin to a similar extent as extractive GH and (2) further demonstrate that this action is not obliterated by blocking the circulating converting enzyme.


Structural and bioactive properties of 3-O-methylfunicone.
In recent years, the ongoing need for novel pharmaceuticals to be introduced in human medicine has substantially benefited from the widespread research activity on the role of bioactive microbial compounds involved in the regulation of interactions with other organisms. A good example is represented by 3-O-methylfunicone, a benzo-γ-pyrone metabolite at first characterized on account of the antifungal aptitude of the producing strain, which has later become more valuable for its antiproliferative and pro-apoptotic properties resulting in a series of studies on human tumor cell lines. An overview of aspects concerning molecular structure, sources, and biological properties of this compound is offered in the present paper.


Infant mental health in Malaysia.
The Infant Mental Health system in Malaysia is described, beginning with cultural and religious practices that influence mental health practices. Second, a description of the Malaysian mental health system, including historical influences, is given. Third, policy and services for young children with mental health problems are described. Finally, recommendations for future steps for developing an effective infant mental health system are presented, including the development of infant mental health policies by the government, increased personnel training, increased community mental health resources, integration of culture into the mental health system, and finally, development of appropriate screening and assessment instruments and systems.


OpiA, a Type Six Secretion System Substrate, Localizes to the Cell Pole and Plays a Role in Bacterial Growth and Viability in Francisella tularensis LVS.
Francisella tularensis is an intracellular pathogen and the causative agent of tularemia. The F. tularensis type six secretion system (T6SS) is required for a number of host-pathogen interactions, including phagolysosomal escape and invasion of erythrocytes. One known effector of the T6SS, OpiA, has recently been shown to be a phosphatidylinositol-3 kinase. To investigate the role of OpiA in erythrocyte invasion, we constructed an opiA-null mutant in the live vaccine strain, F. tularensis LVS. OpiA was not required for erythrocyte invasion; however, deletion of opiA affected growth of F. tularensis LVS in broth cultures in a medium-dependent manner. We also found that opiA influenced cell size, gentamicin sensitivity, bacterial viability, and the lipid content of F. tularensis A fluorescently tagged OpiA (OpiA-emerald-green fluorescent protein [EmGFP]) accumulated at the cell poles of F. tularensis, which is consistent with the location of the T6SS. However, OpiA-EmGFP also exhibited a highly dynamic localization, and this fusion protein was detected in erythrocytes and THP-1 cells in vitro, further supporting that OpiA is secreted. Similar to previous reports with F. novicida, our data demonstrated that opiA had a minimal effect on intracellular replication of F. tularensis in host immune cells in vitro However, THP-1 cells infected with the opiA mutant produced modestly (but significantly) higher levels of the proinflammatory cytokine tumor necrosis factor alpha compared to these host cells infected with wild-type bacteria. We conclude that, in addition to its role in host-pathogen interactions, our results reveal that the function of opiA is central to the biology of F. tularensis bacteria.IMPORTANCEF. tularensis is a pathogenic intracellular pathogen that is of importance for public health and strategic defense. This study characterizes the opiA gene of F. tularensis LVS, an attenuated strain that has been used as a live vaccine but that also shares significant genetic similarity to related Francisella strains that cause human disease. The data presented here provide the first evidence of a T6SS effector protein that affects the physiology of F. tularensis, namely, the growth, cell size, viability, and aminoglycoside resistance of F. tularensis LVS. This study also adds insight into our understanding of OpiA as a determinant of virulence. Finally, the fluorescence fusion constructs presented here will be useful tools for dissecting the role of OpiA in infection.


TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation.
TL1A is a tumor necrosis factor-like molecule that mediates a strong costimulation of T-helper (T(H)) 1 cells. Expression of TL1A is increased in the mucosa of Crohn's disease patients and murine models of ileitis. The aim of this study was to determine the possible role of TL1A in chronic intestinal inflammation. We used dextran sodium sulfate (DSS)-induced chronic colitis to investigate the effects of TL1A on the development of colitis. The cytokine profile in the gut-associated lymphoid tissue (GALT) was measured. Neutralizing anti-TL1A antibodies were injected intraperitoneally into DSS-induced chronic colitis and G protein alphai2(-/-) T-cell transfer colitis models. Severity of colitis was evaluated by body weight, colon length, histology, and cytokine production. DSS-induced chronic colitis was characterized by the infiltration of CD4(+) T cells. TL1A, death receptor 3, interferon (IFN)-gamma, and interleukin (IL)-17 were increased significantly in GALT of DSS-treated mice. TL1A up-regulated both IFN-gamma production from T(H)1 cells and IL-17 production from T(H)17 cells in GALT CD4(+) T cells. Furthermore, IFN-gamma and IL-17 production from CD4(+) T cells, induced by IL-12 and IL-23 respectively, was enhanced synergistically by combination with TL1A. Anti-TL1A antibody prevented chronic colitis and attenuated established colitis by down-regulation of both T(H)1 and T(H)17 activation. Our results reveal that TL1A is an important modulator in the development of chronic mucosal inflammation by enhancing T(H)1 and T(H)17 effector functions. The central role of TL1A represents an attractive, novel therapeutic target for the treatment of Crohn's disease patients.


Identification of the full-length β-actin sequence and expression profiles in the tree shrew (Tupaia belangeri).
The tree shrew (Tupaia belangeri) diverges from the primate order (Primates) and is classified as a separate taxonomic group of mammals - Scandentia. It has been suggested that the tree shrew can be used as an animal model for studying human diseases; however, the genomic sequence of the tree shrew is largely unidentified. In the present study, we reported the full-length cDNA sequence of the housekeeping gene, β-actin, in the tree shrew. The amino acid sequence of β-actin in the tree shrew was compared to that of humans and other species; a simple phylogenetic relationship was discovered. Quantitative polymerase chain reaction (qPCR) and western blot analysis further demonstrated that the expression profiles of β-actin, as a general conservative housekeeping gene, in the tree shrew were similar to those in humans, although the expression levels varied among different types of tissue in the tree shrew. Our data provide evidence that the tree shrew has a close phylogenetic association with humans. These findings further enhance the potential that the tree shrew, as a species, may be used as an animal model for studying human disorders.


Cardiac amyloidosis presenting as pseudo-hypertrophic cardiomyopathy.
Both cardiac amyloidosis and hypertrophic cardiomyopathy may result in excessive hypertrophy of the myocardium, which can be seen on echocardiography. While in most patients the two conditions are easily differentiated, we present in this report a case of amyloidosis that mimicked hypertrophic cardiomyopathy so closely that it required endomyocardial biopsy to establish the diagnosis.


[Clinical characteristics of urticaria in children versus adults].
To study the clinical characteristics of urticaria in children versus adults, and to provide reference for the etiological analysis, disease evaluation, and treatment of urticaria in children. The clinical data of 2 411 patients with urticaria who visited the Department of Dermatology at Xiangya Hospital of Central South University from January 2013 to May 2017 were collected to study their socio-demographic characteristics. The clinical characteristics of urticaria were compared between the 68 children and 672 adults of the 740 patients with complete follow-up data. Among the 411 pediatric patients, 314 (76.4%) had acute urticaria; among the 2 000 adult patients, 896 (44.8%) had chronic spontaneous urticaria. The causes of acute urticaria in children included infection (41%, 16/39). The accompanying symptoms of acute urticaria in children mainly included abdominal pain and diarrhea (44%, 17/39), while those in adults mainly included chest distress and shortness of breath (32%, 11/34). Compared with the adult patients, the pediatric patients had significantly lower chronic urticaria activity scores before and after treatment (P<0.05), a significantly higher rate of response to second-generation antihistamines (82.1% vs 62.2%; P<0.05), and a significantly higher proportion of individuals with a personal and family history of urticaria (P<0.05). Acute urticaria is more commonly seen than chronic urticaria in children with urticaria, and the main accompanying symptoms are abdominal pain and diarrhea, which are different from adults with urticaria. Chronic urticaria has a better treatment outcome in children than in adults. The most frequently seen cause of acute urticaria is infection in children. Atopic children may be susceptible to urticaria.


Selection of metric for indoor-outdoor source apportionment of metals in PM2.5 : mg/kg versus ng/m3.
Trends in the elemental composition of fine particulate matter (PM2.5 ) collected from indoor, outdoor, and personal microenvironments were investigated using two metrics: ng/m3 and mg/kg. Pearson correlations that were positive using one metric commonly disappeared or flipped to become negative when the other metric was applied to the same dataset. For example, the correlation between Mo and S in the outdoor microenvironment was positive using ng/m3 (p < 0.05) but negative using mg/kg (p < 0.05). In general, elemental concentrations (mg/kg) within PM2.5 decreased significantly (p < 0.05) as PM2.5 concentrations (µg/m3 ) increased-a dilution effect that was observed in all microenvironments and seasons. An exception was S: in the outdoor microenvironment, the correlation between wt% S and PM2.5 flipped from negative in the winter (p < 0.01) to positive (p < 0.01) in the summer, whereas in the indoor microenvironment, this correlation was negative year-round (p < 0.05). Correlation analyses using mg/kg indicated that elemental associations may arise from Fe-Mn oxyhydroxide sorption processes that occur as particles age, with or without the presence of a common anthropogenic source. Application of mass-normalized concentration metrics (mg/kg or wt%), enabled by careful gravimetric analysis, revealed new evidence of the importance of indoor sources of elements in PM2.5 .


Comparison of posterior decompression techniques and conventional laminectomy for lumbar spinal stenosis.
To compare the efficacy of posterior decompression techniques with conventional laminectomy for lumbar spinal stenosis. The Embase, PubMed, and Cochrane Library databases were searched with no language limitations from inception to January 13, 2022. The main outcomes were functional disability, perceived recovery, leg and back pain, complications. A random effects model was used to pooled data. Risk ratio (RR), mean difference (MD) and 95% confidence interval (CI) were used to report results. The study protocol was published in PROSPERO (CRD42022302218). 14 trials including 1,106 participants were included in the final analysis. Bilateral laminotomy was significantly more efficacious in improve functionality than laminectomy [MD: -2.94; (95% CI, -4.12 to -1.76)]. Low incidence of iatrogenic instability due to bilateral laminectomy compared with laminectomy [RR: 0.11; (95% CI, 0.02 to 0.59)]. In addition, between those who received bilateral laminotomy and those undergoing laminectomy, the result showed significant difference regarding recovery [RR: 1.31; (95% CI, 1.03 to 1.67)]. This study provides evidence that bilateral laminotomy has advantages in functional recovery, postoperative stability, and postoperative rehabilitation outcomes. Further research is needed to determine whether posterior techniques provide a safe and effective option for conventional laminectomy.


Stability of union after tibial shaft fracture. Analysis by a non-invasive technique.
The stability of union following the conservative treatment of tibial shaft fractures has been examined in 157 patients by a non-invasive method. With this technique it is possible to ascertain when the fragments are united and whether the strength of union is sufficient for full weight-bearing without protection. The mean time required for union was 14.0 +/- 9.2 weeks, with a range of 4 to 48 weeks. In 31 cases union was judged to be delayed; in 22 of these, intended operations were avoided because repeated stability determinations indicated progressive union. Of nine fracture variables examined, the only ones which significantly affected the time required to achieve union were the age and the weight of the patient. Irrelevant factors were the type and level of the fracture, the energy of trauma, soft-tissue injury and the presence of multiple injuries.


Genotyping of human neutrophil antigens by polymerase chain reaction sequence-based typing.
Genotyping for human neutrophil antigen (HNA) systems is required in the investigation of disorders involving alloimmunisation to HNA. We established a polymerase chain reaction sequence-based typing method for genotyping HNA and determined the genotype and allele frequencies of HNA in the Zhejiang Han population of China. Four hundred, healthy unrelated Zhejiang Han individuals were recruited. Specific primers for HNA were designed and the polymerase chain reaction amplification conditions were optimised. Amplification amplicons were purified with enzyme digestion and then sequenced. The frequencies of the FCGR3B*01 and FCGR3B*02 alleles were 0.613 and 0.387; no FCGR3B*03 allele was found. The frequencies of the SLC44A2*1 and SLC44A2*2 alleles were 0.654 and 0.346, respectively, while the frequencies of the ITGAL*1 (HNA-5a) and ITGAL*2 (HNA-5b) alleles were 0.896 and 0.104. Only ITGAM*1 (HNA-4a) allele was found in this study. Six single nucleotide polymorphisms were confirmed on sequenced regions separate from HNA polymorphisms, including FCGR3B (IVS3+39G>A and IVS3+52G>A), CD177(172A>G), SLC44A2 (IVS5-44A>G and IVS7-15T>C) and ITGAM (IVS3+118T>C). The polymerase chain reaction sequence-based typing method for genotyping HNA is reliable. These data of HNA alleles frequencies could contribute to the analysis of alloimmunisation to HNA in China.


On the chordae structure and dynamic behaviour of the mitral valve.
We develop a fluid-structure interaction (FSI) model of the mitral valve (MV) that uses an anatomically and physiologically realistic description of the MV leaflets and chordae tendineae. Three different chordae models-complex, 'pseudo-fibre' and simplified chordae-are compared to determine how different chordae representations affect the dynamics of the MV. The leaflets and chordae are modelled as fibre-reinforced hyperelastic materials, and FSI is modelled using an immersed boundary-finite element method. The MV model is first verified under static boundary conditions against the commercial finite element software ABAQUS and then used to simulate MV dynamics under physiological pressure conditions. Interesting flow patterns and vortex formulation are observed in all three cases. To quantify the highly complex system behaviour resulting from FSI, an energy budget analysis of the coupled MV FSI model is performed. Results show that the complex and pseudo-fibre chordae models yield good valve closure during systole but that the simplified chordae model leads to poorer leaflet coaptation and an unrealistic bulge in the anterior leaflet belly. An energy budget analysis shows that the MV models with complex and pseudo-fibre chordae have similar energy distribution patterns but the MV model with the simplified chordae consumes more energy, especially during valve closing and opening. We find that the complex chordae and pseudo-fibre chordae have similar impact on the overall MV function but that the simplified chordae representation is less accurate. Because a pseudo-fibre chordal structure is easier to construct and less computationally intensive, it may be a good candidate for modelling MV dynamics or interaction between the MV and heart in patient-specific applications.


Bisfunctionalized Janus molecules.
[reaction: see text] Bisfunctionalized dendritic multiester molecules were synthesized by combined protection-deprotection and divergent-convergent-divergent sequences in high yields leading to dendritic molecules that combine two functionally different surfaces, polar aliphatic arborol and nonpolar gallate ether moieties, resulting in a two-faced Janus molecule.


Recent advances in the biodegradation of polyethylene terephthalate with cutinase-like enzymes.
Polyethylene terephthalate (PET) is a synthetic polymer in the polyester family. It is widely found in objects used daily, including packaging materials (such as bottles and containers), textiles (such as fibers), and even in the automotive and electronics industries. PET is known for its excellent mechanical properties, chemical resistance, and transparency. However, these features (e.g., high hydrophobicity and high molecular weight) also make PET highly resistant to degradation by wild-type microorganisms or physicochemical methods in nature, contributing to the accumulation of plastic waste in the environment. Therefore, accelerated PET recycling is becoming increasingly urgent to address the global environmental problem caused by plastic wastes and prevent plastic pollution. In addition to traditional physical cycling (e.g., pyrolysis, gasification) and chemical cycling (e.g., chemical depolymerization), biodegradation can be used, which involves breaking down organic materials into simpler compounds by microorganisms or PET-degrading enzymes. Lipases and cutinases are the two classes of enzymes that have been studied extensively for this purpose. Biodegradation of PET is an attractive approach for managing PET waste, as it can help reduce environmental pollution and promote a circular economy. During the past few years, great advances have been accomplished in PET biodegradation. In this review, current knowledge on cutinase-like PET hydrolases (such as TfCut2, Cut190, HiC, and LCC) was described in detail, including the structures, ligand-protein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts were highlighted, such as improving the PET hydrolytic activity by constructing fusion proteins. The review is expected to provide novel insights for the biodegradation of complex polymers.


Capillary glucose meter accuracy and sources of error in the ambulatory setting.
Hand-held glucose meters are used throughout the health system by both patients with diabetes and also by health care practitioners. Glucose meter technology is constantly evolving. The current generation of meters and strips are quick to use and require a very small volume of blood. This review aims to describe meters currently available in New Zealand, for use in the ambulatory setting. It also aims to discuss the limits of meter performance and provide technical information that is relevant to the clinician, using locally available data. Commoner causes and consequences of end-user (patient and health professional) error are illustrated using clinical case examples. No meter offers definite advantages over other meters in all clinical situations, rather meters should be chosen because they fit the needs of individual patients and because the provider is able to offer appropriate educational and quality assurance backup to the meter user. A broad understanding of the advantages and disadvantages of the subsidised meter systems available in New Zealand will help the health practitioner decide when it is in the best interests of their patients to change or update meter technology.


Vasectomy: psychological effects and pre-operative counseling.
Modern thinking with regard to the psychological side effects of vasectomy are outlined and the importance of initial motivation stressed. Reasons for anticipating psychological failure are listed. The process of counselling is discussed leading from the patient's statement of reasons for the operation, through his expressed fears of probing his unexpressed fears and thence to an explanation of the procedure and follow-up necessities.


NF-κB-dependent IRF1 activation programs cDC1 dendritic cells to drive antitumor immunity.
Conventional type 1 dendritic cells (cDC1s) are critical for antitumor immunity. They acquire antigens from dying tumor cells and cross-present them to CD8+ T cells, promoting the expansion of tumor-specific cytotoxic T cells. However, the signaling pathways that govern the antitumor functions of cDC1s in immunogenic tumors are poorly understood. Using single-cell transcriptomics to examine the molecular pathways regulating intratumoral cDC1 maturation, we found nuclear factor κB (NF-κB) and interferon (IFN) pathways to be highly enriched in a subset of functionally mature cDC1s. We identified an NF-κB-dependent and IFN-γ-regulated gene network in cDC1s, including cytokines and chemokines specialized in the recruitment and activation of cytotoxic T cells. By mapping the trajectory of intratumoral cDC1 maturation, we demonstrated the dynamic reprogramming of tumor-infiltrating cDC1s by NF-κB and IFN signaling pathways. This maturation process was perturbed by specific inactivation of either NF-κB or IFN regulatory factor 1 (IRF1) in cDC1s, resulting in impaired expression of IFN-γ-responsive genes and consequently a failure to efficiently recruit and activate antitumoral CD8+ T cells. Last, we demonstrate the relevance of these findings to patients with melanoma, showing that activation of the NF-κB/IRF1 axis in association with cDC1s is linked with improved clinical outcome. The NF-κB/IRF1 axis in cDC1s may therefore represent an important focal point for the development of new diagnostic and therapeutic approaches to improve cancer immunotherapy.


Vertically aligned zinc oxide nanowires electrodeposited within porous polycarbonate templates for vibrational energy harvesting.
A piezoelectric nanogenerator has been fabricated using a simple, fast and scalable template-assisted electrodeposition process, by which vertically aligned zinc oxide (ZnO) nanowires were directly grown within a nanoporous polycarbonate (PC) template. The nanowires, having average diameter 184 nm and length 12 μm, are polycrystalline and have a preferred orientation of the [100] axis parallel to the long axis. The output power density of a nanogenerator fabricated from the as-grown ZnO nanowires still embedded within the PC template was found to be 151 ± 25 mW m(-3) at an impedance-matched load, when subjected to a low-level periodic (5 Hz) impacting force akin to gentle finger tapping. An energy conversion efficiency of ∼4.2% was evaluated for the electrodeposited ZnO nanowires, and the ZnO-PC composite nanogenerator was found to maintain good energy harvesting performance through 24 h of continuous fatigue testing. This is particularly significant given that ZnO-based nanostructures typically suffer from mechanical and/or environmental degradation that otherwise limits their applicability in vibrational energy harvesting. Our template-assisted synthesis of ZnO nanowires embedded within a protective polymer matrix through a single growth process is thus attractive for the fabrication of low-cost, robust and stable nanogenerators.


A comparative study of tooth and dental arch dimensions in Jewish children of different ethnic descent. I. Kurds and Yemenites.
Dental casts of 99 Kurdish and 98 Yemenite Jewish children evenly distributed between the sexes, aged 12 years, were measured for mesiodistal and buccolingual tooth dimensions, and arch depth and width. Dental dimensions showed significant differences between the two groups in certain permanent teeth in mesiodistal length, while in the buccolingual diameter the differences did not reach statistical significance. Dental arch form in Kurdish children was more rounded due to significantly bigger arch width, while arch depth was not significantly different from Yemenites. Intragroup sex differences were found in both groups with reference to arch dimensions, while in the dental parameters they were more strongly expressed in Kurdish children.


X23D-Intraoperative 3D Lumbar Spine Shape Reconstruction Based on Sparse Multi-View X-ray Data.
Visual assessment based on intraoperative 2D X-rays remains the predominant aid for intraoperative decision-making, surgical guidance, and error prevention. However, correctly assessing the 3D shape of complex anatomies, such as the spine, based on planar fluoroscopic images remains a challenge even for experienced surgeons. This work proposes a novel deep learning-based method to intraoperatively estimate the 3D shape of patients' lumbar vertebrae directly from sparse, multi-view X-ray data. High-quality and accurate 3D reconstructions were achieved with a learned multi-view stereo machine approach capable of incorporating the X-ray calibration parameters in the neural network. This strategy allowed a priori knowledge of the spinal shape to be acquired while preserving patient specificity and achieving a higher accuracy compared to the state of the art. Our method was trained and evaluated on 17,420 fluoroscopy images that were digitally reconstructed from the public CTSpine1K dataset. As evaluated by unseen data, we achieved an 88% average F1 score and a 71% surface score. Furthermore, by utilizing the calibration parameters of the input X-rays, our method outperformed a counterpart method in the state of the art by 22% in terms of surface score. This increase in accuracy opens new possibilities for surgical navigation and intraoperative decision-making solely based on intraoperative data, especially in surgical applications where the acquisition of 3D image data is not part of the standard clinical workflow.


Regulation of rat gastric H+/K(+)-ATPase alpha-subunit mRNA by omeprazole.
The H+/K(+)-ATPase is the dimeric enzyme responsible for H+ secretion by the gastric parietal cells. The present study examined the response of rat fundic mRNA levels of H+/K(+)-ATPase alpha-subunit and somatostatin to the inhibition of H+/K(+)-ATPase enzyme activity and gastric pH elevation by oral omeprazole administration. Omeprazole inhibits the alpha-subunit of H+/K(+)-ATPase covalently and stabilizes stimulated morphology of the parietal cell. After a single administration of omeprazole (100 mg/kg), H+/K(+)-ATPase alpha-subunit mRNA levels increased significantly by 57% at 3 h and remained elevated for 6 h, returning to the basal level by 24 h. After multiple administrations of omeprazole (100 mg/kg per day, every 24 h for 3 days), H+/K(+)-ATPase alpha-subunit mRNA levels were already elevated at the time of the last dose, reached maximum at 6 h (95% increase above control), and returned to the pre-treatment level after 36 h. Nuclear run-on assay indicated H+/K(+)-ATPase gene transcription was significantly increased by omeprazole pretreatment in vivo. In contrast, a significant decrease in fundic somatostatin mRNA occurred at 12 h after a single dose, and the inhibition was more pronounced and lasted longer after multiple doses of omeprazole. These data indicate that omeprazole, while effectively inhibiting H+/K(+)-ATPase activity, induces H+/K(+)-ATPase gene expression in the parietal cells. An inverse relationship exists between the regulation of somatostatin gene expression in fundic D-cells and H+/K(+)-ATPase gene expression. The increase in H+/K(+)-ATPase alpha-subunit mRNA could be due to alterations in extracellular gastrin/somatostatin ratios or could be induced by intracellular effects of omeprazole.


Bias Formulas for Estimating Direct and Indirect Effects When Unmeasured Confounding Is Present.
Mediation analysis examines the influence of intermediate factors in the causal pathway between an exposure and an outcome. It yields estimates of the direct effect of the exposure on the outcome and of the indirect effect through the intermediate variable. Both estimates can be biased if the relationship between the mediator and the outcome is confounded. In this article, we study the effect of unmeasured confounding on direct and indirect effect estimates for a continuous mediator and an outcome that may be either binary, count, or continuous. We formulate the effect of the confounder on the intermediate and on the outcome directly in regression models, which makes the formulas intuitive to use by applied users. The formulas are derived under the assumption that the confounder follows a normal distribution. In simulations, the formulas for a linear response model performed well, also as it did when the unmeasured confounder was binary. For a rare binary outcome, the formulas for logistic regression performed well if the unmeasured confounder followed a normal distribution, but for a binary confounder the bias in the direct effect was overcorrected. We applied the formulas to data from a case-control study (Leiden Thrombophilia Study) on risk factors for venous thrombosis. This showed that unmeasured confounding can severely bias the estimates of direct and indirect effects.


Comparison of two beclomethasone dipropionate inhalation aerosol spacer combinations in the treatment of asthma.
Fifty-five asthmatics, previously treated with inhaled steroids (mean age 48 years, range 16-68 years, mean duration of the disease 10 years, range 1-35 years) participated in this multicentric 2-phase trial. The patients were in good clinical condition (basal FEV1 3.02 litres (1.38-6.29), 90% (48-131%) of predicted values; mean (range)). In the first phase (randomized, double-blind crossover study) 2 beclomethasone dipropionate (BDP) inhalation aerosol preparations (MDI) were administered through collapsible spacer. In the second phase (open, randomized, parallel group comparison), 1 of the preparations was administered via collapsible and the other via traditional large volume spacer. The total daily dose of inhaled beclomethasone was 1,000 micrograms. The evaluation of efficacy was based on peak flow monitoring (PEFR) carried out at home twice daily and on FEV1 measured in spirometry at control visits after the run-in period and after each 4-weeks treatment period. Side-effects and asthma symptoms were recorded on patient diaries. The patients were asked to evaluate the treatment efficacy and the use and handling of the MDI-spacer combinations with Visual Analog Scale (VAS) at the end of each treatment period. No statistically significant differences were found in PEFR or FEV1 between the treatments during whole study. The asthma symptom scores were low as well as the use of concomitant inhaled sympathomimetics which indicates good and equal efficacy of the preparations. The MDI-spacer combinations were equally well tolerated. According to the VAS scores, the collapsible spacer was easier to use and statistically significantly easier to handle than traditional large volume spacer.


3D image-based adapted high-dose-rate brachytherapy in cervical cancer with and without interstitial needles: measurement of applicator shift between imaging and dose delivery.
Using 3D image-guided adaptive brachytherapy for cervical cancer treatment, it often means that patients are transported and moved during the treatment procedure. The purpose of this study was to determine the intra-fractional longitudinal applicator shift in relation to the high risk clinical target volume (HR-CTV) by comparing geometries at imaging and dose delivery for patients with and without needles. Measurements were performed in 33 patients (71 fractions), where 25 fractions were without and 46 were with interstitial needles. Gold markers were placed in the lower part of the cervix as a surrogate for HR-CTV, enabling distance measurements between HR-CTV and the ring applicator. Shifts of the applicator relative to the markers were determined using planning computed tomography (CT) images used for planning, and the radiographs obtained at dose delivery. Differences in the physical D90 for HR-CTV due to applicator shifts were simulated individually in the treatment planning system to provide the relative dose variation. The maximum distances of the applicator shifts, in relation to the markers, were 3.6 mm (caudal), and -2.5 mm (cranial). There was a significant displacement of -0.7 mm (SD = 0.9 mm) without needles, while with needles there was no significant shift. The relative dose variation showed a significant increase in D90 HR-CTV of 1.6% (SD = 2.6%) when not using needles, and no significant dose variation was found when using needles. The results from this study showed that there was a small longitudinal displacement of the ring applicator and a significant difference in displacement between using interstitial needles or not.


Entomobrya (Collembola, Entomobryidae) for the Canary Islands.
This paper examines a single genus of springtails (Collembola, Entomobryidae, Entomobrya) across the Canary Islands archipelago. A great sampling effort carried out more than 20 years ago, and over several years, allows us to present the distribution of the genus with the presence of 17 species, some better represented by their abundance than others. In addition to some species present in continental Europe or elsewhere in the world, or those already reported for the Canary Islands (e.g., E. multifasciata (Tullberg, 1871), E. nigrocincta Denis, 1923, E. palmensis Jordana Baquero, 2010, E. quinquelineata Börner, 1901 and E. unostrigata Stach, 1930), 12 new species have been detected and described, representing 71% of the total species found. All new species have been named in honour of important persons to the history of the Canary Islands, including some leaders. A combination of colouring patterns and other morphological characteristics that are easy to observe in most specimens (Katz et al. 2015a, b) have been used for the identification of the specimens, as is usual for the genus (Christiansen 1958), in addition to the dorsal macrochaetotaxy formula proposed by Jordana Baquero (2005). Without this formula, many specimens could not have been identified or distinguished from already described species because the colourations -in many cases-show ranges so broad as not to be diagnostic. In some species, the range of colouration can range from totally clear to totally dark, including several intermediate forms. Colour could be a good indicator of the species captured, taking into account that it fades over time with exposure to ethyl alcohol and could turn to different tones. Notwithstanding the above, a recent paper by Ding et al. (2018), show a certain correlation between the color pattern and the specific differentiation by means of DNA studies.


Molecular Genotyping of Chlamydia trachomatis in Iraqi Married Pregnant and Non-Pregnant Women.
It has been approved that the infection caused by Chlamydia trachomatis (C. trachomatis) is one of the major causes of infertility and adverse birth outcomes in populations. The C. trachomatis epidemiology among childbearing-age women in Iraq has not been recognized yet. This study aimed to detect the prevalence of C. trachomatis infection among pregnant and non-pregnant women using the polymerase chain reaction (PCR) assay and phylogenetic analysis of local isolates. In total, 200 endocervical swabs were collected from adult married pregnant (n=100) and non-pregnant women (n=100) from June to July 2021. Targeting the omp1 gene, 9% of the total samples were positive for C. trachomatis, and significant increases were reported among non-pregnant compared to pregnant women. The PCR products of five positive local isolates were selected randomly, sequenced, and documented in the National Centre for Biotechnology Information (NCBI) with the accession numbers OK094104.1, OK094105.1, OK094106.1, OK094107.1, and OK094108.1. Analysis of the homology sequence of the local and NCBI-BLAST isolates revealed a significant association with the Russian (MF288585.1) isolate. Statistical analysis of reproductive data revealed a higher prevalence, odds ratio (OD), and risk in asymptomatic, compared to symptomatic cases. Although no significant variation was detected in prevalence rate among single and multiple symptomatic women, increases were observed in OD values and risk of multiple symptomatic women. Reportedly, chronic pelvic pain was more prevalent than pelvic inflammatory diseases, ectopic pregnancy, and infertility in single symptomatic women. Regarding the demographic characteristics (i.e., age, the place of residence, and occupation), prevalence and risk of infection were higher in women who were <30 years, lived in urban areas, and had a job, compared to women who were ≥30 years, lived in suburban and rural areas, and had a free job. In conclusion, the course of chlamydial infections is usually unpredictable, diverse, and asymptomatic and has remained almost unrecognized. Therefore, PCR-based methods can apply successfully to detect C. trachomatis in both pregnant and non-pregnant women.


Living with hematologic cancer: Recommendations, solutions.
Patients with hematologic cancers such as leukemia, lymphoma, and multiple myeloma are living longer than ever. The survival rate of patients with most hematologic cancers has doubled since 1974, and these once-terminal diagnoses are now chronic health conditions. This article reviews the care of patients with hematologic cancers, including those previously treated for childhood, adolescent, and young-adult cancers, discusses the role of primary care in a multidisciplinary team approach, and reviews innovative ways to deliver needed care.


Influenza A infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor.
A 68-year-old Japanese woman infected with influenza A developed thrombotic thrombocytopenic purpura (TTP) 2 days after having a fever. Routine laboratory tests on admission suggested a diagnosis of disseminated intravascular coagulation. However, ADAMTS13 assays showed an extremely low level of plasma ADAMTS13 activity with a high titer of anti-ADAMTS13 inhibitor (IgG). Despite high-dose methylprednisolone therapy with daily plasma exchange for 3 consecutive days, the patient died of pulmonary congestion complicated by cardiac failure. Our experience here provides the first evidence that influenza A infection is sufficient to trigger TTP by producing the anti-ADAMTS13 IgG inhibitor.


The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control of virulence factor expression from the novel eno ralp3 epf sagA pathogenicity region.
Many Streptococcus pyogenes (group A streptococcus [GAS]) virulence factor- and transcriptional regulator-encoding genes cluster together in discrete genomic regions. Nra is a central regulator of the FCT region. Previous studies exclusively described Nra as a transcriptional repressor of adhesin and toxin genes. Here transcriptome and proteome analysis of a serotype M49 GAS strain and an isogenic Nra mutant of this strain revealed the complete Nra regulon profile. Nra is active in all growth phases tested, with the largest regulon in the transition phase. Almost exclusively, virulence factor-encoding genes are repressed by Nra; these genes include the GAS pilus operon, the capsule synthesis operon, the cytolysin-mediated translocation system genes, all Mga region core virulence genes, and genes encoding other regulators, like the Ihk/Irr system, Rgg, and two additional RofA-like protein family regulators. Surprisingly, our experiments revealed that Nra additionally acts as a positive regulator, mostly for genes encoding proteins and enzymes with metabolic functions. Epidemiological investigations revealed strong genetic linkage of one particular Nra-repressed regulator, Ralp3 (SPy0735), with a gene encoding Epf (extracellular protein factor from Streptococcus suis). In a serotype-specific fashion, this ralp3 epf gene block is integrated, most likely via transposition, into the eno sagA virulence gene block, which is present in all GAS serotypes. In GAS serotypes M1, M4, M12, M28, and M49 this novel discrete genetic region is therefore designated the eno ralp3 epf sagA (ERES) pathogenicity region. Functional experiments showed that Epf is a novel GAS plasminogen-binding protein and revealed that Ralp3 activity counteracts Nra and MsmR regulatory activity. In addition to the Mga and FCT regions, the ERES region is the third discrete chromosomal pathogenicity region. All of these regions are transcriptionally linked, adding another level of complexity to the known GAS growth phase-dependent regulatory network.


Epoetin alpha in elective coronary and valve surgery in Jehovah's Witnesses patients. Experience in 45 patients.
The religious beliefs of Jehovah's Witnesses who refuse homologous and autologous blood transfusion poses serious problems for surgeons when operating on patients requiring a mean transfusion requirement of =/>2 units of blood. After a number of encouraging studies in a randomised sample of patients 2-3 and after the treatment of some Jehovah's Witnesses 1, a group of 45 patients (23 females and 22 males) underwent elective heart surgery between June 1998 and December 2000. The patients, who were all Jehovah's Witnesses, received pre-treatment with epoetin alpha and ferrous sulphate. In the light of recent studies, it was also decided to repeat medullary preconditioning using the same intervals but with a higher dose. The patients underwent surgery involving myocardial revascularisation, mitral and/or aortic valve replacement, associated interventions, valvuloplasty and ascending aortic aneurysms. After obtaining informed and signed consent, the treatment protocol comprised the administration of 140 IU/kg epoetin alpha three times a week for 3 weeks associated with oral ferrous sulphate 3 times a day. Hematochemical levels (hemoglobin, free hemoglobin, hematocrit, ferritin, transferrin, haptoglobin, reticulocytes, iron levels) were monitored from admission to Day Hospital to discharge. No patient in the study required blood transfusion. The short, medium and long-term follow-up reconfirmed the substantial reliability of this drug linked to the absence of collateral effects.


[Validation of a health survey questionnaire focusing on risk factors for coronary artery disease in a group of public employees in Juiz de Fora, Minas Gerais State, Brazil].
The validity of a health survey questionnaire used in a family health promotion program to identify individuals at risk of developing coronary artery disease (CAD) was studied in a random sample of 297 State public employees in Juiz de Fora, Minas Gerais State, Brazil. The sample was stratified by sex, and subjects were 40 years of age or older. Results obtained in interviews were compared to laboratory and clinical data. We assessed the questionnaire's sensitivity, specificity, and positive and negative predictive values in relation to questions about current or previous history of diabetes, hypertension, smoking, and high cholesterol. Among individuals with at least one altered clinical or laboratory test, 81% (total sensitivity) were identified by the referred risk inquiry when reporting at least one risk factor. Sheffield and New Zealand tables were used to determine the individuals with increased risk of developing CAD and to assess if they would also be identified by the health survey questionnaire. The sensitivity for identifying this subgroup was 100%.


Genetic parameters for yield traits of cows treated or not treated with bovine somatotropin.
The objective of this study was to estimate genetic correlations between yield traits of cows treated with bovine somatotropin (bST) and the same yield traits of untreated cows. Lactation records from registered Holstein cows were divided by parity into 3 data sets: 1, 2, and 3 through 5. Approximately 10% of the records in each data set were from cows treated with bST. The numbers of records of treated and untreated cows in the data sets were 4,337 and 48,765; 3,730 and 37,796; and 3,645 and 33,957. Two-trait animal models (records for cows treated or not treated) were used to estimate genetic parameters for milk production traits and somatic cell score (SCS). Estimates of heritability for milk yield for records of treated and untreated cows for the 3 data sets were 0.13, 0.16, and 0.09, and 0.18, 0.18, and 0.14, respectively, with estimates of repeatability of 0.50 and 0.41 for data set 3. Estimates of heritability for fat yield for records of treated and untreated cows were 0.31, 0.16, and 0.12, and 0.27, 0.21, and 0.16. Estimates of repeatability were 0.50 and 0.43 for data set 3. Heritability estimates for protein yield for records of treated and untreated cows were 0.13, 0.17, and 0.12, and 0.20, 0.23, and 0.16, with estimates of repeatability of 0.52 and 0.47. Estimates of heritability for SCS for treated and untreated cows were 0.08, 0.15, and 0.13, and 0.11, 0.13, and 0.13 with repeatability estimates of 0.52 and 0.45. Estimates of genetic correlations between milk yields with and without bST treatment in lactations 1, 2, and 3 to 5 were all 0.99. Estimates of genetic correlations for fat and protein yields were 0.96 for all data sets. Estimates for SCS were 0.99. Estimates of genetic correlations between records of treated and untreated cows were large enough to conclude that records of treated and untreated cows could be considered to be one trait, with treatment as a fixed effect to account for differences in means.


Impact of Micellar Vehicles on in situ Intestinal Absorption Properties of Beta-Lapachone in Rats.
The aim of the present study was to examine the effect of micellar systems on the absorption of beta-lapachone (b-lap) through different intestinal segments using a single-pass rat intestinal perfusion technique. B-lap was solubilized in mixed micelles composed of phosphatidylcholine and sodium deoxycholate, and in sodium lauryl sulfate (SLS)-based conventional micelles. Both mixed micelles and SLS micelles improved the in situ permeability of b-lap in all intestinal segments tested although the mixed micellar formulation was more effective in increasing the intestinal absorption of b-lap. The permeability of b-lap was greatest in the large intestinal segments. Compared with SLS micelles, the effective permeability coefficient values measured with mixed micelles were 5- to 23-fold higher depending on the intestinal segment. Our data suggest that b-lap should be delivered to the large intestine using a mixed micellar system for improved absorption.


Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities.
Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic activity is a central player in chronic inflammatory diseases including cancers. Therefore, blockade of the IL-6 signalling pathway has become a target for the therapy of diverse cancers such as multicentric Castleman's disease (CD), multiple myeloma and solid tumours including renal, prostate, lung, colorectal and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6 receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone or in combination with conventional chemotherapy. Human trials have demonstrated the ability to block IL-6 activity and in multicentric CD lead to durable clinical response and longer disease stabilisation. However, the efficacy of these treatments is still debatable for other cancers. New generation therapeutics in development such as Clazakizumab, Sarilumab, and soluble gp130-Fc have the additional features of improved binding affinity, better specificity with reduced adverse effects. A deeper understanding of the immunological basis of these agents, as well as of the challenges that are faced by immunotherapy-based products in clinical trials, will help select the most promising anti-IL-6/IL-6R therapies for large scale use. Concurrently, current research efforts to personalize treatments may help in the treatment of patients that would greatly benefit from IL-6 blocking therapies.


Characterization of plasma and cerebrospinal fluid human angiotensinogen and des-angiotensin I-angiotensinogen by direct radioimmunoassay.
Angiotensinogen and the product of its hydrolysis by renin, des-angiotensin I-angiotensinogen, were quantitated in human plasma and in cerebrospinal fluid (CSF) by a direct RIA. This assay was developed using polyclonal antibodies raised against pure human angiotensinogen. The antibodies recognized only primate angiotensinogen and des-angiotensin I-angiotensinogen. Results obtained with the direct RIA were compared with those of the indirect assay which measures angiotensinogen through angiotensin I liberated by an excess of renin. Both assays gave almost identical results in normal subjects whereas in three different conditions characterized by a high renin level (severe hypertension plus low sodium diet, converting enzyme inhibition, and adrenal insufficiency) higher results were obtained by the direct assay. This difference between the results of both methods was attributed to des-angiotensin I-angiotensinogen accumulation which is detected only in the direct assay. CSF angiotensinogen had similar immunochemical properties to plasma angiotensinogen and could also be measured by the direct RIA. Isoelectric focusing of plasma angiotensinogen and des-angiotensin I-angiotensinogen revealed a similar microheterogeneity. Microheterogeneity was also a characteristic of CSF angiotensinogen, but its isoelectric point was more basic than plasma angiotensinogen.


The differentiation-inducing effect of Nordy on HPV-16 subgenes-immortalized human endocervical cells H8.
The lipoxygenase inhibitor nordihydroguaiaretic acid, a natural product purified from Larrea divaricata and Guaiacum officinale, showed a marked capacity to induce differentiation of various human malignant tumor cell lines. Nordy, a derivative of nordihydroguaiaretic acid, has been shown to effectively inhibit the growth of malignant human tumors transplanted in mice. However, it is unknown whether Nordy plays an important role in inducing the differentiation effects of human papillomavirus (HPV)-16 subgenes-immortalized human endocervical cells H8. In this study, we showed that Nordy arrested H8 cells in the G0/G1 phase, promoted cell differentiation in morphology, downregulated the expression of HPV-16 E6 mRNA and nuclear antigen Ki67, and inhibited telomerase activity on HPV-16 subgenes-immortalized human endocervical cells H8. Taken together, Nordy could suppress proliferation by inhibiting proliferation-related events and promote cell differentiation in H8 cell. The results suggested that Nordy might be a potential tumor therapeutic agent.


Trends in the risks of melanoma as a second primary cancer among cancer patients in the Netherlands, 1989-2008.
The aim of this study is to assess time trends of the risk of melanoma as a second primary cancer (MSPC) among cancer patients in the Netherlands during 1989-2008. Data from the population-based Netherlands Cancer Registry (NCR) were used for an analysis of time trends in the risk of MSPC in a fixed inception cohorts design (1989-1990, 1996-1997, and 2003), with similar lengths of follow-up. Standardized incidence ratios and absolute excess risks (AERs) were calculated to estimate the relative risks and excess absolute risks of MSPC. Differential time trends of risk in MSPC were observed, that is, decreasing for standardized incidence ratios and increasing for AERs in both sexes, but not reaching significance. Over time, AER changed from 24 to 72 per 10 000 person years (P for trend=0.01) in male patients with a previous melanoma during 2-5 years of follow-up, whereas among women with a first squamous cell carcinoma of skin, AER increased markedly (P for trend=0.3) over time during the first year of follow-up, coinciding with a decrease during the 2-5 years of the follow-up period (P for trend=0.1). MSPCs diagnosed later during follow-up were thicker than those diagnosed earlier, this difference being only statistically significant among male patients with a previous melanoma. The observed favorable risk trend among female patients coincided with thicker MSPCs than male patients. Differential risk trends were observed for MSPC among cancer patients during the past two decades in the Netherlands that did not seem to be affected by greater awareness of the disease. As the stage distribution of MSPCs worsened during follow-up, efforts should be made towards an earlier diagnosis of MSPC.


Interleukin-12-producing CD103+ CD11b- CD8+ dendritic cells are responsible for eliciting gut intraepithelial lymphocyte response against Encephalitozoon cuniculi.
Microsporidia, which belong to the kingdom Fungi, are important opportunistic pathogens in HIV-infected populations and organ transplant recipients that are often associated with a broad range of symptoms, such as diarrhea, nephritis, and encephalitis. Natural infection occurs via the oral route, and as a consequence, gut immunity plays an important role in restricting the dissemination of these pathogens. Studies from our laboratory have reported that the pathogens induce a rapid intraepithelial lymphocyte (IEL) response important for host protection. Although mucosal dendritic cells (DC) are likely involved in triggering an antigen-specific IEL response, the specific subset(s) responsible has yet to be identified. Toward this goal, we demonstrate a very important role for mucosal CD11b(-) CD8(+) DC in the initiation of an antigen-specific IEL in vivo. Effectively, after Encephalitozoon cuniculi infection, CD11b(-) CD8(+) DC were activated in the lamina propria (LP) and acquired the ability to process retinoic acid (RA). However, this subset did not produce interleukin 12 (IL-12) but upregulated CD103, which is essential for migration to the mesenteric lymph nodes (MLN). Interestingly, CD103(+) CD11b(-) CD8(+) DC in the MLN, in addition to processing RA, also secreted IL-12 and were responsible for gut imprinting specificity on mucosal CD8 T cells. To the best of our knowledge, this is the first report describing the importance of MLN CD103(+) CD11b(-) CD8(+) DC isolated from infected animals in the generation of an IEL response against a live pathogen.


Information infrastructure for inter-organizational mental health services: an actor network theory analysis of psychiatric rehabilitation.
In the supply of mental health services to communities, data and information are managed not only by clinical organizations, but also by welfare state agencies and charities. The aim of this study is to use methods of analysis from actor network theory to identify organizational interventions necessary for the development of an information infrastructure for inter-organizational mental health services. Data was collected in a project aimed at developing an information system that supports inter-organizational psychiatric rehabilitation in a Swedish municipality. Three organizational interventions were identified: an integrated service policy defined by the national government, a common legal framework allowing sharing of high-level client data, and commissioned support for local inter-agency workspaces. It is concluded that organizational interventions must be regarded when configuring an information infrastructure for mental health services. Organizational interventions should also routinely be addressed in systems design methods to be used in inter-organizational settings.


Immediate effect of static and proprioceptive neuromuscular facilitation stretching on hip adductor flexibility in female ballet dancers.
The aim of the present study was to investigate the immediate effects of static and proprioceptive neuromuscular facilitation (PNF) stretching on the flexibility of hip adductors in female ballet dancers. Forty-five subjects (age: 28.5 ± 8.0 years; minimum two years of ballet training) were randomly assigned to three groups: PNF (contract-release technique), Static, and Control. Subjects in the PNF and Static groups performed four sets of 30 second stretching with an interval of 30 seconds between sets. The control group stayed at rest for the same time spent by the PNF and Static groups during the stretching sessions. Maximal range of motion was measured before and immediately after the experimental and control protocols in all groups. The results indicated significant differences between pre- and post-stretching flexibility in both PNF and Static groups (p < 0.0001; effect size = 0.24 and 0.39, respectively), whereas no change was identified in the Control group (p = 0.265). However, no differences in post-exercise flexibility were found between PNF and Static groups (p = 0.235). It is concluded that static and PNF stretching methods provoked similar post-exercise acute effects on the maximal range of motion of hip adductors in highly flexible female ballet dancers.


Oriented Nanofibrous Polymer Scaffolds Containing Protein-Loaded Porous Silicon Generated by Spray Nebulization.
Oriented composite nanofibers consisting of porous silicon nanoparticles (pSiNPs) embedded in a polycaprolactone or poly(lactide-co-glycolide) matrix are prepared by spray nebulization from chloroform solutions using an airbrush. The nanofibers can be oriented by an appropriate positioning of the airbrush nozzle, and they can direct growth of neurites from rat dorsal root ganglion neurons. When loaded with the model protein lysozyme, the pSiNPs allow the generation of nanofiber scaffolds that carry and deliver the protein under physiologic conditions (phosphate-buffered saline (PBS), at 37 °C) for up to 60 d, retaining 75% of the enzymatic activity over this time period. The mass loading of protein in the pSiNPs is 36%, and in the resulting polymer/pSiNP scaffolds it is 3.6%. The use of pSiNPs that display intrinsic photoluminescence (from the quantum-confined Si nanostructure) allows the polymer/pSiNP composites to be definitively identified and tracked by time-gated photoluminescence imaging. The remarkable ability of the pSiNPs to protect the protein payload from denaturation, both during processing and for the duration of the long-term aqueous release study, establishes a model for the generation of biodegradable nanofiber scaffolds that can load and deliver sensitive biologics.


Myopericarditis in a Male Adolescent Following the Second Shot of COVID-19 Pfizer m-RNA Vaccine: Typical Example and Analysis of 110 Single Case Reports.
One of the most powerful weapons against COVID-19 is vaccines. After the worldwide spread of the disease, m-RNA vaccines were authorized not only in adult patients, but also in children and adolescents aged 12-18. Since then, alarming reports of cases of myocarditis and/or pericarditis have been noted, primarily involving males after the second vaccine shot. A typical example of myopericarditis occurring in an adolescent a few days after the second shot of an m-RNA vaccine is described here. An in-depth review of all 110 single case reports published up to July 2022 with related features and outcomes is also presented. This is the first extensive analysis focused solely on a significant number of single case reports, which have usually been excluded from systematic reviews and meta-analyses carried out in the field. The analysis presented here confirms that most cases occurred in males after the second injection of an m-RNA vaccine. Cases were mild and responsive to the usual medical treatment. What is newly reported is that not only adolescents, but also older people, especially females, were affected by this adverse event.


Children's exposure to outdoor food advertising near primary and secondary schools in Australia.
Previous research has highlighted children's frequent exposure to advertisements of unhealthy food and beverages on television. However, the food industry is increasingly utilising non-broadcast channels such as outdoor advertising (eg billboards, bus shelters, shop fronts) for product marketing. Few studies have investigated children's exposure to outdoor food advertising around primary and secondary schools. This study aimed to quantify the presence and content of outdoor food advertisements within a 500 m radius of primary and secondary schools in Perth, Western Australia. A cross-sectional design was used to capture outdoor advertisements within a 500 m radial buffer around the school boundary. The INFORMAS protocol for monitoring outdoor advertising around child-serving institutions was used. Sixty-four primary and secondary schools in Perth, Australia, were selected using random sampling within socio-economic and population density strata. In total, 5636 outdoor advertisements were identified within a 500 m radius of all 64 schools combined and 30% were for food. Of the 1708 food advertisements, 74% were for unhealthy (non-core) food. The most frequently advertised food products were alcohol, fast food and sugar-sweetened beverages. Only 8% of food advertisements featured a healthy product. The majority of schools (75%) had at least one food advertisement within 500 m (mean 36, range 3-190). Schools in lower socio-economic areas had more food advertisements and a significantly higher proportion of unhealthy food advertisements within 250 m. Outdoor advertising around schools constitutes a potential frequent source of children's exposure to unhealthy food and alcohol advertising. SO WHAT?: Policy interventions restricting the content of outdoor food advertising near schools are needed.


Host-guest interactions derived multilayer perylene diimide thin film constructed on a scaffolding porphyrin monolayer.
The development of methods to grow well-ordered chromophore thin films on solid substrates is of importance because such surface-associated arrays have potential applications in the generation of functional electronic and optical materials and devices. In this article, we demonstrate a straightforward layer-by-layer (LBL) supramolecular deposition strategy to prepare numerous layers (up to 19) of functionalized perylene diimide (PDI) chromophores built upon a covalent scaffolding multivalent porphyrin monolayer. Our thin film formation strategy employs water as the immersion solvent and exploits the β-cyclodextrin-adamantane host-guest couple in addition to PDI based aromatic stacking. Within the resultant film the porphyrin scaffold is oriented close to parallel to the glass substrate while the PDI chromophores are aligned closer to the surface normal. Together, the porphyrin monolayer and the multi-PDI layers exhibit a large absorption bandwidth in the visible spectrum. Importantly, because a self-assembly strategy was utilized, when a single monolayer of PDI is deposited on the porphyrin scaffolding layer, this PDI monolayer can be readily disassembled by washing with DMF leading to the regeneration of the porphyrin monolayer. The PDI thin film can subsequently be regrown from the regenerated porphyrin surface. The reported LBL strategy will be of broad interest for researchers developing well-organized chromophoric films and materials due to its simplicity as well as the added advantage of being performed in sustainable and cost-effective aqueous media.


Intrathoracic meningocele in association with neurofibromatosis: report of a case.
A case of intrathoracic meningocele associated with neurofibromatosis is reported. Computed tomography (CT) demonstrated that the paravertebral mass had a characteristic low attenuation coefficient compatible with liquid content. CT-myelography further confirmed the diagnosis. We recommend that though intrathoracic meningocele is rare, it should be kept in mind when making a differential diagnosis in cases where the patient has neurofibromatosis with a posterior mediastinal mass.


Preliminary results from using the Panjabi adaptation of the Aphasia Screening Test.
The Panjabi adaptation of the Aphasia Screening Test (AST) has been used with a small group of stroke patients and the preliminary results are reported. All the patients are described and their test results plotted. Observations are made about the test procedure, with recommendations for its further use.


Pediatric TSH Reference Intervals and Prevalence of High Thyroid Antibodies in the Lebanese Population.
The aims of this study are to establish reference values for TSH in Lebanese schoolchildren; to look at the relationship between TSH and age, gender, BMI, socioeconomic status (SES), and thyroid antibodies (TAb); and to investigate the prevalence of abnormal TAb in this population. 974 Lebanese schoolchildren aged 8-18 years were recruited from 10 schools of different SES. Third-generation TSH, TPO-Ab, and Tg-Ab measurements were performed using the IMMULITE chemiluminescent immunoassay. The mean TSH is 2.06 ± 1.05 μUI/ml. TSH values are inversely correlated with age (p < 0.0001), are higher in boys than in girls (resp., 2.14 ± 1.10 and 1.98 ± 0.99 μUI/ml, p = 0.017), and are positively correlated with BMI (p < 0.0001). They are also significantly higher in subjects from low-SES schools (p = 0.03) and in girls with positive TAb (p = 0.026). In boys, TSH is independently associated with age, BMI, and schools' SES (p = 0.01, p = 0.03, and p = 0.026, resp.) while in girls, the association is only significant for age and TAb (p = 0.0001 and p = 0.015, resp.). The prevalence of TAb is 4.3% (3% for TPO-Ab and 2.1% for Tg-Ab). Our results showed higher TSH values in the pediatric Lebanese population compared to western populations. TSH varies according to age, gender, BMI, and SES and is associated in girls with TAb.


Synchronization of mammalian cells and nuclei by centrifugal elutriation.
Synchronized populations of large numbers of cells can be obtained by centrifugal elutriation on the basis of sedimentation properties of small round particles, with minimal perturbation of cellular functions. The physical characteristics of cell size and sedimentation velocity are operative in the technique of centrifugal elutriation also known as counterstreaming centrifugation. The elutriator is an advanced device for increasing the sedimentation rate to yield enhanced resolution of cell separation. A random population of cells is introduced into the elutriation chamber of an elutriator rotor running in a specially designed centrifuge. By increasing step by step the flow rate of the elutriation fluid, successive populations of relatively homogeneous cell size can be removed from the elutriation chamber and used as synchronized subpopulations. For cell synchronization by centrifugal elutriation early log S phase cell populations are most suitable where most of the cells are in G1 and S phase (>80%). Protocols for the synchronization of nuclei of murine pre-B cells and high-resolution centrifugal elutriation of CHO cells are given. The verification of purity and cell cycle positions of cells in elutriated fractions includes the measurement of DNA synthesis by [(3)H]-thymidine incorporation and DNA content by propidium iodide flow cytometry.


Spatial distribution of FIR rotationally excited CH+ and OH emission lines in the Orion Bar PDR.
The methylidyne cation (CH+) and hydroxyl (OH) are key molecules in the warm interstellar chemistry, but their formation and excitation mechanisms are not well understood. Their abundance and excitation are predicted to be enhanced by the presence of vibrationally excited H2 or hot gas (~500-1000 K) in photodissociation regions with high incident FUV radiation field. The excitation may also originate in dense gas (> 105 cm-3) followed by nonreactive collisions with H2, H, and electrons. Previous observations of the Orion Bar suggest that the rotationally excited CH+ and OH correlate with the excited CO, a tracer of dense and warm gas, and formation pumping contributes to CH+ excitation. Our goal is to examine the spatial distribution of the rotationally excited CH+ and OH emission lines in the Orion Bar in order to establish their physical origin and main formation and excitation mechanisms. We present spatially sampled maps of the CH+ J=3-2 transition at 119.8 µm and the OH Λ-doublet at 84 µm in the Orion Bar over an area of 110″×110″ with Herschel (PACS). We compare the spatial distribution of these molecules with those of their chemical precursors, C+, O and H2, and tracers of warm and dense gas (high-J CO). We assess the spatial variation of CH+ J=2-1 velocity-resolved line profile at 1669 GHz with Herschel HIFI spectrometer observations. The OH and especially CH+ lines correlate well with the high-J CO emission and delineate the warm and dense molecular region at the edge of the Bar. While notably similar, the differences in the CH+ and OH morphologies indicate that CH+ formation and excitation are strongly related to the observed vibrationally excited H2. This, together with the observed broad CH+ line widths, indicates that formation pumping contributes to the excitation of this reactive molecular ion. Interestingly, the peak of the rotationally excited OH 84 µm emission coincides with a bright young object, proplyd 244-440, which shows that OH can be an excellent tracer of UV-irradiated dense gas. The spatial distribution of CH+ and OH revealed in our maps is consistent with previous modeling studies. Both formation pumping and nonreactive collisions in a UV-irradiated dense gas are important CH+ J=3-2 excitation processes. The excitation of the OH Λ-doublet at 84 µm is mainly sensitive to the temperature and density.


Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic.
The COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact. A Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention. Analysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0-21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p < 0.001) and inability to obtain therapies (p < 0.001) and surgeries (p < 0.001). Guardian responses from CARD had increased reports of worsening behavior (p = 0.01). Providers increased availability of in-person and virtual therapies and visits and made referrals for additional care to address this. In a survey of medical providers, five out of six program directors who received the responses to this survey found this questionnaire helpful in caring for their patients. This quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result.


Congenital urethrocutaneous fistula: Case report with review of literature.
We are presenting two cases of congenital urethrocutaneous fistula on ventral penile shaft. Congenital urethral fistula is an extremely rare, but easily manageable anomaly that may be confused with hypospadias. Awareness of the entity will avoid complications. This condition may be associated with other anomalies like congenital hernias and anorectal malformations. Treatment of this entity is individualized according to site of fistula, associated anomalies and condition of the distal urethra. All the principles of hypospadias surgery should be strictly followed.


Correction: Escape of anions from geminate recombination in THF due to charge delocalization.
Correction for 'Escape of anions from geminate recombination in THF due to charge delocalization' by Hung-Cheng Chen et al., Phys. Chem. Chem. Phys., 2017, 19, 32272-32285.


Expiratory flow limitation in large and small airways.
Obstructive airways diseases constitute 75% of all chronic respiratory diseases. This article briefly reviews the physlologic basis for flow limitation in large and small airways. Application of the physiologic principles described can lead to a better understanding of the normal mechanics of breathing and the various alterations resulting from diseases that limit airflow.


[Safety and immunogenicity of a new inactivated hepatitis A vaccine].
To evaluate the safety and immunogenicity of a new inactivated hepatitis A virus (HAV) vaccine. In a randomized controlled trail thirty-one HAV-seronegative adults were enrolled and randomly assigned to either study group or control group. Subjects in the study group were given 1000 units of the new inactivated HAV vaccine, with a booster at 3 months. Subjects in the control group were given 720 ELISA units Havrix, produced by SmithKline Beecham Biologicals, with a subsequent dose at 3 months. Local and systematic reactions and serum response to the vaccines were compared between the two groups. Mild local reactions were noted in one subject from the study group and two from the control group after primary vaccination. Mild systematic reactions were reported in two subjects from each group after primary vaccination and in one subject from the study group after booster vaccination. Seroconversion rates were 94%, 100%, and 100% in the study group at 1, 3, and 4 (1 month after booster) month, respectively. The corresponding figures were 73%, 80% and 100% in the control group. Geometric mean antibody titers were 139.2 mIU/ml, 137.7 mIU/ml, and 1 066.7 mIU/ml at 1, 3, and 4 months,respectively, in the study group,and 104.3 mIU/ml, 111.3 mIU/ml, and 760.7 mIU/ml in the control group. The new inactivated hepatitis A vaccine was safe and highly immunogenic.


Red blood cells bearing CD4 bind to gp120 covered plates and aggregate with cells expressing gp120.
Full-length recombinant CD4 (rCD4) was bound to human red blood cell membranes using a low-pH incubation procedure. The red blood cells bearing recombinant CD4 (RBC-rCD4+) specifically bound to gp 120-covered plates. The binding showed a threshold effect at low rCD4 concentrations per RBC. The binding of RBC-rCD4+ to gp120 plates was not inhibited by plasma proteins (incubation in human blood plasma). Preincubation of the RBC-rCD4+ with monoclonal anti-CD4 antibodies blocked the binding to the gp120-covered plates. Incubation of chinese hamster ovary (CHO) fibroblasts, which constitutively express the HIV envelope protein gp120 with RBC-rCD4+, resulted in the formation of large cell aggregates. These in vitro data suggest that RBC-rCD4+ retain affinity for gp120 and thus could have potential therapeutical value in AIDS treatment.


Polycation-induced cell membrane permeability does not enhance cellular uptake or expression efficiency of delivered DNA.
Polycationic materials commonly used to delivery DNA to cells are known to induce cell membrane porosity in a charge-density dependent manner. It has been suggested that these pores may provide a mode of entry of the polymer-DNA complexes (polyplexes) into cells. To examine the correlation between membrane permeability and biological activity, we used two-color flow cytometry on two mammalian cell lines to simultaneously measure gene expression of a plasmid DNA delivered with four common nonviral vectors and cellular uptake of normally excluded fluorescent dye molecules of two different sizes, 668 Da and 2 MDa. We also followed gene expression in cells sorted based on the retention of endogenous fluorescein. We have found that cell membrane porosity caused by polycationic vectors does not enhance internalization or gene expression. Based on this single-cell study, membrane permeability is found to be an unwanted side effect that limits transfection efficiency, possibly through leakage of the delivered nucleic acid through the pores prior to transcription and translation and/or activation of cell defense mechanisms that restrict transgene expression.


Electrophysiological correlates of semantic anticipation during speech comprehension.
Words that are more predictable given a previous context show facilitated processing over low predictable ones. Such facilitation has been traditionally viewed as associated with reduced amplitudes in the N400 component. However, this effect is observed during the presentation of the target word, and it does not provide direct information about the prediction processes engaged before. To overcome this, we investigated neural correlates of anticipation prior to target words using an auditory paradigm. The semantic context of the sentences varied in the degree of contextual constraint, with sentences of high, low or no constraint. The final word presented could be either congruent -the best completion- or incongruent. We inserted a noticeable 1000ms delay before the final word of a sentence. The ERP analysis of the delay period unveiled a slow potential, with an amplitude that was more negative as contextual constraint increased. We also observed a canonical N400 modulation to semantic fit and cloze probability, and we report, for the first time to our knowledge, a delay in the onset of the N400 effect for low levels of contextual constraint. This study provides novel electrophysiological data that contributes to the better comprehension of the processes involved in speech processing with evidence in favour of anticipatory models of language processing.


Therapeutic drug monitoring for biological medications in inflammatory bowel disease.
Therapeutic drug monitoring (TDM) is the measurement of serum drug concentrations and anti-drug-antibodies (ADA) for biologic therapies used to treat inflammatory bowel disease (IBD). The aim of this article is to review the current literature concerning reactive and proactive TDM for both adults and children with IBD. Although optimal trough concentration windows for some of these medications are not well defined, there is mounting evidence to suggest that reactive TDM is associated with favorable therapeutic outcomes, including less immunogenicity, greater drug exposure, and a decreased risk of treatment failure. Moreover, while the exact mechanism of loss of response is not fully elucidated, the vast majority of studies have reported a decreased incidence of nonresponse and secondary loss of response when TDM is implemented. Proactive TDM, while even less understood in the literature, employs a schedule of preemptive analysis of serum trough concentrations to accordingly adjust the patient's biologic dosage. Proactive TDM may decrease the need for IBD-related surgery/hospitalization, and therefore merits future studies of investigation.


Molecular Typing of Staphylococcus aureus Isolated from Patients with Autosomal Dominant Hyper IgE Syndrome.
Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3). This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with Candida and Staphylococcus aureus. It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci. However, these alterations have not been characterized at the species- and strain-level. Since S. aureus infections are influenced by strain-specific expression of virulence factors, information on colonizing strain characteristics may provide insights into host-pathogen interactions and help guide management strategies for treatment and prophylaxis. The aim of this study was to determine whether the immunodeficiency of AD-HIES selects for unique strains of colonizing S. aureus. Using multi-locus sequence typing (MLST), protein A (spa) typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the S. aureus isolates (n = 13) found on the skin of twenty-one patients with AD-HIES. We found a low diversity of sequence types, and an abundance of strains that expressed methicillin resistance, Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxins K and Q (SEK, SEQ). Our results indicate that patients with AD-HIES may often carry antibiotic-resistant strains that harbor key virulence factors.


Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection.
The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylusvulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6%) and prevalence (95.40%) were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be done concerning Th1/Th2 balance and cross-reactivity of S. vulgaris and Cyathostomins spp. at the base of serological and molecular investigation.


Synthesis of free and ligated 1,2-thiaphosphetanes - expanding the pool of strained P-ligands.
While P(v) 1,2-oxaphosphetanes were investigated in great detail over the past decades, the knowledge about P(v) 1,2-thiaphosphetanes is rather scarce, and P(iii) derivatives are unknown. Herein, we present the synthesis of the first P(iii) complex derivatives formed in the coordination sphere of group 6 metals and, additionally, the first unligated P(iii) 1,2-thiaphosphetanes. The latter display an unusually low HOMO-LUMO gap thus constituting excellent candidates for redox-cycling organocatalysts.


Subnormal levels of POLγA cause inefficient initiation of light-strand DNA synthesis and lead to mitochondrial DNA deletions and progressive external ophthalmoplegia [corrected].
The POLG1 gene encodes the catalytic subunit of mitochondrial DNA (mtDNA) polymerase γ (POLγ). We here describe a sibling pair with adult-onset progressive external ophthalmoplegia, cognitive impairment and mitochondrial myopathy characterized by DNA depletion and multiple mtDNA deletions. The phenotype is due to compound heterozygous POLG1 mutations, T914P and the intron mutation c.3104 + 3A > T. The mutant genes produce POLγ isoforms with heterozygous phenotypes that fail to synthesize longer DNA products in vitro. However, exon skipping in the c.3104 + 3A > T mutant is not complete, and the presence of low levels of wild-type POLγ explains patient survival. To better understand the underlying pathogenic mechanisms, we characterized the effects of POLγ depletion in vitro and found that leading-strand DNA synthesis is relatively undisturbed. In contrast, initiation of lagging-strand DNA synthesis is ineffective at lower POLγ concentrations that uncouples leading strand from lagging-strand DNA synthesis. In vivo, this effect leads to prolonged exposure of the heavy strand in its single-stranded conformation that in turn can cause the mtDNA deletions observed in our patients. Our findings, thus, suggest a molecular mechanism explaining how POLγ mutations can cause mtDNA deletions in vivo.


[Efficacy of lomustine, teniposide, doxorubicin, bleomycin and prednisone (LTABP) or adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) in the treatment of malignant lymphogranulomatosis resistant to MOPP].
LTABP regimen was applied to 18 patients in IIB and IV stage of malignant lymphogranulomatosis resistant to MOPP. The obtained results were compared with historical control group of 18 patients with similar stage of the disease treated according to ABVD regimen. In both regimens courses were repeated every 28 days or more rarely, when leucopenia and thrombocytopenia prolonged. Only patients who had received at least 3 courses were analysed. In the LTABP group the complete remission was obtained in 10 cases (55%) while partial remission in 6 (33%). In the group treated with ABVD complete remission was obtained in 4 cases (22%) and partial in 9 cases (50%). In the LTABP group 11 patients are still alive and remain in complete remission, while in ABVD group--4 patients. The most frequent side effects in both groups included leucopenia, thrombocytopenia and symptoms of gastrointestinal intolerance. The LTABP regiment allows to obtain higher percentage of the complete remission than ABVD.


Brain xanthophyll content and exploratory gene expression analysis: subspecies differences in rhesus macaque.
The dietary xanthophylls, lutein and zeaxanthin, accumulate in primate retina and brain, and emerging evidence indicates neural lutein content may be beneficial for cognition. Neural xanthophyll content in primates varies greatly among individuals, and genetic factors are likely to be significant contributors. Subspecies of rhesus macaques originating from different geographic locations are known to differ genetically, but the effect of origin on gene expression and carotenoid status has not been determined. The study objective was to determine whether xanthophyll status and expression of carotenoid-related genes, as well as genes with known variants between subspecies, differ between the brains of adult rhesus monkeys of Indian and Chinese origin. Samples of prefrontal cortex, cerebellum, and striatum were collected from adult monkeys (n = 9) fed a standard stock diet containing carotenoids. Serum and brain carotenoids were determined using reverse-phase high-performance liquid chromatography. For each brain region, RNA sequencing and real-time quantitative polymerase chain reaction were used to determine differentially expressed genes between the subspecies. Indian-origin monkeys had higher xanthophyll levels in brain tissue compared to Chinese-origin monkeys despite consuming similar amounts of dietary carotenoids. In a region-specific manner, four genes related to carotenoid and fatty acid metabolism (BCO2, RPE65, ELOVL4, FADS2) and four genes involved in the immune response (CD4, CD74, CXCL12 LTBR) were differentially expressed between Indian- and Chinese-origin monkeys. Expression of all four genes involved in carotenoid and fatty acid metabolism were correlated with brain xanthophyll concentration in a region-specific manner. These results indicate that origin is related to differences in both gene expression and xanthophyll content in the brain. Findings from this study may have important implications regarding genetic diversity, lutein status, and cognition in primates.


Liraglutide directly protects cardiomyocytes against reperfusion injury possibly via modulation of intracellular calcium homeostasis.
Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglutide can perform direct protective effects on cardiomyocytes against reperfusion injury. In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation (H/R) induction. Cardiomyocytes apoptosis was detected by fluorescence TUNEL. Mitochondrial membrane potential (ΔΨm) and intracellular reactive oxygen species (ROS) was assessed by JC-1 and DHE, respectively. Fura-2/AM was used to measure intracellular Ca2+ concentration and calcium transient. Immunofluorescence staining was used to assess the expression level of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). In vivo experiments, myocardial apoptosis and expression of SERCA2a were detected by colorimetric TUNEL and by immunofluorescence staining, respectively. In vitro liraglutide inhibited cardiomyotes apoptosis against H/R. ΔΨm of cardiomyocytes was higher in liraglutide group than H/R group. H/R increased ROS production in H9C2 cells which was attenuated by liraglutide. Liraglutide significantly lowered Ca2+ overload and improved calcium transient compared with H/R group. Immunofluorescence staining results showed liraglutide promoted SERCA2a expression which was decreased in H/R group. In ischemia/reperfusion rat hearts, apoptosis was significantly attenuated and SERCA2a expression was increased by liraglutide compared with H/R group. Liraglutide can directly protect cardiomyocytes against reperfusion injury which is possibly through modulation of intracellular calcium homeostasis.