[Transoral approach to thyroid gland in the experiment].
To develop minimally invasive and safe endoscopic access to thyroid gland. Transoral pre-mandibular video-assisted gas-free access to thyroid gland was developed in experimental study that included 19 human cadavers. Stereometric modeling defined the evaluation criteria including the form of basal arch of lower jaw and its height. There was no conflict of instruments in working chamber under platysma. Additional trocar was deployed to resolve the conflict between working parts of instruments during thyroid gland mobilization. The angle of operative action between the instruments is close to 90°. Trocar hole is used for drainage. The access provides good visualization of recurrent laryngeal nerve, upper and lower thyroid arteries and parathyroid gland. It is less traumatic compared with other extra-cervical accesses to thyroid glands.


Elastomeric negative acoustic contrast particles for affinity capture assays.
This report describes the development of elastomeric capture microparticles (ECμPs) and their use with acoustophoretic separation to perform microparticle assays via flow cytometry.We have developed simple methods to form ECμPs by cross-linking droplets of common commercially available silicone precursors in suspension followed by surface functionalization with biomolecular recognition reagents. The ECμPs are compressible particles that exhibit negative acoustic contrast in ultrasound when suspended in aqueous media, blood serum, or diluted blood. In this study, these particles have been functionalized with antibodies to bind prostate specific antigen and immunoglobulin (IgG). Specific separation of the ECμPs from blood cells is achieved by flowing them through a microfluidic acoustophoretic device that uses an ultrasonic standing wave to align the blood cells, which exhibit positive acoustic contrast, at a node in the acoustic pressure distribution while aligning the negative acoustic contrast ECμPs at the antinodes. Laminar flow of the separated particles to downstream collection ports allows for collection of the separated negative contrast (ECμPs) and positive contrast particles (cells). Separated ECμPs were analyzed via flow cytometry to demonstrate nanomolar detection for prostate specific antigen in aqueous buffer and picomolar detection for IgG in plasma and diluted blood samples. This approach has potential applications in the development of rapid assays that detect the presence of low concentrations of biomarkers in a number of biological sample types.


The effect of protamine on the epicardial microflow and the graft flow in open-heart surgery.
To evaluate the effect of coronary revascularization on myocardial perfusion and surgical outcome regarding graft flow, we used laser Doppler flowmetry to assess the epicardial microcirculation in patients undergoing coronary artery bypass grafting (CABG) or valve replacement (VR) and electromagnetic flowmetry to measure graft flow in the CABG group. In the CABG group, the preoperative mean laser Doppler flow rate (LDF) in the epicardium of the left ventricle significantly increased at the end of cardiopulmonary bypass (CPB) (22 +/- 7 arbitrary units (AU) to 60 +/- 13 AU, p < 0.001). This value further increased 10 min after protamine infusion (66 +/- 14 AU, p < 0.01), but was significantly reduced 30 min later (51 +/- 14 AU, p < 0.002). Compared to the post-CPB value (34 +/- 10 ml/min) before protamine infusion, the mean graft flow (ml/min) to this area significantly increased 10 min after protamine infusion (41.3 +/- 10 ml/min, p < 0.001) but significantly decreased 30 min later (29 +/- 9 ml/min, p < 0.001). The preoperative mean LDF in the VR group was significantly higher than in the CABG group (p < 0.01). In the CABG group, there was a positive correlation between the LDF and graft flow at the end of CPB (r = 0.788) and 10 (r = 0.767) and 30 (r = 0.784) min after protamine infusion. This study shows that coronary bypass grafting increases the myocardial microcirculation which, together with graft flow, could give an early indication of the effect of surgery on myocardial microcirculation. Furthermore, protamine was found to be one of the factors contributing to graft flow reduction postoperatively and, therefore, newer methods of heparin reversal may be desirable.


[Development of an oligoarginine peptide displaying rapid cell penetration for improved intestinal absorption].
Arginine-rich peptides, including oligoarginines (Rn, n=7-12) are cell penetrating peptides (CPPs) and are useful for the intracellular delivery of membrane-impermeable substances. Endocytosed arginine-rich peptides can become trapped in endosomes, and the avoidance of endosomal retention is necessary for achieving effective cytosolic translocation. Our group has succeeded in enhancing the cellular uptake of oligoarginines by introducing short hydrophobic penetration accelerating sequences (Pas). The effectiveness of a Pas segment in improving the oligoarginine-mediated intracellular delivery of a biofunctional peptide was demonstrated through the efficient inhibition of glioma cell growth by a p53 C-terminal-derived retro-inverso peptide. The CPPs were expected to increase the penetration efficiency of low-permeability drugs through the intestinal epithelial cell layer into blood. Drugs conjugated to oligoarginines via a chemically stable linker tend to be retained in the negatively charged intracellular compartment due to the strongly cationic peptides. Our group has proposed the use of a self-cleavable linker strategy that effectively releases the drugs from the oligoarginine peptide. Chemical-triggered self-cleavage produces the parent drug via intramolecular imide formation under physiological conditions. The designed model drug-oligoarginine conjugates were converted with the half-life (t1/2) values of 9-100 min. Conjugates possessing a short t1/2 of 9-10 min improved the transport rate of the parent model drug in a Caco-2 monolayer permeation assay. The Pas attachment to the oligoarginine was also found to be effective in this permeation assay. The Pas attachment may provide a new platform for facilitating arginine-rich CPP-mediated cargo transport.


Epidemic models with nonlinear infection forces.
Epidemic models with behavior changes are studied to consider effects of protection measures and intervention policies. It is found that intervention strategies decrease endemic levels and tend to make the dynamical behavior of a disease evolution simpler. For a saturated infection force, the model may admit a stable disease-free equilibrium and a stable endemic equilibrium at the same time. If we vary a recovery rate, numerical simulations show that the boundaries of the region for the persistence of the disease undergo the changes from the separatrix of a saddle to an unstable limit cycle. If the inhibition effect from behavior changes is weak, we find two limit cycles and obtain bifurcations of the model as the population size changes. We also find that the disease may die out although there are two endemic equilibria.


Modulation by head and trunk positions of the vestibulo-spinal reflexes evoked by galvanic stimulation of the labyrinth. Observations by labyrinthine evoked EMG.
Modulation by head and trunk positions of the vestibulo-spinal reflexes was studied in the soleus muscle activities induced by galvanic stimulation of the labyrinth. The stimulation was applied using a bipolar-biaural method with the cathode on the right ear and the anode on the left ear. The intensity was 1 mA and duration 3 s. 1) When the labyrinth was stimulated with the head facing forward, soleus muscle activities increased on the right side and decreased on the left, with a latency of about 100 ms. In spite of the same stimulation, activities of the soleus muscle on both sides decreased with the head rotated to the right and increased with the head rotated to the left. 2) The responses in upper-body rotation were the same as in the case of head rotation. 3) In trunk rotation, some cases showed the same responses as with the trunk facing forward in rotation to the right and left, while others showed changes in muscular activities with the head rotation caused by rotating the trunk. 4) Changes in labyrinthine evoked EMG by head and trunk positions were considered to be due to interaction of vestibular and proprioceptive inputs on the interneurons of the spinal cord.


The Impact of Probiotic Soy Milk Consumption on Oxidative Stress Among Type 2 Diabetic Kidney Disease Patients: A Randomized Controlled Clinical Trial.
Diabetic kidney disease (DKD) is one the most important complications of diabetes leading to end-stage renal disease. This study aimed to determine the effects of probiotic soy milk consumption on oxidative stress biomarkers in type 2 DKD patients. Forty-eight patients were randomly assigned to consume a diet containing 200 mL/day probiotic soy milk in the intervention group or soy milk in the control condition. As determinants of oxidative stress, malondialdehyde, 8-iso-prostaglandin F2α, oxidized glutathione, total antioxidant capacity, reduced glutathione (GSH), glutathione peroxidase, and glutathione reductase were measured after 8 weeks of intervention according to the standard protocol. Between groups analysis showed that DKD patients in the probiotic soy milk group had a higher mean value of GSH compared with those in the soy milk group. In the final adjusted model, this difference remained significant. Consistently, oxidized glutathione concentration was significantly reduced among patients in the probiotic soy milk group. Also, for activity levels of antioxidant enzymes including glutathione peroxidase and glutathione reductase, significant increased levels were observed between 2 intervention groups in the final adjusted model. However, no significant reduction of the serum 8-iso-prostaglandin F2α or malondialdehyde and no induction of TAC concentrations within and between the 2 groups in the crude and adjusted models were detected. Overall, the results demonstrate that probiotic soy milk consumption could improve some oxidative stress factors among DKD patients. Further longitudinal studies with consideration of individual variation should be conducted.


Establishment of typical adult CT dose indicators for PET-CT scans in Slovenia.
The aim was to determine typical values of diagnostic reference level (DRL) quantities for the computed tomography (CT) part of the most common positron emission tomography-computed tomography (PET-CT) procedures in Slovenia. The most common PET-CT procedures were identified, and data collated for 565 patients imaged in all three PET-CT units in Slovenia during a time span of 11 months. As the number of facilities is too low to establish national DRLs, we followed ICRP recommendations and determined typical values of DRL quantities as the median values of the pooled set of data. Mean, median, and standard deviation of CT dose index (CTDIvol) and total dose length product (DLP) for the CT part of the most common PET-CT procedures were determined for pooled data as well as for each PET-CT unit. The data were compared between all three units to identify possible outliers that would likely benefit from optimization. Three most common CT protocols covering approximately 2/3 of all PET-CT imaging performed in Slovenia were considered: from the base of the cranium to the middle of the femur, from the top of the head to the middle of the femur, and for the whole-body PET-CT. The established typical values in terms of total DLP were 295, 359, and 676 mGyċcm, respectively; and in terms of CTDIvol3.05, 3.22, and 3.60 mGy, respectively. Comparing the data between all three units showed significantly higher (p< 0.001) patient doses on one unit, indicating a need for optimization. The results present the first-time data on the national typical values of DRL quantities for the CT part of most common PET-CT procedures in Slovenia. While the determined typical values are within the DRL values established in some other countries, significant differences were found between the individual units included in the study.


Phycocyanin alpha-subunit gene of Anacystis nidulans R2: cloning, nucleotide sequencing and expression in Escherichia coli.
The cloning and nucleotide sequence determination of the Anacystis nidulans R2 phycocyanin (PC) alpha-subunit gene are described. A 3.0-kb PstI fragment of Anacystis nidulans R2 genomic DNA cloned in plasmid pUC8 was found to hybridize with a heptadecameric oligodeoxynucleotide probe. Sequencing using synthetic primers revealed the presence of the PC alpha-subunit gene and the 3' proximal end of the beta-subunit gene. The alpha-gene is separated from the upstream beta-gene by a spacer length of 51 bp. The deduced amino acid (aa) sequence of the alpha-subunit protein is identical, except for 5 aa, to that of A. nidulans 6301 and is highly homologous (77%) to that reported for Agmenellum quadruplicatum PR6. The 16-kDa alpha-subunit protein, detected by immunoadsorption, was fortuitously expressed in Escherichia coli from the lacZ promoter of the cloning vehicle pUC8.


Design of chemically stable, potent, and efficacious MDM2 inhibitors that exploit the retro-mannich ring-opening-cyclization reaction mechanism in spiro-oxindoles.
Inhibition of the MDM2-p53 protein-protein interaction is being actively pursued as a new anticancer therapeutic strategy, and spiro-oxindoles have been designed as a class of potent and efficacious small-molecule inhibitors of this interaction (MDM2 inhibitors). Our previous study showed that some of our first-generation spiro-oxindoles undergo a reversible ring-opening-cyclization reaction that, from a single compound in protic solution, results in an equilibrium mixture of four diastereoisomers. By exploiting the ring-opening-cyclization reaction mechanism, we have designed and synthesized a series of second-generation spiro-oxindoles with symmetrical pyrrolidine C2 substitution. These compounds undergo a rapid and irreversible conversion to a single, stable diastereoisomer. Our study has yielded compound 31 (MI-1061), which binds to MDM2 with Ki = 0.16 nM, shows excellent chemical stability, and achieves tumor regression in the SJSA-1 xenograft tumor model in mice.


IRES-dependent translation of the long non coding RNA meloe in melanoma cells produces the most immunogenic MELOE antigens.
MELOE-1 and MELOE-2, two highly specific melanoma antigens involved in T cell immunosurveillance are produced by IRES-dependent translation of the long « non coding » and polycistronic RNA, meloe. In the present study, we document the expression of an additional ORF, MELOE-3, located in the 5' region of meloe. Data from in vitro translation experiments and transfection of melanoma cells with bicistronic vectors documented that MELOE-3 is exclusively translated by the classical cap-dependent pathway. Using a sensitive tandem mass spectrometry technique, we detected the presence of MELOE-3 in total lysates of both melanoma cells and normal melanocytes. This contrasts with our previous observation of the melanoma-restricted expression of MELOE-1 and MELOE-2. Furthermore, in vitro stimulation of PBMC from 6 healthy donors with overlapping peptides from MELOE-1 or MELOE-3 revealed a very scarce MELOE-3 specific T cell repertoire as compared to the abundant repertoire observed against MELOE-1. The poor immunogenicity of MELOE-3 and its expression in melanocytes is consistent with an immune tolerance towards a physiologically expressed protein. In contrast, melanoma-restricted expression of IRES-dependent MELOE-1 may explain its high immunogenicity. In conclusion, within the MELOE family, IRES-dependent antigens represent the best T cell targets for immunotherapy of melanoma.


Syndromic dystelephalangy.
We report an 8-year-old boy with a distinctive facial phenotype, deformities of fingers and toes and limitation of knee movement of unknown etiology. He had a round face, a long nose, a thin upper lip, a small mouth and micrognathia. In spite of microcephaly and retarded speech development secondary to hearing loss his mental development was within normal limits. The most distinctive radiographic abnormality was hypoplasia of the distal end of the middle phalanges with radial deviation of the distal phalanges.


A Rare Case of Opsoclonus Myoclonus Ataxia Syndrome Post Viral Illness.
Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare inflammatory neurological disorder characterized by ocular, motor, behavioral, language, and sleep disturbances. It usually affects infants and young children but may affect adults. A 28-year-old male was brought to our emergency ward with complaints of involuntary spontaneous eye movements and jerky movements of limbs with imbalance while walking. He had a history of short febrile illness 10 days prior. His magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid (CSF) analysis, and other routine investigations were normal. The patient was treated with injectable methylprednisolone (1 g) given for five days along with other supportive therapy. A significant reduction in the opsoclonus, myoclonus, and ataxia was seen on a six-month follow-up. OMAS should be identified early to avoid the use of inappropriate medications, and immunotherapy must be provided as early as possible in order to prevent irreversible neurological damage.


Reference Gene Validation for Quantitative PCR Under Various Biotic and Abiotic Stress Conditions in Toxoptera citricida (Hemiptera, Aphidiae).
The regulation of mRNA expression level is critical for gene expression studies. Currently, quantitative reverse transcription polymerase chain reaction (qRT-PCR) is commonly used to investigate mRNA expression level of genes under various experimental conditions. An important factor that determines the optimal quantification of qRT-PCR data is the choice of the reference gene for normalization. To advance gene expression studies in Toxoptera citricida (Kirkaldy), an important citrus pest and a main vector of the Citrus tristeza virus, we used five tools (GeNorm, NormFinder, BestKeeper, ΔCt methods, and RefFinder) to evaluate seven candidate reference genes (elongation factor-1 alpha [EF1α], beta tubulin [β-TUB], 18S ribosomal RNA [18S], RNA polymerase II large subunit (RNAP II), beta actin (β-ACT), alpha tubulin, and glyceraldhyde-3-phosphate dehydrogenase) under different biotic (developmental stages and wing dimorphism) and abiotic stress (thermal, starvation, and UV irradiation) conditions. The results showed that EF1α and 18S were the most stable genes under various biotic states, β-ACT and β-TUB during thermal stress, EF1α and RNAP II under starvation stress, and RNAP II, β-ACT, and EF1α under UV irradiation stress conditions. This study provides useful resources for the transcriptional profiling of genes in T. citricida and closely related aphid species.


Frustrated Radical Pairs in Organic Synthesis.
Frustrated radical pairs (FRPs) describe the phenomenon that two distinct radicals─which would otherwise annihilate each other to form a closed-shell covalent adduct─can coexist in solution, owing to steric repulsion or weak bonding association. FRPs are typically formed via spontaneous single-electron transfer between two sterically encumbered precursors─an oxidant and a reductant─under ambient conditions. The two components of a FRP exhibit orthogonal chemical properties and can often act in cooperativity to achieve interesting radical reactivities. Initially observed in the study of traditional frustrated Lewis pairs, FRPs have recently been shown to be capable of homolytically activating various chemical bonds. In this Perspective, we will discuss the discovery of FRPs, their fundamental reactivity in chemical bond activation, and recent developments of their use in synthetic organic chemistry, including in C-H bond functionalization. We anticipate that FRPs will provide new reaction strategies for solving challenging problems in modern organic synthesis.


Focused-ion-beam-assisted magnet fabrication and manipulation for magnetic field detection applications.
A focused-ion-beam-assisted technique intended for ultrasmall, hard-magnet fabrication has been developed. By means of ion-beam-induced milling and deposition, reduced-size NdFeB magnets were extracted from a macroscopic quarry and bonded to the surface of a thin-film bulk acoustic resonator (FBAR). Electrical characterization of the FBAR before and after bonding of the magnet was carried out, thus observing both a downshifting of the resonance frequency and a reduction of the quality factor of the resonator. The magnetic behavior of the nanomagnet has been confirmed by means of magnetometry measurements based on atomic force microscopy.


Social Workers in Pediatric Oncology: A Qualitative Study in Iranian Context.
Background: As professionals, social workers have a special position in relation to considering the needs of children with cancer and their families. Hence, it is important to recognize the experiences and challenges of social workers to improve care of their clients. Method: This study was a qualitative content analysis that aimed to determine a comprehensive understanding of pediatric oncology social workers' experiences in Iran. In total, 19 social workers participated in the study. A purposeful sampling method was applied until reaching data saturation. Data were collected using semi-structured interviews and field observations. Then, the gathered data were analyzed through face content analysis. The study lasted from 2015 to 2017. Finding: Concepts extracted from social workers' experiences consisted of the nature of oncology work, lack of professional competence, low organizational support and professional inferiority that were related to main concept of "exhausting and stressful service". The results indicated that social workers' involvement in stressful and emotionally demanding situations and facing with professional and organizational challenges caused personal exhaustion. Conclusion: In addition to explaining the social workers' experiences and related factors, the results emphasize the importance of taking care of service providers to prevent them becoming stressed and exhausted. It is also important to protect patients from the consequences of stressed and exhausted care providers so further research is recommended to develop specific intervention.


Er:YAG Laser Dental Treatment of Patients Affected by Epidermolysis Bullosa.
Aim. The purpose of this study was to evaluate the efficacy of Er:YAG laser used for treating hard dental tissue in patients with epidermolysis bullosa (EB). Methods. We report two cases of EB in which an Er:YAG laser was used for conservative treatments. In the first case, the Er:YAG laser (2,940 μm, 265 mJ, 25 Hz) was used to treat caries on a deciduous maxillary canine in an 8-year-old male patient affected by dystrophic EB. In the second case, we treated a 26-year-old female patient, affected by junctional EB, with generalized enamel hypoplasia, and an Er:YAG laser (2,940 μm, 265 mJ, 25 Hz) was used to remove the damaged enamel on maxillary incisors. Results. The use of the Er:YAG laser, with the appropriate energy, was effective in the selective removal of carious tissue and enamel hypoplasia. During dental treatment with the Er:YAG laser, patients required only a few interruptions due to the absence of pain, vibration, and noise. Conclusions. Laser treatment of hard dental tissues is a valuable choice for patients affected by EB since it is less invasive compared to conventional treatment, resulting in improved patient compliance.


Predictive value of pelvic incidence in progression of spondylolisthesis.
Retrospective analysis of pelvic incidence and other radiographic parameters as a predictor of progression of isthmic spondylolisthesis. To evaluate the predictive value of various radiographic parameters, including pelvic incidence, in determining the risk for progression of lumbosacral isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA Although pelvic incidence has recently been shown to be positively correlated to the severity of spondylolisthesis, it has not been confirmed as a predictor of spondylolisthetic progression. Thirty-six patients who have undergone primary posterior lumbosacral fusion for isthmic spondylolisthesis at our institution from 1977 to 2001 were retrospectively analyzed. There were 24 females and 12 males with a mean age of 21.3 +/- 2.0 years (range, 12 to 53 y). Twenty-two patients had high-grade (Meyerding class III, IV, V) and 14 patients had low-grade (Meyerding class I, II) spondylolisthesis, respectively. Factors evaluated included age, gender, neurologic deficits, reason for surgery, and documented evidence of progression. Slip percentage, high-grade or low-grade slip, slip angle, sacral inclination, sacral rounding, trapezoidal L5 vertebra, and pelvic incidence were measured from immediate preoperative standing lateral radiographs. These factors were statistically analyzed for risk of progression. Continuous variables were analyzed using one-way analysis of variance. Nominal variables were analyzed using chi2 test. Pelvic incidence (P = 0.66) was not predictive of spondylolisthetic progression. Of the other radiographic measurements, slip percentage (P < 0.001), slip angle (P = 0.016), and high-grade spondylolisthesis (P < 0.0001) were highly predictive of progression. Interestingly, sacral inclination (P = 0.33) was not predictive of progression. Pelvic incidence cannot adequately predict the probability of spondylolisthetic progression. Analysis of the other clinical and radiographic parameters revealed that slip percentage and high-grade spondylolisthesis remain the most positive predictors of progression.


Live 3D echocardiography: a replacement for traditional 2D echocardiography?
We describe the development of real-time 3D imaging and review the previously used versions of 3D echocardiography so that the reader will appreciate why current developments truly do represent a quantum leap in the technology. Three-dimensional echocardiography has now been shown to have several advantages over 2D echocardiography, particularly for volume measurements, visualization of septal defects, and whole-valve evaluation. Given these data, it is clear that 3D echocardiography is here to stay and soon will become part of routine echocardiographic examinations.


[Inhibition of telomerase activity by ribozyme targeted to human telomerase transcriptase].
Human telomerase reverse transcriptase (hTERT) is the catalytic subunit and the key factor which controls the telomerase activity,so it is the best choice to inhibit telomerase through controling hTERT expression.In this work,a hammer head ribozyme directed against the hTERT mRNA (hTERTRZ) was designed and synthesized to serve as a telomerase inhibitor. In order to test its in vitro cleavage activity, two in vitro transcription plasmids containing hTERTRZ and hTERT gene respectively were constructed. Ribozyme RNA and DIG-labeled-hTERT were synthesized by in vitro transcription. In vitro cleavage reactions were carried out by mixing the hTERTRZ with DIG-labeled-hTERT under different reaction conditions, and cleavage bands were detected by digoxin chemiluminescent assay. hTERTRZ showed a specific cleavage activity against the hTERT used as template. To investigate its in vivo effect of telomerase inhibition in tumor cells, a eukaryotic expression plasmid containing the hTERT ribozyme gene was introduced into HeLa cells and hepatoma cells by using LipofectAMINE. In the transfectants, the level of intact hTERT mRNA and the telomerase activity were clearly reduced, and the telomere length of these clones was apparently shortened at the beginning period, then kept a fixed value without further shortening. All the transfectants with ribozyme grew clearly more slowly than the parental cell line. The doubling time of the tansfectants prolonged compared to the negative control, but no apparent apoptosis was shown even at their 37th passage. These findings suggest the potential application of this ribozyme as a new theraputic agent directed against immortalized cancer cells.


Health challenges of mothers with special needs children in Pakistan and the importance of integrating health social workers.
There is concern that mothers of special needs children in developing countries like Pakistan are neglected populations facing hidden health challenges. The aim of this study was to investigate the kinds of health challenges mothers experience and to highlight the role of health social workers in supporting the needs of mothers. Twenty-one mothers were sampled across three cities and findings were analyzed through a thematic content analysis approach. Findings revealed that mothers faced significant and salient challenges under eight sub-categories of mental health and six sub-categories of physical health. We recommend that health social workers collaborate with healthcare practitioners to improve health services for mothers and also coordinate with other social workers, community members, and policymakers for improving both social and structural support for special needs families.


Analysis of Early Neurovascular Complications of Pediatric Supracondylar Humerus Fractures: A Long-Term Observation.
Purpose. Analysis of early vascular and nerve complications of supracondylar humerus fractures in children. Material and Methods. 220 children hospitalized in the Pediatric Trauma-Orthopedic Department in the years 2004-2014. The group consisted of 143 males and 77 females. Results. Acute neurovascular complications occurred in 16.81% of patients with displaced supracondylar fracture (37 children). Nerve damage was found in 10% of patients with displaced fracture (22 children). The most injured nerve was median nerve; this complication occurred in 15 patients (68.18%). The total nerve function returned after average of 122 days (0-220 days after surgery). Symptoms of vascular injury occurred in 7.7% children with displaced fracture (17 children). Conclusions. (1) In children with supracondylar fracture the most often injured nerve is median nerve. (2) The incidence of vascular and nerve complications positively correlates with the progression of fracture according to Gartland classification.


Protective role of melatonin in myocardial oxidative damage induced by mercury in murine model.
This study was designed to investigate the electrophysiological, hemodynamic and biochemical parameters of mercuric chloride and methylmercury exposure on cardiovascular functions and its modulation by melatonin in vivo. Wistar albino rats were divided into six group containing 10 animals each. Mercuric chloride (3.75 µM/L) in drinking water and methylmercury (0.5 mg/kg/day) through gavage, given for 1 month, induced a statistically significant increase (p < 0.001) in left ventricular end diastolic pressure, blood and cardiac tissue mercury content and myocardial lipid peroxides compared to control. Significant attenuation (p < 0.05) of baroreflex sensitivity and depletion of myocardial endogenous antioxidants (p < 0.001) viz. Reduced glutathione (GSH) and superoxide dismutase (SOD) were also found in the mercury-exposed groups as compared to control group. Mercury exposure followed by subacute treatment with melatonin (4 µg/mL/day) in drinking water for 1 month significantly lowered (p < 0.01) left ventricular end diastolic pressure and lipid peroxide levels and increased baroreceptor sensitivity (p < 0.001) and also levels of GSH and SOD (p < 0.001) as compared to mercury-exposed rats. The results of our study provide clear evidence that elevated oxidative stress and altered baroreflex mechanisms caused by mercury intoxication may be the contributing factors responsible for impairment of cardiovascular functions and melatonin may exhibit cardioprotective property against subacute heavy metal intoxication and enhance the antioxidant defense against mercury-induced oxidative myocardial injury in rats.


Skeletally Tunable Seven-Membered-Ring Fused Pyrroles.
We describe a copper-mediated method that enables the synthesis of seven-membered-ring fused pyrroles (7-mrFPs). The protocol proceeds via an in situ spiro-intermediate ring expansion and tolerates a library of 7-mrFP derivatives with a broad range of functional groups in a simple step with tangible parameters and substrate adaptations. These rare 7-mrFPs are now accessible on a millimolar scale, and selected examples exhibit high antioxidant activity.


Quantification of C. globosum spores in house dust samples.
Chaetomium globosum is one of the most common fungi that grows in damp buildings and occurs in agricultural and forestry workplaces. Using sera from atopic patients, we characterized and purified an extracellular chitosanase (Chg47) from C. globosum that is antigenic to humans. The study reports the production of monoclonal antibodies to the protein. Three capture ELISAs were developed for Chg47 for detection of spores and spore and mycelial fragments in dust samples using different mono- and polyclonal antibody combinations. One method is based on an enhanced biotinylated polyclonal antibody as the secondary antibody and coating anti-IgM to capture one of two clones of IgM monoclonal antibodies as the capture antibody. The other method makes use of an enhanced rabbit polyclonal antibody as both the primary and capture antibody. The detection limit of the double PAb method for the Chg47 antigen was 7.6 pg/ml. When the anti-IgM+10B3 clone was used, the detection limit was 61 pg/ml and for anti-IgM+5F12, 122 pg/ml. The detection limit of double PAb method is comparable to methods for the allergen and spores of Aspergillus versicolor in house dust and is more sensitive than other immunoassays for allergens in house including for Stachybotrys chartarum, Aspergillus fumigatus and Alternaria alternata. All three methods had limited cross-reactivity to fungi common in house dust representing a diverse array of taxa.


N-Heterocyclic Olefins on a Silicon Surface.
The adsorption of N-heterocyclic olefins (NHOs) on silicon is investigated in a combined scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory study. We find that both of the studied NHOs bind covalently, with ylidic character, to the silicon adatoms of the substrate and exhibit good thermal stability. The adsorption geometry strongly depends on the N-substituents: for large N-substituents, an upright adsorption geometry is favored, while a flat-lying geometry is found for the NHO with smaller wingtips. These different geometries strongly influence the quality and properties of the obtained monolayers. The upright geometry leads to the formation of ordered monolayers, whereas the flat-lying NHOs yield a mostly disordered, but denser, monolayer. The obtained monolayers both show large work function reductions, as the higher density of the flat-lying monolayer is found to compensate for the smaller vertical dipole moments. Our findings offer new prospects in the design of tailor-made ligand structures in organic electronics and optoelectronics, catalysis, and material science.


Hydrogen peroxide pretreatment of perfused canine vessels induces ICAM-1 and CD18-dependent neutrophil adherence.
Cytotoxic products of neutrophils (polymorphonuclear leukocytes, PMNs) contribute to ischemia-reperfusion injury of several tissues. Hydrogen peroxide (H2O2), one of the cytotoxic products of PMNs, also promotes the adherence of PMNs to cultured vascular endothelial cells in vitro. The present study was undertaken to determine if H2O2 also augmented adhesion of PMNs to intact vessels perfused ex vivo and to determine if H2O2-induced PMN adherence to intact canine carotid arteries and external jugular veins or to cultured canine venous endothelium is mediated by specific adherence ligands on the neutrophil and/or the endothelium. Vessels were perfused for 20 minutes with oxygenated Krebs-Henseleit bicarbonate buffer with and without H2O2, washed with buffer alone, and then exposed to 111In-labeled isolated PMNs (10(7) cells/vessel) under static conditions for up to 20 minutes before being washed again. Residual radioactivity retained by the washed vessel was counted as an index of PMN retention. The adherence of unlabeled PMNs to cultured endothelial cells was determined by a visual assay method after pretreatment of the endothelium with H2O2 for brief periods followed by washing. Perfusion of vessels with H2O2 produced a transient, concentration-dependent increase in PMN adhesion to both canine carotid arteries and external jugular veins that was two to four times that of control values at 1 mmol/l and declined at higher H2O2 concentrations. Peak retention of PMNs by canine carotid arteries occurred 10 minutes after exposure to 1 mmol/l H2O2 and then rapidly declined to control values; this effect was replicated by a second 20-minute exposure of canine carotid arteries to 1 mmol/l H2O2 60 minutes after the first exposure. Scanning and transmission electron microscopy revealed not only adherence of PMNs to but migration through the vascular endothelium of the carotid artery after H2O2 perfusion. The endothelium was intact in H2O2-treated arteries not exposed to PMNs. H2O2-induced PMN retention was completely inhibited by addition of catalase or the hydroxyl radical scavenger dimethylthiourea to the perfusate by incubation of the PMN with a monoclonal antibody (Mab) against CD18 (R15.7) or by perfusion of the H2O2-treated vessel with CL18/6, a Mab against canine ICAM-1 (intercellular adhesion molecule-1). Similar effects of Mabs on PMN adhesion to H2O2-pretreated cultured endothelium were noted. The retention of PMNs by vessels mechanically denuded of endothelial cells was markedly increased. H2O2 pretreatment of these vessels did not further augment PMN adherence, and no inhibitory effect of R15.7 was noted. Incubation of carotid arteries and PMNs with a specific platelet-activating factor antagonist, WEB2086, completely inhibited the H2O2-induced increased PMN retention by these vessels. These results indicate that H2O2 in the absence of evidence for permanent endothelial cell injury, can induce a transient, reversible, platelet-activating factor-dependent adherence of PMNs to vessels by mechanisms that depend on an intact endothelium and involve CD18 on the PMN and ICAM-1 on the endothelium.


A method to measure the frequencies of individual half cells in a dumbbell cavity.
Dumbbell fabrication is a midprocess for manufacturing an elliptical superconducting rf cavity. In order to understand how a welding shrinkage affects a dumbbell's frequencies and length, we need to measure the exact frequencies of each individual half cell of a dumbbell. To improve such a calculation precision and to simplify the calculation formulae, based on a two-coupled oscillator model and a cavity perturbation theory, a new formula to calculate the individual half-cell frequencies of a dumbbell or the individual cavity frequencies of a two-cavity coupling system has been developed, and its performance has been confirmed by using a dumbbell simulation. This formula can be applied to any kind of rf cavities with electric, magnetic, or electromagnetic coupling, if a coupling hole between two coupling cavities is small compared to the wavelength. Compared to other calculation formulae, this formula simplifies the calculation process of the individual resonator frequencies of a coupling system considerably, and it can also improve the calculation precision than that of a normal calculation method. Another advantage of this new method is that we do not need to consider a coupling factor between two resonators during a testing for an individual resonator frequency of an oscillator. The developed formula has been successfully used to tune the PEFP dumbbells.


Impact of sawfly defoliation on growth of Scots pine Pinus sylvestris (Pinaceae) and associated economic losses.
Needle defoliation by diprionid sawflies decreases the increment and timber yield of Scots pine Pinus sylvestris L. The aim of this study was to provide approximate estimates of this decrease and preliminary estimates of the economic value of growth losses and tree mortality. Growth loss after needle damage by Diprion pini (Linnaeus) was studied in western Finland. Increment cores were sampled for radial growth measurements from trees subjected to slight, moderate and heavy defoliation. A literature survey was carried out to estimate radial growth losses after defoliation by Neodiprion sertifer (Geoffroy). Calculations for economic consequences were based on previous estimates and on the ongoing 9th Finnish National Forest Inventory. Moderate defoliation by N. sertifer and D. pini reduced volume growth by 21% and 86% and heavy defoliation by 38% and 94%, respectively. Tree mortality in defoliated stands was recorded as approximately 4% after an outbreak of N. sertifer and 30% after an outbreak of D. pini. The estimated average economic value of the losses due to reduced growth and tree mortality reached $40 ha-1 after a single-year outbreak of N. sertifer and $310 ha-1 in the case of D. pini. These preliminary estimates of economic losses indicate a much higher impact of pine sawflies than those revealed by the few earlier studies in Europe.


Free-Rider Games for Cooperative Spectrum Sensing and Access in CIoT Networks.
With the rapid development of technologies such as wireless communications and the Internet of Things (IoT), the proliferation of IoT devices will intensify the competition for spectrum resources. The introduction of cognitive radio technology in IoT can minimize the shortage of spectrum resources. However, the open environment of cognitive IoT may involve free-riding problems. Due to the selfishness of the participants, there are usually a large number of free-riders in the system who opportunistically gain more rewards by stealing the spectrum sensing results from other participants and accessing the spectrum without spectrum sensing. However, this behavior seriously affects the fault tolerance of the system and the motivation of the participants, resulting in degrading the system's performance. Based on the energy-harvesting cognitive IoT model, this paper considers the free-riding problem of Secondary Users (SUs). Since free-riders can harvest more energy in spectrum sensing time slots, the application of energy harvesting technology will exacerbate the free-riding behavior of selfish SUs in Cooperative Spectrum Sensing (CSS). In order to prevent the low detection performance of the system due to the free-riding behavior of too many SUs, a penalty mechanism is established to stimulate SUs to sense the spectrum normally during the sensing process. In the system model with multiple primary users (PUs) and multiple SUs, each SU considers whether to free-ride and which PU's spectrum to sense and access in order to maximize its own interests. To address this issue, a two-layer game-based cooperative spectrum sensing and access method is proposed to improve spectrum utilization. Simulation results show that compared with traditional methods, the average throughput of the proposed TL-CSAG algorithm increased by 26.3% and the proposed method makes the SUs allocation more fair.


Stark Spectroscopy of Rubrene. I. Electroabsorption Spectroscopy and Molecular Parameters.
Electroabsorption spectroscopy investigation and the determination of molecular parameters for rubrene dispersed in a poly(methyl methacrylate) (PMMA) matrix are reported. The features of the band system in the absorption spectrum in PMMA are analogous to those in solutions. The changes in the electric dipole moment and the polarizability between the excited and ground states are determined from analysis of the Stark effect in the absorption band. The change in the transition dipole moment in the presence of an external electric field is also observed. Although rubrene is predicted to be classified as a nonpolar molecule, there is a contribution of the difference in the electric dipole moment between the excited and ground states to the electroabsorption spectrum. The origin of the nonzero difference in the electric dipole moment is argued. Stark fluorescence spectroscopy investigation is reported in Part II of this series.


Structural insights into the binding of small ligand molecules to a G-quadruplex DNA located in the HIV-1 promoter.
Targeting guanine (G)-rich DNA sequences, folded into non-canonical G-quadruplex (G4) structures, by small ligand molecules is a promising strategy for gene therapy of various diseases. There is experimental proposal that, among eight studied ligands, nitidine chloride - NC and a benzo phenanthridine derivative - BPD have the highest binding affinity for such a sequence (5'-T1G2G3C4C5T6G7G8G9C10G11G12G13A14C15T16G17G18G19-3') in the HIV-1 promoter, indicating that an anti-HIV-1 prodrug may regulate the expression of the promoter. Herein, this experimental indication is elaborated by using molecular docking simulations and by characterizing the modes of binding of the eight natural molecules to the particular G4. Moreover, the configurational entropy, as an upper bound of the true entropy contribution to the free energy in noncovalent binding, is employed to see into the structural changes experienced by the G4-DNA upon ligand binding. For various parts (complete structure, backbone, system of all bases, bases of G-tetrads) of the G4-DNA structure, a subtle molecular dynamics (MD) is exploited to determine the change of asymptotic (for infinitely long MD simulation) configurational entropy, being the thermodynamic consequence of DNA flexibility change upon complex formation. While NC increases rigidity of G4 (mainly through the system of all nucleobases), BPD increases flexibility of G4 (more than 50% stems from the sugar-phosphate backbone). These insights are further dissected and substantiated by considering the configurational entropy contributions at the level of individual base pairs making the two G-tetrads (G2G7G13G17 and G3G8G12G18) and by exploring the estimates of the total intra-base pair and inter-base pair entropies. This work makes the structural origin of enhanced stability of G4-DNA more certain - useful information when attempting to design optimal G4-DNA binders.


[Comparison of the outcomes of spontaneous pneumothorax treated with early or delayed air drainage].
to explore the outcomes between the early or delayed air drainage for spontaneous pneumothorax. the present prospective study was designed to evaluate the efficacy and complications. 242 patients with primary spontaneous pneumothorax were randomly allocated to early (< 72 h) group (n = 142) or delayed (> 6 d) exhaust air group (n = 122), the recent success rates, average time in hospital, recurrences rates, and pleura adhesion rates were evaluated. average time in hospital: early group and delayed group respectively was (18 ± 6) d vs (6 ± 2) d. In early group, the amount of pneumothorax was between 20% to 50%, 51 cases were aspirated and 44 of them were increased after first aspiration, whom were subsequently treated by intercostal drainage. Size of pneumothorax more than 50%, 98 patients treated by intercostal drainage.12 of 142 patients with persistence leak air transferred to surgery. In delayed group, all of 122 aspirations were successful at the first time. There were significant differences between the 2 groups in recent successful rate. 29 of the 128 patients in early group and 5 of the 115 had a relapsing pneumothorax. During the 2 year follow-up period, 79 of the 128 patients in early group and none of the 115 had radiographic pleural adhesions appearances. the time of air drainage was associated with outcomes of primary spontaneous pneumothorax. These data suggest that delayed intervention is an effective initial treatment strategy for patients with PSP, with a shorter time in hospital, fewer pleural adhesions and lower recurrence rates.


Representation of providers on health planning boards.
PL 93-641, The National Health Planning and Resources Development Act of 1974, called for broad representation of health care providers, in addition to consumers, on Health Systems Agency (HSA) governing boards. Analysis of data submitted to the U.S. Department of Health, Education, and Welfare by the HSAs indicated that HSA provider board members are not representative of the overall provider work force or general population. Direct providers outnumber indirect providers by roughly seven to one. Physicians and hospital-nursing administrators are overrepresented, and nurses and other provider groups underrepresented, in relation to their numbers in the work force. Evidence also shows that HSA provider board members are mostly white males, although nonwhites and females are significantly represented in the work force and population.


Diagnostic Performance, Triage Safety, and Usability of a Clinical Decision Support System Within a University Hospital Emergency Department: Algorithm Performance and Usability Study.
Computerized clinical decision support systems (CDSSs) are increasingly adopted in health care to optimize resources and streamline patient flow. However, they often lack scientific validation against standard medical care. The purpose of this study was to assess the performance, safety, and usability of a CDSS in a university hospital emergency department setting in Kuopio, Finland. Patients entering the emergency department were asked to voluntarily participate in this study. Patients aged 17 years or younger, patients with cognitive impairments, and patients who entered the unit in an ambulance or with the need for immediate care were excluded. Patients completed the CDSS web-based form and usability questionnaire when waiting for the triage nurse's evaluation. The CDSS data were anonymized and did not affect the patients' usual evaluation or treatment. Retrospectively, 2 medical doctors evaluated the urgency of each patient's condition by using the triage nurse's information, and urgent and nonurgent groups were created. The International Statistical Classification of Diseases, Tenth Revision diagnoses were collected from the electronic health records. Usability was assessed by using a positive version of the System Usability Scale questionnaire. In total, our analyses included 248 patients. Regarding urgency, the mean sensitivities were 85% and 19%, respectively, for urgent and nonurgent cases when assessing the performance of CDSS evaluations in comparison to that of physicians. The mean sensitivities were 85% and 35%, respectively, when comparing the evaluations between the two physicians. Our CDSS did not miss any cases that were evaluated to be emergencies by physicians; thus, all emergency cases evaluated by physicians were evaluated as either urgent cases or emergency cases by the CDSS. In differential diagnosis, the CDSS had an exact match accuracy of 45.5% (97/213). The usability was good, with a mean System Usability Scale score of 78.2 (SD 16.8). In a university hospital emergency department setting with a large real-world population, our CDSS was found to be equally as sensitive in urgent patient cases as physicians and was found to have an acceptable differential diagnosis accuracy, with good usability. These results suggest that this CDSS can be safely assessed further in a real-world setting. A CDSS could accelerate triage by providing patient-provided data in advance of patients' initial consultations and categorize patient cases as urgent and nonurgent cases upon patients' arrival to the emergency department.


Sedation practices in palliative care services across France: a nationwide point-prevalence analysis.
Terminally ill patients may require sedation to relieve refractory suffering. The prevalence and modalities of this practice in palliative care services remain unclear. This study estimated the prevalence of all sedation leading to a deep unconsciousness, whether transitory, with an undetermined duration, or maintained until death, for terminally ill patients referred to a home-based or hospital-based palliative care service. We conducted a national, multicentre, observational, prospective, cross-sectional study. In total, 331 centres participated, including academic/non-academic and public/private institutions. The participating institutions provided hospital-based or home-based palliative care for 5714 terminally ill patients during the study. In total, 156 patients received sedation (prevalence of 2.7%; 95% CI, 2.3 to 3.2); these patients were equally distributed between 'transitory', 'undetermined duration' and 'maintained until death' sedation types. The prevalence was 0.7% at home and 8.0% in palliative care units. The median age of the patients was 70 years (Q1-Q3: 61-83 years); 51% were women and 78.8% had cancers. Almost all sedation events occurred at a hospital (90.4%), mostly in specialised beds (74.4%). In total, 39.1% of patients were unable to provide consent; only two had written advance directives. A collegial procedure was implemented in 80.4% of sedations intended to be maintained until death. Midazolam was widely used (85.9%), regardless of the sedation type. This nationwide study provides insight into sedation practices in palliative care institutions. We found a low prevalence for all practices, with the highest prevalence among most reinforced palliative care providers, and an equal frequency of all practices.


Studies on the metabolism of propafenone. 2nd comm.: studies on the biotransformation in the dog.
Following administration of 14C- and 2H-labelled propafenone hydrochloride (2-(2'-hydroxy-3'-propylaminopropoxy)-omega-phenyl-propiophenone hydrochloride) to beagle dogs, the metabolites were isolated from urine and bile and analysed by mass spectrometry. Reference substances were synthesized on the basis of the structures postulated from the mass spectra and compared with the substances isolated from the biological material. Propafenone was absorbed completely following i.d. administration and eliminated mainly with the bile. Within 28 h 10% of the dose was excreted with the urine and 87% with the bile. Propafenone was extensively metabolized. Less than 1% of the dose was recovered as unchanged substance in urine and bile. The urinary and biliary metabolites were almost exclusively conjugated. The main metabolite, accounting for more than 30% of the dose, was propafenone glucuronide, followed by conjugates of hydroxylated propafenone derivatives with glucuronic acid and sulphuric acid. 5-Hydroxy-propafenone, a propafenone derivative hydroxylated in the middle aromatic ring, and a derivative hydroxylated in the omega-phenyl ring each accounted for about 15% of the dose. Besides these monohydroxy metabolites, two other O-methylated catechol-like derivatives, substituted in the different aromatic rings were recovered. The remainder of the metabolic products identified were mainly substances resulting from degradation of the propoxyamine side chain.


HDAC3 is critical in tumor development and therapeutic resistance in Kras-mutant non-small cell lung cancer.
HDAC3 is one of the main targets of histone deacetylase (HDAC) inhibitors in clinical development as cancer therapies, yet the in vivo role of HDAC3 in solid tumors is unknown. We identified a critical role for HDAC3 in Kras-mutant lung cancer. Using genetically engineered mouse models (GEMMs), we found that HDAC3 is required for lung tumor growth in vivo. HDAC3 was found to direct and enhance the transcription effects of the lung cancer lineage transcription factor NKX2-1 to mediate expression of a common set of target genes. We identified FGFR1 as a critical previously unidentified target of HDAC3. Leveraging this, we identified that an HDAC3-dependent transcriptional cassette becomes hyperactivated as Kras/LKB1-mutant cells develop resistance to the MEK inhibitor trametinib, and this can be reversed by treatment with the HDAC1/HDAC3 inhibitor entinostat. We found that the combination of entinostat plus trametinib treatment elicits therapeutic benefit in the Kras/LKB1 GEMM.


Formulation and evaluation of mouth dissolving tablets of the Etoricoxib.
The demand for mouth dissolving tablets has been growing during the last decade especially for elderly and children who have swallowing difficulties. Etoricoxib is a new non-steroidal anti-inflammatory drug (NSAID) with selective cox-2 inhibitory activity, selective inhibition of cox-2 provides anti-inflammatory and analgesic activity it is commonly used for osteo-arthritis, rheumatoid arthritis, primary dysmenorrhoea, post operative dental pain and acute gout. The main criteria for mouth dissolving tablets are to disintegrate or dissolve rapidly in oral cavity with saliva in 15 sec to 60 sec with need of water. The disintegrants used should fulfill the criteria by disintegrating the tablets in specified time limit.in the present investigation variety of super disintegrants like primogel, kollidone, Ac-Di-sol, L-HPMC, L-HPC, were selected and tablets were prepared by direct compression method in different concentration like 4% and 8%. The prepared tablets were evaluated for weight variation, hardness, friability, in vitro disintegration time, wetting time, in vitro dissolution study, etc. formulation f-9 shows the lowest disintegration time (44 sec) and wetting time (52 sec). In vitro dissolution studies revealed that formulation F-9 containing 8% L-HPC showed 97% drug release at the end of 20 min.


Uncovering Highly-Excited State Mixing in Acetone Using Ultrafast VUV Pulses and Coincidence Imaging Techniques.
Understanding the ultrafast dynamics of highly excited electronic states of small molecules is critical for a better understanding of atmospheric and astrophysical processes, as well as for designing coherent control strategies for manipulating chemical dynamics. In highly excited states, nonadiabatic coupling, electron-electron interactions, and the high density of states govern dynamics. However, these states are computationally and experimentally challenging to access. Fortunately, new sources of ultrafast vacuum ultraviolet pulses, in combination with electron-ion coincidence spectroscopies, provide new tools to unravel the complex electronic landscape. Here we report time-resolved photoelectron-photoion coincidence experiments using 8 eV pump photons to study the highly excited states of acetone. We uncover for the first time direct evidence that the resulting excited state consists of a mixture of both ny → 3p and π → π* character, which decays with a time constant of 330 fs. In the future, this approach can inform models of VUV photochemistry and aid in designing coherent control strategies for manipulating chemical reactions.


Serological study of parvovirus B19 infection in women with recurrent spontaneous abortions.
The feto-pathogenic association of parvovirus B19 (B19) has been sparingly studied in women with abortion, but not in women with recurrent spontaneous abortions (RSA). Serum samples from 116 women with RSA who were pre-screened for S-TORCH, Chlamydia trachomatis infections, anatomical, chromosomal, endocrinal abnormality and Rh incompatibility and those who had no such known causes of abortion were included in the study. Sera were also collected from 136 normal pregnant women and 120 normal non-pregnant women as disease and normal control respectively. All sera were tested at 1:400 dilutions for B19 IgM by in-house ELISA using cloned and baculovirus expressed VP1 and VP2 antigens of B19. The frequency of anti-B19 IgM antibodies in women with RSA was 19.8%, in pregnant females it was 11% and in normal non-pregnant female was 5%. Sera of 23 women with RSA which were positive for B19 IgM tested negative for B19 DNA by PCR. Patients with RSA should be screened for B19 infection and guidelines for treatment should emerge.


[The gamma globulin-fibrinogen index in the differential diagnosis of decompensated cirrhosis and primary liver cancer].
The gammaglobulin-fibrinogen index (GgF) was determined in 30 healthy subjects and 160 patients with chronic hepatic diseases related to HB infection. The group included 60 cases of chronic active hepatitis, 60 with compensated cirrhosis, 28 with decompensated cirrhosis, and 12 with primary hepatic carcinoma. The GgF index was found to be useful for preliminary diagnosis of the hepatic neoplasm and for differentiation of similar clinical pictures of decompensated cirrhosis and primary hepatic carcinoma.


Rapid, transcript-specific changes in splicing in response to environmental stress.
While the core splicing machinery is highly conserved between budding yeast and mammals, the absence of alternative splicing in Saccharomyces cerevisiae raises the fundamental question of why introns have been retained in approximately 5% of the 6000 genes. Because ribosomal protein-encoding genes (RPGs) are highly overrepresented in the set of intron-containing genes, we tested the hypothesis that splicing of these transcripts would be regulated under conditions in which translation is impaired. Using a microarray-based strategy, we find that, within minutes after the induction of amino acid starvation, the splicing of the majority of RPGs is specifically inhibited. In response to an unrelated stress, exposure to toxic levels of ethanol, splicing of a different group of transcripts is inhibited, while the splicing of a third set is actually improved. We propose that regulation of splicing, like transcription, can afford rapid and specific changes in gene expression in response to the environment.


The kids are alright: growth and stability in personality development from adolescence to adulthood.
This longitudinal study provides a comprehensive analysis of continuity and change in personality functioning from age 18 to age 26 in a birth cohort (N = 921) using the Multidimensional Personality Questionnaire (A. Tellegen, 1982). Data were analyzed using 4 different methods: differential continuity, mean-level change, individual differences in change, and ipsative change. Convergent evidence pointing toward personality continuity, as opposed to change, was found. The personality changes that did take place from adolescence to adulthood reflected growth in the direction of greater maturity; many adolescents became more controlled and socially more confident and less angry and alienated. Consistent with this, greater initial levels of maturity were associated with less personality change over time. The results indicate that the transition from adolescence to young adulthood is marked by continuity of personality and growth toward greater maturity.


Mixed Small-Molecule Matrices Improve Nanoparticle Dispersibility in Organic Semiconductor-Nanoparticle Films.
Controlling the dispersibility of nanocrystalline inorganic quantum dots (QDs) within organic semiconductor (OSC):QD nanocomposite films is critical for a wide range of optoelectronic devices. This work demonstrates how small changes to the OSC host molecule can have a dramatic detrimental effect on QD dispersibility within the host organic semiconductor matrix as quantified by grazing incidence X-ray scattering. It is commonplace to modify QD surface chemistry to enhance QD dispersibility within an OSC host. Here, an alternative route toward optimizing QD dispersibilities is demonstrated, which dramatically improves QD dispersibilities through blending two different OSCs to form a fully mixed OSC matrix phase.


Integrated single-cell and bulk RNA sequencing in pancreatic cancer identifies disulfidptosis-associated molecular subtypes and prognostic signature.
Pancreatic cancer (PC) is known for its high degree of heterogeneity and exceptionally adverse outcome. While disulfidptosis is the most recently identified form of cell death, the predictive and therapeutic value of disulfidptosis-related genes (DRGs) for PC remains unknown. RNA sequencing data with the follow-up information, were retrieved from the TCGA and ICGC databases. Consensus clustering analysis was conducted on patient data using R software. Subsequently, the LASSO regression analysis was conducted to create a prognostic signature for foreseeing the outcome of PC. Differences in relevant pathways, mutational landscape, and tumor immune microenvironment were compared between PC samples with different risk levels. Finally, we experimentally confirmed the impact of DSG3 on the invasion and migration abilities of PC cells. All twenty DRGs were found to be hyperexpressed in PC tissues, and fourteen of them significantly associated with PC survival. Using consensus clustering analysis based on these DRGs, four DRclusters were identified. Additionally, altogether 223 differential genes were evaluated between clusters, indicating potential biological differences between them. Four gene clusters (geneClusters) were recognized according to these genes, and a 10-gene prognostic signature was created. High-risk patients were found to be primarily enriched in signaling pathways related to the cell cycle and p53. Furthermore, the rate of mutations was markedly higher in high-risk patients, besides important variations were present in terms of immune microenvironment and chemotherapy sensitivity among patients with different risk levels. DSG3 could appreciably enhance the invasion and migration of PC cells. This work, based on disulfidoptosis-related genes (DRGs), holds the promise of classifying PC patients and predicting their prognosis, mutational landscape, immune microenvironment, and drug therapy. These insights could boost an improvement in a better comprehension of the role of DRGs in PC as well as provide new opportunities for prognostic prediction and more effective treatment strategies.


Hybrid membrane filtration-advanced oxidation processes for removal of pharmaceutical residue.
Reports of pharmaceuticals exist in surface water and drinking water around the world, indicate they are ineffectively remove from water and wastewater using conventional treatment technologies. The potential of adverse effect of these pharmaceuticals on public health and aquatic life, also their continuos accumulation have raised the development of water treatment technologies. Hybrid treatment processes like membrane filtration and advance oxidation processes (AOPs) are likely to give rise to efficient simultaneous degradation and separation mechanisms. Conventional membrane filtration techniques can remove the majority of contaminants, but the smallest, undegraded, and stabilized pharmaceutical wastes persist in the treated water. After some 20 years, researchers have recognized the important role of AOPs in the treatment of pharmaceutical wastewater because these technologies are capable of oxidizing recalcitrant, toxic, and non-biodigradable compounds into numerous by-products and finally, inert end-products via the intermediacy of hydroxyl and other radicals. Evidently, membranes are subjected to the fouling phenomenon by the contaminants in wastewater, hence resulting in a reduction of clean water flux and increase in energy demand. In such situations, these membrane hybrid AOPs exert a complementary effect in the elimination of membrane fouling, thus enhancing the performance of the membrane. Therefore, in this review, we describe the basic aspects of the removal and transformation of certain pharmaceuticals via membranes and AOPs. In addition, information and evidences on membrane hybrid AOPs in the field of pharmaceutical wastewater treatment is also presented.


\'Ber\ing' it all.
Revealing ourselves in a psychotherapy group, as well as bearing witness to what others reveal, encourages trust among group members and increases our ability to access knowledge, our feelings, our intuitions, and our imaginations. The author, a trainee in a postgraduate group psychotherapy program, describes some of her initial experiences as a group member in a process group and as a group leader. Bearing the experience of being bare in a psychotherapy group, as a member or as a leader, is no easy task. The various meanings of bare and bear as it relates to group participation are explored in this paper through the analysis of the author's dream and through other personal and professional anecdotes.


Technical Note: A fast online adaptive replanning method for VMAT using flattening filter free beams.
To develop a fast replanning algorithm based on segment aperture morphing (SAM) for online replanning of volumetric modulated arc therapy (VMAT) with flattening filter free (FFF) beams. A software tool was developed to interface with a VMAT research planning system, which enables the input and output of beam and machine parameters of VMAT plans. The SAM algorithm was used to modify multileaf collimator positions for each segment aperture based on the changes of the target from the planning (CT/MR) to daily image [CT/CBCT/magnetic resonance imaging (MRI)]. The leaf travel distance was controlled for large shifts to prevent the increase of VMAT delivery time. The SAM algorithm was tested for 11 patient cases including prostate, pancreatic, and lung cancers. For each daily image set, three types of VMAT plans, image-guided radiation therapy (IGRT) repositioning, SAM adaptive, and full-scope reoptimization plans, were generated and compared. The SAM adaptive plans were found to have improved the plan quality in target and/or critical organs when compared to the IGRT repositioning plans and were comparable to the reoptimization plans based on the data of planning target volume (PTV)-V100 (volume covered by 100% of prescription dose). For the cases studied, the average PTV-V100 was 98.85% ± 1.13%, 97.61% ± 1.45%, and 92.84% ± 1.61% with FFF beams for the reoptimization, SAM adaptive, and repositioning plans, respectively. The execution of the SAM algorithm takes less than 10 s using 16-CPU (2.6 GHz dual core) hardware. The SAM algorithm can generate adaptive VMAT plans using FFF beams with comparable plan qualities as those from the full-scope reoptimization plans based on daily CT/CBCT/MRI and can be used for online replanning to address interfractional variations.


Prevalence of hypertension in adults with intellectual disability in the Netherlands.
Literature on the prevalence of hypertension in people with intellectual disability (ID) is mostly based on file studies or on measurements limited to the age group below 50 years. We measured and calculated the prevalence of hypertension in adults with ID and studied the distribution of hypertension in relation to age, gender, diagnosis of Down's syndrome and level of ID. In an observational cross-sectional study, standardized blood pressure measurements were obtained from 258 randomly selected adult clients of three Dutch care providers for people with ID. Hypertension was defined as a mean systolic blood pressure above 140 mm Hg on repeated measurements. The overall prevalence rate of hypertension was 17.4% (95% CI 12.28-22.46). This was comparable to the prevalence in the general Dutch population. No accurate blood pressure measurement could be performed in 28.4% of people with severe and profound ID owing to repetitive physical activity or resistance. Hypertension was significantly related to older age and absence of Down's syndrome; no correlation with gender or level of ID could be shown. The risk factor hypertension should be detected and treated in the same manner as in the general population following national guidelines.


Longitudinal Association between Obesity and Dental Caries in Adolescents.
To investigate the longitudinal association between obesity and dental caries among adolescents. The present cohort study was conducted among a random sample of 12-year-old adolescents in Hong Kong. Two rounds of follow-up were performed when the participants were aged 15 and 18 years. A total of 668 participants were included at age 12 years, and 282 of them completed all 3 phases of data collection. Body mass index, waist circumference, waist-to-hip (WHR) ratio, waist-to-height ratio, and triceps skinfold thickness were measured as indices of obesity. Dental caries were assessed by the number of decayed, missing, and filled permanent teeth (DMFT). The percentage of underweight adolescents increased significantly from 6.0% to 23.8% during the observation period (P <.001). Body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio were related to frequency of tooth brushing at age 15 and 18 years. The prevalence of dental caries was 25.5%, 53.2%, and 62.1% at 12, 15 and 18 years, respectively. At age 18 years, mean DMFT of participants whose WHR at age 15 years was below the median value was 0.707 times (ie, 29.3%) lower than the DMFT of those whose WHR was above the median (P = .028). Participants with greater DMFT at age 15 demonstrated significantly increased probability of having WHR above the median (OR 1.135; 95% CI 1.01-1.28; P = .041) at age 18 years. There is longitudinal association between central obesity and dental caries experience among adolescents aged 15-18 years.


Controlling oscillator coherence by delayed feedback.
We demonstrate that the coherence of a noisy or chaotic self-sustained oscillator can be efficiently controlled by the delayed feedback. We develop a theory of this effect, considering noisy systems in the Gaussian approximation. We obtain a closed equation system for the phase diffusion constant and the mean frequency of oscillation. For weak feedback and strong noise, the theory is in good agreement with the numerics. We discuss possible applications of the effect for the synchronization control.


Current Trends in Antifungal Prophylaxis for High-Risk Neonates in Neonatal Intensive Care Units in India: A Nationwide Survey.
Background Prophylactic antifungals are often used in high-risk babies in neonatal intensive care units (NICUs) to reduce invasive fungal infections (IFIs). However, existing guidelines regarding prophylactic antifungal usage do not clearly define the high-risk population. This study aimed to assess the practices related to prophylactic antifungal use in NICUs in India. Methods For this cross-sectional study, an online structured questionnaire was completed by neonatologists who worked in level 3 NICUs in 12 states in India during the period June 2022 to August 2022. Results Data from 151 NICUs were analyzed. 71.7% of respondents were from private hospitals, and 28.3% were from government hospitals. Nearly one-fourth of the units (28.5%) used antifungal prophylaxis in all extremely low birth weight (ELBW) babies, while another one-fourth (25.8%) used a case-based approach. The remaining NICUs (45.7%) did not use prophylactic antifungals. Among the users, the preferred antifungal was fluconazole; 3 mg/kg and 6 mg/kg were the dosage regimens used. The commonly used interval for administering fluconazole was 72 hours (69.2% of units). The intravenous route was the preferred route of administration (84.1%). Factors that influenced the non-users were the low incidence of fungal infections in their NICUs and concern about the development of resistance. It was noted that the users felt strongly about the need for further recommendations from pediatric societies and more studies on the efficacy of antifungals. Conclusion There is considerable variation in the use of prophylactic antifungals across NICUs in India. Among the users, uniformity in the choice of antifungal and interval of administration was observed. Further recommendations from pediatric societies, including the definitions of neonates at-risk of fungal infections, are required to ensure consistency in practice and help clinicians decide whether or not to use prophylactic antifungals.


Synthesis and antibacterial evaluation of 1,2,3,4-tetrahydro-4-oxo-1,8-naphthyridine-3-carboxylic acid esters, carbonitriles, and carboxamides.
A series of 1,2,3,4-tetrahydro-4-oxo-1,8-naphthyridine-3-carboxylic acid esters, carbonitriles, and carboxamides (2a-k) was synthesized and initially evaluated (dose range 50-400 mg/kg) in mice infected with Escherichia coli. Only two derivatives, the ethyl and butyl esters of 1-ethyl-1,2-dihydro-4-hydroxy-7-methyl-1,8-naphthyridine-3-carboxylic acid, protected the animals against E. coli and several other gram-negative bacterial pathogenic infections. A pro-drug type of mechanism appears to be operable since neither agent showed in vitro activity.


Concentration of polycyclic aromatic hydrocarbons (PAHs) in moss (Hypnum cupressiforme) from Hungary.
Mosses of the species Hypnum cupressiforme were collected from different parts of Hungary to investigate the air quality of the region. The concentrations of polycyclic aromatic hydrocarbons (PAHs) in species were determined. Low molecular weight PAHs (up to three ring compounds) contribute more than 99% to the concentrations of PAHs in Moss samples. The pattern of PAHs suggests local sources rather than long-range transport of contamination in the air. Possible local sources are industrial, urban, and traffic activities. The results indicate incomplete combustion of fuel is largely responsible for the air quality of the area.


Availability of folates from some foods.
Availability of folic acid from seven commonly used Indian foods and from yeast was studied in normal human subjects. The method consisted of measuring urinary excretion of folate after the ingestion of a known amount of food folate. The mean availiability of folic acid from different foods was more than 50%, except from brewer's yeast wherein approximately only 10% of folate was available.


Conscious and unconscious proportion effects in masked priming.
The global neuronal workspace theory [Dehaene, S., & Naccache, L. (2001). Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework. Cognition, 79, 1-37.] proposes that it is impossible for an unconscious stimulus to be used strategically to enhance task performance (bottom-up effect), while a fully consciously perceived stimulus can be used to improve task performance (top-down effect). Two experiments were designed to investigate these hypotheses. In a first experiment we investigated whether a manipulation of the proportion of Arabic/number word targets had a top-down effect. Since the subjects were fully aware of the target, we expected that this manipulation could be used to enhance task performance. In a second experiment we determined whether a manipulation of the proportion of Arabic/number word primes had a bottom-up effect. Since the subjects were unaware of the prime, we hypothesized that they would be unable to use the manipulation to enhance task performance and therefore the manipulation would have no effect. Both hypotheses were largely confirmed.


Dot-in-Circle Sign - A Diagnostic MRI Sign for "Madura Foot".
Mycetoma is a slowly progressive localised, granulomatous, subcutaneous tissue infection common among adult males aged 20 - 50 years. The causing agents include both bacteria (actinomycetoma) and fungi (eumycetoma). This chronic infection was described in literature as Madura foot and eventually mycetoma, due to its etiology. Early clinical diagnosis before the appearance of sinuses and grains (aggregates of organism surrounded by granulation tissue, which are discharged from the draining sinuses) is difficult. Early diagnosis is important due to the therapeutic implications. Although biopsy and microbiological cultures provide definitive diagnosis. Delay in diagnosis may lead to amputation of the affected part. The recently described "dot-in-circle" sign on magnetic resonance imaging (MRI) is easy to recognise and highly specific. We present a case of histologically proven mycetoma with characteristic MRI features.


[Safety of blood transfusion at the international level. The role of WHO].
Blood safety is an international public health challenge, particularly since the emergence of HIV AIDS. Recognizing the gross disparities between countries in the adequacy of national blood supplies and the risks arising from poorly organized services, particularly in developing countries, the World Health Organization has developed a global strategy for blood safety and availability. Dr N. Dhingra, coordinator, blood transfusion safety, WHO Headquarters, and Dr V. Hafner, focal point for blood safety in the WHO regional office for Europe, present the main features of this strategy: well-organized, nationally coordinated blood transfusion services with quality systems in all areas; the collection of blood only from voluntary non-remunerated blood donors from low-risk populations; the quality-assured testing of all donated blood; the safe and appropriate use of blood and blood products; and global collaboration for blood safety. WHO's programs, some difficulties encountered and outcomes are also described in this article.


Serum enzymes; variations of activity in disease of muscle.
In a study of 58 patients with various diseases of muscle or of the neuromuscular system, the serum activity of various enzymes was measured. Abnormal elevation of serum activities of aldolase, lactic dehydrogenase and, to a lesser extent, glutamic-oxalacetic transaminase and phosphohexose isomerase, was an almost constant feature in patients with progressive muscular dystrophy. These elevations were very frequent in dermatomyositis, common in acute cerebral vascular accidents, and rarely seen in other neurological disorders. Abnormal serum activity of iso-citric dehydrogenase was not observed in the course of the present study. Supplementary protein feeding of patients with muscular dystrophy had no effect on serum enzyme activity, no consistent effect on urinary creatine excretion and no effect on the strength of the patient or the course of the disease. Dystrophic muscles from a dystrophic strain of mice showed a decrease in activity of lactic dehydrogenase and aldolase below that of control muscle and an increase of iso-citric dehydrogenase activity. These findings, taken with the differences in serum activities of lactic dehydrogenase, aldolase and isocitric dehydrogenase in the dystrophic animals, support the conclusion that dystrophic animals handle these soluble enzymes in quite different ways.


Correlation between surface free energy and surface constitution.
Self-assembled monolayers (SAMs) of alkylsiloxanes on elastomeric PDMS (polydimethylsiloxane) were used as model systems to study interactions between surfaces. Surface free energies (gammasv) of these chemically modified surfaces were estimated by measuring the deformations that resulted from the contact between small semispherical lenses and flat sheets of the elastomer under controlled loads. The measured surface free energies correlated with the surface chemical compositions of the SAMs and were commensurate with the values estimated from the measurements of contact angles. This study provides direct experimental evidence for the validity of estimates of the surface free energies of low-energy solids obtained from contact angles.


Effects of exogenous zinc on the physiological characteristics and enzyme activities of Passiflora edulis Sims f. edulis seedlings.
Passionflower (Passiflora edulis Sims) is widely distributed in tropical and subtropical areas for edible, medicinal and skin care product processing, and the market demand is large. Zinc (Zn) is a necessary trace element for plant growth and development. In many countries, the content of Zn in soil is low and/or bioavailability is low. The exogenous application of Zn has become a common agronomic measure in agriculture. However, the effect of Zn on the physiological characteristics and enzyme activity of passionflower seedlings is not clear. In this study, pot experiments were conducted to analyse the effects of different concentrations of Zn (0, 200, 400, 800 mg kg-1) on the plant growth, photosynthetic pigments, osmotic regulators, membrane system and antioxidant enzyme system of purple passionflower (Passiflora edulis Sims f. edulis) seedlings, and Pearson correlation and principal component analyses were performed. The results showed that (1) the 200 mg kg-1 Zn treatment increased the contents of chlorophyll a (37.65%), chlorophyll b (41.22%), chlorophyll a+b (38.59%) and carotenoids (29.74%). The value of chlorophyll a/b changed little and had no effect on leaf growth. (2) The contents of proline (Pro) and malondialdehyde (MDA) in P. edulis Sims f. edulis seedlings treated with 400 mg kg-1 Zn increased significantly by 116.84% and 42.69%, respectively. The activities of catalase (CAT) and peroxidase (POD) increased by 16.82% and 18.70%, respectively. Superoxide dismutase (SOD), leaf area (LA), leaf perimeter (LP) and leaf width (LW) decreased significantly by 47.20%, 19.75%, 8.32% and 11.97%, respectively. (3) 800 mg kg-1 Zn significantly increased the contents of Pro (202.56%) and MDA (26.7%) and the activities of CAT (16.00%) and POD (67.00%), while the soluble sugar (SS), SOD, LA, LP and LW decreased significantly by 36.67%, 32.86%, 23.36%, 8.32% and 11.18%, respectively. (4) There was a significant positive correlation between Pro and photosynthetic pigments and between SOD and leaf growth and a significant negative correlation between POD and SS and between SOD and MDA. (5) A low concentration (200 mg kg-1) of Zn promoted the growth of P. edulis Sims f. edulis seedlings and allowed stress caused by high Zn concentrations to be tolerated. The results of this study can provide a reference for the application of Zn fertilizer to P. edulis Sims f. edulis.


Cloning and expression of selected ABC transporters from the Arabidopsis thaliana ABCG family in Pichia pastoris.
Phytohormones play a major role in plant growth and development. They are in most cases not synthesized in their target location and hence need to be transported to the site of action, by for instance ATP-binding cassette transporters. Within the ATP-binding cassette transporter family, Pleiotropic Drug Resistance transporters are known to be involved in phytohormone transport. Interestingly, PDRs are only present in plants and fungi. In contrast to fungi, there are few biochemical studies of plant PDRs and one major reason is that suitable overexpression systems have not been identified. In this study, we evaluate the expression system Pichia pastoris for heterologous overexpression of PDR genes of the model plant Arabidopsis thaliana. We successfully cloned and expressed the potential phytohormone transporters PDR2 and PDR8 in P. pastoris. Sucrose gradient centrifugation confirmed that the overexpressed proteins were correctly targeted to the plasma membrane of P. pastoris and initial functional studies demonstrated ATPase activity for WBC1. However, difficulties in cloning and heterologous overexpression might be particular obstacles of the PDR family, since cloning and overexpression of White Brown Complex 1, a half-size transporter of the same ABCG subfamily with comparable domain organization, was more easily achieved. We present strategies and highlight critical factors to successfully clone plant PDR genes and heterologously expressed in P. pastoris.


Isolation and culture of human muscle-derived stem cells able to differentiate into myogenic and neurogenic cell lineages.
Skeletal-muscle-derived stem cells seem to be a distinct population of immature progenitors of satellite cells, but their functional properties remain unclear, especially in human adult tissue. We investigated their differentiation in samples of skeletal muscle obtained from adults undergoing cardiovascular surgery. Samples were obtained from the brachioradialis muscle of 12 patients in whom the radial artery was the conduit for myocardial revascularisation. The stem cells were isolated by a procedure similar to that used for rat gastrocnemius and cultured in medium optimised for growth of neural stem cells. Cytometry was used for phenotypic characterisation and immunocytochemistry and RT-PCR to assess differentiation. Immunohistochemistry was used to examine engraftment of skeletal-muscle-derived stem cells into injured rat spinal cord. The skeletal-muscle stem cells consisted of two distinct types: one with the typical spindle morphology of satellite cells, the other of rounded cells. Some cultures could be maintained for longer than 6 months. The cells were mainly positive for desmin and to a lesser extent CD105, vimentin, and AC133/CD133, but negative for FLK-1/KDR, CD34, CD31, CD45, von Willebrand factor, Ve-cadherins, and BCL2. After in-vitro differentiation, the cells were able to organise skeletal-muscle fibres and stained positively for striated-muscle actin, smooth-muscle actin, and desmin. Moreover, they differentiated into astrocytes and neurons, as confirmed by positive staining for characteristic proteins. Adult human skeletal muscle includes a population of progenitor stem cells that can generate cells of the same lineage and cells with neurogenic properties. Muscle may therefore be a tissue source for the isolation of pluripotent stem cells for development of cell-based therapies for human myogenic and neurogenic diseases.


Glucose-6 phosphate dehydrogenase deficiency and psychotic illness.
Mr. T, a 28-year-old unmarried male, a diagnosed case of Glucose-6 Phosphate Dehydrogenase (G6PD) deficiency since childhood, presented with 13 years of psychotic illness and disturbed biological functions. He showed poor response to antipsychotics and mood stabilizers and had three prior admissions to Psychiatry. There was a family history of psychotic illness. The General Physical Examination and Systemic Examination were unremarkable. Mental Status Examination revealed increased psychomotor activity, pressure of speech, euphoric affect, prolixity, delusion of persecution, delusion of grandiosity, delusion of control, thought withdrawal and thought insertion, and second and third person auditory hallucinations, with impaired judgment and insight. A diagnosis of schizophrenia paranoid type, with a differential diagnosis of schizoaffective disorder manic subtype, was made. This case is being reported for its rarity and atypicality of clinical presentation, as well as a course of psychotic illness in the G6PD Deficiency state,with its implications on management.


Children's mental health during the COVID-19 pandemic: a population-based cohort study in the United States.
Examine children's mental health symptoms, including changes during the COVID-19 pandemic. The COVID Experiences Surveys, designed to be representative of the U.S. household population, were administered online to parents of children aged 5-12 years (wave 1 (W1), October-November 2020, n = 1561; wave 2 (W2), March-May 2021, n = 1287). We modeled changes in children's symptoms of anxiety, depression, and psychological stress and examined associations between demographic characteristics, COVID-19 related experiences, and protective factors with symptoms across both waves using generalized estimating equations. Based on parent-report, children's symptoms of anxiety and depression decreased from W1 to W2 (Δ t-score anxiety = -1.8 [95% confidence intervals (CI): -2.5, -1.0]; Δ t-score depression = -1.0 [CI: -1.7, -0.3]). Psychological stress remained consistent. Across waves, older children and children with an emotional, mental, developmental, behavioral, physical, or medical condition were more likely to have specific poor mental health symptoms. Poor mental health symptoms were more likely among children with several contextual stressors (e.g., economic stress, parental emotional strain) and less likely among children with protective factors (e.g., daily routines, neighborhood cohesion). Establishing programs that support mental health, improving access to mental health services, and fostering collaborations to advance children's mental health is important.


Deformity correction planning for hindfoot, ankle, and lower limb.
Many patients with foot and ankle deformities have concurrent deformities (osseous and soft tissue), with or without limb length discrepancies. Lower extremity deformities and limb length discrepancies typically result from trauma, congenital abnormality, avascular necrosis, previous surgery, nonunion, and malunion. Limb deformity correction requires extensive surgical experience because many considerations and factors apply to realignment. The considerations and factors regarding realignment are highlighted throughout this article.


Global role of the protein kinase Gcn2 in the human pathogen Candida albicans.
The pathogen Candida albicans responds to amino acid starvation by activating pseudohyphal development and the expression of amino acid biosynthetic genes (GCN response). In Saccharomyces cerevisiae, the GCN response is dependent on Gcn2, which regulates the translation of the transcription factor Gcn4. Therefore, we examined the role of Gcn2 in C. albicans by using molecular, cellular, and genomic approaches. We show that C. albicans GCN2 encodes an eIF2alpha kinase, like its S. cerevisiae homologue. However, GCN4 appears to be regulated mainly at the transcriptional level in C. albicans. Furthermore, the inactivation of C. albicans Gcn2 only partially attenuates growth under amino acid starvation conditions and resistance to the histidine analogue 3-aminotriazole. Our comparison of the Gcn4 and Gcn2 regulons by transcript profiling reinforces the view that Gcn2 contributes to, but is not essential for, the activation of general amino acid control in C. albicans.


Nature of atomic bonding and atomic structure in the phase-change Ge2Sb2Te5 glass.
Using electronic structure calculations, we demonstrate a global valence alternation in the amorphous Ge2Sb2Te5, a prototype phase-change alloy for data storage. The resulting p bonding profoundly influences the local atomic structure, leading to right-angle components similar to those in the crystalline counterpart of this chalcogenide glass. The dominance of p bonding is revealed by (i) distributions of the coordination number (CN) and the bond angle, for truly bonded atoms determined based on the electron localization function, and (ii) a direct evaluation of the p (and s) orbital occupation probability for the CN=3 Ge atoms that form 90 degree bonds with neighbors.


Ebola, Zika, Corona…What Is Next for Our World?
In the past century, there have been several pandemics. Within the context of global health, these pandemics have often been viewed from the lens of determinants such as population, poverty, and pollution. With an ever-changing world and the COVID-19 pandemic, the current global determinants of public health need to be expanded. In this editorial, we explore and redefine the major determinants of global public health to prevent future pandemics. Policymakers and global leaders should keep at heart the determinants suggested hereby in any planning, implementation, and evaluation of efforts to improve global public health and prevent pandemics.


Hydrogen bond network between amino acid radical intermediates on the proton-coupled electron transfer pathway of E. coli α2 ribonucleotide reductase.
Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides in all organisms. In all Class Ia RNRs, initiation of nucleotide diphosphate (NDP) reduction requires a reversible oxidation over 35 Å by a tyrosyl radical (Y122•, Escherichia coli) in subunit β of a cysteine (C439) in the active site of subunit α. This radical transfer (RT) occurs by a specific pathway involving redox active tyrosines (Y122 ⇆ Y356 in β to Y731 ⇆ Y730 ⇆ C439 in α); each oxidation necessitates loss of a proton coupled to loss of an electron (PCET). To study these steps, 3-aminotyrosine was site-specifically incorporated in place of Y356-β, Y731- and Y730-α, and each protein was incubated with the appropriate second subunit β(α), CDP and effector ATP to trap an amino tyrosyl radical (NH2Y•) in the active α2β2 complex. High-frequency (263 GHz) pulse electron paramagnetic resonance (EPR) of the NH2Y•s reported the gx values with unprecedented resolution and revealed strong electrostatic effects caused by the protein environment. (2)H electron-nuclear double resonance (ENDOR) spectroscopy accompanied by quantum chemical calculations provided spectroscopic evidence for hydrogen bond interactions at the radical sites, i.e., two exchangeable H bonds to NH2Y730•, one to NH2Y731• and none to NH2Y356•. Similar experiments with double mutants α-NH2Y730/C439A and α-NH2Y731/Y730F allowed assignment of the H bonding partner(s) to a pathway residue(s) providing direct evidence for colinear PCET within α. The implications of these observations for the PCET process within α and at the interface are discussed.


Prevalence of Comorbidities in Active and Reserve Service Members Pre and Post Traumatic Brain Injury, 2017-2019.
To understand the prevalence of comorbidities associated with traumatic brain injury (TBI) patients among active and reserve service members in the U.S. Military. Active and reserve SMs diagnosed with an incident TBI from January 2017 to October 2019 were selected. Nineteen comorbidities associated with TBI as identified in the literature and by clinical subject matter experts were described in this article. Each patient's medical encounters were evaluated from 6 months before to 2 years following the initial TBI diagnoses date in the Military Data Repository, if data were available. Time-to-event analyses were conducted to assess the cumulative prevalence over time of each comorbidity to the incident TBI diagnosis. We identified 47,299 TBI patients, of which most were mild (88.8%), followed by moderate (10.5%), severe (0.5%), and of penetrating (0.2%) TBI severity. Two years from the initial TBI diagnoses, the top five comorbidities within our cohort were cognitive disorders (51.9%), sleep disorders (45.0%), post-traumatic stress disorder (PTSD; 36.0%), emotional disorders (22.7%), and anxiety disorders (22.6%) across severity groups. Cognitive, sleep, PTSD, and emotional disorders were the top comorbidities seen within each TBI severity group. Comorbidities increased pre-TBI to post-TBI; the more severe the TBI, the greater the prevalence of associated comorbidities. A large proportion of our TBI patients are afflicted with comorbidities, particularly post-TBI, indicating many have a complex profile. The military health system should continue tracking comorbidities associated with TBI within the U.S. Military and devise clinical practices that acknowledge the complexity of the TBI patient.


Cytogenetic remission with imatinib therapy in hypereosinophilic syndrome with trisomy 8 and resolution of severe cardiac dysfunction.
We report a 50-year-old patient with idiopathic hypereosinophilic syndrome with trisomy 8 who experienced a complete and durable hematological and cytogenetic remission with low-dose imatinib therapy. He also had a significant reversal of cardiac dysfunction with a reduction in cardiac hypertrophy, resolution of pericardial effusion and mitral and tricuspid regurgitation. He remained in remission 3 years after therapy.