tRNA Dysregulation in Neurodevelopmental and Neurodegenerative Diseases.
Transfer RNAs (tRNAs) decode messenger RNA codons to peptides at the ribosome. The nuclear genome contains many tRNA genes for each amino acid and even each anticodon. Recent evidence indicates that expression of these tRNAs in neurons is regulated, and they are not functionally redundant. When specific tRNA genes are nonfunctional, this results in an imbalance between codon demand and tRNA availability. Furthermore, tRNAs are spliced, processed, and posttranscriptionally modified. Defects in these processes lead to neurological disorders. Finally, mutations in the aminoacyl tRNA synthetases (aaRSs) also lead to disease. Recessive mutations in several aaRSs cause syndromic disorders, while dominant mutations in a subset of aaRSs lead to peripheral neuropathy, again due to an imbalance between tRNA supply and codon demand. While it is clear that disrupting tRNA biology often leads to neurological disease, additional research is needed to understand the sensitivity of neurons to these changes.


Interconnected or disconnected? Promotion of mental health and prevention of mental disorder in the digital age.
To date there have been few peer-reviewed studies on the feasibility, acceptability and effectiveness of digital technologies for mental health promotion and disorder prevention. Any evaluation of these evolving technologies is complicated by a lack of understanding about the specific risks and possible benefits of the many forms of internet use on mental health. To adequately meet the mental health needs of today's society, psychiatry must engage in rigorous assessment of the impact of digital technologies.


Effects of hyperbaric and hyperoxic conditions on the disposition of drugs: theoretical considerations and a review of the literature.
1. Hyperbaric or hyperoxic or both conditions may affect the disposition of drugs by (1) changes in the catalytic activity of drug metabolizing enzymes, (2) hemodynamic changes and (3) changes in membrane permeability, affecting drug distribution. 2. In isolated microsome preparations from rat liver, the metabolism rate of aniline, but not of amidopirin, is reduced by hyperoxia. In vivo, the clearance of salicylic acid is enhanced in the dog at 2.8 ATA and 100% O2, but not at 6 ATA and air, for reasons that are still unknown. The disposition of theophylline, pentobarbital or pethidine is not affected in dogs by hyperbaric or hyperoxic conditions. 3. In human volunteers, hyperbaric or hyperoxic or both conditions do not affect the disposition of gentamycin (2.4 bar, 100% O2), caffeine or lidocaine (2.5 bar, 100% O2). 4. In conclusion, a single exposure to hyperbaric or hyperoxic conditions does not seem to affect single-dose pharmacokinetics of drugs eliminated by the kidney (gentamycin) or by the liver with a capacity-limited clearance (pentobarbital, theophylline, caffeine) or with a perfusion-limited clearance (pethidine, lidocaine). The enhancement of salicylic acid clearance in dogs under hyperoxic conditions remains unclear.


External Iliac Artery Laceration Caused by Hip Prosthesis Migration.
Hip arthroplasty is a common and safe intervention in orthopedic surgery. However, the proximity of this joint to large vessels makes the occurrence of vascular injury a rare but serious and possibly lethal complication of this surgical technique. Acute vascular injuries in the context of a hip arthroplasty have variable etiologies and clinical presentations, and are more common in revision surgeries and in situations of medial intrapelvic migration and of chronic infection of the hip prosthesis. In the present article, the authors present a case of acute and late major vascular complication in the context of hip arthroplasty revision. The patient developed an acute laceration of the external iliac artery caused by chronic and progressive medial intrapelvic acetabular migration of the hip prosthesis associated with chronic infection.


Structural role of osteocalcin and osteopontin in energy dissipation in bone.
Non-collagenous proteins are a vital component of bone matrix. Amongst them, osteocalcin (OC) and osteopontin (OPN) hold special significance due to their intimate interaction with the mineral and collagenous matrix in bone. Both proteins have been associated with microdamage and fracture, but their structural role in energy dissipation is unclear. This study used bone tissue from genetic deficient mice lacking OC and/or OPN and subjected them to a series of creep-fatigue-creep tests. To this end, whole tibiae were loaded in four-point bending to 70% stiffness loss which captured the three characteristic phases of fatigue associated with initiation, propagation, and coalescence of microdamage. Fatigue loading preceded and followed creep tests to determine creep and dampening parameters. Microdamage in the form of linear microcracks and diffuse damage were analyzed by histology. It was shown that OC and OPN were 'activated' following stiffness loss associated with fatigue damage where they facilitated creep and dampening parameters (i.e. increased energy dissipation). More specifically, post-fatigue creep rate and dampening were significantly greater in wild-types (WTs) than genetic deficient mice (p < 0.05). These results were supported by microdamage analysis which showed significant increase in creep-associated diffuse damage formation in WTs compared to genetic deficient groups (p < 0.05). Based on these findings, we propose that during local yield events, OC and OPN rely on ionic interactions of their charged side chains and on hydrogen bonding to dissipate energy in bone.


INDO/SCF-CI calculations and structural spectroscopic studies of some complexes of 4-hydroxyacetanilide.
The electronic energies among different possible structures of 4-hydroxyacetanilide (paracetamol) (PA) molecule, were calculated using INDO method and it has been concluded that its structure has C(s) point group symmetry of the cis-form. The ionization potential, electron affinity, dipole moment and binding energy have been calculated. The calculated electronic transitions of the cis-form of PA using SCF-CI method have good coincidence with the electronic absorption spectrum. The temperature effect on the electronic spectrum of PA confirms the presence of one conformer only. The electronic spectra of PA compound were studied in different polar- and non-polar solvents and the hydrogen bonding as well as the orientation energies of the polar solvents were determined from the mixed solvents studies. Complexes of PA with various metal ions such as, Cu(II), Zn(II) or Fe(II) ions of ratio 2:1, respectively, have been prepared and their structure has been confirmed by elemental analysis, atomic absorption spectra, IR spectra and (1)H NMR spectra and finally it can be concluded that the structure of the complexes has C2h point group symmetry in which two PA molecules are chelated to any one of the metal ions, Cu(II), Zn(II) and Fe(II) ions.


Successful vitrification of mouse ovaries using less-concentrated cryoprotectants with Supercool X-1000 supplementation.
The purpose of our study was to investigate the feasibility of using less-concentrated cryoprotectants supplemented with ice blocker Supercool X-1000 to vitrify ovarian tissues. Mouse ovaries were cryopreserved in different concentrations of vitrification solution alone or with Supercool X-1000, and fresh non-frozen ovaries were used as control. The proportions of morphological normality of follicles, normal GCs in follicular fluids and developing to blastocysts were higher in 12.5% ethylene glycol (EG) + 12.5% dimethylsulfoxide (DMSO) with Supercool X-1000 than those of treated in 10% EG + 10% DMSO or 15% EG + 15% DMSO alone or with Supercool X-1000. In conclusion, the inclusion of Supercool X-1000 in less-concentrated vitrification solution was effective to improve the efficiency and efficacy of cryopreservation of ovarian tissues.


Hemispheric differences over frontal theta-band power discriminate between stimulus- versus memory-driven saccadic eye movement.
Although several electrophysiological studies have demonstrated the role of theta band during the execution of different visuospatial attention tasks, this study is the first to directly investigate the role of theta power during the planning, execution and cognitive control of saccadic eye movements (SEMs). The current study aims at addressing this issue by investigating absolute theta power over the frontal cortex during the execution of random and fixed SEMs. Twelve healthy volunteers, performed two tasks involving different conditions in the planning, execution and cognitive control of SEMs while their brain activity pattern was recorded using quantitative electroencephalography. We found an interaction between SEM condition and electrode (F3, F4, Fz), and a main effect of time point and electrode. Our key finding revealed that the stimulus presentation induces different patterns over frontal theta power increase between the left and right hemisphere. We conclude that right and left frontal regions are an important factor to discriminate between memory- versus stimulus-driven SEMs, and speculate on their different contributions to visuospatial attention.


Release of substance P from the enteric nervous system: direct quantitation and characterization.
A dynamic system has been developed in which in vitro release of substance P (SP) from two longitudinal muscle-myenteric plexus strips from the guinea-pig ileum is obtained during continuous superfusion and measured directly by using a highly sensitive radioimmunoassay specific for SP. Electrical stimulation (0.5-40 Hz) produced a marked increase in the rate of release of SP. The magnitude of the increase in the rate of electrically evoked release was dependent on the frequency of stimulation but this dependence did not appear to be linear over the entire range tested. Electrically evoked release elicited by 20 Hz stimulation was reduced by 95% by omitting Ca++ from the superfusion buffer or by cooling the preparation to 3 degrees C. Pretreatment with tetrodotoxin (1 micrograms/ml for 15 min) substantially reduced the magnitude of the increase in the rate of release of SP but did not abolish it. Despite tetrodotoxin pretreatment, a significant portion (53%) of the electrically induced increase in SP release remained. The ability of electrical stimulation to release SP from the myenteric plexus in amounts sufficient to produce a physiological response in a Ca++- and temperature-dependent fashion in combination with data provided by indirect pharmacological experiments strongly suggests that SP functions as a neurotransmitter in the enteric nervous system.


Toward a steady-state pore limit electrophoresis dimension for native proteins in two-dimensional polyacrylamide gel electrophoresis.
Polyacrylamide gel electrophoresis in linear pore gradients (4.8 to 48% T, 5% CBis) provides for migration arrest, in a practical sense, after about 5000 Vh for proteins of 290 and 450 kDa, but not for smaller proteins over 20,000 Vh. The arrest is not due to inadequate field strength nor is it caused by water redistribution within pore gradient gels. The possibility is being discussed that exponential pore gradients, and a higher or a lower degree of crosslinking suggested by the literature may be remedies for the present failure to arrest the migration of smaller proteins.


Bone metabolism in the osteopetrotic rat mutation microphthalmia blanc.
We have examined parameters of bone metabolism in a new mutation, microphthalmia blanc (mib), in the rat exhibiting a skeletal sclerosis at birth that improves with age. There were no significant differences in the rate of bone formation during the first postnatal month except a temporary reduction in mutants at 3 weeks that coincided with compromised nutrition at weaning. At birth the ruffled border in mutant osteoclasts was absent or poorly developed and mRNA analyses of mutant bone compared to normal bone showed significant reductions in the messages for the osteoclast-specific genes carbonic andydrase II and tartrate-resistant ATPase. These distinctive ultrastructural and molecular differences were not present 1 month later. These data show that the transient osteopetrosis in mib rats results from a perinatal reduction in ultrastructural and enzymatic features of active osteoclasts and is not complicated by elevations in bone formation. The molecular basis for both the production and resolution of these abnormalities deserves further study.


Acute myocardial ischemia enhances the vanilloid TRPV1 and serotonin 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats.
The Bezold-Jarisch reflex is characterized by a sudden bradycardia associated with hypotension induced by the activation of the vanilloid TRPV1 and serotonin 5-HT(3) receptors. This reflex is associated with several health conditions, including myocardial infarction. The aim of the present study was to elucidate the influence of acute experimental myocardial ischemia on the reflex bradycardia induced by anandamide and phenylbiguanide, agonists of the TRPV1 and 5-HT(3) receptors, respectively. In urethane-anesthetized rats, the rapid iv injection of anandamide (0.6 μmol/kg) or phenylbiguanide (0.03 μmol/kg) decreased heart rate (HR) by about 7-10% of the basal values. Myocardial ischemia (MI) was induced by ligation of the left anterior coronary artery. The agonists were injected 5 min before MI (S(1)) and 10, 20 and 30 min thereafter (S(2)-S(4)). MI potentiated the anandamide-induced reflex bradycardia by approximately 105% at S(2) and 70% at S(3) but had no effect at S(4). This amplificatory effect of MI was virtually abolished by the TRPV1 receptor antagonist capsazepine (1 μmol/kg) and was not modified by the cannabinoid CB(1) receptor antagonist rimonabant (0.1 μmol/kg). MI also amplified the reflex bradycardia elicited by phenylbiguanide by approximately 110, 60 and 90% (S(2), S(3) and S(4), respectively), and this effect was sensitive to the 5-HT(3) receptor antagonist ondansetron (3 μmol/kg). In conclusion, our results suggest that acute myocardial ischemia augments the Bezold-Jarisch reflex induced via activation of TRPV1 and 5-HT(3) receptors located on sensory vagal nerves in the heart.


Hospital-acquired influenza: a synthesis using the Outbreak Reports and Intervention Studies of Nosocomial Infection (ORION) statement.
Nosocomial influenza outbreaks occur in almost all types of hospital wards, and their consequences for patients and hospitals in terms of morbidity, mortality and costs are considerable. The source of infection is often unknown, since any patient, healthcare worker (HCW) or visitor is capable of transmitting it to susceptible persons within hospitals. Nosocomial influenza outbreak investigations should help to identify the source of infection, prevent additional cases, and increase our knowledge of disease control to face future outbreaks. However, such outbreaks are probably underdetected and underreported, making routes of transmission difficult to track and describe with precision. In addition, the absence of standardised information in the literature limits comparison between studies and better understanding of disease dynamics. In this study, reports of nosocomial influenza outbreaks are synthesised according to the ORION guidelines to highlight existing knowledge in relation to the detection of influenza cases, evidence of transmission between patients and HCWs and measures of disease incidence. Although a body of evidence has confirmed that influenza spreads within hospitals, we should improve clinical and virological confirmation and initiate active surveillance and quantitative studies to determine incidence rates in order to assess the risk to patients.


Outcomes of patients with esophageal and gastric cancer in Sri Lanka: A retrospective survival analysis.
Esophageal carcinoma is the fourth most common cancer among males and sixth most common cancer among females in Sri Lanka. Gastric cancer is less common, but its incidence is gradually rising. We conducted a retrospective analysis of survival of esophageal and gastric cancer patients treated at National Cancer Institute, Maharagama, Sri Lanka. Patients with esophageal and gastric cancer treated in three selected oncology units of the National Cancer Institute, Maharagama during 2015 and 2016 were included in the study. Data on clinical and pathological factors were extracted from clinical records. Overall survival (OS), defined as time to death or loss to follow-up, was the primary endpoint. Univariate and multivariate analyses of survival were performed using the log-rank test and Cox proportional-hazard model, respectively. The study population comprised 374 patients with a median age of 62 years (interquartile range 55-70). Majority (64%) were male and had squamous cell carcinoma (58%). In the sample, 20% were gastric cancers, while 71% were esophageal cancers, and 9% had gastro-esophageal junction tumors. The 2-year OS was 19% in patients treated with curative intent (95% confidence interval [CI] 14-26 months) with those receiving neoadjuvant chemotherapy, followed by radical surgery having the highest survival (P < 0.001, hazard ratio 0.25 [95% CI 0.11-0.56]). Median OS was 2 months (95% CI 1-2 months) in patients treated with palliative intent. Our results suggest that the outcome of patients with esophageal and gastric cancer is poor in Sri Lanka. Early detection and greater utilization of multimodality treatment could improve outcomes of these patients.


Providing a framework of principles for conceptualising the Fontan circulation.
The Fontan operation remains the final palliation for thousands of patients with complex congenital heart disease. By creating a Fontan circuit, control of cardiac output and congestion is wrested away from the ventricle and new haemodynamic forces take control. Understanding how to control the flow in the Fontan circuit will enable clinicians to improve patient management and possibly prevent future complications. CONCLUSION: This review proposes a framework of principles to conceptualise the functionality and limitations of a Fontan circulation.


Homelessness, organ donation, transplantation, and a call for equity in the United States.
While social justice is a pillar that society seeks to uphold, in the area of organ transplantation, social justice, equity, and inclusion fail in the unbefriended and undomiciled population. Due to lack of social support of the homeless population, such status often renders these individuals ineligible to be organ recipients. Though it can be argued that organ donation by an unbefriended, undomciled patient benefits the greater good, there is clear inequity in the fact that homeless individuals are denied transplants due to inadequate social support. To illustrate such social breakdown, we describe two unbefriended, undomiciled patients brought to our hospitals by emergency services with diagnoses of intracerebral haemorrhage that progressed to brain death. This proposal represents a call to action to remediate the broken system: how the inherent inequity in organ donation by unbefriended, undomiciled patients would be ethically optimized if social support systems were implemented to allow for their candidacy for organ transplantation.


Recovery of Viable Staphylococcus aureus in Corn and Green Beans Stored at Ambient Temperature.
Staphylococcus aureus was recovered from post-process inoculated commercially canned green beans after periods of up to 6 weeks of storage and from inoculated commercially canned corn after up to 26 weeks of storage under various conditions. Variance in duration of viability of the culture was apparently due to intrinsic factors of the food and presence of inoculated competing organisms. Drying of the inoculated corn had no effect on viability of the test culture, but drying shortened its length of viability in green beans.


Subthalamic nucleus deep brain stimulation does not alter growth factor expression in a rat model of stable dopaminergic deficiency.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been a highly effective treatment option for mid-to-late-stage Parkinson's disease (PD) for decades. Besides direct effects on brain networks, neuroprotective effects of STN-DBS - potentially via alterations of growth factor expression levels - have been proposed as additional mechanisms of action. In the context of clarifying DBS mechanisms, we analyzed brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels in the basal ganglia, motor and parietal cortices, and dentate gyrus in an animal model of stable, severe dopaminergic deficiency. We applied one week of continuous unilateral STN-DBS in a group of stable 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats (6-OHDASTIM) in comparison to a 6-OHDA control group (6-OHDASHAM) as well as healthy controls (CTRLSTIM and CTRLSHAM). BDNF and GDNF levels were determined via ELISAs. The 6-OHDA lesion did not result in a persistent alteration in either BDNF or GDNF levels in a model of severe dopaminergic deficiency after completion of the dopaminergic degeneration. STN-DBS modestly increased BDNF levels in the entopeduncular nucleus, but even impaired BDNF and GDNF expression in cortical areas. STN-DBS does not increase growth factor expression when applied to a model of completed, severe dopaminergic deficiency in contrast to other studies in models of modest and ongoing dopaminergic degeneration. In healthy controls, STN-DBS does not influence BDNF or GDNF expression. We consider these findings relevant for clinical purposes since DBS in PD is usually applied late in the course of the disease.


Fruit maturation patterns of Carya spp. (Juglandaceae): an intra-crown analysis of growth and reproduction.
Fruit survival patterns, from fertilization to maturation, were examined for Carya ovata and C. tomentosa in a New Jersey USA forest. We observed fruiting and shoot growth characteristics over a 3-yr period to determine: (1) the patterns of fruit survivorship (from initiation to maturity) within and among years, (2) the relationships between shoot growth, fruit initiation, and fruit survival to maturity, and (3) the influence of phytophagous insects on fruit survival. We found that within years, smaller infructescences (1-2 fruits) exhibited greater relative survivorship than larger ones (3-4 fruits); however, absolute nut production was greatest for mid-sized infructescences (2-3 fruits). Among years, fruit survivorship varied considerably within populations. Across the 3-yr period we observed average fruit survivorship to be convex, linear, and concave, respectively. Likewise, shoot characteristics (length, width, number of leaves) varied concomitantly (decreasing fruit survivorship was accompanied by decreasing shoot length and number of leaves). Within years, we found no strong relationship between shoot characteristics and infructescence size and survival. The patterns of tree-to-tree variation suggested a strong genetic basis to shoot growth and fruit maturation. However, patterns of variation within and among years also indicated a strong environmental influence on these traits as well. Natural phytophagy by insects was observed to be low (<5%); however, shoot defoliations of 10-25% were not uncommon. Experimental defoliations (ambient, 10-15%, 20-40%, and 75-100%) did not result in reduced survival to maturity. Collectively, the data suggest that year-to-year variability in shoot growth has a greater influence on fruit maturation patterns than within year fruit-shoot relations.


Insights into cell entry and intracellular trafficking of peptide and protein drugs provided by electron microscopy.
For widening the arsenal of protein and peptide therapeutics that act within cells, their cell-entry mechanisms, intracellular trafficking and distribution need to be characterized in detail. Immunofluorescence microscopy has been a prevalent tool for these studies. However, due to the limited resolution, it is often complemented with other methods. This article focuses on the perspectives of electron microscopy in tracking the intracellular delivery and trafficking of proteins, peptides and their carriers. This review introduces the electron microscopy techniques and labeling methods currently used for studying the cellular whereabouts of peptides and proteins with a focus on their intracellular trafficking. Since cell-penetrating peptides have widely been harnessed as carriers for proteins and peptides, and their usage is rapidly expanding, a particular emphasis has been placed on their applications and cell-entry mechanisms.


New oxovanadium(IV) complexes overcame drug resistance and increased in vitro cytotoxicity by an apoptotic pathway in breast cancer cells.
In order to examine the anticancer potential of oxovanadium(IV) complexes with thiosemicarbazone, two new complexes were prepared starting from 2-thenoyltrifluoroacetone-S-methylthiosemicarbazone. The complexes with tetradentate thiosemicarbazone ligand were characterized by elemental analysis, IR, ESI MS, and single-crystal X-ray diffraction analysis. Cytotoxicity on breast cancer cells, MDA-MB-231 and MCF-7, was determined by MTT assay. Cisplatin was positive control and the results were compared with those of the normal cells, HUVEC and 3T3. The complexes exhibited greater activity on cancer cells than cisplatin, but they were cytotoxic at several times higher concentrations in the healthy cells. In our study, the presence of thiophene and fluoro groups in the oxovanadium(IV) complexes with thiosemicarbazone increased greatly the cytotoxic activity of the complexes on breast cancer cells. Moreover, the complexes induced apoptosis-mediated cell death and also reduced the expression of MDR-1 or P-glycoprotein and ABCG2. As a result, the findings indicated that the complexes have selective cytotoxicity on breast cancer cells and can overcome multidrug resistance. These properties of the complexes make it possible to be a potential anticancer drug candidate for breast cancer treatment.


Excess filaggrin in keratinocytes is removed by extracellular vesicles to prevent premature death and this mechanism can be hijacked by Staphylococcus aureus in a TLR2-dependent fashion.
Filaggrin (FLG) protein is indispensable for multiple aspects of the epidermal barrier function but its accumulation in a monomeric filaggrin form may initiate premature keratinocytes death; it is unclear how filaggrin levels are controlled before the formation of storing keratohyalin granules. Here we show that keratinocyte-secreted small extracellular vesicles (sEVs) may contain filaggrin-related cargo providing a route of eliminating excess filaggrin from keratinocytes; blocking of sEV release has cytotoxic effects on those cells. Filaggrin-containing sEVs are found in plasma in both healthy individuals and atopic dermatitis patients. Staphylococcus aureus (S. aureus) enhances packaging and secretion of filaggrin-relevant products within the sEVs for enhanced export via a TLR2-mediated mechanism which is also linked to the ubiquitination process. This filaggrin removal system, preventing premature keratinocyte death and epidermal barrier dysfunction, is exploited by S. aureus which promotes filaggrin elimination from the skin that could help safeguard bacterial growth.


Effects of CYP1A2 and ADORA2A Genotypes on the Ergogenic Response to Caffeine in Professional Handball Players.
Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (-163C > A, rs762551; characterized such as "fast" (AA genotype) and "slow" caffeine metabolizers (C-carriers)) and ADORA2A (1976T > C; rs5751876; characterized by "high" (TT genotype) or "low" sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women; daily caffeine intake = 60 ± 25 mg·d-1) ingested 3 mg·kg-1·body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 × 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the -163C > A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T > C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8-4.3%, p = 0.001-0.022, effect size = 0.17-0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg·kg-1·bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.


An unusual etiology of abdominal pain in children.
The first case of cholecystitis acalculous by Cryptosporidium in onco-hematology pediatric patient was described in this work.


The Camino intracranial pressure sensor: is it optimal technology? An internal audit with a review of current intracranial pressure monitoring technologies.
To audit the reliability of the Camino intracranial pressure (ICP) sensor (Camino Laboratories, San Diego, CA) in our clinical practice as part of a continuing quality assurance program, and to assess its relative usefulness as compared with currently available ICP monitoring technologies that we reviewed. Prospective audit of ICP device reliability and function in 50 patients with head injuries. Zero drift was recorded immediately after the ICP device was removed from the patient. Dynamic frequency response bench testing of each functioning catheter from 0 to 30 Hz and static calibration testing from 0 to 100 mmHg during environmental temperature variation from 22 to 40 degrees C were carried out. Zero drift (range, -13 to 22 mmHg; median, -1 mmHg) was recorded immediately after the devices were removed from patients. Seventeen (50%) of the devices tested for zero drift had absolute drifts of at least 3 mmHg. There was no correlation between recorded zero drift and duration of monitoring (r = 0.154, P = 0.207). Five sensors (10% of those tested) failed during patient monitoring and were replaced. Static and dynamic calibration tests of the functioning sensors were within the manufacturer's specifications. However, the sensitivity of the devices to environmental temperature remains a problem. The Camino ICP sensor remains one of the most popular ICP monitoring devices for use in patients with traumatic brain injuries. However, our recent in-house assessment demonstrated the robustness of the device to be less than adequate during routine practice. In this study, more than 50% exhibited zero drift greater than 3 mmHg, which is unacceptable in a catheter tip ICP monitoring device in which zero drift and calibration cannot be checked in vivo. A review of the literature revealed that other available ICP monitoring devices may prove to be more reliable and thus more appropriate for routine clinical measurement of ICP.


Advancement in nanotechnology for treatment of rheumatoid arthritis: scope and potential applications.
Rheumatoid arthritis is a hyperactive immune disorder that results in severe inflammation in synovial joints, cartilage, and bone deterioration, resulting in immobilization of joints. Traditional approaches for the treatment of rheumatoid arthritis are associated with some limiting factors such as suboptimal patient compliance, inability to control the progression of disorder, and safety concerns. Therefore, innovative drug delivery carriers for efficient therapeutic delivery at inflamed synovial sites with better safety assessment are urgently needed to address these issues. From this perspective, nanotechnology is an outstanding alternative to traditional drug delivery approaches, and it has shown great promise in developing novel carriers to treat rheumatoid arthritis. Considering the current research and future application of nanocarriers, it is believed that nanocarriers can be a crucial element in rheumatoid arthritis treatment. This paper covers all currently available pathophysiological aspects of rheumatoid arthritis and treatment options. Future research for the reduction of synovial inflammation should focus on developing multifunction nanoparticles capable of delivering therapeutic agents with improved safety, efficacy, and cost-effectiveness to be commercialized.


Response to vincristine and Procarbazine of recurrent medulloblastomas. Report of 2 cases.
2 cases of recurrent medulloblastomas are described who both responded to vincristine alone and in combination with procarbazine. The combination of vincristine and procarbazine is discussed and recommended for chemotherapy of medulloblastomas. The effectiveness of adjuvant chemotherapy after the primary treatment should be investigated.


Imaging findings of benign peripheral nerve sheath tumor in jaw.
The aim of this study was to investigate the imaging characteristics of peripheral nerve sheath tumors (PNSTs) in the jaw. Imaging studies of 6 patients were retrospectively reviewed. Conventional radiography, computed tomography, and magnetic resonance imaging were performed in all patients. A fusiform lesion continuous with the nerve was observed in 2 cases, with the tumor arising within the inferior alveolar canal. In the other 4 cases, with the tumor arising outside the canal, the tumor had protruded and eroded into the bone. Protrusion was also present in 1 of the 2 cases, with the tumor arising within the canal. A target or fascicular sign was observed each in 1 case. A fusiform lesion continuous with the nerve and a target or fascicular sign was only present in a few cases. The PNSTs, however, showed a tendency to protrude into the bone.


Exertion-induced rhabdomyolysis with acute renal failure and disseminated intravascular coagulation in sickle cell trait.
From 1970 to 1974, among thousands of trainees seen at two large military installations who were subjected to the same physical and environmental stresses, only four recruits were hospitalized because of acute exertional rhabdomyolysis, renal failure and coagulopathy. The illness followed the performance of vigorous exercise. These four patients had sickle cell trait. In an attempt to explain this association, the data in these four cases are summarized. The hypothesis is then developed that rhabdomyolysis and endothelial damage, terminating in severe coagulopathy, may more likely occur in patients with sickle cell trait who are subjected to virorous physical exertion.


Effects of quinone derivatives on an experimental tumor.
In continuation of studies on the activity of known solid tumor inhibitors, four acetylated glycosyl derivatives of 1,4-quinones were prepared and tested against Ehrlich ascitic tumor. All four compounds significantly inhibited growth of this neoplasm. UV, IR, and mass spectra are given for the three new synthetic quinone derivatives.


Marginal zone lymphoma of the breast-A diminished role for surgery.
Primary breast lymphoma by definition is localized to one or both the breasts with or without involvement of regional lymph nodes with no other extra mammary site involvement. Role of surgery in the treatment armamentarium is less well defined. A 62year old post-menopausal lady was found to have 1.2×1.2×0.6cm mass in the left breast on diagnostic mammography. Core needle biopsy reveals marginal zone lymphoma. Complete staging work-up was performed which was negative for regional spread and metastatic foci. She was diagnosed to have a localized stage IE extra nodal low grade marginal zone lymphoma of the MALT type involving breast. She received radiotherapy to the breast and is in remission at follow up after one year. Accurate diagnosis requires adequate tissue biopsy either by a core needle or a surgical biopsy for histopathologic evaluation and immunophenotyping. Immunohistochemically the tumors are positive for pan B-cell markers (CD 19, CD 20, CD22, and CD 79a) and lack T cell markers. For stage IE Marginal zone lymphoma radiotherapy alone and for stage IIE combined chemo-radiation offers the best possible control of the disease. Progression free survival for MZL is better than diffuse large B-cell lymphoma. At present the best evidence support radiotherapy in localized disease and combined chemo-radiation in advanced disease. Role of surgery is minimal and is seen in case of diagnostic dilemma. Rarity of the diagnosis precludes large scale prospective studies making therapeutic decisions difficult and challenging.


Quinacrine is not a vital fluorescent probe for vesicular ATP storage.
Quinacrine, a fluorescent amphipathic amine, has been used as a vital fluorescent probe to visualize vesicular storage of ATP in the field of purinergic signaling. However, the mechanism(s) by which quinacrine represents vesicular ATP storage remains to be clarified. The present study investigated the validity of the use of quinacrine as a vial fluorescent probe for ATP-storing organelles. Vesicular nucleotide transporter (VNUT), an essential component for vesicular storage and ATP release, is present in very low density lipoprotein (VLDL)-containing secretory vesicles in hepatocytes. VNUT gene knockout (Vnut-/-) or clodronate treatment, a VNUT inhibitor, disappeared vesicular ATP release (Tatsushima et al., Biochim Biophys Acta Molecular Basis of Disease 2021, e166013). Upon incubation of mice's primary hepatocytes, quinacrine accumulates in a granular pattern into the cytoplasm, sensitive to 0.1-μM bafilomycin A1, a vacuolar ATPase (V-ATPase) inhibitor. Neither Vnut-/- nor treatment of clodronate affected quinacrine granular accumulation. In vitro, quinacrine is accumulated into liposomes upon imposing inside acidic transmembranous pH gradient (∆pH) irrespective of the presence or absence of ATP. Neither ATP binding on VNUT nor VNUT-mediated uptake of ATP was affected by quinacrine. Consistently, VNUT-mediated uptake of quinacrine was negligible or under the detection limit. From these results, it is concluded that vesicular quinacrine accumulation is not due to a consequence of its interaction with ATP but due to ∆pH-driven concentration across the membranes as an amphipathic amine. Thus, quinacrine is not a vital fluorescent probe for vesicular ATP storage.


[Preliminary study of the quality of life of glaucoma patients in the district of Sousse (Tunisia): Sociodemographic and clinical associations].
To assess the vision-specific quality-of-life (VS-QoL) of glaucoma patients followed at Farhat Hached university hospital, Sousse-Tunisia, and identify clinical and sociodemographic factors potentially affecting it. This was a cross-sectional study enrolling one-hundred twenty patients followed for primary open angle glaucoma (POAG). All the patients successfully responded to the Arabic version of the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ 25). Quality of life was quantified in terms of scores (0-100) and correlated with sociodemographic and clinical factors. One hundred and twenty patients were studied. The mean age was 62.38±10.68years. The global mean score (GMS) score was 70.11±18.45% ranging from 23.71 to 98%. Urban residence was associated with a better total score (P=0.01). Educational background was correlated with the subscale scores of distant activities (P=0.01), social functioning (P=0.03), physical activity limitations (P=0.01) and peripheral vision (P=0.01). The total NEI-VFQ 25 had a statistically significantly negative correlation with the duration of the glaucoma (P=0.002), the cup to disc ratio of the better and the worse eye (P<10-4), the visual acuity of the better and the worse eye (P<10-4), but not with the intraocular pressure. A higher number of glaucoma medications had a negative impact on the total score (P=0.03) and the subscales of physical activity limitations (P=0.04) and driving (P=0.002). Vision-specific quality of life of glaucoma patients, as measured by the NEI-VFQ 25, is correlated to many sociodemographic and clinical elements. QoL evaluation is an essential factor to be considered in the management of glaucoma patients. In our context, research should be directed first to the validation of a questionnaire in the local dialect.


Long-term cognitive outcomes after cerebral sinovenous thrombosis in childhood.
To assess long-term cognitive function in children after cerebral sinovenous thrombosis (CSVT). Children with CSVT, who had neuropsychological testing for intellectual ability, executive function, attention, language, or behavior, were included in a prospective observational study. Outcomes were compared with normative means using one-sample t-tests. Predictors of abnormal function were examined using logistic regression. Fifty children with CSVT were included (median age at diagnosis 2y 10mo, interquartile range 7d-6y 10mo; 35 males, 15 females). The median follow-up time was 4 years 2 months (interquartile range 2y 8mo-6y 4mo). Compared with normative means, children with CSVT had lower mean (± standard deviation) full-scale IQ, working memory, and processing speed scores (93.3±16, p=0.01; 93.6±16, p=0.04; 93.7±15.3, p=0.02 respectively). They also had lower scores in executive function, attention, and language domains. Refractory seizure at presentation was associated with a trend in behavioral problems (odds ratio [OR] 6.3, 95% confidence interval [CI] 0.9-46, p=0.07). Females were less likely to experience processing speed difficulties (OR 0.22, 95% CI 0.04-1.3, p=0.09). Incomplete recanalization was associated with a greater risk of abnormal verbal comprehension (OR 5.3, 95% CI 0.93-30.5, p=0.059). Children with CSVT as a group performed below age expectations on standardized neuropsychological tests, although there was variability across individuals and cognitive domains. Larger studies are needed to evaluate predictors of cognitive deficits in children with CSVT.


Sources of polycyclic aromatic hydrocarbons in marine sediments from southern and northern areas of the Norwegian continental shelf.
Variability in levels and sources of polycyclic aromatic hydrocarbons (PAH) in sediments from one large sea area off the coast of northern Norway ("North area", NA) have been compared to similar data from another large area off the coast of southern Norway ("South area", SA). Samples from NA were collected at the Norwegian continental shelf in south-western Barents Sea and north-eastern Norwegian Sea. Samples from SA were from the Norwegian Trench and the Skagerrak. Sediment cores have been dated, characterised by grain size distribution (GS) and organic carbon content (TOC), and the composition of PAH and geochemical biomarkers (alkanes and triterpanes) studied to provide an insight into the different sources of PAH. Generally, PAH levels are higher in sediments from SA compared to NA. A mixture of pyrogenic and petrogenic sources contribute to PAH levels in SA, while the contents of petrogenic PAH is negligible in surface sediments in NA. At some locations in NA, petrogenic PAH levels are elevated in the deepest sediment layers from pre-industrial times, indicating a natural input of petroleum through seepage. Occurrence of elevated levels of microbial hopanoids (hopenes) in the deepest sediment layers at some locations both in the north and the south indicate the presence of petroleum.


Risk factors for development of left ventricular thrombus after first acute anterior myocardial infarction-association with anticardiolipin antibodies.
Left ventricular thrombus(LVT] formation is a frequent complication in patients with acute anterior myocardial infarction(MI). LVT is associated with increased risk of embolism and higher mortality rates after acute MI. Anticardiolipin antibodies (ACA) are immunoglobulins that react with phospholipid-binding proteins interfering with the prothrombin activator complex. The effects of phospholipids on pathophysiology of cardiovascular thrombotic events are well known. In this study, we aimed to evaluate the importance of clinical and biochemical parameters including anticardiolipin antibodies on left ventricular thrombus formation after acute anterior MI. Seventy patients with a first anterior AMI were prospectively and consecutively enrolled. Patients with previous MI, autoimmune disease, collagen vascular disease and arterial or venous thrombosis history were excluded from this study. At the time of hospitalization, key demographic and clinical characteristics were collected including age, gender, ethanol intake and presence of traditional risk factors for atherosclerosis (hypertension, diabetes, smoking, hyperlipidemia, positive family history). Patients were evaluated for echocardiographic data, blood chemistry and ACA. Two-dimensional and Doppler echocardiographic examinations were performed in all patients within the first week and at 14 days after MI. LV thrombus was detected in 30 (42.8%) patients. ACA IgM levels were significantly higher in the patient group with LV thrombus than in the group without thrombus (12.44 ±4.12 vs. 7.69 ± 4.25 mpl, p = 0,01). ACA IgG levels were also found higher in the group with LV thrombus (24.2 ± 7.5 vs.17.98 ± 6.45 gpl, p = 0.02). Multivariate analyses revealed diabetes mellitus, higher WMSI, lower MDT and higher ACA IgM and higher ACA IgG levels as independent predictors of left ventricular thrombus formation. Our data demonstrate that beside the low ejection fraction, lower MDT and higher wall motion score index, modestly elevated ACA IgM and ACA IgG levels are associated with LV thrombus formation in patients with anterior MI.


A review of the growing trend towards heteroatoms-doped carbon dots based on dopamine acting as a hybrid agent and detected analyte.
Dopamine (DA) is a biomolecule that plays a critical part in the functioning of our brains by promoting motivation, maintaining focus, and altering mood. Excessive or low-level concentrations of DA in the human brain led to a dangerous neurological disorder. It is significantly important to trace the precise amount of DA to prevent such risky brain disease. Recently, heteroatoms-doped carbon dots (H-CDs) have attracted great attention for their capacity to detect biomolecules, metal ions, organic solvents, chemical dyes, etc. In this review, we have provided a comprehensive summary of the emerging trends in the heteroatom functional dopamine-doped carbon dots (DA-CDs), which are based on DA used as starting substances or functionalizing agents. Our analysis encompasses a detailed exploration of the synthetic methods, physical and chemical properties of carbon dots derived from dopamine, as well as their diverse range of applications. Additionally, we have also discussed the application of H-CDs in the dopmine detection by using various fluorescent, colorimetric, and electrochemical techniques.


Hepatitis E Virus Species C Infection in Humans, Hong Kong.
Hepatitis E virus (HEV) variants belonging to Orthohepevirus species A (HEV-A) are the primary cause of human hepatitis E. However, we previously reported that Orthohepevirus species C genotype 1 (HEV-C1), a divergent HEV variant commonly found in rats, also causes hepatitis in humans. Here, we present a clinical-epidemiological investigation of human HEV-C1 infections detected in Hong Kong, with an emphasis on outcomes in immunocompromised individuals. A surveillance system for detecting human HEV-C1 infections was established in Hong Kong. Epidemiological and clinical characteristics of HEV-C1 cases identified via this system between 1 August 2019 and 31 December 2020 were retrieved. Phylogenetic analysis of HEV-C1 strain sequences was performed. Infection outcomes of immunocompromised individuals with HEV-A and HEV-C1 infections were analyzed. HEV-C1 accounted for 8 of 53 (15.1%) reverse-transcription polymerase chain reaction (RT-PCR)-confirmed HEV infections in Hong Kong during the study period, raising the total number of HEV-C1 infections detected in the city to 16. Two distinct HEV-C1 strain groups caused human infections. Patients were elderly and/or immunocompromised; half tested negative for HEV immunoglobulin M. Cumulatively, HEV-C1 accounted for 9 of 21 (42.9%) cases of hepatitis E recorded in immunocompromised patients in Hong Kong. Immunocompromised HEV-C1 patients progressed to persistent hepatitis at similar rates (7/9 [77.8%]) as HEV-A patients (10/12 [75%]). HEV-C1 patients responded to oral ribavirin, although response to first course was sometimes poor or delayed. Dedicated RT-PCR-based surveillance detected human HEV-C1 cases that evade conventional hepatitis E diagnostic testing. Immunosuppressed HEV-C1-infected patients frequently progress to persistent HEV-C1 infection, for which ribavirin is a suitable treatment option.


Pneumopyopericardium mimicking an inferior ST elevation myocardial infarction with regional electrocardiogram changes: a case report.
Pneumopyopericardium is a rare disease with poor prognosis. The usual presentation is with fever, shortness of breath and haemodynamic compromise. The Electrocardiogram changes associated with this disease entity would be similar to pericarditis such as concave shaped ST elevations in all leads with PR sagging. Pneumopyopericardium mimicking an acute ST Elevation Myocardial Infarction, with regional Electrocardiogram changes has hitherto not been described in world literature. We describe the case of a 48 year old native Sri Lankan man, presenting with chest pain and Electrocardiogram changes compatible with an Acute ST Elevation Myocardial Infarction, subsequently found to have Pneumopyopericardium secondary to an oesophageal tear. Retrospective history revealed repetitive vomiting due to heavy alcohol consumption, prior to presentation. It unfortunately led to a fatal outcome. Pneumopyopericardium may mimic an acute ST elevation myocardial infarction with associated regional Electrocardiogram changes. A high degree of suspicion should be maintained and an adequate history should always be obtained prior to any intervention in all ST Elevation Myocardial Infarction patients.


Nonsurgical retreatment of teeth with periapical lesions previously managed by either endodontic or surgical intervention.
The purpose of this study was to evaluate the outcome of nonsurgical retreatment of teeth with periapical lesions, which had been previously managed by either endodontic or surgical intervention, and to identify factors that might influence the prognosis. Seventy-five endodontically and 11 surgically treated teeth with persisting periapical lesions ranging in size from 2 to 11 mm in diameter were included in this study. The teeth were nonsurgically retreated, using calcium hydroxide as intracanal medicament, and were followed for a period of 2 to 8 years. Clinical and radiographic assessment of retreatment showed that complete healing for all cases was 61.6% with an additional category of incomplete healing of 14%; 24.4% failed. The size of the periapical lesions and previous surgical treatment had marginally negative influences on the prognosis, but the differences were not statistically significant. The favourable results of this study demonstrated that nonsurgical root canal retreatment is an alternative to surgical intervention of postendodontic or postsurgical failure.


Poor reproducibility of the MRI measurement of distal femoral torsion.
Recent publications on patient-specific instrumentation for total knee arthroplasty have reported considerable variability in the axial positioning of the cutting guides for the femoral component. These personalized cutting guides are manufactured based on bone shape data, generated from magnetic resonance imaging (MRI) or computed tomography (CT). The goal of this study was to compare the reproducibility and accuracy of distal femoral torsion (DFT) values measured using these two imaging modalities. We hypothesized that MRI does not reproducibly and consistently measure DFT and is not as accurate as CT scan. Anonymized radiology records from 54 patients that included MRI and CT scans of the knee were read in random order by two observers, on two separate occasions. These records were from patients being considered for a meniscal or osteochondral graft and who had their knee explored, but who had not undergone femoral or tibial surgery and were free of osteoarthritis. The DFT was estimated using the posterior condylar angle (PCA), using both its anatomical and surgical definitions. The intra- and inter-observer reproducibility of the MRI and the differences relative to CT scan measurements were analysed. The average intra-observer difference for the MRI evaluation of the anatomical PCA was 0.8±1.2°; it was 0.4±0.9° for the surgical PCA. More than 1° difference from the average was found in 8 cases (14%) using the anatomical PCA measurement and 4 cases (7.4%) when using the surgical PCA (P=0.4). The intraclass correlation coefficients (ICCs) were 0.67 (95% CI: 0.33-0.85) and 0.74 (95% CI: 0.47-0.89) for the anatomical and surgical PCA, respectively. The average inter-observer difference for the MRI evaluation of the anatomical PCA was 1.6±1.4°; it was 1.5±1.0° for the surgical PCA. More than 1° difference from the average was found in 27 cases (50%) using the anatomical PCA measurement and 22 cases (40%) when using the surgical PCA (P=0.4). The ICCs were 0.31 (95% CI: 0.14-0.65) and 0.48 (95% CI: 0.06-0.75) for the anatomical and surgical PCA, respectively. The average differences between the CT and MRI measurements were 1.4±1.1° (0.2-5°) and 1.1±0.8° (0-3.6°) for the anatomical and surgical PCA, respectively. Greater than 1° difference between CT and MRI was found in 29 records (54%) for the anatomical PCA and in 18 records (33%) for the surgical PCA (P=0.03). DFT measurement on MRI is more reproducible and consistent when using the surgical PCA. MRI measurements differed by more than 1° relative to CT measurements in more than one-third of cases. Level III.


Prostacyclin regulates spinal nociceptive processing through cyclic adenosine monophosphate-induced translocation of glutamate receptors.
Prostacyclin (PGI2) is known to be an important mediator of peripheral pain sensation (nociception) whereas little is known about its role in central sensitization. The levels of the stable PGI2-metabolite 6-keto-prostaglandin F1α (6-keto-PGF1α) and of prostaglandin E2 (PGE2) were measured in the dorsal horn with the use of mass spectrometry after peripheral inflammation. Expression of the prostanoid receptors was determined by immunohistology. Effects of prostacyclin receptor (IP) activation on spinal neurons were investigated with biochemical assays (cyclic adenosine monophosphate-, glutamate release-measurement, Western blot analysis) in embryonic cultures and adult spinal cord. The specific IP antagonist Cay10441 was applied intrathecally after zymosan-induced mechanical hyperalgesia in vivo. Peripheral inflammation caused a significant increase of the stable PGI2 metabolite 6-keto-PGF1α in the dorsal horn of wild-type mice (n = 5). IP was located on spinal neurons and did not colocalize with the prostaglandin E2 receptors EP2 or EP4. The selective IP-agonist cicaprost increased cyclic adenosine monophosphate synthesis in spinal cultures from wild-type but not from IP-deficient mice (n = 5-10). The combination of fluorescence-resonance-energy transfer-based cyclic adenosine monophosphate imaging and calcium imaging showed a cicaprost-induced cyclic adenosine monophosphate synthesis in spinal cord neurons (n = 5-6). Fittingly, IP activation increased glutamate release from acute spinal cord sections of adult mice (n = 13-58). Cicaprost, but not agonists for EP2 and EP4, induced protein kinase A-dependent phosphorylation of the GluR1 subunit and its translocation to the membrane. Accordingly, intrathecal administration of the IP receptor antagonist Cay10441 had an antinociceptive effect (n = 8-11). Spinal prostacyclin synthesis during early inflammation causes the recruitment of GluR1 receptors to membrane fractions, thereby augmenting the onset of central sensitization.


Sexual dimorphic expression of putative antennal carrier protein genes in the malaria vector Anopheles gambiae.
To obtain a better understanding of the olfactory processes that allow mosquitoes to identify human hosts, a molecular study has been performed to identify and characterize molecules in the olfactory signalling pathway of the African malaria vector Anopheles gambiae. Using cDNA libraries from antennae of females and males, a collection of cDNAs encoding odorant binding proteins and other novel antennal proteins were isolated and characterized, which represent various families of putative carrier proteins with homologues in other insects. Using filter array hybridizations and quantitative RT PCR, regulation and gender specificity of expression of these genes was investigated. Significant differences in steady-state levels of some of these putative carrier protein genes were detected between the sexes and after blood feeding in females.


Unilateral renal agenesis associated with additional congenital abnormalities of the urinary tract in a Pekingese bitch.
An eight-month-old Pekingese bitch with urinary incontinence was found to have three congenital anomalies of the urinary tract: left renal agenesis, bilateral ectopic ureters with a left cranial blind-ending ureter, and urinary bladder hypoplasia. The diagnoses were made by retrograde vaginourethrography, excretory urography, ultrasonography and duplex Doppler ultrasonography. Although urological anomalies associated with renal agenesis have been frequently observed, a cranial blind-end ectopic ureter has not, to the authors' knowledge, been described in the bitch. The dog was managed medically with a restricted protein diet because of a compromised unilateral kidney with hydronephrosis and hydroureter.


Rapid in-solution preparation of somatic and meiotic plant cell nuclei for high-quality 3D immunoFISH and immunoFISH-GISH.
Though multicolour labelling methods allow the routine detection of a wide range of fluorescent (immuno)probe types in molecular cytogenetics, combined applications for the simultaneous in situ detection of proteins and nucleic acids are still sporadic in plant cell biology. A major bottleneck has been the availability of high-quality plant nuclei with a balance between preservation of 3D ultrastructure and maintaining immunoreactivity. The aim of this study was to develop a quick and reliable procedure to prepare plant nuclei suitable for various combinations of immunolabelling and fluorescence in situ hybridisation methods (immunoFISH-GISH). The mechanical removal of the cell wall and cytoplasm, instead of enzymatic degradation, resulted in a gentle, yet effective, cell permeabilisation. Rather than manually releasing the nuclei from the fixed tissues, the procedure involves in-solution cell handling throughout the fixation and the preparation steps as ended with pipetting the pure nuclei suspension onto microscope slides. The optimisation of several critical steps is described in detail. Finally, the procedure is shown to be compatible with immunolabelling, FISH and GISH as well as their simultaneous combinations. A simple plant cell nuclei preparation procedure was developed for combined immunolabelling-in situ hybridisation methods. The main and critical elements of the procedure are: a short period of fixation, incorporation of detergents to facilitate the fixation of tissues and the penetration of probes, tissue grinding to eliminate unwanted cell components, and an optimal buffer to handle nuclei. The procedure is time efficient and is easily transferable without prior expertise.


Core characteristics of the competent general practice trainer, a Delphi study.
The specific skills, attitude, knowledge, and personality characteristics, which should define the competent GP-trainer have been subject of research for many years. What are the most important of these characteristics have yet to be delineated. The aim of this study is to identify which characteristics are prerequisite for a competent GP-trainer. A modified Delphi procedure was used to answer the research question. Earlier qualitative research using focus groups identified 43 characteristics defining the competent GP-trainer. These characteristics were the subject of the Delphi procedure in which 48 experts chosen from the entire field of Dutch General Practice Training participated. After two rounds of the Delphi procedure, 37 characteristics were identified as being important for a competent GP-trainer. The characteristics which were ranked as the most important were 1. a competent GP-trainer is good at giving feedback, 2. dares to give feedback, 3. is critical of the GP-trainee and the learning process, 4. is good at communicating with the GP-trainee, and 5. has respect for the trainee. An important new characteristic has been identified: "being able to inspire reflection in the trainee". The core characteristics of the GP-trainer as identified in this research project, form a profile for the ideal GP-trainer to be used as a blueprint for objectives of schooling and for the assessment of GP-trainers.


Role of IGF-I signaling in muscle bone interactions.
Skeletal muscle and bone rely on a number of growth factors to undergo development, modulate growth, and maintain physiological strength. A major player in these actions is insulin-like growth factor I (IGF-I). However, because this growth factor can directly enhance muscle mass and bone density, it alters the state of the musculoskeletal system indirectly through mechanical crosstalk between these two organ systems. Thus, there are clearly synergistic actions of IGF-I that extend beyond the direct activity through its receptor. This review will cover the production and signaling of IGF-I as it pertains to muscle and bone, the chemical and mechanical influences that arise from IGF-I activity, and the potential for therapeutic strategies based on IGF-I. This article is part of a Special Issue entitled "Muscle Bone Interactions".


Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles.
The purpose of the present study was to investigate the possibility of targeting an anti-Alzheimer's drug tacrine in the brain using polymeric nanoparticles. Rats obtained 1mg/kg of tacrine by intravenous injection in the form of three preparations: (1) a simple solution in phosphate buffered saline, (2) bound to poly(n-butylcyanoacrylate) nanoparticles, and (3) bound to poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 (Tween 80). After 1h of post injection the rats were killed by decapitation and tacrine concentration in brain, liver, lungs, spleen and kidneys was analyzed by HPLC. A higher concentration of drug tacrine was observed in liver, spleen and lungs with the nanoparticles in comparison to the free drug. The accumulation of drug tacrine in the liver and spleen was reduced, when nanoparticles were coated with 1% polysorbate 80. In the brain a significant increase in tacrine concentration was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the uncoated nanoparticles and the free drug. In conclusion, the present study demonstrates that the brain concentration of intravenously injected tacrine can be enhanced by binding to poly(n-butylcyanoacrylate) nanoparticles, coated with 1% the nonionic surfactant polysorbate 80.


The architectonics of programmable RNA and DNA nanostructures.
The past several years have witnessed the emergence of a new world of nucleic-acid-based architectures with highly predictable and programmable self-assembly properties. For almost two decades, DNA has been the primary material for nucleic acid nanoconstruction. More recently, the dramatic increase in RNA structural information led to the development of RNA architectonics, the scientific study of the principles of RNA architecture with the aim of constructing RNA nanostructures of any arbitrary size and shape. The remarkable modularity and the distinct but complementary nature of RNA and DNA nanomaterials are revealed by the various self-assembly strategies that aim to achieve control of the arrangement of matter at a nanoscale level.


[Nutrition surveys in children attending kindergartens in the city of Cordoba].
A nutritional inquest was carried out in 1857 children attending kindergartens in Córdoba, Argentina, in 1974. Determinations were made for the socioeconomical level each child belonged (NES) and clinical and anthropometric examinations. Nutritional inquests were carried out in 414 of these children, psychological examinations in 51, and biochemical inquests in 61 children.


Extraordinary popular delusions and the madness of crowds: puncturing the epoetin bubble--lessons for the future.
Recent trials, and meta-analyses, have cast further doubt on the clinically desirable and safe range for increasing haemoglobin in chronic kidney disease using erythropoiesis-stimulating agents. In this article, I review the current dilemmas we face, suggest key clinical and biological research priorities, and conclude that we need to be brave enough to admit our present shortcomings, and then perhaps adopt a more patient-focused, individualized approach to anaemia management.


KRAS and GNAS mutations and p53 overexpression in biliary intraepithelial neoplasia and intrahepatic cholangiocarcinomas.
Similar to the pancreatic intraepithelial neoplasia (PanIN)-pancreatic carcinoma sequence model, intrahepatic cholangiocarcinoma (ICC) also reportedly follows a stepwise carcinogenesis process through the a precursor lesion: biliary intraepithelial neoplasia (BilIN). For this study, the authors investigated the status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) mutations and tumor protein 53 (p53) overexpression in the stepwise process of cholangiocarcinogenesis. Thirty patients with hepatolithiasis were surveyed, and their lesions were categorized as follows: non-neoplastic large bile duct (LBD) (n = 12), peribiliary gland (PBG) (n = 9), BilIN-1 (low-grade dysplasia; n = 12), BilIN-2 (high-grade dysplasia; n = 16), and BilIN-3 (noninvasive or in situ carcinoma; n = 10). KRAS mutation at codons 12 and 13 and GNAS mutations at codon 201 were analyzed using genomic DNA extracted from isolated lesions by laser capture microdissection [corrected]. Immunohistochemical expression of p53 also was evaluated in BilIN lesions, ICCs, and extrahepatic cholangiocarcinomas (ExCCs). A prevalence of KRAS mutations was identified in patients with ICC (31.5%), BilIN-3 (30%), and BilIN-2 (43.8%) compared with BilIN-1 (25%). Furthermore, KRAS mutations were detected in LBD lesions (41.7%) and PBG lesions (44.4%), and these mutations were observed with greater frequency in patients who had BilIN with KRAS mutations. GNAS mutations were not identified in any of the ICCs or other lesions examined. The overexpression of p53 was not identified in BilIN lesions and was less frequent in ICCs (18.2%) compared with ExCCs (38.1%) and gallbladder carcinomas (61.5%). KRAS mutations, which were present in approximately 33% of BilIN lesions, occurred as an early molecular event during the progression of BilIN to ICC, whereas p53 overexpression was identified as a late molecular event. Furthermore, the current results indicted that BilIN also may arise from LBD and PBG lesions in patients who have hepatolithiasis with KRAS mutations.


Acute supraglottitis in adults in Finland: review and analysis of 308 cases.
The aim of this article is to study the clinical features, management, and outcome in adult patients with acute supraglottitis. Retrospective review. We searched the medical records from our database from the years 1989 to 2009 using codes of international statistical classification of diseases and related health problems for acute epiglottitis or supraglottitis. In total, 308 patients were identified. Incidence of acute supraglottitis increased from 1.88 (first decade) to 4.73 per 100,000 cases (second decade) (P = .05). The mean age of the patients was 49 years old with a slightly male predominance. Sore throat and odynophagia were the most common symptoms. Concomitant disease were common among the patients. Isolated inflammation of epiglottis without involvement of other supraglottic tissue was detected only in 51 patients. Intravenous cephalosporins were the most common empiric antibiotic treatment regimen. Intravenous corticosteroids were administered to half of the cases. Streptococcus was the most common organism in throat cultures. In total, 45 patients needed airway intervention. Complications were rare and mortality was 0.6% in our series. Acute supraglottitis in adults seems to be a different entity than epiglottitis in children, and inflammation does not usually exclusively involve the epiglottis. Early diagnosis seems to decrease the need for airway intervention and to permit the successful treatment of the patient with intravenous antibiotics and corticosteroids. Streptococcus appears as the dominant causative microorganism. However systemic diseases and other local infections that compromise the regional supraglottic immunity may increase the risk for acute supraglottitis.


The Prognostic Value of Cancer Stem Cell Markers in Cervical Cancer: A Systematic Review and Meta-Analysis.
Prognostic biomarkers in cervical cancer are widely investigated, including cancer stem cell (CSC) markers. However, their significance remains uncertain. This study aimed to determine the role of cervical cancer stem cell (CCSC) markers for survival. We conducted a systematic review and meta-analysis (PROSPERO CRD42021237072) of studies reporting CCSC markers as the prognostic predictor based on PRISMA guidelines. We included English articles investigating associations of CCSCs expression in tissue tumor with overall survival (OS) or disease-free survival (DFS) from PubMed, EBSCO, and The Cochrane Library databases. The quality of studies was analyzed based on Newcastle-Ottawa Quality Assessment Scale. From 413 publications, after study selection with inclusion and exclusion criteria, 22 studies were included. High expressions of CCSC markers were associated with poor OS and DFS (HR= 1.05, 95% CI: 1.03 - 1.07, P <0.0001; HR= 1.31, 95% CI: 1.09 - 1.17, P <0.00001; respectively). Sub-analysis of individual CCSC markers indicated significant correlations between CD44 (HR= 1.14, 95% CI: 1.07 - 1.22, P 0.0001), SOX2 (HR= 1.58, 95% CI: 1.17 - 2.14, P 0.003), OCT4 (HR= 1.03, 95% CI: 1.01 - 1.06, P 0.008), ALDH1 (HR= 1.36, 95% CI: 1.13 - 1.64, P 0.001), and CD49f (HR= 3.02, 95% CI: 1.37 - 6.64, P 0.006) with worse OS; OCT4 (HR= 1.14, 95% CI 1.06 - 1.22, P 0.0003), SOX2 (HR= 1.11, 95% CI: 1.06 - 1.16, P <0.0001), and ALDH1 (HR= 1.22, 95% CI: 1.10 - 1.35, P 0.0002) with poor DFS. We did not conduct a meta-analysis for MSI-1 and CK17 because only one study investigated those markers. Expressions of OCT4, SOX2, and ALDH1 were associated with poor OS and DFS in cervical cancer tissue. These markers might have potential roles as prognostic biomarkers to predict unfavorable survival.


Effect of brushing with sonic and counterrotational toothbrushes on the bond strength of orthodontic brackets.
The purpose of this study was to evaluate the effect of brushing with both a sonic and mechanical counter rotary power toothbrush on the bond strength of orthodontic brackets. Forty-five extracted teeth were divided into three random groups and had orthodontic brackets bonded to them. One group was brushed with a counterrotational toothbrush, the Interplak, one group with a sonic toothbrush, the Sonicare, and a third group was not brushed and was held as a control. After the equivalent of 2 years brushing, the teeth were placed in an Instron machine and the shear force to remove the brackets was recorded. Group 1, the counter rotary power brush, had a mean of 107.5 kg/cm2, the second group, the sonic brush, had a mean of 79.7 kg/cm2, and the control group had a mean of 125. 4 kg/cm2. Single factor analysis of variance followed by the Fisher-Hayter Multiple Comparison Procedure showed a statistically significant difference between the sonic power brush and the control (P <.01), but no significant difference between the counter rotary and the control (P >.05). There was no significant difference between the two power brushes (P >.05).


Reversing microtubule-directed chemotherapeutic drug resistance by co-delivering α2β1 inhibitor and paclitaxel with nanoparticles in ovarian cancer.
Previous reports indicated that integrins associated signals are tightly related to tumor progression. Here, we observed elevated expression of integrin α2β1 in tumor tissues from microtubule-directed chemotherapeutic drugs (MDCDs) resistant patients compared with the samples from chemosensitive patients. More importantly, we sorted the integrin α2β1+ tumor cells and found those cells revealed high MDCDs resistance, whereas MDCDs shows effective cytotoxicity to those integrin α2β1- tumor cells in vitro and in vivo. Mechanistically, we demonstrated that integrin α2β1 could induce MDCDs resistance through the activation of the PI3K/AKT pathway. Applying MPEG-PLA to co-encapsulate the integrin α2β1 inhibitor E7820 and MDCDs could effectively reverse MDCDs resistance, resulting in enhanced anticancer effects while avoiding potential systemic toxicity in vitro and in vivo. In conclusion, the expression of integrin α2β1 contributes to MDCDs resistance, while applying E7820 combination treatment by MPEG-PLA nanoparticles could reverse the resistance.


Faecal thiaminase in clinically normal sheep associated with outbreaks of polioencephalomalacia.
Three flocks in which in with one of more sheep had succumbed to polioencephalomalacia (cerebrocortical necrosis) were used for faecal thiaminase studies. Up to one third of the clinically normal animals in these flocks to be excreting thiaminase on any one day and over half the flock could be thiaminase excretors at some time during an outbreak. The possible detrimental effects of sub-clinical thiamine antagonism in sheep are therefore worthy of consideration. Thiaminase excretion by individual animals was variable and sometimes intermittent. It was unaffected by changes in diet, pasture or enviroment. In two of the flocks multiple cases of polioencephalomalacia followed the administration of the anthelmintics, levamisole hydrochloride and thiabendazole. This aspect merits further investigation in view of the widespread use of anthelmintics of this type, especially as the profuse diarrhoea which can be associated with outbreaks of polioencephalomalacia may be wrongly attributed to gastro-intestinal parasitism.


De-agglomeration and homogenisation of nanoparticles in coal tar pitch-based carbon materials.
The aim of the work was to characterise coal tar pitch (CTP) modified with selected nanoparticles as a binder precursor for the manufacture of synthetic carbon materials. Different factors influencing the preliminary preparative steps in the preparation of homogenous nanoparticle/CTP composition were studied. Graphene flakes, carbon black and nano-sized silicon carbide were used to modify CTP. Prior to introducing them into liquid CTP, nanoparticles were subjected to sonication. Various dispersants were used to prepare the suspensions, i.e. water, ethanol, dimethylformamide (DMF) and N-methylpyrrolidone (NMP).The results showed that proper dispersant selection is one of the most important factors influencing the de-agglomeration process of nanoparticles. DMF and NMP were found to be effective dispersants for the preparation of homogenous nanoparticle-containing suspensions. The presence of SiC and carbon black nanoparticles in the liquid pitch during heat treatment up to 2000 °C leads to the inhibition of crystallite growth in carbon residue.


A Hospital-Based Study of Iodine Nutrition Status of Breastfeeding Mothers in Bangladesh.
Adequacy of iodine nutrition status in breastfeeding mothers is vital in preventing iodine deficiency disorder (IDD) in neonates and children. The aim of the study was to assess urinary iodine status in breastfeeding mothers attending Bangabandhu Sheikh Mujib Medical University (BSMMU) hospital in Bangladesh. In this cross-sectional study carried out from January 2014 to January 2015, urinary iodine (UI; μgm/L) level of 266 mothers (age 26.6 ± 4.7 years (mean ± SD), exclusively breastfeeding: 132 and nonexclusively breastfeeding: 134), recruited on consecutive basis from BSMMU outdoor and indoor, were measured in spot urine following the wet digestion method. Median UI in the participants was 298.6 (interquartile range, IQR 206.6-454.9) μgm/L and only 6.4% lactating mother had low UI (i.e. <100 μgm/L). There was no difference of median UI in relation to exclusive or nonexclusive breast feeding, presence of goiter, parity, and age of breastfed baby (p=ns for all). But median UI was higher in older subjects (≥30 years vs. <30 years: 364.4 (228.4-529.9) vs. 283.7 (205.4-434.0); median (IQR) p=0.040)), with good socioeconomic condition (good vs. average or less: 328.2 (243.8-510.0) vs. 274.4 (200.0-433.3); median (IQR); p=0.020), and in those who are aware regarding the importance of iodine (aware vs. unaware: 316.6 (225.2-506.3) vs. 270.1 (196.0-407.2); median (IQR); p=0.018). The proportion of participants with UI < 100 μgm/L was similar in all the groups. Logistic regressions to predict deficient UI status revealed none of the variables to be an independent predictor. This study indicates that deficient iodine nutrition status in Bangladeshi breastfeeding mothers is not frequent at present.


[Tubular secretion of cardiotrast in the progeny of rats receiving it throughout pregnancy].
Administration of cardiotrast (50-80 mg twice a day subcutaneously) during pregnancy was shown to induce a significant suppression of tubular secretion of the xenobiotic in the offspring. When cardiotrast was given only in the postnatal period, tolerance failed to develop.


(Z)-1,1-Dicyano-2-(4-fluoro-phen-yl)-3-(1-hexyl-pyridin-1-ium-4-yl)prop-2-en-1-ide.
The title compound, C(22)H(22)FN(3), exists as a zwitterion with the negative charge on the dicyano-methanide group and the positive charge on the pyridinium N atom. The mol-ecule adopts a Z conformation about the central C=C bond. The dihedral angle between the pyridinium and benzene rings is 65.65 (5)°. Weak C-H⋯N hydrogen bonding is present in the crystal structure.


Bipolar radiofrequency in the human meniscus. Comparative study between patients younger and older than 40 years of age.
To morphohistologically evaluate the effect of four increasing intensities of bipolar radiofrequency (RF) on the human meniscus and to compare the changes seen in the menisci from patients younger and older than 40 years old. Thirty fresh menisci were divided in two groups. Group 1: 12 menisci from patients younger than 40 y.o.; Group 2: 18 menisci from patients older than 40 y.o. Groups 1 and 2 were divided in four zones and subjected in vitro, for 3 s, to four intensities of bipolar RF energy. The samples were studied macroscopically, and microscopically. Thermal changes were present between 0 and 4000 microm from the meniscal surface, with an average of 1699 microm (S.D. 740), and was significantly higher on the ablation than the coagulation group (p<0.001). We found a significant difference between the depth of thermal changes in the menisci from patients younger and older than 40 years old at medium intensities of RF energy (p=0.038 and p=0.044). Although bipolar RF can cause deep thermal changes (up to 4000 microm) on the human meniscus, this effect depends on the magnitude of the energy applied. When comparing the effect between younger and older patients, the changes were deeper in the older group when RF was applied at medium intensities. Based on our findings, we recommend to exert precaution when applying RF energy at medium intensities in the degenerative meniscus, due to a deeper thermal effect in this group.


Novel hybrid total artificial heart with integrated oxygenator.
There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable cardiopulmonary support system that integrates an implantable oxygenator with a hybrid, dual-support, continuous-flow total artificial heart (TAH). The TAH has a centrifugal flow pump that is rotating about an axial flow pump. By attaching the hollow fiber bundle of the oxygenator to the base of the TAH, we establish a new cardiopulmonary support technology that permits a patient to be ambulatory during usage. In this study, we investigated the design and improvement of the blood flow pathway from the inflow-to-outflow of four oxygenators using a mathematical model and computational fluid dynamics (CFD). Pressure loss and gas transport through diffusion were examined to assess oxygenator design. The oxygenator designs led to a resistance-driven pressure loss range of less than 35 mmHg for flow rates of 1-7 L/min. All of the designs met requirements. The configuration having an outside-to-inside blood flow direction was found to have higher oxygen transport. Based on this advantageous flow direction, two designs (Model 1 and 3) were then integrated with the axial-flow impeller of the TAH for simulation. Flow rates of 1-7 L/min and speeds of 10,000-16,000 RPM were analyzed. Blood damage studies were performed, and Model 1 demonstrated the lowest potential for hemolysis. Future work will focus on developing and testing a physical prototype for integration into the new cardiopulmonary assist system.


Patient-Reported Outcomes for Fully Vaccinated COVID-19 Patients Over 6 Weeks: The Experiences of Clinical Breakthrough Cases.
While coronavirus disease 2019 (COVID-19) vaccines have high rates of efficacy, fully vaccinated individuals can become infected with COVID-19. Among this population, symptoms tend to be less severe and shorter lasting. Less is known about how vaccinated individuals who contract COVID-19 experience the disease through patient-reported outcomes (PROs) and how this changes over time. The aim of this study was to describe the physical, mental, and social health PROs for fully vaccinated individuals who contracted COVID-19 over a 6-week period. Prospective design using the Patient-Reported Outcomes Measurement Information System short-form (PROMIS-10) collected through a mobile application-based platform. 1114 fully vaccinated patients who tested positive for COVID-19 at a large US health system and engaged with the study on or after 1 March 2021 and reported onset of illness prior to 1 November 2021. Global physical and mental health PROMIS-10 T-scores for the 6-week period, component PROMIS-10 questions for the 6-week period, and component PROMIS-10 questions restricted to a subset of participants for the first month to measure individual recovery were analyzed. Mean global physical and mental health T-scores increased over time and remained within one standard deviation of the population mean. At baseline, at least 40% of participants reported good health for all component questions except Fatigue (25%), and the proportion reporting good health increased over time for all questions, with the largest improvements in Fatigue (25.5 to 67.5%), Pain (59.1 to 82.8%), and Emotional Problems (42.3 to 62.5%). Over the first month, the greatest positive changes in individual recovery were observed for Fatigue (65.0%), Pain (53.0%), and Emotional Problems (41.1%); at least 30% of respondents reported no change in at least one category, and the greatest decreases were for Usual Social Activities (23.9%), Social Satisfaction (23.2%), and Mental Health (21.8%). This study provides an important step towards better understanding the impact of 'breakthrough' COVID-19 infections on clinically engaged, fully vaccinated patients' physical and mental health to improve support for their treatment and recovery.


Treatment of chronic radiculopathy of the first sacral nerve root using neuromobilization techniques: A case study.
The engagement of the first sacral nerve root is one of the most common etiologies in Sciatic Pain Syndrome (SPS). Different interfering methods are used in the physical therapy of people with SPS including physical modalities, exercise therapy, traction, and joint and neuromobilization, depending on the symptoms and radiculopathy phase. The present case study attempts to describe neuromobilization methods in treating chronic radiculopathy of the first sacral nerve root, as well as its abnormal neurodynamic responses. The patient was a 36-year-old man with lower back pain during construction work 9 months before, and presenting with complaint of burning pain and tingling in his left Posterior part of the thigh and leg. Active extension, rotation, and lateral flexion of the trunk in standing position had a complete range with no pain. SLR and Slump neurodynamic tests revealed that with increasing sensitive elements, there appeared to be abnormal sciatic nerve tension, and complaint due to returning burn and tingling in the posterior part of the thigh and leg. MRI findings revealed intervertebral disc dehydrations at L3-4, L4-5, and L5-S1 levels, as well as postero-lateral protrusion in L5-S1 intervertebral disc. Following three routine physical therapy sessions, with no improvement, neuromobilization technique was used for 6 sessions. The usual routine physical therapy methods did have any visible impact in solving the patient's problems during daily-life activities and physical diagnosis findings, yet, following neuromobilization technique, the assessment at the beginning of the eleventh session and the patient's follow-ups two months later showed that his problems during daily-life activities and in neurodynamic tests were totally solved. Abnormal neurodynamic responses and consequently symptoms in patients with chronic radiculopathy may be due to a pathomechanic problem and deficiency in neural adjustment for movement and tension transfer. Neuromobilization techniques can increasingly useful in treatment of abnormal neural tensions and removing chronic radiculopathy symptoms.


Comparison of hair manifestations in cardio-facio-cutaneous and Costello syndromes highlights the influence of the RAS pathway on hair growth.
Abnormal hair growth is a defining feature of RASopathies, syndromes caused by germline mutations in the RAS pathway. However, detailed hair manifestations and the mechanisms of altered hair growth in RASopathies are poorly delineated. To identify distinguishing clinical features and investigate how the RAS pathway influences hair growth by performing a systematic and detailed side-by-side comparison of hair manifestations in cardio-facio-cutaneous syndrome (CFCS) and Costello syndrome (CS), two RASopathies caused by mutations in the downstream and upstream elements of the RAS pathway, respectively. Sixteen individuals with CFCS and 23 individuals with CS were enrolled. Mutation data were recorded. Scalp hair, eyebrows and eyelashes of individuals with CFCS or CS were examined for texture, colour, density and morphology. Scalp hairs were examined by light microscopy. While both syndromes displayed abnormal hair, striking differences were observed, including darker and thicker scalp hair and sparse eyebrows and eyelashes in CFCS. By contrast, synophrys, trichomegaly and abnormalities of the scalp hair shafts were observed in CS. Possible correlation with straight hair and genotype was observed in CS. The results emphasize the role of the RAS pathway in hair growth, improve accuracy of clinical diagnosis of CFCS and CS and provide a foundation for identification of therapeutic targets.


The value of retropharyngeal soft tissue measurements in trauma of the adult cervical spine. Cervical spine soft tissue measurements.
Widening of the retropharyngeal soft tissue space (RSTS) has been interpreted as a sign of cervical spine trauma. Widely differing measurements are reported in the literature. However it is clear that, using the currently acceptable limits of normal, a large number of patients without spinal injury are subjected to further tests. The RSTS on lateral cervical spine radiographs of 318 patients with a history of cervical spine trauma were measured at the C2-C4 level. The values for patients found to be normal or with fractures/dislocations were evaluated. Statistical analysis of the results demonstrates a considerable overlap in the RSTS of normal and abnormal patients. Therefore we suggest that RSTS measurements are of limited diagnostic value. Using the statistical probability of abnormality, guidelines that indicate which patients may require additional study are suggested.


Influence of decalcifying agents on immunoreactivity of formalin-fixed, paraffin-embedded tissue.
The influence of eight decalcifying agents on the immunoreactivity of formalin-fixed, paraffin-embedded tissue for immunoglobulins, lysozyme, factor VIII-related antigen and keratin was studied using the unlabelled antibody peroxidase-antiperoxidase (PAP) method. Limited studies were also performed on tissues fixed in acid-formalin mixtures. All tissues were stained using an indirect immunoperoxidase method with mouse monoclonal antibodies to IgM, kappa and lambda light chains. The results suggest that, with controlled trypsinization of sections, it was possible to obtain optimal immunostaining for all tested antigens, with adequate preservation of histological structure, after decalcification in neutral EDTA or 10% aqueous acetic or formic acid. Tissue treated with agents containing mineral acids exhibited variable immunoreactivity and impaired counterstaining.


Comparison of central venous catheter in brachiocephalic vein and internal jugular vein for the incidence of complications in patients undergoing radiology.
Central venous catheter (CVC) is an essential part of modern medical care that delivers the drugs, intravenous fluids, and intravenous feeding to the vein. So far, limited studies have been carried out on the brachiocephalic vein (BCV) in adults. This study aimed to compare the CVC in the internal jugular vein (IJV) and BCV in order to ease of access and incidence of complication such as infectious and mechanical complications. This clinical trial was performed on 52 patients who underwent BCV and the IJV catheterization. The patients were compared in two groups of IJV and BCV in order to facilitate catheterization and measure the success rate and catheterization-induced complications. The difference between the two groups was analyzed by Independent t-test and Chi-square tests. Overall, 52 patients underwent intravenous catheterization. The success rate of catheterization in the first attempt was 100%. The problems of catheterization procedure in the IJV group (11.5%) were greater than the BCV group (6.6%). There was no significant difference between the two groups regarding the duration of catheterization, pneumothorax, emphysema, hematoma, arterial puncture, infection, and complete thrombosis, whereas the partial thrombosis in the IJV group (30.76%) was significantly (P < 0.05) greater than the BCV group (23.07%). Catheterization in both brachiocephalic and the IJV is an appropriate, highly efficient, stable, and safe procedure and ultrasound-guided catheterization is very reliable and safe method.


A dual mechanism of action of the anticancer agent F 11782 on human topoisomerase II alpha.
F 11782 is a novel epipodophyllotoxin that targets eukaryotic topoisomerases and inhibits enzyme binding to DNA. While F 11782 has not been found to stabilize either topoisomerase I or topoisomerase II covalent complexes, drug treatment appears to result in DNA damage. F 11782 has also been shown to inhibit the DNA nucleotide excision repair (NER) pathway. Bisdioxopiperazine-resistant small cell lung cancer (SCLC) OC-NYH/Y165S and Chinese hamster ovary (CHO) CHO/159-1 cells having functional Y49F and Y165S mutations in the topoisomerase II alpha isoform were both resistant to F 11782. The catalytic activity of purified human Y50F and Y165S mutant topoisomerase II alpha (Y50F in the human protein corresponds to Y49F in the CHO protein) was likewise resistant to the inhibitory action of F 11782. F 11782 was also found to induce a non-covalent salt-stable complex of human topoisomerase II with DNA that was ATP-independent. F 11782 thus displays a dual mechanism of action on human topoisomerase II alpha, reducing its affinity for DNA while also stabilizing the protein bound in the form of a salt-stable complex. Our results suggest that topoisomerase II alpha is a target of F 11782 in vivo, and that F 11782 may act as a novel topoisomerase II poison.


Resident Duty Hour Compliance and Sleep after Transitioning to a Night Float System: A Prospective Observational Study in an Academic Urology Program.
Our urology residency program transitioned to a night float system, where dedicated residents cover nights and are off duty during the day. Junior residents previously covered 5 hospitals every 5 to 7 nights and worked the following day (home call). This prospective observational study compared the 2 systems before and after the transition. A validated survey was administered to residents and faculty to evaluate patient care, communication, quality of life, resident education, and duty hour violations. A separate survey was administered to nurses evaluating the on-call resident. Sleep was measured using actigraphy. Survey response rates were 80% to 100%. Junior residents rated night float as equivalent to home call for surgical case volume and superior in all other respects (p <0.05). Senior residents rated night float as superior for continuity of care, compassion, safety, efficiency for the day team, communication with nurses, quality of life, and time for reading and research (p <0.05). Faculty rated night float as superior for efficiency for the day team, handoffs, quality of life, and time for research (p <0.05). Nurses rated night float higher for availability, knowledge of plan for patient, respectfulness, communication, and ability to identify the resident on call (p <0.05). Mean duration of sleep was 2.5 and 7.1 hours for home call and night float, respectively (p <0.001). Junior residents reported fewer violations of the 80-hour and 8-hour-off rules with night float (p <0.001). Physicians and nurses perceived night float to improve multiple domains. Residents slept more and had fewer duty hour violations on night float.


Comparison of tumescent local anesthesia vs normal anesthesia technology in upper blepharoplasty in Asian women.
Blepharoplasty is the most common type of plastic surgery, used to improve most of the eyelid skin sag caused by aging. In the past, local infiltration anesthesia was widely used in blepharoplasty. Tumescent local analgesia (TLA) is safe and reliable method for anesthesia, even children can use this method. This research aimed to systematically compare the differences between conventional local infiltration anesthesia and TLA in blepharoplasty. One hundred and seventy-eight bilateral upper blepharoplasty patients participated in this research. Visual analog scale (VAS) was employed to evaluate the postoperative pain in the patients. Periorbital appearances are based on light photography and judged by both medical and nonmedical panel. The use of TLA decreased the surgery duration but had no influence on the other surgery characteristics of upper blepharoplasty. Using TLA for anesthesia in bilateral upper blepharoplasty generated less pain than using local infiltration anesthesia. At day 7 after upper blepharoplasty, the rate of generation of both ecchymosis and erythema in normal anesthesia (NA) side were higher than in TLA side. The satisfaction of patients after upper blepharoplasty was not influenced by the use of different anesthesia methods. Compared with the normal anesthesia technology, the use of TLA in the upper blepharoplasty shortened the surgery duration, alleviated the postoperative pain, and mitigated the generation of ecchymosis and erythema. So, TLA is suitable for the performance of anesthesia in blepharoplasty.