Amygdala DCX and blood Cdk14 are implicated as cross-species indicators of individual differences in fear, extinction, and resilience to trauma exposure.
Doublecortin (DCX) has long been implicated in, and employed as a marker for, neurogenesis, yet little is known about its function in non-neurogenic brain regions, including the amygdala. This study sought first to explore, in rodents, whether fear learning and extinction modulate amygdala DCX expression and, second, to assess the utility of peripheral DCX correlates as predictive biomarkers of trauma response in rodents and humans. Pavlovian conditioning was found to alter DCX protein levels in mice 24 h later, resulting in higher DCX expression associated with enhanced learning in paradigms examining both the acquisition and extinction of fear (p < 0.001). This, in turn, is associated with differences in freezing on subsequent fear expression tests, and the same relationship between DCX and fear extinction was replicated in rats (p < 0.001), with higher amygdala DCX levels associated with more rapid extinction of fear. RNAseq of amygdala and blood from mice identified 388 amygdala genes that correlated with DCX (q < 0.001) and which gene ontology analyses revealed were significantly over-represented for neurodevelopmental processes. In blood, DCX-correlated genes included the Wnt signaling molecule Cdk14 which was found to predict freezing during both fear acquisition (p < 0.05) and brief extinction protocols (p < 0.001). High Cdk14 measured in blood immediately after testing was also associated with less freezing during fear expression testing (p < 0.01). Finally, in humans, Cdk14 expression in blood taken shortly after trauma was found to predict resilience in males for up to a year post-trauma (p < 0.0001). These data implicate amygdala DCX in fear learning and suggest that Cdk14 may serve as a predictive biomarker of trauma response.


A scheme for describing injury events.
To develop a data collection system that provides a more comprehensive picture of the components of the preinjury and injury phases of injury events than is usually available in medical records. Based on a scheme originally designed for study of occupational injuries among off-shore petroleum drilling workers, eight data areas were designated and lists of categories were developed to permit applicability to a general injury surveillance program. Medical records for 1600 injured patients treated at the Medical Center Hospital of Vermont were reviewed to determine current frequency of recording such information. A scheme for injury surveillance was designed that included location of the event, general and specific activities at time of injury, work relationship, nature of the event, animal or person contact, products or materials being used and those causing injury, and energy type and mechanism. An acceptable scheme has been developed that can be used for general surveillance, or modified to focus in greater detail on specific environments, products, or event types.


Long-term results of biliary atresia in the era of liver transplantation.
The purpose of this study was to analyze the survival of patients with biliary atresia (BA) after Kasai operation and liver transplantation (LT) and to analyze the factors affecting survival. Seventy-two patients diagnosed with BA were operated on between April 1995 and December 2009 and retrospectively analyzed. Out of the 72 patients, 59 received Kasai operation and 13 received LT without prior Kasai operation. Twenty-seven patients received LT after Kasai operation. Survival with native liver was 39 % at 10 years. With the application of LT, overall 10-year survival for patients with BA was 94.9 %. Among patients alive with native livers after Kasai operation, 14 patients (58.3 %) have at least one complication associated with biliary cirrhosis and portal hypertension. Age at which Kasai operation was performed (60 days) and postoperative normalization of bilirubin were independent risk factors for survival with the native liver, according to multivariate analysis (HR 2.90, p = 0.033 and HR 9.89, p = 0.002). Survival of BA patients has greatly increased in the era of LT. However, many patients surviving with native livers after Kasai operation continue to have signs of biliary cirrhosis and abnormal liver function.


New strategies for the evaluation of the nadir bone marrow following induction in acute myeloid leukemia.
Patients with acute myeloid leukemia (AML) routinely undergo a bone marrow biopsy 7-10 days after induction chemotherapy to evaluate treatment effectiveness. Measuring blast count by morphology alone has been the standard hematopathologic technique. Although helpful to guide future treatment decisions, the early bone marrow does not predict well which patients will achieve complete remission, and ultimately be cured. New methods of assessing early treatment effectiveness are being developed. This review summarizes the current utility of early bone marrow evaluations and looks toward future developments. More sensitive techniques than light microscopy are available to analyze the presence or absence of leukemia after treatment. These include flow-cytometry and polymerase chain reaction-based assays, and their use is playing a larger role in monitoring therapy effectiveness after induction and during consolidation. Importantly, novel techniques including enzymatic amplification staining (performed on bone marrow samples) and noninvasive molecular imaging have been studied and may play a role in future therapy asessment. Identifying and implementing new tools to measure therapy effectiveness will be an important component of improving outcomes for patients with AML.


Quantitative assessment of the gait improvement effect of LSVT BIG® using a wearable sensor in patients with Parkinson's disease.
The main effects of Lee Silvermann Voice Treatment-BIG® therapy (LSVT-BIG) on gait function are improvements in gait speed and stride length. Considering the mechanism of this improvement, LSVT-BIG may affect joint angles of the lower extremities. Therefore, further investigation of the effect of LSVT-BIG on gait function, especially joint angles, is needed. Patients with Parkinson's disease (PD) who were eligible for LSVT-BIG were recruited. We measured the following items pre- and post-LSVT-BIG: MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Functional Independence Measure (FIM), timed up and go test (TUG), and gait parameters using RehaGait®. Gait parameters included gait speed, stride duration and length, the standard deviation of stride duration and length, cadence, the ratio of the stance/swing phase, and the flexion and extension angles of the hip, knee, and ankle joints. Range of motion (ROM) was calculated as the difference of values between the maximum flexion and extension angles of each joint. Twenty-four participants completed the LSVT-BIG. Significant improvement was observed in the MDS-UPDRS (mean changes: Part I, -2.4 points; Part II, -3.5 points; Part III -8.9 points), TUG (-0.61 s), gait speed (+0.13 m/s), stride length (+0.12 m), flexion and extension angles and ROM of the hip joints (flexion, +2.0°; extension, +2.0; ROM, +4.0°). Enlargement in ROM of the hip joint was strongly correlated with increase in gait speed and stride length (r = 0.755, r = 0.804, respectively). LSVT-BIG enlarged flexion and extension angles and ROM of the hip joint significantly. Change of ROM of the hip joint was directly related to the increase in stride length and gait speed observed in patients with PD after LSVT-BIG.


Supernormal conduction in the accessory pathway of patients with overt or concealed ventricular pre-excitation.
It was recently shown that supernormal conduction in the diseased His-Purkinje system is more common than previously thought, and is always associated with prolongation of refractoriness. To assess whether supernormal conduction could also occur in the accessory pathway of patients with ventricular pre-excitation, 21 patients with manifestly prolonged refractoriness in the accessory pathway were studied. Under these conditions, programmed atrial stimulation revealed a phase of supernormal conduction in 16 (76%) of the 21. Therefore, what was believed to be a nonexistent or exceptional physiologic event was shown to be a rather common finding, at least under certain circumstances. Supernormal conduction occurred in all 7 patients with an anterograde refractory period of 480 to 980 ms, and in 5 of 10 patients with a refractory period greater than 1.0 second or with no anterograde conduction. Supernormal conduction could not be demonstrated in four patients with a refractory period less than or equal to 440 ms, but appeared in all four patients after the refractory period was prolonged by a rapid rate of stimulation or administration of ajmaline. The electrophysiologic changes underlying the occurrence of supernormal conduction in the accessory pathway are similar to those previously reported for the bundle branch system. The demonstration of supernormal conduction in the accessory pathway may uncover the presence of concealed ventricular pre-excitation. Supernormal conduction over the accessory pathway may facilitate a rapid ventricular response during atrial fibrillation, even if the refractory period is prolonged.


Defective elongation of fatty acids in a recessive 25-hydroxycholesterol-resistant mutant cell line.
The Chinese hamster ovary recessive mutant, crB, has been selected for its resistance to the cytotoxic effects of 25-hydroxycholesterol in sterol-free media (Sinensky, M., Logel, J., and Torget, R. (1982) J. Cell. Physiol. 113, 314-319). Growth of crB in a chemically defined lipid-poor medium is very slow and is enhanced by a mixture of saturated and unsaturated fatty acids. Incorporation of [3H]acetate into total fatty acids is 4-fold lower in crB compared to that in parental Chinese hamster ovary K1 and in contrast to the wild-type cells, crB cells are unable to synthesize either stearate or oleate. In addition, crB cells can not elongate exogenous palmitate, while they are capable of desaturating exogenous stearate. The mutant cells are also pleiotropically defective in the regulation of mRNA levels for the enzymes of cholesterol biosynthesis. 25-Hydroxycholesterol is a poor regulator of the synthesis and degradation of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase in crB in comparison to the wild-type Chinese hamster ovary K1 cells. The defect in the elongation of fatty acids is reversed in revertants of crB selected for their ability to grow in lipid-poor medium. Such revertants exhibit normal regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity by 25-hydroxycholesterol. Regulation of reductase activity in crB cells can also be restored by supplementing the culture medium with a mixture of fatty acids that restores normal growth rate. The defective regulation of reductase in crB does not appear to be due to nonspecific adverse effects of fatty acid starvation nor is it due to any gross change in the fatty acid composition of cellular phospholipids. These results strongly suggest a direct relationship between the fatty acid auxotrophy of crB and defective regulation of the enzymes of cholesterol biosynthesis.


Debris-Filled Duodenal Diverticulum and Lemmel's Syndrome.
We report a case of a 73-year-old woman affected by Lemmel's syndrome, a rare type of obstructive jaundice caused by a periampullary duodenal diverticulum. The patient was admitted to the Emergency Department for pneumonia associated with mild epigastric pain and vomiting. While hospitalized for antibiotic treatment, the appearance of jaundice led us to discover a periampullary duodenal diverticulum by endoscopy and CT scan. The jaundice was successfully managed endoscopically with removal of food debris from the diverticulum.


Otorrhea as a sign of medical treatment failure in acute otitis media: two cases with silent mastoiditis complicated with facial palsy.
We report two children with otitis media who developed facial palsy despite prompt antibiotic therapy. Brain images revealed silent mastoiditis. Persistent otorrhea may be a cautious sign of medical treatment failure or complication of acute otitis media, including mastoiditis or facial palsy. Delayed identification of coexisting mastoiditis or hesitation over surgical intervention may lead to treatment failure and complications. Adequate intravenous antibiotics and myringotomy provide reasonable and appropriate management to prevent permanent sequelae.


Endoscopic ear surgery - a complement to microscopic ear surgery.
Wullstein, the founder of modern microscopic ear surgery, already used an oto-endoscope intraoperatively. However, it is only after the recent development of modern video-endoscopy with high-definition, 4K, and 3‑dimensional imaging that endoscopically guided surgery of the middle ear is gaining some importance. Key ventilation routes like the isthmus tympani and the epitympanic diaphragm can be visualized far better using an endoscope than with a microscope. Going through the external meatus, surgery of middle ear pathologies is possible without external incision. This type of primary endoscopic ear surgery has to be distinguished from secondary endoscopic ear surgery, where standard microscopic ear surgery is supplemented by endoscopic surgery. Having to hold the endoscope in one hand, surgery has to be performed single-handedly, which is awkward. In cases of extensive bone removal or excessive bleeding, the view through the endoscope lens is obscured; therefore; the endoscope cannot fully substitute the microscope. It is, however, an interesting adjunct to microscopic ear surgery.


TMEM189 negatively regulates the stability of ULK1 protein and cell autophagy.
ULK1 is crucial for initiating autophagosome formation and its activity is tightly regulated by post-translational modifications and protein-protein interactions. In the present study, we demonstrate that TMEM189 (Transmembrane protein 189), also known as plasmanylethanolamine desaturase 1 (PEDS1), negatively regulates the proteostasis of ULK1 and autophagy activity. In TMEM189-overexpressed cells, the formation of autophagesome is impaired, while TMEM189 knockdown increases cell autophagy. Further investigation reveals that TMEM189 interacts with and increases the instability of ULK1, as well as decreases its kinase activities. The TMEM189 N-terminal domain is required for the interaction with ULK1. Additionally, TMEM189 overexpression can disrupt the interaction between ULK1 and TRAF6, profoundly impairs K63-linked polyubiquitination of ULK1 and self-association, leading to the decrease of ULK1 stability. Moreover, in vitro and in vivo experiments suggest that TMEM189 deficiency results in the inhibition of tumorigenicity of gastric cancer. Our findings provide a new insight into the molecular regulation of autophagy and laboratory evidence for investigating the physiological and pathological roles of TMEM189.


Aspects of intracerebral hematomas--an update.
In Norway, there are approximately 16000 strokes each year and 15% of these are caused by intracerebral hematomas. Intracerebral hemorrhage (ICH) results from the rupture of blood vessels within the brain parenchyma. ICH occurs as a complication of several diseases, the most prevalent of which is chronic hypertension. When hemorrhage develops in the absence of a pre-existing vascular malformation or brain parenchymal lesion, it is denoted primary ICH. Secondary ICH refers to hemorrhage complicating a pre-existing lesion. Primary ICH is the most common type of hemorrhagic stroke, accounting for approximately 10% of all strokes. Despite aggressive management strategies, the 30-day mortality remains high, at almost 50%, with the majority of deaths occurring within the first 2 days. At 6 months, only 20-30% achieve independent status. This article is based on clinical experience, modern therapeutic guidelines for the treatment of intracerebral hematomas and up-to-date medical literature found in Medline. The article discusses the pathophysiology, clinical aspects, treatment, and the prognosis of intracerebral hematomas. Advances in diagnosis, prognosis, pathophysiology, and treatment over the past few decades have significantly advanced our knowledge of ICH; however, much work still needs to be carried out. Future genetic and epidemiologic studies will help identify at-risk populations and hopefully allow for primary prevention. Randomized controlled studies focusing on novel therapeutics should help to minimize secondary injury and hopefully improve morbidity and mortality.


Design, synthesis and biological studies of survivin dimerization modulators that prolong mitotic cycle.
Survivin, a member of the inhibitor of apoptosis protein (IAP) family proteins, has essential roles in cell division and inhibition of apoptosis. Several clinical studies in cancer patients have shown that the elevated levels of survivin correlate with aggressiveness of the disease and resistance to radiation and chemotherapeutic treatments. Survivin is an integral component of chromosomal passenger complex (CPC) where it binds to borealin and INCENP through its dimerization interface. Thus, disruption of functional survivin along its dimer interface with a small molecule is hypothesized to inhibit the proliferation of cancer cells and sensitize them to therapeutic agents and radiation. Recently, a small molecule (Abbott8) was reported to bind at the dimerization interface of survivin. Further development of this compound was accomplished by computational modeling of the molecular interactions along the dimerization interface, which has led to the design of promising survivin dimerization modulators. Two of the most potent survivin modulators, LLP3 and LLP9 at concentrations between 50 and 100nM, caused delay in mitotic progression and major mitotic defects in proliferating human umbilical vein endothelial cells (HUVEC) and prostate cancer cells (PC3).


Contamination profile of aflatoxin M1 residues in milk supply chain of Sindh, Pakistan.
Aflatoxin M1 (AFM1) is a potent carcinogen, teratogen and mutagen found in the milk when lactating animals consume feed contaminated with aflatoxin B1 (AFB1). In the present study, the contamination of AFM1 was evaluated in the milk supply chain of the province of Sindh, Pakistan. For the broader profiling of targeted toxin, enzyme-linked immunosorbent assay (ELISA) was used for the determination of AFM1 in both branded and non-branded milk samples. The results showed that 96.43% of samples (81 out of 84) were contaminated with AFM1 in the range of 0.01-0.76 μg/L. The average contamination level was 0.38 μg/L. The determined values of AFM1 in the collected milk samples were above the standard limit of the European Commission while 70% of the samples exceeded levels established by United States regulations. According to these results, the estimated daily intake of AFM1 for adults was determined as 3.1 ng/kg of body weight per day.


Formation of Nucleophilic Allylboranes from Molecular Hydrogen and Allenes Catalyzed by a Pyridonate Borane that Displays Frustrated Lewis Pair Reactivity.
Here we report the in situ generation of nucleophilic allylboranes from H2 and allenes mediated by a pyridonate borane that displays frustrated-Lewis-pair reactivity. Experimental and computational mechanistic investigations reveal that upon H2 activation, the covalently bound pyridonate substituent becomes a datively bound pyridone ligand. Dissociation of the formed pyridone borane complex liberates Piers borane and enables a hydroboration of the allene. The allylboranes generated in this way are reactive towards nitriles. A catalytic protocol for the formation of allylboranes from H2 and allenes and the allylation of nitriles has been devised. This catalytic reaction is a conceptually new way to use molecular H2 in organic synthesis.


Blood pressure and impairment of endothelium-dependent relaxation in spontaneously hypertensive rats.
Correlation between hypertension and impairment of endothelium-dependent relaxation was demonstrated using aortae from certain strains of rats with various levels of spontaneous hypertension. It was also observed that the impairment of endothelium-dependent relaxation is the secondary change due to hypertension, and the level and duration of hypertension is the determinant factor of the impairment.


Please get me out of here: The difficult decision making in fit-to-fly assessments for international fixed-wing air ambulance operations.
With international travel for leisure and business almost back to pre-pandemic levels, demand for repatriation due to illness and injury abroad is increasing [1,2]. In any repatriation, there is considerable pressure on all involved to organize a rapid transport back home. Delay in such action may be perceived by the patient, relatives, and the public as an attempt by the underwriter to hold off on an expensive air ambulance mission [3-5]. Review of the available literature and analysis of assistance and air ambulance Companies' infrastructure and processes to identify risk and benefit of executing or delaying aeromedical transport for international travellers. While patients of almost any severity can be safely transported over great distances in modern air ambulance aircraft, immediate transport is not always in the patient's best interest. Each call for assistance requires a complex and dynamic risk-benefit analysis with multiple stakeholders involved to achieve an optimized outcome. Opportunities for risk mitigation within the assistance team include active case management with clearly assigned ownership, as well as medical and logistical experience with knowledge on local treatment opportunities and limitations. On the air ambulance side, modern equipment, experience, standards and procedures as well as accreditation can reduce risk. Each patient evaluation remains a highly individual risk-benefit assessment. Optimal outcomes require a clear understanding of responsibilities, flawless communication and significant expertise among the key decision-makers. Negative outcomes are mostly associated with insufficient information, communication, inadequate experience or a lack of ownership/assigned responsibility.


Young and older good learners have higher levels of brain nicotinic receptor binding.
Neuronal alphabeta heteromeric and alpha7 homomeric nicotinic acetylcholine receptors (nAChRs) were compared in 4- and 27-month rabbits selected for learning proficiency. Sixty 4- and 60 27-month rabbits received the alpha7 nAChR agonist (MEM-3389), galantamine, or vehicle during training in trace eyeblink classical conditioning. Brain tissue from the best and worst young and older learners was analyzed with radioligand binding. Vehicle-treated 4- and 27-month good learners had higher alphabeta heteromeric nAChR binding in hippocampus and temporal-parietal cortex than poor learners, and this result was replicated in both age groups of rabbits treated with galantamine. Results indicate that anatomically more numerous nAChRs or functional activation of a greater number of nAChRs may characterize animals demonstrating optimal learning. During normal aging the expression of high-affinity binding sites declines. Age-related changes in the expression of hippocampal alphabeta heteromeric nAChRs may account for some of the documented age-related impairment in learning. However, individual differences in alphabeta heteromeric nAChRs also exist early in life, as better learning in 4-month rabbits was associated with significantly higher binding.


Remarkably fast and selective aromatization of Hantzsch esters with MoOCl4 and MoCl5: a chemical model for possible biologically relevant properties of molybdenum-containing enzymes.
Mo(VI) and Mo(V) salts both react selectively with Hantzsch esters to produce substitute pyridines in good-to-excellent yield (75-99%). The remarkable reactivity and selectivity of MoOCl(4) under reflux of acetonitrile and MoCl(5) in dichloromethane at room temperature encouraged us to propose that molybdenum-containing enzymes (such as xanthine or aldehyde oxidase) also participate to some degree in the metabolism of 1,4-dihydropyridine drugs in the liver analogous to NADH in the respiratory chain.


Concomitant use of levothyroxine and interacting medications in U.S. ambulatory care visits.
Levothyroxine (LT4) is the third most commonly prescribed medication in the United States. It is a narrow therapeutic index medication, and thus can be impacted by drug-drug interactions, which are primarily available over-the-counter. The prevalence and associated factors with concomitant interacting drugs with LT4 is limited since over-the-counter products are not routinely captured in many drug databases. This study aimed to characterize the concomitant use of LT4 with interacting drugs at ambulatory care visits in the United States. A cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) from 2006 to 2018 was completed. Ambulatory care visits in the United States involving adult patients with a LT4 prescription were included in the analysis. The primary outcome was initiation or continuation of a selected concomitant interacting drug which impacts LT4 absorption (e.g., proton pump inhibitor) in a patient visit in conjunction with LT4. The authors analyzed 372,942,000 visits (weighted from a sample of 14,880) with a reported LT4 prescription. Concomitant use of interacting drugs with LT4 occurred in 24.4% of visits in which 80% of interacting drugs were proton pump inhibitors. Ages 35-49 years (adjusted odds ratio [aOR], 1.59), 50-64 years (aOR, 2.27), and ≥65 years (aOR, 2.87) compared to 18-34 years, female (aOR 1.37) versus males, and visits in 2014 or later (aOR, 1.27) versus 2006-2009 were associated with increased odds of concomitant interacting drug use in multivariable analysis. At ambulatory care visits between 2006 and 2018, concomitant use of LT4 and interacting drugs impacted one-quarter of patient visits. Increased age, females, and visits later in the study period were associated with increased odds for concomitant interacting drugs. Additional work is needed to identify downstream consequences of concomitant use.


Kinetics of torquetenovirus DNA load in a recent kidney transplant recipient with mild SARS-CoV-2 infection and a failed antibody response.
Kidney transplant (KT) recipients are at an increased risk for severe COVID-19 because of their immunosuppressed state. A 42-year-old KT patient was diagnosed with COVID-19 three months after KT. Despite lymphopenia and several risk factors, he had a mild disease course. Nasopharyngeal real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 became negative 48 days after detection. SARS-CoV-2 IgG antibodies became negative after day 40. TTV DNA load increased with the onset COVID-19 and reduced after its resolution. This is the first report where TTV DNA load was measured during the course of COVID-19.


The feasibility of a search filter for the adverse effects of nondrug interventions in MEDLINE and Embase.
Authors and indexers are increasingly including terms for adverse drug effects in the titles, abstracts, or indexing of records in MEDLINE and Embase. However, it is not clear if this is the same for studies with nondrug adverse effects data. We therefore assessed the feasibility of using adverse effects terms when searching MEDLINE or Embase to retrieve papers of nondrug adverse effects. A collection of papers that reported data on nondrug adverse effects was sought from included studies of systematic reviews. Each included study was analysed to ascertain whether the corresponding record in MEDLINE and Embase included adverse effects terms in the title, abstract, or indexing. From 9129 records screened from DARE, 30 reviews evaluating nondrug adverse effects met our inclusion criteria. From these, 635 unique papers were included in our analysis. Sensitive searches for adverse effects required generic and specific named adverse effects terms using the title, abstract, and indexing. Records relating to surgical interventions were more likely to contain adverse effects terms than records relating to nonsurgical interventions. Using any adverse effects terms in the title, abstract or indexing in MEDLINE and Embase would have identified an average of 94% of papers on surgical adverse effect interventions per systematic review and 72% of papers on nonsurgical adverse effects per systematic review. Hence, while a generic nondrug adverse effect search filter may not yet be feasible, a filter for the adverse effects of surgical interventions may be within reach.


[Frequency of association of cardiac and urinary abnormalities].
In 680 cases of congenital heart disease, the authors discovered 49 uropathies (i.e. 7.2%) diagnosed thanks to a film of the urinary apparatus taken during angiocardiography. These uropathies were encountered mainly during ventricular septal defects, pulmonary stenosis and Fallot's tetralogy. The diagnostic value of the film during angiocardiography is great as it revealed 22 out of 49 uropathies (i.e. 44.9%) clinically silent until then.


Human papillomavirus multiplex ligation-dependent probe amplification assay for the assessment of viral load, integration, and gain of telomerase-related genes in cervical malignancies.
We evaluated the reliability of a novel multiplex ligation-dependent probe amplification (MLPA) assay in detecting integration of human papillomavirus (HPV) based on the viral E2/E6 copy number ratio in formalin-fixed and paraffin-embedded cervical lesions. The MLPA results were compared with those of amplification of papillomavirus oncogene transcripts for RNA, detection of integrated papillomavirus sequences for DNA, and HPV fluorescence in situ hybridization (FISH). DNA was isolated from 41 formalin-fixed and paraffin-embedded HPV-positive cervical lesions (cervical intraepithelial neoplasia grade 3 lesions, squamous cell carcinomas, and adenocarcinomas) for MLPA analysis. From 13 matching frozen samples, DNA and RNA were isolated for the detection of integrated papillomavirus sequences and/or the amplification of papillomavirus oncogene transcripts, respectively. Integrated HPV16, HPV18, or both were identified. The MLPA assay detected viral integration in 12 of these 13 cases, and episomal copies also were detected in 7 cases. In 20 of the 24 cases with exclusive viral integration or episomal viral copies as detected by FISH, MLPA confirmed the physical status of the virus. In the cases classified as mixed by FISH, the presence of excess episomal copies complicated the recognition of viral integration by MLPA. Furthermore, the feasibility of detecting gain of the telomerase genes with the HPV MLPA assay was evaluated. The MLPA confirmed the FISH data in 12 of 13 cases in which the status of copy number gain for telomerase RNA component was known. In conclusion, the HPV MLPA assay can be performed on routinely processed cervical lesions for the detection of viral load and HPV integration.


Exposure measurement of aflatoxins and aflatoxin metabolites in human body fluids. A short review.
Aflatoxins are highly toxic secondary fungal metabolites mainly produced by Aspergillus flavus and A. parasiticus. Human exposure to aflatoxins may result directly from ingestion of contaminated foods, or indirectly from consumption of foods from animals previously exposed to aflatoxins in feeds. This paper focuses on exposure measurement of aflatoxins and aflatoxin metabolites in various human body fluids. Research on different metabolites present in blood, urine, breast milk, and other human fluids or tissues including their detection techniques is reviewed. The association between dietary intake of aflatoxins and biomarker measurement is also highlighted. Finally, aspects related to the differences between aflatoxin determination in food versus the biomarker approach are discussed.


The model organism as a system: integrating 'omics' data sets.
Various technologies can be used to produce genome-scale, or 'omics', data sets that provide systems-level measurements for virtually all types of cellular components in a model organism. These data yield unprecedented views of the cellular inner workings. However, this abundance of information also presents many hurdles, the main one being the extraction of discernable biological meaning from multiple omics data sets. Nevertheless, researchers are rising to the challenge by using omics data integration to address fundamental biological questions that would increase our understanding of systems as a whole.


Fatigue-related changes in stance leg mechanics during sidestep cutting maneuvers.
The increased number of women participating in sports has been paralleled by a greater knee injury rate in women compared to men. Among these injuries, those occurring to the anterior cruciate ligament are commonly observed during sidestep cutting maneuvers. In addition, general fatigue appears to correlate with injuries to the passive structures during a game. The purpose of the study was to examine the fatigue-related changes in lower limb mechanics during a cutting maneuver in female athletes. Twelve college female soccer players were recruited. Sidestep cutting maneuvers were performed prior to, and after a fatiguing exercise (60-min shuttle run). Fatigue state was evaluated by calculating power output from countermovement jumps performed before and after the shuttle run. Three-dimensional stance leg hip, knee and ankle kinematics and kinetics during the cutting task were calculated and reported as initial ground contact angle, ranges of motion and peak moments of the stance phase. Cutting maneuver stance leg mechanics were analyzed through repeated measures two-way ANOVAs (P<0.05). Jumping power output decrements suggested fatigue was induced. Sagittal and frontal planes kinematics and kinetics of the cutting task did not change after fatigue. In the transverse plane, the hip, knee and ankle joints were more externally rotated at touchdown, and during stance the knee underwent greater internal rotation. Increased knee internal rotation has potentially important implication for increased injury risk when combined with unexpected perturbation faced in a game. Also, the fact that the sub-maximal level of fatigue did not lead to greater dynamic changes suggests a possible threshold of fatigue before function is dramatically affected.


Genetic polymorphism of ferula mushroom growing on Ferula sinkiangensis.
Mating tests, internal transcribed spacer (ITS) sequence analysis, intergenic spacer 1-restriction fragment length polymorphism (IGS1-RFLP), IGS1 sequence analysis, and IGS2-RFLP analysis were carried out on isolates of 17 morphologically different Pleurotus mushrooms collected on Ferula sinkiangensis. The isolates were divided, based on mating tests and ITS sequence analysis, into two groups identical to P. eryngii var. ferulae and P. nebrodensis, respectively. Single spores from these two groups were incompatible, but those from P. eryngii var. ferulae and P. eryngii were compatible and combined to produce 56.25% dikaryon mycelia with clamp connections. The ITS of P. eryngii var. ferulae and P. nebrodensis (GenBank accession no. AY311408) were both 638 bp in size but differed by 3% in sequence. P. eryngii var. ferulae and P. eryngii (GenBank accession no. AY368658) were identical in ITS size and sequence. P. nebrodensis was the dominant population of Pleurotus mushroom growing on F. sinkiangensis. It exhibited genetic diversity. The two species could also be distinguished by IGSI-RFLP, similar to identification by mating tests and ITS sequence analysis. Difference in IGS1-RFLP existed between P. eryngii var. ferulae and P. nebrodensis. The sequence difference reached 2.28%. Both IGS1 size and IGS1-RFLP were similar among the different samples of P. nebrodensis. The 17 isolates were separated into five types based on IGS2 size and IGS2-RFLP, with both interspecies and extraspecies differences. P. nebrodensis exhibited polymorphism and was divided into four types. These results agreed with macroscopic differences. IGS2 might be the effective domain of genetically polymorphic ribosomal DNA in P. nebrodensis mushrooms found in Xinjiang, China.


Dissimilatory sulfate reduction in the archaeon 'Candidatus Vulcanisaeta moutnovskia' sheds light on the evolution of sulfur metabolism.
Dissimilatory sulfate reduction (DSR)-an important reaction in the biogeochemical sulfur cycle-has been dated to the Palaeoarchaean using geological evidence, but its evolutionary history is poorly understood. Several lineages of bacteria carry out DSR, but in archaea only Archaeoglobus, which acquired DSR genes from bacteria, has been proven to catalyse this reaction. We investigated substantial rates of sulfate reduction in acidic hyperthermal terrestrial springs of the Kamchatka Peninsula and attributed DSR in this environment to Crenarchaeota in the Vulcanisaeta genus. Community profiling, coupled with radioisotope and growth experiments and proteomics, confirmed DSR by 'Candidatus Vulcanisaeta moutnovskia', which has all of the required genes. Other cultivated Thermoproteaceae were briefly reported to use sulfate for respiration but we were unable to detect DSR in these isolates. Phylogenetic studies suggest that DSR is rare in archaea and that it originated in Vulcanisaeta, independent of Archaeoglobus, by separate acquisition of qmoABC genes phylogenetically related to bacterial hdrA genes.


All-on-4 Concept Update.
Over the past 17 years, the All-on-4 treatment concept has been a reliable and predictable modality to rehabilitate edentulous jaws with immediate function as full-arch prostheses. This article highlights clinically relevant data compiled by numerous All-on-4 investigators including complications and their remedies, occlusion and cantilever trends, implant size utilization, and controversial topics. We provide insights for navigating the complexities of medically diverse populations, faced by our daily practice, with a focus on patient avoidance, risk factors for implant and prosthetic failures, in hopes to minimize complications so clinicians would choose this treatment with confidence.


Bone Morphogenetic Proteins in Anterior Cervical Fusion: A Systematic Review and Meta-Analysis.
Bone morphogenetic proteins (BMPs) have been commonly used as a graft substitute in spinal fusion. Although the U.S. Food and Drug Administration issued a warning on life-threatening complications of recombinant human BMPs (rhBMPs) in cervical spine fusion in 2008, their off-label use has been continued. This investigation aimed to review the evidence for the use of rhBMP-2 and rhBMP-7 in anterior cervical spine fusions. A comprehensive search was performed through Ovid (MEDLINE), PubMed, and Embase. The risk of bias assessment was according to the recommended criteria by the Cochrane Back and Neck group and MINORS (Methodological Index for Non-Randomized Studies). A wide array of radiographic and clinical outcomes including the adverse events were collated. Eighteen articles (1 randomized and 17 nonrandomized) were eligible for inclusion. The fusion rate was higher with use of rhBMP in most studies and our meta-analysis of the pooled data from 4782 patients confirmed this finding (odds ratio, 5.45; P < 0.00001). Altogether, the rhBMP and control groups were comparable in patient-reported outcomes. However, most studies tended to show a significantly higher incidence of overall complication rate, dysphagia/dysphonia, cervical swelling, readmission, wound complications, neurologic complications, and ossification. Application of rhBMPs in cervical spine fusion yields a significantly higher fusion rate with similar patient-reported outcomes, yet increased risk of life-threatening complications. Thus, we do not recommend the use of rhBMP in anterior cervical fusions.


Consequences of contaminant mixture on the dynamics and functional diversity of bacterioplankton in a southwestern Mediterranean coastal ecosystem.
Contamination of coastal environments is often due to a complex mixture of pollutants, sometimes in trace levels, that may have significant effects on diversity and function of organisms. The aim of this study was to evaluate the short-term dynamics of bacterioplankton exposed to natural and artificial mixtures of contaminants. Bacterial communities from a southwestern Mediterranean ecosystem, lagoon and the bay (offshore) of Bizerte were exposed to i) elutriate from resuspension of contaminated sediment, and ii) an artificial mixture of metals and herbicides mimicking the contamination observed during sediment resuspension. Elutriate incubation as well as artificial spiking induced strong enrichments in nutrients (up to 18 times), metals (up to six times) and herbicides (up to 20 times) relative to the in situ concentrations in the offshore station, whereas the increases in contaminants were less marked in the lagoon station. In the offshore waters, the artificial mixture of pollutants provoked a strong inhibition of bacterial abundance, production and respiration and significant modifications of the potential functional diversity of bacterioplankton with a strong decrease of the carbohydrate utilization. In contrast, incubation with elutriate resulted in a stimulation of bacterial activities and abundances, suggesting that the toxic effects of pollutants were modified by the increase in nutrient and DOM concentrations due to the sediment resuspension. The effects of elutriate and the artificial mixture of pollutants on bacterial dynamics and the functional diversity were less marked in the lagoon waters, than in offshore waters, suggesting a relative tolerance of lagoon bacteria against contaminants.


An educational programme based on salutogenesis theory on childbirth fear and delivery method among nulliparous women: A mixed methods research protocol.
Designing, executing and testing a training intervention based on enhanced concepts of salutogenesis theory for managing fear of childbirth and choice of delivery method among nulliparous women. A Sequential-Exploratory Mixed Methods Research. In the first phase (qualitative approach), the determinants of childbirth fear among nulliparous women will be explored. In the second phase (systematic review), the factors of childbirth fear among them will be summarized. In the third phase, the content of the educational intervention is developed based on the common factors of childbirth fear obtained from the previous two phases of the study. In the fourth phase (randomized controlled trial), two intervention and the control groups will be compared based on primary and secondary outcomes. Using salutogenesis theory in a few interventional studies on various health areas has produced promising results. Based on the evidence, women had less sense of coherence with a strong childbirth fear. Therefore, developing an effective intervention based on this theory can probably help manage childbirth fear and reduce the costs of any potential consequences.


Long-term administration of ninjin'yoeito to treat frailty in older adults: A case series.
Frailty among older people is strongly associated with undernutrition and is likely to cause sarcopenia, which results in a reduction in muscle mass. Although several studies have investigated the benefits of diet changes and exercise therapy in reducing frailty in older adults, few have focused on the use of drug therapy to treat frailty. We report on three cases of older adults (2: female and 1: male) who presented at our clinic with frailty. Their demographics, grip strength, and muscle quality scores were measured at baseline, and they were administered ninjin'yoeito and followed up at 6, 12, and 24 months. Patient 1 was an 82-year-old man with a grip strength of 16.00 kg on the left and a muscle quality score of 35 points. After 24 months, his grip strength was 21.40 kg on the left, and he had a muscle quality score of 47 points. Similarly, despite serious underlying diseases, at each follow-up, the other two patients showed marked improvement in grip strength, and their muscle quality score either increased or remained stable. These results indicate that ninjin'yoeito has considerable potential for improving frailty and sarcopenia in older patients.


Tea extract inhibits intestinal absorption of glucose and sodium in rats.
The effect of tea extract on the intestinal absorption of glucose and sodium was studied in rats. Tea extract reduced the mucosal uptake of glucose and its portal plasma concentration, but was without any effect on its serosal transport. The mucosal uptake of sodium was similarly inhibited. The tea extract reduced also the in vitro activity of the Na(+)-K+ ATPase in an intestinal mucosal homogenate. These data are consistent with the hypothesis that an active ingredient in tea reduced sodium extrusion from the enterocytes by inhibiting the Na(+)-K+ pump, thus destroying the gradient needed for the mucosal transport of glucose.


The morphology of the normal aortic valve as compared with the aortic valve having two leaflets.
We studied 30 normal aortic valves and 64 aortic valves with only two leaflets to examine their morphologic components. The components of the aortic valve are the leaflets, the sinuses, and the interleaflet triangles. The first part of our study shows the relationship of these component parts of the normal aortic valve to the other cardiac structures. The second part shows a wide variation in the architecture of valves having two leaflets. Having produced criteria for the number of sinuses and the number of leaflets, we discovered that previous criteria used in the definition of valves with two leaflets are inadequate when the whole valvular complex is considered. Only seven valves in the study have two leaflets supported by two sinuses. The evidence points to the other valves having started with three leaflets but becoming bicuspid during either intrauterine or postnatal life.


Systemic scleroderma. Clinical and pathophysiologic aspects.
Systemic scleroderma is a generalized disease of connective tissue involving mainly the skin, the gastrointestinal tract, the lungs, the heart, and the kidneys. It can be present in different forms, of which acroscleroderma, with limited cutaneous and extracutaneous involvement, and diffuse scleroderma within a more rapid progression are most characteristic. Circulating antibodies against antinucleolar antigens are present in most patients with systemic scleroderma. They are helpful for establishing a classification and for determining the prognosis of the disease; their involvement in the pathogenesis, however, is still unclear. Alterations of the blood vessels and induction of fibroblasts by potent mediators are thought to play an important role in the early phase of scleroderma. Therefore early diagnosis is required, which then can initiate vasoactive therapy. In patients with systemic scleroderma, who also suffer from additional myositis, interstitial lung diseases, or arthritis, anti-inflammatory treatment with prednisolone and azathioprine is suggested. Development and progression of fibrosis cannot yet be influenced sufficiently. Only D-penicillamine affecting cross-linking of collagen has been widely used in scleroderma and has some beneficial effect.


Mild vocal fold paresis: understanding clinical presentation and electromyographic findings.
The implications of mild vocal fold hypomobility are incompletely understood. This study describes the clinical, electromyographic, and probable etiologic findings in patients who presented with complaints of dysphonia and whose physical examination revealed vocal fold paresis as a factor possibly contributing to their voice complaints. A retrospective chart review of all patients who presented to a tertiary laryngology referral center over a 13-month period, who had a clinical diagnosis of mild vocal fold hypomobility and who underwent laryngeal electromyography, were included in the study. A total of 22 patients completed the medical evaluation of their voice complaint. Of these patients, 19 (86.4%) were found to have evidence of neuropathy on laryngeal electromyography. The clinical picture indicated the following probable origins for the vocal fold paresis: goiter/thyroiditis (7/22 or 31.8%), idiopathic (4/22 or 18.2%), viral neuritis (4/22 or 18.2%), trauma (3/22 or 13.6%), and Lyme's disease (1/22 or 4.5%). This article describes the clinical entity of mild vocal fold hypomobility and associated flexible laryngoscopic, rigid strobovideolaryngoscopic, and laryngeal electromyographic findings.


Resurrection of Cortinarius coalescens: taxonomy, chemistry, and ecology.
Cortinarius coalescens Kärcher & Seibt is a rare European species of the subgenus Phlegmacium, section Phlegmacioides, neglected in recent molecular studies. New primers (CortF and CortR) designed for species in the section Phlegmacioides allowed to obtain ITS rDNA sequence data from the holotype collection of C. coalescens; according to the results, this epithet has priority over C. crassorum Rob. Henry ex Rob. Henry, C. pardinus Reumaux, and C. parargutus Bidaud, Moënne-Locc. & Reumaux. Morphological and ecological observations on recent collections of C. coalescens from the Czech Republic in comparison with the co-occurring C. largus are discussed. Nomenclatural and taxonomic comments on C. tomentosus Rob. Henry, C. balteatotomentosus Rob. Henry, and C. subtomentosus Reumaux are also provided. So far, C. coalescens is known with certainty from Germany, France, and the Czech Republic, where it grows in deciduous forests on acid to neutral soils. Arsenic and its compounds were determined in C. coalescens and related species of the section Phlegmacioides: C. largus, C. pseudodaulnoyae, and C. variecolor. Total arsenic concentrations were in the range 3.6-30.2 mg kg-1 (dry matter) and arsenobetaine was the major arsenic compound.


[No free water in the treatment of "hyperosmolar diabetic coma": treatment control by comparing serum and CSF (author's transl)].
Some serum and CSF concentrations were measured in five patients with severe hyperosmolar coma (mean blood sugar = 58.9 mmol/l; osmolarity = 406 mosmol/l). A gradual decrease of serum osmolarity prevented the development of an osmotic gradient between CSF and extracellular space. Insulin treatment (1-20 IU/h) with a motor infusion pump and infusion of hypertonic solutions decreased serum osmolarity by 2-4 mosmol/l X h. The faster fall of glucose in the extracellular space was compensated by hypertonic saline infusions (up to 365 mosmol/l). All patients survived.


Plastic zone range of a roadway considering the creep effect.
The plastic zone range is an important parameter in the analysis of damage characteristics and the degree of damage to the rock surrounding a roadway. Based on the establishment of a plastic zone calculation model considering the creep effect, this paper obtains the characteristics of the change in the plastic zone damage range with time by solving the model. Additionally, the validity of the model is verified by field experiments. The research results can provide guidance for gas pressure measurement and gas drainage in coal mines.


Screening and identifying cucurbitacins and cucurbitacin glycosides in Cucumis sativus using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry combined with in-source fragmentation and alkali adduct ions.
Cucumber, as a popular fruit and vegetable, has tremendously contributed to providing a sufficient and high-quality food supply. However, the cucumber plant metabolites, which may possess potential benefits for human health, were rarely reported. In addition, rapid detection of these metabolites from the complex biological matrix of cucumber samples is a tremendous challenge. A rapid detection method was established to systematically screen cucurbitacins and cucurbitacin glycosides in cucumber plants by combining high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC-Q-TOF-MS) with in-source fragmentation (ISF). Moreover, the alkali cations, including acetic acid, 0.1% LiCl, 0.1% NH4 Cl, 0.1% NaCl, and 0.1% KCl, were added to the mobile phase for improving the ion response. The fragmentation pathways of seven cucurbitacins and cucurbitacin glycosides were primarily investigated. The characteristic ISF ions at m/z 501.3211 and 503.3367 were identified and employed to screen 40 cucurbitacins and cucurbitacin glycosides from the complex biological matrix. Their structures were identified by their tandem mass spectrometry (MS/MS) spectra and fragmentation pathways of references. Finally, the metabolic distribution and network of cucurbitacins and cucurbitacin glycosides in cucumber plants were also proposed. This work marks the first systematic and comprehensive study of the metabolites in cucumber plants using HPLC-Q-TOF-MS technology, providing a template for screening and identifying the triterpenoids from other plant-derived medicines or food.


Surgical Outcomes of Endoscopic Versus Conventional Septoplasty.
The most common cause of nasal obstruction is a deviated nasal septum. It causes breathing difficulties and may eventually also cause sinusitis, epistaxis, sleep disturbances and snoring. The traditional surgeries of the nasal septum improve the nasal airway but do not fulfil the essential criteria in most instances. Endoscopic septoplasty is a fast-developing concept and gaining popularity as it provides a direct targeted approach to the septal anatomic deformity allowing a minimally invasive procedure under excellent visualization. The aim of this study is to compare the post-operative morbidity among conventional and endoscopic septoplasty. The present prospective study was conducted on 50 patients having deviated nasal septum. Patients were randomly divided into two groups of 25 each. Out of 50 patients, in 25 patients (Group A) Conventional septoplasty was done, whereas in other 25 patients (Group B) endoscopic septoplasty was done. The patients were followed up post-operatively at 2 weeks, 4 weeks and 8 weeks. Study Design: comparative study. The mean of operating time (min) in Group A was 60.47 ± 8.16 which was significantly higher as compared to Group B (39.7 ± 6.73). (p value < .0001). The Mean of blood loss (mL) was significantly higher in Group A (88.67 ± 8.77) as compared to Group B. (54.6 ± 7.18). (p value < .0001). Post-operative NOSE score at one month was 7.33 ± 1.5 in group A which was significantly higher as compared to Group B (5 ± 1.41). (p value = 0.0007) whereas post-operative NOSE score at 3 months in Group A was 6.53 ± 1.25 which was significantly higher as compared to Group B (4.4 ± 1.78). Proportion of post-operative complications was comparable in Group A and Group B (No complication 80% vs. 92% respectively). According to the present study, both the conventional and endoscopic septoplasty procedures were effective in relieving nasal obstruction in the patients. Endoscopic septoplasty showed significantly better result than conventional septoplasty in terms of time taken for surgery, blood loss during the surgery, post-operative complications and in terms of quality of life as assessed by NOSE Score.


Comparison of two procedures for laparoscopic-assisted vaginal hysterectomy of large myomatous uteri.
To evaluate whether laparoscopic bipolar coagulation of uterine vessels (LBCUV) and supracervical amputation improve laparoscopic-assisted vaginal hysterectomy (LAVH). Prospective, randomized, longitudinal study (Canadian Task Force classification II-1). Private practice, university-affiliated hospital. Sixty-four women (age 31-52 yrs) with symptomatic myomatous uteri larger than 12 weeks on bimanual examination. LAVH with or without LBCUV and laparoscopic supracervical amputation followed by trachelectomy. LBCUV and laparoscopic supracervical amputation followed by trachelectomy and removal of the specimen vaginally were performed successfully in 29 women (group A). Hysterectomy was performed successfully in 32 comparable patients (group B) with severing of the round ligament, ovarian ligament, or infundibulopelvic ligament, and preparation of the bladder flap in the laparoscopic phase, and severing of uterine vessels and cardinal-uterosacral ligament complex through the vagina. Average blood loss was 169.8 and 308.7 ml in groups A and B, respectively (p <0.05); average operating time was 126.4 and 152.8 minutes, respectively (p <0.05); hemoglobin decreased on average 0.9 and 1.7 g/100 ml, respectively (p <0.05). Conclusion. LBCUV and laparoscopic supracervical amputation followed by trachelectomy reduce operating time and blood loss in LAVH, and allow conversion of many abdominal procedures to laparoscopy.


Planning a maternal-fetal medicine program. Relationship to obstetricians.
The success of a consultation program is dependent on the ready availability of skilled subspecialty advice that is nonthreatening and sensitive to the needs of the referring obstetrician.


Parenchymal liver metastasis in advanced ovarian cancer: Can bowel involvement influence the frequency and the related mortality rate?
This retrospective study estimates the frequency of parenchymal liver metastasis (PLM) and the overall survival (OS) rate of patients with FIGO Stage IIIC-IV Advanced Epithelial Ovarian Cancer (EOC) with bowel involvement. Between November 2008 and July 2020, all consecutive patients with FIGO Stage IIIC-IV EOC who underwent Visceral Peritoneal Debulking and bowel resection(s) at the Gynaecological Oncology Unit of "Centro di Riferimento Oncologico (CRO)", Aviano, Italy, without evidence of PLM at pre-operative imaging assessment, were included in the study. The presence and the time of the onset of PLM during the follow-up period were detected by diagnostic imaging (CT-scan, Ultrasound and PET). The OS of patients with and without PLM was compared. Considering the bowel's layers, the association between depth of bowel involvement, number of PLM, and the relative OS rate was evaluated. The median follow-up period was 47.3 (12-138) months. PLM occurred in 24/72 (33.0%) cases; the average onset time of PLM was 13 months. PLM was associated with increased significant mortality risk and an average OS of 33.2 versus 56.8 months (p < 0.001). The risk of developing PLM correlated directly with the depth of bowel involvement. However, there was no statistical difference between the layers in terms of OS at the end of the observational period. PLM occurred more frequently among patients with EOC and bowel involvement. The PLM arose within 15 months of follow-up and the frequency increased according to the depth of involvement. Particularly, the difference is remarkably higher starting from muscular layer where the total number of PLM arose significantly (p = 0.02). Although there was no significant difference among the infiltrated bowel layers in terms of OS, patients with bowel involvement up to muscular had a dramatic reduction in the OS rate during the first 30 months of follow-up.


Effects of repeated cycles of sterilisation on the mechanical characteristics of titanium miniplates for osteosynthesis.
This study investigates the changes occurring in the mechanical characteristics of osteosynthesis titanium miniplates when exposed to repeated sterilization cycles. For this study Medicon (c) titanium miniplates were used. The characteristics of miniplates were evaluated using the Penetration Resistance test, MSC/Pal2 Software, and the Finite Elements Method (F.E.M.). Surface roughness measurements were also carried out. Statistical analysis was conducted using the One way ANOVA model. The significance level was set at >0.05. The one way ANOVA analysis between HV value and increased sterilization cycles showed P>0.029; between the Ra value and increased sterilization cycles it was P>0.325; between the Rq value and increased sterilization cycles it was P>0.703. The Finite Element Model shows an amplified deformed shape of the miniplate at a load of 196 [N]. At this load value the equivalent 'von Mises stress' reaches the value of sigmaP0.2, shown by the ASTM F 67-95 standard. Stress distribution comparison between the six-holed plate and the equivalent straight miniplate shows more consistent behaviour for the Medicon (c) miniplate. The rigidity of the Medicon (c) miniplate is 14.46, lower than that for the equivalent straight miniplate (R=23.4). The ANOVA analysis between the break load and increased sterilization cycles showed P>0.175; between the break position and increased sterilization cycles it showed P>0.016. Experimental static tests have shown that all tested miniplates did not have notable differences and this suggests that sterilization cycles do not affect mechanical characteristics.


Transformation between 2D covalent organic frameworks with distinct pore hierarchy via exchange of building blocks with different symmetries.
Transformation between 2D covalent organic frameworks (COFs) via exchange of molecular building blocks with different symmetries has been realized, which gives rise to the conversion between 2D COFs with distinct pore hierarchy. This type of monomer replacement has expanded the scope of the building-unit-exchange-based COF-to-COF transformation strategy.


[Measuring accommodation time with a laptop computer].
Presently, there are no completely reliable examinations such as focus from a distant place to a near place during daily work. We developed a simple testing system for accommodation time using a 5 m chart and a laptop computer. We studied 177 healthy peoples. They turned their eyes from the 5 m chart to the display of the personal computer at about 70 cm in front of the eyes. We measured the minimum time(MTC) for recognizing three Kanji(Chinese characters) randomly chosen from a total of 15 characters on the display. The MTCs with + 1.25 D added were shorter than those with complete correction. The MTCs in both conditions extended with age. In subjects less than 40 years old, the MTCs measured with both eyes were significantly shorter than those with a single eye completely corrected. In subjects over 40 years old, there was no difference. The MTCs were shorter significantly with complete correction than with + 1.25 D added. The MTCs decreased as the accommodative amplitude increased. There is significant correlation between the accommodative amplitude and the MTCs. We can use the MTCs as one method of measuring time of accommodation.


Factors responsible for the discrepancy between IL28B polymorphism prediction and the viral response to peginterferon plus ribavirin therapy in Japanese chronic hepatitis C patients.
IL28B polymorphisms serve to predict response to pegylated interferon plus ribavirin therapy (PEG IFN/RBV) in Japanese patients with chronic hepatitis C (CHC) very reliably. However, the prediction by the IL28B polymorphism contradicted the virological response to PEG IFN/RBV in some patients. Here, we aimed to investigate the factors responsible for the discrepancy between the IL28B polymorphism prediction and virological responses. CHC patients with genotype 1b and high viral load were enrolled in this study. In a case-control study, clinical and virological factors were analyzed for 130 patients with rs8099917 TT genotype and 96 patients with rs8099917 TG or GG genotype who were matched according to sex, age, hemoglobin level and platelet count. Higher low-density lipoprotein (LDL) cholesterol, lower γ-glutamyltransferase and the percentage of wild-type phenotype at amino acids 70 and 91 were significantly associated with the rs8099917 TT genotype. Multivariate analysis showed that rs8099917 TG or GG genotype, older age and lower LDL cholesterol were independently associated with the non-virological responder (NVR) phenotype. In patients with rs8099917 TT genotype (predicted as virological responder [VR]), multivariate analysis showed that older age was independently associated with NVR. In patients with rs8099917 TG or GG genotype (predicted as NVR), multivariate analysis showed that younger age was independently associated with VR. Patient age gave rise to the discrepancy between the prediction by IL28B polymorphism and the virological responses, suggesting that patients should be treated at a younger age.


Increased Risk of Osteoporosis in Depressive Patients with Erectile Dysfunction: A Cross-sectional Study from Malaysia.
Depression imposes numerous changes on depressive men, promoting for low bone mineral density (BMD) and erectile dysfunction (ED), yet no published data on exploring the possible association between these two disorders among depressive men. We therefore investigated whether low BMD is associated with ED among depressive men and highlighted the possible mutual underlying factors that might give rise to these two disorders in this specific group of patients. In this cross-sectional study, 119 depressive men were recruited and their sociodemographic and clinical characteristics were obtained. Erectile function was evaluated using the 5-item International Index of Erectile Function. All patients received a calcaneal BMD scanning. Chi-square test was conducted to determine if a significant association exists between ED and low BMD. Of the study participants, ninety patients reported ED, while 29 patients reported no ED. Within the ED group, there was a significantly higher proportion of patients with low BMD compared to the non-ED group (85.6% vs. 62.1%, P = 0.006). In addition, among younger participants (i.e., aged < 50 years old), the difference in T-score between ED patients (Md = -2.2, n = 41) and non-ED patients (Md = -1.3, n = 20) was significant (P = 0.001); but held no significance among older participants. While our findings are considered prefatory, we reported that low BMD was significantly associated with ED in depressive men and that only among young depressive patients, BMD was significantly lower in ED patients compared to non-ED patients. More research investigating these findings and the possible underlying mechanisms for such association are warranted.


Detecting intermolecular NOEs by means of a novel DPFGSE pulse sequence. Application to the solvation of carbohydrates in binary mixtures.
We present a pulse sequence based on solute-to-solvent NOE enhancement and aimed at the detection of intermolecular NOE's. Thus, a W3 pulse cluster is used to selectively filter the solvent signals in a DPFGSE sequence. The sequence has been tested on a sample of glucose dissolved in two binary aqueous mixtures (water-acetonitrile and water-DMSO). We show how the resulting enhancements may derive from intermolecular cross-relaxation or, in the water-DMSO sample, also from chemical exchange. In each case, a quantitative interpretation of the data is also supplied, both in terms of local enrichment in one specific solvent (preferential solvation), and by means of a kinetic model for a two-site chemical exchange.


Anti-photoaging potential of Botulinum Toxin Type A in UVB-induced premature senescence of human dermal fibroblasts in vitro through decreasing senescence-related proteins.
This study was aimed to evaluate the anti-photoaging effects of Botulinum Toxin Type A (BoNTA) in Ultraviolet B-induced premature senescence (UVB-SIPS) of human dermal fibroblasts (HDFs) in vitro and the underlying mechanism. We established a stress-induced premature senescence model by repeated subcytotoxic exposures to Ultraviolet B (UVB) irradiation. The aging condition was determined by cytochemical staining of senescence-associated β-galactosidase (SA-β-gal). The tumor suppressor and senescence-associated protein levels of p16(INK-4a), p21(WAF-1), and p53 were estimated by Western blotting. The G1 phase cell growth arrest was analyzed by flow cytometry. The mRNA expressions of p16, p21, p53, COL1a1, COL3a1, MMP1, and MMP3 were determined by real-time PCR. The level of Col-1, Col-3, MMP-1, and MMP-3 were determined by ELISA. Compared with the UVB-irradiated group, we found that the irradiated fibroblasts additionally treated with BoNTA demonstrated a decrease in the expression of SA-β-gal, a decrease in the level of tumor suppressor and senescence-associated proteins, a decrease in the G1 phase cell proportion, an increase in the production of Col-1 and Col-3, and a decrease in the secretion of MMP-1 and MMP-3, in a dose-dependent manner. Taken together, these results indicate that BoNTA significantly antagonizes premature senescence induced by UVB in HDFs in vitro, therefore potential of intradermal BoNTA injection as anti-photoaging treatment still remains a question.


Herba Artemisiae annuae tea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: a randomized double-blind clinical trial.
Tea preparations from the herb Artemisia annua L. (Aa) which is used in traditional Chinese medicine might offer an inexpensive way of producing artemisinin drugs locally. We compared Aa with sulfadoxine-pyrimethamine (SP) in the treatment of uncomplicated falciparum malaria in semi-immune adults. After seven days, the cure rate was 7/10 for the Aa compared to 7/9 for SP; this dropped to 4/10 for Aa and 4/9 for SP at day 14 and to 1/9 for Aa and 3/8 for SP at day 28.


A multicentre randomized/controlled trial of a conventional versus modestly accelerated radiotherapy in the laryngeal cancer: influence of a 1 week shortening overall time.
To compare in a phase III study the loco-regional control, disease-free survival and overall survival induced by an accelerated regimen (AF) as compared with conventional regimen (CF) and to analyze the early and late post-radiation morbidity in both arms. Patients with age < or = 75, WHO 0-1, suitable for a radical course of radiotherapy T1-T3, N0, M0, stage of glottic and supraglottic laryngeal cancer were randomized to either CF: 66Gy given in 33 fractions over 45 days or AF: 66Gy given in 33 fractions over 38 days (2 fractions every Thursday). A total of 395 patients were included from 05.1995 to 12.1998. Early toxicity: At the end of radiotherapy patients treated with AF complained for more severe reactions than patients treated with CF. In 8 weeks after treatment completion patients treated with AF complained only for more severe pain on swallowing (P=0.027). In 4 months after treatment completion all types of toxicity except for skin teleangiectasia (P=0.001) were similar in the two groups. Loco-regional control: comparison between CF and AF showed no difference in terms of loco-regional control (P=0.37). The improvement in AF in terms of loco-regional control is estimated to be 3-5% in comparison with conventional regimen and is not significant. The intensity of reactions after 4 months was similar in both arms, what suggests the possibility of further shortening of the overall time by few days or enhancing the total dose within the limits of acceptable morbidity.


Molecular mechanisms of syncytin-1 in tumors and placental development related diseases.
Human endogenous retroviruses (HERVs) have evolved from exogenous retroviruses and account for approximately 8% of the human genome. A growing number of findings suggest that the abnormal expression of HERV genes is associated with schizophrenia, multiple sclerosis, endometriosis, breast cancer, bladder cancer and other diseases. HERV-W env (syncytin-1) is a membrane glycoprotein which plays an important role in placental development. It includes embryo implantation, fusion of syncytiotrophoblasts and of fertilized eggs, and immune response. The abnormal expression of syncytin-1 is related to placental development-related diseases such as preeclampsia, infertility, and intrauterine growth restriction, as well as tumors such as neuroblastoma, endometrial cancer, and endometriosis. This review mainly focused on the molecular interactions of syncytin-1 in placental development-related diseases and tumors, to explore whether syncytin-1 can be an emerging biological marker and potential therapeutic target.


Changes of plasma insulin, urea, amino acids and rumen metabolites in somatotropin treated dairy cows.
An experiment was performed to evaluate the effects of somatotropin on plasma free amino acid, urea and insulin concentrations and rumen fermentation pattern and to assess their relationships. Four Italian Friesian dairy cows fitted with rumen cannulae were used in a switch-back design. Slow releasing recombinant bovine somatotropin (640 mg/cow) was injected every 28 days for two consecutive periods. Rumen fluid and blood samples were collected before and after feeding at 0, 7 and 21 days after rbST injection. Exogenous rbST increased plasma insulin concentration and the insulin response to feeding, and decreased plasma urea and free essential and branched chain amino acid concentrations. rbST did not affect rumen fermentation pattern. No correlation was found between rumen and plasma parameters measured after feeding. Our results are consistent with the notion that the main effect of somatotropin is post-absorptive.


Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S-Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt.
Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase P1 (GSTP1) genes are involved in the metabolism of many carcinogens. Polymorphisms in these genes with altered enzyme activity have been reported. The present study evaluated the synergistic effect between CYP1A1 and GSTP1 gene polymorphisms and smoking on development of HCV-related liver disease and hepatocellular carcinoma (HCC). The patients group comprised 40 patients with HCC and 40 patients with liver cirrhosis. The control group comprised 40 healthy subjects having no history of malignancy. The genetic polymorphisms were studied using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) technique on blood samples. The number of current or former smoker among HCC and cirrhotic patients as well as the median Pack/year of cigarette smoked were significantly higher in HCC and liver cirrhotic patients than in control group. Subjects with CYP1A1 gene variants (m1 and m3) had no significant risk to develop cirrhosis or HCC compared to control group. Individuals carrying the Ile/Val genotype of GSTP1 had a significant increased risk of HCC (OR of 2.2, 95 % CI 1.143-4.261) and had larger tumor size. No significant risk was observed on combining both genes variants or on combining smoking with variants of both genes. In conclusion, the GSTP1 Ile/Val genotype and Val allele are associated with an increased risk of HCC. CYP1A1 and GSTP1 genes variants interaction did not increase the risk of HCC.


Placebo effects in pain.
Placebo effects influence symptom perceptions and treatment outcomes. Placebo effects can be explored in laboratory settings controlling for natural history and expectations. Such a mechanistic approach to neurological disorders has been implemented in the domain of chronic clinical pain and other neurological disorders. This article therefore focuses on definitions and historical notes related to placebo effects and mechanisms of placebo effects in chronic pain. Knowledge on mechanisms of placebo effects could inform current clinical practice for the treatment of neurological disorders by focusing on patients (and providers) expectations for outcome optimization.


Anesthetic considerations in HELLP syndrome.
HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is an obstetric complication with heterogonous presentation and multisystemic involvement. It is characterized by microangiopathic hemolytic anemia, elevated liver enzymes by intravascular breakdown of fibrin in hepatic sinusoids and reduction of platelet circulation by its increased consumption. In terms of these patients' anesthetic management, it is essential to consider some details: (1) effective, safe perioperative management by a multidisciplinary approach, and quick, good communication among clinical specialists to achieve correct patient management; (2) neuroaxial block, particularly spinal anesthesia, is the first choice to do the cesarean if there is only moderate, but not progressive thrombocytopenia; (3) if a general anesthesia is required, it is necessary to control the response to stress produced by intubation, especially in patients with either severe high blood pressure or neurological signs, or to prevent major cerebral complications; (4) invasive techniques, e.g., as tracheostomy, arterial, and deep-vein canalization, should be considered; (5) if contraindication for neuroaxial anesthesia exists, rapid sequence intubation with general anesthesia should be regarded as an emergency in patients with full stomach; (6) increased risk of difficult airways should be taken into account. Optimal patient management can be chosen after considering the risks and benefits of each anesthetic technique, and based on good knowledge of these patients' pathophysiological conditions. Later, close patient monitoring is recommended for potential development of hemorrhagic complications, disseminated intravascular coagulation (DIC), or eclampsia.


Medication initiation rates are not directly comparable across secondary fracture prevention programs: reporting standards based on a systematic review.
To examine the methods used to calculate the reported medication initiation rates in secondary fracture prevention programs. A systematic review was conducted on postfracture interventions that aimed to improve osteoporosis management in an orthopedic environment. Two authors independently reviewed eligible articles to determine the numerator and denominator used to calculate the rates of antiresorptive medication initiation based on author reports. In interventions with numerator and denominator combinations that appeared to be comparable, we examined the inclusion and exclusion criteria to confirm comparability. Fifty-seven articles reporting on 64 interventions were eligible for the review. A total of 28 different combinations of numerators and denominators to calculate rates were reported for medication initiation across 49 of the 64 interventions. After examining the inclusion and exclusion criteria for rates that appeared to be comparable, the highest number of interventions with a comparable rate was 3. Reporting processes for antiresorptive medication initiation outcomes in secondary fracture prevention programs used heterogeneous standards that prevented useful comparison of programs. Applying different numerator and denominator combinations meant that the same observed number of patients could have resulted in different reported rates. We propose standards for reporting medication initiation rates in such programs.


Circular Production, Designing, and Mechanical Testing of Polypropylene-Based Reinforced Composite Materials: Statistical Analysis for Potential Automotive and Nuclear Applications.
The circularity of polymer waste is an emerging field of research in Europe. In the present research, the thermal, surface, mechanical, and tribological properties of polypropylene (PP)-based composite produced by injection molding were studied. The pure PP matrix was reinforced with 10, 30, and 40% wt. of pure cotton, synthetic polyester, and polyethylene terephthalate post-consumer fibers using a combination of direct extrusion and injection molding techniques. Results indicate that PP-PCPESF-10% wt. exhibits the highest value of tensile strength (29 MPa). However, the values of tensile and flexural strain were lowered with an increase in fiber content due to the presence of micro-defects. Similarly, the values of modulus of elasticity, flexural modulus, flexural strength, and impact energy were enhanced due to an increase in the amount of fiber. The PP-PCCF-40% wt. shows the highest values of flexural constant (2780 MPa) and strength (57 MPa). Additionally, the increase in fiber loadings is directly proportional to the creation of micro-defects, surface roughness, abrasive wear, coefficient of friction, and erosive wear. The lowest average absolute arithmetic surface roughness value (Ra) of PP and PP-PCCF, 10% wt., were 0.19 µm and 0.28 µm. The lowest abrasive wear value of 3.09 × 10-6 mm3/Nm was found for pure PP. The erosive wear value (35 mm3/kg) of PP-PCCF 40% wt. composite material was 2 to 17 times higher than all other composite materials. Finally, the single-step analysis of variance predicts reasonable results in terms of the p-values of each composite material for commercial applications.


The effect of different slaughter methods on the post mortem glycolysis of muscle in lambs.
Differences in muscular activity and rates of decline in the pH of the M. longissimus dorsi of lambs subjected to different methods of stunning and slaughter were observed. Lambs electrically stunned by a head-to-leg method had significantly lower initial pH values as compared to animals stunned by an electrical head-only method, or by captive bolt, or without any form of stunning prior to slaughter. When electrical stunning by a head-to-leg method was combined with low voltage (24 V) electrical stimulation during slaughter and bleeding, mean pH values declined at the highest rate and fell to approximately 6.0 within two hours of slaughter. This last procedure, therefore, has the potential to greatly reduce times between slaughter and freezing without increasing the risk of cold shortening and the associated toughness of meat.


Sequence Context Influences the Structure and Aggregation Behavior of a PolyQ Tract.
Expansions of polyglutamine (polyQ) tracts in nine different proteins cause a family of neurodegenerative disorders called polyQ diseases. Because polyQ tracts are potential therapeutic targets for these pathologies there is great interest in characterizing the conformations that they adopt and in understanding how their aggregation behavior is influenced by the sequences flanking them. We used solution NMR to study at single-residue resolution a 156-residue proteolytic fragment of the androgen receptor that contains a polyQ tract associated with the disease spinobulbar muscular atrophy, also known as Kennedy disease. Our findings indicate that a Leu-rich region preceding the polyQ tract causes it to become α-helical and appears to protect the protein against aggregation, which represents a new, to our knowledge, mechanism by which sequence context can minimize the deleterious properties of these repetitive regions. Our results have implications for drug discovery for polyQ diseases because they suggest that the residues flanking these repetitive sequences may represent viable therapeutic targets.


Optimal cut-off value of reverse remodeling to predict long-term outcome after cardiac resynchronization therapy in patients with ischemic cardiomyopathy.
Whether the optimal cut-off value of left ventricular (LV) reverse remodeling is different in patients with ischemic cardiomyopathy (ICM) vs. non-ischemic cardiomyopathy (NICM) is unclear. This study aimed to clarify this value in patients with ICM and NICM. LV reverse remodeling was defined as a reduction in LV end-systolic volume (LVESV) at 6 months after cardiac resynchronization therapy (CRT). The clinical endpoint was the combination of cardiac death and first hospitalization for worsening heart failure. Ninety-one of 372 patients had ICM. Event-free survival rates did not differ between ICM and NICM groups (66.8% vs. 78.9%; p=0.12). Receiver operating characteristics analysis revealed a 9% reduction in ESV as the optimal cut-off value to predict the composite endpoint in patients with ICM and a 15% reduction in patients with NICM. Multivariate analysis revealed that reductions in ESV of ≥15% and ≥9% were independent predictors of the composite endpoint, as were left bundle branch block (LBBB) and B-type natriuretic peptide (BNP) at 6 months after CRT. In combination with LBBB and BNP, reduction in ESV ≥9% had a higher, but not significant, C-statistics value than ESV ≥15% (0.854, 95% CI 0.729-0.940 vs. 0.801, 95% CI 0.702-0.908, p=0.07). The optimal cut-off value of a reduction in LVESV was lower in patients with ICM than in patients with NICM.


Nanoparticle Delivered VEGF-A siRNA Enhances Photodynamic Therapy for Head and Neck Cancer Treatment.
Photodynamic therapy (PDT) is believed to promote hypoxic conditions to tumor cells leading to overexpression of angiogenic markers such as vascular endothelial growth factor (VEGF). In this study, PDT was combined with lipid-calcium-phosphate nanoparticles (LCP NPs) to deliver VEGF-A small interfering RNA (siVEGF-A) to human head and neck squamous cell carcinoma (HNSCC) xenograft models. VEGF-A were significantly decreased for groups treated with siVEGF-A in human oral squamous cancer cell (HOSCC), SCC4 and SAS models. Cleaved caspase-3 and in situ TdT-mediated dUTP nick-end labeling assay showed more apoptotic cells and reduced Ki-67 expression for treated groups compared to phosphate buffered saline (PBS) group. Indeed, the combined therapy showed significant tumor volume decrease to ~70 and ~120% in SCC4 and SAS models as compared with untreated PBS group, respectively. In vivo toxicity study suggests no toxicity of such LCP NP delivered siVEGF-A. In summary, results suggest that PDT combined with targeted VEGF-A gene therapy could be a potential therapeutic modality to achieve enhanced therapeutic outcome for HNSCC.


Combined Measures of Dynamic Bone Quality and Postural Balance--A Fracture Risk Assessment Approach in Osteoporosis.
We evaluated functional measures of neuromuscular integrity and bone's resistance to fracture as a combined tool in discriminating osteoporosis patients with and without fractures. Functional aspects of neuromuscular integrity were quantified with a noninvasive measure of static and dynamic functional postural stability (FPS), and fracture resistance was obtained with bone shock absorption in patients with osteoporosis aged 65-85 and compared our measures with dual-energy X-ray absorptiometry and Fracture Risk Assessment Tool (FRAX [World Health Organization Collaborating Center for Metabolic Bone Diseases, Sheffield, UK]) in women with osteoporosis, some with and some without vertebral fractures. Patients with vertebral fracture showed larger static FPS (postural sway excursion) in the mediolateral and anterior-posterior directions, suggesting poorer balance. Most of the variables of dynamic FPS showed significant differences between fracture and no-fracture groups (e.g., the fracture group took significantly longer during turning, implying poorer dynamic balance control). Also, compared with healthy control subjects, all 4 dynamic FPS responses for osteoporosis patients with and without fracture were significantly poorer, suggesting potential risk for falls. In summary, patients with osteoporosis who have vertebral fractures (compared with patients with similarly low bone mineral density and other nonfracture risk fractures) have not only lower bone shock absorption damping (ζ) but also increased postural imbalance.


Sonographic evaluation of the portal venous system after elective endoscopic sclerotherapy of esophageal varices.
In order to evaluate possible changes in the portal venous system after endoscopic sclerosis of esophageal varices, 25 cirrhotic patients underwent abdominal ultrasonography before the first session of sclerotherapy and after eradication of esophageal varices had been achieved. The caliber of the portal, splenic, and superior mesenteric veins was measured sonographically in each case. Sonographic results were compared statistically before and after sclerotherapy. Neither evidence of significant variations in the caliber of the portal veins nor thrombotic obliteration was seen. These results support the view that sclerotherapy has no significant negative side effects on the portal venous system.


The role of brassinosteroids in the regulation of the plasma membrane H+-ATPase and NADPH oxidase under cadmium stress.
The present research aim was to define the role of brassinosteroids (BRs) in plant adaptation to cadmium stress. We observed a stimulating effect of exogenous BR on the activity of two plasma membrane enzymes which play a key role in plants adaptation to cadmium stress, H+-ATPase (EC 22.214.171.124) and NADPH oxidase (EC 22.214.171.124). Using anti-phosphothreonine antibody we showed that modification of PM H+-ATPase activity under BR action could result from phosphorylation of the enzyme protein. Also the relative expression of genes encoding both PM H+-ATPase and NADPH oxidase was affected by BR. To confirm the role of BR in the cadmium stimulating effect on activity of both studied plasma membrane enzymes, an assay in the presence of a BR biosynthesis inhibitor (propiconazole) was performed. Moreover, as a tool in our work we used commercially available plant mutants unable to BR biosynthesis or with dysfunctional BR signaling pathway, to further confirm participation of BR in plant adaptation to heavy metal stress. Presented results demonstrate some elements of the brassinosteroid-induced pathway activated under cadmium stress, wherein H+-ATPase and NADPH oxidase are key factors.


Modulation of the bacterial CobB sirtuin deacylase activity by N-terminal acetylation.
In eukaryotic cells, the N-terminal amino moiety of many proteins is modified by N-acetyltransferases (NATs). This protein modification can alter the folding of the target protein; can affect binding interactions of the target protein with substrates, allosteric effectors, or other proteins; or can trigger protein degradation. In prokaryotes, only ribosomal proteins are known to be N-terminally acetylated, and the acetyltransferases responsible for this modification belong to the Rim family of proteins. Here, we report that, in Salmonella enterica, the sirtuin deacylase CobB long isoform (CobBL) is N-terminally acetylated by the YiaC protein of this bacterium. Results of in vitro acetylation assays showed that CobBL was acetylated by YiaC; liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to confirm these results. Results of in vitro and in vivo experiments showed that CobBL deacetylase activity was negatively affected when YiaC acetylated its N terminus. We report 1) modulation of a bacterial sirtuin deacylase activity by acetylation, 2) that the Gcn5-related YiaC protein is the acetyltransferase that modifies CobBL, and 3) that YiaC is an NAT. Based on our data, we propose the name of NatA (N-acyltransferase A) in lieu of YiaC to reflect the function of the enzyme.


A Meta-Analysis of Maternal Prenatal Depression and Anxiety on Child Socioemotional Development.
Observed associations between maternal prenatal stress and children's socioemotional development have varied widely in the literature. The objective of the current study was to provide a synthesis of studies examining maternal prenatal anxiety and depression and the socioemotional development of their children. Eligible studies through to February 2018 were identified using a comprehensive search strategy. Included studies examined the association between maternal prenatal depression or anxiety and the future development of their children's socioemotional development (eg, difficult temperament, behavioral dysregulation) up to 18 years later. Two independent coders extracted all relevant data. Random-effects meta-analyses were used to derive mean effect sizes and test for potential moderators. A total of 71 studies met full inclusion criteria for data analysis. The weighted average effect size for the association between prenatal stress and child socioemotional problems was as follows: odds ratio (OR) = 1.66 (95% CI = 1.54-1.79). Effect sizes were stronger for depression (OR = 1.79; 95% CI = 1.61-1.99) compared to anxiety (OR = 1.50; 95% CI = 1.36-1.64). Moderator analyses indicated that effect sizes were stronger when depression was more severe and when socio-demographic risk was heightened. Findings suggest that maternal prenatal stress is associated with offspring socioemotional development, with the effect size for prenatal depression being more robust than for anxiety. Mitigating stress and mental health difficulties in mothers during pregnancy may be an effective strategy for reducing offspring behavioral difficulties, especially in groups with social disadvantage and greater severity of mental health difficulties.


Posterior segment Intra-Ocular Implant (IOL) dislocation: Predisposing factors, surgical management, outcome analysis.
To evaluate the predisposing factors, management and visual prognosis of intraocular Lens (IOL) dislocation into the posterior segment. The cases of posterior IOL dislocation from January 2012 to May 2017 at 2 centers were reviewed. Only eyes with dislocations requiring IOL explantation or repositioning were included. Predisposing factors, interval between cataract surgery and IOL dislocation, circumstances of onset, management, and postoperative complications are reported. 72 eyes of 72 patients were included. The mean age was 67.6 years. 47 patients (68%) were men. The mean time interval from cataract surgery to IOL dislocation was significantly shorter in the out-of-the bag group than the in-the-bag IOL dislocation group (3.8 months vs 132 months, P=0.002). Predisposing factors for out-of-the-bag IOL dislocation were mainly capsular rupture and/or zonular dehiscence (83%) after complicated cataract surgery. The predisposing factors for in-the-bag IOL dislocation were high myopia (40%), pseudoexfoliation syndrome (40%), previous vitrectomy (38%), or Marfan syndrome (3%) with uneventful cataract surgery. The type of luxated implant was mainly a 3-piece foldable IOL (50%), followed by foldable one-piece IOL (28%) and a rigid one-piece IOL (17%). Most cases of posterior chamber IOL dislocation occurred spontaneously (80%) without a trigger event. Management consisted of a posterior approach in 24 cases (33%) or an anterior approach in 48 cases (67%), associated with IOL repositioning in 20 eyes (28%), and IOL replacement in 34 eyes (47%). Finally, 18 eyes (25%) were left aphakic. Postoperative complications occurred in 7 cases (9.7%). Predisposing factors and time from cataract surgery to IOL dislocation were different for out-of-the bag versus in-the-bag IOL dislocation. Management of IOL dislocation varied considerably, depending on surgeon preference and experience. Surgery for IOL dislocation significantly improved best corrected visual acuity and was associated with a low complication rate.


Consideration of the importance of measuring thermal discomfort in biomedical research.
Core temperature stability is the result of a dynamically regulated balance of heat loss and gain, which is not reflected by a simple thermometer reading. One way in which these changes manifest is in perceived thermal comfort, 'feeling too cold' or 'feeling too hot', which can activate stress pathways. Unfortunately, there is surprisingly little preclinical research that tracks changes in perceived thermal comfort in response to either disease progression or various treatments. Without measuring this endpoint, there may be missed opportunities to evaluate disease and therapy outcomes in murine models of human disease. Here, we discuss the possibility that changes in thermal comfort in mice could be a useful and physiologically relevant measure of energy trade-offs required under various physiological or pathological conditions.


Use of a lighted flexible catheter as a detector for accidental oesophageal intubation through the intubating laryngeal mask: a preliminary study.
We have evaluated the use of a prototype lighted flexible catheter using the transillumination of the light through the soft tissues of the neck, as a detector of the accidental oesophageal intubation during the tracheal intubation through the intubating laryngeal mask. Two hundred patients undergoing general anaesthesia were studied. Accidental oesophageal intubation occurred in 12 patients (6%) during the first intubating attempt and was diagnosed by noting absence of glow on the neck during the tracheal tube advancement and was confirmed by capnography. However, 11/12 (92%) of the above patients were finally intubated successfully, using the lighted flexible catheter. In one patient persistent accidental oesophageal intubation occurred and was classified as failure.


Relationship Between Parental Postnatal Distress and 5-Year Mental Health Outcomes of Children Born at <30 Weeks and at Term.
The purpose of this study was to compare mental health symptoms and diagnoses at age 5 years between children born <30 weeks' gestation and their term-born peers and associations with postnatal symptoms of depression and anxiety in their mothers and fathers. Parents of children born <30 weeks' gestation (n = 106) and at term (n = 105) completed measures of anxiety and depression symptoms within 4 weeks of birth and questionnaires assessing child socioemotional symptoms and mental health/neurodevelopmental diagnostic criteria at age 5 years. At age 5 years, children born <30 weeks' gestation were more likely to show clinically concerning levels of total difficulties (odds ratio [OR] = 3.97, 95% confidence interval [CI], 1.21-13.05), emotional problems (OR = 3.71, 95% CI, 1.14-12.15), and inattention/hyperactivity problems (OR = 4.34, 95% CI, 1.51-12.47) than term-born peers. They also showed higher rates of mental health/neurodevelopmental diagnoses than their term-born peers (18% vs 9%), although evidence for the group difference was weak ( p = 0.08). Maternal postnatal anxiety and depression symptoms were related to poorer child mental health outcomes in many domains. There was little evidence that paternal postnatal anxiety/depression symptoms were related to child outcomes or that any associations varied by birth group. Children born <30 weeks' gestation showed more mental health symptoms than their term-born peers at age 5 years. Maternal postnatal distress was associated with poorer child mental health across both groups, reinforcing the need for early identification and support of mental health distress in the postnatal period to improve longer-term child well-being.