Clinical and molecular characterization of thirty Chinese patients with congenital lipoid adrenal hyperplasia.
Congenital lipoid adrenal hyperplasia (LCAH), as the most severe form of congenital adrenal hyperplasia (CAH), is caused by mutations in the steroidogenic acute regulatory protein (STAR). Affected patients were typically characterized by adrenal insufficiency in the first year of life and present with female external genitalia regardless of karyotype. Non-classic LCAH patients usually present from 2 to 4 years old with glucocorticoid deficiency and mild mineralocorticoid deficiency, even develop naturally masculinized external genitalia at birth when they have 46,XY karyotype. We described thirty patients from unrelated Chinese families, including three non-classic LCAH ones. Four novel mutations were reported, including c.556A > G, c.179-15G > T, c.695delG and c.306 + 3_c.306 + 6delAAGT. The c.772C > T is the most common STAR mutation in Chinese population, suggesting a possibility of founder effect. Enzymatic activity assay combined with clinical characteristics showed a good genotype-phenotype correlation in this study. Residual STAR activity more than 20 % may be correlated with non-classic LCAH phenotype. We support the perspective that onset age may be affected by multiple factors and masculinization should be the main weighting factor for diagnosis of non-classic LCAH. Compared with 46,XX LCAH patients, less 46,XY ones were found in our report. A less comprehensive inspection and an easy diagnosis due to classical phenotype both would reduce the possibility of 46,XY LCAH patients to be referred to specialists or geneticists.


The California Verbal Learning Test--second edition: test-retest reliability, practice effects, and reliable change indices for the standard and alternate forms.
The California Verbal Learning Test - second edition (CVLT-II) is one of the most widely used neuropsychological tests in North America. The present study evaluated the 1-month test-retest reliability and practice effects associated with the standard and alternate forms of the CVLT-II in a sample of 195 healthy adults. Eighty participants underwent repeat assessment using the standard form of the CVLT-II on both occasions, whereas the remaining 115 individuals received the standard form at baseline and the alternate form at follow-up. Consistent with prior research, results revealed generally large test-retest correlation coefficients for the primary CVLT-II measures in both the standard/standard (range=0.80-0.84) and standard/alternate (range=0.61-0.73) cohorts. Despite exhibiting slightly lower test-retest reliability coefficients, participants in the alternate form group displayed notably smaller practice effects (Cohen's d range=-0.01 to 0.18) on the primary indices relative to individuals who received the standard form on both occasions (Cohen's d range=0.27-0.61). Reliable change indices were also generated and applied to primary CVLT-II variables to determine the base rates of significant improvements (range=2-10%), declines (range=0-7%), and stability (range=85-97%) in performance over time. Overall, findings from this study support the test-retest reliability of the standard and alternate forms of the CVLT-II in healthy adults and may enhance the usefulness of this test in longitudinal neuropsychological evaluations.


Effects of swab materials and transport media on Aujeszky's disease virus.
The effect of swab materials on the recovery of Aujeszky's disease virus from various transport media held at 4 degrees C was investigated over a five day period. No significant loss in infectivity was found in control preparations, approximately 50 per cent of infectivity was recovered from fluids containing applicator wire and approximately 10 per cent from fluids containing polyester fibre or cotton wool. Virus recovery from fluids containing wooden applicator sticks ranged from no virus recovery in protein free media to from 1 to 10 per cent in protein containing media. Freezing followed by thawing was the most effective of the physical methods used for eluting virus from swab materials.


Dispersal distance as a benefit of myrmecochory.
Nutrient-enrichment and predator avoidance are generally considered the major benefits of myrmecochory, but this is apparently not so in Australia where some of the greatest known concentrations of myrmecochorus plants occur. Here I demonstrate that distance dispersal is a potential benefit of myrmecochory in the Australian environment. Although mean dispersal distance at a site in southeastern Australia was only 2.1 m, the dispersal curve was characterised by a narrow peak and long tail. A dispersal curve of this shape has been shown by Green (1983) to be optimal when safe sites for seedling establishment are rare, as is typically the case for Australian myrmecochores in the absence of fire. Both mean disperal distance and shape of the dispersal curve are influenced strongly by nest density and dispersion, population size, and territoriality of seed-dispersing ants. I argue that distance dispersal is likely to be a benefit of myrmecochory throughout Australia, independent of any targeting of seeds to ant nests.


Assessment of academic achievements in m-learning.
The paper analyzes the teaching experiment regarding the use of mobile apps in the assessment of student learning. The study involved survey and self-description methods offered to students and instructors to assess the effectiveness of using mobile apps in learning. The study was conducted among 320 s-year students of the I.M. Sechenov First Moscow State Medical University and 8 instructors between September 1 and December 28, 2021, during the academic semester. Socrative and Plickers apps have been found to contribute to: better learning (φ* = 8.94, p ≤ 0.01); developing cognitive motivation among students resulting from diverse learning resources used with apps (φ* = 7.6, p ≤ 0.01); convenience of learning activities because students can work with the app both in the classroom and at home (φ* = 13.66, p ≤ 0.01); improved digital competence (φ* = 2.4, p ≤ 0.05). The research findings can be used by instructors in universities and secondary schools. Since didactic opportunities offered by mobile apps are quite significant, and considering other positive results of their use, this technology may be considered as an important tool for training young people and strengthening their cognitive motivation.


Four sulfur mustard exposure cases: Overall analysis of four types of biomarkers in clinical samples provides positive implication for early diagnosis and treatment monitoring.
In one event, Chinese male individuals accidentally exposed to unknown chemicals and emerged erythema or blisters on contacted organism derma, then hospitalized. To identify the causative agents, blood, urine and exudate samples were collected from the patients during the therapeutic course. Five established liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS methods were employed to analyze the samples. Here, an overall analysis of four types of sulfur mustard biomarkers, including the hydrolysis/oxidation products, β-lyase metabolites, DNA adducts and hemoglobin adducts, was conducted toward the samples from exposed individuals. The results of all the four types of biomarkers in different biomedical matrices showed high relevance, and verified that this exposure is indeed originated from sulfur mustard. The concentrations of the biomarkers in specimens revealed a good correlation with the severity of the patient's symptom. The concentration-time profile demonstrated that most of the biomarkers quickly achieved maximum at the beginning of the course, and then decreased and kept a detectable level until the 7th day after exposure. The DNA adducts in urine samples still appeared on the 30th day, and the N-terminal valine adducts in hemoglobin could be monitored for over 90 days, which was meaningful for the concurrent study of clinical samples. To the best of our knowledge, this work provides the total analysis and profile of four categories of biomarkers in human specimens for the first time, and the good accordance between concentration and level of burns, between time course and biomarkers will be of great importance for early diagnosis and medical treatment monitoring of sulfur mustard exposure.


Synovium stem cell-derived matrix enhances anti-inflammatory properties of rabbit articular chondrocytes via the SIRT1 pathway.
Autologous chondrocyte implantation (ACI) is a promising approach to repair cartilage defects; however, the cartilage trauma-induced inflammatory environment compromises its clinical outcomes. Cell-derived decellularized extracellular matrix (DECM) has been used as a culture substrate for mesenchymal stem cells (MSCs) to improve the cell proliferation and lineage-specific differentiation. In this study, DECM deposited by synovium-derived MSCs was used as an in vitro expansion system for rabbit articular chondrocytes and the response of DECM-expanded chondrocytes to pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was evaluated. Compared with those grown on tissue culture polystyrene (TCPS), the proliferation rate was significantly improved in DECM-expanded chondrocytes. TCPS- and DECM-expanded chondrocytes were isolated and induced to redifferentiation in a high-density pellet culture. DECM-expanded chondrocytes exerted a stronger resistance to 1 ng/mL of IL-1β than TCPS-expanded cells, but the production of cartilage matrix in both groups was inhibited by 5 ng/mL of IL-1β. When exposed to 1 or 5 ng/mL of TNF-α, DECM-expanded chondrocytes showed higher levels of cartilage matrix synthesis than TCPS-expanded cells. In addition, the gene expression of IL-1β- or TNF-α-induced matrix degrading enzymes (MMP3, MMP9, MMP13, and ADAMTS5) was significantly lower in DECM-expanded chondrocytes than TCPS-expanded cells. Furthermore, we found that SIRT1 inhibition by nicotinamide completely counteracted the protective effect of DECM on chondrocytes in the presence of IL-1β or TNF-α, indicating that the SIRT1 signaling pathway was involved in the DECM-mediated enhancement of anti-inflammatory properties of chondrocytes. Taken together, this work suggests that stem cell-derived DECM is a superior culture substrate for in vitro chondrocyte expansion by improving proliferation and enhancing the anti-inflammatory properties of chondrocytes. DECM-expanded chondrocytes with enhanced anti-inflammatory properties hold great potential in clinically ACI-based cartilage repair.


Complex Genetics of Cardiovascular Traits in Mice: F2-Mapping of QTLs and Their Underlying Genes.
In this chapter, we will use the example of the identification of Tnni3k as a modulator of cardiac conduction to introduce you to the use of a murine F2-generation intercross as a powerful method for the identification of novel genes relevant for cardiovascular traits. Murine F2-progeny is a genetically diverse panel of mice with differences in phenotype manifestations, e.g. cardiovascular traits such as cardiomyopathy and ECG parameters. This chapter discusses the best strategies for using F2-mice for genetic mapping. Moreover, we provide an example of the feasibility of identification of new genes modulating cardiac function utilizing the technique of mapping quantitative trait loci (QTLs) and a systems genetics integration of available genetic, gene expression, and phenotypic data.


Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery.
Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001). PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF.


Facilitators and Inhibitors to Assessing Entrustable Professional Activities in Pediatric Residency.
Research on entrustable professional activities (EPAs) has focused on EPA development with little attention paid to implementation experiences. This constructivist grounded theory study sought to begin filling this gap by exploring the experiences of pediatric residency programs with implementing EPA-based assessment. Interviews with 19 program leader and clinical competency committee participants from 13 sites were held between January and July 2019. Participants were asked about their experiences with implementing EPA-based assessment. Data collection and analysis were iterative. Participants described a range of facilitators and inhibitors that influenced their efforts to implement EPA-based assessment. These fell into 4 thematic areas: 1) alignment of EPA construct with local views of performance and assessment, 2) assessing EPAs illuminates holes in the residency curriculum, 3) clinical competency committee structure and process impacts EPA-based assessment, and 4) faculty engagement and development drives ability to assess EPAs. Areas described as facilitators by some participants were noted to be inhibitors for others. The sum of a program's facilitators and inhibitors led to more or less ability to assess EPAs on the whole. Finally, the first area functions differently from the others; it can shift the entire balance toward or away from the ability to assess EPAs overall. This study helps fill a void in implementation evidence for EPA-based assessment through better understanding of facilitators and inhibitors to such efforts.


Regulatory mechanisms for glycogenolysis and K+ uptake in brain astrocytes.
Recent advances in brain energy metabolism support the notion that glycogen in astrocytes is necessary for the clearance of neuronally-released K(+) from the extracellular space. However, how the multiple metabolic pathways involved in K(+)-induced increase in glycogen turnover are regulated is only partly understood. Here we summarize the current knowledge about the mechanisms that control glycogen metabolism during enhanced K(+) uptake. We also describe the action of the ubiquitous Na(+)/K(+) ATPase for both ion transport and intracellular signaling cascades, and emphasize its importance in understanding the complex relation between glycogenolysis and K(+) uptake.


Serum neurofilament light chain measurements following nerve trauma.
Optimal functional recovery following peripheral nerve injuries (PNIs) is dependent upon early recognition and prompt referral to specialist centres for appropriate surgical intervention. Technologies which facilitate the early detection of PNI would allow faster referral rates and encourage improvements in patient outcomes. Serum Neurofilament light chain (NfL) measurements are cheaper to perform, easier to access and interpret than many conventional methods used for nerve injury diagnosis, such as electromyography and/or magnetic resonance imaging assessments, but changes in serum NfL levels following traumatic PNI have not been investigated. This pre-clinical study aimed to determine whether serum NfL levels can: (1) detect the presence of a nerve trauma and (2) delineate between different severities of nerve trauma. A rat sciatic nerve crush and common peroneal nerve crush were implemented as controlled animal models of nerve injury. At 1-, 3-, 7- and 21-days post-injury, serum samples were retrieved for analysis using the SIMOA® NfL analyser kit. Nerve samples were also retrieved for histological analysis. Static sciatic index (SSI) was measured at regular time intervals following injury. Significant 45-fold and 20-fold increases in NfL serum levels were seen 1-day post-injury following sciatic and common peroneal nerve injury, respectively. This corresponded with an eightfold higher volume of axons injured in the sciatic compared to the common peroneal nerve (p < .001). SSI measurements post-injury revealed greater reduction in function in the sciatic crush group compared with the common peroneal crush group. NfL serum measurements represent a promising method for detecting traumatic PNI and stratifying their severity. Clinical translation of these findings could provide a powerful tool to improve the surgical management of nerve-injured patients.


Anterior segment variations after posterior chamber phakic intraocular lens implantation in myopic eyes.
To evaluate anterior segment variations after posterior chamber phakic intraocular lens (pIOL) implantation in myopic eyes. Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Cohort study. Patients with high myopia were scheduled for nontoric Implantable Collamer Lens pIOL or toric Implantable Collamer Lens pIOL implantation. Anterior segment optical coherence tomography was performed to evaluate the anterior segment variations over time and the impact of physiologic accommodation and change in brightness after pIOL implantation. Slitlamp photography of the anterior segment was taken after pupil dilation to calculate pIOL rotation. There was significantly improved visual acuity and refractive status after implantation of both pIOLs. Anterior segment axial variations had good stability 6 months postoperatively. However, nontoric pIOL rotation occurred in 1 eye 7 months postoperatively and rotation of the toric pIOL occurred in 2 eyes at 3 months and 6 months. Stimulations of -4.0 diopters (D) and -8.0 D led to significant changes in anterior chamber depth (ACD) based on the lens (ACD-lens), ACD after pIOL implantation, distance between the pIOL posterior surface and the lens anterior surface (pIOL-lens), and pupil diameter. Increasing ambient light brightness could reduce the ACD-lens and pIOL-lens. Both pIOLs had good axial stability in myopic eyes 6 months postoperatively; however, rotational stability over time could not be determined. The physiologic adjustment and change in brightness could influence the anterior segment significantly in eyes with a pIOL.


[Experimental studies on the effect of labyrinth anesthesia].
Injection of tetracaine into the tympanic cavity inhibits, independently of histologic lesions of the round window membrane, the active electrogenic pump in the stria vascularis cells. The DC potential in the endolymph is reduced with increasing doses of tetracaine, while the K+-Cl- activity is unchanged for 120 min. This drug does not alter the permeability of Reissner's membrane. Near the stria vascularis area, the oxygen pressure in the endolymph increases significantly after the effects of 4% tetracaine.


Continuous melatonin administration accelerates resynchronization following phase shifts of a light-dark cycle.
Circadian rhythms of most passerine birds and some reptiles depend to a considerable extent on the presence of periodic melatonin, which is considered to be part of the central pacemaking system. Recent results on house sparrows have suggested that melatonin, apart from its periodic effects on the circadian system, may also exert effects derived from a constant action: Continuous melatonin applied through subcutaneously implanted silastic tubing enhanced the synchronization response to a low-amplitude light-dark zeitgeber, indicating some kind of sensitization to zeitgeber stimuli. In the present study we tested the prediction derived from these results, that speed of resynchronization after a phase shift of a light-cycle should be enhanced if melatonin is continuously administered. We found that, indeed, house sparrows required less time to resynchronize to an 8 h advance or delay phase shift of a low-amplitude light-dark cycle while carrying a silastic implant filled with melatonin than while carrying an empty implant. The effect is suggested to result from either one or a combination of the following mechanisms: (i) An increased circadian visual sensitivity, (ii) a diminished amplitude of the circadian oscillation, iii) an altered feedback of the locomotor activity to the oscillatory system.


Ultrasound of the shoulder and elbow.
Ultrasound examination of the shoulder and elbow requires careful technique, appreciation of normal anatomy, and appropriate high-end equipment. Ultrasound provides detailed diagnostic information. Its accuracy is comparable to that of MRI in the assessment of the rotator cuff. Ultrasound is cheaper than MRI and is preferred by patients.


Tibial osteomyelitis due to Aspergillus flavus in a heart transplant patient.
Aspergillus flavus was identified as the causative organism of a case of osteomyelitis involving the proximal epiphysis of the left tibia in a heart transplant patient. History revealed a previous pretibial wound due to a fall in the street as the consequence of a sudden cardiac arrest. Surgical debridement combined with fungostatic treatment including amphotericin B and itraconazole was followed by clinical improvement, although the fungus could still be recovered by culture on subsequent samples.


Clinical characteristics and management of paroxysmal junctional tachycardia in the elderly.
The proportion of elderly subjects is in progress. While atrial fibrillation is the most frequent arrhythmia after the age of 70 years, other tachycardias also occur in the elderly. The aim of this study is to assess the clinical and electrophysiological characteristics of paroxysmal junctional tachycardia (PJT) in patients older than 70 years. Eight hundred sixteen patients aged from 8 to 93 years have been consecutively recruited for PJT. Among them, 141 (17%) were older than 70 years. The clinical, electro-physiology and therapeutic data were studied. Forty-eight men and 93 women with an age range from 70 to 93 years (mean 76+/-5) were admitted for recurrent PJT. They were associated to cardiac decompensation in 10 cases, syncope in 26 cases, acute coronary syndrome in 14 cases and unexplained acute vascular event in 5 cases. The electro-physiological mechanism of the PJT was similar to the younger patients with a majority of nodal reentrant tachycardia (73%). Atypical nodal tachycardias were more frequent than in the youth (15 versus 4%). PJT ablation was indicated more frequently in elderly patients than in younger patients (79 versus 57%), but complications (7% versus 2.5%) and failures, especially related to atrial fibrillation induction (19% versus 5%) were more frequent in elderly patients. Junctional tachycardias are not rare in the elderly and should not be missed. A cautious medical treatment can be impeded by the presence of conduction troubles or comorbidities. If this approach is not efficacious, these subjects might take benefit from curative ablation, with still a 10% failure rate.


Biomanipulation impacts on per-and polyfluoroalkyl substances accumulation and trophic transfer in an eutrophic lake.
Manipulation of freshwater food web through species introduction has been used to control the increasing algae in the Wuliangsuhai Lake, which affects not only the pathways of carbon source and energy transfer, but also the transfer of contaminants through food web. Food web relationships between biomanipulation area (BMA) and non-biological manipulation area (NBMA) were investigated using stable carbon (δ13C) and nitrogen (δ15N) isotope analysis. In BMA, the δ13C values in fish species were enriched while δ15N depleted due to the increased inter-species competition. Among the same fish species between BMA and NBMA, lower trophic levels were observed in BMA. Concentrations of target PFASs (ΣPFAS) in fish from BMA were significantly (p < 0.05) lower than those from NBMA. Whilst elevated trophic magnification factors (TMFs) of PFASs, especially for perfluoroalkyl carboxylic acids (PFCAs) with long carbon chain length (C9-10), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) were exhibited in BMA. We found that biomanipulation through species introduction played an important role in control over lake eutrophication and trophic transfer patterns of PFASs in biota from the altered aquatic ecosystem.


AlphaScreen-based homogeneous assay using a pair of 25-residue artificial proteins for high-throughput analysis of non-native IgG.
Therapeutic IgG becomes unstable under various stresses in the manufacturing process. The resulting non-native IgG molecules tend to associate with each other and form aggregates. Because such aggregates not only decrease the pharmacological effect but also become a potential risk factor for immunogenicity, rapid analysis of aggregation is required for quality control of therapeutic IgG. In this study, we developed a homogeneous assay using AlphaScreen and AF.2A1. AF.2A1 is a 25-residue artificial protein that binds specifically to non-native IgG generated under chemical and physical stresses. This assay is performed in a short period of time. Our results show that AF.2A1-AlphaScreen may be used to evaluate the various types of IgG, as AF.2A1 recognizes the non-native structure in the constant region (Fc region) of IgG. The assay was effective for detection of non-native IgG, with particle size up to ca. 500 nm, generated under acid, heat, and stirring conditions. In addition, this technique is suitable for analyzing non-native IgG in CHO cell culture supernatant and mixed with large amounts of native IgG. These results indicate the potential of AF.2A1-AlphaScreen to be used as a high-throughput evaluation method for process monitoring as well as quality testing in the manufacturing of therapeutic IgG.


Investigation of a liposomal oxaliplatin drug formulation by capillary electrophoresis hyphenated to inductively coupled plasma mass spectrometry (CE-ICP-MS).
A capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS) method was developed for separation of the free oxaliplatin drug substance from liposome-entrapped oxaliplatin. Simultaneous determination of phosphorous and platinum opened the possibility to simultaneously monitor the liposomes (phospholipids) and platinum-based drug. In order to suppress the interferences, argon gas was used as a collision gas in ICP-MS. A detection limit of 29 ng/mL of platinum and a precision of 2.9% (for 10 μg/mL of oxaliplatin standard) were obtained. Measurement of the total concentration of free and encapsulated oxaliplatin by CE-ICP-MS was compared with total determination by ICP-MS after microwave digestion and showed a good agreement. A liposomal formulation of oxaliplatin based on PEGylated liposomes was used as a model drug formulation. Studies of accelerated drug release induced by sonication and phospholipase A(2) catalyzed hydrolysis were performed. It was demonstrated that the CE-ICP-MS was an efficient in vitro characterization method in the development and quality assurance purposes of lipsome-based formulation of metallodrugs.


Dynamics of linear protein polymer disassembly.
This report presents a kinetic model for endwise depolymerization of linear, self-assembling protein systems. We develop a reliable method for predicting the shape of depolymerization curves (remaining polymer weight versus time) on the basis of the initial polymer length distribution. Computer simulations are used to illustrate changes in the polymer length distribution and average polymer weight during disassembly. In addition, our method provides an accurate determination of the microscopic rate constant for subunit release. Application of this analysis to dilution-induced and cold induced disassembly of microtubules is illustrated in the preceding paper (Karr, T.L., Kristofferson, D., and Purich, D.L. (1980) J. Biol. Chem. 255, 8560-8566). A survey of other possible applications of this treatment to microtubules, flagella, F-actin, and tobacco mosaic virus protein is included.


Li-Fraumeni syndrome heterogeneity.
Clinical variability is commonly seen in Li-Fraumeni syndrome. Phenotypic heterogeneity is present among different families affected by the same pathogenic variant in TP53 gene and among members of the same family. However, causes of this huge clinical spectrum have not been studied in depth. TP53 type mutation, polymorphic variants in TP53 gene or in TP53-related genes, copy number variations in particular regions, and/or epigenetic deregulation of TP53 expression might be responsible for clinical heterogeneity. In this review, recent advances in the understanding of genetic and epigenetic aspects influencing Li-Fraumeni phenotype are discussed.


Premenstrual Dysphoric Disorder: Epidemiology and Treatment.
Recently designated as a disorder in the DSM-5, premenstrual dysphoric disorder (PMDD) presents an array of avenues for further research. PMDD's profile, characterized by cognitive-affective symptoms during the premenstruum, is unique from that of other affective disorders in its symptoms and cyclicity. Neurosteroids may be a key contributor to PMDD's clinical presentation and etiology, and represent a potential avenue for drug development. This review will present recent literature on potential contributors to PMDD's pathophysiology, including neurosteroids and stress, and explore potential treatment targets.


The amount of prey brought into the nest attains a maximum in May, which in the years of an outbreak of Tortrix viridana is not much higher than during the times of latency of this insect, and depends at least partly on weather in summer. The crop volume of foraging ants reaches maxima in spring and late summer, probably depending on the abundance of the main producer of honey-dew, Lachnus roboris L. The sugar concentration of crop fluid fluctuates around a mean of 0.25 g/cm3 in summer and decreases in autumn. The nitrogen concentration attains maxima in spring and autumn, corresponding to maxima of nitrogen concentration in honey-dew. Moreover, the quantity of arthropod nitrogen in the crop increases in spring.The larger amount of prey brought into the nest during the occurrence of Tortrix viridana does not affect the number of ants running out, the number of ants climbing trees, the ranges of activity of the nest populations as well as the quantity of honey-dew collected. Apparently ants are capable of regulating to a certain extent the quantity of honey-dew and the amount of prey collected in spring. Furthermore, they select the different sources of honey-dew or prey according to abundance and productivity of the latter. They do not become specialized exploiters of the most productive source of food.


Early alcohol onset: clinical and demographic characteristics of service-seeking youth.
Alcohol use in early adolescence is associated with increased health concerns and other negative consequences. Given the needs of this vulnerable population, it is critical to understand their risk factors and clinical characteristics. This cross-sectional study explores the clinical and demographic characteristics of service-seeking youth with and without early alcohol use onset. 655 youth seeking services at a Canadian substance use and concurrent disorder service participated. Evaluations of mental health, substance use, demographic characteristics, and other risk factors were collected and compared among youth who reported an age of onset for alcohol use of under 14 years of age versus 14 years or older. Youth who started using alcohol before age 14 were significantly more likely to report mental health difficulties, indicate use of a greater number of substances, and report experiencing more crime and violence problems. They also reported exposure to more types of trauma. Notably, more problems with crime and violence were significantly, and uniquely associated with an earlier age of alcohol use onset in a multivariate model. The present study identifies unique and clinically significant differences among youth who initiated alcohol use in early adolescence compared to later in adolescence. Stronger integrations between mental health and substance use services for youth with early alcohol use should be considered, given the vulnerability and concurrent difficulties they tend to face.


(E)-N'-[(E)-3-Phenyl-allyl-idene]benzo-hydrazide.
In the title mol-ecule, C(16)H(14)N(2)O, the dihedral angle between the two phenyl rings is 23.5 (6)°. In the crystal, N-H-O hydrogen bonds link mol-ecules into chains running along the a axis.


Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus.
Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. In a retrospective cohort study, kidney function was evaluated pre- and postoperatively by measured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 2000 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, target trough levels 10-15 ng/mL, and corticosteroids, n = 203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5-8 ng/mL, delayed until day three, and mycophenolate mofetil 2000 mg/day, n = 343). Mean mGFR was similar between groups at wait-listing (85.3 vs 84.1 ml/min/1.73m², p = 0.60), but higher in the revised treatment group at 3 (56.8 vs 63.4 ml/min/1.73m², p = 0.004) and 12 months post-transplant (60.9 vs 69.7 ml/min/1.73m², p<0.001); this difference remained after correcting for multiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p<0.001), and graft-survival better (p = 0.01). Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death.


An alternative methodology for planning baggage carousel capacity expansion: A case study of Incheon International Airport.
Intensifying competition for air transportation passengers has led airports to research optimal designs and determine the infrastructure expansion capacities of their terminals. As a result, many researchers have studied this subject from a variety of perspectives. In this study, we propose an alternative methodology of determining the expansion of baggage carousel capacity over a series of steps that includes both a simulation and a cost-benefit analysis. The methodology consists of three stages. In the first stage, we forecast the volume of arriving passengers (excluding transfer passengers) and aircraft traffic with an autoregressive integrated moving average (ARIMA) model. Next, we conduct an elaborate analysis to estimate passenger delay using a discrete event simulation model in which we consider the conveyor load and the baggage carousel allocation to aircraft rates. Finally, we determine a plan to expand baggage carousel capacity that accounts for expansion costs and passenger benefits. Construction and conveyor costs were applied to expansion costs, and capacity expansion leads to passenger benefits due to reduced waiting time. Using a real case with 23 candidate baggage carousels at Incheon International Airport during 2013-2015, our experiments demonstrate the strength of the proposed methodology in planning appropriate capacity expansion that reflect the operational flow of passengers within the airport based on the future trend of passenger demand. In particular, our results show that carousel no. 18 should be expanded during the first quarter of 2013, carousels no. 17 and no. 19 should be expanded in 2014, and carousel no. 5 should be expanded in 2015 to obtain optimal benefit-cost ratios of 1.65, 1.79, and 1.76 for each year, respectively.


Preventing second cancers in cancer survivors.
To provide a systematic review of the secondary prevention practices of cancer survivors guided by the Interaction Model of Client Health Behavior. Articles published in peer-reviewed journals from 1996-2007. Despite their increased risk for second cancers, few cancer survivors maintain regular follow-up with a clinician knowledgeable of late effects. Cancer screening rates for cancer survivors are below optimal levels recommended for the general population. Multiple antecedents explain survivors' health practices. Few tested interventions are available to promote secondary prevention practices among cancer survivors. Cancer survivors are less likely to adopt secondary prevention practices than individuals without a cancer history. Nurses can encourage cancer survivors to adopt secondary prevention practices by providing positive reinforcement, support, and education. As more comprehensive, evidence-based guidelines for longitudinal care become available, nurses will be able to provide care to survivors with greater confidence and certainty.


Reduced expression of bone morphogenetic protein receptor IA in pancreatic cancer is associated with a poor prognosis.
The expression of SMAD4, the central component of the transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling pathways, is lost in 50% of pancreatic cancers and is associated with a poor survival. Although the TGF-β pathway has been extensively studied and characterised in pancreatic cancer, there is very limited data on BMP signalling, a well-known tumour-suppressor pathway. BMP signalling can be lost not only at the level of SMAD4 but also at the level of BMP receptors (BMPRs), as has been described in colorectal cancer. We performed immunohistochemical analysis of the expression levels of BMP signalling components in pancreatic cancer and correlated these with survival. We also manipulated the activity of BMP signalling in vitro. Reduced expression of BMPRIA is associated with a significantly worse survival, primarily in a subset of SMAD4-positive cancers. In vitro inactivation of SMAD4-dependent BMP signalling increases proliferation and invasion of pancreatic cancer cells, whereas inactivation of BMP signalling in SMAD4-negative cells does not change the proliferation and invasion or leads to an opposite effect. Our data suggest that BMPRIA expression is a good prognostic marker and that the BMP pathway is a potential target for future therapeutic interventions in pancreatic cancer.


INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN ANGIOID STREAKS: Four-Year Follow-up.
To analyze retrospectively the efficacy of intravitreal ranibizumab injections for the management of choroidal neovascularization in patients with angioid streaks over a long term. In this "nonrandomized," double-center, retrospective, interventional case series, a consecutive series of patients affected with choroidal neovascularization associated with angioid streaks were treated with intravitreal ranibizumab injections (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus photography, optical coherence tomography, and fluorescein angiography were examined before and after treatment. The primary endpoint was the percentage of eyes with stable or improved visual acuity at the end of follow-up (loss of less than 3 Early Treatment Diabetic Retinopathy Study lines). Secondary endpoints were the percentage of eyes with stable or decreased macular thickness on optical coherence tomography (less than a 10% increase in macular thickness) and the percentage of eyes with persistent leakage on fluorescein angiography at the last observation carried forward. Thirty-five eyes of 27 patients were treated with repeated intravitreal ranibizumab injections (mean of 9.9 ± 7.2 injections, range 2-26) for a mean of 48.6 ± 17.1 months (range 8-66). At the end of follow-up, best-corrected visual acuity was stabilized or improved in 22 of 35 eyes (62.9%). Macular thickness had stabilized or decreased in 16 of 35 eyes (45.7%). At the last follow-up examination, on fluorescein angiography, no further leakage was observed in 27 of 35 eyes (77.1%). In this large series of patients with choroidal neovascularization associated with angioid streaks followed for 4 years, ranibizumab injections allowed stabilization of best-corrected visual acuity in most eyes. Ranibizumab appear as an effective therapeutic option in CNV associated with angioid streaks over long time.


Unusual MRI appearance of diffuse subcortical heterotopia or "double cortex" in two children.
Two children with mild epilepsy and learning and behaviour problems had magnetic resonance imaging (MRI) scans showing an almost identical generalised disorders of neuronal migration. Their computer tomography (CT) scans showed abnormal hypodense white matter. The MRI showed a four layered appearance of the cerebral parenchyma extending from the frontal to the occipital region. There was a normal appearance to the white matter in the periventricular region which had an abnormally smooth junction with a thick diffuse layer of heterotopic grey matter. This was surrounded by a thin layer of white matter which had normal digitations with the overlying cortex. The appearance of the overlying cortex was normal. These and other recently described cases broaden the concept of generalised disorders of neuronal migration and illustrate that it is possible to have a generalised cerebral malformation with few clinical consequences.


Three Nordic countries responding to COVID-19 - Eldercare perspectives.
Comparative international studies show that about half of the deceased in the COVID-19 pandemic were persons living in institutional and residential eldercare. As seniors are the most affected age group, we aim to study if and to what extent the eldercare services were included in the National Pandemic Plans, and how they were included in the response during the first phase of the pandemic in Finland, Iceland, and Sweden. We use the CRISMART approach to crisis documentation and analysis in comparing national response to the pandemic for the eldercare sector. The method enables comparison of extraordinary crisis situations from the decision-making and policy-making perspective. We found that there were both similarities and differences in the preparedness of the three Nordic countries, as well as in how they responded to the pandemic. In all three countries the focus of the national responses framed the problem as a health and healthcare services' problem. We also found value conflicts in the response between the value of protection versus social contact and self-determination and hence relating to the quality of eldercare. Keeping in mind the proportional increase of elderly people, care challenges, and future crises, we must strengthen the position of local social services within the emergency management systems to enhance disaster resilience and sustainability of our societies.


"Who would know better than the girls in white?" Nurses as experts in postwar magazine advertising, 1945-1950.
American advertising in the period immediately following the Second World War portrayed nurses as trusted advisers and capable professionals and frequently pictured them performing skilled work, including dispensing medicine and assisting in surgery. Advertisements published in a range of magazines whose target audiences varied by gender, race, age, and class show that nurses in postwar advertisements embodied two broad categories of representation: (a) medical authority, scientific progress, and hospital cleanliness; and (b) feminine expertise, especially in female and family health. Typically portrayed as young white women--although older nurses were occasionally depicted and black nurses appeared in advertisements intended for black audiences-nurses were especially prominent in advertisements for menstrual and beauty products, as well as products related to children's health. Although previous scholarly examinations of nurses in postwar mass media have emphasized their portrayal as hypersexual and incompetent, this investigation posits postwar advertising as a forum that emphasized nurses' professionalism, as well as complex expectations surrounding women's professional and domestic roles.


A new glove puncture detection system.
A new glove detection system has been developed for early and accurate detection of a hole in the glove. It consists of an inner glove colored by a green dye and outer glove. When a breach in the outer glove occurs, the inner glove develops a dark patch around the needle puncture hole, a visible indicator for immediate glove change. Using a computerized needle penetration system, the immediate and maximal penetration forces as well as the work required for needle penetration of this new double glove was significantly greater than those encountered with either the inner or outer glove tested separately. In addition to hole detection, this double glove provides increased protection against needle penetration.


Peripheral circumferential retinal scatter photocoagulation for treatment of proliferative sickle retinopathy.
Twenty-nine patients (40 eyes) with proliferative sickle retinopathy (PSR) were treated with circumferential argon laser scatter photocoagulation to zones of peripheral retinal capillary nonperfusion. Each eye was examined in a prospective fashion, with a mean follow-up of 1.4 years. Following scatter treatment, 26% of the pre-existing sea fans regressed completely, 57% regressed partially, 17% remained stable, and none showed progression. In only one eye did de novo neovascularization develop. The results compare favorably with the natural history of PSR (Condon et al, 1980), in which de novo lesions occurred in 58%, and the visual acuity was decreased to less than 20/200 in 12% of affected eyes. Severe iatrogenic complications reported following direct focal treatment of sea fans, such as vitreous hemorrhage, progressive traction retinal detachment, retinal breaks, and choroidal-retinal-vitreal neovascularization were virtually eliminated.


The role of sediment type in growth and fecundity of mud snails (Hydrobiidae).
We test the hypothesis that body size and population density of the deposit-feeding gastropod, Hydrobia truncata, are greater in muddy than in sandy habitats as a result of faster growth on fine- compared to coarse-grained sediments. We refute this hypothesis using a combination of field measurements and laboratory experiments. Three out of three populations tested had higher maximal growth rates and two of three populations approached their asymptotic size more quickly on sand than on silt-clay fractions of natural sediment. Growth decreased with increasing snail density and was as high or higher on sand as on silt-clay at all densities. Two populations were more fecund on sand than on silt-clay, and fecundity of the third population was not affected by sediment type. We show that the smaller body sizes observed in snails from the sandiest habitat result from late recruitment of these snails, relative to the other populations.


[Acute toxic hepatitis due to drinking water].
Toxic-induced liver disease is uncommon, although the true proportion of cases of hepatotoxicity is unknown, as this entity is underdiagnosed and underreported. The main reasons why toxic-induced liver disease goes unnoticed is the lack of pathognomonic data and the lack of spontaneous reporting by doctors and pharmacists. In some cases, the toxic substance can leave its «signature» in the form of clinical semiology suggestive of an underlying toxic cause. We present a case of hepatotoxicity induced by drinking water (chlorinated), which produced a reactive metabolites syndrome (trihalomethanes from the reaction of chlorine with organic products). Although the clinical presentation was typical, the case posed a diagnostic challenge for the various professionals involved.


A coronary artery disease-associated SNP rs6903956 contributed to asymptomatic hyperuricemia susceptibility in Han Chinese.
To investigate the association of a coronary artery disease (CAD) risk SNP rs6903956 with asymptomatic hyperuricemia (aHU) susceptibility in Han Chinese. Two hundred and twenty one patients with aHU and 447 healthy controls were recruited for this study. SNP rs6903956 were genotyped using TaqMan probe. The overall genotype and allele frequency distribution of the rs6903956 showed significant difference between aHU cases and controls (p<0.001 for genotype and allele, respectively). AA genotype of rs6903956 was significantly associated with aHU (OR=8.672, 95% CI 2.811-26.753, p<0.001) in our Han Chinese aHU cohort. Multivariate logistic regression analysis indicated that rs6903956 might be an independent risk factor for aHU susceptibility (OR=10.642 [2.671-42.400], p=0.001 for codominant model and OR=9.205 [2.336-36.280], p=0.002 for recessive model) after adjustment for some well- known CAD risk factors including age, gender, body mass index, smoking, hypertension, diabetes mellitus, abnormal glycometabolism, lipid abnormality and alcohol intake. No significant genotype-specific difference in uric acid levels was observed in aHU patients and controls. Our findings are the first to establish a genetic link of a CAD-associated rs6903956 with aHU in a Han Chinese population, providing the genetic evidence to support the close relationship between hyperuricemia and CAD.


Chronic Eczema Developing Over Skin Treated for Dermatophytosis in Atopic Patients -Importance of Treating Gently and Intelligently.
A novel observation of chronic eczema developing over the skin of adequately treated lesions of tinea cruris/tinea corporis in six atopic individuals is being shared. We propose that the skin of atopic individuals affected by dermatophytosis be observed for secondary changes even after the complete resolution of the lesions. The use of bland emollients with topical antifungal agents should be encouraged in atopic patients. The extent and duration of the compromised epidermal barrier function of the skin of atopic individuals with dermatophytosis need to be studied further.


The use of language structure by demented patients in a visual search task.
Recent findings suggest that some components of semantic memory are spared by Alzheimer's disease. The present study used a visual-search task to determine whether knowledge of the sequential letter dependencies present in spelling remains intact in demented patients. The speed with which twenty Alzheimer patients, twenty young and twenty old controls searched an array of letters for a target was measured. Arrays varied in how closely they approximated English-spelling patterns (zero-order, and third-order approximations and actual words). Despite differing in their overall speed of response, normal and demented subjects were affected equally by the approximation to English of the stimuli (i.e., both searched words faster than low-order approximations). Thus, knowledge of the probability patterns of spelling appears to remain intact and accessible in the semantic memory of demented patients.


Elevated granulocyte colony-stimulating factor levels predict treatment failure in patients with Kawasaki disease.
Kawasaki disease (KD) is an acute vasculitis in young children, frequently associated with coronary artery aneurysms. The intravenous infusion of high-dose IgG (IVIG) effectively reduces the systemic inflammation and the incidence of coronary artery lesions, although the precise underlying mechanisms are unknown. We performed expression profiling of whole blood cells to investigate the mechanisms underlying the effect of IVIG and to identify biomarkers associated with unresponsiveness to IVIG. We compared the transcript abundance among pre-IVIG and post-IVIG patients and febrile control patients. Then we analyzed the mRNA levels and the protein levels among the different cohort of patients with KD who were either responsive or nonresponsive to the initial IVIG. A total of 298 transcripts were overrepresented or underrepresented in the pre-IVIG patients compared with post-IVIG patients and febrile controls, of which 15 transcripts were differentially expressed in nonresponsive patients with KD compared with responsive patients before IVIG. The protein levels of polycythemia rubra vera 1, which was one of the most variably expressed transcripts in pre-IVIG patients, and the serum granulocyte colony-stimulating factor levels were significantly higher in nonresponsive patients than in responsive patients before the initial IVIG administration. These findings suggest that the variable gene expression profiles were correlated to the responses of patients with KD to IVIG administration. Polycythemia rubra vera 1 and granulocyte colony-stimulating factor levels may be good biomarkers for predicting response to IVIG in patients with KD.


Respiratory event detection by a positive airway pressure device.
Compare automatic event detection (AED) of respiratory events using a positive airway pressure (PAP) device with manual scoring of polysomnography (PSG) during PAP treatment of obstructive sleep apnea (OSA). Prospective PSGs of patients using a PAP device. Six academic and private sleep disorders centers. A total of 148 PSGs from 115 participants with OSA (apnea-hypopnea index [AHI] ≥ 15 events/hr) were analyzed. A signal generated by the PAP device identifying the AED of respiratory events based on airflow was recorded during PSG. The PSGs were manually scored without visualization of the AED signal and scoring of a hypopnea required a ≥ 4% oxygen desaturation. The apnea index (AI), hypopnea index (HI), and AHI by manual score and PAP AED were compared. A customized computer program compared individual events by manual scoring and AED to determine the true positive, false positive, false negative, or true negative events and found a sensitivity of 0.58 and a specificity of 0.98. The AHI, AI, and HI by the two methods were highly correlated. Bland-Altman analysis showed better agreement for AI than HI. Using a manually scored AHI of ≥ 10 events/hr to denote inadequate treatment, an AED AHI ≥ 10 events/hr had a sensitivity of 0.58 and a specificity of 0.94. An AHI < 10 events/hr by PAP AED is usually associated with good treatment efficacy. Differences between manually scored and AED events were primarily due to different criteria for hypopnea detection.


Simultaneous bilateral breast reconstruction with autologous tissue transfer after the removal of injectable artificial materials: a 12-year experience.
Over the years, breast augmentation with injectable artificial materials has presented significant clinical and social problems, particularly in Japan, because of later complications. The authors have used autologous tissue to treat patients who want not only to have these materials removed but also to maintain breast contour. The purpose of this study was to review the clinical outcome of the authors' reconstruction procedures retrospectively. A total of 38 breasts in 19 consecutive cases treated between 1991 and 2002 were reviewed. The patients were all women, ranging in age from 41 to 70 years old (mean age, 53.4 years). The average period from injection to reconstruction was 26.5 years. After removal of the injected materials, both breasts were simultaneously reaugmented with deepithelialized rectus abdominis flaps. The incidence of associated complications was investigated. The 38 flaps consisted of 31 free transverse rectus abdominis musculocutaneous flaps, five pedicled transverse rectus abdominis musculocutaneous flaps, and two pedicled vertical rectus abdominis musculocutaneous flaps. Three flaps with total necrosis (7.9 percent) because of venous thrombosis were found in two cases. Partial flap necrosis was observed in six flaps (15.8 percent). Hematoma requiring a surgical procedure occurred in one case (5.3 percent). Negligible abdominal bulging requiring no additional procedure was found in seven cases (36.8 percent). The complication rate seemed to be relatively high compared with that for breast reconstruction after mastectomy. Nevertheless, autologous tissue transfer may be one of the ideal procedures for breast reaugmentation after the removal of injectable materials, because affected patients prefer not to undergo reaugmentation with other artificial materials.


Increasing the donor and recipient pool-expanded criteria in living kidney donors.
To increase the donor and recipient pool in living related renal transplantation, kidneys from expanded criteria living donors are used more frequently to reduce the general problem of organ shortage. This article presents an overview of the current literature concerning this topic to further improve donor selection and transplant decision making.


Identifying and Targeting Human Tumor Antigens for T Cell-Based Immunotherapy of Solid Tumors.
Cancer elimination in humans can be achieved with immunotherapy that relies on T lymphocyte-mediated recognition of tumor antigens. Several types of these antigens have been recognized based on their cellular origins and expression patterns, while their detection has been greatly facilitated by recent achievements in next-generation sequencing and immunopeptidomics. Some of them have been targeted in clinical trials with various immunotherapy approaches, while many others remain untested. Here, we discuss molecular identification of different tumor antigen types, and the clinical safety and efficacy of targeting them with immunotherapy. Additionally, we suggest strategies to increase the efficacy and availability of antigen-directed immunotherapies for treatment of patients with metastatic cancer.


Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for barnidipine in human plasma.
A sensitive and specific LC-MS-MS assay has been developed and validated for barnidipine (1-benzyl-3-pyrrolidinyl)methyl-2,6-dimethyl-4(m-nitrophenyl)-1,4-dihydr opyridine-3,5-dicarboxylate). The assay involves a simple and rapid solid-phase extraction procedure. Sample analysis was on a Spherisorb S3ODS2 100 mmX2 mm I.D. column, with a Finnigan TSQ 7000 mass spectrometer, using an electrospray interface and selective reaction monitoring (SRM). The intra- and inter-day precision and accuracy, determined as the coefficient of variation and relative error, respectively, were 11.8% or less. The limit of quantitation was 0.03 ng/ml, and the calibration was linear between 0.03 and 3.0 ng/ml. The method has been used successfully for the measurement of over two thousand human plasma samples from pharmacokinetic clinical trials.


Novel Energetic Coordination Polymers Based on 1,5-Di(nitramino)tetrazole With High Oxygen Content and Outstanding Properties: Syntheses, Crystal Structures, and Detonation Properties.
In this study, a series of novel 1,5-di(nitramino)tetrazole (DNAT)-based bimetallic energetic coordination polymers, MK2(DNAT)2·4H2O [M = Fe, Cu, Ni, Co, and Zn], were designed and synthesized in a simple and convenient self-assembly synthetic process. The obtained compounds were fully characterized by IR spectroscopy, multinuclear NMR spectroscopy, elemental analysis, and differential scanning calorimetry (DSC). Additionally, the structures of target compounds were confirmed by single-crystal X-ray diffraction. Based on the room-temperature X-ray densities (2.095-2.138 g cm-3) and the calculated (CBS-QB3) heats of formation (-41.3 to 170.5 kJ mol-1), the detonation properties such as detonation velocities (8,147.0-8,478.4 m s-1) and detonation pressures (29.7-32.8 GPa) were computed using the EXPLO5 v6.04 program. Their excellent energetic properties indicated that they could serve as promising "green" primary explosives for replacement of lead azide (LA).


Applications of three-dimensional imaging techniques in craniomaxillofacial surgery: A literature review.
Three-dimensional (3D) imaging technologies are increasingly used in craniomaxillofacial (CMF) surgery, especially to enable clinicians to get an effective approach and obtain better treatment results during different preoperative and postoperative phases, namely during image acquisition and diagnosis, virtual surgical planning (VSP), actual surgery, and treatment outcome assessment. The article presents an overview of 3D imaging technologies used in the aforementioned phases of the most common CMF surgery. We searched for relevant studies on 3D imaging applications in CMF surgery published over the past 10 years in the PubMed, ProQuest (Medline), Web of Science, Science Direct, Clinical Key, and Embase databases. A total of 2094 articles were found, of which 712 were relevant. An additional 26 manually searched articles were included in the analysis. The findings of the review demonstrated that 3D imaging technology is becoming increasingly popular in clinical practice and an essential tool for plastic surgeons. This review provides information that will help researchers and clinicians consider the use of 3D imaging techniques in CMF surgery to improve the quality of surgical procedures and achieve satisfactory treatment outcomes.


Mutations induced at the white and vermilion loci in Drosophila melanogaster.
The white and vermilion loci in D. melanogaster were selected as target genes for the study of the mutational specificity of ionizing radiation and N-ethyl-N-nitrosourea (ENU) in a whole organism. Analysis of X-ray- and neutron-induced white mutants by a combination of genetic and molecular techniques showed that ionizing radiation induces primarily break-type mutations against a repair-proficient background, the majority of these alterations being deletions. Both very large multi-locus deficiencies and deletions of only a few base pairs were observed. These small deletions are flanked by repeats of 2-3 nucleotides, one copy of which is retained at the new junction. Presumably these small repeats are involved in the generation of the X-ray-induced deletions. In excision-repair-deficient mus201D1 flies, the frequency of whole-body white mutants recovered after X-ray irradiation is the same as in the wild-type strain. The percentage of mosaic mutations, however, is enhanced by a factor 3-4. Analysis by blot hybridization of ENU-induced white mutants strongly indicates that most mutations are due to base-pair changes. This was confirmed by sequence analysis of 25 ENU-induced vermilion mutants. In all mutants the alterations are due to base-pair changes, the majority being GC to AT transitions (61%).


Long-Term Exposure to Ambient Fine Particulate Matter and Renal Function in Older Men: The Veterans Administration Normative Aging Study.
It is unknown if ambient fine particulate matter (PM2.5) is associated with lower renal function, a cardiovascular risk factor. We investigated whether long-term PM2.5 exposure was associated with estimated glomerular filtration rate (eGFR) in a cohort of older men living in the Boston Metropolitan area. This longitudinal analysis included 669 participants from the Veterans Administration Normative Aging Study with up to four visits between 2000 and 2011 (n = 1,715 visits). Serum creatinine was measured at each visit, and eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation. One-year exposure to PM2.5 prior to each visit was assessed using a validated spatiotemporal model that utilized satellite remote-sensing aerosol optical depth data. eGFR was modeled in a time-varying linear mixed-effects regression model as a continuous function of 1-year PM2.5, adjusting for important covariates. One-year PM2.5 exposure was associated with lower eGFRs; a 2.1-μg/m3 interquartile range higher 1-year PM2.5 was associated with a 1.87 mL/min/1.73 m2 lower eGFR [95% confidence interval (CI): -2.99, -0.76]. A 2.1 μg/m3-higher 1-year PM2.5 was also associated with an additional annual decrease in eGFR of 0.60 mL/min/1.73 m2 per year (95% CI: -0.79, -0.40). In this longitudinal sample of older men, the findings supported the hypothesis that long-term PM2.5 exposure negatively affects renal function and increases renal function decline. Mehta AJ, Zanobetti A, Bind MC, Kloog I, Koutrakis P, Sparrow D, Vokonas PS, Schwartz JD. 2016. Long-term exposure to ambient fine particulate matter and renal function in older men: the VA Normative Aging Study. Environ Health Perspect 124:1353-1360; http://dx.doi.org/10.1289/ehp.1510269.


High-performance liquid chromatography of antipyretics on chemically modified porous glass.
An octadecylsilyl porous glass was prepared and used as the packing for reversed-phase high-performance liquid chromatography. Five antipyretic drugs (aspirin, caffeine, guaiacol glycerol ether, 3-hydroxy-p-butyrophenetidine, and phenacetin) were separated in 2 min with a mobile phase of 20% acetonitrile at a flow-rate of 3.0 ml/min. A pharmaceutical preparation, containing aspirin, phenacetin, caffeine and chlorpheniramine maleate was analysed in 2 min with a mobile phase of acetonitrile-water-acetic acid (20:79:1). The packing seems promising for the rapid analysis of pharmaceuticals and biomedical compounds.


Three-dimensional reconstruction of neuroradiological data within a stereotactic frame of reference for surgery of visible targets.
Three-dimensional information obtained with neuroradiological exams performed under stereotactic conditions is displayed on a surgical console within the graphic reconstruction of the geometry of stereotactic frames. Planning of convenient probe trajectories can be carried out taking into account all data derived from different diagnostic techniques.


Binding of [3H] monohydroxytamoxifen in ovarian carcinoma.
A monoclonal antibody (D-547) against human breast cancer oestrogen receptor was used to demonstrate that the oestrogen receptor in ovarian epithelial carcinomata binds [3H]monohydroxytamoxifen. This binding was observed in sedimentation velocity analyses of both cytosol and nuclear compartments. Binding of [3H]monohydroxytamoxifen to the antibody-recognized moiety could be inhibited by diethylstilboestrol or oestradiol, but not by androgen, progestin or corticoid, indicating oestrogen specificity for the binding site. The sedimentation coefficient of the antibody-recognized [3H]monohydroxytamoxifen binding moiety was similar to that when 16 alpha-[125I]iodo-oestradiol was used as the ligand.


Role of amyloid beta (25-35) neurotoxicity in the ferroptosis and necroptosis as modalities of regulated cell death in Alzheimer's disease.
Neuronal cell death as a prominent pathological feature contributes to cognitive decline and memory loss in Alzheimer's disease. We investigated the role of two forms of cell death pathways, ferroptosis and necroptosis, and their interactions following entorhinal cortex (EC) amyloidopathy. The Aβ25-35 was bilaterally injected into the rat's EC, and Morris Water Maze was applied to determine spatial performance one week after Aβ injection. For evaluation of ferroptosis and necroptosis involvement in Aβ induced pathology, ferroptosis inhibitor, Ferrostatin (Fer-1), and necroptosis inhibitor, Necrostatin (Nec-1), were injected into the EC during training days of behavioral test. Our behavioral and histological assessment showed spatial learning and memory impairment, along with neuropathology changes such as cell survival and intracellular Aβ deposits in response to EC amyloidopathy, which were ameliorated by treatment with Fer-1 or Nec-1. The expression of ferroptosis key factors GPX4 and SLC7A11 were decreased and the level of TfR was increased following Aβ toxicity. Also, Necroptosis pathway related factors RIP1, RIP3, and MLKL were modulated by Aβ neurotoxicity. However, application of Fer-1 or Nec-1 could inhibit the hippocampal ferroptosis and necroptosis pathways due to EC amyloidopathy. Our data also demonstrated that Aβ-induced necroptosis suppressed by Fer-1, although Nec-1 had no effect on ferroptosis, indicating that ferroptosis pathway is upstream of necroptosis process in the Aβ neurotoxicity. Moreover, Aβ induced hippocampal mGLUR5 overexpression and reduced level of STIM1/2 recovered by Fer-1 or Nec-1. According to our findings ferroptosis and necroptosis pathways are involved in Aβ neurotoxicity through modulation of mGLUR5 and STIM1/2 signaling.


Heparin-bound transforming growth factor-beta3 enhances neocartilage formation by rabbit mesenchymal stem cells.
Heparin binds growth factors to form a stable complex that maintains the biological activity and can retard the release pattern. To differentiate the embedded the stem cells, heparin-bind transforming growth factor (TGF)-beta3 was mixed with rabbit mesenchymal stem cells encapsulated with thermo-reversible hydrogel. It is suggested that the heparin-bound TGF-beta3 would help to increase the chondrogenic differentiation of rabbit mesenchymal stem cells in thermo-reversible hydrogel. To determine the optimal condition for neocartilage formation, we characterized hydrogel constructs with growth factor release profiles, confocal laser microscopy, reverse transcription-polymerase chain reaction analysis, and histology. Reverse transcription-polymerase chain reaction analysis of the resultant cartilage tissue revealed that a thermo-reversible hydrogels with a heparin-bound TGF-beta3 was optimal for cartilage tissue formation as measured by production of collagen Type II, aggrecan, and SOX9, and cartilage oligomeric matrix protein gene expression. Additionally, the proliferation rate and cartilage specific ECM production were both significantly greater in the presence of heparin-bound TGF-beta3 than in the control. The amount of cartilage-associated ECM proteins was examined by immunohistochemical staining (collagen type II), Safranin-O staining, and Alcian blue staining. These data indicate the potential use of heparin-binding TGFbeta-3 for reconstruction of neocartilage formation.


Transient, early release of glucagon-like peptide-1 during low rates of intraduodenal glucose delivery.
The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (approximately 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1. To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response. Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min. Clinical research laboratory. 27 healthy subjects (24 male; age 36+/-3 years; BMI 25.2+/-0.7 kg/m(2)). Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean+/-SEM. During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P<0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P<0.001), insulin (P<0.001), and blood glucose (P<0.001). In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.


Training Distal Locking Screw Insertion Skills to Novice Trainees: A Comparison Between Fluoroscopic- and Electromagnetic-Guided Techniques.
To compare the effect fluoroscopy or electromagnetic (EM) guidance has on the learning of locking screw insertion in tibial nails in surgical novices. A randomized, prospective, controlled trial was conducted involving 18 surgical trainees with no prior experience inserting locking screws in intramedullary nails. After a training session using fluoroscopy, participants underwent a pretest using fluoroscopic guidance. Participants were then randomized into either the fluoroscopy or EM group and were further trained using their respective technique. Post, retention, and transfer tests were conducted. Outcomes included task completion, drill attempts, screw changes, and radiation time. Intragroup comparisons revealed that the EM group used significantly less drill attempts during the post and retention tests compared with the pretest (P = 0.016 and P = 0.016, respectively). Intergroup comparisons revealed that the EM group was (1) more likely to complete the task during the retention test (P = 0.043) and (2) had significantly less radiation time during the post and retention tests (P = 0.002 and P = 0.003, respectively). Radiation time in the EM group during the transfer test increased to a level equal to what the fluoroscopy group used during the post and retention tests (P = 0.71 and P = 0.92, respectively). No other significant between-group differences occurred. EM guidance may be safely used to assist in the training of surgical novices in the skill of distal locking screw insertion. Not only does this technology significantly improve the ability to complete the task and decrease radiation use but also it does so without compromising skill acquisition. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Could the Topping-Off Technique Be the Preventive Strategy against Adjacent Segment Disease after Pedicle Screw-Based Fusion in Lumbar Degenerative Diseases? A Systematic Review.
The "topping-off" technique is a new concept applying dynamic or less rigid fixation such as hybrid stabilization device (HSD) or interspinous process device (IPD) for the purpose of avoiding adjacent segment disease (ASD) proximal to the fusion construct. A systematic review of the literature was performed on the effect of topping-off techniques to prevent or decrease the occurrence of ASD after lumbar fusion surgery. We searched through major online databases, PubMed and MEDLINE, using key words related to "topping-off" technique. We reviewed the surgical results of "topping-off" techniques with either HSD or IPD, including the incidence of ASD at two proximal adjacent levels (index and supra-adjacent level) as compared to the fusion alone group. The results showed that the fusion alone group had statistically higher incidence of radiographic (52.6%) and symptomatic (11.6%) ASD at the index level as well as higher incidence (8.1%) of revision surgery. Besides, the HSD (10.5%) and fusion groups (24.7%) had statistically higher incidences of radiographic ASD at supra-adjacent level than the IPD (1%). The findings suggest that the "topping-off" technique may potentially decrease the occurrence of ASD at the proximal motion segments. However, higher quality prospective randomized trials are required prior to wide clinical application.


Anaesthesia for patients with cardiac disease. Preoperative management.
Patients with cardiac disease have an increased risk of mortality and morbidity from anaesthesia and surgery. Adequate recognition of cardiac disease and its pathophysiological consequences will lead to appropriate preoperative management, which can greatly reduce these risks to the patient.


Evaluation of thyrotoxicosis during pregnancy with color flow Doppler sonography.
To determine whether color flow Doppler sonography (CFDS) is useful in differentiating Graves vs non-Graves thyrotoxicosis during pregnancy, when nuclear imaging is contraindicated. Ten pregnant women with thyrotoxicosis were divided into Graves, and non-Graves, disease groups and were evaluated by CFDS for thyroid volume, vascularity, and inferior thyroid artery (ITA) flow velocity. Each patient was matched with a euthyroid woman of the same pregnancy duration. Of the 10 patients, 3 were diagnosed with Graves disease, 4 with gestational toxicosis, and 3 with destructive thyroiditis. Those in the Graves disease group had a greater thyroid gland volume (18.9+/-1.5 cm3 vs 12.1+/-2.4 cm3; P<0.05), greater thyroid vascularity, and greater ITA flow velocity than those in the non-Graves disease group (92+/-13 cm/s vs 20.4+/-2.4 cm/s; P<0.05). There was no significant difference in the corresponding values between the patients with gestational toxicosis and those with destructive thyroiditis or between them and their healthy controls. Thyroid evaluation by CFDS is useful for the differential diagnosis of thyrotoxicosis in pregnant women.


LRSAM1 E3 ubiquitin ligase promotes proteasomal clearance of E6-AP protein.
Numerous proteins participate and actively contribute to the various cellular mechanisms, where several of them are crucial for regular metabolism, including survival. Thus, to maintain optimal cellular physiology, cells govern protein quality control functions with the assistance of comprehensive actions of molecular chaperones, the ubiquitin-proteasome system, and autophagy. In the ubiquitin-proteasome pathway, few quality control E3 ubiquitin ligases actively participate against misfolded protein aggregation generated via stress conditions. But how these quality control E3s active expression levels returned to basal levels when cells achieved re-establishment of proteostasis is still poorly understood. Our current study demonstrated that LRSAM1 E3 ubiquitin ligase promotes the proteasomal degradation of quality control E3 ubiquitin ligase E6-AP. We have observed the co-localization and recruitment of LRSAM1 with E6-AP protein and noticed that LRSAM1 induces the endogenous turnover of E6-AP. Partial depletion of LRSAM1 elevates the levels of E6-AP and affects overall cell cycle regulatory proteins (p53 and p27) expression, including the rate of cellular proliferation. The current finding also provides an excellent opportunity to better understand the basis of the E6-AP associated pathomechanism of Angelman Syndrome disorder. Additionally, this study touches upon the novel potential molecular strategy to regulate the levels of one quality control E3 ubiquitin ligase with another E3 ubiquitin ligase and restore proteostasis and provide a possible therapeutic approach against abnormal protein aggregation diseases.


Significant sensitivity improvement of alternating current driven-liquid discharge by using formic acid medium for optical determination of elements.
A method has been developed to improve the performance of alternating-current electrolyte atmospheric liquid discharge (ac-EALD) optical emission spectrometry for the determination of elements. Significant enhancement of emission intensity was achieved by adding organic substance into the nitric acid electrolyte solutions. Under the optimized conditions, 3% (v/v) formic acid in nitric acid (pH 1.0) produced 13 times enhancement for Ag and 7% (v/v) formic acid resulted in 17 times enhancement for Cd. The emission of Pb was even enhanced 78 times in the presence of 3% formic acid. In addition, the signal stability was also improved compared with that in the absence of organic substances. Repeatability was 0.8% for 0.1 mg L(-1) Ag, 0.7% for 0.2 mg L(-1) Cd and 2.6% for 1 mg L(-1) Pb standard solutions (n=5). The limits of detection of Ag, Cd and Pb were 1, 17 and 45 μg L(-1), respectively. The accuracy of the method was demonstrated by determination of elements in simulated natural water samples (GBW(E)080402 and GBW(E)080399).


Pin tract infection with contemporary external fixation: how much of a problem?
To determine the incidence of pin tract infection.DESIGN Retrospective chart review. Level 1 trauma center in an urban community. A total of 285 patients with 285 fractures over a 4-year period (1997-2001). External fixation. Incidence of pin tract infection. Of 285 fractures, 32 (11.2%) were complicated by infection. The incidence of infection according to montage was 3.9% (3/77) for ring fixators, which was significantly different (P < 0.04) from the 12.9% incidence (23/178) for unilateral fixators and the 20.0% incidence (6/30) for hybrid fixators (P = 0.004). The incidences of pin tract infection for the unilateral fixator group and the hybrid fixator group were not significantly different. Patients with hybrid external fixators had a similar risk of pin tract infection as patients who had unilateral fixators. The infection rate in the ring fixator group was significantly lower than the hybrid external and unilateral fixator groups.


Attenuation of hydrochlorothiazide-induced hypokalemia in dogs by a beta-adrenergic blocking drug, timolol.
Hydrochlorothiazide, administered at 1, 3 and 9 mg/kg/day p.o. for 4 days, produced a dose-dependent lowering of plasma potassium and an elevation in plasma renin activity in unanesthetized dogs. When plasma renin activity was suppressed in diuretic-treated dogs by the potent beta-adrenergic receptor-blocking drug, timolol (0.5, 2 mg/kg/day p.o. for 4 days), the hypokalemia and hyperreninemia were significantly less pronounced. The data suggest that beta-adrenergic blocking drugs can be used to antagonize these side effects of diuretics.


Is neutrophil/lymphocyte ratio a useful marker to predict the severity of pre-eclampsia?
To evaluate the relationship of neutrophil/lymphocyte ratio (NLR) with proteinuria and blood pressure level in patients with pre-eclampsia and to investigate whether or not NLR has a role in predicting the severity of pre-eclampsia. The study comprised 30 healthy pregnant females (Group 1), 37 females with mild pre-eclampsia (Group 2) and 40 with severe pre-eclampsia (Group 3). All the study participants were statistically compared in respect of demographic data, proteinuria levels, and blood pressure levels. Age, body mass index, and gestational weeks were similar in all the groups. Maternal NLR was determined to be significantly high in the pre-eclamptic patients (Groups 2 and 3) compared to the healthy pregnant patients (Group 1) (p=0.017). NLR was significantly higher in the severe pre-eclampsia group than in the mild pre-eclampsia group (p=0.032). A significant positive correlation was determined in correlation analysis between NLR and proteinuria (p=0.013, r=0.319). There was also a significant and positive correlation between NLR and systolic/diastolic arterial pressure (p=0.007, r=0.285; p=0.044, r=0.213, respectively). In conclusion, while NLR was determined as significantly high in patients with pre-eclampsia, to be able to use this in the classification of the severity of pre-eclampsia, there is a need for further studies on a more extensive population.


Superoxide radical-scavenging effects from polymorphonuclear leukocytes and toxicity in human cell lines of newly synthesized organic selenium compounds.
Synthetic organic selenium compounds such as 2-phenyl-1,2-benzisoselenazol-3(2H)-one may show glutathione peroxidase-like antioxidant activity. Recently, we synthesized new organic selenium compounds that are thought to be effective antioxidants. To study their possible applications as antioxidants, we evaluated two selenoureas, N,N-dimethylselenourea and 1-selenocarbamoylpyrrolidine, and two tertiary selenoamides, N-(phenylselenocarbonyl)-piperidine and N,N-diethyl-4-chloroselenobenzamide, for their superoxide radical (O2-)-scavenging effects and toxicity. We measured (O2-)-scavenging effects in polymorphonuclear leukocytes (PMNs) with a specific, sensitive and real-time kinetic chemiluminescence method. Furthermore, the toxicity of these compounds was measured in some human cell lines and PMNs using the tetrazolium method. Hydrogen peroxide was measured by a scopoletin method. Finally, translocation of an NADPH oxidase component, p47 phagocyte oxidase, to the cell membrane was investigated by confocal laser scanning microscopy. N,N-Dimethylselenourea and 1-selenocarbamoylpyrrolidine effectively scavenged (O2-) released from 4beta-phorbol 12-myristate 13-acetate-stimulated PMNs, and the 50% inhibitory concentrations were 6.8 +/- 2.2 and 6.5 +/- 2.5 microm, respectively. N-(Phenylselenocarbonyl)-piperidine and N,N-diethyl-4-chloroselenobenzamide also effectively scavenged (O2-) from PMNs, and the 50% inhibitory concentrations were 11.3 +/- 4.8 and 20.3 +/- 6.4 microm, respectively. Selenoureas showed very low toxicity in human cell lines and PMNs, even at high concentrations, whereas tertiary selenoamides were cytotoxic. These compounds did not produce significant amounts of hydrogen peroxide from 4beta-phorbol 12-myristate 13-acetate-stimulated PMNs. None of the compounds significantly affected the translocation of p47 phagocyte oxidase. Selenoureas acted as effective antioxidants and showed low toxicity in some human cells. Thus, these compounds might be new candidates as antioxidative substances.


[Mismanagement of chest trauma; sequels and the possibility of repair (author's transl)].
60 persons with a chest trauma were treated during the past years. In a number of cases the injuries and the resulting complications were of so serious a nature that their repair was attended by the greatest difficulties. The most serious and initially unrecognized complications comprised: 1) tracheo-bronchial defects, partly of traumatic origin and partly arising during intensive care; 2) failure to detect rupture of the diaphragm with displacement of visceral organs into the thoracic cavity; 3) insufficient evacuation of blood or fluid from the pleural cavity; 4) failure to diagnose irreparable damage to part of the lungs. Means to repair these lesions are reviewed; the necessity for long-term observation of these cases is emphasized.


The effect of 24-hour sleep deprivation and anaerobic exercise on the expression of BAX, BCL2, BMAL1 and CCAR2 genes in peripheral blood mononuclear cells after L-arginine supplementation.
Sleep deprivation disrupt the circadian clock and exercise performance. Defective oxidative stress caused by sleep deprivation may affect the expression of genes involved in cell apoptosis. Since a number of studies have shown the anti-apoptotic effect of L-arginine, so the aim of this study was to evaluate the effect of eight weeks of L-arginine supplementation on the expression of brain and muscle ARNT-like protein 1 (BMAL1), cell cycle and apoptosis regulator 2 (CCAR2), and BAX and BCL2 genes during sleep deprivation and acute anaerobic exercise. Participants included 20 healthy men age 26-35 years, randomized into the L-arginine intervention group (n = 10) and a placebo control (n = 10). The running-based anaerobic sprint test (RAST) was used for anaerobic exercise. Intervention subjects took one 1000 mg L-arginine tablet daily for 8 weeks. The Real-Time PCR method was used to determine apoptosis gene expression in peripheral blood mononuclear cells (PBMCs). Acute anaerobic exercise and sleep deprivation both increased the expression of BAX and CCAR2 genes, and decreased the expression of BCL2 and BMAL1 genes (p < 0.05 for all). L-arginine supplementation increased the expression of BMAL1 and BCL2 genes and decreased the expression of BAX and CCAR2 genes relative to control (p < 0.05). L-Arginine controlled the increase in expression of BAX and CCAR2 genes and the decrease in expression of BCL2 and BMAL1 genes in response to sleep deprivation and acute anaerobic exercise (p < 0.05). Our results showed that 24-hour sleep deprivation and acute anaerobic exercise increased the expression of pro-apoptotic genes (BAX and CCAR2) and decreased the expression of anti-apoptotic genes (BCL2 and BMAL1), although the effect of sleep deprivation is greater. In this situation, L-arginine supplementation may balance the apoptotic state of peripheral blood mononuclear cells. However, any recommendation about this needs further research.


Alteration of delta-6-desaturase (FADS2), secretory phospholipase-A2 (sPLA2) enzymes by Hot-nature diet with co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.
The effect of nutrition and dietary supplements as environmental factors has been suggested as possible factors affecting both disease risk and progression in on the course of multiple sclerosis with complex genetic-risk profiles. This study was aimed to assess regulation of surface-membrane enzymes such as Delta-6-desaturase (FADS2), secretory Phospholipase A2(sPLA2) by hemp seed and evening primrose oils as well as Hot-natured dietary intervention in relapsing remitting multiple sclerosis (RRMS) patients. In this double blind, randomized trial, 100 RRMS patients with Extended disability status score (EDSS)<6 were allocated into 3 groups: "Group A" who received co-supplemented hemp seed and evening primrose oils along with advised Hot nature diet; "Group B", who received olive oil; "Group C", who received the co-supplemented oils. Clinically EDSS and functional score as well as biochemical parameters [blood cells polyunsaturated fatty acid (PUFA), FADS2, sPLA2] were assessed at baseline and after 6 months. Mean follow-up was 180±2.9SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration 6.80±4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in EDSS and functional score were found in the groups A and C while EDSS and pyramidal score showed significant increase in group B. Alteration of biochemical parameters showed improvement in groups A and C whereas there was worsening condition for group B after the intervention. The co-supplemented hemp seed and evening primrose oils with Hot nature diet can have beneficial effects in improving clinical symptoms and signs in RRMS patients which were confirmed by regulation of surface-membrane enzymes.


Use of TARA hemiarthroplasty in advanced osteonecrosis.
The results of 25 TARA hemiarthroplasty procedures performed on 21 patients with radiographically documented Ficat stages III and IV osteonecrosis are reported. The average patient age at the time of surgery was 37.6 years (range, 22-55 years). The average length of follow-up study was 37 months (range, 25-60 months). Preoperative Harris hip scores averaged 51 points (range, 22-69 points). Postoperative scores averaged 90 points (range, 66-100 points). Good or excellent results were obtained in 22 of 25 hips. There were no cases of infection or component dislocation. Three component revisions were performed in two patients. Four patients required removal of trochanteric wires and one patient had excision of heterotopic ossification. This procedure appears to offer selected young patients with advanced femoral head osteonecrosis a very satisfactory initial result, while preserving many options for subsequent revision procedures.


Posterior C2 Fixation Using Trans-C2 Inferior Articular Process Screws: A Case Series and Technical Note.
Upper cervical fixation with C2 pedicle screw insertion may predispose patients to vertebral artery injury, in particular, patients with craniovertebral junction anomalies. The aim of this study was to describe an alternative technique with trans-C2 inferior articular process screw (C2IAPS) insertion for rigid C2 fixation, which can be used to anchor the C2 vertebra for upper cervical fixation. Records of 19 patients who underwent posterior atlantoaxial fixation using C2IAPS combined with C1 lateral mass screw were retrospectively reviewed. Efficacy was assessed by postoperative imaging and Japanese Orthopaedic Association scores. There were 22 C2IAPSs successfully implanted (3 on both sides and 16 on 1 side). With the exception of 2 screws that had intruded into the outlet of the intervertebral foramen, all screws were safely implanted. Average Japanese Orthopaedic Association scores improved from 11.8 ± 1.9 preoperatively to 15.3 ± 1.3 postoperatively. Bony fusion rate was 100%. For patients who are not eligible for C2 pedicle screw fixation, C2IAPS fixation can be considered as an alternative technique for upper cervical fixation of C2.


Family presence during resuscitation (FPDR): Perceived benefits, barriers and enablers to implementation and practice.
There are a number of perceived benefits and barriers to family presence during resuscitation (FPDR) in the emergency department, and debate continues among health professionals regarding the practice of family presence. This review of the literature aims to develop an understanding of the perceived benefits, barriers and enablers to implementing and practicing FPDR in the emergency department. The perceived benefits include; helping with the grieving process; everything possible was done, facilitates closure and healing and provides guidance and family understanding and allows relatives to recognise efforts. The perceived barriers included; increased stress and anxiety, distracted by relatives, fear of litigation, traumatic experience and family interference. There were four sub themes that emerged from the literature around the enablers of FPDR, these included; the need for a designated support person, the importance of training and education for staff and the development of a formal policy within the emergency department to inform practice. In order to ensure that practice of FPDR becomes consistent, emergency personnel need to understand the need for advanced FPDR training and education, the importance of a designated support person role and the evidence of FPDR policy as enablers to implementation.


Which tissue adhesive for wounds?
We studied the three available tissue adhesives comparing their ease of technique, wound healing, satisfaction, merits and complications when treating childhood lacerations. Children presenting with uncomplicated wounds <2.5cm and <6h since the injury were studied. There were 17 children in each group. Results were compared for the individual tissue adhesive and the technique-contact and non-contact. The application was considered pain free in 82% of the non-contact technique and 56% for the contact technique-pain in 18 and 44%, respectively (P=0.062). Parents were satisfied in 88 and 94% for the contact and non-contact techniques, respectively (P=0.505) and the authors in 76 and 94% (P=0.119). The glove stuck to the wound in nine instances and was damaged once while breaking the container. The scab persisted in all scalp applications for 9-25 days. The adhesive effect was similar in all three. Indermil was considered to be the best among the three. Non-contact, droplet instillation (rather than contact application as was suggested for Dermabond and Histoacryl) was felt more comfortable.


The effect of reactive oxidant generation in acute exercise-induced proteinuria in trained and untrained rats.
Exercise-induced proteinuria is a common consequence of physical activity, although its mechanism is not clear. We investigated whether free radicals generated during exercise play a role in post-exercise proteinuria in sedentary and treadmill-running trained rats, separately. Sedentary and trained rats were randomly divided into four sub-groups: control, antioxidant treatment, exhaustive exercise and an exhaustive exercise plus antioxidant treatment group. Antioxidant therapy was applied by intragastric catheter for 4 weeks with vitamin C (ascorbic acid, 50 mg x kg(-1) x day(-1)) and vitamin E (alpha-tocopherol, 20 mg x kg(-1).day(-1)). Twenty-four-hour urine samples were used for measuring protein levels and protein electrophoresis. Thiobarbituric acid (TBARS) and glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities were assayed in blood and tissues. Increased urinary protein levels and mixed type proteinuria in electrophoresis were identified after exhaustive exercise in sedentary rats. Erythrocyte, kidney and muscle TBARS levels were significantly elevated in this group. Antioxidant treatment prevented the increase in urinary protein levels, TBARS levels and the occurrence of mixed type proteinuria after exhaustive exercise in sedentary rats. Exhaustive exercise in trained rats resulted in elevation of urine protein levels and mixed type proteinuria although kidney TBARS levels were not changed compared to those of the trained controls. Antioxidant therapy in trained and exhausted-trained animals resulted in decreased TBARS levels in the kidney but it did not affect urinary-increased protein levels or electrophoresis in exhausted animals. This findings suggest that the exercise-induced oxidant stress may contribute to post-exercise proteinuria in sedentary rats. However, this mechanism may not be responsible for proteinuria in trained rats.


Amphiphiles as hydrophobicity regulator: fine tuning the surface hydrophobicity of an electropolymerized film.
Smart clean surfaces exhibiting reversible superhydrophilic to superhydrophobic transitions have been widely fabricated. A myriad of complex fabricating procedures have evolved over the years. Here, we demonstrate an apparently simple approach, wherein we utilized the attractive interaction between an unfabricated electropolymerized film and negative charge bearing amphiphilic molecules to precisely control the hydrophobicity of the surface of the film. We also demonstrate the use of different hydrophobic molecules to plug the voids created by the uneven distribution of the attached amphiphiles' long hydrocarbon tails on the film surface. Water drop contact angle revealed that by the used technique, surface hydrophobicity can be tuned to any desired value. Moreover, the film surface exhibited a high adhesive force toward the water droplets, thus preventing them from rolling or dropping down. In addition, the tuning process can be completely reversed and repeated by altering the applied potential. The interaction between the amphiphiles and the film surface was confirmed by ATR-IR. Scanning electron micrographs revealed that the film surface underwent no morphological modifications upon interaction with the amphiphiles.