Shoulder function in various types of neck dissection. Role of spinal accessory nerve and cervical plexus preservation.
The aim of this study is to determine the effects of two different types of nerve-sparing neck dissection on shoulder function. Even if the spinal accessory nerve is spared in functional neck dissection, some degree of shoulder syndrome may occur. The role of the cervical plexus in shoulder function and the effects of dissection of level 5 are emphasized. Twenty-six patients with laryngeal carcinoma were studied prospectively. Seventeen anterolateral and 15 functional neck dissections were performed. Electromyographic evaluation was carried out in all patients to assess spinal accessory nerve function preoperatively and at the sixth week and sixth month postoperatively. Shoulder disability was evaluated by a questionnaire (shoulder pain disability index) and goniometric measurements were done preoperatively and at the sixth postoperative month. In patients who underwent anterolateral neck dissection, the goniometric results were better than in the functional neck dissection group. The questionnaire results also showed better quality of life of patients who underwent anterolateral neck dissection. Electrophysiological evaluation of the trapezius muscles of both groups at the sixth week showed significant differences. The distal motor latency values of the anterolateral neck dissection group were shorter than those of the other group. Electrophysiological evaluation at the sixth postoperative month showed shorter distal latency values in the anterolateral dissection group, without statistical significance. Preservation of the cervical plexus and less disturbance of the spinal accessory nerve are important to diminish postoperative shoulder disability. The type of neck dissection has an important influence on shoulder function.


Gene characterization and transcription analysis of two new ammonium transporters in pear rootstock (Pyrus betulaefolia).
Ammonium is the primarily nitrogen source for plant growth, but the molecular basis of ammonium acquisition in fruit species remains poorly understood. In this study, we report on the characterization of two new ammonium transporters (AMT) in the perennial tree Pyrus betulaefolia. In silico analyses and yeast complementation assays revealed that both PbAMT1;3 and PbAMT1;5 can be classified in the AMT1 sub-family. The specific expression of PbAMT1;3 in roots and of PbAMT1;5 in leaves indicates that they have diverse functions in ammonium uptake or transport in P. betulaefolia. Their expression was strongly influenced by ammonium availability. In addition, the transcript level of PbAMT1;5 was significantly affected by the diurnal cycle and senescence hormones. They conferred the ability to uptake nitrogen to the yeast strain 31019b; however, the (15)NH4 (+) uptake kinetics of PbAMT1;3 were different from those of PbAMT1;5. Indeed, PbAMT1;3 had a higher affinity for (15)NH4 (+), and pH changes were associated with this substrates' transport in yeast. The present study provides basic gene features and transcriptional information for the two new members of the AMT1 sub-family in P. betulaefolia and will aid in decoding the precise roles of AMTs in P. betulaefolia physiology.


The genetics of childhood psychiatric disorders: a decade of progress.
To review the literature over the past decade on the genetics of childhood neuropsychiatric disorders. A computerized search was performed for articles published in the past decade, and selected papers were highlighted. The past decade of research has illuminated the complex genetics of early-onset mental disorders. Advances in statistical methodologies and laboratory-based gene-hunting techniques are laying the foundation for a deeper understanding of both the biological and environmental factors that contribute to mental illness. Researchers are on the verge of identifying and characterizing genetic vulnerabilities involved in common childhood psychiatric syndromes. Although the study of the genetics of childhood psychiatric disorders has advanced significantly over the past decade, considerable work remains. The identification of genes conferring vulnerability to psychiatric illnesses will have the potential to transform the field by providing insight into both biological and environmental determinants that contribute to serious developmental and psychiatric disorders in children and adolescents. These advances promise new understanding and new avenues for prevention and treatment. They will also present physicians and families with significant clinical and ethical challenges.


Long-term outcome after angioplasty of symptomatic internal carotid artery stenosis with and without stent.
Carotid angioplasty and stenting (CAS) has widely replaced balloon angioplasty (percutaneous transluminal angioplasty, PTA) in the treatment of internal carotid artery stenosis (ICAS). Here we assess whether the use of stents increases the safety and long-term efficacy of angioplasty in patients with ICAS. Our aim was to test the hypothesis that the long-term efficacy of CAS is superior to that of PTA. At the University Medical Center Hamburg-Eppendorf, PTA was performed from 1990 to 1997 and CAS was performed from 1998 to 2006. All patients undergoing these procedures were symptomatic. Selection and follow-up examinations were performed by independent vascular neurologists. Follow-up terms were 1, 3, 6 and 12 months, then annually. In the PTA group (n=71), 2.8% of the patients showed severe periinterventional complications (i.e. lasting neurological deficits). Of these 71 patients, 57.7% were followed up for an average period of 51 months. Stenosis >70% was observed in 9.8% of the PTA patients, while 4.9% of the patients had ipsilateral occlusions. In the CAS group (n=354), 4.2% of the patients showed severe periinterventional complications. In total, 61% of the CAS patients were followed up for an average period of 25 months, of whom 4.6% showed stenosis of >70% and 1.9% had ipsilateral occlusions. Periprocedural complications and new symptoms that appeared during follow-up occurred at a rate of 5.6% (PTA) and 5.9% (CAS). There was no difference in the rate of annual ipsilateral events (1.1% in PTA vs. 1.3% in CAS, p=1.000) Overall, the use of stents, rather than PTA only, shows no beneficial clinical effect in the treatment of ICA stenosis. While the rate of restenosis may be significantly reduced, this merely suggests that the impact of restenosis is less apparent than expected.


Wheat germ cytoplasmic ribosomes. Localization of 7-methylguanosine and 6-methyladenosine by electron microscopy of immune complexes.
Nucleoside analysis of the RNA from the small subunit of wheat germ cytoplasmic ribosomes shows 1 mol each of N7-methylguanosine and N6-methyladenosine/mol of RNA. Antibodies directed against each methylated nucleoside were used to localize these residues within the subunit by electron microscopy of immune complexes. Antibodies to 7-methylguanosine bound 40 S subunits at a single site, at or slightly above the division between the upper and lower segments of the particle and on the surface furthest from the platform (or large lobe) of the subunit. This site is essentially equivalent to that previously seen with Escherichia coli and chloroplast 30 S subunits (Trempe, M. R., Ohgi, K., and Glitz, D. G. (1982) J. Biol. Chem. 257, 9822-9829). Antibodies to N6-monomethyladenosine were induced in rabbits with a nucleoside-albumin conjugate and shown to be specific for the modified nucleoside. Electron microscopy of antibody-subunit complexes placed the methyladenosine residue in a position that is essentially indistinguishable from that of 7-methylguanosine.


Global Rostral Midbrain Syndrome (GRMS) and Corpus callosum infarction in the context of shunt overdrainage.
We report 3 cases of Global rostral midbrain syndrome (GRMS) and Corpus Callosum (CC) infarction, in the context of hydrocephalus followed by shunt dysfunction and slit ventricles. Prior shunt implantation had been indicated for adult-onset hydrocephalus secondary to aqueductal stenosis of varying causes. All three patients had been stable for months before developing repeated shunt dysfunctions, ultimately progressing to parkinsonism, Parinaud syndrome, akinetic mutism, pyramidal signs, cognitive impairment, CC infarction and slit ventricles, in the context of CSF overdrainage. Parkinsonism-related symptoms responded to dopa in all cases, but Parinaud syndrome and cognitive impairment persisted. Although GRMS has been described in the context of a transtentorial pressure gradient after shunt blockage, in these three cases with similar clinical presentation, reverse transtentorial pressure gradient and slit ventricles due to shunt overdrainage was the likely cause. The authors discuss the role of CC infarction and provide a detailed analysis after gathering previously described data, to unify information under a recognizable clinical entity and better understand the underlying pathophysiology, treatment options and outcome.


A national study of Continuous Professional Competence (CPC) amongst pre-hospital practitioners.
Internationally, continuing professional competence (CPC) is an increasingly important issue for all health professionals. With the introduction of the first CPC framework for Emergency Medical Technicians (EMTs) and the imminent introduction of CPC for Paramedics and Advanced Paramedics (APs) in Ireland, this study aimed to identify attitudes towards CPC and factors that might influence such a framework. All EMTs (n = 925), Paramedics and APs (n = 1816) registered in Ireland were invited by email to complete an anonymous on-line survey. The study instrument was designed based on continuous professional development (CPD) questionnaires used by other healthcare professions. Quantitative and qualitative analyses were performed. The overall response rates were: EMTs 43% (n = 399), Paramedics and APs 43% (n = 789), with 82% of APs and 38% of Paramedics participating. The majority of participants in all groups agreed that registration was of personal importance and that evidence of CPC should be maintained; 39% of Paramedics/APs and 78% of EMTs believed that persistent failure to meet CPC requirements should mandate denial of registration. From a pre-determined list of activities, in excess of 88% of all respondents indicated practical training scenarios, cardiac re-certification, e-learning supplemented by related practice, and training with simulation manikins were most relevant to these roles. However, least relevant to them were: e-learning alone (Paramedic/AP 36%; EMT 35%); project work (Paramedic/AP 27%; EMT 48%); and appraisal of journal articles (Paramedic/AP 24%; EMT 39%). Irish EMTs, Paramedics and Advanced Paramedics were supportive of CPC and favoured a 'mixed' model approach which includes: blended learning, practical skills, simulation, practical/team-based exercises, e-learning combined with practical skills, and evidence of patient contact. It is hoped that these insights will inform the CPC guidelines to be introduced.


Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies.
Relapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease. From a series of 85 686 clinical cases, DNA was extracted from 40 µm of formalin-fixed paraffin embedded (FFPE) sections for 623 consecutive SGC. CGP was carried out on hybridization-captured, adaptor ligation-based libraries (mean coverage depth, >500×) for up to 315 cancer-related genes. Tumor mutational burden was determined on 1.1 Mb of sequenced DNA. All classes of alterations, base substitutions, short insertions/deletions, copy number changes, and rearrangements/fusions were determined simultaneously. The clinically more indolent SGC including adenoid cystic carcinoma, acinic cell carcinoma, polymorphous low-grade adenocarcinoma, mammary analog secretory carcinoma, and epithelial-myoepithelial carcinomas have significantly fewer genomic alterations, TP53 mutations, and lower tumor mutational burden than the typically more aggressive SGCs including mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified, carcinoma NOS, and carcinoma ex pleomorphic adenoma. The more aggressive SGCs are commonly driven by ERBB2 PI3K pathway genomic alterations. Additional targetable GAs are frequently seen. Genomic profiling of SGCs demonstrates important differences between traditionally indolent and aggressive cancers. These differences may provide therapeutic options in the future.


Fatalism in the context of COVID-19: Perceiving coronavirus as a death sentence predicts reluctance to perform recommended preventive behaviors.
To manage the spread of coronavirus, health entities have urged the public to take preventive measures such as social distancing and handwashing. Yet, many appear reluctant to take these measures. Research is needed to understand factors underlying such reluctance, with the aim of developing targeted health interventions. We identify associating coronavirus with death as one such factor. 590 participants completed surveys in mid-March 2020, which included attitudes toward coronavirus, preventive behavioral intentions, and sociodemographic factors. Associating coronavirus with death negatively predicted intentions to perform preventive behaviors. Further, associating coronavirus with death was not evenly distributed throughout the sample and was related with a number of sociodemographic factors including age, race, and availability of sick leave. Following recommended preventive measures to slow the spread of coronavirus appears to relate to the degree to which people associate coronavirus with death. These findings can be used by public health researchers and practitioners to identify those for whom targeted health communication and interventions would be most beneficial, as well as to frame health messaging in ways that combat fatalism.


What predicts improvement of sexual function after pelvic floor surgery? A follow-up study.
To analyze factors predictive for changes in sexual function after pelvic floor surgery and explore differences between stress urinary incontinence (SUI) and pelvic organ prolapse (POP) surgery. Prospective observational study. St Olav Hospital, Trondheim University Hospital, Norway. Of 346 mailed questionnaires for women scheduled for SUI and POP surgery, 65 questionnaires were available for analysis together with examination findings before and 1 year after surgery. Postal questionnaires including Prolapse and Incontinence Sexual Function Questionnaire (PISQ 12), Hopkins Symptom Checklist 5 for psychological distress, questions from the validated Body Image Questionnaire, a general health question, questions addressing goals for improvement after surgery, clinical findings based on the Pelvic Organ Prolapse Quantification System and Brief Sexual Function Index for partners. Uni- and multivariate linear regressions adjusting for age were performed. Change in PISQ 12 score at follow-up. Sexual function significantly improved in the total group (p = 0.000). After stratification into SUI and POP surgery, improvement only remained significant after SUI surgery (p = 0.001). Improvement for the total group was predicted by good health or coital incontinence, whereas psychological distress or the goal of improved defecation predicted deterioration. For women undergoing SUI surgery, increasing age, parity or the goal of improving sexuality or body image predicted improvement, while for women undergoing POP surgery, menopausal status or anterior colporrhaphy predicted improvement. Significantly improved sexuality was observed after pelvic floor surgery. Predictive factors for change differed for women undergoing SUI surgery and and those undergoing POP surgery.


Safety and Effectiveness of Retrograde Arterial Access for Endovascular Treatment of Critical Limb Ischemia.
Retrograde arterial access (RA) of the popliteal, tibial, or pedal arteries may facilitate endovascular treatment of complex infrainguinal lesions in patients with critical limb ischemia (CLI). Here, we assess the safety and efficacy of this technique. A retrospective review of prospectively collected institutional data (consecutive M2S entries) was performed to identify patients with CLI undergoing peripheral vascular intervention from February 2012 through December 2017. Demographics, comorbidities, procedural characteristics, and outcomes were analyzed, and comparisons were made between outcomes of patients undergoing RA and those undergoing a standard antegrade access (SA) approach. Five hundred sixty-six patients were identified, of whom 26 (4.6%) underwent RA. Of these, 4 were accessed via the popliteal artery (15.4%), 13 via the tibial vessels above the ankle (50.0%), and 9 via pedal vessels (34.6%). RA facilitated procedural success in 96.2% of cases. There were no instances of distal embolization, perforation, or loss of distal target with RA. Primary, primary assisted, and secondary patency rates were consistently lower for RA patients than for SA patients, as was limb salvage and amputation-free survival. No difference was seen in overall survival. RA represents a viable and safe option for revascularization when SA fails. Although outcomes are poorer than SA, this technique can be useful in CLI patients, especially when open surgical revascularization is not an option.


Fit of three porcelain-fused-to-metal marginal designs in vivo: a scanning electron microscope study.
This study examined the comparative fit in vivo of three types of PFM crown margins. Marginal openings were measured with an SEM on replicas derived from elastomeric impressions. There was no significant difference among beveled metal margins, metal butt margins, or porcelain butt margins either before or after cementation at the 95% confidence level. This study has shown that it is possible under clinical conditions to consistently produce porcelain butt margins with less than 50 micron marginal opening in PFM restorations.


Measurement of CI-979 (a candidate drug for the treatment of age-related disorders of cognition) in human plasma by capillary gas chromatography with nitrogen-selective detection.
A specific and highly sensitive method for the measurement of CI-979 in human plasma is described. The compound and internal standard were extracted from alkalinized plasma with methyl tert.-butyl ether and analyzed by capillary gas chromatography with nitrogen-selective detection. The method was demonstrated to be accurate and precise. Since the limit of quantitation was 0.10 ng/ml, this method was suitable for clinical pharmacokinetic studies in which subjects received repeated administration of 0.5-2.5 mg CI-979 every 6 h.


Submerged macrophyte seed bank in a Mediterranean temporary marsh: abundance and relationship with established vegetation.
The abundance and composition of the submerged macrophyte seed bank in the Doñana marsh (southwestern Spain) was evaluated to assess its relationship with the overlying vegetation. The results obtained demonstrate the existence of a dense seed-bank, both in terms of the number of seeds and their biomass, which represented about 10% (5% for angiosperms and >20% for Charophyta) of the total plant biomass, which ensures the maintenance of the annual submerged macrophyte populations of the seasonally inundated Donñana marsh. Seed bank and established vegetation were coupled, as reflected in the existence of significant correlations between their structure and abundance. This coupling was lacking for Charophyta, whose oospores are widespread and abundant across the marsh, even at locations where they are absent, or rare, in the established vegetation. These differences between the seed bank of annual angiosperms and Charophyta appear to reflect, in part, structural differences between angiosperm seeds and Charophyta oospores, with important ecological consequences. An important aspect of these differences is the allocation of Charophyta reproductive effort to many small propagules lacking embryo storage, compared to those of angiosperms, which ensures their efficient dispersal and numerical abundance in the seed bank.


The mediating effect of pet attachment support between loneliness and general health in older females living in the community.
The relationship between loneliness and general health was investigated in 159 older females living in the community. Pet attachment support, a variable tested as a mediator of this relationship, was examined also. Participants completed the Revised UCLA Loneliness Scale, a Pet Attachment scale, and the Psychological General Well-Being Schedule: general health subscale. A negative relationship between loneliness and general health decreased when controlling for pet attachment support as a coping mechanism. The findings from this study support that pet attachment support has a mediating effect on the relationship between loneliness and general health in this sample of older females. Implications for community health nurses and public policy are discussed.


Pleural liquid pressure at the caudal border of the lung.
Model simulation indicates that pressure recorded through a capsule, when lung border is under it, is essentially equal to pressure of pleural liquid (Pliq) surrounding lung border, though only a strip of capsule membrane is exposed to this liquid (the rest is facing diaphragm and lung). At the top of the right 8th or 9th intercostal space of dogs in left lateral posture Pliq recorded through a capsule at transit of lung border during inspiration (bor. I) or expiration (bor. E) was -19.7 +/- 1.1 and -11.2 +/- 0.3 cm H2O, respectively. Pliq recorded simultaneously through a cannula on the flat surface of lung in 5th or 6th intercostal space (corrected for 1 cm lower height) was -18.7 +/- 1.4 and -12.4 +/- 0.8 cm H2O. Similar values of Pliq on lung border and on flat surface of lung, despite different kinds of deformation and different measuring devices, provide further evidence that Pliq is more subatmospheric than pleural surface pressure. Seventy percent of difference in Pliq between bor. I and bor. E was accounted for by: (a) corresponding difference in pleural surface pressure, and (b) greater tidal change of liquid than surface pressure. Possible factors accounting for the remaining 30% are discussed.


The association between prolonged sleep onset latency and heart rate dynamics among young sleep-onset insomniacs and good sleepers.
A blunting of heart rate (HR) reduction during sleep has been reported to be associated with increased all-cause mortality. An increased incident of cardiovascular events has been observed in patients with insomnia but the relationship between nighttime HR and insomnia remains unclear. Here we investigated the HR patterns during the sleep onset period and its association with the length of sleep onset latency (SOL). Nineteen sleep-onset insomniacs (SOI) and 14 good sleepers had their sleep analyzed. Linear regression and nonlinear Hilbert-Huang transform (HHT) of the HR slope were performed in order to analyze HR dynamics during the sleep onset period. A significant depression in HR fluctuation was identified among the SOI group during the sleep onset period when linear regression and HHT analysis were applied. The magnitude of the HR reduction was associated with both polysomnography-defined and subjective SOL; moreover, we found that the linear regression and HHT slopes of the HR showed great sensitivity with respect to sleep quality. Our findings indicate that HR dynamics during the sleep onset period are sensitive to sleep initiation difficulty and respond to the SOL, which indicates that the presence of autonomic dysfunction would seem to affect the progress of falling asleep.


Surgical management of distal humerus gunshot fractures: descriptive case series.
The purpose of this study was to report our 5 years surgical experience and the rate of neurovascular injury following gunshot fractures of the distal humerus in a in level-1 Trauma Centre in South Africa. A retrospective case series of 25 consecutive adult gunshot injuries to the distal humerus. Demographic and injury data were extracted from clinical case notes and electronic operative records. Imaging archives were used to classify fractures according to the AO/OTA classification. Twenty-five male patients, with mean age of 32-years-old, sustained gunshot injuries to the distal humerus. Eleven patients had multiple gunshots. Forty-four percent of patients underwent Computed Tomography Angiography (CTA), 20% had confirmed brachial artery injury. Limbs with vascular injury were salvaged with arterial repair and external fixation. Fractures were extra-articular in 20 cases (80%). Nineteen fractures were classified as highly comminuted. Nerve injuries occurred in 52% and were all managed expectantly. Only 32% of patients attended follow-up beyond 3 months. These are rare challenging injuries with high rates of neurovascular damage. This demographic of patients is poorly compliant with follow up highlighting the need for high-quality early care. Brachial artery injury should be excluded with CTA and can be managed with arterial repair and external fixation. All fractures in this series were surgically managed with conventional anatomical plate and screw fixation techniques. For nerve injury, we advocate expectant management. IV.


Depression and anxiety symptoms among returning workers during the COVID-19 period in East China.
To determine the prevalence of depression and anxiety and associated factors among returning workers with different epidemic experience in East China. A cross-sectional study was conducted among 2435 employees from the enterprises located in Deqing (low-risk epidemic area) and Taizhou (high-risk epidemic area) of East China in March 2020. An online questionnaire covered information on sociodemographic and lifestyle factors as well as knowledge, attitude, behavior and experience about COVID-19. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) were applied to assess depression and anxiety symptoms, respectively. Logistic regression model was used to estimate adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) for depression and anxiety symptoms associated with risk factors. The participants were aged 36.3 ± 9.2 years on average, and nearly half of them were female. Overall, the prevalence of depression, anxiety and both were 19.4%, 12.3% and 9.8%, and decreased with age. After adjustment for covariates, 16 or more years of education, being a white-collar worker or working in the high-risk epidemic area were significantly associated with increased risks of both depression and anxiety, in contract regular physical exercise was associated with decreased risks of both mental disorders. The depression and anxiety problems were prevalent among returning workers during the COVID-19 period. Targeted psychological interventions should be developed and implemented to improve their mental health.


Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases.
Hypoxia-inducible factor 1 (HIF-1) functions as a master regulator of oxygen homeostasis by mediating a wide range of cellular and systemic adaptive physiological responses to reduced oxygen availability. In this review, we will summarize recent progress in elucidating the molecular mechanisms of HIF-1 activation, focusing on the role of oxygen-dependent prolyl and asparaginyl hydroxylases in hypoxia signal transduction.


Infectious arthritis as the single manifestation of sporotrichosis: serology from serum and synovial fluid samples as an aid to diagnosis.
Sporotrichosis is a generally cutaneous, granulomatous, chronic and benign infection. Less frequently the disease may affect the joints. Articular involvement is usually characterized by monoarthritis in the absence of systemic symptoms, generally preceded by skin lesions, and frequently affects immunosuppressed individuals. We describe here the case of a healthy patient presenting knee arthritis without skin lesions, diagnosed as sporotrichosis, and treated with oral itraconazole. Serology used in this case was an invaluable tool for the diagnosis of sporotrichosis arthritis lacking skin lesions.


Formation of Highly Ordered Molecular Porous 2D Networks from Cyano-Functionalized Porphyrins on Cu(111).
We investigated the adsorption of three related cyano-functionalized tetraphenyl porphyrin derivatives on Cu(111) by scanning tunneling microscopy (STM) in ultra-high vacuum (UHV) with the goal to identify the role of the cyano group and the central Cu atom for the intermolecular and supramolecular arrangement. The porphyrin derivatives studied were Cu-TCNPP, Cu-cisDCNPP, and 2H-cisDCNPP, that is, Cu-5,10,15,20-tetrakis-(p-cyano)-phenylporphyrin, Cu-meso-cis-di(p-cyano)-phenylporphyrin and 2H-meso-cis-di(p-cyano)-phenylporphyrin, respectively. Starting from different structures obtained after deposition at room temperature, all three molecules form the same long-range ordered hexagonal honeycomb-type structure with triangular pores and three molecules per unit cell. For the metal-free 2H-cisDCNPP, this occurs only after self-metalation upon heating. The structure-forming elements are pores with a distance of 3.1 nm, formed by triangles of porphyrins fused together by cyano-Cu-cyano interactions with Cu adatoms. This finding leads us to suggest that two cyano-phenyl groups in the "cis" position is the minimum prerequisite to form a highly ordered 2D porous molecular pattern. The experimental findings are supported by detailed density functional theory calculations to analyze the driving forces that lead to the formation of the porous hexagonal honeycomb-type structure.


Mechanisms of thrombin receptor agonist specificity. Chimeric receptors and complementary mutations identify an agonist recognition site.
Identification of the docking interactions by which peptide agonists activate their receptors is critical for understanding signal transduction at the molecular level. The human and Xenopus thrombin receptors respond selectively to their respective hexapeptide agonists, SFLLRN and TFRIFD. A systematic analysis of human/Xenopus thrombin receptor chimeras revealed that just two human-for-Xenopus amino acid substitutions, Phe for Asn87 in the Xenopus receptor's amino-terminal exodomain and Glu for Leu260 in the second extracellular loop, conferred human receptor-like specificity to the Xenopus receptor. This observation prompted complementation studies to test the possibility that Arg5a in the human agonist peptide might normally interact with Glu260 in the human receptor. The mutant agonist peptide SFLLEN was a poor agonist at the wild type human receptor but an effective agonist at a mutant human receptor in which Glu260 was converted to Arg. An "arginine scan" of the receptor's extracellular surface revealed additional complementary mutations in the vicinity of position 260 and weak complementation at position 87 but not elsewhere in the receptor. Strikingly, a double alanine substitution that removed negative charge from the Glu260 region of the human receptor also effectively complemented the SFLLEN agonist. The functional complementation achieved with single Arg substitutions was thus due at least in part to neutralization of a negatively charged surface on the receptor and not necessarily to introduction of a new salt bridge. By contrast, charge neutralization did not account for the gain of responsiveness to SFLLRN seen in the human/Xenopus receptor chimeras. Thus two independent approaches, chimeric receptors and arginine scanning for complementary mutations, identified the Glu260 region and to a lesser degree Phe87 as important determinants of agonist specificity. These extracellular sites promote receptor responsiveness to the "correct" agonist and inhibit responsiveness to an "incorrect" agonist. They may participate directly in agonist binding or regulate agonist access to a nearby docking site.


[Study of the postural profile and spinal static for menopausal-women with chronic low back pain].
To study postural and spinal static modifications associated with chronic low back pain in menopausal women. Clinical appreciation of static spinal profile in sagittal plane; postural evaluation on the Balance Master Neurocom force platform by the modified clinical test for the sensory interaction on balance (modified CTSIB test); Radiological evaluation of spinal and pelvic parameters as well as the sagittal profile according to the Roussouly classification. Spinal curves clinical measurement and the sway velocity of the pressure center on the Balance Master Neurocom do not show significant difference between the two groups. While the pressure center position in the anteroposterior axis shows significant difference between the two groups (p=0.02) with a more backwards projection found in chronic low back pain subjects. Radiological evaluation shows sagittal shelter significantly superior, sacral slope significantly lower and the type 1 of lumbar lordosis more frequent in chronic low back pain women compared to healthy women. In menopausal women, chronic low back pain seems to be associated with lower sacal slope, the type 1 of lumbar lordosis more frequent and behindly projection of pressure center.


Electrical stimulation of the rat diencephalon: differential effects of interrupted stimulation on on- and off-responding.
Rats were trained to turn on and to turn off electrical stimulation of the hypothalamus. Breaking trains of stimulation into bursts of pulses separated by intervals of no-stimulation attenuated off-responding more than on-responding. Current intensity was raised in an attempt to maintain a constant level of performance when either burst duration was decreased or interburst interval was increased. Current increases necessary to maintain on-responding were consistently smaller than the increments required to maintain off-responding. At shorter burst durations, off-responding usually ceased while on-responding continued. Four interpretations of the results are discussed: (1) temporal integration characteristics of the underlying neural systems, (2) reward adaptation, (3) electrode location, and (4) procedural artifacts. Only the first explanation which holds that the buildup of activity in the rewarding system is more rapid than in the aversive system is consistent with all the results. If correct, this conclusion indicates that multiple effects of electrical stimulation at a single brain site can be differentiated by manipulating the temporal pattern of the stimulation.


5-Fluorouracil cardiotoxicity: left ventricular dysfunction and effect of coronary vasodilators.
Seven patients developed clinical features simulating myocardial ischemia less than 72 hours after 12 of 13 separate intravenous 5-fluorouracil administrations; 9 episodes were associated with chest pain, 3 with hypotension, 3 with ventricular tachycardia and 1 with cardiogenic shock. Left ventricular dysfunction was demonstrated by echocardiography in 5 separate episodes, 2 with interval improvement upon repeat echocardiograms. Pretreatment with nitrates and/or calcium channel blockers failed to prevent recurrence of cardiotoxicity during 5 of 6 repeat 5-fluorouracil administrations. Therapy with 5-fluorouracil is associated with cardiotoxicity simulating myocardial ischemia with left ventricular dysfunction. Pretreatment with coronary vasodilators may not prevent this phenomenon.


A retrospective study of air quality associated with teratogenic pathogen screening in women of reproductive age in southern China.
Adverse pregnancy outcomes are associated with a poor ambient atmospheric environment. Infections by teratogenic pathogens such as cytomegalovirus (CMV) and herpes simplex virus (HSV) are the main cause of the worse pregnant outcomes. However, environmental factors governing these infections are uncertain and epidemiological studies are limited. An epidemiological study on relationships between air pollutants and antibodies against teratogenic pathogens will be explored. In total, 5475 women of childbearing age were enrolled in the study between January 2018 and December 2019 in a hospital in Shantou, China. Antibodies against pathogens were measured by electrochemical luminescence. Everyday air quality data, concerning particulate matter (PM), sulfur dioxide (SO2), nitrogen dioxide (NO2), and other parameters, were acquired from a government web site, and the relationships between them were evaluated with nonparametric and multivariate linear regression analyses. Not only titers of herpes simplex virus HSV(I+II) IgGs in spring, but also titers of cytomegalovirus IgG (CMV IgG) and HSV I IgG in autumn, both had positive associations with concentrations of SO2. When PM2.5 or PM10 exposure is elevated, HSV(I+II) IgGs, TOX IgM should be paid more attention in spring or summer. Air pollution may be crucial for teratogenic pathogen infections. This study highlights air pollution could increase the risk of teratogenic pathogen infection, implying stronger measures should be taken to protect air environment and screenings of associated antibody should be strengthened in different season.


Implementation of Early Diagnosis and Intervention Guidelines for Cerebral Palsy in a High-Risk Infant Follow-Up Clinic.
Cerebral palsy is the most common physical disability in childhood, and is mostly diagnosed after age 2 years. Delays in diagnosis can have negative long-term consequences for children and parents. New guidelines for early cerebral palsy diagnosis and intervention were recently published, after systematic review of the evidence by international multidisciplinary experts aiming to decrease age at diagnosis. The current study tested the feasibility of implementing these guidelines in an American clinical setting. We designed a stepwise implementation process in a neonatal intensive care follow-up clinic. Efficacy was tested by comparing 10-month pre- and post-implementation periods. Clinic visit types, cerebral palsy diagnosis, provider competencies and perspectives, and balancing measures were analyzed. Changes to infrastructure, assessments, scheduling algorithms, documentation and supports in diagnosis or counseling were successfully implemented. Number of three- to four-month screening visits increased (255 to 499, P < 0.001); mean age at diagnosis decreased (18 to 13 months, P < 0.001). Clinic team awareness of early diagnosis and interventions increased (P < 0.001). There was no decrease in family satisfaction with overall clinic function. Opportunities for improvements included documentation for transitioning patients, generalizabilty across hospital clinics, systematic identification of high-risk status during hospitalization, and need for cerebral palsy care guidelines for infants under age 2 years. We demonstrated for the first time in a US clinical setting the feasibility of implementation of international early diagnosis and treatment guidelines for cerebral palsy. This process is adaptable to other settings and underscores the necessity of future research on cerebral palsy treatments in infancy.


Recent progress in solid-state nuclear magnetic resonance of half-integer spin low-γ quadrupolar nuclei applied to inorganic materials.
An overview is presented of recent progress in the solid-state nuclear magnetic resonance (NMR) observation of low-γ nuclei, with a focus on applications to inorganic materials. The technological and methodological advances in the last 20 years, which have underpinned the increased accessibility of low-γ nuclei for study by solid-state NMR techniques, are summarised, including improvements in hardware, pulse sequences and associated computational methods (e.g., first principles calculations and spectral simulation). Some of the key initial observations from inorganic materials of these nuclei are highlighted along with some recent (most within the last 10 years) illustrations of their application to such materials. A summary of other recent reviews of the study of low-γ nuclei by solid-state NMR is provided so that a comprehensive understanding of what has been achieved to date is available.


Activity and Life After Survival of a Cardiac Arrest (ALASCA) and the effectiveness of an early intervention service: design of a randomised controlled trial.
Cardiac arrest survivors may experience hypoxic brain injury that results in cognitive impairments which frequently remain unrecognised. This may lead to limitations in daily activities and participation in society, a decreased quality of life for the patient, and a high strain for the caregiver. Publications about interventions directed at improving quality of life after survival of a cardiac arrest are scarce. Therefore, evidence about effective rehabilitation programmes for cardiac arrest survivors is urgently needed. This paper presents the design of the ALASCA (Activity and Life After Survival of a Cardiac Arrest) trial, a randomised, controlled clinical trial to evaluate the effects of a new early intervention service for survivors of a cardiac arrest and their caregivers. The study population comprises all people who survive two weeks after a cardiac arrest and are admitted to one of the participating hospitals in the Southern part of the Netherlands. In a two-group randomised, controlled clinical trial, half of the participants will receive an early intervention service. The early intervention service consists of several consultations with a specialised nurse for the patient and their caregiver during the first three months after the cardiac arrest. The intervention is directed at screening for cognitive problems, provision of informational, emotional and practical support, and stimulating self-management. If necessary, referral to specialised care can take place. Persons in the control group will receive the care as usual. The primary outcome measures are the extent of participation in society and quality of life of the patient one year after a cardiac arrest. Secondary outcome measures are the level of cognitive, emotional and cardiovascular impairment and daily functioning of the patient, as well as the strain for and quality of life of the caregiver. Participants and their caregivers will be followed for twelve months after the cardiac arrest.A process evaluation will be performed to gain insight into factors that might have contributed to the effectiveness of the intervention and to gather information about the feasibility of the programme. Furthermore, an economic evaluation will be carried out to determine the cost-effectiveness and cost-utility of the intervention. The results of this study will provide evidence on the effectiveness of this early intervention service, as well as the cost-effectiveness and its feasibility. Current Controlled Trials [ISRCTN74835019].


Autocrine regulators of MC3T3-E1 cell proliferation.
MC3T3-E1 cells, a clonal osteoblast-like mouse calvarial cell line, secrete several growth regulating factors. These regulators include insulin-like growth factor (IGF) type I, transforming growth factor beta (TGF-beta), and IGF-II in descending order of abundance. MC3T3-E1 cells in culture also produce two IGF binding proteins (IGFBP), M(r) 25 and 32 kD, having sequence identity with IGFBP-4 and IGFBP-6, respectively. In addition, this is the first observation that osteoblast-like bone cells in culture produce IGFBP-6. To determine if growth factors produced by MC3T3-E1 cells have autocrine actions on these cells, the effects of IGF-I, IGF II, TGF-beta 1, and IGFBP-4 on MC3T3-E1 cell proliferation were determined. Exogenous addition of IGF-I and IGF-II stimulated MC3T3-E1 cell proliferation, but TGF-beta 1 and IGFBP-4 inhibited MC3T3-E1 cell proliferation. Based on these findings, we conclude that MC3T3-E1 cells in culture produce autocrine regulators of MC3T3-E1 cell proliferation and that the actions of IGFs may also be regulated by IGFBPs produced by these same cells.


Associations between polymorphisms in the SYK promoter and susceptibility to sporadic colorectal cancer in a Southern Han Chinese population - a short report.
Down-regulated expression of the putative tumor suppressor gene spleen tyrosine kinase (SYK) is strongly associated with the development of various cancers, including colorectal cancer (CRC). SYK gene promoter polymorphisms have been shown to be involved in the pathogenesis of multiple malignant tumors. In this study, we investigated associations of SYK gene promoter polymorphisms with the susceptibility to colorectal cancer development in a Southern Han Chinese population. SNPs in the promoter region of the human SYK gene were identified using in silico analysis tools, linkage disequilibrium analysis, and a search for likely transcription factor binding sites via TFSEARCH in the NCBI SNP database (gene ID: 6850). Based on this information, -803A>T and -534T>C were selected as candidates for further analysis. TaqMan-MGB probe analyses were performed in 567 CRC patients and 569 age- and gender-matched healthy controls for SYK gene promoter genotyping. Associations between CRC risk and SNPs were estimated using an unconditional logistic regression model, and environmental risk factors were included in a multivariate logistic regression model for correction. The frequencies of the TA and TT genotypes and the T allele of the -803A>T SNP were found to be significantly higher in the CRC patients compared to the healthy individuals of the control group (P=0.020, 0.023, and 0.013, respectively). Synergistic effects between -803A>T genotypes (i.e., TA+TT) and age (≤60 years; P=0.039), male gender (P=0.011), smoking (P=0.005), drinking alcohol (P=0.002), and high BMI (≥24.0 kg/m2; P=0.009) were found to increase the risk to develop CRC by stratified analyses. The SYK -803 A>T genotypes TA and TT are independent risk factors for CRC development in Han Chinese in Southern China, and an association with TA+TT genotypes appears predominant among younger patients, male patients, patients with a high BMI, and patients who smoke or drink alcohol.


New microsurgical applications: implications for the infrastructures of plastic surgery.
As a technical innovation, microsurgery has changed concepts and strategies throughout plastic surgery. The infrastructures of plastic surgery currently are evolving in ways that make the identity and future of the specialty uncertain. Microsurgery also may be a basis for fresh thoughts in these areas of infrastructure. This article touched on some areas where microsurgery could be an important element in organizational development, namely patient population identification, economic strategies, academic organization, and medical education. More thorough exploration of these ideas and identification of others may result in a new foundation for plastic surgery with microsurgery as a key element.


Communication and Activation in Pain to Enhance Relationships and Treat Pain with Equity (COOPERATE): Rationale, study design, methods, and sample characteristics.
Chronic pain is associated with profound negative effects, and racial disparities are well-documented in chronic pain treatment. In addition, Black patients report poorer communication with providers and exhibit lower levels of patient activation (self-management self-efficacy) than White patients. Although the causes of healthcare disparities are complex and require intervention at multiple levels, empowering patients is one critical path to achieving health equity. The current study is a coaching intervention focused on increasing patient activation and building communication skills for Black patients with chronic pain. In this randomized controlled trial, 250 Black patients with chronic pain were randomized to either the coaching intervention or an attention control arm. Intervention patients attended 6 telephone-delivered individual coaching sessions over 12 weeks. Coaching focused on clarifying and prioritizing goals and on communication skills, such as agenda setting. The primary outcome is patient activation. Secondary outcomes include communication self-efficacy, pain intensity and interference, and psychological functioning. Having the knowledge and confidence to participate in one's pain care, coupled with the skills needed to effectively communicate with providers, is essential to optimize chronic pain care. This is particularly important for Black patients who often experience lower quality pain care. Interventions such as COOPERATE hold promise for helping patients to acquire the requisite tools to take greater control of their chronic pain care. clinicaltrials.gov, # NCT03562793.


Polypropionate lactones of deoxysugars glycosides from slime mold Lycogala epidendrum.
Two novel polypropionate lactone glycosides (1 and 2, i.e. lycogalinosides A and B) were isolated from the slime mold Lycogala epidendrum. Their structures, including the absolute configurations of the hydroxyl and methyls groups, were determined by means of extensive spectroscopic data such as mass, IR, UV, and 1D and 2D NMR spectra and chemical degradation followed by spectroscopic and chromatographic analysis. Compounds 1 and 2 are unique in structure containing a 2-deoxy-alpha-L-fucopyranosyl-(1-4)-6-deoxy-beta-D-gulopyranosyl unit and a beta-D-olivopyranosyl-(1-4)-beta-D-fucopyranosyl unit, respectively, and showed growth inhibitory activities against Gram-positive bacteria.


Percutanenous therapies for mitral regurgitation.
Percutaneous therapies for the treatment of mitral regurgitation have emerged rapidly over the past several years. Most of the percutaneous approaches are modifications of existing surgical approaches to mitral annuloplasty or leaflet repair. Most of the percutaneous devices are based on surgical approaches. Catheter-based leaflet repair with the MitraClip is accomplished using an implantable clip to mimic the surgical edge-to-edge technique. Percutaneous annuloplasty can be achieved indirectly via the coronary sinus, or directly from retrograde left ventricular access. Several of these percutaneous approaches have been successfully used in trials or are in the early stages of use in practice.


Liposome and polymeric micelle-based delivery systems for chlorophylls: Photodamage effects on Staphylococcus aureus.
Chlorophyll derivatives (Chls), loaded in F-127 polymeric micelles and DPPC liposomes as drug delivery systems (DDS), have been shown to be remarkable photosensitizers for photodynamic inactivation (PDI). Assays of photoinactivation of Staphylococcus aureus bacteria (as biological models) showed that the effectiveness of Chls in these nanocarriers is dependent on photobleaching processes, photosensitizer locations in DDS, singlet oxygen quantum yields, and Chl uptake to bacteria. These are factors related to changes in Chl structure, such as the presence of metals, charge, and the phytyl chain. The photodynamic activity was significantly greater for Chls without the phytyl chain, i.e., phorbides derivatives. Furthermore, the inactivation of S. aureus was increased by the use of liposomes compared to micelles. Therefore, this research details and shows the high significance of the Chl structure and delivery system to enhance the photodynamic activity. It also highlights the chlorophylls (particularly phorbides) in liposomes as promising photosensitizers for PDI.


Novel and Emerging Therapeutics for Primary Prevention of Cardiovascular Disease.
Cardiovascular disease is responsible for 205 deaths per 100,000 persons annually and is the leading cause of death worldwide. The public health burden of cardiovascular disease is expected to continue to grow as the prevalence of many cardiovascular risk factors increases. Several novel classes of glucose-lowering, lipid-lowering, and weight-loss therapeutics have shown mortality benefits in outcomes trials. However, a large proportion of subjects in those trials had established cardiovascular disease, so, as a result, the role of these novel therapeutics in primary cardiovascular prevention is controversial. In this review, we highlight recent advances in the pharmacotherapeutic management of the cardiovascular risk factors of hyperglycemia, dyslipidemia, and obesity. We examine key subgroups within recent cardiovascular outcome trials, weigh the risks and benefits of several novel therapeutics, and provide practical insight into the use of these agents. Our article concludes with a look toward the future and provides the practitioner and scientist with an early view of emerging therapeutics that may play an important role in primary cardiovascular prevention.


Dyserythropoiesis and severe anaemia associated with malaria correlate with deficient interleukin-12 production.
Complex cytokine interactions occur during blood-stage malaria which offer a unique opportunity to study their influence on the pathogenesis of malarial anaemia. Plasmodium chabaudi AS susceptible A/J mice experience severe and fatal anaemia whereas resistant C57BL/6 (B6) mice survive following moderate anaemia. In this study we analysed the role of IL-12 in erythropoiesis and tested whether the levels of IL-12 produced in these mice correlated with the extent of anaemia. In vitro, IL-12 significantly enhanced the numbers of erythroid burst (BFU-E) and colony forming units (CFU-E) in bone marrow and spleen cells from normal and day 7 infected A/J and B6 mice. Despite the presence of IL-12 in vitro, the level of splenic erythropoiesis in infected A/J mice was significantly lower than in B6 mice. Moreover, sera from infected B6 mice, but not A/J mice, significantly up-regulated erythropoiesis in vitro and this enhancement correlated with several fold higher levels of IL-12 in the sera of B6 compared to A/J mice. Furthermore, the erythropoietic potentiating effect of sera from infected B6 mice was abrogated following depletion of IL-12. Taken together, these findings suggest that defective IL-12 production in A/J mice during the early course of infection may result in fatal anaemia.


Reduced plasma leptin concentrations in bulimia nervosa.
Leptin is a protein produced by the ob-ob gene which inhibits food intake. Plasma levels have previously been reported to be altered in obesity and anorexia nervosa (AN) but not bulimia nervosa (BN). We measured fasting plasma leptin levels by radioimmunoassay in 53 subjects carefully studied at NIMH, including 37 women meeting DSM-III-R criteria for BN [10 with concurrent AN (body mass index (BMI)=14.1+/-1.4), 27 without AN (BMI=20.4+/-1.6)] and 16 normal control women (NCs) (BMI=21.1+/-2.0). Patients were medication-free and abstinent from bingeing and purging for three to four weeks prior to study. Plasma leptin levels were significantly correlated to BMI (r=0.41, P<0.002), weight (kg, r=0.43, P<0.001), and percent average body weight (%ABW, r=0.45, P<0.001) in the total group. Plasma leptin levels were lower in the BN subjects (3.4+/-2.5 ng/ml) compared to the NCs (6.1+/-2.6 ng/ml, P<0.001, ANCOVA) even after controlling for BMI and weight. There was no significant difference between BN subjects with AN (n=10, 2.6+/-2.6 ng/ml) and those without AN (n=27, 3.8+/-2.4 ng/ml), despite lower BMI in BN with AN. Furthermore, leptin levels were decreased in BN without AN compared with healthy controls, even though BMI was comparable in these two subgroups. Plasma leptin concentrations were negatively correlated with baseline plasma cortisol levels (n=49, r=-0.49, P<0.001) and positively correlated with prolactin responses following L-tryptophan (n=49, r=0.37, P<0.009) and m-chlorophenylpiperazine (n=52, r=0.24, P<0.09). This is the first known report of decreased plasma leptin levels in BN. The decrement in leptin concentration is not related to BMI, body weight, or the presence or absence of BN. HPA axis activation as well as serotonin dysregulation may be related to decreased leptin levels, which may in turn contribute to disinhibited eating in BN. Although current leptin levels were not correlated with self-reported previous binge frequency, the role of leptin in the pathophysiology of BN deserves further study.


Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats.
Serotonin (5-hydroxytryptamine, or 5-HT) is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies. However, there is little information on the contribution of different 5-HT receptors in reversal learning. Thus, we investigated the effects of systemic administration of the 5-HT(2A) antagonist M100907 (0, 0.01, 0.03, and 0.1 mg/kg, i.p.) and the 5-HT(2C) antagonist SB 242084 (0, 0.1, 0.3, and 1.0 mg/kg, i.p.) on the performance of an instrumental two-lever spatial discrimination and serial spatial reversal learning task, where both levers were presented and only one was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of within-session reversals was presented. Neither M100907 nor SB 242084 altered performance during spatial discrimination and retention of the previously reinforced contingencies. M100907 significantly impaired reversal learning by increasing both trials to criterion (only at the highest dose) and incorrect responses to criterion in Reversal 1, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, SB 242084 improved reversal learning by decreasing trials and incorrect responses to criterion in Reversal 1, with significantly fewer perseverative responses. These data support the view that 5-HT(2A) and 5-HT(2C) receptors have distinct roles in cognitive flexibility and response inhibition. The improved performance in reversal learning observed following 5-HT(2C) receptor antagonism suggests these receptors may offer the potential for therapeutic advances in a number of neuropsychiatric disorders where cognitive deficits are a feature, including obsessive-compulsive disorder.


Alkali halide clusters produced by fast ion impact.
The most abundant geometries and relative stabilities of alkali halide clusters with a (XY)(n) (o) configuration (e.g., LiF, NaCl, KBr) are described. Five main series were obtained: linear, cyclic, cubic, arc strips and nanotubes. The stability analysis shows that higher members are likely to be formed from the lower member of the same series and/or from two building blocks (n = 1, 2). The energy analysis (D-plot) indicates that the most compact ones (e.g., cubic and nanotubes) present higher stability when compared to the linear, cyclic and arc strip structures; moreover, relative stability between the cubic and nanotube series varies with the cluster size.


Sudden unexplained death in schizophrenia patients: An autopsy-based comparative study from China.
Explainable sudden deaths in schizophrenia patients due to both cardiac (SCD) and non-cardiac causes (SNCD) have been extensively documented. However, sudden unexplained death (SUD) in this cohort remains to be elucidated. This study retrospectively analyzed 18 SUD cases that underwent systematic autopsy at our institutes during the period 2010-2022. The etiological, demographic, and autopsy features of the SUD cases were then compared with 37 year-matched sudden explainable deaths (23 SCD cases and 14 SNCD cases). Our results showed that the average age of the SUD was 39.0 ( ± 8.4) years, with the disease duration of 11.8 ( ± 8.1) years and a male/female ratio of 11:7. Most cases occurred during daytime (72.2%) and outside of hospital (77.8%). A large proportion of the SUD cases (77.8%) had persistent psychiatric episodes before death. Clozapine was found to be the most commonly used antipsychotic (33.3%), followed by Olanzapine (27.8%), Risperidone (27.8%) and Chlorpromazine (27.8%) in the SUD cases. When compared among groups, the SUD cases showed significantly younger ages (p = 0.035), lower heart weight (p = 0.004) and lower proportion of Clozapine use (p = 0.045). The presence of persistent psychiatric episodes was significantly higher in the SUD group than in any explainable deaths (p = 0.018) and was an independent risk factor for SUD (OR = 4.205, p = 0.040). This is the first autopsy-based study of SUD cases from China. We conclude that a stable mental state maintained by antipsychotics (i.e., Clozapine) is vital to schizophrenia patients.


Left atrial myxoma simulating a systemic disease with pleural-pericardial effusion. Detection by two-dimensional echocardiography.
Clinical symptoms of cardiac myxomas are often very confusing. We observed a 46-year-old woman with a left atrial myxoma simulating systemic disease with pleural-pericardial effusion. We think that like other systemic symptoms effusion (which to our knowledge has not been previously described in literature) can be attributed to the result of tumor secretion or necrosis. In fact, soon after surgical removal of the tumor, all pathological signs disappeared.


Acid-base and potassium homeostasis.
Acid-base balance and potassium disorders are often clinically linked. Importantly, acid-base disorders alter potassium transport. In general, acidosis causes decreased K(+) secretion and increased reabsorption in the collecting duct. Alkalosis has the opposite effects, often leading to hypokalemia. Potassium disorders also influence acid-base homeostasis. Potassium depletion causes increased H(+) secretion, ammoniagenesis and H-K-ATPase activity. Hyperkalemia decreases ammoniagenesis and NH4(+) transport in the thick ascending limb. Some combined potassium and acid-base disorders involve indirect factors such as aldosterone, impaired renal function, volume depletion, and diarrhea. In summary, disorders of potassium and acid-base homeostasis are mechanistically linked and clinically important.


[An infant with a swelling of the cheek].
A 2-weeks-old girl was presented with a swelling of the right parotid gland, due to acute suppurative parotitis caused by Staphylococcus aureus.


Menstrual migraine and intermittent ergonovine therapy.
The treatment of patients suffering with menstrual migraine is sometimes a difficult and frustrating problem for the physician. As many menstrual migraine headaches are refractory to abortive therapy, prophylactic therapy is often needed. Ergonovine maleate, an ergot derivative with vasoconstrictive properties, has been used with some success in migraine headache patients. Forty patients who were treated with intermittent prophylactic ergonovine were studied over six months. The patients ranged in age from 22 to 40 years, and all suffered with menstrual migraine headaches which were refractory to abortive therapy. Each patient took ergonovine maleate 0.2 mg three to four times daily during menses and recorded headache occurrence and severity. After three months, 24 patients (60%) reported significantly less severe attacks, six patients (15%) reported less frequent headaches and 14 patients (35%) reported no improvement. After six months there was a decrease in effectiveness with 20 patients (50%) reporting significantly less severe headaches and two patients (5%) reporting less frequent headaches. This limited study suggests that ergonovine maleate may be of value in the treatment of difficult menstrual migraine patients.


Serum antibodies to H+,K+-ATPase, serum pepsinogen A and Helicobacter pylori in relation to gastric mucosa morphology in patients with low or low-normal concentrations of serum cobalamins.
To compare the diagnostic performance of serum antibodies to H+,K+-ATPase (EC 188.8.131.52), serum pepsinogen A (EC 188.8.131.52) and the Schilling test in diagnosing chronic atrophic body gastritis; to study the interrelationships between H+,K+-ATPase antibodies, serology for Helicobacter pylori, and gastric morphology. Patients with suspected cobalamin deficiency and serum cobalamin < 200 micromol/l were investigated using upper gastrointestinal endoscopy, the Schilling test and serum tests for H+,K+-ATPase antibodies, pepsinogen A, and H. pylori. The Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. Ninety seven consecutively referred patients. Sensitivity and specificity of assays for serum H+,K+-ATPase antibodies, serum pepsinogen A, and the Schilling test. Assays of serum antibodies to H+,K+-ATPase and of serum pepsinogen A displayed equal diagnostic sensitivity for atrophic gastritis (around 0.90 for the severe forms) and higher than that for the Schilling test (0.65). The diagnostic specificity for pepsinogen A (1.0) was higher than for H+,K+-ATPase antibodies (about 0.80). The prevalence of antral gastritis and positivity for H. pylori antibodies declined with the transition of body gastritis into severe atrophy, while the prevalence of H+,K+-ATPase antibodies increased. Pepsinogen A is preferable to serum H+,K+-ATPase antibodies in the diagnosis of gastric body mucosal atrophy. The formation of H+,K+-ATPase antibodies does not seem to be a primary event in the development of gastric body muscosal atrophy.


A two-staged adsorption/thermal desorption GC/MS online system for monitoring volatile organic compounds.
Real-time online monitoring of volatile organic compounds (VOCs) in ambient air is crucial for timely and effective human health protection. Here, we developed an innovative, automated two-staged adsorption/thermal desorption gas chromatography/mass spectrometry (GC/MS) system for real-time online monitoring of 117 regulated volatile organic compounds (VOCs). This system comprised a sampling unit, water management trap, two-staged adsorption/thermal desorption unit, thermoelectric coolers (TECs), and a commercial GC/MS system. By implementing a micro-purge-and-trap (MP & T) step and a two-staged adsorption/thermal desorption unit, the presence of interfering substances was effectively minimized. The utilization of a heart-cutting GC, combined with a single MS detector, facilitated the precise separation and detection of 117 C2-C12 VOCs, while circumventing the identification and coelution challenges commonly associated with traditional GC-FID or GC-FID/MS methods. The performance of our newly developed online system was meticulously optimized and evaluated using standard gas mixtures. Under optimal conditions, we achieved impressive results, with R2 values ≥ 0.9946 for the standard linear curves of all 117 VOCs, demonstrating a precision (RSD) ranging from 0.2% to 6.4%. When applied in the field monitoring, the concentration drifts for 10 ppbv standard gas mixtures were 0.01-5.64% within 24 h. Our study developed a system for online monitoring of 117 atmospheric VOCs with relatively high accuracy and robustness.


[Cardiac tumors--clinical symptoms, diagnostic approaches, and therapeutic aspects].
Cardiac tumors are rare; however, they pose diagnostic and therapeutic challenges on the physician and, in most cases, interdisciplinary approaches are necessary. The present article summarizes the most frequent cardiac tumors and discusses the diagnostic aspects and therapeutic consequences. The focus of this article is on primary cardiac tumors.


Habitat selection in two species of short-horned grasshoppers : The role of thermal and hydric stresses.
The roles of thermal and hydric stress in habitat selection by two species of short-horned grasshoppers was investigated through field and laboratory studies and computer simulation experiments. Psoloessa delicatula was found to possess an elaborate repertoire of thermoregulatory postures and shade seeking behavior. This grasshopper was found in habitats in the shortgrass prairie in which bare patches of ground were common. It was found to regulate its body temperature to a relatively constant level over the course of a sunny day. Eritettix simplex was found in patches of dense vegetation, and its body temperature was usually similar to ambient temperature. During controlled laboratory experiments, E. simplex nymphs lost water rapidly and thus were presumed to be restricted to more mesic environments where desiccation stress is less. A thermal energy budget model was constructed and showed that the habitat selected by P. delicatula would allow behavioral thermoregulation whereas the habitat selected by E. simplex should preclude regulation of body temperature by behavioral means.


Polypyrrole-coated capillaries for capillary zone electrophoresis.
Fused-silica capillaries are permanently coated by silanization with 3-{[3-(N-pyrrole)-2-hydroxypropyl]amino}propyltriethoxysilane followed by oxidative polymerization of the pyrrole moieties with iron (III) or peroxodisulfate in the presence of chloride, perchlorate, or dextransulfate as anions. This approach allows to modulate the EOF in its magnitude as well as in its direction. With the small anions chloride and perchlorate, the EOF is reversed below pH 5 while with the large dextransulfate polyanions (DS) the EOF is relatively constant over the pH range from 2.5 to 9.4. This can be of advantage at low pH, at which the EOF of uncoated capillaries is close to zero. Application for separation of some herbicides is shown. The lifetime of PP-modified capillaries is satisfactory: the decrease in EOF is less than 3% during 80 analyses (160 min) and less than 5% over three months of storage. The reproducibility of capillary modification is about 5% (RSD of EOF).


Effects of elevated carbon dioxide and elevated temperature on morphological, physiological and anatomical responses of Eucalyptus tereticornis along a soil phosphorus gradient.
Eucalypts are likely to play a critical role in the response of Australian forests to rising atmospheric CO2 concentration ([CO2]) and temperature. Although eucalypts are frequently phosphorus (P) limited in native soils, few studies have examined the main and interactive effects of P availability, [CO2] and temperature on eucalypt morphology, physiology and anatomy. To address this issue, we grew seedlings of Eucalyptus tereticornis Smith across its P-responsive range (6-500 mg kg-1) for 120 days under two [CO2] (ambient: 400 μmol mol-1 (Ca) and elevated: 640 μmol mol-1 (Ce)) and two temperature (ambient: 24/16 °C (Ta) and elevated: 28/20 °C (Te) day/night) treatments in a sunlit glasshouse. Seedlings were well-watered and supplied with otherwise non-limiting macro- and micro-nutrients. Increasing soil P supply increased growth responses to Ce and Te. At the highest P supplies, Ce increased total dry mass, leaf number and total leaf area by ~50%, and Te increased leaf number by ~40%. By contrast, Ce and Te had limited effects on seedling growth at the lowest P supply. Soil P supply did not consistently modify photosynthetic responses to Ce or Te. Overall, effects of Ce and Te on growth, physiological and anatomical responses of E. tereticornis seedlings were generally neutral or negative at low soil P supply, suggesting that native tree responses to future climates may be relatively small in native low-P soils in Australian forests.


Chromosomal and extrachromosomal instability of the cyclin D2 gene is induced by Myc overexpression.
We examined the expression of cyclins D1, D2, D3, and E in mouse B-lymphocytic tumors. Cyclin D2 mRNA was consistently elevated in plasmacytomas, which characteristically contain Myc-activating chromosome translocations and constitutive c-Myc mRNA and protein expression. We examined the nature of cyclin D2 overexpression in plasmacytomas and other tumors. Human and mouse tumor cell lines that exhibited c-Myc dysregulation displayed instability of the cyclin D2 gene, detected by Southern blot, fluorescent in situ hybridization (FISH), and in extrachromosomal preparations (Hirt extracts). Cyclin D2 instability was not seen in cells with low levels of c-Myc protein. To unequivocally demonstrate a role of c-Myc in the instability of the cyclin D2 gene, a Myc-estrogen receptor chimera was activated in two mouse cell lines. After 3 to 4 days of Myc-ER activation, instability at the cyclin D2 locus was seen in the form of extrachromosomal elements, determined by FISH of metaphase and interphase nuclei and of purified extrachromosomal elements. At the same time points, Northern and Western blot analyses detected increased cyclin D2 mRNA and protein levels. These data suggest that Myc-induced genomic instability may contribute to neoplasia by increasing the levels of a cell cycle-regulating protein, cyclin D2, via intrachromosomal amplification of its gene or generation of extrachromosomal copies.


Cross-domain, soft-partition clustering with diversity measure and knowledge reference.
Conventional, soft-partition clustering approaches, such as fuzzy c-means (FCM), maximum entropy clustering (MEC) and fuzzy clustering by quadratic regularization (FC-QR), are usually incompetent in those situations where the data are quite insufficient or much polluted by underlying noise or outliers. In order to address this challenge, the quadratic weights and Gini-Simpson diversity based fuzzy clustering model (QWGSD-FC), is first proposed as a basis of our work. Based on QWGSD-FC and inspired by transfer learning, two types of cross-domain, soft-partition clustering frameworks and their corresponding algorithms, referred to as type-I/type-II knowledge-transfer-oriented c-means (TI-KT-CM and TII-KT-CM), are subsequently presented, respectively. The primary contributions of our work are four-fold: (1) The delicate QWGSD-FC model inherits the most merits of FCM, MEC and FC-QR. With the weight factors in the form of quadratic memberships, similar to FCM, it can more effectively calculate the total intra-cluster deviation than the linear form recruited in MEC and FC-QR. Meanwhile, via Gini-Simpson diversity index, like Shannon entropy in MEC, and equivalent to the quadratic regularization in FC-QR, QWGSD-FC is prone to achieving the unbiased probability assignments, (2) owing to the reference knowledge from the source domain, both TI-KT-CM and TII-KT-CM demonstrate high clustering effectiveness as well as strong parameter robustness in the target domain, (3) TI-KT-CM refers merely to the historical cluster centroids, whereas TII-KT-CM simultaneously uses the historical cluster centroids and their associated fuzzy memberships as the reference. This indicates that TII-KT-CM features more comprehensive knowledge learning capability than TI-KT-CM and TII-KT-CM consequently exhibits more perfect cross-domain clustering performance and (4) neither the historical cluster centroids nor the historical cluster centroid based fuzzy memberships involved in TI-KT-CM or TII-KT-CM can be inversely mapped into the raw data. This means that both TI-KT-CM and TII-KT-CM can work without disclosing the original data in the source domain, i.e. they are of good privacy protection for the source domain. In addition, the convergence analyses regarding both TI-KT-CM and TII-KT-CM are conducted in our research. The experimental studies thoroughly evaluated and demonstrated our contributions on both synthetic and real-life data scenarios.


Residues, potential source and ecological risk assessment of polycyclic aromatic hydrocarbons (PAHs) in surface water of the East Liao River, Jilin Province, China.
The environmental risks posed by polycyclic aromatic hydrocarbons (PAHs) and the diversity of their anthropogenic origins make them a global issue. Therefore, it is of utmost significance for protecting the aquatic environment and the growth of neighboring populations to identify their possible origins and ecological risk. Here, we detail the contamination profiles of 15 PAHs found in the East Liao River's surface waters in Jilin Province and use the receptor model Absolute Principal Component Analysis - Multiple Linear Regression (APCS-MLR) and diagnostic ratios method to identify the primary potential sources of pollution. Based on the natural hazard risk formation theory (NHRFT), an ecological risk assessment (ERA) model for PAHs in the East Liao River was developed. The method assesses the ecological risk status of PAHs by integrating the risk quotient (RQ) approach and the DPSIRM (driving force, pressure, state, impact, response, management) conceptual framework. Total concentrations in the surface water body were between 396.42 and 624.06 ng/L, with an average of 436.99 ng/L. The source research revealed that coal, biomass, and traffic emission sources are the most likely PAH contributors to the East Liao River. The ERA found that the majority of the sites' locations of the study were at low risk for PAHs in surface water bodies (30.7 % and 32.2 %, respectively), while only a tiny percentage of sites were at high or very high risk (1.8 % and 13.6 %). The study results provide theoretical support for the East Liao River's ecological, environmental protection, and policy formulation.


Preliminary studies on the primary structure of rat liver dihydropteridine reductase.
Cyanogen bromide cleavage of reductively alkylated homogeneous rat liver dihydropteridine reductase afforded several peptide fragments identifiable by polyacrylamide electrophoresis of which 6 (CB-1 to CB-6) could be individually isolated by C8 reverse phase HPLC. Each was characterised by N-terminal amino acid analysis and sequence information was derived for CB-1, CB-4 and CB-6. The blocked N-terminal of the holoenzyme was identified as pyroglutamate and the C-terminal sequence was obtained by sequential degradation.


Off-label uses of rituximab in dermatology.
Since its approval in 1997 by the FDA, rituximab has been approved for use in certain B-cell lymphomas and treatment-resistant rheumatoid arthritis. Over the past 10 years, many case reports have indicated rituximab's efficacy in a number of inflammatory conditions in dermatology. This article includes a review of the mechanism of action, dosing, and side effect profile, as well as a review of the current literature on off-label uses of the CD20(+) B-cell antagonist rituximab.


Unique drought resistance strategies occur among monkeyflower populations spanning an aridity gradient.
Annual plants often exhibit drought-escape and avoidance strategies to cope with limited water availability. Determining the extent of variation and factors underlying the evolution of divergent strategies is necessary for determining population responses to more frequent and severe droughts. We leveraged five Mimulus guttatus populations collected across an aridity gradient within manipulative drought and quantitative genetics experiments to examine constitutive and terminal-drought induced responses in drought resistance traits. Populations varied considerably in drought-escape- and drought-avoidance-associated traits. The most mesic population demonstrated a unique resource conservative strategy. Xeric populations exhibited extreme plasticity when exposed to terminal drought that included flowering earlier at shorter heights, increasing water-use efficiency, and shifting C:N ratios. However, plasticity responses also differed between populations, with two populations slowing growth rates and flowering at earlier nodes and another population increasing growth rate. While nearly all traits were heritable, phenotypic correlations differed substantially between treatments and often, populations. Our results suggest drought resistance strategies of populations may be finely adapted to local patterns of water availability. Substantial plastic responses suggest that xeric populations can already acclimate to drought through plasticity, but populations not frequently exposed to drought may be more vulnerable.


[Combination of bla(VIM-1) and qnrS2 on the same plasmid in Klebsiella oxytoca and Klebsiella pneumoniae isolates in Seville].
Combined resistance to quinolones and β-lactams is common in Enterobacteriaceae. The appearance in enterobacteria coding for metallo-β-lactamases and determinants of plasmid-mediated quinolone resistance are an emerging problem in our country. The susceptibility was determined by E-test. The resistance genes were detected by PCR and the corresponding plasmids were characterised. This study describes 2 strains (1 Klebsiella oxytoca, 1 Klebsiella pneumoniae) carrying the genes qnrS2 and blaVIM-1 in a transferable plasmid of 70-Kb isolated in surveillance cultures at the University Hospital Virgen Macarena in Seville. This is the first combination of qnrS2 and bla(VIM-1) on the same non-typeable plasmid isolated in our centre.


Localization of a novel inositol 1,4,5-trisphosphate binding protein, p130 in rat brain.
We have isolated a novel inositol 1,4,5-trisphosphate binding protein with molecular mass of 130 kDa (p130), homologous to phospholipase C-delta1 in amino acid sequence but with no catalytic activity. Here we report the expression and localization of p130 at the mRNA level in rat brain. Northern blotting showed that gene expression encoding p130 was most abundant in brain. Brain localization of p130-mRNA using an in situ hybridization technique revealed that in the cerebellum, the mRNA was detected in the granular cell and Purkinje cell layers, and cerebellar nuclei. In the cerebrum, the mRNA was localized in hippocampal pyramidal cells, dentate granule cells and pyramidal and/or granule cells of the cerebral cortex. The brain localization of p130-mRNA was similar to that of the beta-subtype of phospholipase C, indicating that p130 may be mainly involved in phospholipase Cbeta-mediated signaling.


A novel thermostable β-1,3-1,4-glucanase from Thermoascus aurantiacus and its application in oligosaccharide production from oat bran.
Fermentation conditions for β-1,3-1,4-glucanase (TaGlu34) production in submerged culture by a thermophilic fungus, Thermoascus aurantiacus CAU830 were optimized. The highest enzyme activity of 3741 U/mL was obtained, and the crude enzyme was purified to homogeneity with a purification fold of 7.3 and a recovery yield of 11.6%. The molecular mass of the purified enzyme was estimated to be approximately 34 kDa on SDS-PAGE. TaGlu34 was most active at pH 6.0 and 75 °C, respectively. It showed excellent thermostability with thermal denaturing half-lives of 209, 130 and 69 min at 50, 60 and 70 °C, respectively. TaGlu34 exhibited strict substrate specificity towards barley β-glucan (13,527 U/mg), oat β-glucan (12,502 U/mg) and lichenan (9225 U/mg), but displayed no activity on other tested polysaccharides including laminarin, xylan, pullulan, CMC and starch. TaGlu34 hydrolyzed barley β-glucan and lichenan to yield both mainly disaccharide and trisaccharide, suggesting that it should be an endo type β-1,3-1,4-glucanase. Furthermore, TaGlu34 efficiently degraded the β-glucan component in oat bran to produce mainly oligosaccharides with degrees of polymerization (DP) 3-5, with the highest conversion ratio of 47.1%. The high yield and excellent enzymatic properties of TaGlu34 may make it a good candidate in industries.


Application of Kotter's Theory of Change to Achieve Baby-Friendly Designation.
Creating an environment that optimally supports exclusive breastfeeding can require a cultural transformation. Our initial attempt at obtaining Baby-Friendly Hospital Initiative (BFHI) designation was unsuccessful when surveyors determined insufficient enculturation of BFHI practices. Using Kotter's theory of change, we overcame the barriers, enhanced our practices, and effectively transformed the culture, and our facility ultimately became the first maternity hospital in Pennsylvania to obtain BFHI designation. Nursing leadership was essential to this process. Our experience serves as a template for others seeking to achieve Healthy People 2020 goals related to breastfeeding.


Couple relationship experiences of siblings and siblings-in-law of persons with intellectual disabilities.
This study examined how siblings and siblings-in-law of persons with intellectual disabilities experience the establishment of and processes within the couple relationship. In-depth semi-structured interviews with 12 siblings and 12 siblings-in-law of persons with intellectual disabilities were analysed using thematic analysis. The participants did not perceive their special siblinghood as detrimental to their couple relationships. Siblings-in-law's prior acquaintance with persons with disabilities and professional support provided to the family of origin emerged as contributing factors. The effect of the siblinghood on the couple relationship was both positive and negative. The findings support the importance of the acceptance of others who are different, including in couple relationships when a sibling or sibling-in-law has intellectual disabilities, and underscore the role of professional therapists.


Arp2/3 complex activity is necessary for mouse ESC differentiation, times formative pluripotency, and enables lineage specification.
Mouse embryonic stem cells (mESCs), a model for differentiation into primed epiblast-like cells (EpiLCs), have revealed transcriptional and epigenetic control of early embryonic development. The control and significance of morphological changes, however, remain less defined. We show marked changes in morphology and actin architectures during differentiation that depend on Arp2/3 complex but not formin activity. Inhibiting Arp2/3 complex activity pharmacologically or genetically does not block exit from naive pluripotency, but attenuates increases in EpiLC markers. We find that inhibiting Arp2/3 complex activity delays formative pluripotency and causes globally defective lineage specification as indicated by RNA sequencing, with significant effects on TBX3-depedendent transcriptional programs. We also identify two previously unreported indicators of mESC differentiation, namely, MRTF and FHL2, which have inverse Arp2/3 complex-dependent nuclear translocation. Our findings on Arp2/3 complex activity in differentiation and the established role of formins in EMT indicate that these two actin nucleators regulate distinct modes of epithelial plasticity.


Bioabsorbable stenting in peripheral artery disease.
Arterial stenting has been broadly utilized for the management of peripheral arterial occlusive disease. The evolution of stent materials has led to the introduction of newer bioabsorbable scaffolds that have been extensively evaluated in the treatment of coronary artery disease. However, the utilization of bioabsorbable stents in the lower extremities remains challenging and has not been evaluated in the same degree. There are not many trials focusing on major outcomes of treatment with bioabsorbable stents or comparing them with other therapeutic choices such as surgery or angioplasty only. The aim of this review is to report current status on bioabsorbable stenting in peripheral artery disease treatment as well as to present the results of all major relevant trials. Moreover, future expectations and challenges with this type of stents are discussed as well.


Classic 18.5- and 21.5-kDa myelin basic protein isoforms associate with cytoskeletal and SH3-domain proteins in the immortalized N19-oligodendroglial cell line stimulated by phorbol ester and IGF-1.
The 18.5-kDa classic myelin basic protein (MBP) is an intrinsically disordered protein arising from the Golli (Genes of Oligodendrocyte Lineage) gene complex and is responsible for compaction of the myelin sheath in the central nervous system. This MBP splice isoform also has a plethora of post-translational modifications including phosphorylation, deimination, methylation, and deamidation, that reduce its overall net charge and alter its protein and lipid associations within oligodendrocytes (OLGs). It was originally thought that MBP was simply a structural component of myelin; however, additional investigations have demonstrated that MBP is multi-functional, having numerous protein-protein interactions with Ca²⁺-calmodulin, actin, tubulin, and proteins with SH3-domains, and it can tether these proteins to a lipid membrane in vitro. Here, we have examined cytoskeletal interactions of classic 18.5-kDa MBP, in vivo, using early developmental N19-OLGs transfected with fluorescently-tagged MBP, actin, tubulin, and zonula occludens 1 (ZO-1). We show that MBP redistributes to distinct 'membrane-ruffled' regions of the plasma membrane where it co-localizes with actin and tubulin, and with the SH3-domain-containing proteins cortactin and ZO-1, when stimulated with PMA, a potent activator of the protein kinase C pathway. Moreover, using phospho-specific antibody staining, we show an increase in phosphorylated Thr98 MBP (human sequence numbering) in membrane-ruffled OLGs. Previously, Thr98 phosphorylation of MBP has been shown to affect its conformation, interactions with other proteins, and tethering of other proteins to the membrane in vitro. Here, MBP and actin were also co-localized in new focal adhesion contacts induced by IGF-1 stimulation in cells grown on laminin-2. This study supports a role for classic MBP isoforms in cytoskeletal and other protein-protein interactions during membrane and cytoskeletal remodeling in OLGs.


Development and characterization of an integrated silicon micro flow cytometer.
This paper describes an innovative integrated micro flow cytometer that presents a new arrangement for the excitation/detection system. The sample liquid, containing the fluorescent marked particles/cells under analysis, is hydrodynamically squeezed into a narrow stream by two sheath flows so that the particles/cells flow individually through a detection region. The detection of the particles/cells emitted fluorescence is carried out by using a collection fiber placed orthogonally to the flow. The device is based on silicon hollow core antiresonant reflecting optical waveguides (ARROWs). ARROW geometry allows one to use the same channel to guide both the sample stream and the fluorescence excitation light, leading to a simplification of the optical configuration and to an increase of the signal-to-noise ratio. The integrated micro flow cytometer has been characterized by using biological samples marked with standard fluorochromes. The experimental investigation confirms the success of the proposed microdevice in the detection of cells.


Impact of Hepatectomy for Advanced Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombus.
Optimal treatment strategies for advanced hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) remain controversial. Therefore, this study aimed to assess the impact and predictive factors of hepatectomy for HCC with macroscopic PVTT. This study included 100 patients who presented with intraoperatively confirmed PVTT extending to the first portal branch (Vp3), main portal trunk, or opposite-side portal branch (Vp4) between June 2000 and December 2019. Their postoperative outcomes and predictive factors for survival were evaluated. Of the 100 patients, 37 (37%) and 63 (63%) had Vp3 and Vp4 PVTTs, respectively. Moreover, 42 (42%) and 58 (58%) patients underwent R0/1 and R2 hepatectomies, respectively. The median survival time (MST) of all patients with Vp3/4 PVTT was 14.5 months; the 1- and 3-year overall survival rates were 59.6 and 16.8%, respectively. The MSTs of patients with Vp3 and Vp4 PVTTs were 16.1 and 14.3 months, respectively (P = 0.7098). The MSTs of patients who underwent R0/1 and R2 hepatectomies were 14.3 and 14.9 months, respectively (P = 0.3831). All assessed tumor factors (including the Vp status [Vp3 or Vp4], type of resection [R0/1 or R2], intrahepatic maximal tumor size, intrahepatic tumor number, and the existence of extrahepatic metastasis) did not influence the overall survival significantly. Tumor factors, such as the presence of a Vp3/4 PVTT, have a strong impact on survival; however, other multiple tumor factors have a limited impact. Hepatectomy can be an effective treatment option for HCC with Vp3/4 PVTT, and its indications should be considered.


Type II diabetes mellitus and menopause: a multinational study.
Type II diabetes mellitus causes metabolic changes that may lead to early menopause and worsen climacteric symptoms. To determine the risk factors for type II diabetes mellitus and assess the impact of this disease on the age of menopause and on climacteric symptoms. A total of 6079 women aged between 40 and 59 years from 11 Latin American countries were requested to answer the Menopause Rating Scale and Goldberg Anxiety-Depression Scale. The prevalence of diabetes was 6.7%. Diabetes mellitus was associated with arterial hypertension (odds ratio (OR) 4.49; 95% confidence interval (CI) 3.47-5.31), the use of psychotropic drugs (OR 1.54; 95% CI 1.22-1.94), hormonal therapy (OR 1.46; 95% CI 1.11-1.92), ≥ 50 years of age (OR 1.48; 95% CI 1.17-1.86), overweight or obese (OR 1.47; 95% CI 1.15-1.89), and waist circumference ≥ 88 cm (OR 1.32; 95% CI 1.06-1.65). Factors associated with lower risk of diabetes were the use of hormonal contraceptives (OR 0.55; 95% CI 0.35-0.87), alcohol (OR 0.73; 95% CI 0.54-0.98) and living in cities > 2500 meters above sea level (OR 0.70; 95% CI 0.53-0.91) or with high temperatures (OR 0.67; 95% CI 0.51-0.88). In turn, diabetes tripled the risk of menopause in women under 45 years of age. Diabetes did not increase the risk of deterioration of quality of life due to climacteric symptoms. Menopause does not increase the risk of type II diabetes mellitus. Diabetes is associated with early menopause in women under 45 years of age.


General synthesis of 3-substituted alkenyl GABA as potential anticonvulsants.
Stereospecific synthesis of cis and trans 3-substituted vinyl-gamma-aminobutyric acid analogs were obtained by either a Claisen rearrangement or a Wittig reaction from common diene precursors.


Simple quantitative PCR analysis for allelic Pten loss in tumor progression.
We describe a simple method to accurately detect and quantify both Pten mutation and allele-specific loss using allele-specific PCR analysis. Our approach used a heterozygous genomic DNA with one wild-type and one mutant Pten allele as a reference at a single concentration to calculate the percent ratio of the wild-type Pten gene for the detection of allele-specific gene loss. With a standard curve, ratios from PCR data were used to quantitate the wild-type Pten allele copy number loss in tumor specimens. We demonstrate the utility of our approach to calculate allele-specific Pten loss during tumor progression and show that our approach generates quantitative data that are comparable to those obtained from digital droplet PCR. As a method to detect both mutation and allele-specific gene loss, our approach is less subject to the variability of sample amount that are often very limited in clinical analysis. Since conventional PCR is easy to be carried out, our method simplifies the workflow in any laboratory and would provide significant advantages for simplicity to quantify allele-specific gene loss.


Experimental retinal neovascularization induced by intravitreal tumors.
Adult rabbit retinal vessels underwent neovascularization in response to tumor implantation within the vitreous body. The neovascular response was presumably elicited by the tumor angiogenesis factor (TAF). The response of adult retinal vessels to an angiogenic stimulus raises the possibility that a similar substance may cause retinal neovascularization in humans, and that in normal conditions the vitreous may be able to suppress angiogenic activity.


Surgical treatment of metatarsalgia. Long-term evaluation of 105 cases.
The authors present a long-term evaluation of a special treatment of metatarsalgia. The results are based on clinical findings, footprints and radiographs. The postoperative results provide a satisfactory evaluation of our technique and understanding of the biomechanics in the foot.


Serial proton spectroscopy in a case of adult-onset subacute sclerosing panencephalitis.
A case of subacute sclerosing panencephalitis in a 27-year-old man was serially evaluated with proton magnetic resonance spectroscopy. Metabolic abnormalities included decreased N-acetylaspartate and elevated choline and myo-inositol in a lesion visible on magnetic resonance imaging and in normal-appearing white matter. Lactate appeared increased within the lesion. Metabolic impairment was persistent after intrathecal interferon-alpha treatment. Spectroscopy pointing to ongoing inflammation, gliosis, and possible membrane turnover was more sensitive than imaging in detecting widespread pathology within the white matter.


Comparison of semi-quantitative and visual assessment of early MRI signal evolution in acute ischaemic stroke.
The evaluation of DWI/FLAIR mismatch in ischaemic stroke patients with unknown, time from onset can determine the treatment strategy. This approach is based on, visual assessment and may be subject to insufficient inter-rater agreement. To compare the inter-rater agreement of visual evaluation of FLAIR MRI and proposed region of interest (ROI) semiquantitative method in large vessel occlusion (LVO) strokes. Five readers have analysed MRIs of 104 patients obtained within six hours of the onset of stroke symptoms resulting from LVO visually and semi-quantitatively. For the semiquantitative analysis, a ROI method was used to obtain relative signal intensity compared to the unaffected side. Cut-off values of 1.15 and 1.10 were tested. The analysis yielded FLAIR-positive (abnormal) and negative (normal) findings. Percentage agreement and Fleiss kappa coefficients were calculated. The visual agreement of 5/5 readers and ≥ 4/5 readers occurred in 31% and 59% of cases respectively. Semi-quantitative evaluation using a cut-off value of 1.15 increased the agreements to 67% and 88% respectively. The agreement of visual evaluation was fair. The semi-quantitative method utilising the cut-off of 1.15 had moderate agreement although it increased the number of FLAIR-negative results compared to the visual evaluation. A low cut-off value of 1.10 didn't improve the agreement significantly. The inter-rater agreement of visual evaluation of FLAIR in patients with short-duration large vessel occlusion stroke was fair. The high cut-off value of semiquantitative evaluation increased the agreement although it changed the proportion of FLAIR positive and negative results.