In the ventromedial nucleus of the rat hypothalamus, GABA-immunolabeled neurons are abundant and are innervated by both enkephalin- and GABA-immunolabeled axon terminals.
Immunohistochemical-labeling for the neurochemicals gamma-aminobutyric acid (GABA) and enkephalin are abundant in the ventromedial nucleus of the hypothalamus (VMN). In VMN, both GABA and enkephalin may function to regulate feeding behavior, as well as other hormone-controlled behaviors. Importantly, in several brain areas, enkephalin is often thought to modulate GABAergic neurotransmission. Therefore, we used dual-labeling immunohistochemistry with electron microscopic analysis to study the circuitry of neurons containing GABA- and/or enkephalin-labeling within the VMN. Somato-dendritic profiles containing GABA-labeling were three fold more abundant than GABA-labeled axon terminals (117 soma or dendrites vs. 34 axons). In addition, axon terminals containing GABA-labeling sometimes synapsed onto GABA-labeled somata or dendrites (25% or 9/34). In contrast, under these conditions labeling for enkephalin was primarily restricted to axon terminals, which were very abundant throughout VMN. Enkephalin-containing terminals accounted for a large fraction (25% 23/92) of the axons in contact with GABA-labeled dendrites, although they also contacted unlabeled dendrites. These observations suggest that a population of VMN neurons are GABAergic. These may be either local circuit 'interneurons' or projection neurons. In addition, GABA-labeled VMN neurons may be regulated by either enkephalin or GABA. These morphologic observations provide the basis for disinhibitory mechanisms to function within the VMN.


Nitrogen, sulfur and oxygen co-doped carbon-armored Co/Co9S8 rods (Co/Co9S8@N-S-O-C) as efficient activator of peroxymonosulfate for sulfamethoxazole degradation.
In this study, nitrogen, sulfur and oxygen co-doped carbon armored cobalt sulfide (Co/Co9S8@N-S-O-C) composite was synthesized, characterized and used to activate peroxymonosulfate (PMS) for the degradation of sulfamethoxazole (SMX). SMX (0.04 mM) can be completely degraded within 20 min in the presence of 0.8 mM PMS and 0.1 g/L Co/Co9S8@N-S-O-C composite. The first-order kinetics constant of SMX degradation was 0.307 min-1, and the mineralization of SMX was 30.1 %. The Quenching experiments of the free radicals and the identification of degradation products demonstrated that sulfate radicals played a dominant role in SMX degradation. The degradation rate of SMX increased with temperature, and activation energy was calculated to be 48.6 kJ/mol. The degradation rate of SMX increased firstly then decreased with increase of pH. Chloridion and humic acid decreased the degradation rate of SMX no matter what their initial concentration was. The effect of carbonate on SMX degradation depended on its initial concentration. Co/Co9S8@N-S-O-C composite showed good stability, the removal efficiency of SMX was 98.4 % in the fifth experiment. Based on the characterization results of the catalyst before and after use, it was concluded that cobalt, sulfur, pyridnic N and graphitic N were responsible for PMS activation.


Food limitation of a Delaware salt marsh population of the mummichog, Fundulus heteroclitus (L.).
The relationship of the mummichog, Fundulus heteroclitus, to its food supply was examined using 8 m x 20 m enclosures under field conditions. Density effects were examined by stocking these enclosures with fish at densities ranging from 1/8 to four times the natural population density. Mean growth rate in each pen was estimated from measurements on individually marked fish. Fish enclosed at normal density grew at the same rate as fish from the natural population, indicating that caging had minimal effects on growth rate. When enclosed below natural density, mummichogs had a growth rate that was 2-3 times higher than that of the natural population. Fish enclosed at four times normal density had a negative mean growth rate, a higher mortality rate than fish enclosed at natural density, and no egg production.In further experiments, food was added to the same type of enclosure at fish densities ranging from one-half to four times natural density. Food additions had a positive effect on growth rate at all densities. Food additions also caused egg production of fish enclosed at the highest density to increase to a rate equivalent with the natural population. We conclude that the total food supply may regulate the maximum size of the Canary Creek mummichog population by affecting the individual growth rate, mortality rate, and fecundity.


Evaluation of Penicillium expansum for growth, patulin accumulation, nonvolatile compounds and volatile profile in kiwi juices of different cultivars.
Patulin (PAT) contamination and changes of nonvolatile and volatile compounds caused by Penicillium expansum in fresh juices of 8 kiwi cultivars were investigated. Growth and PAT production of P. expansum were greater at 25°C than at 4°C. P. expansum grew in kiwi juices under pH ranging from 2.75 to 3.27 and produced 45.10-268.88μg/mL of PAT at 25°C. Decreases occurred in malic acid and soluble protein; while consumption and production simultaneously happened for reducing sugar, total soluble solid, titratable acid, citric acid, ascorbic acid and total phenolics. A large number of volatile organic compounds (VOCs) were produced during infection and each cultivar presented a distinct profile. Most of the alcohols, acids, ketones and phenols increased while aldehydes decreased. VOCs that were specific to infected kiwi juices are potential biomarkers for GC-MS analysis of kiwifruit infected by P. expansum.


Study on the material basis of Dahuang Zhechong pill of anti-hepatoma effect by promoting vascular normalization.
Dahuang Zhechong Pill (DHZCP) is a traditional Chinese medicine prescription used to treat many diseases especially chronic liver disease accompanied by promotion of vascular normalization. In this work, UPLC-Q-TOF-MS/MS analysis was applied to identify the chemical components absorbed in the blood. HIF-1α, VEGF, Ang2 and Tie2 related to vascular normalization were detected to determine the dynamic changes of pharmacodynamic indicators. Then, the spectrum-effect relationship between the UHPLC fingerprint and pharmacodynamic indicators was evaluated dynamically using partial least squares (PLS). As a result, 103 components were identified from rat serum samples, including 56 original compounds and 47 metabolites. According to the PLS, active constituents of DHZCP acting on HIF-1α, VEGF, Ang2 and Tie2 (8, 15, 17 and 20) were found. In subsequent experiments on cells, 7/11 components of HIF-1α/VEGF were found in HepG2 and HUVEC cells, and 11/14/2 components of HIF-1α/VEGF/Tie2. The main pharmacodynamic components of DHZCP in promoting vascular normalization were successfully identified by the spectrum-effect relationship analysis.


Pyoderma gangrenosum of the breast: a diagnosis not to be missed.
Pyoderma gangrenosum (PG) is a non-infectious purulent ulcerative disease triggered mainly by chronic inflammatory bowel disease, monoclonal gammapathy, polyarthritis and haematological malignancies; exceptionally, it can be triggered by surgery alone. When PG is associated with fever, it can mimic infectious cellulitis. When it is located on the breast, unnecessary and deleterious surgical debridement may be performed. We present two cases of PG of the breast. The first is a postoperative PG and the second was associated with acute myeloid leukaemia - both led to unnecessary surgery. Several elements may have helped to make the diagnosis: nipples little affected by PG, symmetrical lesions on both breasts, other similar lesions elsewhere on the body, resistance to wide spectrum antibiotherapy, complete blood count abnormalities and negativity of bacterial culture. We propose an index to help the surgeon in his decision to realise a surgical debridement or to postpone it and consider the diagnosis of PG.


Inflammatory peptide in spinal cord: evidence that the mediator of antidromic vasodilatation is not substance P.
Extracts from rat and bovine spinal cord were found to have 300-1000 times more cutaneous oedema-inducing activity than could be attributed to their substance P-like activity estimated by assay on guinea-pig ileum. The activity on both assay systems was reduced in cord extracts from rats pretreated as neonates with capsaicin. Results of assays of fractions obtained from gel-filtration chromatography indicated that an agent, in the molecular size range for peptides, was present in spinal cord extracts, which possessed some of the properties of substance P but was not identical to it.


The Effects of Spectacles or Orthokeratology on the Tear Film in Children and Adolescents.
Myopia prevalence among adolescents is increasing annually. While orthokeratology (OK) is effective for controlling myopia progression, it may also be detrimental. We investigated tear film parameters [including tear mucin 5AC (MUC5AC) concentration] in children and adolescents with myopia treated with spectacles or OK compared with those with emmetropia. This prospective case-control study enrolled children (aged 8-12 years; 29 and 39 with myopia treated with OK and spectacles, respectively, and 25 with emmetropia) and adolescents (aged 13-18 years; 38 and 30 with myopia treated with OK and spectacles, respectively, and 18 with emmetropia). We recorded the ocular surface disease index (OSDI), visual analog scale (VAS) score, tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), meibomian gland score (meiboscore), ocular redness score, and tear MUC5AC concentration in the emmetropia, spectacle (after 12 months of spectacle wearing), and OK (baseline, and after 1-, 3-, 6-, and 12-month use) groups. We observed changes from baseline to 12 months in the OK group and compared parameters among the spectacle, 12-month OK, and emmetropia groups. The 12-month OK group differed significantly from the spectacle and emmetropia groups in most indicators among children and adolescents (P < 0.05). Differences were not noticeable between the spectacle and emmetropia groups (only PVAS < 0.05 among the children). In the OK group, the 12-month NIBUT was significantly decreased (P < 0.05) in both age groups; the upper meiboscore was increased at 6 and 12 months (both P < 0.05) among children; ocular redness scores were higher at 12 months than at baseline (P = 0.007), 1 month (P < 0.001), and 3 months (P = 0.007) among children; and the MUC5AC concentration was decreased at 6 and 12 months among adolescents, but only at 12 months among children (all P < 0.05). Long-term OK can negatively influence the tear film in children and adolescents. Moreover, changes are masked by spectacle wearing. This trial is registered with "ChiCTR2100049384."


Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens.
Antiandrogens are in use alone and in combination with other agents as hormonal therapy for prostate cancer. We conducted studies on the androgen-responsive human prostate cancer cell line LNCaP to determine the direct effects of three antiandrogens (hydroxyflutamide, RU23908, and cyproterone acetate) on hormone-responsive human prostate cancer cells in culture. Dihydrotestosterone (DHT) stimulated the growth of LNCaP cells in a dose-dependent fashion. These cells contained approximately 31,000 high-affinity (Kd = 9 x 10(-10) M) androgen binding sites per cell. In the absence of any androgenic stimulation, all three antiandrogens tested showed agonistic properties by increasing the cell number and uptake of [3H]-thymidine. Competitive uptake studies using [3H]-R1881, a nonmetabolized androgen, showed that the three antiandrogens inhibited specific R1881 uptake with IC50s of 0.9 x 10(-7) M for hydroxyflutamide, 2 x 10(-7) M for RU23908, and 1 x 10(-7) M for cyproterone acetate. It is not known whether these unexpected agonistic effects are due to an altered receptor, previously unmasked agonistic properties of the antiandrogens, or emergence of a hypersensitive clone of cells.


Implications of parents' work travel on youth adjustment.
Guided by ecological, work-family spillover and crossover frameworks, this study examined mechanisms linking parental work travel (i.e., nights per year) to youth adjustment (i.e., externalizing and internalizing behaviours) through youth's perceptions of parenting (i.e., knowledge, solicitation) with traveller and youth gender as moderators in a sample of 78 children in 44 two-parent families residing in the United States. The findings from multilevel analyses suggested that mothers' travel nights predicted lower levels of maternal knowledge, with variation by traveller and youth gender. Mothers' and fathers' work travel and perceived parenting were predictors of youth's externalizing behaviours, whereas only fathers' work travel and perceived parenting were predictors of youth's internalizing behaviours. Tests of indirect effects indicated that maternal work travel linked to youth's externalizing behaviours through youth's perceptions of maternal knowledge. These findings add to our limited understanding of work-family issues for parents who have the unique work demand of frequently travelling.


Physical characterization of swine and human skin: Correlations between Raman spectroscopy, Tensile testing, Atomic force microscopy (AFM), Scanning electron microscopy (SEM), and Multiphoton microscopy (MPM).
Swine dorsum is commonly utilized as a model for studying skin wounds and assessment of dermatological and cosmetic medicaments. The human abdomen is a common location for dermatological intervention. This study provides a correlation between spectral, mechanical, and structural characterization techniques, utilized for evaluating human abdominal skin and swine dorsum. Raman spectroscopy (RS), tensile testing, ballistometry, AFM, SEM, and MPM were utilized to characterize and compare full-thickness skin properties in swine and human model. RS of both species' skin types revealed a similar assignment of vibrations in the fingerprint and the high wavenumber spectral regions. Structural imaging and mechanical characterization using ballistometry and tensile testing displayed differences in the inherent functional properties of human and swine skin. These differences correlated with variations in the Raman peak ratios, collagen intensity measured using SEM and MPM and collagen density measured using AFM. A comprehensive evaluation of swine skin as a suitable substitute for human skin for mechanical and structural comparisons was performed. This data should be considered for better understanding the swine skin model for cutaneous drug delivery and wound applications. Additionally, correlation between RS, tensile testing, AFM, SEM, and MPM was performed as skin characterization tools.


Cytogenetic heterogeneity in blast crisis (BC) of chronic myelogenous leukemia (CML).
New cytogenetic findings are reported in a patient who entered into an accelerated blastic phase of chronic myelogenous leukemia (CML). The cytogenetic findings of this case can be described as 46, xy, t (5;7) (q 31;q 11), t (9;22) (q 34;q 11), Ph'. The prognostic implications in such patients with rare and unusual cytogenetic findings are discussed.


Psychometric properties of the Indonesian Fonseca anamnestic index and the presence/severity of temporomandibular disorders among Indonesian young adults.
The psychometric properties of the Indonesian FAI (FAI-I) and presence/severity of temporomandibular disorders (TMDs) among Indonesian young adults were explored. The FAI-I was developed following the INfORM guidelines and used to determine the presence/severity of TMDs. Internal consistency/test-retest reliability were examined with Cronbach's alpha/intra-class correlation (ICC) coefficients. Construct/criteria validity were established by correlating (Spearman) the FAI-I to the five major TMD symptoms (5 Ts) and OHIP-14 (p < 0.05). Five hundred-one participants (mean age 19.73 ± 1.27 years; 75.2% women) were recruited from a local University. Of these, 40.7% had no TMD, while 49.9%, 8.8%, and 0.6% had mild, moderate, and severe TMD. While Cronbach's α = 0.57 and ICC = 0.72, correlation coefficients to total 5 Ts and OHIP-14 were 0.53 and 0.47, respectively. The FAI-I had low internal consistency, good test-retest reliability, and good validity. Moderate-to-severe TMD was experienced by 9.4% of the young adults examined.


The ruthenium-catalysed selective synthesis of mono-deuterated terminal alkynes.
We report an efficient catalytic method for the synthesis of mono-deuterated terminal alkynes directly from deuterium oxide, catalysed by a Ru(II) pincer complex in which the reaction proceeds via Ru-acetylide intermediates and amine-amide metal-ligand cooperation.


Kinetics of reduction of the oxidized primary electron donor of photosystem II in spinach chloroplasts and in Chlorella cells in the microsecond and nanosecond time ranges following flash excitation.
Absorption changes (deltaA) at 820 nm, following laser flash excitation of spinach chloroplasts and Chlorella cells, were studied in order to obtain information on the reduction time of the photooxidized primary donor of Photosystem II at physiological temperatures. In the microsecond time range the difference spectrum of deltaA between 750 and 900 nm represents a peak at 820 nm, attributable to a radical-cation of chlorophyll a. In untreated dark-adapted material the signal can be attributed solely to P+-700; it decays in a polyphasic manner with half-times of 17 microseconds, 210 microseconds and over 1 ms. The oxidized primary donor of Photosystem II (P+II) is not detected with a time resolution of 3 microseconds. After treatment with 3--10 mM hydroxylamine, which inhibits the donor side of Photosystem II, P+II is observed and decays biphasically (a major phase with t1/2=20--40 microseconds, and a minor phase with t1/2 congruent to 200 microseconds), probably by reduction by an accessory electron donor. In the nanosecond range, which was made accessible by a new fast-response flash photometer operating at 820 nm, it was found the P+II is reduced with a half-time of 25--45 ns in untreated dark-adapted chloroplasts. It is assumed that the normal secondary electron donor is responsible for this fast reduction.


Serotonin involvement during in vitro conditioning of Hermissenda.
To determine if serotonin may be involved in associative conditioning-produced changes in the excitability and photoresponses of Type B photoreceptors, isolated nervous systems were exposed to an in vitro conditioning procedure in the presence or absence of drugs that alter normal serotonergic neurotransmission. Pairings of light and intracellular depolarization of a caudal hair cell (in vitro conditioning) produced a pairing-specific depolarization of Type B photoreceptors that was accompanied by an increase in resting input resistance. Treatment of nervous systems with pharmacological agents which disrupt 5-HT neurotransmission attenuated membrane potential and input resistance changes of Type B photoreceptors. These drugs included serotonin uptake inhibitors (imipramine, fluoxetine), a receptor antagonist (bufotenine), and a neurotoxin (5,7-dihydroxytryptamine; 5, 7-DHT). Yohimbine, an alpha 2-receptor antagonist, was without effect. These results, and those in the accompanying papers, suggest that serotonin modulates Type B photoreceptor excitability during associative conditioning.


Factors affecting the longevity of sub-surface horizontal flow systems operating as tertiary treatment for sewage effluent.
Compared with other forms of domestic wastewater treatment, reed beds require very little in the way of operational and maintenance input. This is even more markedly the case with tertiary treatment systems (than with secondary treatment systems) where the necessary maintenance amounts to only a few days/year. Unfortunately, in practice this frequently results in them receiving little or no attention at all. Tertiary treatment reed beds are not a "fit and forget" solution but they are often treated this way because they are very forgiving and abuse-tolerant. After a number of years a few of these tertiary reed beds have deteriorated to an extent whereby they are close to failing to comply with the regulator's requirements. Severn Trent Water Ltd has recognised this situation and has committed a budget for a programme of reed bed maintenance. This work has started with a survey of the condition of their beds and particularly to determine the common problems and hence the maintenance regime required. Five main problems occurred either singly or in combination namely: (a) sludge deposition; (b) above surface flooding (partially caused by (a), (c), and (d)); (c) inlet flow distributor problems/clogging; (d) outlet collector problems/incorrect level; (e) weed infestation.


Orbital cysticercosis: A case report.
A 22 years old male presented to us with a history of lid swelling and chemosis of conjunctiva since 2 days. The patient had a history of convulsions 4 days back and 2 months back. The patient had undergone a CT scan which showed granulomas in temporal and parietal lobes. The patient was started on Anti tuberculosis treatment by the Physician. The Patient underwent USG B scan which revealed cysticercosis cyst in the anterior orbit inferiorly .The patient was treated with albendazole and wysolone for a month. The patient was reviewed after 1 month .The lesion resolved with the treatment both clinically and on USG.


Outcome of ulcerative colitis after treatment with transdermal nicotine.
Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects. A randomized, comparative study. Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopic signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment. Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group. Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids.


Establishment of functional imprinting of the H19 gene in human developing placentae.
We have found that the imprinted H19 gene can be expressed either biallelically or monoallelically in the developing human placentae. H19 biallelic expression is confined to the placenta until 10 weeks of gestation, after which it becomes exclusively maternal, and does not affect allele-specificity or levels of IGF2 expression. The promoter region of H19 is hypomethylated at all stages of placental development, while the 3' portion shows progressive methylation of the paternal allele with gestation. Our observations demonstrate that the establishment of functional H19 imprinting occurs during the early development of the placenta and provide an opportunity to understand the mechanism by which the H19 primary imprint is manifested in somatic cells.


Effects of membrane acting-drugs on plasmodium species and sickle cell erythrocytes.
The effects of several membrane-acting drugs on malaria and sickle cell anemia was studied. In the initial experiments, propranolol and W-7 were shown to increase red cell density. In vitro, these drugs inhibited the growth of P. falciparum. However, in vivo experiments using the murine malarial parasite, P. vinckei, demonstrated little, if any, anti-parasite activity with the doses of drugs employed. Subsequently, prostaglandin oligomeric derivatives were found to inhibit the growth of P. falciparum in vitro and P. vinckei in vivo. Since prostaglandin oligomers inhibited the formation of dense, dehydrated cells (irreversible sickle cells), they may also have therapeutic efficacy in sickle cell anemia.


Intensity-modulated radiotherapy and cisplatin-based chemotherapy for anal cancer: long-term outcomes at a single institution.
To evaluate oncological outcomes and late toxicities in a retrospective series of patients with locally-extended anal squamous cell carcinoma (ASCC), treated with curative Intensity Modulated Radiotherapy (IMRT) and chemotherapy. ASCC patients who underwent chemo-radiotherapy with IMRT from 2010 to 2020 were included. Oncological outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS) and event-free survival (EFS). Late toxicity was detected according to CTCAE v.5.0 and RTOG late radiation morbidity scoring system. Ninety-five patients were included. Most patients (83%) received chemotherapy with oral Fluoropyrimidine plus Cisplatin. The median follow-up was 5.5 years. The OS was 85.2%, 82.1% and 79.3% at 3, 5 and 8 years, respectively. The DFS was 73.1%, 70%, and 65.3% at 3, 5 and 8 years, respectively; 3, 5 and 8 years CFS was 86.2%, 84.3% and 84.3%, respectively. The EFS was 71%, 67.9% and 63.1%, at 3, 5 and 8 years, respectively. On univariable analysis, a statistically significant lower OS was found for patients with T3-T4 stage (HR = 4.58, p = 0.005) and overall treatment time (OTT) ≥ 47 days (HR = 3.37, p = 0.038). A statistically significant lower DFS was reported for patients with T3-T4 stage (HR = 2.72, p = 0.008) and Serum Squamous Cell Carcinoma Antigen (SCC) value post-RT > 1.5 (HR = 2.90, p = 0.038.). Ten severe late toxicity (≥ G3) events were reported in 8 patients (8.6%). Our data confirm IMRT concomitant with a Cisplatin-based chemotherapy as an effective treatment of ASCC, ensuring acceptable long-term toxicities and good oncological outcomes.


Lynch syndrome: clinical, pathological, and genetic insights.
Lynch syndrome as the most common hereditary colorectal cancer syndrome and the most common cause of hereditary endometrial cancer is characterized by an autosomal dominant inheritance with a penetrance of 85-90%. The molecular genetic underlying mechanism is a mutation in one of the mismatch repair genes. In order to identify patients with Lynch syndrome, a nuclear family history should be ascertained and matched with the Amsterdam criteria. A different approach for identification is the adherence to Bethesda criteria and subsequent testing for microsatellite instability. In patients with unstable tumors as an indicator for mismatch repair deficiency, genetic counseling and mutation analysis are warranted. For families fulfilling the Amsterdam criteria, intensified screening is recommended, even if a pathogenic mutation is not identified. Individuals from families with a proven pathogenic mutation that are tested negative are at normal population risk for cancers and may be dismissed from intensified surveillance. Prophylactic surgery in high-risk individuals without neoplasia is not generally recommended. At the time of a colon primary, however, extended surgery should be discussed in the light of a high rate of metachronous cancers. The worries of impairing functional results have now been evaluated in the light of quality of life in a large international cohort. Interestingly, extended (prophylactic) surgery does not lead to inferior quality of life with equal perioperative risks. Therefore, taking the risk reduction into account, extended surgery at the time of the first colon primary should at least be discussed, if not recommended. Also, prophylactic hysterectomy and bilateral oophorectomy at the time of a colorectal primary should be recommended if family planning has been completed.


[Possibilities for HIV inactivation in homologous bone transplants].
Recently, the availability of bone allografts has declined dramatically, due to the three-month HIV test which is often difficult to obtain. Accordingly, there is a search for methods to inactivate HIV in bone allografts without compromising the biologic quality of the grafts. Chemical substances require long exposure and desorption times, to ensure that no toxic agents remain within the bone before actual transplantation. X-ray inactivation leads to complete loss of any osteoinductive properties of the allografts, according to some authors. In addition, the high doses that are necessary are difficult to apply. Autoclaving has been practiced in some instances, but all experimental results and some more recent clinical observations warn that osteoinductive properties of the allografts are lost during the autoclaving process. Lower temperatures (56 degrees C) are sufficient to warrant inactivation of HIV, and some experimental results and preliminary clinical observations indicate that moderate heat treatment of bone allografts in a water bath may become a useful method for virus inactivation of bone allografts.


Oxygenation and flow in the limbs: Novel methods to characterize peripheral artery disease.
Peripheral arterial disease (PAD) affects approximately 8 million Americans and is associated with high morbidity and increased mortality. Current therapies for PAD are limited and development of new therapeutic agents is needed. Present diagnostic methods for PAD are insensitive to the subtle microvascular and metabolic changes that occur beyond macrovacular stenosis and therefore may be less useful endpoints for clinical trials. Phosphorus-31 magnetic resonance (MR) spectroscopy, MR muscle perfusion, and MR oximetry are novel methods capable of evaluating both the macrovascular and microvascular changes that occur in PAD patients.


Chronic active Epstein-Barr virus infection (CAEBV) successfully treated with allogeneic peripheral blood stem cell transplantation.
We report a pediatric case of CAEBV and T cell-based Hodgkin's-like disease successfully treated with allo PBSCT from an HLA-matched sibling. The diagnosis of CAEBV was made from clinical signs and the presence of the EBV genome in PBMC and tumor cells. Conditioning with busulfan (BU) + etoposide (VP16) + cyclophosphamide (CY) was effective and well tolerated. EBV was totally eradicated by 3 months after allo PBSCT. Although she suffered from chronic GVHD of the liver, she has been well and free of disease for 47 months since PBSCT. We suggest allo PBSCT for CAEBV as a potent therapeutic strategy for eradication of the EBV genome and allowing immunological reconstitution.


Bilateral subclavian artery aneurysm associated with idiopathic cystic medial necrosis.
Although cystic medial necrosis, either idiopathic or associated with Marfan's syndrome, usually becomes manifest as an ascending aortic aneurysm, aortic insufficiency, aortic dissection, or a combination of these disorders, a rare case of bilateral subclavian artery aneurysm secondary to idiopathic cystic medial necrosis has occurred. Subclavian artery aneurysms most commonly represent poststenotic dilatation from anterior scalene or cervical rib compression, occasionally are associated with generalized arteriosclerotic peripheral vascular disease, and rarely are secondary to syphilitic or mycotic infections. Subclavian artery aneurysms have a major risk of rupture, embolus, or thrombosis, and therefore should be repaired. A reverse saphenous vein or prosthetic bypass graft from the carotid to the axillary artery provides adequate flow to the upper extremity. The aneurysm should be completely excised if possible, since reexpansion through small collaterals or through insufficient closure by ligation can occur and compress the brachial plexus after successful bypass. The clinical presentation, angiographic findings, and operative repair of a subclavian artery aneurysm secondary to cystic medial necrosis are described.


The role of survivin as a new target of diagnosis and treatment in human cancer.
Survivin has recently been identified as a novel inhibitor of apoptosis (IAP). Unlike other members of the IAP family, survivin is characterized by a unique structure that contains a single baculovirus IAP repeat and no really interesting new gene (RING) finger motifs, and it is expressed in many common human cancers, but not in normal tissues. Survivin regulates the G(2)/M phase of the cell cycle by associating with mitotic spindle microtubules, and it directly inhibits caspase-3 and caspase-7 activity. During tumorigenesis, survivin expression is inversely correlated with apoptosis inhibition and positively correlated with proliferation and angiogenesis. Inhibition of apoptosis by survivin predicts poor prognosis and shorter survival in human cancers. The molecular detection of occult cancer by the targeting of survivin as a novel molecular marker is useful, and micrometastasis detected by immunohistochemical staining for survivin reveals inhibition of apoptosis and the acceleration of cell proliferation. In in-vitro and in-vivo studies, survivin targeting with antisense and survivin mutants induces apoptosis, reduces tumor growth potential, and sensitizes cells to chemotherapeutic drugs and X-irradiation. These results suggest that survivin may have the potential to function as a new target for the diagnosis and treatment of cancer.


Defining a New Prognostic Index for Stage I Nonseminomatous Germ Cell Tumors Using CXCL12 Expression and Proportion of Embryonal Carcinoma.
Up to 50% of patients diagnosed with stage I nonseminomatous germ cell tumors (NSGCTs) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up front. Late toxicities from chemotherapy are increasingly recognized. Based on a potential biologic role in germ cells/tumors and pilot data, our aim was to evaluate tumor expression of the chemokine CXCL12 alongside previously proposed markers as clinically useful biomarkers of relapse. Immunohistochemistry for tumor expression of CXCL12 was assessed as a biomarker of relapse alongside vascular invasion, histology (percentage embryonal carcinoma), and MIB1 staining for proliferation in formalin-fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCTs. TE08/TE22 trial patients had a 76.4% 2-year relapse-free rate, and both CXCL12 expression and percentage embryonal carcinoma provided prognostic value independently of vascular invasion (stratified log rank test P = 0.006 for both). There was no additional prognostic value for MIB1 staining. A model using CXCL12, percentage embryonal carcinoma, and VI defines three prognostic groups that were independently validated. CXCL12 and percentage embryonal carcinoma both stratify patients' relapse risk over and above vascular invasion alone. This is anticipated to improve the stratification of patients and identify high-risk cases to be considered for adjuvant therapy.


Controlling pesticide release via structuring agropolymer and nanoclays based materials.
The potential use of nanoclays for modulating transfer properties of active agents in bio-sourced polymers was explored. For this purpose, new pesticide formulations were designed by combining wheat gluten, ethofumesate (model pesticide) and three montmorillonites (MMT) using a bi-vis extrusion process. Controlled release properties, evaluated through release experiments in water, were discussed in relation to the material formulations and their resulting structure. Partition coefficients were calculated from experimental data and diffusivity values were identified with a Fick's second law mechanistic model. The effect of temperature on release pattern was also evaluated and the activation energy of diffusion was determined. Ethofumesate release was slowed down for all wheat gluten based-formulations as compared to the commercial product. This slow release effect was increased in the presence of hydrophobic MMTs, due to a higher affinity for ethofumesate than for wheat gluten. Contrarily, hydrophilic MMT, displaying a greater affinity for wheat gluten than for ethofumesate seemed ineffective to slow down its release despite the tortuous pathway achieved through a well-exfoliated structure. To conclude, the release mechanisms would be rather governed by pesticide/MMT interactions than MMT/polymer matrix in the case of a hydrophobic pesticide such as ethofumesate and a hydrophilic matrix such as wheat gluten.


Herbal medicine and acupuncture relieved progressive bulbar palsy for more than 3 years: A case report.
Progressive bulbar palsy (PBP) is a type of motor neuron disease (MND). The main symptoms include dysarthria, dysphagia, tongue muscle atrophy and fasciculations. This disease is generally severe and develops rapidly. Due to the lack of effective treatment, many patients with MND in China turn to traditional Chinese medicine treatment for help. We successfully relieved dysphagia and sialorrhea in a patient with PBP for 3 years with herbal medicine and acupuncture. The patient was a 68-years-old woman with PBP and suffered from severe dysphagia and sialorrhea. Progressive bulbar palsy. Chinese herbal medicine and acupuncture. After 4 months of herbal medicine and acupuncture treatment, dysphagia and sialorrhea were relieved considerably. The patient's condition has been stable for more than 3 years and continues to be treated with Chinese herbal medicine and acupuncture. Our case suggests that alternative therapies such as herbal medicine and acupuncture may be effective in alleviating the symptoms of MND/PBP. However, standardized clinical studies are still required to verify the effectiveness and safety.


Capillary gas chromatography-mass spectrometry of ecdysteroids.
Fully trimethylsilylated ecdysteroids have been analysed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) using flexible fused-silica capillary columns. Best results were obtained using columns coated with cross-bonded apolar (OV-1 type) stationary phases. By employing capillary GC-MS with selected-ion monitoring (SIM), very sensitive and selective analyses for ecdysteroids are possible. Detection limits of 10 and 100 pg have been determined for 20-hydroxyecdysone and ecdysone, respectively. At this level of sensitivity, capillary GC-SIM-MS constitutes a complementary means of ecdysteroid analysis to high-performance liquid chromatography (HPLC) with monitoring of the eluent fractions by radioimmunoassay (RIA), but with the advantage of enhanced selectivity. Examples are given of the application of capillary GC-SIM-MS and HPLC-RIA in combination to investigate the nature and concentration of ecdysteroids at the picogram level in three helminth species.


Schizophrenia in the genetic era: a review from development history, clinical features and genomic research approaches to insights of susceptibility genes.
Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.


Genetic structure of personality factors and bipolar disorder in families segregating bipolar disorder.
Bipolar disorder (BPD) has been associated with variations in personality dimensions, but the nature of this relationship has been unclear. In this study, the heritabilities of BPD and the Big Five personality factors and the genetic correlations between BPD and personality factors are reported. The participants in this study were 1073 individuals from 172 families of Mexican or Central American ancestry. Heritabilities and genetic correlations were calculated under a polygenic model using the maximum-likelihood method of obtaining variance components implemented in the SOLAR software package. Heritabilities of 0.49, 0.43, and 0.43 were found for the narrowest phenotype (schizoaffective bipolar and bipolar I), the intermediate phenotype (schizoaffective bipolar, bipolar I, and bipolar II), and the broadest phenotype (schizoaffective bipolar, bipolar I, bipolar II, and recurrent depression), respectively. For the Big Five personality factors, heritabilities were 0.25 for agreeableness, 0.24 for conscientiousness, 0.24 for extraversion, 0.23 for neuroticism, and 0.32 for openness to experience. For the narrowest phenotype, a significant negative correlation (-0.32) with extraversion was found. For the broadest phenotype, negative correlations were found for agreeableness (-0.35), conscientiousness (-0.39), and extraversion (-0.44). A positive correlation (0.37) was found with neuroticism. It is not possible to determine whether aspects of personality are factors in the development of bipolar disorder or vice versa. The short form of the NEO does not provide the ability to examine in detail which facets of extraversion are most closely related to bipolar disorder or to compare our results with studies that have used the long version of the scale. This study establishes a partial genetic basis for the Big Five personality factors in this set of families, while the environmental variances demonstrate that non-genetic factors are also important in their influence on bipolar and personality phenotypes. BPD may be most associated with decreased extraversion (less interaction with one's surroundings) because patients spend more time in depressive than manic states.


Muscarinic stimulation of prostanoid synthesis by the isolated rat trachea: calcium dependency and effect of cortisol and cigarette smoke.
Tracheal prostanoid synthesis was stimulated by parasympathomimetics: arecoline greater than carbachol = methacholine greater than acetylcholine much greater than arecaidine. McNA343, dimethyl phenyl piperazinium (DMPP), nicotine, potassium and isoprenaline were without effect. Prostanoid synthesis was also stimulated by Ca2+ ionophore A23187 and arachidonic acid (AA). Carbachol-stimulated prostanoid synthesis was inhibited by cholinergic antagonists (atropine greater than ipratropium bromide much greater than gallamine greater than pirenzepine); adrenaline and isoprenaline were without effect. Carbachol-stimulated prostanoid synthesis was also inhibited by the Ca2+-channel blockers, nifedipine, diethylstilboestrol and TMB-8. Hydrocortisone and betamethasone inhibited carbachol- and A23187-stimulated, but not AA-stimulated, prostanoid synthesis following an 18 h tissue culture. Cigarette smoke extracts had a biphasic effect on carbachol-, A23187- and AA-stimulated prostanoid synthesis (potentiation at low concentrations, inhibition at high concentrations of extracts). These data demonstrate (1) that rat tracheal prostanoid synthesis is stimulable by activation of muscarine receptor-linked Ca2+ mobilisation, and (2) that tracheal prostanoid synthesis may be involved in secretion of mucus, the disruption of which by cigarette smoking may be related to the pathophysiology of airway disease.


Percutaneous retrieval of a right atrioventricular embolus.
Percutaneous retrieval of a 12-cm-long serpiginous clot lodged in the right atrium and ventricle is reported. Following bilateral common femoral vein puncture, a Bird's Nest cava filter was first positioned ready to deploy immediately below the renal veins via the right femoral vein. From the left femoral vein, a Cook intravascular retrieval basket was advanced to the right atrium. Under transthoracic echocardiographic visualization, the basket was used to engage, trap, and gently withdraw the clot in a single long strand below the prepositioned inferior vena cava filter. The filter was immediately deployed, leaving the clot trapped inferior to the renal veins, in the cava and left iliac vein. The patient remained well and asymptomatic at discharge.


Short-term changes in the anaerobic digestion microbiome and biochemical pathways with changes in organic load.
Fluctuations in organic loading rate are frequently experienced in practical-scale anaerobic digestion systems. These impose shocks to the microbiome leading to process instability and failure. This study elucidated the short-term changes in biochemical pathways and the contributions of microbial groups involved in anaerobic digestion with varying organic load shocks. A mixture of starch and hipolypeptone corresponding to a carbon-to‑nitrogen ratio of 25 was used as substrate. Batch vial reactors were run using acclimatized sludge fed with organic load varying from 0 to 5 g VS/L. Methane yield decreased with increasing organic load. The microbiome alpha diversity represented as the number of operational taxonomic units (OTUs) and the Shannon index both decreased with organic load indicating microbiome specialization. The biochemical pathways predicted using PICRUSt2 were analyzed along with the corresponding contributions of microbial groups leading to a proposed pathway of substrate utilization. Genus Trichococcus (order Lactobacillales) increased in contribution to starch degradation pathways with increase in organic load while genus Macellibacteroides (order Bacteroidales) was prominent in contribution to bacterial anaerobic digestion pathways. Strictly acetoclastic Methanosaeta increased in prominence over hydrogenotrophic Methanolinea with increase in organic load. Results from this study provide better understanding of how anaerobic digesters respond to organic load shocks.


Pathologic investigation of cutaneous stretch.
Unevenly stretched skin of the back of rats resulted in microscopic as well as light microscopic features of wounding with subsequent repair as a result of the trauma due to this type of stretch. In skin evenly stretched, dermal collagen was markedly thickened and homogeneous as compared to controls. The increased thickness of evenly stretched skin despite its increase in surface area is consonant with views indicating that stretch may increase the synthesis of diminish the degradation of dermal collagen. The validity of this conclusion, however, is dependent upon the premise that the evenly stretched skin is also "wounded" since this latter would be required to account for the rapid turnover of collagen in these rather acute experiments. This implies a defect at a molecular or biochemical level since no qualitative structural alterations were detected by the conventional techniques employed.


The value of oxygen index and base excess in predicting the outcome of neonatal acute respiratory distress syndrome.
This study aimed to identify the predictors and threshold of failure in neonatal acute respiratory distress syndrome. Newborns with severe acute respiratory distress syndrome aged 0-28 days and gestational age ≥36 weeks were included in the study if their cases were managed with non-extra corporal membrane oxygenation treatments. Patients were divided into two groups according to whether they died before discharge. Predictors of non-extra corporal membrane oxygenation treatment failure were sought, and the threshold of predictors was calculated. A total of 103 patients were included in the study. A total of 77 (74.8%) survived hospitalization and were discharged, whereas 26 (25.2%) died. Receiver operating characteristic analysis of oxygen index, pH, base excess, and combinations of these indicators demonstrated the advantage of the combination of oxygen index and base excess over the others variables regarding their predictive ability. The area under the curve for the combination of oxygen index and base excess was 0.865. When the cut-off values of oxygen index and base excess were 30.0 and -7.4, respectively, the sensitivity and specificity for predicting death were 77.0% and 84.0%, respectively. The model with base excess added a net reclassification improvement of 0.090 to the model without base excess. The combination of oxygen index and base excess can be used as a predictor of outcomes in neonates receiving non-extra corporal membrane oxygenation treatment for acute respiratory distress syndrome. In neonates with acute respiratory distress syndrome, if oxygen index >30 and base excess <-7.4, non-extra corporal membrane oxygenation therapy is likely to lead to death.


Lexidactylophobia: the (irrational) fear of fingerspelling.
Fingerspelling is a system of manually representing the graphemes of a spoken language used by members of Deaf communities worldwide. Yet, at least within the North American educational system, fingerspelling appears to be largely discounted in favor of sign usage, despite its high potential for linkage to the orthographical system of English and literacy development. The author describes fingerspelling in connection with how it is used within the American Deaf community, and also describes the development of fingerspelling skills in deaf (and hearing) children. He also describes how deaf adults use fingerspelling to promote literacy development in young deaf children. Strategies for increasing the use of fingerspelling by teachers and parents of the Deaf are outlined.


Quantitative pretreatment EEG predicts efficacy of ACTH therapy in infantile epileptic spasms syndrome.
This study aimed to determine the correlation between outcomes following adrenocorticotrophic hormone (ACTH) therapy and measurements of relative power spectrum (rPS), weighted phase lag index (wPLI), and graph theoretical analysis on pretreatment electroencephalography (EEG) in infants with non-lesional infantile epileptic spasms syndrome (IESS). Twenty-eight patients with non-lesional IESS were enrolled. Outcomes were classified based on seizure recurrence following ACTH therapy: seizure-free (F, n = 21) and seizure-recurrence (R, n = 7) groups. The rPS, wPLI, clustering coefficient, and betweenness centrality were calculated on pretreatment EEG and were statistically analyzed to determine the correlation with outcomes following ACTH therapy. The rPS value was significantly higher in the delta frequency band in group R than in group F (p < 0.001). The wPLI values were significantly higher in the delta, theta, and alpha frequency bands in group R than in group F (p = 0.007, <0.001, and <0.001, respectively). The clustering coefficient in the delta frequency band was significantly lower in group R than in group F (p < 0.001). Our findings demonstrate the significant differences in power and functional connectivity between outcome groups. This study may contribute to an early prediction of ACTH therapy outcomes and thus help in the development of appropriate treatment strategies.


On the frequency of height values.
We count algebraic numbers of fixed degree d and fixed (absolute multiplicative Weil) height H with precisely k conjugates that lie inside the open unit disk. We also count the number of values up to H that the height assumes on algebraic numbers of degree d with precisely k conjugates that lie inside the open unit disk. For both counts, we do not obtain an asymptotic, but only a rough order of growth, which arises from an asymptotic for the logarithm of the counting function; for the first count, even this rough order of growth exists only if k ∈ { 0 , d } or gcd ( k , d ) = 1 . We therefore study the behaviour in the case where 0 < k < d and gcd ( k , d ) > 1 in more detail. We also count integer polynomials of fixed degree and fixed Mahler measure with a fixed number of complex zeroes inside the open unit disk (counted with multiplicities) and study the dynamical behaviour of the height function.


Circadian rhythm in the number of granulated vesicles in the pinealocytes of mice. Effects of sympathectomy and melatonin treatment.
Adult, Charles River CD-1, male mice were housed in an environmental control chamber under strict conditions of controlled light (12D/12L) and temperature. The mice were sacrificed at various times throughout the twenty-four hour clock and their pineals prepared routinely for electron microscopy. The number of dense-cored or granulated vesicles present in the polar terminals of pinealocytes were quantitated in thin cross sections through pericapillary areas. A distinct circadian rhythm was observed in the number of granulated vesicles with a three- to four-fold difference between late photoperiod maximum and late dark period minimum. The rhythm was abolished by bilateral superior cervical ganglionectomy. These results are consistent with the hypothesis that the granulated vesicles are synthesized and stored in the pinealocytic cytoplasm during the photoperiod under the tropic influence of norepinephrine, and are released during the dark period when melatonin synthesis is greatest. Melatonin, administered as daily intraperitoneal doses of 50 microgram over a period of five days, was observed to increase markedly the number of pinealocytic granulated vesicles during the light period, but led during the dark period to a decrease in their numbers to levels below that of diluent-treated controls. It may be that melatonin stimulates the synthesis and/or release of granulated vesicles which represent the packaged form of a major secretory product.


Estimating rate of change for nonlinear trajectories in the framework of individual measurement occasions: A new perspective on growth curves.
Researchers are often interested in examining between-individual differences in within-individual processes. If the process under investigation is tracked for a long time, its trajectory may show a certain degree of nonlinearity, so that the rate of change is not constant. A fundamental goal of modeling such nonlinear processes is to estimate model parameters that reflect meaningful aspects of change, including the parameters related to change and other parameters that shed light on substantive hypotheses. However, if the measurement occasion is unstructured, existing models cannot simultaneously estimate these two types of parameters. This article has three goals. First, we view the change over time as the area under the curve (AUC) of the rate of change versus time ([Formula: see text]) graph. Second, using the instantaneous rate of change midway through a time interval to approximate the average rate of change during that interval, we propose a new specification to describe longitudinal processes. In addition to obtaining the individual change-related parameters and other parameters related to specific research questions, the new specification allows for unequally spaced study waves and individual measurement occasions around each wave. Third, we derive the model-based interval-specific change and change from baseline, two common measures to evaluate change over time. We evaluate the proposed specification through a simulation study and a real-world data analysis. We also provide OpenMx and Mplus 8 code for each model with the novel specification.


A 'chemically-gated' photoresponsive compound as a visible detector for organophosphorus nerve agents.
We describe a versatile and convenient visible detection method for organophosphorus compounds based on a colorless 'pro-photoresponsive' organic molecule that undergoes photochemical ring-closing to produce a colored isomer only after it reacts with vapors of the phosphorylating agent.


Significance of ACADM mutations identified through newborn screening of MCAD deficiency in Japan.
Since the first case was detected in 2000, there has been a remarkable increase in Japanese patients diagnosed with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. Genetic analysis has revealed a spectrum of mutations that is quite different from those observed in Caucasian populations. In 2014, Japan initiated nationwide newborn screening (NBS) for MCAD using tandem mass spectrometry (MS/MS). It is an urgent issue to assess the risk of acute metabolic decompensation from the respective novel mutations found thus far. To evaluate the pathogenic effect of each mutation, we established a eukaryotic cell expression system and prepared 11 mutant proteins identified in five symptomatic patients and eight MS/MS-NBS-positive newborns, as well as two common Caucasian mutations, p.K329E (c.985G>A) and p.Y67H (c.157C>T) for comparison. The expression of four mutant proteins (p.Q45R, p.P92L, p.P128X and p.Y397N) were severely impaired, whereas the others expressed normally, as did p.K329E and p.Y67H. Based on their dehydrogenase activities toward n-octanoyl-CoA, we determined three mutations (p.R53C, p.R281S and p.G362E) to be disease-causing, two mutations having (p.R17H and p.M274V) to be of marginal risk, and two mutations (p.K271E and p.I416T) as benign. Their allele-specific activities were as a whole in accordance with those estimated from the results of measurement in peripheral blood mononuclear cells. As most of the mutations detected in the Japanese population are unique, prudent genetic and enzymatic analysis is essential to precisely evaluate the latent risk of clinical onset for screening-positive newborns.


Transjugular intrahepatic portosystemic shunt is associated with significant changes in mitral inflow parameters.
Liver cirrhosis is associated with hyperdynamic circulation which can result in heart failure. Transjugular intrahepatic portosystemic shunt (TIPS) due to increase of cardiac output is a stressful stimulus for cardiovascular system. Therefore, new methods for early detection of heart failure are needed. Transmitral flow is a marker of diastolic dysfunction. To analyze short- and long-term effect of TIPS procedure on transmitral flow. 55 patients (38 men and 17 women, 55.6 ± 8.9 years) with liver cirrhosis treated with TIPS were enrolled in the study. Echocardiography was performed before, 24 h, 7, 30 and 180 days after the procedure. During 6 month follow up 22 patients died. Results. Left ventricle end-diastolic diameter was increasing during the follow-up [baseline: 47 (44.7-51.2) mm, day 7: 50 (46.5-51.3) mm, p < 0.05; day 30: 49.5 (46.7-55.2) mm, p < 0.01; 6 months: 52.5 (48.3-55.2) mm, p < 0.01)]. The peak early filling velocity (E) was significantly increasing [before: 75.5 (60.5-87.3) cm/s, 24 h: 88 (74.3-109.7), p < 0.01; day 7: 89 (81.5-105) p < 0.01; 1 month: 94 (82.7-108.5) p < 0.01; 6 month: 91 (80.1-120.2) p < 0.01]. Peak late atrial filling velocity (A) significantly increased within 24 h after the procedure: 85.1 (76.2-99.5) vs. 91.2 (81.5-104.5) cm/s, p < 0.05. The E/A ratio was increasing during the follow up (baseline: 0.88, 24 h after: 0.89, 1 week: 1.0, 30 days: 1.13, 6 month: 1.06 p < 0.01). Hemodynamic changes following TIPS procedure can be monitored using echocardiography. Transmitral flow analysis can serve as a useful tool for evaluating of diastolic function in these patients.


Analysis of hyponatraemia associated post-operative mortality in 3897 hip fracture patients.
Hyponatraemia is common in hospitalised patients. In recent years the relationship between hyponatraemia and bone metabolism, falls and fractures has become more established. This study evaluates the prevalence of hyponatraemia (plasma sodium<135mmol/l) in 3897 patients undergoing operative treatment for hip fracture and the relationship between hyponatraemia and mortality in these patients. Hyponatraemia was an independent risk factor for increased post-operative mortality on multivariate analysis. Median age at admission was 83 years. Hyponatraemia was present in 19.1% of patients with hip fracture on admission, 29.5% of patients in the first 24h post-operatively and 20% of patients at discharge. There was a significant association between hyponatraemia and time from admission to surgery indicating that patients admitted with hyponatraemia waited longer. The median follow-up time was 863 (range 0-4352) days. There were 2460 deaths (63.1% of the original 3897 patients) prior to the censor date. A total of 1144 patients (29.4% of the original 3897 patients) died within 12 months of discharge. Median time to death for patients with and without hyponatraemia on admission was 34 months (SE 1.7 months) and 41 months (SE 2.5 months) respectively (p=0.003). Median time to death for patients with and without hyponatraemia within 24h post-operatively was 35 months (SE 2.5 months) and 42 months (SE 1.7 months) respectively (p=0.004). Following elimination of other independent variables associated with increased mortality, hyponatraemia on admission was associated with an increased risk of death (adjusted HR 1.15, p=0.005). Post-operative hyponatraemia was also associated with an increased risk of death (adjusted HR 1.15, p=0.006). Trends suggested that hyponatraemia within 48h of discharge was associated with an increased risk of death (adjusted HR 1.15, p=0.636). Hyponatraemia is common in elderly patients with hip fractures both at initial presentation and during admission. In this vulnerable patient group, hyponatraemia may delay time to definitive surgery and is a potentially reversible cause of increased post-operative mortality. Every effort should be made to identify and correct hyponatraemia in hip fracture patients.


Mental status evaluation in older adults with cancer: Development of the Mental Health Index-13.
The Mental Health Index (MHI) is widely used as a measure of mental health status, but has not been evaluated in the geriatric oncology population. This study evaluated the MHI-17 in a geriatric oncology population, to establish validity and scoring rules. The Carolina Senior Registry (NCT01137825) was used to obtain data for 686 patients with cancer 65 and older who completed the MHI-17. The 17-item patient-reported measure produces one total score summing across four domains: anxiety, depression, positive affect, and sense of belonging. Cronbach's alpha (α), confirmatory factor analyses (CFA), item-response theory (IRT) analyses, and differential item functioning (DIF) analyses were used to evaluate internal consistency and validity. The revised MHI retained the 13 best-fitting items from the MHI-17 and resulted in a final model that included two subscales: anxiety (four items, RMSEA 0.11; CFI 0.99; TLI 0.98) and depression (9 items, RMSEA 0.10; CFI 0.96; TL 0.95). IRT analyses of the four anxiety items indicated good fit (RMSEA 0.08) and precise measurement of adults with poor mental health, and the nine depression items also fit well (RMSEA 0.05). No meaningful differences were found by sex, education, or treatment stage. Scores were developed to provide meaningful norms. The new MHI-13 is a shorter, more accurate way to assess mental health in older adults with cancer and most importantly allows clinicians to separately identify anxiety and/or depression - a clinically important distinction as treatment differs among these two types of mental health impairment.


Prolactin awareness: an essential consideration for physical health in schizophrenia.
Elevations in serum prolactin levels (hyperprolactinaemia) are a common side effect of conventional and some atypical antipsychotic treatments. In patients with schizophrenia, the adverse effects of antipsychotic-induced hyperprolactinaemia on physical health (e.g. fertility problems, sexual dysfunction and reduced bone mineral density) are gaining attention. Accumulating evidence shows consistent 'prolactin-raising' effects of conventional antipsychotics and risperidone compared with other current atypical antipsychotics, which are more likely to have 'prolactin-sparing' properties. Prolactin-sparing antipsychotics (for example, aripiprazole and quetiapine) tend to show lower frequencies of hyperprolactinaemia-associated side effects. In recent studies, aripiprazole-treated patients have demonstrated lower prolactin levels compared with patients receiving other prolactin-sparing antipsychotics. There is a lack of robust recommendations for monitoring prolactin elevation among patients receiving antipsychotics. Decreasing the antipsychotic dose or switching to a prolactin-sparing medication are possible management options for antipsychotic-induced hyperprolactinaemia. There is a need to increase awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia.


Labyrinthitis in chronic otitis media.
Labyrinthitis is the most frequent complication of chronic otitis media (COM). Retrospective analysis of 1,210 patients operated due to COM was carried out. Circumscribed labyrinthitis was found in 17.2% and deafness in 1.2% of patients. To evaluate the effect of labyrinthitis on bone conduction (BC) we measured BC threshold in a group of 140 patients with unilateral COM without labyrinthitis and in a group of 42 patients with unilateral COM with labyrinthitis. BC threshold of the healthy ear was subtracted from the BC threshold of the affected ear in the same patient to eliminate presbyacusis. There was no significant difference in bone conduction threshold between the patients with circumscribed labyrinthitis and patients with COM without labyrinthitis. The incidence of labyrinthitis was higher in patients with cholesteatoma than in patients without cholesteatoma. Management of labyrinthine fistula is presented.


Pseudoseptic pseudogout in progressive pseudorheumatoid arthritis of childhood.
Progressive pseudorheumatoid arthritis of childhood is an uncommon arthropathy of unknown aetiology, which is related to spondyloepiphyseal dysplasia tarda. Previous reports have noted the absence of joint inflammation in this disease. An adult is described here with this arthropathy, who developed episodic acute inflammatory arthritis that mimicked septic arthritis, but proved to be pseudogout. The relation between pseudogout and progressive pseudorheumatoid arthritis of childhood is discussed.


[Supportive care for malignant melanoma].
In the systemic therapy of malignant melanoma, many forms of chemotherapy, immunotherapy, polychemotherapy and immunopolychemotherapy are being use. When administering such forms of therapy, optimal supportive care is essential. Important aspects include control of nausea and vomiting, prophylaxis and treatment of bone marrow failure, reducing fatigue and being alert to cutaneous side effects. Specific recommendations for all of these dermato-oncologic problems are provided in detail.


Mutagenic and cytotoxic activities of Limonium globuliferum methanol extracts.
Unmonitored use of plant extractions alone or in combination with drugs may cause important health problems and toxic effects. Limonium (Plumbaginaceae) plants are known as antibacterial, anticancer and antivirus agent. But it is possible that this genus may have toxic effects. This study evaluated the mutagenic and cytotoxic effects of Limonium globuliferum (Boiss. et Heldr.) O. Kuntze (Plumbaginaceae) acetone/methanol (2:1), and methanol extracts of root, stem, and leaf. Different parts of this species were used in order to compare the mutagenic and cytotoxic effects of these parts. Ames test was carried out with S. typhimurium TA98, and TA100 strains. Strains were incubated at 37 °C for 72 h. MDBK cell line was used in MTT test. 10,000, 1000, 100, 10, 1 and 0.1 µg/plate concentrations of plant extracts were used in Ames test. 50, 25, 12.5, 6.25 and 3.125 µg/ml concentrations of root, stem and leaf acetone/methanol (2:1) and methanol extracts were used in MTT test. Ames test results indicated that only methanol leaf extract (10,000 µg/plate) had mutagenic activity. L. globuliferum root methanol extracts (3.125 and 6.25 µg/ml) increased the proliferation rates. Root acetone/methanol (2:1) extracts were found highly cytotoxic in all treatments. The results indicated that leaf extracts had lower cytotoxic effects than root and stem extracts. High concentrations of L. globuliferum stem and leaf methanol extracts showed cytotoxic activity in all treatment periods while low concentrations of the stem methanol extracts increased the proliferation rates.


Further evidence for the presence of a thiazoline ring in the isoleucylcysteine dipeptide intermediate in bacitracin biosynthesis.
Isoleucylcysteine dipeptide, a first intermediate peptide in bacitracin biosynthesis, was liberated from the enzyme protein and oxidized with manganese dioxide in dimethylsulfoxide. The resulting oxidation product was identified by thin-layer chromatography as 2-(2-methyl-l-oxobutyl)-thiazole-4-carboxylic acid which has been isolated from the hydrolysate of bacitracin F. This result shows that the intermediate dipeptide contains a thiazoline ring, and that the thiazoline ring is synthesized at the dipeptide stage in the process of peptide chain elongation in bacitracin biosynthesis. Improbability of non-enzymatic dehydrative cyclization of the dipeptide is discussed.


Hairy cell leukaemia-variant: Disease features and treatment.
Hairy cell leukaemia-variant (HCL-V) is a rare B-cell malignancy that affects elderly males and manifests with splenomegaly, lymphocytosis and cytopenias without monocytopenia. The neoplastic cells have morphological features of prolymphocytes and hairy cells. The immunophenotype is that of a clonal B-cell CD11c and CD103 positive but, unlike classical HCL, CD25, CD123 and CD200 negative. The spleen histology is similar to classical HCL and the pattern of bone marrow infiltration is interstitial and/or intrasinusoidal. Mutations of the immunoglobulin heavy chain (IGVH) are seen in two thirds of cases with a preferential VH4-34 family usage. There is no distinct chromosomal abnormality but del17p13 and mutations of the TP53 gene are frequent. Mutations in the MAP2K1 gene have been documented in half of the cases. The course is chronic with median survivals of 7-9 years. Patients are refractory to purine analogues and the most effective therapy is the combination of 2-chlorodeoxyadenosine and Rituximab.


Bacterial tracheitis: a resurfacing airway emergency.
Children presenting to the emergency department with symptoms of upper respiratory distress represent a diagnostic and therapeutic challenge. An acute onset associated with fever most often indicates epiglottitis or laryngotracheobronchitis. Presented here is a case of acute bacterial tracheitis, a life-threatening entity that apparently has reemerged recently. Prompt recognition is essential but can be difficult. Historical perspectives, clinical features, and pitfalls in diagnosis and management are discussed.


Sequential based analysis of Intima-Media Thickness (IMT) in common carotid artery studies.
Carotid Intima-Media Thickness (IMT) is used widely to assess an individual's risk of myocardial infarction and stroke. Although significant associations have been showed, IMT as used in major studies does not improve prediction of cardiovascular events much compared to traditional risk factors. Therefore, a new approach to IMT-measurements is sought-after by examining the wall structure continuously throughout several heart cycles. Computerized single-image analysis (IA) and sequential analysis (SA) were used to assess latter's capability in predicting risk of cardiovascular disease and to compare both. Healthy subjects (mean+/-S.D., age 46.1+/-5.6 years, n=490) were compared with subjects suffering from confirmed coronary artery disease (CAD) (mean+/-S.D., age 47.3+/-6.2 years, n=51). SA could differentiate between both groups better then single IA, especially when looking at the maximal and mean IMT-values (SA<-->IA, p<0.01<-->p<0.05). The area under the curve (AUC) for maximal and mean IMT was greater for sequences then for single images as well. Due to our findings sequential analysis can offer an extensive and complete examination of the carotid wall with a maximal reduction of bias. Commonly used IA may disguise vascular conditions and therefore the patient's risk, since IMT-values, as proven with SA, seems to usually be higher. Therefore, the need for further studies arises, examining if and to what extend common IMT-studies underestimate differences between groups.


Barnase and barstar: two small proteins to fold and fit together.
Barnase and barstar are the extracellular ribonuclease and its intracellular inhibitor produced by Bacillus amyloliquefaciens. Both are small single-chain proteins and thus are suitable for application to the study of how a protein's sequence directs its fold. Barnase has neither disulfide bonds nor non-peptide components and unfolds reversibly in what closely approximates a two-state reaction. The genes for both these proteins have been cloned in E. coli. Expression of barstar is necessary to counter the lethal effect of expressed active barnase. Site-directed mutagenesis is being used to answer specific and general questions relating to protein folding and protein-protein interaction.


Reduction of free-roaming cat population requires high-intensity neutering in spatial contiguity to mitigate compensatory effects.
When free-roaming in natural areas, the domestic cat (Felis silvestris catus) is ranked high among the most destructive alien species. Near human dwellings, it might pose a risk to humans, impair sanitation, and suffer from poor welfare. Cats' popularity as companion animals complicates their population control. Thus, culling is often replaced by a fertility control method called "trap–neuter–return/release" (TNR), considered more humane. Despite the extensive application of TNR, a long-term controlled study was never performed to test its effectiveness. We present a uniquely designed controlled field experiment for examining TNR effectiveness. The study was performed over a 12-y period, divided into preintervention and mixed- and full-intervention phases, and spanned a 20-km2 urban area. Trends of cat, intact-female, and kitten counts, cat reproduction, and carcass reports were compared among study phases and areas with different neutering intensities. The cat population increased during the first two study phases and did not decline in highly neutered populations, presumably due to cat immigration. Expansion of high-intensity neutering to the entire city in the full-intervention phase (>70% neutering percentage) reversed cat population growth, reaching an annual approximately 7% reduction. This population reduction was limited by a rebound increase in cat reproduction and longevity. We conclude that cat population management by TNR should be performed with high intensity, continuously, and in geographic contiguity to enable population reduction. To enhance management effectiveness and mitigate compensatory effects, we recommend further evaluating an integrated strategy that combines TNR with complementary methods (e.g., vital resource regulation, ill cat euthanasia, and adoption).


Effects of some GABAergic agents on quinine-induced seizures in mice.
The effects of some GABAergic agents on seizures induced by quinine were studied in mice. Muscimol, AOAA, DABA and baclofen significantly protected mice against quinine-induced convulsions. Bicuculline effectively enhanced quinine-induced convulsions, and significantly attenuated the protective effects of muscimol, AOAA and DABA against convulsions induced by quinine. Diazepam and phenobarbitone significantly protected mice against convulsions induced by quinine. However, phenytoin did not affect quinine-induced seizures to any significant degree. These results indicate that the convulsant effect of quinine may be due to a disturbance in the status of the GABAergic system.


Pyrosequencing analysis of bacterial diversity in soils contaminated long-term with PAHs and heavy metals: Implications to bioremediation.
Diversity, distribution and composition of bacterial community of soils contaminated long-term with both polycyclic aromatic hydrocarbons (PAHs) and heavy metals were explored for the first time following 454 pyrosequencing. Strikingly, the complete picture of the Gram positive (+ve) and Gram negative (-ve) bacterial profile obtained in our study illustrates novel postulates that include: (1) Metal-tolerant and PAH-degrading Gram -ves belonging to the class Alphaproteobacteria persist relatively more in the real contaminated sites compared to Gram +ves, (2) Gram +ves are not always resistant to heavy metal toxicity, (3) Stenotrophomonas followed by Burkholderia and Pseudomonas are the dominant genera of PAH degraders with high metabolic activity in long-term contaminated soils, (4) Actinobacteria is the predominant group among the Gram +ves in soils contaminated with high molecular weight PAHs that co-exist with toxic heavy metals like Pb, Cu and Zn, (5) Microbial communities are nutrient-driven in natural environments and (6) Catabolically potential Gram +/-ves with diverse applicability to remediate the real contaminated sites evolve eventually in the historically-polluted soils. Thus, the most promising indigenous Gram +/-ve strains from the long-term contaminated sites with increased catabolic potential, enzymatic activity and metal tolerance need to be harnessed for mixed contaminant cleanups.


Barriers and facilitators to COVID-19 vaccine uptake among Australian health professional students during the pandemic: a nationwide study.
Using a cross-sectional online survey we investigated knowledge, attitudes, and risk perception about COVID-19 vaccination and identified factors influencing vaccine uptake among Australian health professional students from October 2021 to January 2022. We analysed data from 1114 health professional students from 17 Australian universities. Most participants were enrolled in nursing programs (n = 958, 86.8%), and 91.6% (n = 858) of the participants received COVID-19 vaccination. Approximately 27% believed COVID-19 was no more serious than seasonal influenza and that they had a low risk of acquiring COVID-19. Nearly 20% disagreed that COVID-19 vaccines in Australia were safe and perceived they were at higher-risk of acquiring COVID infection than the general population. Higher-risk perception viewing vaccination as their professional responsibility, and vaccine mandate strongly predicted vaccination behaviour. Participants consider COVID-19 information from health professionals, government websites, and World Health Organization as the most trusted information sources. The findings highlight that healthcare decision-makers and university administrators need to monitor students' hesitancy with vaccination to improve students' promotion of the vaccination to the general population.


Gas-chromatographic and mass-spectrometric analysis of the odor of human feces.
Gas-chromatographic and mass-spectrometric analysis of human fecal samples was performed to identify the volatile compounds responsible for fecal odor. The compounds identified with fecal odor were the methyl sulfides methanethiol, dimethyl disulfide, and dimethyl trisulfide. Skatole and indole, the benzopyrrole volatiles believed to be responsible for fecal odor, in fact elaborated a napthalenelike "mothball" odor in the crystalline state as well as after purging from feces. A small amount of hydrogen sulfide gas was also identified in fecal samples. The components responsible for fecal odor are complex and may be influenced by dietary and endogenous contributions. However, the major components are methyl sulfide compounds rather than skatole and indole as is currently believed.


Coagulation inhibitors in pulmonary cancer patients.
Pulmonary cancer patients are known to have an elevated risk to suffer from thromboembolic complications. Because hereditary deficiencies of coagulation inhibitors antithrombin III, protein C and protein S are known to cause thromboembolic events it was the aim of our study to search for acquired alterations of these proteins in pulmonary cancer patients. We could demonstrate antithrombin III and protein C to be within the normal range in patients suffering from pulmonary carcinoma. In contrast, in patients suffering from metastatic pulmonary carcinoma bound protein S was increased, while free protein S was significantly reduced. In some patients the decrease of free protein S was comparable to the diminution observed in hereditary protein S deficient patients. A high positive correlation was observed between C4b-binding protein and bound protein S, indicating C4b-binding protein to be a regulatory protein for the shift from free and anticoagulatory active to bound and anticoagulatory inactive protein S. In conclusion, the decrease of free protein S is one source for thromboembolic complications in pulmonary cancer patients. For interpretation of altered free protein S levels it is useful to measure C4b-binding protein.


The role of prostaglandins in the nociceptive response induced by intraperitoneal injection of zymosan in mice.
Intraperitoneal injection of zymosan (1 mg in 0.5 ml saline) in mice induces a transient writhing response accompanied by the synthesis of small amounts of prostaglandin E2(PGE2, less than 2 ng) and larger amounts of PGI2 (200 ng per mouse), measured as its non-enzymatic breakdown product, 6-keto-PGF1 alpha. Although both centrally-acting analgesics (morphine, clonidine) and prostaglandin biosynthesis inhibitors (aspirin, indomethacin, ibuprofen) blocked the writhing response to intraperitoneal injection of zymosan, only the latter reduced prostaglandin levels in the peritoneal cavity. The writhing response correlated equally well with PGE2 levels and 6-keto-PGF1 alpha levels when data from mice treated with centrally-acting analgesics were excluded. However, intraperitoneal injection of PGI2, but not PGE2, reversed the analgesia induced by indomethacin in zymosan-injected mice. Centrally-acting agents, but not ibuprofen, blocked the ability of PGI2 to reverse the analgesic activity of indomethacin. PGI2 (2 micrograms per mouse), injected intraperitoneally in otherwise untreated mice, induced writhing. These data indicate that PGI2 is the prostaglandin involved in mediation of the writhing response to zymosan and that prostaglandin biosynthesis inhibitors, but not centrally-acting analgesics, exert their analgesic activity by reducing the peritoneal level of PGI2. It is possible that PGI2 may have the ability to stimulate pain receptors directly in the mouse peritoneal cavity, in addition to its previously recognized ability to sensitize pain receptors to other pain-producing stimuli.


An uncertainty principle in chromosome positioning.
Chromosomes are non-randomly positioned in the mammalian interphase nucleus. It is not known how patterns of chromosome positions are established or to what degree spatial arrangements of chromosomes change during the cell cycle, especially during mitosis. Two reports have applied in vivo microscopy to track chromosomes in space and time. The results highlight the inherently imperfect and probabilistic nature of chromosome positioning in the cell nucleus.


Fluoroquinolone-induced liver injury: three new cases and a review of the literature.
Fluoroquinolones are popular and widely used in primary care and hospital settings. Premarketing studies showed a favourable side-effect profile. However, significant morbidity and the need for liver transplantation for acute liver failure have been reported. We reviewed the available data on liver damage linked to fluoroquinolones. A systematic search of case reports on the MEDLINE database encompassing the years 2000-2011 was carried out. Additional references were found by a manual search of the retrieved paper. We also describe three new cases of hepatotoxicity attributable to fluoroquinolones seen at our Unit. Thirty-five cases were retrieved from MEDLINE (51.4% male). According to the RUCAM scale, liver injury was classified as hepatocellular (51.4%), cholestatic (28.6%) or mixed (20.0%). Older age (≥ 65 years) was present in 42.8%. The time between initiation of treatment and hepatic injury ranged from 1 to 39 days (median 8 days). According to the RUCAM score, our cases were classified to be "highly probable" or "probable". Only one patient underwent liver biopsy, which showed the features of liver damage linked to drug exposure. Liver enzymes from all patients return to normal range within 4 weeks of withdrawal. Only one patient showed a renal failure, associated with liver injury, with a need for haemodialysis for 3 weeks. Fluoroquinolones are substantially safe antibiotics. Although fluoroquinolone-related hepatic injury occurs infrequently, its consequences can be severe. Patients should also be cautioned to avoid re-exposure to other members of the fluoroquinolone class.


Subcutaneous late phase responses are augmented during local inhalational tolerance in a murine asthma model.
Acute exposure of sensitized mice to antigen elicits allergic airway disease (AAD) characterized by Th2 cytokine-dependent pulmonary eosinophilia, methacholine hyperresponsiveness and antigen-specific IgE elevation. However, chronic exposure induces a local inhalational tolerance (LIT), with resolution of the airway responses but persistent systemic IgE production. To further determine if systemic immunologic responses were maintained during LIT, we assessed subcutaneous late phase responses to ovalbumin in this model. Sensitized and AAD mice developed small subcutaneous responses to ovalbumin, with footpad thickness increasing to 113.7 and 113.6% of baseline, respectively. In comparison, LIT mice developed marked foot swelling (141.6%). Histologic examination confirmed increased inflammation in the chronic animals, with a significant contribution by eosinophils. Thus, the resolution of airway inflammatory responses with chronic antigen inhalation is a localized response, not associated with loss of systemic responses to antigen.


Current Emergency Department Disposition of Patients With Acute Heart Failure: An Opportunity for Improvement.
Emergency department (ED) providers play a critical role in the stabilization and diagnostic evaluation of patients presenting with acute heart failure (AHF), and EDs are key areas for establishing current best practices and future considerations for the disposition of and decision making for patients with AHF. These elements include accurate risk assessment; response to initial treatment and shared decision making concerning optimal venue of care; reframing of physicians' risk perceptions for patients presenting with AHF; exploration of alternative venues of care beyond hospitalization; population-level changes in demographics, management and outcomes of HF patients; development and testing of data-driven pathways to assist with disposition decisions in the ED; and suggested outcomes for measuring success.


Effect of aliskiren on proteinuria in non-diabetic chronic kidney disease: a double-blind, crossover, randomised, controlled trial.
To evaluate the proteinuria-lowering effect of a renin inhibitor (aliskiren), compared to placebo and to an angiotensin-converting enzyme inhibitor (perindopril), in patients with non-diabetic chronic kidney disease. A randomised, double-blind, crossover trial was performed in 14 patients with nondiabetic chronic kidney disease with 24-h mean proteinuria of 2.01 g (95% CI, 1.36–2.66) and estimated creatinine clearance of 93±6.8 ml/min. The study consisted of five treatment periods. The patients were randomly assigned to receive aliskiren (150 mg), aliskiren (300 mg), perindopril (5 mg), perindopril (10 mg) or placebo. Aliskiren and perindopril reduced proteinuria. These effects were dose-dependent. Furthermore, 24-h proteinuria was reduced by 23% (mean 95% CI; 2–44) by treatment with aliskiren (150 mg), by 36% (95% CI, 17–55; P<0.001) with aliskiren (300 mg), by 7.1% (95% CI, 11–26) with perindopril (5 mg) and by 25% (95% CI, 11–39; P<0.05) with perindopril (10 mg), compared to placebo. No significant difference was found between the effects of aliskiren and perindopril. Aliskiren significantly reduced proteinuria. The antiproteinuric effect is probably similar to that of perindopril, for equivalent hypotensive dosages. The renin inhibitor provides a promising alternative approach for the treatment of patients with chronic proteinuric non-diabetic kidney disease.


Reflexes and neurologists.
Neurologists are particularly concerned with elicitation of reflexes, interpret them as indicative of levels of the nervous system and its development or dissolution. This article reviews selected aspects of reflex action. No longer simply reflexology, clinical neurology will still make new observations about reflexes and, more relevant, clinical neurologists will enjoy the process. The breadth of interests of George Bruyn is a permanent reminder to future neurologists of what complexities can be constructed on basic observations such as have been done on "our" reflexes.


Antimony nanocrystals self-encapsulated within bio-oil derived carbon for ultra-stable sodium storage.
Integrating carbon-coating and nanostructuring has been considered as the most promising strategy to accommodate the dramatic volume expansion represented by high-capacity antimony (Sb) upon sodiation. Suitable coating source and synthetic strategy that are both economical and strong are yet to be explored. In this regard, by using renewable bio-oil as carbon source and self-wrapping precursor, robust Sb@C composite anode with Sb nanoparticles homogeneously impregnated into the cross-linked 2D ultrathin carbon nanosheets is developed via a facile NaCl template-assisted self-assembly and followed carbothermal reduction method. Such judiciously crafted interconnected macroporous framework can mitigate of mechanical stress and alleviate the volume change of inner Sb, guaranteeing high-performance sodium-ion battery anode. At a current density of 0.1 A g-1, ultrahigh reversible capacity of 520 mAh g-1 can be achieved. Notably, a stable capacity of 391 mAh g-1 is even retained after 500 cycles at 1 A g-1. Such a facile and cost-effective synthetic method is promising for high-performance sodium-ion batteries.


The Effects of Opioids on Cognition in Older Adults With Cancer and Chronic Noncancer Pain: A Systematic Review.
Opioids are prescribed to manage moderate-to-severe pain and can be used with older adults; however, they may lead to several adverse effects, including cognitive impairment. To identify, appraise, and synthesize evidence on the impact of opioids on cognition in older adults with cancer/chronic noncancer pain, and screening tools/neuropsychological assessments used to detect opioid-induced cognitive impairment. A systematic literature review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (international prospective register of systematic reviews registration: CRD42018092943). MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library, and Web of Science were searched up to December 2018. Randomized controlled trials, quasi-experimental studies, and observational studies of adults aged 65 years and older with cancer/chronic noncancer pain taking opioids were included. A narrative synthesis was conducted. From 4036 records, 10 met inclusion criteria. Five studies used one screening tool, and five studies used a range of neuropsychological assessments; assessing 14 cognitive domains. Most studies demonstrated no effect of opioid use on cognitive domains, whereas four studies showed mixed effects. In particular, attention, language, orientation, psychomotor function, and verbal working/delayed episodic memory were worsened. Changes to cognitive function were predominantly observed in studies with higher mean doses of opioids (120-190.7mg oral morphine equivalent daily dose). Both improvements and impairments to cognition were observed in studies with higher mean opioid doses. In clinical practice, a brief screening tool assessing attention, language, orientation, psychomotor function, and verbal working/delayed episodic memory may be beneficial to detect worsening cognition in older adults with chronic pain using opioids.


Effective saccharification of lignocellulosic barley straw by mechanocatalytical pretreatment using potassium pyrosulfate as a catalyst.
The catalytic conversion of lignocellulosic biomass is attractive due to the feasible generation of valuable products such as reducing sugars which constitute the basic substrates for chemical and transportation fuel production, as well as the production of renewable hydrogen. This study shows the efficient conversion of lignocellulose, especially hemicellulose, into reducing sugars such as xylose and galactose, by mechanocatalysis using potassium pyrosulfate, K2S2O7, as an effective salt catalyst. Ball milling was performed, introducing a mechanical force which, combined with chemical pretreatment, leads to reducing sugar yields (40%) almost as high as when commonly used sulfuric acid was employed. Kinetic experiments as well as the optimization of the saccharification process are presented.


The natural history of long-term cardiac pacing.
During the past ten years, 504 patients have received one or more pacemakers for complete heart block or other arrhythmia. Of these patients, 306 (61%) are alive. Actuarial analysis shows a steady attrition of 9.4% per year for the first five years, decreasing to 7% per year for the second five years. The overall survival was decreased for patients with congestive heart failure and advanced age and was not affected by the history of Stokes-Adams attacks, initial pulse rate below 50 per minute, or a QRS duration greater than 0.12 second prior to pacing. Cardiac problems were the primary cause of death in 71% of the patients. The natural history of patients with permanent pacemakers depends, more than any other factor, on the function of the left ventricle.


Changes of heavy metal concentrations in farmland soils affected by non-ferrous metal smelting in China: A meta-analysis.
Long-term human smelting activities have resulted in substantial heavy metals (HMs) pollution of farmland soils around smelting sites, and the safety of farmland products is critical for human health. The current study focuses on HMs in farmland soils surrounding a single smelter, therefore the impact of smelting on a national scale needs to be investigated further. This study was based on 116 papers and 1143 sets of relevant data for meta-analysis, and a hierarchical mixed-effects model was used to quantify the changes of HMs concentrations in farmland soils affected by non-ferrous metal smelting on a national scale, as well as their relationships with relevant explanatory variables in China. Results showed that: (i) non-ferrous metal smelting substantially increased farmland soils HMs concentrations (323%), with each HM concentration increasing in the following order: Cd (2753%) > Pb (562%) > Hg (455%) > Zn (228%) > Cu (158%) > As (107%) > Ni (52%); (ii) the highest increase of HMs in vegetable fields (361%), but not significant in comparison to other farmland categories, and the increase of Pb, Zn, Cu and As concentrations were significantly different in different types of smelting areas; (iii) the increase of Hg was significantly higher in the northern region than in the southern region, and the opposite increase of Cu; (iv) the soil depth from 0 to 40 cm was significantly affected by smelting, and the increase of multiple HMs were significantly positively correlated with soil pH and negatively correlated with distance; (v) the other explanatory variables (farmland category and soil organic matter) were not significantly related to the effect of smelting. The results can provide some reference for protecting and restoring farmland soils around smelting areas.


Digital templating without a calibration marker is accurate at predicting implant size for hip hemiarthroplasty.
This study aims to assess the accuracy of digital templating for hip hemiarthroplasty using radiographs without calibration. Two independent, blinded observers retrospectively utilised digital software to template 50 consecutive patients who had hip hemiarthroplasty. The templated parameters (head size, offset and stem size) derived from pre-operative radiographs were compared to the actual prosthetic sizes used intra-operatively. Inter and intra-observer variabilities were calculated. Both observers correctly templated the offset and head size (± 2 mm) used in 90% (n = 45) of cases. The femoral stem size (± 1 size) was correctly predicted by templating in over 84% of the cases (n = 42). Inter-observer agreement was excellent for femoral head size with an intra-class correlation coefficients (ICC) of 0.94, substantial for offset (k = 0.7) but only fair for stem size (k = 0.27). ICC values comparing the actual prostheses inserted with the template values were excellent for head size (ICC = 0.96), substantial to near perfect for offset (k = 0.78, 0.85) and fair to moderate (k = 0.24, 0.45) for stem size. Digital templating of radiographs without calibration can be used to accurately and reliably predict femoral head size and offset at a set magnification of 120%. Femoral stem size, however, is more difficult to template adequately on pre-operative radiographs without calibration.