Frequencies and distribution of kdr and Ace alleles that cause insecticide resistance in house flies in the United States.
House flies (Musca domestica L) are nuisances and vectors of pathogens between and among humans and livestock. Population suppression has been accomplished for decades with pyrethroids and acetylcholinesterase (AChE) inhibitors, but recurrent selection has led to increased frequency of alleles conferring resistance to those two classes of active ingredients (Geden et al., 2021). A common mechanism of resistance to both classes involves an altered target site (mutations in Voltage gated sodium channel (Vgsc) for pyrethroids or in Ace for AChE inhibitors). As part of ongoing efforts to understand the origin, spread and evolution of insecticide resistance alleles in house fly populations, we sampled flies in 11 different US states, sequenced, and then estimated frequencies of the Vgsc and Ace alleles. There was substantial variation in frequencies of the four common knockdown resistance alleles (kdr (L1014F), kdr-his (L1014H), super-kdr (M918T + L10414F) and 1B (T929I + L1014F) across the sampled states. The kdr allele was found in all 11 states and was the most common allele in four of them. The super-kdr allele was detected in only six collections, with the highest frequencies found in the north, northeast and central United States. The kdr-his allele was the most common allele in PA, NC, TN and TX. In addition, a novel super-kdr-like mutation in mutually exclusive exon 17a was found. The overall frequencies of the different Ace alleles, which we name based on the amino acid present at the mutation sites (V260L, A316S, G342A/V and F407Y), varied considerably between states. Five Ace alleles were identified: VAGF, VAVY, VAGY, VAAY and VSAY. Generally, the VSAY allele was the most common in the populations sampled. The susceptible allele (VAGF) was found in all populations, ranging in frequency from 3% (KS) to 41% (GA). Comparisons of these resistance allele frequencies with those previously found suggests a dynamic interaction between the different alleles, in terms of levels of resistance they confer and likely fitness costs they impose in the absence of insecticides.


China: Two steps forward, one step back for new AIDS rights organization.
A new AIDS law centre has been established in China, and continues to operate, despite a pre-Olympics crackdown on AIDS groups by Chinese authorities.


Thymic atrophy via estrogen-induced apoptosis is related to Fas/FasL pathway.
A convincing body of evidence indicates that estrogen has significant immunomodulatory properties, including induction of thymic involution. However, it is unclear whether or not estrogen induces thymic involution by triggering apoptosis depended on Fas-FasL interactions. In the present study, estradiol-17beta (E(2)) was used to treat rats by gavages at 10, 1, 0.1, 0.01, and 0 ng/kg/day, respectively. Atrophy of thymus was determined by in situ morphological examination. Apoptotic cells were identified by terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labeling (TUNEL) assay. A semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method was used to analyze Fas and FasL mRNA levels. The results showed that E(2) induced thymic atrophy, increased the rates of apoptotic death, and enhanced the Fas/FasL mRNA levels. These findings suggested that Fas/FasL-mediated apoptosis involved in the induction of thymic atrophy by E(2).


Plant Phenols as Antibiotic Boosters: In Vitro Interaction of Olive Leaf Phenols with Ampicillin.
The antimicrobial properties of olive leaf extract (OLE) have been well recognized in the Mediterranean traditional medicine. Few studies have investigated the antimicrobial properties of OLE. In this preliminary study, commercial OLE and its major phenolic secondary metabolites were evaluated in vitro for their antimicrobial activities against Escherichia coli and Staphylococcus aureus, both individually and in combination with ampicillin. Besides luteolin 7-O-glucoside, OLE and its major phenolic secondary metabolites were effective against both bacteria, with more activity on S. aureus. In combination with ampicillin, OLE, caffeic acid, verbascoside and oleuropein showed additive effects. Synergistic interaction was observed between ampicillin and hydroxytyrosol. The phenolic composition of OLE and the stability of olive phenols in assay medium were also investigated. While OLE and its phenolic secondary metabolites may not be potent enough as stand-alone antimicrobials, their abilities to boost the activity of co-administered antibiotics constitute an imperative future research area.


[REMEEX® system for the treatment of male urinary stress incontinence: our experience].
We evaluate the effectiveness of REMEEX® (readjustable sling) for the treatment of male urinary stress incontinence (SUI). Between February 2007 and December 2009, 14 male patients with mild to severe SUI were operated with the use of REMEEX® system. The origin of incontinence was radical open prostatectomy (n=9), laparoscopic prostatectomy (n=4) and TUR (n=1). We evaluate postoperatively complications in three groups: intraoperatively, early complications (before 1 month) and late complications (after 1 month). Follow up was done at 1, 3, 6 and 12 months after intervention. The mean age was 68,5 years (range: 62-71). The average follow-up time was 18,6 months (range: 10,1-35,2). The mean of readjustment was 3,7 (range: 1-6). Twelve patients were readjusted during the early period (24-72h after intervention). The mesh was removed in 3 cases (21,4%) owing to infection in one and the others because patients didn't want more system readjustment. There were four (28,5%) intraoperative bladder perforations. The early complication more frequent was acute urinary retention with five cases (35,7%). To the year of follow-up 41,7% of the patients are totally continent (5/12) and 33,3% presents light urinary incontinence (4/12). The REMEEX® system for the treatment of male SUI presents (in our experience) a 75% of good results (continent patients or patients with light urinary incontinence) at the year of follow-up with a high rate of light complications. Readjustment are frequent at the first six months after intervention and it's necessary an intense follow-up. We need more studies that evaluate the long-term efficiency of this system.


A special type of senile plaque, possibly an initial stage.
It is customary to distinguish "primitive", "classic" and "compact" ("burned out") senile plaques in Alzheimer's disease and senile dementia of the Alzheimer type (SDAT). Primitive plaques are characterized by altered neurites without accumulation of amyloid, classic plaques by an amyloid core surrounded by altered neurites and compact plaques by amyloid without pathological neurites. Here we describe a further type of plaque in which no amyloid or obviously altered neurites could be found by light microscopy with appropriate stains. This type of plaque was found mainly in the lateral entorhinal region and could be recognized by a slightly more intense staining and an altered texture of the neuropil in a spherical area having the same size as an early or mature plaque (100-150 microns in diameter). In non-serial paraffin sections (3-4 microns thick), a dark, silver-positive cell measuring 10-12 microns in diameter was found in the center of 49 out of 400 such plaques (about 12%), which is the expected frequency if one assumes that every plaque contains such a cell and measures itself about 125 microns. In fact, the reconstruction of 15 plaques (from four different patients) by means of serial sections demonstrated the presence of a central cell in each of them suggesting that this cell is an essential component of this plaque type. The central cell did not react with antibodies against cells of the mononuclear phagocyte lineage, such as alpha-1-antichymotrypsin, alpha-1-antitrypsin, leucocyte common antigen and lysozyme.(ABSTRACT TRUNCATED AT 250 WORDS)


Ring-opening polymerisation of coordination compounds: a silver(I) network with both ring and polymer components.
The terpyridyl ligand 2,6-C5H3N{C(=O)N(Me)-4-C5H4N}2, 1, combined with silver(I) salts to give the complexes [Ag2(1)2][BF4]2, 2, and [{Ag3(1)2}n][CF3SO3]3n, 3; the network structure of complex contains both macrocyclic units [Ag2(mu-1)2]2+ and ring-opened polymeric units [{Ag(mu-1)}n]n+.


Antioxidant and cytotoxic activities of xanthones from Cudrania tricuspidata.
The new catecholic xanthone, 1,3,7-trihydroxy-4-(1,1-dimethyl-2-propenyl)-5,6-(2,2-dimethylchromeno)-xanthone (1), was isolated from the root bark of Cudrania tricuspidata together with seven known xanthones. The structures were fully characterized by analysis of physical and spectral (UV, IR, mass, and NMR) data. Relationships between the structural characteristics of xanthones and their antioxidant activities (DPPH, superoxide, and hydroxyl radical) were studied. Among the range of catecholic xanthones, 6,7-dihydroxyl xanthones (3-8) exhibited a strong scavenging effect on the DPPH radical. When one of the catecholic hydroxyl groups was protected as in compounds 1 and 2, DPPH radical scavenging activity was markedly decreased (IC(50)>200microM). DPPH activities were consistent with electrochemical response by cyclic voltammetry. Interestingly, compounds (1, 2) which had the weak activities on DPPH, exhibited both potent superoxide and hydroxyl radical scavenging activities. The strong activity on the hydroxyl radical of compounds (1, 2) could be rationalized by their chelating effect with iron (Fe(2+)) due to a redshift of its complex. The catecholic xanthones (3-8), being able to convert quinone methide intermediate, showed potent cytotoxicities against human cancer cell lines (HT-29, HL-60, SK-OV3, AGS, and A549). In particular, compounds 3, 6, and 7 had strong cytotoxic activities against AGS (LD(50)<5microM). DNA fragmentation patterns induced by catecholic xanthones revealed that tumor cell death was due to apoptosis.


Surface-enhanced Raman scattering of picolinamide, nicotinamide, and isonicotinamide: unusual carboxamide deprotonation under adsorption on silver nanoparticles.
Surface-Enhanced Raman Scattering (SERS) of picolinamide, nicotinamide, and isonicotinamide has been studied on silver colloids at pH⩾7. The wavenumbers of the SERS bands assigned to 1; νring and ν(C-X) vibrational modes show important blue-shifts (ca. +50cm(-1)) with respect to the Raman spectra, whereas the Amide III bands undergo red-shifts up to -50cm(-1). We demonstrate that these shifts are originated by the deprotonation of the carboxamide groups which link to the metal through the nitrogen and oxygen atoms of the respective azanion groups. In order to support this conclusion, theoretical DFT force field calculations have been carried out, confirming that the pyridinecarboxamides interact with the metallic surface in their deprotonated forms as benzamide does.


C101, a novel 4-amino-piperidine derivative selectively blocks N-type calcium channels.
N-type Ca2+ channels located on presynaptic nerve terminals regulate neurotransmitter release, including that from the spinal terminations of primary afferent nociceptors. Pharmacological and ion-channel gene knockdown approaches in animals have revealed N-type Ca2+ channels to be particularly attractive molecular targets for the discovery and development of new analgesic drugs. In recent years, some non-peptide small molecular N-type Ca2+ channel blockers have been reported. However, low selectivity and some side effects limit their further development. To overcome these disadvantages, some new compounds were designed and synthesized in our institute by optimizing the 4-amino-piperidine template. C101, one of these compounds, was demonstrated to block N-type Ca2+ channels with higher selectivity. It was found that C101 produced concentration-dependent inhibition on N-type Ca2+ channels expressed in Xenopus oocytes with an IC50 is 2.2+/-0.6 microM. The current-voltage relationship was not altered after 2-min exposure to C101. However, the steady-state inactivation relationship curve was shifted to more negative potentials for channels. Therefore, it seemed that C101 blocks the inactivated channel. C101 did not present any remarkable effects on voltage-gated potassium, sodium channels in cultured rat hippocampal neurons, and L-, P/Q-, R-type calcium channels and HERG channels expressed in Xenopus oocytes. The results suggested that C101 was a high selective blocker targeting N-type Ca2+ channels, and may have a potential to be developed as a novel analgesic agent.


Benefits of exercise training in patients on continuous ambulatory peritoneal dialysis.
We examined the effects of a 12-week exercise program on the exercise tolerance, blood biochemistry, blood pressure (BP) control, cardiac function, and quality-of-life (QOL) scores in 13 patients undergoing continuous ambulatory peritoneal dialysis (CAPD; six men, seven women; mean age, 46.5+/-12.8 years; mean duration on dialysis, 4.8+/-3.8 years). The patients underwent exercise training on treadmill, bike, and arm ergometers thrice weekly. Seven CAPD patients matched for age, sex, and duration on dialysis served as controls. The mean peak aerobic capacity (VO2peak) of the exercisers increased by 16.2% after training (pre- and postexercise, 17.2+/-5.2 v 20.0+/-6.4 mL/kg/min; P=0.004). Although there were no significant changes in serum urea, creatinine, albumin, and hematocrit levels; left ventricular diastolic/systolic diameters; and ejection fraction, an increasing trend of high-density lipoproteins (HDLs) was observed in the exercisers (baseline v postexercise, 33+/-11 v 40+/-14 mg/dL; P=0.06). Twenty-four-hour ambulatory BP monitoring showed a significant increase in daytime systolic BP in the exercisers (pre- and postexercise, 142+/-26 v 157+/-22 mm Hg; P=0.003), but no significant changes could be found in the ambulatory daytime diastolic BP, nocturnal BP, and resting clinic BP. The patients' QOL improved after training, with better scores in two Kidney Disease Quality of Life scales (KDQOL): burden of kidney disease and physical functioning. Two mild and uncomplicated hypotensive episodes were reported in two patients immediately after training. No changes occurred in exercise capacity, blood biochemistry, BP profile, and QOL scores in the controls. We conclude that structured aerobic exercise is safe and can improve the exercise tolerance and QOL outcomes in CAPD patients.


Browning deficiency and low mobilization of fatty acids in gonadal white adipose tissue leads to decreased cold-tolerance of transglutaminase 2 knock-out mice.
During cold-exposure 'beige' adipocytes with increased mitochondrial content are activated in white adipose tissue (WAT). These cells, similarly to brown adipose tissue (BAT), dissipate stored chemical energy in the form of heat with the help of uncoupling protein 1 (UCP1). We investigated the effect of tissue transglutaminase (TG2) ablation on the function of ATs in mice. Although TG2+/+ and TG2-/- mice had the same amount of WAT and BAT, we found that TG2+/+ animals could tolerate acute cold exposure for 4h, whereas TG2-/- mice only for 3h. Both TG2-/- and TG2+/+ animals used up half of the triacylglycerol content of subcutaneous WAT (SCAT) after 3h treatment; however, TG2-/- mice still possessed markedly whiter and higher amount of gonadal WAT (GONAT) as reflected in the larger size of adipocytes and lower free fatty acid levels in serum. Furthermore, lower expression of 'beige' marker genes such as UCP1, TBX1 and TNFRFS9 was observed after cold exposure in GONAT of TG2-/- mice, paralleled with a lower level of UCP1 protein and a decreased mitochondrial content. The detected changes in gene expression of Resistin and Adiponectin did not provoke glucose intolerance in the investigated TG2-/- mice, and TG2 deletion did not influence adrenaline, noradrenaline, glucagon and insulin production. Our data suggest that TG2 has a tissue-specific role in GONAT function and browning, which becomes apparent under acute cold exposure.


Clinical value of vasodilator test with inhaled nitric oxide for predicting long-term response to oral vasodilators in pulmonary hypertension.
Acute vasodilator tests with prostacyclin (PGI2) or inhaled nitric oxide (iNO) are used to select patients with pulmonary arterial hypertension (PAH) who should be treated with oral vasodilators. The haemodynamic effects of PGI2 and iNO are different, and the limits for considering a vasodilator response as significant are controversial. The study was aimed to investigate the diagnostic performance of acute vasodilator testing with iNO and PGI2 in predicting the clinical outcome after 1 year treatment with oral vasodilators. Twenty-seven patients with severe PAH were studied. Nineteen patients were treated with oral vasodilators and their outcome after 1 year was qualified as favourable or unfavourable. The diagnostic performance of vasodilator tests in predicting this outcome was evaluated using receiver operating characteristics (ROC) curves. The acute effects of iNO and PGI2 on pulmonary artery pressure (PAP) were similar. By contrast, PGI2 produced more marked changes on cardiac output and pulmonary vascular resistance than iNO (P<0.05). The evolution at 1 year was favourable in 11 patients and unfavourable in 8. Patients with favourable evolution showed greater decrease of PAP with iNO than with PGI2 (P<0.05). The decrease of PAP with iNO had the greatest predictive value on the clinical outcome (area under ROC curve, 0.83). We conclude that in patients with PAH, acute vasodilator testing with iNO is preferable to PGI2 because it reflects more consistently the changes in pulmonary vascular tone. The acute decrease of PAP with iNO is the best predictor of the long-term response to oral vasodilator treatment.


The effect of family-centered empowerment model on burden of care in parents and blood glucose level of children with type I diabetes family empowerment on burden of care and HbA1C.
Parents play a critical role in caring for their children with diabetes and bear a significant burden of care. Health education has increasingly focused on empowering parents through new strategic methods. The present study aims to investigate the impact of a family-centered empowerment model on the burden of care in parents and blood glucose levels of children with type I diabetes. An interventional study was conducted in Kerman, Iran, where 100 children with type I diabetes and their parents were randomly selected as participants. The study aimed to implement a family-centered empowerment model in the intervention group, which consisted of four stages (educational phase, increasing self-efficacy, improving self-confidence, and evaluation) over a period of one month. The control group received routine training. The Zarit Caregiver Burden questionnaire and HbA1c log sheet were utilized to evaluate the effectiveness of the intervention. Questionnaires were administered before, after, and two months post-intervention, and data were analyzed using SPSS 15. Non-parametric tests were employed, and statistical significance was set at p < 0.05. Before the study, no significant differences in demographic variables, level of burden of care, or HbA1C levels were observed between the two groups (p < 0.05). After the intervention, the burden of care score in the intervention group was significantly lower than that in the control group, both immediately post-intervention and two months later (P < 0.0001). Additionally, the median HbA1C levels in the intervention group were significantly lower than those in the control group after two months (6.5 in the intervention group and 9 in the control group) (P < 0.0001). The findings of this study suggest that the implementation of a family-centered empowerment model is an effective strategy for reducing the burden of care on parents of children with type 1 diabetes and for controlling the HbA1C levels of these children. Based on these results, it is recommended that healthcare professionals consider incorporating this approach into their educational interventions.


B-cell targeting agents in the treatment of multiple sclerosis.
The aims of this article are to discuss the potential role of B lymphocytes in the pathogenesis of multiple sclerosis (MS) and in the mechanisms of action of approved and emerging disease modifying therapies. Over the last few years, significant progress has been made in the introduction of novel pharmacologic treatments that reduce the frequency of clinical exacerbations and radiological lesion formation in relapsing remitting MS. The mechanisms of action of a number of these disease modifying therapies (DMT) implicate B cells in the pathogenesis, as well as in the regulation, of MS. Further research into B-cell subset trafficking patterns, functional activities and interactions with other immune cells in the context of neuroinflammation is likely to inform the development of future generations of DMT.


[Fatty acid binding protein (FABP)].
Although FABPs have been extensively investigated, their function is not finally established. Based upon their tissue expression, binding affinities, regulation, in vitro effects on fatty acid transfer and upon enzymes, it has been postulated that these proteins play an important role in the transport and metabolism of long-chain fatty acid.


Prospective cohort study by InspECT on safety and efficacy of electrochemotherapy for cutaneous tumors and metastases depending on ulceration.
Electrochemotherapy (ECT) is an effective local treatment for cutaneous tumors. The aim of this study was to compare the effectiveness of ECT in ulcerated vs. non-ulcerated tumors and investigate the effect on tumor-associated symptoms. Twenty cancer centers in the International Network for Sharing Practices on Electrochemotherapy (InspECT) prospectively collected data. ECT was performed following ESOPE protocol. Response was evaluated by lesion size development. Pain, symptoms, performance status (ECOG-Index) and health status (EQ-5D questionnaire) were evaluated. 716 patients with ulcerated (n = 302) and non-ulcerated (n = 414) cutaneous tumors and metastases were included (minimum follow-up of 45 days). Non-ulcerated lesions responded to ECT better than ulcerated lesions (complete response 65 % vs. 51 %, p = 0.0061). Only 38 % (115/302) with ulcerated lesions before ECT presented with ulcerated lesions at final follow-up. Patients with ulcerated lesions reported higher pain and more severe symptoms compared to non-ulcerated lesions, which significantly and continuously improved following ECT. In non-ulcerated lesions however, pain spiked during the treatment. No serious adverse events were reported. ECT is a safe and effective local treatment for cutaneous tumors. While ECT improves symptoms especially in patients with ulcerated lesions, data suggest the implementation of a perioperative pain management in non-ulcerated lesions during ECT.


[Single instillation of epirubicin for the prophylaxis of recurrent primary superficial bladder carcinoma].
To determine the feasibility of single dose intravesical epirubicin in the prevention of recurrent superficial bladder carcinoma. We compared the effect of intravesical epirubicin or mitomycin C on tumor recurrence and disease free interval and their side effects after treatment of superficial bladder tumor. 47 postoperative patients with stages Ta to T1 primary superficial bladder carcinoma of grades 1 or 2 were randomized into groups A: single 80 mg epirubicin; B: 40 mg consecutive epirubicin; C: 40 mg consecutive mitomycin C. Patients were followed up for clinical, analytical, and cystoscopic evaluations every 3 months. The disease free intervals of the three groups were found no significant differences (F = 3.25, P > 0.05). The recurrence rate was 6.25% (1/16), 13.3% (2/15), 12.5% (2/16) (chi(2) = 0.496, P > 0.05) in groups A, B, and C at 1 year, and 33.3% (5/15), 26.7% (4/15), 25% (4/16) (chi(2) = 0.290, P > 0.05) at 3 years after operation, respectively. Side effects of group A (13.3%) were lower than those of group B (46.7%) or C (43.8%) (chi(2) = 14.56, P < 0.01). Single dose of epirubicin given intravesically immediately after tumor resection is effective in preventing tumor recurrence.


Conformational stability of bovine holo and apo adrenodoxin--a scanning calorimetric study.
Holo and apo adrenodoxin were studied by differential scanning calorimetry, absorption spectroscopy, limited proteolysis, and size-exclusion chromatography. To determine the conformational stability of adrenodoxin, a method was found that prevents the irreversible destruction of the iron-sulfur center. The approach makes use of a buffer solution that contains sodium sulfide and mercaptoethanol. The thermal transition of adrenodoxin takes place at Ttrs = 46-57 degrees C, depending on the Na2S concentration with a denaturation enthalpy of delta H = 300-380 kJ/mol. From delta H versus Ttrs a heat capacity change was determined as delta Cp = 7.5 +/- 1.2 kJ/mol/K. The apo protein is less stable than the holo protein as judged by the lower denaturation enthalpy (delta H = 93 +/- 14 kJ/mol at Ttrs = 37.4 +/- 3.3 degrees C) and the higher proteolytic susceptibility. The importance of the iron-sulfur cluster for the conformational stability of adrenodoxin and some conditions for refolding of the thermally denatured protein are discussed.


Identification of Novel Prognostic Long Non-coding RNAs in Lung Adenocarcinoma Using WGCNA Analysis.
Long non-coding RNAs play crucial role in the tumorigenesis of lung adenocarcinoma (LUAD). However, the function of a large number of lncRNAs in LUAD has not been investigated yet. Weighted gene correlation network analysis (WGCNA) was applied to construct the co-expression module in the TCGA-LUAD cohort. Protein-protein interaction (PPI) network was used to explore the relationship of genes in the key module. The function of the key module on the prognosis in LUAD was analyzed using GO and KEGG analysis. Finally, we constructed the mRNA-lncRNA co-expression network in the key module to identify the hub lncRNAs that play crucial role in the prognosis in LUAD. The most highly expressed 2500 mRNAs and 2500 lncRNAs in the TCGA-LUAD cohort were clustered into 21 modules. After analyzing the correlation between the module and prognostic clinical traits, the Tan module, consisting of 130 genes, was selected as the key module on the prognosis in LUAD. And then, we found that genes in the key module were majorly enriched in ten multiple signaling pathways. Subsequently, we constructed the mRNA-lncRNA co-expression network based on the genes in the key module. Finally, we identified three lncRNAs and nineteen mRNAs that could be the promising prognostic biomarkers for LUAD. We identified three lncRNAs (MIR99AHG, ADAMTS9-AS2, and AC037459.2) and nineteen mRNAs as potential prognostic biomarkers in LUAD, which provided new insight for prognosis monitoring and therapy development in LUAD.


[The environment and health protection of the child].
The authors outline the relationship between environment and children health care. They describe the environmental situations able to produce damages to the children's health.


Resolving controversies on the path to Alzheimer's therapeutics.
Alzheimer's disease constitutes a personal and societal tragedy of immense proportions. Since 1960, research in laboratories and clinics worldwide has elucidated many features of this insidious and ultimately fatal syndrome, and this progress has led to initial human trials of potentially disease-modifying agents. However, some of these agents have already failed. Gnawing controversies and important gaps in our knowledge seem to cast additional doubt on the ability of the field to move forward effectively. Here I discuss some of these looming concerns and offer possible explanations for the major trial failures that suggest they are not predictive of the future. Rigorous preclinical validation of mechanism-based therapeutic agents followed by meticulously designed trials that focus on the cardinal cognitive symptoms and their associated biomarkers in the mild or presymptomatic phases of Alzheimer's disease are likely to lead to success, perhaps in the not-too-distant future.


Efficacy and tolerability of atenolol, nifedipine and their combination in the management of hypertension.
This randomised, double-blind, crossover study investigated the haemodynamic effects of a beta-blocker (atenolol 50mg) and a calcium antagonist (sustained release nifedipine 20mg) given either separately or in combination in 3 groups of patients with mild to moderate essential hypertension. Each treatment was administered twice daily. The fixed combination given twice daily for 4 weeks produced reductions in blood pressure which lasted for at least 12 hours after administration of the final dose. The control of blood pressure by the combination was superior to that achieved by its individual components. Side effects normally associated with nifedipine therapy were less frequent when it was administered with atenolol. Compliance with treatment was good, but it was best when the drugs were given together rather than separately. A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.


Isolate antibody to hepatitis C virus core antigen (C22) by RIBA-2: correlation with HCV-RNA and anti-NS5.
The presence of circulating hepatitis C virus genome (HCV-RNA), elevated ALT levels and antibodies to an NS5-derived synthetic peptide have been examined in 13 subjects with isolate positivity for antibodies to the HCV core antigen (C22) on RIBA-2 testing. All subjects were followed up for 8-18 months (mean 12.4 months). In seven subjects (54%), intermittent or persistent viremia was associated with abnormal ALT levels (6 subjects) and with positivity for antibodies to NS5-peptide (6 subjects). On the other hand, in 6 out of 13 subjects (46%) no viral replication, no liver cytonecrosis and no antibodies to NS5 were found. It is concluded that isolate reactivity to C22 by RIBA-2 is a heterogeneous condition that corresponds to two distinct categories of subjects: those with active HCV infection and those without evidence of virus replication. Although HCV-RNA determination is the most reliable means of identifying HCV carriers, antibodies to NS5 can be a useful marker of virus activity. In fact, antibodies to NS5 were detected in 6 out of 7 viremic patients, compared to 0 out of 6 non-viremic patients (P = 0.004). It remains to be elucidated whether the isolate reactivity to core antigen found in non-viremic subjects represents a specific, HCV-induced antibody response, or is an unrelated crossreactivity.


[Current situation on fertility preservation in cancer patients in Spain: Level of knowledge, information, and professional involvement].
The estimated risks of infertility in childhood cancer due to radiation, chemotherapy and surgery are well known. The involvement of professionals and advances in the different methods of preservation are increasing. However, many patients do not receive information or perform any method of preservation. Questionnaires to paediatric onco-haematology institutions throughout Spain. The questionnaire consisted of 22 questions assessing their usual practices and knowledge about fertility preservation. Fifty members of the Spanish Society of Paediatric Haematology and Oncology, representing 24 of 43 centres, responded. These represented 82% of centres that treated higher numbers of patients. The effect of treatment on fertility was known by 78% of those who responded, with 76% admitting not knowing any guideline on fertility in children or adolescents. As for the ideal time and place to inform the patient and/or family, only 14% thought it should be done in the same cancer diagnosis interview. In clinical practice, 12% of those surveyed never referred patients to Human Reproduction Units, another 12% only did so if the patients showed interest, and 38% only refer patients in puberty. Just over one-third (34%) of those referrals were going to receive highly gonadotoxic treatment. There are clear differences between pre-puberty and puberty patients. The frequency with which some method of fertility preservation is performed in patients is low. All respondents believe that the existence of national guidelines on the matter would be of interest.


Ovarian function during use of a levonorgestrel-releasing IUD.
Ovarian function was studied for two complete menstrual cycles in 9 regularly menstruating women and for 8 weeks in three amenorrhoeic women who had used levonorgestrel-releasing IUDs (LNG-IUD) for more than four years. Nine patients using copper IUDs (Nova-T) were studied for two complete menstrual cycles as controls. According to progesterone levels, 15/17 cycles in women using LNG-IUDs were ovulatory, whereas only 8/17 cycles showed normal follicular growth and rupture as judged by ultrasound. In ovulatory cycles, the peak progesterone levels were lower than in the controls. The preovulatory estradiol and LH peak levels were also lower than in control subjects. SHBG levels were lower in LNG-IUD users than in copper IUD users. It is concluded that, although the dose of levonorgestrel released from the IUD is very low, it probably exerts an effect on the gonadotrophin secretion, which disturbs follicular development in many of the women studied, which in addition to the local effect on the endometrium, contributes to its high contraceptive efficacy.


[Tocilizumab].
IL-6 plays a pivotal role in the pathogenesis of RA. Tocilizumab (TCZ) is a humanized monoclonal antibody to IL-6 receptor, and is now the only biological agent targeting IL-6. The main indication of TCZ for RA patients is those who has been resistant to DMARDs including MTX. TCZ may be also effective for anti-TNF therapy resistant RA. In addition, TCZ can be used effectively as monotherapy. The following screening tests for opportunistic infections should be done before starting TCZ; chest X-ray and tuberculin test or interferon-gamma releasing assay for detecting latent tuberculosis, HBs antigen and HBc antibody for detecting HBV carrier, beta-D-glucan for screening fungal and pneumocystis infection, etc. After starting TCZ, we should be careful for symptoms and signs of infections and allergic reactions, and monitor white blood cell count, liver funtion test and serum lipds.


Structure of an abnormal messenger RNA for argininosuccinate synthetase in citrullinemia.
The structural abnormality of mRNA for argininosuccinate synthetase (ASS) and the structure of immune cross-reactive material for ASS (ASS-CRM) in the liver of a patient with type III citrullinemia were analyzed using dot and Northern blot hybridization, S1 nuclease analysis, and a sensitive enzyme-linked immunosorbent assay. The patient's liver contained no detectable ASS activity, the ASS-CRM content was about 0.5% of that in the control and the ASS mRNA content was almost normal. The ASS mRNA of the case was found to have an apparent structural abnormality; approximately 1.57 kb in length caused by a defect of about 0.1 kb near the 3' end of the coding region. Furthermore, gel filtration analysis revealed that the ASS-CRM had a molecular weight indistinguishable from the control ASS. These results indicate that the abnormal mRNA of the patient was translated in vivo to an immune-cross-reactive protein that was able to form a quaternary structure.


A novel COL1A1 mutation in a family with osteogenesis imperfecta associated with phenotypic variabilities.
Osteogenesis imperfecta (OI) is a heterogeneous disorder that is characterized by bone fragility and systemic complications, and is mainly caused by gene mutations in COL1A1 or COL1A2. A novel COL1A1 splicing mutation, c.750+2T>A, was identified in a Japanese OI family. Only the proband in this family showed various complications, such as heart valve diseases and severe scoliosis. The clinical heterogeneity in the family is discussed in this study.


Reconstitution of testosterone oxidation by purified rat cytochrome P450p (IIIA1).
Cytochrome P450p (IIIA1) has been purified from rat liver microsomes by several investigators, but in all cases the purified protein, in contrast to other P450 enzymes, has not been catalytically active when reconstituted with NADPH-cytochrome P450 reductase and dilauroylphosphatidylcholine. We now report the successful reconstitution of testosterone oxidation by cytochrome P450p, which was purified from liver microsomes from troleandomycin-treated rats. The rate of testosterone oxidation was greatest when purified cytochrome P450p (50 pmol/ml) was reconstituted with a fivefold molar excess of NADPH-cytochrome P450 reductase, an equimolar amount of cytochrome b5, 200 micrograms/ml of a chloroform/methanol extract of microsomal lipid (which could not be substituted with dilauroylphosphatidylcholine), and the nonionic detergent, Emulgen 911 (50 micrograms/ml). Testosterone oxidation by cytochrome P450p was optimal at 200 mM potassium phosphate, pH 7.25. In addition to their final concentration, the order of addition of these components was found to influence the catalytic activity of cytochrome P450p. Under these experimental conditions, purified cytochrome P450p converted testosterone to four major and four minor metabolites at an overall rate of 18 nmol/nmol P450p/min (which is comparable to the rate of testosterone oxidation catalyzed by other purified forms of rat liver cytochrome P450). The four major metabolites were 6 beta-hydroxytestosterone (51%), 2 beta-hydroxytestosterone (18%), 15 beta-hydroxytestosterone (11%) and 6-dehydrotestosterone (10%). The four minor metabolites were 18-hydroxytestosterone (3%), 1 beta-hydroxytestosterone (3%), 16 beta-hydroxytestosterone (2%), and androstenedione (2%). With the exception of 16 beta-hydroxytestosterone and androstenedione, the conversion of testosterone to each of these metabolites was inhibited greater than 85% when liver microsomes from various sources were incubated with rabbit polyclonal antibody against cytochrome P450p. This antibody, which recognized two electrophoretically distinct proteins in liver microsomes from troleandomycin-treated rats, did not inhibit testosterone oxidation by cytochromes P450a, P450b, P450h, or P450m. The catalytic turnover of microsomal cytochrome P450p was estimated from the increase in testosterone oxidation and the apparent increase in cytochrome P450 concentration following treatment of liver microsomes from troleandomycin- or erythromycin-induced rats with potassium ferricyanide (which dissociates the cytochrome P450p-inducer complex). Based on this estimate, the catalytic turnover values for purified, reconstituted cytochrome P450p were 4.2 to 4.6 times greater than the rate catalyzed by microsomal cytochrome P450p.


Quantitative assessment of neuromotor function in workers with current low exposure to mercury vapor.
Evaluation of neuromotor function has been used in several epidemiological studies of workers with long-term exposure to mercury vapor (Hg 0). Some recent studies indicate adverse effects at relatively low exposure levels. In the present study, we used sensitive quantitative methods, developed specifically to detect subtle effects of exposure to toxins on motor function. After exclusion of individuals with neurological diseases or other conditions that may affect performance, 43 chloralkali workers with current low exposure to Hg 0, and 22 age-matched referents remained for further analysis. The median urinary mercury concentration in exposed workers was 5.9 microg/g (range 1.3-25) creatinine (microg/gC), while that in referents was 0.7 microg/gC (range 0.2-4.1). The mean exposure time was 15 years, and the median cumulative mercury index was 161 years x microg/gC in exposed workers. A eurythmokinesimeter (EKM) was used to quantify eye-hand coordination, and a diadochokinesimeter, to measure rapid alternating rotation of the forearms. In general, the differences in performance between the exposed workers and the referents were small. Age was associated with a decrease in speed, more tremor, and longer contact duration between the stylus and the metal targets in performance of rapid pointing movements. Smokers had significantly more tremor, and more contacts per event in the EKM test, than nonsmokers. Taking age, shift work, and smoking habits into account, no significant associations with current or cumulative mercury exposure were found for the majority of the outcome variables from the quantitative tests. In general, this study indicates no significant adverse effects of Hg 0 on neuromotor function at the exposure levels studied.


Association of male factors with recurrent pregnancy loss.
The role of male factors in recurrent pregnancy loss (RPL) is receiving increased attention since sperm quantity and quality, male genetic mutations, as well as epigenetic modifications, have all been associated with RPL. A growing number of studies have been published on the relationship between male factors and RPL; however, these reports are limited due to small sample sizes, inconsistent inclusion criteria, and detection methods. Herein, we investigate the effects of several male factors on RPL from a genetic and non-genetic perspective to aid clinicians in determining the etiology and optimal treatment strategy for patients with RPL.


Endothelialization and the bioactivity of Ca-P coatings of different Ca/P stoichiometry electrodeposited on the Nitinol superelastic alloy.
An alternative approach to improve the cardiovascular stents with less restenosis than drug eluting stents, involves an improvement in endothelialization of implants. In this study, the bio compatibility of the modified Ti-50.9 Ni alloy was investigated. At the first step, a thermo-chemical surface modification process was used to control the Ni release of the alloy. XPS and Raman analysis revealed that the surface of the alloy contains titanium dioxide after the modification process. According to the Ni release test, this surface condition has a good durability in Ringer's solution and offers a standard range to the leached Ni. At the next step, porous Ca-P films were electrodeposited on the modified surface. The results of endothelial cell culture on the coated samples revealed that the Ca-P coating, which has the highest value of Ca/P ratio shows the best result. The coating revealed a moderately wettable surface with a water contact angle of 53.3°. According to Ca content analysis of the cell culture medium, this coating has the lowest amount of Ca as a result of minimum solubility of the coating. In the other Ca-P coatings with lower Ca/P ratios, the solubility of coatings results in the detachment of the cells. Also nano-indentation and SEM studies revealed that the low stiffness in the calcium deficient coating can result in the failure of the coating as a result of the tensions created by the cells.


Sphingosine-1-phosphate signaling: unraveling its role as a drug target against infectious diseases.
Sphingosine-1-phosphate (S1P) signaling is reported in variety of cell types, including immune, endothelial and cancerous cells. It is emerging as a crucial regulator of cellular processes, such as apoptosis, cell proliferation, migration, differentiation and so on. This signaling pathway is initiated by the intracellular production and secretion of S1P through a cascade of enzymatic reactions. Binding of S1P to different S1P receptors (S1PRs) activates different downstream signaling pathways that regulate the cellular functions differentially depending upon the cell type. An accumulating body of evidence suggests that S1P metabolism and signaling is often impaired during infectious diseases; thus, its manipulation might be helpful in the treatment of such diseases. In this review, we summarize recent advances in our understanding of the S1P signaling pathway and its candidature as a novel drug target against infectious diseases.


Ivacaftor restores delayed mucociliary transport caused by Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator dysfunction in rabbit nasal epithelia.
Abnormal chloride (Cl- ) transport dehydrates airway surface liquid (ASL) in sinonasal epithelium leading to mucus stasis and chronic rhinosinusitis. As an experimental epithelium, rabbit tissue provides an excellent representation of human sinus disease, and the rabbit sinusitis model is both established and well suited for therapeutic interventions in vivo. Our objective in this study was to evaluate whether ivacaftor reverses the consequences of Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Rabbit nasal cavities were assessed for responsiveness to ivacaftor in vivo (by nasal potential difference [NPD] assay). Rabbit nasal epithelial (RNE) cultures were incubated with an ultrafiltrate of P aeruginosa (PAO1 strain) for 4 hours and tested for acquired CFTR dysfunction. Markers of mucociliary function, including airway surface liquid depth (ASL), periciliary liquid depth (PCL), ciliary beat frequency (CBF), and mucociliary transport (MCT), were measured by micro-optical coherence tomography (μOCT) after PAO1 and/or ivacaftor incubation. Ivacaftor resulted in a significant mean NPD polarization of 21.8 ± 2.1 mV, which was significantly greater than that seen in the low Cl- control (12.9 ± 1.3; p = 0.01). PAO1 exposure induced a state of acquired CFTR dysfunction in rabbit nasal epithelium as measured by forskolin-stimulated short-circuit current (ISC ) (control, 37.0 ± 1.1 μA/cm2 ; PAO1, 24.4 ± 1.1 μA/cm2 ; p < 0.001). RNE cultures exposed to PAO1 had inhibited mucociliary function, whereas coincubation with ivacaftor restored mucociliary clearance, as measured by μOCT. In rabbit nasal epithelium, ivacaftor robustly stimulates CFTR-mediated Cl- secretion and normalizes ASL and CBF in PAO1-induced acquired CFTR dysfunction. Preclinical testing of CFTR potentiators as therapy for P aeruginosa rabbit sinusitis is planned.


Polymorphism of delta-aminolevulinic acid dehydratase in Basque populations.
Human red cell delta-aminolevulinic acid dehydratase (ALADH; EC 126.96.36.199) polymorphism was studied in three population samples of the Basque Country. The frequency of the ALADH2 was around 0.08 and similar to that in other European countries.


Spirulina supplementation in a mouse model of diet-induced liver fibrosis reduced the pro-inflammatory response of splenocytes.
Treatment of liver fibrosis is very limited as there is currently no effective anti-fibrotic therapy. Spirulina platensis (SP) is a blue-green alga that is widely supplemented in healthy foods. The objective of this study was to determine whether SP supplementation can prevent obesity-induced liver fibrosis in vivo. Male C57BL/6J mice were randomly assigned to a low-fat or a high-fat (HF)/high-sucrose/high-cholesterol diet or an HF diet supplemented with 2·5 % SP (w/w) (HF/SP) for 16 or 20 weeks. There were no significant differences in body weight, activity, energy expenditure, serum lipids or glucose tolerance between mice on HF and HF/SP diets. However, plasma alanine aminotransferase level was significantly reduced by SP at 16 weeks. Expression of fibrotic markers and trichrome stains showed no differences between HF and HF/SP. Splenocytes isolated from HF/SP fed mice had lower inflammatory gene expression and cytokine secretion compared with splenocytes from HF-fed mice. SP supplementation did not attenuate HF-induced liver fibrosis. However, the expression and secretion of inflammatory genes in splenocytes were significantly reduced by SP supplementation, demonstrating the anti-inflammatory effects of SP in vivo. Although SP did not show appreciable effect on the prevention of liver fibrosis in this mouse model, it may be beneficial for other inflammatory conditions.


Cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine versus single screening and treatment for the control of malaria in pregnancy in Papua, Indonesia: a provider perspective analysis from a cluster-randomised trial.
Malaria infection during pregnancy is associated with serious adverse maternal and birth outcomes. A randomised controlled trial in Papua, Indonesia, comparing the efficacy of intermittent preventive treatment with dihydroartemisinin-piperaquine with the current strategy of single screening and treatment showed that intermittent preventive treatment is a promising alternative treatment for the reduction of malaria in pregnancy. We aimed to estimate the incremental cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine compared with single screening and treatment with dihydroartemisinin-piperaquine. We did a provider perspective analysis. A decision tree model was analysed from a health provider perspective over a lifetime horizon. Model parameters were used in deterministic and probabilistic sensitivity analyses. Simulations were run in hypothetical cohorts of 1000 women who received intermittent preventive treatment or single screening and treatment. Disability-adjusted life-years (DALYs) for fetal loss or neonatal death, low birthweight, moderate or severe maternal anaemia, and clinical malaria were calculated from trial data and cost estimates in 2016 US dollars from observational studies, health facility costings and public procurement databases. The main outcome measure was the incremental cost per DALY averted. Relative to single screening and treatment, intermittent preventive treatment resulted in an incremental cost of US$5657 (95% CI 1827 to 9448) and 107·4 incremental DALYs averted (-719·7 to 904·1) per 1000 women; the average incremental cost-effectiveness ratio was $53 per DALY averted. Intermittent preventive treatment with dihydroartemisinin-piperaquine offers a cost-effective alternative to single screening and treatment for the prevention of the adverse effects of malaria infection in pregnancy in the context of the moderate malaria transmission setting of Papua. The higher cost of intermittent preventive treatment was driven by monthly administration, as compared with single-administration single screening and treatment. However, acceptability and feasibility considerations will also be needed to inform decision making. Medical Research Council, Department for International Development, and Wellcome Trust.


Ambient oscillatory mode assessment in power system using an advanced signal processing method.
Estimation of electromechanical mode properties is crucial in modern power systems for providing the operators with an adequate indication of the stress in the system. Measurement-based approaches use signal processing algorithms for mode identification and parameter estimation. This paper presents a novel framework for the assessment of low-frequency oscillation modes using real-world synchrophasor data with minimum computational effort. A nonstationary approach known as Time-Varying Filter based Empirical Mode Decomposition (TVF-EMD) technique is used to identify the dominant low-frequency modes present in the ambient PMU data. The combination of TVF-EMD with Teager Kaiser Energy Operator (TKEO) precisely estimates the instantaneous mode parameters, such as frequency, amplitude, and damping ratio. The efficacy of the proposed approach is demonstrated by applying it in a synthetic signal, simulated data of a standard IEEE test system, and in real-world PMU data of the Indian power grid. The proposed method is compared with the existing methodologies and the observations reveal that the proposed method has robust performance in estimating the instantaneous mode features in the power system with less computational complexities.


The prevalence of persistent coughs in a rural community in the Lango district of Uganda.
During a survey of disease due to M. ulcerans in a small rural community in Uganda in 1971 individuals were asked whether they had a cough and how long it had been present. Nine thousand one hundred and seventy-two were questioned. Of these, 4.0% of males and 4.2% of females reported a cough of longer than 1 month's duration. Of 909 aged 50 years or more the proportion was 7.9% being higher in females (9.8%) than in males (6.5%).


Schistosoma japonicum: the pathology of experimental infection.
The pathology of experimental schistosomiasis japonica is reviewed and compared with the pathology of schistosomiasis japonica in man and to some aspects of schistosomiasis mansoni and schistosomiasis haematobia in experimental animals. The induction of granulomas around Schistosoma japonicum eggs depends upon cell mediated immunity, as do the reactions to Schistosoma mansoni and Schistosoma haematobium eggs. However, the modulation of the reaction to S. japonicum eggs can be greatly influenced by antibody, while antibody has no effect on the granulomas around S. mansoni eggs. Adult worm pairs of S. japonicum tend to cluster in the mesenteric venules, and most eggs are laid in a few sites. This leads to large, focal intestinal lesions similar to the discrete lesions produced by S. haematobium in the intestine and urinary tract but in contrast to the widespread, diffuse lesions produced by S. mansoni. Comparison with S. japonicum infection in humans is limited chiefly by our scant knowledge of the pathology produced by S. japonicum in infected persons. Most such comparisons are, in any case, limited by the marked differences in the reactions of various experimental host species to the infection and by differences in the reaction of a given host species to different strains of the parasite.


CHRONOFALLS: A multicentre nurse-led intervention in the chronoprevention of in-hospital falls in adults.
Falls are among the most common and serious adverse events for hospitalised patients. In-hospital falls pose a major medical and economic challenge for public health worldwide. Nevertheless, the issue is often addressed without regard to certain relevant variables such as the time of the fall. The aim of this study was to determine the effect of the implementation of a nurse-led intervention based on the temporal patterns of falls and their aetiology on the occurrence of falls. A mixed-method research design was carried out in three phases: a) a longitudinal prospective study (audits, chronobiological analyses and implementation of a multicentre nurse-led intervention based on temporal patterns of falls); b) a retrospective study of fall records; and c) a qualitative study based on focus groups. The protocol was published in 2021. A difference was observed in the number of fall records before and after the chronopreventive intervention (retrospective: 64.4% vs. 35.6%; p < 0,001). According to the interrupted series analysis, considering the influence of the COVID-19 pandemic, a reduction in falls of 2.96% (95% CI 1.70%-4.17%) was observed. The concepts of falls, the COVID-19 pandemic and the causes of non-registration have emerged as categories for qualitative analysis. A multicentric nurse-led program based on tailored organisational, educational and behavioural chronopreventive measures seems to lead to a reduction in the number of in-hospital falls. The findings of the present study, highlighting the implementation of chronopreventive measures, can serve as a basis for future health policies. The project was registered on the Clinical Trials Registry NCT04367298 (29/04/2020).


Hoffman-Tinel sign. The realities.
The Hoffman-Tinel sign, although originally described by Paul Hoffman, is commonly referred to as the Tinel sign. It is one of the most commonly used tests in the clinical evaluation of periperhal nerves. The sign is used in the diagnosis of compression neuropathies, such as carpal and cubital tunnel syndromes, but it is also useful in the diagnosis of a variety of neurological maladies. Despite controversy, the Hoffman-Tinel sign remains important in the diagnosis of peripheral neuropathies and for the evaluation of the regenerating nerve after injury.


Quality of life of patients with bilateral oophorectomy before the age of 45 for the treatment of endometriosis.
The study aimed to evaluate the quality of life and associated factors among women who underwent bilateral oophorectomy (BO) before the age of 45 for the treatment of deep infiltrating endometriosis (DIE). This cross-sectional study was carried out in 52 women who were treated from January 2014 to December 2019 in 2 public and private DIE surgical centers in Toulouse. All women answered the Menopausal Quality of Life questionnaire (MenQOL). Mean MenQOL scores were compared according to age at BO, smoking, BMI, level of education, delay between BO and the survey and post-BO hormone replacement therapy (HRT) using Mann-Whitney and Anova tests. Spearman's correlation coefficient was used to analyze the correlations between all the MEnQOL domain scores and clinical variables. The variables associated with the outcomes in univariate analyses with p < 0.2 were jointly evaluated using multiple linear regression. The mean age at the time of the survey was 43.4 ± 3.4 years while the mean age at BO was 40.5 ± 3.4 years. The mean MenQOL score was 3.96 (± 1.45), with the highest scores in the sexual (4.77) and vasomotor (4.01) domains. BMI and smoking were independently and significantly associated with the mean total MenQOL score, all domain scores being significantly higher in overweight/obese women. A trend towards worse MenQOL scores was found in patients who had BO before the age of 41. We did not find any difference according to whether or not they were taking HRT. This is a first study evaluating quality of life in a specific population of oophorectomized women under the age of 45 using MenQOL for DIE. While BO is effective in relieving pain in women with severe DIE, the induced premature menopause is associated with a poor quality of life, which deserves further attention.


Smart phone assisted quinoline-hemicyanine based fluorescent probe for the selective detection of glutathione and the application in living cells.
Quinoline appended hemicyanine 6MIM with strong ICT character was successfully synthesized through simple condensation reaction of 6-methoxy-2-chloro-3-formyl quinoline with 2-benzothiazolinium iodide. The photophysical characteristics of synthesized probe revealed that it would selectively detect glutathione (GSH) when it compared with different amino acids including biothiols and the detection limit is found to be 100 nM. The turn off sensor is due to thiol-halogen SNAr nucleophilic substitution between 6MIM and thiol group in glutathione. More importantly, the biosensor 6MIM was effectively applied in the fluorescence bioimaging of GSH in living cells with low cell toxicity. The colorimetric detectable color change of 6MIM-GSH has been effectively integrated with smartphone assisted RGB color value application with lowest detection value of 120 nM.


First in-human experience with a novel robotic platform and Magnetic Surgery System.
Magnetic technologies have been introduced to reduce invasiveness of surgical procedures. This study was aimed to analyse the performance of a novel combined magnetic-robotic controller as an enhanced accessory to the Magnetic Surgical System in laparoscopic cholecystectomy (LC). This was a prospective study of 10 consecutive patients undergoing LC with this novel surgical system. Ten patients were included, nine were female. The mean age was 30.3 ± 9 years. All patients had chronic cholecystitis. Procedures were completed successfully. The median operative time was 50 ± 11 min. The system performed effectively in all cases with no need of additional interventions. There were no device-related complications or side effects. All patients were discharged the same day. Recovery was uneventful during follow-up. This study demonstrates the first in-human successful performance of surgeries utilizing a novel combination of magnetic and robotic technologies in one integrated system.


Regulation of actin cytoskeleton dynamics by Arf-family GTPases.
Small GTPases of the Arf family are best known for their role in vesicular transport, wherein they nucleate the assembly of coat proteins at sites of carrier vesicle formation. However, accumulating evidence indicates that the Arfs are also important regulators of actin cytoskeleton dynamics and are involved in a variety of actin-based processes, including cell adhesion, migration and neurite outgrowth. The mechanisms of this regulation are remarkably diverse, ranging from the integration of vesicular transport with cytoskeleton assembly to the direct regulation of Rho-family GTPase function. Here, we review recent progress in our understanding of how Arfs and their interacting proteins function to integrate membrane and cytoskeletal dynamics.


[Analysis of schistosomiasis situation at a surveillance site in Kailhua County, Zhejiang Province from 2008 to 2014].
To master the dynamics of schistosomiasis situation in Kaihua County, so as to provide the evidence for formulating the prevention and control scheme. According to the "Schistosomiasis Monitoring Work Program in Zhejiang Province", the Oncomelania hupensis snail status, schistosome infections of residents and livestock, and the influencing factors were investigated. Totally 62 snail sites were discovered, the area with snails was 2.30 hm2, the snail density was 0.023 snail/0.1 m2, and the snail status declined with time. No schistosome infected snails, local residents, mobile people or livestock were found. The endemic situation of schistosomiasis is stable in Kaihua County, but the surveillance of snail situation and mobile population is still needed.


Significance of an Environmental Gas Cell to Obtain a Fully Dehydrated Form and CO2-Pressurized Structure of a Metal-Organic Framework Using In Situ Single-Crystal X-ray Diffraction at 298 K.
The single-crystal X-ray diffraction method was employed to characterize a rigid hydrated metal-organic framework (MOF), [Co2(MA)(INA)·2H2O]n, that displays an affinity toward water molecules under ambient conditions after dehydration. The fully dehydrated form was obtained using an environmental gas cell technique in a stepwise manner followed by its CO2-pressurized structure at 298 K using in situ crystallography.


Impaired proliferation of growth plate chondrocytes in a model of osteogenesis imperfecta.
Short stature is the second conspicuous characteristic of osteogenesis imperfecta (OI), but the etiological mechanism is unclear. The proliferation of growth plate chondrocytes (GPCs) plays an essential role in longitudinal bone growth, and chondrocyte division deficiency can cause shortened limbs. However, few studies have reported the abnormal changes of growth plate and GPCs in OI. In this study, the cell proliferative performance of GPCs in heterozygous Col1a2oim/+ mice were studied and the underlying mechanism was explored by RNA-Sequencing. The results indicated that chondrocytes of Col1a2oim/+ background displayed impaired cell division when compared with cells of wild-type littermates. A group of differentially expressed genes involving chondrocyte proliferation related pathways including cell cycle, TGF-β signaling pathway and Hedgehog signaling pathway were identified. These dysregulated genes and pathways in GPCs of Col1a2oim/+ mice are likely to play an important role in their shortened long bones. Further investigations to reveal the effect of these genes on bone elongation not only facilitate the understanding of OI short stature, but also contribute to developing new treatments.


Impact of Statin Therapy on Plasma Uric Acid Concentrations: A Systematic Review and Meta-Analysis.
The aim of this study was to ascertain the effect size of statins in modulating plasma uric acid concentrations. A search was undertaken of the MEDLINE, SCOPUS, Web of Science and Google Scholar electronic databases. Studies meeting the following criteria were included: (i) randomized controlled trials with either a parallel or crossover design; (ii) investigated the impact of statin therapy on plasma uric acid concentrations; and (iii) presentation of sufficient information on uric acid values at baseline and at the end of follow-up in each group, or presenting the net change. The present meta-analysis suggested a significant reduction in plasma uric acid levels following statin therapy; however, this does not seem to be a class effect as subgroup analysis revealed a significant reduction with atorvastatin and simvastatin only, and not with pravastatin and rosuvastatin. Atorvastatin and simvastatin, but not the other statins, can reduce serum uric acid levels.


Spatial distribution and factors influencing modern contraceptive practice among tribal married women in India: evidence from National Family Health Survey 5 (2019-2021).
The unmet need for family planning has been a public health concern in developing countries, especially in the south-east region. In India, the expanding roles of women has led to a growing need for family planning and contraception. However, tribal women still struggle with reproductive and sexual health issues. Unfortunately, most tribal women are not informed about the potential health risks associated with contraceptive use, as service providers often neglect to provide this information. As a result, tribal women often suffer in silence, which can lead to serious health problems. Thus, the present study aimed to understand the patterns and factors associated with modern contraceptive usage as well as the district level variation in usage among tribal married women. We included 91,976 tribal married women participants aged 15 to 49 years from National Family Health Survey 5 conducted during the years 2019 to 2021. Descriptive statistics were used to compute the prevalence of modern contraceptive usage along with 95% confidence interval (CI) as a measure of uncertainty. The association between various socio-demographic predictors and modern contraceptive usage were assessed by multivariable logistic regression and presented as an adjusted odds ratio (AOR). The overall prevalence of modern contraceptive practices was found to be 53% among tribal married women, which was below the national average. Sterilization was the most preferred method of modern contraceptive, whereas injectables were the least preferred method. More than 80% of the married women get the family planning information from the public health facility and health workers. Districts of eastern and north-eastern states have comparatively less modern contraceptive prevalence than central and southern states. Age, education, parity and access to media were significantly associated with the use of modern methods of contraception. Improving contraceptive use and reducing unmet needs for contraception among tribal women requires sustained efforts from healthcare workers, including Information Education and Communication (IEC) through mass media to raise awareness. A tailored family planning strategy is crucial to address the specific needs of tribal women at both the local and national levels, with adequate resources and monitoring for impact with this India can achieve Total Fertility Rate (TFR) 2.1 among tribals.


Interventional radiology meets immuno-oncology for hepatocellular carcinoma.
Locoregional and systemic therapies are the most used treatment options for patients with hepatocellular carcinoma (HCC). Interventional radiologists have improved and developed novel protocols and devices for both intratumoural ablative approaches with curative intent and various transarterial intrahepatic treatment options, which have continuously improved patient outcomes. Two large phase III randomised clinical trials have demonstrated the efficacy of different immune checkpoint inhibitors either as single agents or in combination in the first-line setting and immunotherapy has become the standard first-line treatment option for patients with advanced HCC. Herein, we discuss advances and perspectives in the area of interventional radiology (IR) and immune-oncology (IO). We summarise results from recent studies and provide an overview of ongoing studies in IR and IO. Based on the significant advances in both areas, we propose that IR and IO need to cover the emerging "discipline" of IR-IO, in which we develop and test novel approaches to combine locoregional therapies with immunotherapy, in order to develop sufficient evidence for them to be considered standard of care for patients with HCC in the near future.


Different mechanisms govern the two-phase Brust-Schiffrin dialkylditelluride syntheses of Ag and Au nanoparticles.
Here we report the first unambiguous identification of the chemical structures of the precursor species involving metal (Au and Ag) ions and Te-containing ligands in the Brust-Schiffrin syntheses of the respective metal nanoparticles, through which the different reaction pathways involved are delineated.


Effects of thyroxine on postnatal cell acquisition in the rat brain.
The effects of treatment with L-thyroxine (3 micrograms by subcutaneous injection daily from birth) on cell acquisition in the rat brain were studied during the first 3 postnatal weeks. In the forebrain, thyroxine has no effect on cell proliferation in the first 6 days, but it causes decreased cell acquisition from 12 to 21 days so that cell number becomes significantly reduced. Estimates of cell proliferation kinetics and of cell death in the lateral ventricular subependymal layer show no apparent abnormality. In the cerebellum, treatment from birth leads to increased cell proliferation during the first week: in comparison with controls, the rate of [3H]thymidine incorporation into DNA, thymidine kinase activity, and the number of cells both in the major germinal site (external granular layer: EGL) and in the whole cerebellum are elevated. This initial effect of thyroxine appears by day 3 and is short-lived, being no longer evident after day 6. The build-up of cell numbers in the EGL at day 6 seems to be related to a preceding, transient retardation of cell migration from this layer rather than to an acceleration of cell replication, since cell cycle parameters are normal. From day 12 the rate of [3H]thymidine incorporation into DNA is severely reduced in treated rats. Advancement of cellular differentiation rather than increased cell death in the EGL appears to be involved in this phenomenon.


In situ alkylation of cysteine residues in a hydrophobic membrane protein immobilized on polyvinylidene difluoride membranes by electroblotting prior to microsequence and amino acid analysis.
For identification of cysteine residues on microsequence analysis it is crucial to derivatize the sulfhydryl groups. This reaction requires a desalting step which often represents a major obstacle, especially if the sample consists of limited amounts of a hydrophobic membrane protein. An alkylation procedure is described, allowing efficient derivatization (greater than 90%) of cysteines and cystines even in low microgram quantities, as revealed by test analyses with lysozyme and a hydrophobic membrane protein. The modified protein is recovered in high yields in a form suitable for both microsequence analysis and amino acid analysis. The method involves electrophoretic desalting by miniaturized Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in situ alkylation after electro-transfer onto polyvinylidene difluoride membranes. Precautions against NH2-terminal blocking during sample preparations are provided. The general applicability of the method is illustrated by the structural characterization of the low abundance membrane receptor for human urokinase plasminogen activator.


Association of dietary fiber and depression symptom: A systematic review and meta-analysis of observational studies.
A potential relationship between depression and the intake of dietary fiber has been hypothesized in several studies. However, no meta-analysis has been conducted so far to explore the association between these two variables. Hence, we designed the present meta-analysis to elucidate the relationship between the intake of dietary fiber and depression. A comprehensive search was performed using the PubMed/Medline, Scopus, Web of Science and Google Scholar databases to identify any relevant studies published from inception to October 2019. Observational studies (cross-sectional and case-control) were included in the analysis. Pooled analysis from the random-effects model of four case-control studies revealed that the consumption of dietary fiber in patients with depression was significantly lower versus healthy controls (WMD: -1.41 mg/dl, 95 % CI: -2.32, -0.51, P = 0.002). No significant heterogeneity was demonstrated among the analyzed studies (I2 = 4.0 %, P = 0.37). By pooling 5 effect sizes of cross-sectional studies (with a total of 97,023 subjects), we demonstrated that a higher dietary consumption of fiber was associated with significantly lower odds of depression (OR = 0.76; 95 % CI: 0.64, 0.90; P = 0.010), with a low heterogeneity seen among the retrieved studies (I2 = 43.9 %; P = 0.12). An increased intake of total dietary fiber is associated with lower odds of depression. Further studies are needed to evaluate the relationship between the different types of dietary fiber and depression.


MITOSTATIN, a putative tumor suppressor on chromosome 12q24.1, is downregulated in human bladder and breast cancer.
Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived cells and solid tumors, respectively. When transiently overexpressed, MITOSTATIN inhibited colony formation, tumor cell growth and was proapoptotic, all features shared by established tumor suppressor genes. We discovered a specific link between MITOSTATIN overexpression and downregulation of Hsp27. Conversely, MITOSTATIN knockdown cells showed an increase in cell growth and cell survival rates. Finally, MITOSTATIN expression was significantly reduced in primary bladder and breast tumors, and its reduction was associated with advanced tumor stages. Our findings support the hypothesis that MITOSTATIN has many hallmarks of a classical tumor suppressor in solid tumors and may play an important role in cancer development and progression.


The Duke myasthenia gravis clinic registry: I. Description and demographics.
The Duke Myasthenia Gravis (MG) Clinic Registry is a disease-specific database containing physician-derived data from patients seen in the Duke MG Clinic since 1980. Data from 1060 MG patients initially seen between 1980 and 2008 were reviewed. Fifty-four percent were male. Symptoms began after age 50 in 66% of males and 42% of females. Peak onset age in males was in their 60's; females had no predominant onset age. Onset age for both sexes increased from 1980 to 2008. Thymoma was present in 8.5%. Weakness was limited to ocular muscles for at least 2 y in 22% and became generalized later in 8.3% of these. Acetylcholine receptor antibodies were present in 78% overall, 82% with generalized MG and 52% with ocular MG (OMG). The distribution of MG disease class was similar in males and females, except that a greater proportion of women experienced myasthenic crisis and men were more likely to have OMG. Data in the Registry permit comprehensive and longitudinal analysis of a validated MG population. Analysis of Registry data shows that the frequency of AChR antibody negative MG, ocular MG, and thymoma are similar to other reports, but the onset age and proportion of males have progressively increased compared to studies published more than 20 y ago. These observations demonstrate the value of collecting comprehensive clinical information and comparing historic and contemporary populations. Other potential uses of Registry data include comparison of outcome measures in different disease subgroups and the response to specific treatments.


Herpes simplex virus type 2 infection, syphilis, and hepatitis B virus infection in Haitian women with human immunodeficiency virus type 1 and human T lymphotropic virus type I infections. The Johns Hopkins University (JHU)/Centre pour le Developpement et la Santé (CDS) HIV Study Group.
Antibodies to herpes simplex virus type 2 (HSV-2), antibodies to hepatitis B virus (HBV) core antigen (anti-HBc), and VDRL antibodies (serologic evidence of syphilis) were evaluated in women known to be infected with human immunodeficiency virus type 1 (HIV-1) (n = 95) or human T lymphotropic virus type I (HTLV-I) (n = 45) and controls (n = 89). HIV-1-seropositive women were more likely than controls to have antibodies to HSV-2 (88% vs. 54%; P less than .001), anti-HBc (67% vs. 43%; P = .008), and VDRL antibodies (21% vs. 8%; P = .02). Similarly, HTLV-I-seropositive women were more likely than controls to have antibodies to HSV-2 (82% vs. 54%; P = .003) and anti-HBc (67% vs. 43%; P = .008). There was no evidence that HIV-1 or HTLV-I predisposed to chronic hepatitis B virus infection. The stronger associations between HIV-1 and HTLV-I with HSV-2 than the associations with syphilis or HBV are consistent with the hypothesis that recurrent disruptions of mucous membranes caused by HSV-2 infections predispose to sexual transmission of HIV-1 and HTLV-I.


Thermal mineralization behavior of PFOA, PFHxA, and PFOS during reactivation of granular activated carbon (GAC) in nitrogen atmosphere.
Waste disposal site is one of the important sinks of chemicals. A significant amount of perfluoroalkyl and polyfluoroalkyl substances (PFASs) such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexanoic acid (PFHxA) have been brought into it. Because of their aqueous solubility, PFASs are released to landfill effluent waters, from which PFASs are efficiently collected by adsorption technique using granular activated carbon (GAC). The exhausted GAC is reactivated by heating processes. The mineralization of PFASs during the reactivation process was studied. Being thermally treated in N2 atmosphere, the recovery rate of mineralized fluorine and PFC homologues including short-chained perfluorocarboxylic acids was determined. If the reagent form of PFOA, PFHxA, and PFOS were treated at 700 °C, the recovery of mineralized fluorine was less than 30, 46, and 72 %, respectively. The rate increased to 51, 74, and 70 %, if PFASs were adsorbed onto GAC in advance; moreover, addition of excess sodium hydroxide (NaOH) improved the recovery to 74, 91, and 90 %. Residual PFAS homologue was less than 1 % of the original amount. Steamed condition did not affect destruction. The significant role of GAC was to suppress volatile release of PFASs from thermal ambient, whereas NaOH enhanced destruction and retained mineralized fluorine on the GAC surface. Comparing the recovery of mineralized fluorine, the degradability of PFOS was considered to be higher than PFOA and PFHxA. Whole mass balance missing 9~26 % of initial amount suggested formation of some volatile organofluoro compounds beyond analytical coverage.


Influence of Fatigue on Cognitive-Motor Function During Unanticipated Landings.
Physical fatigue and cognitive performance have been suggested as risk factors for an anterior cruciate ligament (ACL) injury, and fatigue has also been demonstrated to reduce cognitive processing. The combined effects of fatigue and lower cognitive function during cognitive-challenging movements may increase knee mechanics associated with the ACL injury risk. We hypothesized that (1) knee mechanics would be detrimentally affected by fatigue and associated with baseline cognitive function and (2) fatigue-induced deleterious changes in cognitive performance and knee mechanics would be correlated. Descriptive laboratory study. A total of 22 athletes completed baseline cognitive testing. After performing maximal vertical jumps, they performed a jump-land-jump task based on unanticipated visual cues. Then, they completed a fatigue protocol including countermovement jumps, among other tasks, until the jump height decreased below 90% of their assessed maximum. Immediately after reaching the first fatigue point, they performed another set of jump-landing tasks, followed by repeating the fatigue protocol until the jump height decreased below 85% of their assessed maximum. After reaching the second fatigue point, they performed a final set of jump-landing tasks and repeated the initial cognitive assessment battery. Mixed-effects models revealed that knee flexion decreased through the fatigue protocol (baseline: 61.8°; midpoint: 61.1°; final: 60.1°; P = .003). Stepwise regression showed that fatigue-worsened attentional control corresponded to smaller knee abduction angles (R2adjusted = 51.68%; βstandardized = 1.16; P = .001), and worse reaction time after fatigue correlated with increased knee abduction angles (βstandardized = 0.85; P = .006) after accounting for the role of attentional control. Fatigue induced incremental modifications in sagittal-plane knee mechanics during an unanticipated sports movement. In addition, fatigue induced changes in cognitive function related to ACL injury-relevant knee mechanics. The novel findings regarding fatigue-dependent changes in injury-relevant biomechanics during cognitively challenging movements represent an extension of recent developments in understanding the role of cognition in the ACL injury risk.


Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges.
Cancer progression results from activation of various signaling networks. Among these, PI3K/Akt signaling contributes to proliferation, invasion, and inhibition of apoptosis. Hepatocellular carcinoma (HCC) is a primary liver cancer with high incidence rate, especially in regions with high prevalence of viral hepatitis infection. Autoimmune disorders, diabetes mellitus, obesity, alcohol consumption, and inflammation can also lead to initiation and development of HCC. The treatment of HCC depends on the identification of oncogenic factors that lead tumor cells to develop resistance to therapy. The present review article focuses on the role of PI3K/Akt signaling in HCC progression. Activation of PI3K/Akt signaling promotes glucose uptake, favors glycolysis and increases tumor cell proliferation. It inhibits both apoptosis and autophagy while promoting HCC cell survival. PI3K/Akt stimulates epithelial-to-mesenchymal transition (EMT) and increases matrix-metalloproteinase (MMP) expression during HCC metastasis. In addition to increasing colony formation capacity and facilitating the spread of tumor cells, PI3K/Akt signaling stimulates angiogenesis. Therefore, silencing PI3K/Akt signaling prevents aggressive HCC cell behavior. Activation of PI3K/Akt signaling can confer drug resistance, particularly to sorafenib, and decreases the radio-sensitivity of HCC cells. Anti-cancer agents, like phytochemicals and small molecules can suppress PI3K/Akt signaling by limiting HCC progression. Being upregulated in tumor tissues and clinical samples, PI3K/Akt can also be used as a biomarker to predict patients' response to therapy.


The dicarbon bonding puzzle viewed with photoelectron imaging.
Bonding in the ground state of C[Formula: see text] is still a matter of controversy, as reasonable arguments may be made for a dicarbon bond order of [Formula: see text], [Formula: see text], or [Formula: see text]. Here we report on photoelectron spectra of the C[Formula: see text] anion, measured at a range of wavelengths using a high-resolution photoelectron imaging spectrometer, which reveal both the ground [Formula: see text] and first-excited [Formula: see text] electronic states. These measurements yield electron angular anisotropies that identify the character of two orbitals: the diffuse detachment orbital of the anion and the highest occupied molecular orbital of the neutral. This work indicates that electron detachment occurs from predominantly [Formula: see text]-like ([Formula: see text]) and [Formula: see text]-like ([Formula: see text]) orbitals, respectively, which is inconsistent with the predictions required for the high bond-order models of strongly [Formula: see text]-mixed orbitals. This result suggests that the dominant contribution to the dicarbon bonding involves a double-bonded configuration, with 2[Formula: see text] bonds and no accompanying [Formula: see text] bond.


[Results of cooperation of Experimental and Clinical Chemotherapy, N. N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences (1952-2000)].
Milestones of the Russian antitumor chemotherapy development inseparably associated with the names of N.N. Blokhin, L.F. Larionov and V.I. Astrakhan are reviewed. Since the early 50s of the last century, more than 7,000 generic and synthetic compounds have been studied by the three generations of chemotherapy researchers. 17 antitumor drugs have been developed and passed for clinical trials, 11 of them have been or still are being used in clinic.


PO x /Al2O3 Stacks for c-Si Surface Passivation: Material and Interface Properties.
Phosphorus oxide (PO x ) capped by aluminum oxide (Al2O3) has recently been discovered to provide excellent surface passivation of crystalline silicon (c-Si). In this work, insights into the passivation mechanism of PO x /Al2O3 stacks are gained through a systematic study of the influence of deposition temperature (T dep = 100-300 °C) and annealing temperature (T ann = 200-500 °C) on the material and interface properties. It is found that employing lower deposition temperatures enables an improved passivation quality after annealing. Bulk composition, density, and optical properties vary only slightly with deposition temperature, but bonding configurations are found to be sensitive to temperature and correlated with the interface defect density (D it), which is reduced at lower deposition temperature. The fixed charge density (Q f) is in the range of + (3-9) × 1012 cm-2 and is not significantly altered by annealing, which indicates that the positively charged entities are generated during deposition. In contrast, D it decreases by 3 orders of magnitude (∼1013 to ∼1010 eV-1 cm-2) upon annealing. This excellent chemical passivation is found to be related to surface passivation provided by hydrogen, and mixing of aluminum into the PO x layer, leading to the formation of AlPO4 upon annealing.


A microfluorescent PAS method for the quantitative demonstration of cytoplasmic 1,2-glycols.
Fluorescent microspectrophotometry using dichroic mirror vertical epi-illumination of tissue sections stained with the PAS reaction (periodic acid and pararosaniline Schiff reagent) provides a measure of the relative concentration of 1:2 glycols within and between tissue sections. In PAS reacted sections of agarose gel, pararosaniline Schiff fluorescence increases linearly as the concentration of agarose increases (r=0.97, p less than 0.05). The concentration of glycogen within liver as measured by a phenol-based tissue assay is linearly correlated with pararosaniline Schiff fluorescence of formalin fixed liver sections (r-0.87, p less than 0.05). These relationships are unaffected by alcian blue or hematoxylin. Heretofore the amount of color reaction as measured by densitometry at the pararosaniline absorption peak was claimed to be an unreliable indicator of the amount of reactive glycol present in tissue. Our observations indicate that when the concentration of Schiff reagent exceeds an empiric limit relative to available polysaccharides, the Schiff reagent-tissue complex reflects light at the excitation wavelength instead of fluorescing the emission spectra. This can be circumvented by using dilute pararosaniline-Schiff reagent, shorteining the staining period, and lowering the temperature of the staining medium. While routine PAS staining reactions are followed by washing in running water to develop the red color seen with broad spectrum illumination, water development is unnecessary for the dye-tissue complex to fluoresce. The fluorescent emission peak and the maximum excitation peak of both developed and undeveloped pararosaniline-Schiff-reagent-tissue complexes are 645--50 nm and 540--45 nm, respectively. These spectral characteristics are not changed by binding to oxidation products of different glycoproteins or polysaccharides. Intense exposure to room light, but not 100 repetitive short (0.13 s) exposures, causes partial photodecomposition. Quantitative assessment of cytofluorescence requires definition of the optical system used to measure emission. In the microspectrophotometer employed in this study, dichroic mirrors reflect light with variable efficiency depending on wavelength from the light source to the stage, and variably block light reflected or emitted from the specimen, serving as crude barrier filters. These dichroic mirror characteristics are influenced by the exact nature of the optical coating on the surface of each individual mirror. Since the optical coating on the surface of each individual mirror. Since the optical coating of similar mirrors may vary, the properties of individual mirrors must be considered in the interpretation of spectral data and in determining the proper optical conditions for quantification of cytofluorescence.


[Sensitisation to 'poffertjes' as a result of sleeping on a pillow containing buckwheat].
A 19-year-old man suffered an anaphylactic reaction after eating 'poffertjes' (small Dutch pancakes). This reaction appeared to be the result of an IgE-mediated allergy to buckwheat, a principal ingredient of 'poffertjes'. It is highly likely that the patient was sensitised by sleeping on a pillow stuffed with buckwheat husk.


The natural history of bacteriuria in childhood.
The highest figure for first-time UTI is found in infants below one year of age. These early infections are often pyelonephritic in character, but they are easily overlooked because symptoms are unspecific, high fever and failure to thrive being the most important. It has been shown that delay in start of treatment increases the risk of the child developing pyelonephritic scarring. There is reason to believe that undetected and therefore untreated attacks of pyelonephritis may be associated with renal scarring revealed later in life. This type of renal damage is associated with development of hypertension in about 10 per cent of children and it accounts for around 20 per cent of the children entered into dialysis and transplant programs. Prevention of such long-term problems would be of great value and pyelonephritic scarring is a potentially preventable disease. The majority of infants and young children with UTI are probably managed at the primary care level. It is therefore essential that general practitioners are well informed about the epidemiology of UTI in infancy and childhood and that adequate diagnostic facilities are provided. For example, suprapubic aspiration to obtain uncontaminated urine is a technique that may well be used in an outpatient setting, and dipslide cultures are accurate and inexpensive. In addition to young age, vesicoureteric reflux and repeated attacks of pyelonephritis are risk factors associated with development of renal scarring. Therefore, diagnostic imaging to detect children with anomalies within the urinary tract are especially important in the very young. Furthermore, long-term supervision should be provided and the parents advised to consult the doctor when there is suspicion of a new infection to avoid delay in treatment. There is no reason to perform general screening for bacteriuria in healthy infants. Although bacteriuria may be found in 1 to 2 per cent, asymptomatic children have a very high rate of spontaneous clearing of the bacteriuria and they seem to constitute a low-risk group. Instead, frequent culturing of urine from febrile infants would be much more important.


Use of telepsychiatry to improve care for people with mental illness in rural North Carolina.
Telehealth improves access to medical services, especially for people living in rural areas. In North Carolina, the advantages of telepsychiatry also go beyond improving access. This article describes a diverse program of telehealth and telepsychiatric service delivery and discusses its advantages and disadvantages.


Ion-interactions as driving force in polysaccharide assembly.
The structure of cellulose is characterised by extensive non-covalent interactions. Recent discussions suggest that hydrophobic interactions between polymer chains also play a significant role in governing cellulose solubility. Surprisingly in almost all cellulose shaping processes, chemical systems or solvents are applied, which base on melts or solutions of charged molecules. Ionic interactions play a significant role in the shaping and modification of cellulose based materials. Dependent on the systems used different principles govern the processes and define the results, e.g. formation of associates with alkali hydroxides, ion-exchange reactions to selectively bind multivalent ions at carboxylic groups, adsorption of dissolved polymers through surface charge neutralisation or metal complex formation, where cellulose takes the role of a polymer ligand system. Presence of charged compounds takes a significant role in cellulose swelling and dissolution, but also directs reassembly of polysaccharide material to solid three-dimensional structures.


Pathogenesis of pterygium.
This paper reviews the histological and epidemiological characteristics of pterygium which suggest that chronic exposure to ultraviolet radiation plays an important role in the pathogenesis of this disorder. However, there is conflicting evidence indicating that chronic inflammation from other causes can induce the disease. The results of two epidemiological surveys undertaken in Southern Africa show that pterygium is not closely linked to other chronic actinic disorders such as pinguecula and climatic droplet keratopathy. Pterygia differ from these disorders by their vascularity which is probably induced by chronic inflammation. On histological examination, we found that excised pterygia contained a lymphocytic infiltration consisting predominantly of T cells. In the pathogenesis of pterygium we believe that chronic irritation (from whatever cause) produces a chronic inflammatory cell infiltration with resultant inflammatory oedema, attempt at repair and cell induced angiogenesis. These processes, together with actinic damage, are responsible for the fibrovascular reaction so characteristic of a growing pterygium.


Defining right ventricular dysfunction by echocardiography in normotensive patients with pulmonary embolism.
Although the prognostic value of various echocardiographic parameters of right ventricular dysfunction (RVD) was reported in normotensive patients with acute pulmonary embolism (PE), there is no generally accepted definition of RVD. The aim of the study was to compare echocardiographic parameters for the prediction of an adverse 30‑day outcome and create an optimal definition of RVD. Patients and methods: Echocardiographic parameters including the right ventricular to left ventricular diameter ratio (RV to LV ratio) and tricuspid annular plane systolic excursion (TAPSE) to predict PE‑related mortality, hemodynamic collapse, or rescue thrombolysis within the first 30 days were directly compared in 490 normotensive patients with PE. An adverse outcome (AO) was present in 31 patients (6.3%); 8 of them (1.6%) died due to PE. Systolic blood pressure, RV to LV ratio, and TAPSE were independent predictors of AO. The receiver operator characteristic yielded an area under the curve of 0.737 (0.654-0.819; P <0.001) for the RV to LV ratio and 0.75 (0.672-0.828; P <0.001) for TAPSE with regard to an AO. The hazard ratio for AO was 2.5 for the RV to LV ratio of more than 1 (95% CI, 1.2-5.7; P <0.03) and 3.8 for TAPSE of less than 16 mm (95% CI, 1.74-8.11; P = 0.001). A combined RVD criterion (TAPSE <16 mm and RV to LV ratio >1) was present in 60 patients (12%), and showed a positive predictive value of 23.3% with a high negative predictive value of 95.6% regarding an AO (HR, 6.5; 95% CI, 3.2-13.3; P <0.001). Defining RVD on echocardiography by the RV to LV ratio of more than 1 combined with TAPSE of less than 16 mm identified patients with an increased risk of 30‑day PE‑related mortality, hemodynamic collapse, or rescue thrombolysis, while patients without this sign had a very good 30‑day prognosis.


Screening for toxicity and resistance to paralytic shellfish toxin of shore crabs inhabiting at Leizhou peninsula, China.
The situation of the environment contaminated by paralytic shellfish toxin (PST) in Leizhou peninsula, China, has attracted more attention since seafood poisoning occurred occasionally. In this study, we examined the toxicities of shore crab Leptodius exaratus, Thalamita crenata and Metopograpsus latifrons by mouse assay, resistance to PST by lethal test injection with PST, and discussed the toxicity neutralization of their hemolymph. The results showed 12% of shore crabs possessed toxicity of 4.3-4.4 MU/g. The 100% lethal dose of PST for M. latifrons was about 2 times of those for the other two crab species. The hemolymphs of the crabs were all able to neutralize PST and tetrodotoxin (TTX) toxicity in different extent. The above results indicate shore crabs at this area are exposed to an environment potentially contaminated with PST and/or TTX, and the toxicity neutralizing efficacy of their hemolymph directly affects their resistance to the toxins.