Molecular motion in solid all-trans retinoic acid (vitamin A acid) by proton NMR.
An investigation of the molecular dynamics of all-trans retinoic acid (vitamin A) has been carried out in the solid state by proton NMR. Measurements were made of T1 at 14 and 25 MHz and of second moment at 25 MHz in the temperature range 55 to 420 K for both monoclinic and triclinic forms. In the monoclinic state relaxation was attributed to methyl group reorientation below 250 K and to conformational motion of the cyclohexene ring above this temperature. Activation energies and time constants were derived for the motions. In the triclinic state the same motions were active, but the cyclohexene ring motion was less restricted and some of the methyl group motions were more restricted indicating that hindrances to the motions were at least partly determined by the intermolecular packing arrangements.


Mediterranean Diet and Risk of Rheumatoid Arthritis: Findings From the French E3N-EPIC Cohort Study.
The Mediterranean diet has been reported to be associated with a significant reduction in risk of noncommunicable diseases. We undertook this study to assess the relationship between adherence to the Mediterranean diet and the risk of rheumatoid arthritis (RA), especially in high-risk individuals. The E3N study (Etude Epidémiologique Auprès des Femmes de la Mutuelle Générale de l'Education Nationale) is a French prospective cohort study that has included 98,995 women since 1990. Dietary data were collected via a validated food frequency questionnaire in 1993. Adherence to the Mediterranean diet was assessed using a 9-unit dietary score evaluating consumption of vegetables, legumes, cereal products, fish, meat, dairy products, olive oil, and alcohol. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident RA were estimated using Cox proportional hazards regression models adjusted for age and the main potential confounders, including smoking. Among 62,629 women, we identified 480 incident cases of RA. In the entire study population, the Mediterranean diet adherence score was not associated with RA risk (HR 0.86 [95% CI 0.67-1.09] for high score versus low score; P for trend = 0.09); however, among ever-smokers, a higher score was associated with a decreased risk of RA (HR 0.91 [95% CI 0.84-0.99] for 1-point increase in score; P = 0.03). In ever-smokers, the absolute risks of RA in those with high scores and those with low scores were 38.3 and 51.5 per 100,000 person-years, respectively, compared to 35.8 per 100,000 person-years in never-smokers with high Mediterranean diet scores. Our results suggest that adherence to the Mediterranean diet could reduce the high risk of RA among ever-smoking women. Our results must be confirmed in future research.


Promoting the adoption of residential water conservation behaviors as a preventive policy to sustainable urban water management.
As concerning with water insecurity driven by water scarcity threatens the lives and livelihoods of humanity worldwide, urban water demand management is focused on promoting residential water conservation behaviors (WCBs) as a critical policy response to water scarcity. However, urban water conservation initiatives cannot be successful unless households involve in residential WCBs voluntarily by adopting water curtailment and/or water-efficiency actions. Thus, understanding motivations and mechanisms underlying accepting these two types of WCBs and interpreting their distinctions are primary policy considerations to make sustainable water consumption behaviors. Hence, the purpose of this research was twofold: (1) To explore intentions to household adoption of water curtailment and water-efficiency actions, key corresponding determinants, and distinctions between them; and (2) To evaluate the capability and robustness of the Health Belief Model (HBM) to explain residential WCBs. The present research design was a cross-sectional survey conducted in Tehran, Iran. The outcomes from structural equation modeling indicated that: (1) Water curtailment intention was solely determined by self-efficacy and perceived benefits; (2) In addition to self-efficacy and perceived benefits, perceived severity, cues to action, and perceived barriers were significantly related to water-efficiency intention; (3) While only perceived susceptibility was not a significant determinant for water-efficiency intention, perceived susceptibility, perceived severity, perceived barriers, and cues to action could not significantly explain water curtailment intention; (4) Self-efficacy also emerged as the strongest predictive variable behind intentions to adopt both WCBs; (5) The perceived barriers had a negative significant relationship only with water-efficiency intention; and (6) The HBM could explain 72% and 61% of the variance in households' intentions to adopt water curtailment and water-efficiency actions, respectively. These outcomes supported that the HBM could propose a reliable and practical heuristic theoretical framework to predict residential WCBs. Moreover, the findings confirmed significant differences among socio-psychological factors behind intentions to household adoption of both WCBs, which need to be addressed. The research results introduced numerous implications from theoretical and policy standpoints for improving residential WCBs.


H2 O2 -induced oxidative stress disrupts mitochondrial functions and impairs migratory potential of human epidermal melanocytes.
Reactive oxygen species (ROS) have already been demonstrated to impede the migratory ability in non-melanocytic cell lines by depleting mitochondrial ATP production. Therefore, understanding the mitochondrial metabolic response to migration in the presence of ROS should be a key to understanding repigmentation in vitiligo. This study aimed to investigate the energy mechanism associated with the ROS-mediated attenuation of melanocyte migration. After melanocytes were pretreated with H2 O2 , their ATP production, migratory ability, ultrastructural changes and Mitochondrial Permeability Potential were analysed. The results showed that, in parallel with the decreased ATP production, the migratory ability of melanocytes was significantly inhibited by oxidative stress. Supplementation with exogenous ATP reversed the suppressed ATP-dependent migration of melanocytes. Melanocytes were then stressed with H2 O2 and Agilent Whole Human Genome microarray analysis identified 763 up-regulated mRNAs and 1117 down-regulated mRNAs. Among them, 11 of the encoded proteins were involved in mitochondrial ATP production and their expression levels were verified. The decreased expression of NADH dehydrogenase 2(ND2) , cytochrome c oxidase 1(COX1) and cytochrome c oxidase 3(COX3) was shown to be involved in the depletion of mitochondrial ATP production, which was coupled with the impaired migratory potential. These results indicate that the migration of melanocytes relies heavily on an inexhaustible supply of ATP from mitochondria.


One-pot synthesis of uniform Fe₃O₄ nanospheres with carbon matrix support for improved lithium storage capabilities.
Poly(acrylic acid) (PAA)-entangled Fe(3)O(4) nanospheres are synthesized via a facile solvothermal method. In this system, ethylenediamine plays a very important role to control the uniformity of the nanospheres, and the PAA molecules serve as the carbon source that transforms into a carbon matrix after the heat treatment under an inert atmosphere. These uniform Fe(3)O(4) nanospheres with carbon matrix support manifest greatly enhanced lithium storage properties over prolonged cycling, with a reversible capacity of 712 mA h g(-1) retained after 60 charge/discharge cycles. However, the carbon-free counterpart can only deliver a much lower capacity of 328 mA h g(-1).


Does the white-coat effect in people of African and South Asian descent differ from that in White people of European origin? A systematic review and meta-analysis.
To assess whether the white-coat effect in people of African (Blacks) and South Asian descent differs from that of people of European origin (Whites), and if so, whether this explains demonstrated ethnic variations in blood pressure. A systematic literature review was carried out using Medline 1966-2003, Embase 1980-2003, and citations from references. The meta-analysis was performed using the Cochrane review manager software (RevMan version 4.2; Oxford, UK). Eight studies were examined, four studies from the UK and four from the USA. The mean systolic and diastolic white-coat effect was similar in Blacks and Whites. The weighted mean difference in systolic white-coat effect was 0.31 [confidence interval 95% (CI)=-1.96, 2.57; P=0.79] and in diastolic white-coat effect was 0.18 (95% CI=-1.70, 1.35; P=0.82). Two studies reported on South Asians. Both systolic and diastolic white-coat effect was significantly lower in South Asians than in Whites; the weighted mean difference in systolic white-coat effect was -8.90 (95% CI=-13.04, -4.76; P<0.0001) and in diastolic white-coat effect was -4.66 (95% CI=-7.29, -2.03; P<0.0001). The blood pressure differences between Blacks and Whites are unlikely to be a result of variations in white-coat effect. In contrast, the slightly lower clinic blood pressure in some South Asian populations such as Bangladeshis might be partly caused by a low white-coat effect but more studies are needed in this subject.


SETD1A-mediated H3K4me3 methylation upregulates lncRNA HOXC-AS3 and the binding of HOXC-AS3 to EP300 and increases EP300 stability to suppress the ferroptosis of NSCLC cells.
Histone methyltransferases are crucial regulators in non-small cell lung cancer (NSCLC) development. This study explored the mechanism of histone methyltransferase SET domain containing 1A (SETD1A)-mediated H3K4me2 methylation in NSCLC cell ferroptosis and provides novel targets for NSCLC treatment. Upon downregulation of SETD1A in NSCLC cell lines, cell proliferation potential, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities, iron content, and SETD1A, long noncoding RNA HOXC cluster antisense RNA 3 (lncRNA HOXC-AS3), E1A binding protein p300 (EP300), glutathione peroxidase 4 (GPX4) expressions were determined via cell counting kit-8, ELISA, iron assay kits, RT-qPCR, and western blot. Enrichment levels of SETD1A and H3K4me3 in the HOXC-AS3 promotor were measured via chromatin immunoprecipitation, and the binding of HOXC-AS3 and EP300 was analyzed via RNA immunoprecipitation. Rescue experiments were performed to confirm their roles in NSCLC cell ferroptosis. Xenograft tumor models were established to validate the role of SETD1A in vivo. SETD1A, H3K4me3, HOXC-AS3, and EP300 were highly-expressed in NSCLC cells. Silencing SETD1A inhibited NSCLC cell proliferation, increased MDA and iron levels, and decreased SOD, GSH, and GPX4 levels. SETD1A downregulation reduced H3K4me3 level, HOXC-AS3 expression, the binding of HOXC-AS3 to EP300, and EP300 stability. Overexpression of HOXC-AS3 or EP300 reversed the promotion of silencing SETD1A on NSCLC cell ferroptosis. Silencing SETD1A reduced tumor volume and weight and positive rate of ki67 and increased ferroptosis through the HOXC-AS3/EP300 axis. SETD1A-mediated H3K4me2 methylation promoted HOXC-AS3 expression, binding of HOXC-AS3 to EP300, and EP300 stability, thereby suppressing NSCLC cell ferroptosis.


Physiologic and hemodynamic considerations in blood pressure control while maintaining organ perfusion.
Essential hypertension remains a significant contributor to mortality, despite treatments effective in decreasing blood pressure. A major reason mortality remains high may be that the conventional stepped-care approach does not always reduce blood pressure in a physiologic manner, which may result in metabolic derangements and elicitation of undesirable reflex mechanisms. Use of the stepped-care approach does not take into account fundamental hemodynamic differences associated with a hypertensive patient's age, race and weight. A nonphysiologic approach in the use of antihypertensive agents may be associated with progression of left ventricular hypertrophy, metabolic derangements, arrhythmias, sudden death, and increased atherosclerotic and nephrosclerotic complications. Considerations of the alterations in cardiovascular structure that can occur in light of the activity of the renin-angiotensin system, the sympathetic nervous system and transcellular calcium flux are discussed as to how they affect long-term survival.


Rational dosing of antimicrobial drugs: animals versus humans.
The rational dosing of antimicrobial drugs depends on knowledge of physiology, anatomy and pathology, including disease condition, and in major respects these differ between animals and humans and between species of animal. These differences lead to species variation in drug pharmacokinetics, which can be profound. This review highlights selected aspects of species differences in pharmacokinetics and considers underlying mechanisms by reference to ruminant and non-ruminant mammals, birds, fish and bees. For all species it is desirable and should be possible to design dosage schedules based on knowledge of drug pharmacokinetics and pharmacodynamics. There have been many attempts to integrate pharmacokinetic and pharmacodynamic data to provide dosage schedules which optimize efficacy and minimize opportunities for the development of antimicrobial resistance in both laboratory animal studies and human clinical trials. However, there have been relatively few studies in animal species of major veterinary interest. This review summarizes recent studies in four ruminant species (calf, sheep, goat and camel) which have used PK-PD integration to determine for the fluoroquinolone, danofloxacin, AUC/MIC ratios producing (a) bacteriostasis (b) bactericidal activity and (c) elimination of bacteria. Future possible developments in dosage schedule design are considered.


Quantitative structure-activity relationship studies of vitamin D receptor affinity for analogues of 1alpha,25-dihydroxyvitamin D3. 1: WHIM descriptors.
The weighted holistic invariant molecular (WHIM) approach has been applied to the study of the VDR affinity of 86 vitamin D analogues. A model able to describe more than 71% of the variance in the experimental activity was developed with the use of the mentioned approach. In contrast, none of three different approaches, including the use of BCUT, Galvez topological charge indices, and 2D autocorrelations descriptors, was able to explain more than 38% of the variance in the mentioned property, even with more variables in the equation.


Temporopolar Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy: A Two-Dimensional Anatomical Operative Video.
Mesial temporal lobe epilepsy is the most frequent type of focal epilepsy in young adults and the most commonly reported in surgical series worldwide.1,2 When seizures become refractory to drug therapy, they are unlikely to remit spontaneously, and for the 30% of patients with epilepsy that is refractory to antiepileptic drugs, resection of the mesial temporal lobe structures provides seizure control rates of 70%-80%.3,4 The transsylvian route for amygdalohippocampectomy has been used at our institution for many years, evolving from the first description of Yasargil through the inferior circular sulcus of insula to the most recent one through the amygdala trying to preserve the temporal stem.5,6 Despite good outcomes according to the Engel classification, analysis of late postoperative magnetic resonance imaging scans of our patients showed a high incidence of temporal pole atrophy and potential gliosis.7,8 Therefore, we decided to keep the transsylvian route, but we removed a portion of the temporal pole anterior to the limen insula, resulting in a temporopolar amygdalohippocampectomy.4,9 Temporopolar amygdalohippocampectomy demonstrated good temporal stem preservation, good visual outcomes, and good memory results.4 We also advocate that the transsylvian route has the potential to provide a superior view and resection of the piriform cortex, that is associated with seizure outcome after surgery.10 We present a case of a 42-year-old woman who had refractory seizures secondary to mesial temporal lobe epilepsy and underwent temporopolar amygdalohippocampectomy with a good outcome, remaining seizure-free (Engel IA) (Video 1). The patient provided consent for surgery and video publication.


Identifying risk controls for future advanced brain-computer interfaces: A prospective risk assessment approach using work domain analysis.
Brain-computer interface (BCI) technologies are progressing rapidly and may eventually be implemented widely within society, yet their risks have arguably not yet been comprehensively identified, nor understood. This study analysed an anticipated invasive BCI system lifecycle to identify the individual, organisational, and societal risks associated with BCIs, and controls that could be used to mitigate or eliminate these risks. A BCI system lifecycle work domain analysis model was developed and validated with 10 subject matter experts. The model was subsequently used to undertake a systems thinking-based risk assessment approach to identify risks that could emerge when functions are either undertaken sub-optimally or not undertaken at all. Eighteen broad risk themes were identified that could negatively impact the BCI system lifecycle in a variety of unique ways, while a larger number of controls for these risks were also identified. The most concerning risks included inadequate regulation of BCI technologies and inadequate training of BCI stakeholders, such as users and clinicians. In addition to specifying a practical set of risk controls to inform BCI device design, manufacture, adoption, and utilisation, the results demonstrate the complexity involved in managing BCI risks and suggests that a system-wide coordinated response is required. Future research is required to evaluate the comprehensiveness of the identified risks and the practicality of implementing the risk controls.


Impact of neck node radioresponsiveness on the regional control probability in patients with oropharynx and pharyngolarynx cancers managed by definitive radiotherapy.
We reviewed a series of 1,666 patients with squamous cell carcinoma of the oropharynx and pharyngolarynx treated with definitive radiation therapy to determine whether or not radioresponsiveness of the metastatic neck nodes is a reliable indicator of their radiocurability. In a determined group of 708 patients with clinically positive neck nodes, only one third of the adenopathies (247/759) completely regressed at the completion of the treatment. At 6 months, only ten percent of the nodes remained palpable. Lymph node clearance rates and halving diameter times were tumor size-dependent. Node clearance rate was also influenced by the site of the primary lesion. The impact of various parameters, both intrinsic and extrinsic to the tumor behavior, is discussed. Neck control probability was significantly higher for complete responders. In this group, the ultimate node control was as good for adenopathies larger than 6 cm as for the smaller ones. Tumor control probability directly related to clearance rate following radiotherapy. Finally, therapeutic implications are derived for nodal dose adjustments and optimal applicability of radiosurgical combinations.


Tumour radiological appearance evaluated by enhanced CT correlates with tumour progression and survival in curable gallbladder cancer.
Surgical resection has been proposed for curable gallbladder cancer (GBCA); however, optimal preoperative evaluation and resection planning methods remain unestablished. The aim of this study was to establish the types of CT tumour radiological appearances in GBCA with a focus on its association with clinicopathologic features and its prognostic impact in curable GBCA. In all, 118 patients surgically treated for GBCA were identified and CT tumour radiological appearances were reviewed. Models were established and internally validated. Clinicopathologic variables and prognostic impact were analysed for correlation with tumour radiological appearance. The classification and distribution of tumour radiological appearance in these patients was Type 1 (n = 14), Type 2 (n = 60), Type 3 (n = 21), Type 4 (n = 18), and undetermined (n = 5). Among the 113 patients, a higher tendency of T stage and incidence of lymph node metastasis was observed from Type 1 to Type 4. Most Type 1 patients were T1 stage, they have no lymph node involvement or recurrence. With a median follow-up of 25 months (range, 1-135 months), a clear prognostic difference was observed among the 4 types after surgical treatment (p < 0.001). Type 1 patients showed 100% 5-year survival rate. Among the 66 T2 tumours, both tumour location and tumour radiological appearance effectively stratified patient prognosis (p < 0.001, p = 0.007). Introducing tumour radiological appearance into tumour location enabled further prognostic stratification of the 35 T2h tumours (p < 0.001). Type of CT tumour radiological appearance is a predictor of tumour biology. It may improve preoperative evaluation and resection planning.


Long-time clinical experience in patient setup for several particle therapy clinical indications: management of patient positioning and evaluation of setup reproducibility and stability.
Accurate patient positioning is crucial in particle therapy due to the geometrical selectivity of particles. We report and discuss the National Center for Oncological Hadrontherapy (CNAO) experience in positioning accuracy and stability achieved with solid thermoplastic masks fixed on index base plates and assessed by daily orthogonal X-ray imaging. Positioning data were retrospectively collected (between 2012 and 2018) and grouped according to the treated anatomical site. 19696 fractions of 1325 patients were evaluated.The study was designed to assess:(i) the number of fractions in which a single correction vector was applied(SCV);(ii) the number of fractions in which further setup verification was performed (SV);(iii) the number of fractions in which SV lead to an additional correction within (MCV<5min) or after (MCV>5min) 5 minutes from the first setup correction;(iv) the systematic (Σ) and random (σ) error components of the correction vectors applied. A SCV was applied in 71.5% of fractions, otherwise SV was required. In 30.6% of fractions with SV, patient position was not further revised. In the remaining fractions, MCV<5min and MCV>5min were applied mainly in extracranial and cranial sites respectively.Interfraction Σ was ≤ 1.7 mm/0.7° and σ was ≤ 1.2 mm/0.6° in cranial sites while in extracranial sites Σ was ≤ 5.5 mm/0.9° and σ was ≤4.4 mm/0.9°. Setup residuals were submillimetric in all sites. In cranial patients, maximum intrafractional Σ was 0.8 mm/0.4°. This report extensively quantifies inter- and intrafraction setup accuracy on an institutional basis and confirms the need of image guidance to fully benefit from the geometrical selectivity of particles. The reported analysis provides a board institutional data set on the evaluation of patient immobilization and bony anatomy alignment for several particle therapy clinical indications.


NO mediates the effect of the synthetic natriuretic peptide NPCdc on kidney and aorta in nephrectomised rats.
NPCdc is a synthetic natriuretic peptide that was originally derived from another peptide, the NP2_Casca, isolated from Crotalus durissus cascavella venom. These molecules share 70% structural homology with natriuretic peptides obtained from different species, including humans. NP2_Casca induces vasorelaxation and increases nitric oxide levels independently of natriuretic peptide receptors A and B. This study aimed to investigate whether NPCdc-induced hypotension in control rats and rats with a reduced kidney mass is associated with effects on the glomerular filtration rate, NADPH oxidase activity and components downstream of natriuretic peptide receptor C (NPR-C). Anaesthetized Wistar rats that were subjected to a sham operation and 5/6 nephrectomy (5/6Nx) were infused with saline (vehicle) or NPCdc (7.5 μg/kg/min) for 70 min. The NPCdc treatment decreased the mean arterial pressure and NADPH oxidase activity while simultaneously increasing the glomerular filtration rate, fractional Na+ excretion and nitric oxide level. After 70 min, the levels of p-AKT Ser-473, p-eNOS Ser-1177, p-nNOS Ser-1417 and p-iNOSTyr-151 were not affected. However, p-ERK1/2 Thr-202/Tyr-204 levels were altered. Thus, nitric oxide and components of NPR-C signalling mediate the effects of NPCdc. The results suggest a potential therapeutic application of this peptide for cardiorenal syndrome.


Endodontic access of all-ceramic crowns.
This study determines the effects of access opening on all-ceramic (Dicor) crowns. Forty-two extracted permanent teeth were selected to represent the various types of human teeth. Crown preparations were completed, polysulfide impressions made, and stone dies poured. The dies were forwarded to a commercial dental laboratory for fabrication of the restorations. The crowns were luted to the prepared teeth and endodontic access openings were completed by using established criteria for access preparation. The crowns were removed and examined by direct vision, transillumination, stereomicroscopy, and scanning electron microscopy. Two crowns fractured during access preparation, seven crowns exhibited craze lines, and 29 crowns exhibited chipping of the ceramic material adjacent to the access opening. There was no significant difference in the extent of chipping with diamond or carbide instrumentation. However, carbide instrumentation caused more fractures and craze lines than did diamond instrumentation.


[Determination of the binding site of testis-specific nucleoporin BS-63 to transportin (karopherin beta 2) and the proof of their combination in vitro].
To locate the binding site of testis-specific nucleoporin BS-63 to transportin (karopherin beta 2) and confirm their combination in vitro. Constructed different fragments of C terminal BS-63 was employed to localize the binding site of the testis-specific nucleoporin BS-63 to transportin by yeast two-hybrid system technique pull-down test was used to identify the interaction between the purified expressed fragments of BS-63 0.6 K and transportin in vitro. BS-63 binding site to transportin was shortened from 1.6 kb to 0.6 kb which included a Ran binding domain (RanBD). SDS-PAGE and Western blot tests confirmed the recombinant purified protein coded by 0.6 kb fragment of BS-63 cDNA could interact with transportin in vitro. In germ cells, the function of the testis-specific nucleoporin BS-63 localized at cytoplasmic side of NPC importing cargoes into nuclear may be accomplished by transportin cooperation.


Inhibition of RNA cleavage but not polyadenylation by a point mutation in mRNA 3' consensus sequence AAUAAA.
A single U leads to G transversion in the 3' consensus sequence AAUAAA of the adenovirus early region 1A gene was constructed and the effect of this mutation on processing of the 3' end of the nuclear early region 1A RNAs was analysed. The results demonstrate that the intact AAUAAA is not required for RNA polyadenylation but is required for the cleavage step preceding polyadenylation to occur efficiently.


The hypercalcemic Walker carcinosarcoma 256 of the rat causes an increase in serum 1,25-dihydroxyvitamin D3.
We have studied vitamin D metabolism in rats with the transplantable hypercalcemic Walker carcinosarcoma 256, which is a well characterized animal model for humoral hypercalcemia of malignancy. 25-Hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations were determined in blood samples obtained from parathyroidectomized (PTX) female rats at different time intervals after intramuscular tumor cell inoculation. We observed a dramatic increase in serum 1,25(OH)2D3 (280 +/- 184 vs. 98 +/- 31 pmol/l) 6 days after tumor cell injection and 4 days after the initial rise of serum calcium, whereas 25(OH)D3 tended to decrease. In a separate control experiment we compared this to the effect of exogenous parathyroid hormone in PTX rats and found similar results. In contrast, rats exhibited no change in vitamin D metabolite blood concentration after inoculation of the normocalcemic Yoshida sarcoma, which obviously does not interfere with vitamin D metabolism. We conclude that the humoral bone-resorbing agent produced by the Walker tumor cells causes elevation of serum 1,25(OH)2D3 concentration by this fulfilling an additional criterion of PTH-like activity.


Androgen receptor in prostate cancer: cause or cure?
Growth of prostate tumours is dependent on androgens. Hence, therapy involves removing androgens and opposing their effects using antiandrogens. This is initially successful but inevitably fails and tumours recur. The cause of this transition to hormone-independence, and the precise role of the androgen receptor in this, is a matter of considerable debate. A recent study used a mouse model to assess the effects of increased androgen receptor expression in the prostate and found that, whereas increased expression of wild-type receptor had no effect, a mutation of the androgen receptor caused it to have oncogenic properties. This goes some way to elucidating how the androgen receptor affects tumour growth, and provides an exciting model for further study of androgen receptor mutations in prostate cancer.


Erratum: Dihydroartemisinin suppresses proliferation, migration, the Wnt/β-catenin pathway and EMT via TNKS in gastric cancer.
[This corrects the article DOI: 10.3892/ol.2021.12949.].


Effects of gabapentin on experimental somatic pain and temporal summation.
Gabapentin is used for treatment of neuropathic pain, but its effect on different somatic pain modalities and integrative mechanisms are not completely understood. The aim of this double-blind, placebo-controlled experimental pain study, conducted on 20 healthy volunteers, was to examine the effect of a single dose of 1200 mg gabapentin on multi-modal experimental cutaneous and muscle pain models. The following pain models were applied: (1) pain thresholds to single and repeated cutaneous and intramuscular electrical stimulation (temporal summation to 5 stimuli delivered at 2 Hz); (2) stimulus-response function relating pain intensity scores (visual analog scale, VAS) to increasing current intensities for electrical skin and muscle stimuli (single and repeated, determined at baseline); and (3) the pain intensity (VAS) and pain areas after intramuscular injection of hypertonic saline. Pain assessments were performed prior to, and at 4, 6, and 8 hours after medication. When responses were averaged across the post-dose times, gabapentin: (1) significantly increased the temporal summation pain threshold in skin compared with placebo (P = .03); (2) significantly reduced the area under the pain intensity curve to hypertonic saline injections in the muscle (P = .02); and (3) significantly reduced the area of pain evoked by hypertonic saline (P = .03). Gabapentin reduces temporal summation of skin stimuli at pain threshold intensities; this may have potential as a biomarker for drugs with efficacy on neurogenic pain. The data also suggest that tonic muscle pain is responsive to gabapentin treatment and suggest further clinical studies.


Dental hygiene participation in managing incipient and hidden caries.
With the advent of new caries detection devices that allow early detection, dental hygienists can intervene in the demineralization process and work with the patient toward remineralization through patient self-care procedures and the professional application of topical fluorides. The focus of this article is on caries detection devices, caries risk assessment, agents used to prevent dental caries, and the development of self-care plans for patients that include prevention, intervention, and therapeutic components.


The mediating role of resilience in the relationship between social support and quality of life among patients after radical cystectomy: A structural equation model analysis.
This study aimed to examine the relationship between social support and quality of life in urostomy patients and identify the mediating role of resilience in that relationship. A cross-sectional design. Participants included 232 patients who were recruited from a tertiary hospital in Beijing during March 2020 and August 2020. They completed questionnaires about perceived social support, resilience and ostomy-related quality of life. Structural equation modelling was performed to analyse the data. The mean age of patients was 65.79 (SD = 8.67) years, and the mean length of time after surgery was 42.14 (SD = 15.76) months. Urostomy patients' quality of life, social support and resilience were all above moderate. Social support had a positive direct effect on the quality of life and a positive indirect effect on the quality of life through the mediating role of resilience.


Genome-wide DNA methylation analysis reveals layer-specific methylation patterns in deer antler tissue.
This paper explored using of deer antlers as a model for studying rapid growth and cartilage formation in mammals. The genes and regulatory mechanisms involved in antler chondrogenesis are poorly understood, however, previous research has suggested that DNA methylation played a key role in antler regeneration. By using fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP), this study measured DNA methylation levels in cartilage (CA) and reserve mesenchyme (RM) cells and tissues. Results showed that RM cells (RMCs) DNA methylation levels were significantly lower than those of CA, suggesting that DNA demethylation may be involved in antler fast cartilage differentiation. The study also identified 20 methylated fragments specific to RMCs or CA using the methylation-sensitive amplified polymorphism (MSAP) technique and confirmed these findings using southern blot analysis. The data provide the first experimental evidence of a link between epigenetic regulation and rapid cartilage differentiation in antlers.


Forces exerted by conventional and self-ligating brackets during simulated first- and second-order corrections.
Our aim in this study was to comparatively assess the forces generated from conventional and self-ligating bracket systems during the late leveling and alignment stage, specifically for first- and second-order movement. Three types of brackets were selected: Orthos2 (Ormco, Glendora, Calif), Damon2 (Ormco), and In Ovation-R (GAC, Bohemia, NY). The brackets were bonded on resin replicas constructed from a model of an aligned mandibular arch, and a 0.014 x 0.025-in copper-nickel-titanium wire (Ormco) was placed. First- and second-order corrections-buccolingual and intrusion-extrusion movements-were simulated on the orthodontic measurement and simulation system. A 2-mm displacement was applied on the x-axis and a 1-mm displacement on the z-axis, both in 0.1-mm intervals; 5 repetitions were performed for each wire-bracket-interval combination, and new brackets and archwires were used for each trial. The forces generated by manipulation of the bracket in the 2 directions were recorded directly with the orthodontic measurement and simulation system software and were statistically analyzed with 2-way ANOVA, with bracket and displacement as the discriminating variables. Group differences were further analyzed with the Tukey post-hoc comparisons test with the family error rate set at the 0.05 level. In the first-order correction, the direction showed a significant effect on force magnitude, with inward (lingual) movement having lower force levels for the In Ovation-R. No significant difference was found between the Damon2 and the conventional appliance for this movement. In the second-order model, no difference was noted between the 2 self-ligating brackets in magnitude of force, but the conventional bracket showed higher force levels, which accounted for 20%, or 1 N, of the increase in magnitude. The effect of the direction of displacement (intrusion vs extrusion) on force variation did not produce a significant effect. The forces generated by first- and second-order corrections in self-ligating appliances do not show a consistent pattern and depend on the wire, the direction of movement, and the design of the ligating component.


Changes in urinary delta-aminolevulinic acid at low lead exposure level with special reference to production activity.
A 7-year follow-up survey on 53 workers was carried out in a lead storage battery factory to evaluate the significance of urinary delta-aminolevulinic acid (ALA) and blood lead in a work environment where lead in the air was considered to be about or less than the current occupational exposure limit. While lead in the blood and ALA in the urine had a good correlation to each other cross-sectionally as well as longitudinally, geometric means of lead concentrations in the workroom air samples which were collected following grid sampling strategy, did not correlate with ALA in urine significantly. On the contrary, the semiannual production of batteries significantly correlated with changes in mean ALA in urine. The questionnaire survey proved that the prolongation in work hours, lead to an increase in the mean ALA in urine as well as a higher incidence of higher-than-normal urinary ALA. The results clearly demonstrated the importance of the biological indicators, such as lead in blood and urinary ALA, as well as the necessity of paying attention to non-industrial hygiene factors, such as the production rate of batteries and the length of the daily shift, for the protection of the workers' health when lead in the air is moderate.


Progressive supranuclear palsy: electomyographic examinations of eye muscles.
Electromyographic examination of vertical and lateral extraocular muscles was carried out in five patients suffering from progressive supranuclear palsy, and incapable of performing voluntary vertical eye movements. No evidence of a lower motor neurone lesion or paradoxical innervation of eye muscles was noted. Reciprocal inhibiton of antagonist vertical muscles though present in oculocephalic (doll's head) stimulation, was incomplete on attempted voluntary movement. This factor is held to be the probable immediate cause of the vertical gaze palsy.


Reducing viral contamination from finger pads: handwashing is more effective than alcohol-based hand disinfectants.
Hand hygiene is important for interrupting transmission of viruses through hands. Effectiveness of alcohol-based hand disinfectant has been shown for bacteria but their effectiveness in reducing transmission of viruses is ambiguous. To test efficacy of alcohol hand disinfectant against human enteric and respiratory viruses and to compare efficacy of an alcohol-based hand disinfectant and handwashing with soap and water against norovirus. Efficacies of a propanol and an ethanol-based hand disinfectant against human enteric and respiratory viruses were tested in carrier tests. Efficacy of an alcohol-based hand disinfectant and handwashing with soap and water against noroviruses GI.4, GII.4, and MNV1 were tested using finger pad tests. The alcohol-based hand disinfectant reduced the infectivity of rotavirus and influenza A virus completely within 30s whereas poliovirus Sabin 1, adenovirus type 5, parechovirus 1, and MNV1 infectivity were reduced <3 log10 within 3 min. MNV1 infectivity reduction by washing hands with soap and water for 30s (>3.0 ± 0.4 log10) was significantly higher than treating hands with alcohol (2.8 ± 1.5 log10). Washing with soap and water for 30s removed genomic copies of MNV1 (>5 log10), noroviruses GI.4 (>6 log10), and GII.4 (4 log10) completely from all finger pads. Treating hands with propanol-based hand disinfectant showed little or no reduction to complete reduction with mean genomic copy reduction of noroviruses GI.4, GII.4, and MNV1 being >2.6, >3.3, and >1.2 log10 polymerase chain reaction units respectively. Washing hands with soap and water is better than using alcohol-based hand disinfectants in removing noroviruses from hands.


Diversity of Dopaminergic Neural Circuits in Response to Drug Exposure.
Addictive substances are known to increase dopaminergic signaling in the mesocorticolimbic system. The origin of this dopamine (DA) signaling originates in the ventral tegmental area (VTA), which sends afferents to various targets, including the nucleus accumbens, the medial prefrontal cortex, and the basolateral amygdala. VTA DA neurons mediate stimuli saliency and goal-directed behaviors. These neurons undergo robust drug-induced intrinsic and extrinsic synaptic mechanisms following acute and chronic drug exposure, which are part of brain-wide adaptations that ultimately lead to the transition into a drug-dependent state. Interestingly, recent investigations of the differential subpopulations of VTA DA neurons have revealed projection-specific functional roles in mediating reward, aversion, and stress. It is now critical to view drug-induced neuroadaptations from a circuit-level perspective to gain insight into how differential dopaminergic adaptations and signaling to targets of the mesocorticolimbic system mediates drug reward. This review hopes to describe the projection-specific intrinsic characteristics of these subpopulations, the differential afferent inputs onto these VTA DA neuron subpopulations, and consolidate findings of drug-induced plasticity of VTA DA neurons and highlight the importance of future projection-based studies of this system.


Bioassay-guided discovery of antibacterial agents: in vitro screening of Peperomia vulcanica, Peperomia fernandopoioana and Scleria striatinux.
The global burden of bacterial infections is high and has been further aggravated by increasing resistance to antibiotics. In the search for novel antibacterials, three medicinal plants: Peperomia vulcanica, Peperomia fernandopoioana (Piperaceae) and Scleria striatinux (Cyperaceae), were investigated for antibacterial activity and toxicity. Crude extracts of these plants were tested by the disc diffusion method against six bacterial test organisms followed by bio-assay guided fractionation, isolation and testing of pure compounds. The minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations were measured by the microdilution method. The acute toxicity of the active extracts and cytotoxicity of the active compound were performed in mice and mammalian cells, respectively. The diameter of the zones of inhibition (DZI) of the extracts ranged from 7-13 mm on Escherichia coli and Staphylococcus aureus of which the methylene chloride:methanol [1:1] extract of Scleria striatinux recorded the highest activity (DZI = 13 mm). Twenty-nine pure compounds were screened and one, Okundoperoxide, isolated from S. striatinux, recorded a DZI ranging from 10-19 mm on S. aureus. The MICs and MBCs indicated that the Peperomias had broad-spectrum bacteriostatic activity. Toxicity tests showed that Okundoperoxide may have a low risk of toxicity with an LC50 of 46.88 μg/mL. The antibacterial activity of these plants supports their use in traditional medicine. The pure compound, Okundoperoxide, may yield new antibacterial lead compounds following medicinal chemistry exploration.


Proteomics pipeline for phosphoenrichment and its application on a human melanoma cell model.
Cell signalling is tightly regulated by post-translational modification of proteins. Among them, phosphorylation is one of the most interesting and important. Identifying phosphorylation sites on proteins is challenging and requires strategies for pre-separation and enrichment of the phosphorylated species. We applied four different methods for phospho-enrichment involving TiO2 and IMAC matrix to human melanoma cell lysates of starved A375 induced for 1 h with 1% FBS. Comparison of protocol efficiency was evaluated through peptide concentration, sulphur and phosphorus content and peptide analysis by LC-MS in the collected fractions. Our results underlined that each single method is not sufficient for a comprehensive phosphoproteome analysis. In fact, each methodology permits to identify only a fraction of the phosphoproteome contained in a whole cell lysate. The selection of the most efficient protocols and a combination of two phospho-enrichment methods allowed the assessment of this workflow able to pinpoint the main actors in the phospho-proteome cascade of A375 human melanoma cells treated with Vemurafenib.


Alternate, adjacent 2 and 3:1 meiotic segregation products from a balanced t(13;18) (q12;q11) carrier.
We present a case in which alternate, adjacent 2 and 3:1 meiotic segregations have occurred in the pregnancies of a female carrier of a balanced reciprocal translocation -46,XX,t(13;18) (q12;q11). Products of five conceptions effectively showed trisomy 18q, trisomy 18p or monosomy 18p. This is one of the rare rearrangements which can give rise to a variety of segregation modes including adjacent 2.


Neurological development during toddling age in normal children and children at risk of developmental disorders.
Toddling age (1.5-4 years) is a period in which the quality rather than the quantity of motor functions changes. We examined 305 normal and 43 so called 'risk' children with an examination technique which concentrates on observations of motor functions (grasping, sitting, crawling, standing and walking) in a standardized free field situation. Examples of the changes during toddling age are presented such as the decrease of yoke movements (i.e. shoulder movements during reaching), the increase of trunk motility, of variability of speed during crawling, narrowing of gait width, and an increased ability to avoid objects on the floor and to show maneuverability during walking. All changes occurred in the normal children between the ages of 2 and 3 years. They reflect a 'transformation' of neural functions. Many of the 'risk' children show qualitatively different motor behaviour, which is interpreted as non-optimal and which can be an early sign of neurological impairment. The transformation in neural functions is discussed in terms of neuroanatomical changes during toddling age.


The toxicity, distribution and excretion of ricin holotoxin in rats.
The distribution and excretion of the plant toxin ricin were studied in rats after intravenous injection. 125I-labelled ricin was equal in toxicity to native ricin. Following injection, the liver was the major organ of localisation - 46% of injected dose at 0.5 h. The spleen and muscle were next with 9.9% and 13%, respectively, at 0.5 h. Ricin was relatively concentrated in the spleen (33% of injected dose/g of tissue) compared with the liver (7.4%/g) and the bone marrow (5.5%/g). The concentration in the lymph nodes was very low (1.2%/g). Ricin was quickly cleared from the animal; only 11% of the initial radioactivity remained 24 h later with 70% excreted in the urine. Excretion into the intestine via the bile duct was less than 5% by 24 h, 10-12% of the radioactivity was found in the intestinal contents or intestinal wall between 3 h and 12 h, and much of this was reabsorbed since less than 2% was recovered in faeces.


Vitamin D, parathyroid hormone, and bone mineral content of lumbar spine and femur in primary biliary cirrhosis.
In order to elucidate the pathogenesis and degree of osteopoenia in primary biliary cirrhosis (PBC) we conducted a cross-sectional study of 47 non-selected female patients with biopsy-proven PBC. Bone mineral content (BMC) of the lumbar spine, femoral neck and femoral shaft was determined using dual photon absorptiometry. Compared to healthy females of corresponding decades the PBC patients exhibited significantly decreased mean BMC-values in lumbar spine (88%, P less than 0.05) and femoral neck (92%, P less than 0.05) but not in femoral shaft (96%, NS). Bone mineral content was not significantly associated with duration of liver disease, impairment of liver function (serum concentrations of albumin, clotting factors II + VII + X, bilirubin, alkaline phosphatase galactose elimination capacity or histology), variables reflecting calcium homeostasis (serum concentrations of ionized calcium, parathyroid hormone, vitamin D binding protein, 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3) or previous treatment with glucocorticosteroids. In view of our negative findings we suggest that future studies in this field should focus on physical activity and female sex hormones as determinants for the prevention of osteopoenia in females with primary biliary cirrhosis.


Human neurotropic polyomavirus, JCV, and its role in carcinogenesis.
A number of recent studies have reported the detection of the ubiquitous human polyomavirus, JC virus (JCV), in samples derived from several types of neural as well as non-neural human tumors. The human neurotropic JCV was first identified as the etiologic agent of the fatal demyelinating disease, progressive multifocal leukoencephalopathy, which usually occurs in individuals with defects in cell-mediated immunity, including AIDS. However, upon mounting evidence of the oncogenic potential of the viral regulatory protein, T-antigen, and JCV's oncogenecity in a broad range of animal models, studies were initiated to determine its potential involvement in human carcinogenesis. Initially, the most frequently observed tumors in rodent models, including medulloblastoma, astrocytoma, glioblastoma, and other neural-origin tumors were analysed. These studies were followed by analysis of non-neural tumors such as colorectal carcinomas. In a subset of each tumor type examined, JC viral genomic DNA sequences could be detected by PCR and confirmed by Southern blot hybridization or direct sequencing. In a smaller subset of the tumors, the expression of T-antigen was observed by immunohistochemical analysis. Owing to the established functions of T-antigen including its ability to interact with tumor suppressor proteins such as Rb and p53, and its ability to influence chromosomal stability, potential mechanisms of JCV T-antigen-mediated cellular dysregulation are discussed. Further, as increasing evidence suggests that T-antigen is not required for maintenance of a transformed phenotype, a hit-and-run model for T-antigen-induced transformation is proposed.


Humic substances from sewage sludge compost as washing agent effectively remove Cu and Cd from soil.
Although commercially available biosurfactants are environmentally friendly and effectively remove heavy metals from soil, they are costly. Therefore, this study investigated whether inexpensive humic substances (HS) from sewage sludge compost could effectively remove copper (Cu) and cadmium (Cd) from highly contaminated sandy clay loam (S1) and clay (S2). The optimum HS concentration and pH were determined, as well process kinetics. Under optimum conditions, a single washing removed 80.7% of Cu and 69.1% of Cd from S1, and 53.2% and 36.5%, respectively, from S2. Triple washing increased removal from S1 to almost 100% for both metals, and to 83.2% of Cu and 88.9% of Cd from S2. Triple washing lowered the potential ecological risk (Er(i)) of the soils, especially the risk from Cd. HS substances show potential for treating soils highly contaminated with heavy metals, and HS from other sources should be tested with these and other contaminants.


Feasible etiology of vanishing testis regarding disturbance of testicular development: histopathological and immunohistochemical evaluation of testicular nubbins.
To identify the causes of vanishing testis besides vascular events secondary to testicular torsion. A total of 102 boys with vanishing testis were treated in our hospital from 1984 to 2011. Of these cases, 91 testicular nubbins were excised. Immunohistochemical analysis of testicular nubbins was carried out using anti-Wilms tumor 1 antibody, which is a stable marker of Sertoli cells. Reverse transcription polymerase chain reaction was also carried out using Wilms tumor 1-specific primers. Most testicular nubbins were associated with inguinal lesion (51 patients, 56.0%). Light microscopy showed that 11 patients (12.5%) had seminiferous tubules (with germ cells in three patients [3.4%]), and 77 patients lacked seminiferous tubules, some of which had calcification (26 patients, 29.5%), and/or deposition of hemosiderin (21 patients, 23.9%). Immunohistochemical analysis showed Wilms tumor 1 expression not only in the Sertoli cells of the seminiferous tubules in the seminiferous tubule-positive patients, but also in the interstitium of testicular nubbins in the seminiferous tubule-negative patients. Reverse transcription polymerase chain reaction showed Wilms tumor 1 messenger ribonucleic acid expression in the testicular nubbins of both seminiferous tubule-positive and tubule-negative patients. The presence of Wilms tumor 1-positive cells in the interstitium of vanishing testis lacking seminiferous tubules suggests that the disturbance of testicular development after Sertoli cell differentiation and during testicular tubule formation might be involved in the etiology of vanishing testis.


Transient partial ophthalmoplegia and Horner's syndrome after intraoral local anesthesia.
Local neurological symptoms and signs are infrequent after intraoral anesthesia for dental procedures, thus diagnosis may be challenging for a neurologist unfamiliar with this benign phenomenon. Unnecessary diagnostic procedures may be performed and can be associated with complications. We present a 19-year old woman with transient diplopia, miosis, partial enophthalmia and lacrimation on the side of injection after intraoral anesthesia with prilocaine.


Studies on the membrane glycoprotein defect of En(a-) erythrocytes. III. N-terminal amino acids of sialoglycoproteins from normal and En(a-) red cells.
Sodium dodecylsulphate polyacrylamide gel electrophoretic methods and quantitative analyses of the N-terminal amino acids were applied to the sialoglycoprotein mixture and glycoprotein fractions from normal erythrocyte membranes, as well as preparations from red cells of individuals belonging to the English and Finnish En(a-) families. The data confirm the observation by alternative methods that SS cells exhibit a higher Ss glycoprotein content than ss erythrocytes. The results of end-group analyses suggest that the N-terminal amino acids serine and leucine represent the structures differentiating the MN and the 'M' and 'N' antigens on the MN and Ss glycoproteins respectively. Data from peptide sequence analyses confirm that the glycine/glutamic acid polymorphism at the fifth position of the MN glycoprotein's peptide chain is closely or absolutely linked with the serine/leucine polymorphism at its N-terminal position. As normal (EnaEna) red cells exhibiting 'M' antigenic properties have not been detected, the hypothesis is proposed that the Ss glycoprotein of English En(a-) erythrocytes possesses an MN-Ss hybrid polypeptide chain analogous to those of the delta-beta Lepore haemoglobins.


Replicative stress, stem cells and aging.
DNA synthesis is a remarkably vulnerable phase in the cell cycle. In addition to introduction of errors during semi-conservative replication, the inherently labile structure of the replication fork, as well as numerous pitfalls encountered in the course of fork progression, make the normally stable double stranded molecule susceptible to collapse and recombination. As described in this issue, maintenance of genome integrity in the face of such events is essential to prevent the premature onset of age-related diseases. At the organismal level, the roles for such maintenance are numerous; however, the preservation of stem and progenitor cell pools may be particularly important as indicated by several genetically engineered mouse models. Stresses on stem and progenitor cell pools, in the form of telomere shortening (Terc(-/-)) or other genome maintenance failures (ATR(mKO), Ku86(-/-), LIG4(Y288C), XPD(R722W/R722W), etc.), have been shown to degrade tissue renewal capacity and accelerate the appearance of age-related phenotypes. In the case of telomere shortening, exhaustion of replicative potential appears to be at least partially dependent on the cell cycle regulatory component of the DNA damage response. Therefore, both the genome maintenance mechanisms that counter DNA damage and the cell cycle checkpoint responses to damage strongly influence the onset of age-related diseases and do so, at least in part, by affecting long-term stem and progenitor cell potential.


Factors associated with onset timing, symptoms, and severity of depression identified in the postpartum period.
Unipolar and bipolar depression identified in the postpartum period have a heterogeneous etiology. The objectives of this study are to examine the risk factors that distinguish the timing of onset for unipolar and bipolar depression and the associations between depression onset by diagnosis, and general and atypical depressive symptoms. Symptoms of depression were assessed at 4- to 6-weeks postpartum by the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Symptoms in an obstetrical sample of 727 women. Data were analyzed using ANOVA, Chi-square, and linear regression. Mothers with postpartum onset of depression were more likely to be older, Caucasian, educated, married/cohabitating, have one or no previous child, and have private insurance in contrast to mothers with pre-pregnancy and prenatal onset of depression. Mothers with bipolar depression were more likely to have a pre-pregnancy onset. Three general and two atypical depressive symptoms distinguished pre-pregnancy, during pregnancy, and postpartum depression onset, and the presence of agitation distinguished between unipolar and bipolar depression. The sample was urban, which may not be generalizable to other populations. The study was cross-sectional, which excludes potential late onset of depression (after 4-6 weeks) in the first postpartum year. A collective set of factors predicted the onset of depression identified in the postpartum for mothers distinguished by episodes of unipolar versus bipolar depression, which can inform clinical interventions. Future research on the onset of major depressive episodes could inform prophylactic and early psychiatric interventions.


A case of adolescent pelvic inflammatory disease caused by a rare bacterium: Fusobacterium nucleatum.
Pelvic inflammatory disease (PID) is a polymicrobial infection that typically occurs in sexually active females. PID is rare in premenarchal and/or noncoital young women; however, there are case reports of PID occurring in virginal females. We present the first reported case of PID associated with F. nucleatum. In this unusual case of PID in an adolescent, the responsible organism may have originated from the patient's oral cavity. A 13-year-old noncoital Caucasian female presented to a tertiary children's hospital with fever and acute abdominal/pelvic pain. She had experienced a perforated appendix 14 months prior, which was treated by laparoscopy. Postoperatively, she experienced intermittent episodes of recurrent abdominal pain. During this presentation, the physical examination and ultrasound findings were suspicious for an ovarian torsion. She was taken to the operating room where she had an examination under anesthesia and a diagnostic laparoscopy. Findings at the time of laparoscopy were in keeping with a diagnosis of pelvic inflammatory disease. Oral and pelvic fluid cultures were positive for F. nucleatum. She was subsequently treated with antibiotics and her symptoms resolved. This case highlights the importance of including PID in the differential diagnosis of noncoital adolescent females presenting with an acute abdomen. Although most Fusobacteria infections are periodontal in nature, translocated infections to the pelvis may have long-term implications for reproductive health. This case also highlights the importance of the role of diagnostic laparoscopy in young women who have persistent pain following previous surgery due to the potential of missed pathology or subclinical infection.


Phenyl sulfur mustard derivatives of distamycin A.
The design, synthesis, and cytotoxic activity of novel benzoyl and cinnamoyl sulfur mustard derivatives of distamycin A are described and structure activity relationships are discussed. These sulfur mustards are more potent cytotoxics than corresponding nitrogen mustards in spite of the lower alkylating power, while their sulfoxide analogues are substantially inactive. Cinnamoyl sulfur mustard derivative (7) proved to be one of the most active distamycin-derived cytotoxics, about 1000 times more potent than melphalan.


Functional status and quality of life after transcatheter aortic valve replacement: a systematic review.
The functional and quality-of-life benefits of transcatheter aortic valve replacement (TAVR) have not been established. To evaluate the changes in functional status and quality of life after TAVR. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1 January 2002 to 30 September 2013. Studies of TAVR that reported the New York Heart Association (NYHA) class, Short Form-12/36 Health Survey physical and mental component summary (points), or other measures of functional status. Two reviewers independently extracted the mean change (follow-up minus baseline) in primary outcomes. Because of substantial heterogeneity, data were not pooled; the range of mean change was summarized. We identified 60 observational studies (56 pre–post comparison and 4 head-to-head comparative studies) and 2 randomized, controlled trials (11 205 patients). Most studies showed a clinically important decrease in NYHA class at 6 to 11 months (range, -0.8 to -2.1 classes) and 12 to 23 months (range, -0.8 to -2.1 classes). The improvement in the Short Form-12/36 Health Survey physical component score was clinically important over 12 months (range, 4.9 to 26.9 points), and the change in mental component score was smaller (range, 1.0 to 8.9 points).Clinically important improvements were seen in other disease-specific measures but were less consistently seen in general health measures. Comparative evidence is limited by few head-to-head studies. Survivor bias may have overestimated the benefits. Transcatheter aortic valve replacement provides clinically important benefits in physical function and disease-specific measures of quality of life but modest benefits in psychological and general health measures. More comparative studies on functional status and quality of life are needed for informed treatment decision making.


Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors with distinct Ca(2+) affinities.
Synaptotagmins constitute a large family of membrane proteins implicated in Ca(2+)-triggered exocytosis. Structurally similar synaptotagmins are differentially localized either to secretory vesicles or to plasma membranes, suggesting distinct functions. Using measurements of the Ca(2+) affinities of synaptotagmin C2-domains in a complex with phospholipids, we now show that different synaptotagmins exhibit distinct Ca(2+) affinities, with plasma membrane synaptotagmins binding Ca(2+) with a 5- to 10-fold higher affinity than vesicular synaptotagmins. To test whether these differences in Ca(2+) affinities are functionally important, we examined the effects of synaptotagmin C2-domains on Ca(2+)-triggered exocytosis in permeabilized PC12 cells. A precise correlation was observed between the apparent Ca(2+) affinities of synaptotagmins in the presence of phospholipids and their action in PC12 cell exocytosis. This was extended to PC12 cell exocytosis triggered by Sr(2+), which was also selectively affected by high-affinity C2-domains of synaptotagmins. Together, our results suggest that Ca(2+) triggering of exocytosis involves tandem Ca(2+) sensors provided by distinct plasma membrane and vesicular synaptotagmins. According to this hypothesis, plasma membrane synaptotagmins represent high-affinity Ca(2+) sensors involved in slow Ca(2+)-dependent exocytosis, whereas vesicular synaptotagmins function as low-affinity Ca(2+) sensors specialized for fast Ca(2+)-dependent exocytosis.


A short review on SSF - an interesting process option for ethanol production from lignocellulosic feedstocks.
Simultaneous saccharification and fermentation (SSF) is one process option for production of ethanol from lignocellulose. The principal benefits of performing the enzymatic hydrolysis together with the fermentation, instead of in a separate step after the hydrolysis, are the reduced end-product inhibition of the enzymatic hydrolysis, and the reduced investment costs. The principal drawbacks, on the other hand, are the need to find favorable conditions (e.g. temperature and pH) for both the enzymatic hydrolysis and the fermentation and the difficulty to recycle the fermenting organism and the enzymes. To satisfy the first requirement, the temperature is normally kept below 37 degrees C, whereas the difficulty to recycle the yeast makes it beneficial to operate with a low yeast concentration and at a high solid loading. In this review, we make a brief overview of recent experimental work and development of SSF using lignocellulosic feedstocks. Significant progress has been made with respect to increasing the substrate loading, decreasing the yeast concentration and co-fermentation of both hexoses and pentoses during SSF. Presently, an SSF process for e.g. wheat straw hydrolyzate can be expected to give final ethanol concentrations close to 40 g L-1 with a yield based on total hexoses and pentoses higher than 70%.


The transformation of provisioning systems from an integrated perspective of social metabolism and political economy: a conceptual framework.
Energy, food, or mobility can be conceptualized as provisioning systems which are decisive to sustainability transformations in how they shape resource use and because of emissions resulting from them. To curb environmental pressures and improve societal well-being, fundamental changes to existing provisioning systems are necessary. In this article, we propose that provisioning systems be conceptualized as featuring integrated socio-metabolic and political-economic dimensions. In socio-metabolic terms, material stocks-buildings, infrastructures, and machines, for example-are key components of provisioning systems and transform flows of energy and materials into goods and services. In political-economic terms, provisioning systems are formed by actors, institutions, and capital. We loosely identify and closely analyze, from socio-metabolic and political-economic perspectives, five phases along which provisioning systems are shaped and in which specific opportunities for interventions exist. Relying mainly on examples from the fossil-fueled electricity system, we argue that an integrated conceptualization of provisioning systems can advance understanding of these systems in two essential ways: by (1) facilitating a more encompassing perspective on current forms of provisioning as relying on capitalist regulation and on material stocks and flows and by (2) embedding provisioning systems within their historical context, making it possible to conceive of more sustainable and just forms of provisioning under (radically) altered conditions.


Gravity, the hydrostatic indifference concept and the cardiovascular system.
Gravity, like any acceleration, causes a hydrostatic pressure gradient in fluid-filled bodily compartments. At a force of 1G, this pressure gradient amounts to 10 kPa/m. Postural changes alter the distribution of hydrostatic pressure patterns according to the body's alignment to the acceleration field. At a certain location--referred to as hydrostatically indifferent--within any given fluid compartment, pressure remains constant during a given change of position relative to the acceleration force acting upon the body. At this specific location, there is probably little change in vessel volume, wall tension, and the balance of Starling forces after a positional manoeuvre. In terms of cardiac function, this is important because arterial and venous hydrostatic indifference locations determine postural cardiac preload and afterload changes. Baroreceptors pick up pressure signals that depend on their respective distance to hydrostatic indifference locations with any change of body position. Vascular shape, filling volume, and compliance, as well as temperature, nervous and endocrine factors, drugs, and time all influence hydrostatic indifference locations. This paper reviews the physiology of pressure gradients in the cardiovascular system that are operational in a gravitational/acceleration field, offers a broadened hydrostatic indifference concept, and discusses implications that are relevant in physiological and clinical terms.


Bystander killing of malignant cells via the delivery of engineered thymidine-active deoxycytidine kinase for suicide gene therapy of cancer.
Activity and specificity of chemotherapeutic agents against solid tumors can be augmented via the targeted or localized delivery of 'suicide' genes. Selective activation of specific prodrugs in cells expressing the 'suicide' gene drives their elimination by apoptosis, while also enabling the killing of adjacent bystander cells. Strong bystander effects can compensate for poor 'suicide' gene delivery, and depend on the prodrugs used and mechanisms for the acquisition of activated drug by the bystander population, such as the presence of gap junctional intercellular communications. Although a number of 'suicide' gene therapies for cancer have been developed and characterized, such as herpes simplex virus-derived thymidine kinase (HSV-tk)-based activation of ganciclovir, their limited success highlights the need for the development of more robust approaches. Limiting activation kinetics and evolution of chemoresistance are major obstacles. Here we describe 'suicide' gene therapy of cancer based on the lentivirus-mediated delivery of a thymidine-active human deoxycytidine kinase variant. This enzyme possesses substrate plasticity that enables it to activate a multitude of prodrugs, some with distinct mechanisms of action. We evaluated the magnitude and mechanisms of bystander effects induced by different prodrugs, and show that when used in combination, they can synergistically enhance the bystander effect while avoiding off-target toxicity.


Fast, pseudo-continuous arterial spin labeling for functional imaging using a two-coil system.
A fast, two-coil, pseudo-continuous labeling scheme is presented. This new scheme permits the collection of a multislice subtraction pair in <3 s, depending on the subject's arterial transit times. The method consists of acquiring both control and tag images immediately after a labeling period that matches the arterial transit time. The theoretical basis of the technique, and simulations of the signal during changes in both transit time and perfusion are presented. Experimental data from functional imaging experiments were collected to demonstrate the technique and its characteristics.


Developing an emergency medicine handoff tool: an electronic Delphi approach.
Handoffs at the end of clinical shifts occur with high frequencies in the emergency department setting and they pose an increased risk to patients. There is a need to standardize handoff practices. This study aimed to use an electronic Delphi method to identify the core elements essential for an emergency department physician to physician handoff and propose a framework for implementation. An electronic Delphi-style study with a national panel of board-certified emergency physicians in Saudi Arabia. The panel was conducted over four rounds. The first to identify elements relevant to the end of shift handoff and categorize them into domains, while the remaining three to score and debate individual elements. Twenty-five board-certified emergency physicians from various cities and practice settings were enrolled. All panelists completed the entire Delphi process. Thirty-two elements were identified and classified into 4 domains. The top five rated handoff elements were patient identification, chief complaint history, clinical stability, working diagnosis, and consulting services involved. Panel scores showed convergence as rounds progressed and the final list of elements had a high-reliability score (Cronbach's alpha 0.93). This study yielded an itemized and ranked list of elements that are easy to implement and could be used to standardize patient handoffs by emergency physicians. While this study was conducted on an emergency medicine panel, the methods used may be adapted to develop standardized handoff frameworks that serve different disciplines or practice settings.


Unusual complication of bladder catheterization in child: catheterization of ureter.
Bladder probing is an invasive procedure that is often used by paediatric and other surgeons. We present a case who was ureter catheterized accidentally while placing a probe into the right ureter in an 18 months old female. If different catheter localization is determined during the examination, the process must be terminated immediately and the relevant specialist should be informed right away.


A novel isoform of the orphan receptor RORγt suppresses IL-17 production in human T cells.
T helper (Th)17 cells constitute a distinct subset of CD4(+) helper T cells that is mainly characterized by abundant interleukin (IL)-17 production and is involved in the host defence against bacteria and fungi as well as in the pathogenesis of autoimmune diseases. The retinoic orphan receptor (ROR)γt directs the transcriptional activation of the IL17 gene. Here, we report the presence of a novel RORγt isoform, RORγt-Δ(5-8), which lacks the hinge-encoding exons 5-8 and represses potently IL17 and IL21 gene transcription. It thereby reduces the expression of multiple Th17-assigned cytokines. We propose that RORγt-Δ(5-8) acts as a dominant-negative regulator of RORγt-mediated gene regulation and the balance between the full-length RORγt and the novel repressor isoform may arbitrate IL-17 production in human T cells.


Fasitibant chloride, a kinin B₂ receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats.
Bradykinin, through the kinin B₂ receptor, is involved in inflammatory processes related to arthropathies. B₂ receptor antagonists inhibited carrageenan-induced arthritis in rats in synergy with anti-inflammatory steroids. The mechanism(s) underlying this drug interaction was investigated. Drugs inhibiting inflammatory mediators released by carrageenan were injected, alone or in combination, into the knee joint of pentobarbital anaesthetized rats 30 min before intra-articular administration of carrageenan. Their effects on the carrageenan-induced inflammatory responses (joint pain, oedema and neutrophil recruitment) and release of inflammatory mediators (prostaglandins, IL-1β, IL-6 and the chemokine GRO/CINC-1), were assessed after 6 h. The combination of fasitibant chloride (MEN16132) and dexamethasone was more effective than each drug administered alone in inhibiting knee joint inflammation and release of inflammatory mediators. Fasitibant chloride, MK571, atenolol, des-Arg⁹-[Leu⁸]-bradykinin (B₂ receptor, leukotriene, catecholamine and B₁ receptor antagonists, respectively) and dexketoprofen (COX inhibitor), reduced joint pain and, except for the latter, also diminished joint oedema. A combination of drugs inhibiting joint pain (fasitibant chloride, des-Arg⁹-[Leu⁸]-bradykinin, dexketoprofen, MK571 and atenolol) and oedema (fasitibant chloride, des-Arg⁹-[Leu⁸]-bradykinin, MK571 and atenolol) abolished the respective inflammatory response, producing inhibition comparable with that achieved with the combination of fasitibant chloride and dexamethasone. MK571 alone was able to block neutrophil recruitment. Bradykinin-mediated inflammatory responses to intra-articular carrageenan were not controlled by steroids, which were not capable of preventing bradykinin effects either by direct activation of the B₂ receptor, or through the indirect effects mediated by release of eicosanoids and cytokines.


Characterization of water dissolved organic matter under woody vegetation patches in semi-arid Mediterranean soils.
Woody patches in semiarid environments favor the establishment of other plants. Facilitation may be favored by an increase in soil fertility. Dissolved organic matter (DOM), is the most active fraction of soil organic matter and may contain compounds affecting plant establishment, as allelochemicals, hormone-like substances and metal carriers. However, information on DOM contents and composition in these environments is scarce. In this paper, we study the impact of woody patches on DOM in Stipa tenacissima L. steppes and discuss its implications for community dynamics. DOM under patch- and inter-patch areas, was analyzed for elemental composition, UV-Vis indices and organic acid content. Element concentration and composition in DOM, and organic acid concentration were similar in patch- and inter-patch areas. Yet, soils under patches were richer in DOC, aromatic species and organic acids (particularly fumaric acid) than soils in inter-patch areas. Dominant species affected organic matter concentration and quality in complex ways. Thus, patches dominated by Ephedra fragilis showed higher concentrations of TOC and aromatics than those dominated by other species. Rhamnus lycioides patches showed the highest accumulation of fumaric acid, which may contribute to its successful recruitment rate and expansion in the area. Our results show substantial differences in the amount and composition of DOM and specific compounds affecting soil functionality and plant dynamics. Further studies on the effects of such changes on seedling performance are needed to increase our understanding of plant-plant interactions in semiarid environments.


Abdominal and pelvic hydatid disease during pregnancy.
Hydatid disease is an infection of sheep and cattle. Affected human beings are only chance intermediate hosts. It is a rare condition in pregnancy. We present a 15-week pregnant patient with cysts in the liver and in the right adnexa identified by ultrasonography and magnetic resonance imaging. Diagnosis of hydatid disease was confirmed by an indirect hemagglutination test. The patient underwent laparotomy and a healthy baby was delivered at term.


RB18A regulates p53-dependent apoptosis.
We previously demonstrated that RB18A, a member of TRAP220/DRIP205/PBP family, in vivo acted as a cofactor of transcription by differently regulating p53wt transactivating activity on physiological promoters. Using p53-negative cells transfected with different constructs, we herein demonstrated that RB18A down-regulated p53wt-dependent apoptosis. This biological regulation was due to a specific diminution of p53wt protein level, as level of p53mut and GAPDH proteins was not modified. This p53wt diminution was dependent on proteasome activity, as inhibited by MG-132 inhibitor. This specific p53wt degradation was correlated with an increase in expression of MDM2, which promoted p53wt degradation into proteasome. RB18A up-regulated MDM2 expression by activating MDM2 promoter, even in absence of p53wt. Altogether, these data emphasized that RB18A could regulate p53wt function not only by direct interaction between both proteins, but also by up-regulating promoter activity of MDM2, a p53-regulating partner.


Utilizing a nanocomposite consisting of zinc ferrite, copper oxide, and gold nanoparticles in the fabrication of a metformin electrochemical sensor supported on a glassy carbon electrode.
The conception and development of a new electrochemical sensor is reported for the detection of metformin (MET). Zinc ferrite and copper oxide nanostructure (ZnFe2O4-CuO) and gold nanoparticles (AuNPs) have been used to prepare a nanocomposite in modifying a glassy carbon electrode (GCE). The unique ZnFe2O4-CuO/Au nanocomposite was applied as a sensor for the determination of traces of MET by some electroanalytical techniques. Experimental parameters affecting the results were investigated and optimized. Under the optimum conditions and at a working potential of 0.85 V (vs. Ag/AgCl/3.0 M KCl), the sensor response is linear in the MET range of 1.0 nmol L-1 to 1.0 μmol L-1 MET. The limit of detection (LOD) is 0.3 nmol L-1 (at an S/N ratio of 3) and the sensitivity is 1.13 μA μmol L-1 cm-2. The sensor was applied to the determination of MET in real samples where it gave acceptable results. Graphical abstract.


Permeable polymersomes from temperature and pH dual stimuli-responsive PVCL-b-PLL block copolymers for enhanced cell internalization and lysosome targeting.
A series of dual stimuli-responsive block copolymers comprising temperature-responsive poly(N-vinylcaprolactam) (PVCL) and biodegradable pH-responsive poly(l-lysine) (PLL) of varying chain length were synthesized by a combination of free radical polymerization and ring opening polymerization. The block copolymers formed micelles and vesicles (polymersomes) in response to temperature and pH, respectively, in aqueous solution. The nanoassemblies were characterized by transmission electron microscopy and dynamic light scattering techniques. Encapsulation of both hydrophobic and hydrophilic dyes in the polymersomes was shown. Doxorubicin (DOX) was loaded in the polymersomes and its controlled release in response to the two stimuli, independently and jointly, was studied. The drug was found to be released due to stimuli-induced increased permeability without disassembly of the polymersomes. A significant increase in the cellular uptake of the drug-loaded polymersomes at hyperthermia conditions was demonstrated at 41 °C and release of the drug upon localization in lysosomes was observed. Cellular internalization pathway of the polymersomes was investigated by competitive inhibition assay and a combination of endocytic pathways dominated by caveolae-mediated mechanism was found to be operative.


Pharmacokinetics of ABT-773, a new semi-synthetic ketolide in neutropenic lung-infected mice: a population approach.
ABT-773 is an investigational ketolide antimicrobial agent with an in-vitro bactericidal activity against macrolide-susceptible and -resistant Streptococcus pneumoniae. The pharmacokinetics of this drug candidate were evaluated in lung-infected (108 CFU mL 1 starting inoculum) mice following a single dose (25, 50, 100 or 200 mg kg(-1)) oral administration as a solution in 10% of 95% ethanol and 90% of 0.1 M pH 6.5 phosphate buffer solution. Serum ABT-773 concentrations were measured using a validated HPLC assay with fluorescence detection (excitation at 324 nm and emission at 364 nm). Population pharmacokinetic analysis was performed using the NONMEM computer program. Results from data analysis showed non-linear pharmacokinetics of ABT-773, noted by the increases in half-life (3.1 to 27.2 h) and AUC/dose (23.7 to 149 mg h(-1) L(-1) mg(-1)), with doses from 25 to 200 mg kg(-1). A non-linear one-compartment model with parallel capacity-limited and linear first-order elimination best described the pharmacokinetics of ABT-773 in the mouse. The total volume of distribution was 0.316 L. The clearance for the linear first-order elimination was 0.0027 L h(-1). The Vm and Km were 0.0385 L h(-1) and 0.141 mg L(-1), respectively, for the capacity-limited elimination.


Detection and molecular characterization of chicken infectious anaemia virus in young chicks in Punjab region of north-western India.
Chicken infectious anaemia (CIA) is an important viral disease of chicken causing significant immunosuppression and severe anaemia worldwide. Occurrence of severe disease and mortality is noticed in young chicks (2-3 weeks). Vertical mode of transmission increases chance of infection and persistence of virus among the infected flocks. The current study was conducted in Punjab state for confirmation and genetic characterization of CAV among chicken flocks of various poultry farms. DNA was extracted from the tissue samples and subjected to polymerase chain reaction (PCR) of VP1 gene and whole genome. PCR products were further sequenced for confirmation of chicken infectious anaemia virus (CIAV) genome in the clinical samples. PCR amplification of DNA from the tissue samples yielded expected product size of 1350 bases of VP1 gene and 2.3 kb of whole genome. Out of 16 commercial poultry farms, 11 were confirmed with presence of CIAV, and out of 65 birds, 39 were found positive (60%) for CIAV genes. Among the various organs, the presence of viral gene was detected at highest level in thymus when compared with other organs. It is concluded that chicken infectious anaemia virus detected from Punjab state is closely related to other Indian isolates and neighbouring countries which necessitates need of more intensive studies with a greater number of samples for implementing effective control measures.


Induced type-B reticulum cell neoplasia in mice III. The importance of T-cell proliferation and cellular relocation in accessory cell transformation.
After the transfer of spleen cells from old CBA/T6T6 mice (greater than 75 weeks) into young syngeneic CBA/Ca recipients there usually follows a selective expansion of the donor T-cell population and the emergence of type B reticulum cell neoplasms (RCN-B), also of donor origin though probably derived not from the T-cells but from lymphoid dendritic accessory cells. As few as one million injected cells led to significant donor T-cell hyperplasia and tumour induction. Injection of cells from young donors did not have such consequences. Similar tumours were induced by transferring syngeneic cells in both C57BL and DBA/2 mice, although in the latter strain there was no requirement for the injected cells to derive from old donors. It appeared that T-cell proliferation was independent of donor accessory cells or RCN-B induction, since injection of enriched T-cells led to few tumours, although the T-cell chimaerism was indistinguishable from that in recipients of unseparated spleen cells. Development of tumours, however, seemed to be dependent upon stimulated T-cells. Recipients of spleen cells from old T-cell-deprived mice did not develop tumours; conversely, tumours, mostly of donor origin, were induced in recipients of young syngeneic cells when an extrinsic stimulus to T-cell proliferation was provided by continued allostimulation. The apparent selectivity of tumorigenesis for donor cells has led to the proposal that cellular relocation, as a result of transfer, may be an important predisposing factor in malignant transformation in circumstances of T-cell stimulation provided by antigenic challenge or by transfer of T-cells from old donors.


Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location.
To determine the relative prognostic significance of location (anterior or inferior) and type (Q wave or non-Q wave) of infarction, the hospital course and follow-up outcome (mean duration 30.8 months) of 471 patients with a first infarction were analyzed. Analyses were performed grouping the patients according to infarct location (anterior, n = 253; inferior, n = 218), infarct type (Q wave, n = 323; non-Q wave, n = 148), and both location and type (inferior non-Q wave, n = 85; inferior Q wave, n = 133; anterior non-Q wave, n = 63; and anterior Q wave, n = 190). Patients with anterior infarction had a substantially worse in-hospital and follow-up clinical course compared with those with inferior infarction, evidenced by a larger infarct size (21.2 versus 14.9 g Eq/m2 creatine kinase, MB fraction [MB CK], p less than 0.001), lower admission left ventricular ejection fraction (38.1 versus 55.3%, p less than 0.001) and higher incidence of heart failure (40.7 versus 14.7%, p less than 0.001), serious ventricular ectopic activity (70.2 versus 58.9%, p less than 0.05), in-hospital death (11.9 versus 2.8%, p less than 0.001) and total cumulative cardiac mortality (27 versus 11%, p less than 0.001). Patients with Q wave infarction similarly experienced a worse in-hospital course compared with patients with non-Q wave infarction, evidenced by a larger infarct size (20.7 versus 12.7 MB CK g Eq/m2, p less than 0.001), lower admission left ventricular ejection fraction (43.7 versus 50.6%, p less than 0.001), and a higher incidence of heart failure (31.9 versus 21.6%, p less than 0.05) and in-hospital death (9.3 versus 4.1% p less than 0.05). However, there was no increased rate of reinfarction or mortality in hospital survivors with non-Q wave infarction compared with those with Q wave infarction, and total cardiac mortality was similar (16 versus 21%, p = NS). To evaluate the role of infarct location and type independent of infarct size, patients were grouped according to quartile of infarct size, and outcome was reanalyzed within each group. Patients with anterior infarction demonstrated a lower left ventricular ejection fraction on admission and after 10 days than did patients with inferior infarction, even after adjustment for infarct size, as well as a higher incidence of congestive heart failure and cumulative cardiac mortality.(ABSTRACT TRUNCATED AT 400 WORDS)


Outcome and characteristics of non-measurable myeloma: A cohort study with population-based data from the Swedish Myeloma Registry.
We describe survival in patients with oligo- and non-secretory multiple myeloma (MM). We refer to the whole group as non-measurable MM and compare it with secretory MM. Oligo-secretory MM was defined as M protein in serum <10 g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non-secretory. The groups were also subdivided by Free Light Chains (SFLC) level and ratio. Out of 4325 patients with symptomatic MM in the Swedish Myeloma Registry during 2008-2016 eligible for the study, 389 patients (9%) had non-measurable MM. Out of these, 253 patients (6%) had oligo-secretory and 136 (3%) had non-secretory MM. Median survival for secretory MM was 42.7 months, non-measurable MM 40.2 months, oligo-secretory MM 38.6 months, and non-secretory MM 44.6 months. Difference in overall observed survival was non-significant for all groups when compared with secretory MM. Within non-secretory MM, stem cell transplantation (SCT), 95% being auto-SCT, was significant for superior survival in multivariate analysis (HR 0.048. P = .0015). In this population-based study, we found no difference in survival between oligo- or non-secretory MM when compared with secretory MM. SCT appears to be important also for patients with non-secretory disease.


Accuracy of two-dimensional echocardiography in the diagnosis of aortic arch obstruction.
To evaluate the predictive accuracy of two-dimensional echocardiography in the diagnosis of aortic arch obstruction, 540 consecutive patients aged 2 days to 15 years (mean 2 months) who underwent subsequent cardiac catheterization and angiography were prospectively studied. At angiography, 51 patients had aortic arch obstruction; of these, 35 had juxtaductal coarctation, 15 isthmic hypoplasia and 1 a type B interrupted aortic arch. The presence of arch obstruction was correctly identified with two-dimensional echocardiography in 45 of 51 patients with this condition (overall sensitivity 88%). Two-dimensional echocardiography clearly defined a juxtaductal coarctation in 33 of 35 patients and isthmic hypoplasia in 13 of 15 patients (sensitivity 94% and 73%, respectively). The form and type of interrupted aortic arch were clearly distinguished from other forms and types of arch obstruction. Among the 489 patients without aortic arch obstruction, two-dimensional echocardiography wrongly diagnosed the presence of such obstruction in 9 patients (overall specificity 98%). Forty-six (92%) of the 51 patients had at least one associated intracardiac abnormality. Twenty-two (44%) had a ventricular septal defect, 21 (42%) a bicuspid aortic valve and 4 (18%) subaortic stenosis. Five patients had complex congenital cardiac malformations. All associated abnormalities were prospectively identified with two-dimensional echocardiography. Thus, two-dimensional echocardiography is highly specific in diagnosing aortic arch obstruction. It is less sensitive for the diagnosis of isthmic hypoplasia in the neonatal period.


Double J stent with antireflux device in the prevention of short-term urological complications after cadaveric kidney transplantation: single-center prospective randomized study.
The placement of a double J stent to protect a uretero-vesical anastomosis in a kidney transplant is a widespread procedure performed to reduce the incidence of fistula and stenosis at the anastomosis. However, the presence of a double J stent may cause vesicoureteral reflux (VUR), predisposing one to urinary tract infections (UTIs), which may be a significant source of morbidity for the graft. We evaluated whether a ureteral stent incorporating an antireflux device can reduce the incidence of ureteral reflux and UTIs. From January to December 2003, 44 kidney transplant recipients were randomized to receive a 14-cm 4.8-F double J stent with (group A) or without an anti-reflux device (group B). Primary end points were the reduction of the incidence of VUR and of UTIs. The secondary end point was the graft function, on the basis of mean serum creatinine level at 3, 6, and 12 months. We failed to observe statistically significant differences in terms of either the incidence of VUR and UTIs, or the short-term outcomes of the grafts. We concluded that the anti-reflux device does not have an impact on the incidence of stent-related side effects.


Quality of life in children undergoing tonsillectomy: a cross-sectional survey.
The quality of life in children undergoing tonsillectomy remains unclear. We aimed to analyze the current status and influencing factors of quality of life in children undergoing tonsillectomy, to provide useful insights to clinical postoperative care for children. Children who underwent tonsillectomy in our hospital from June 1, 2021 to October 31, 2022 were selected. The characteristics of children were collected and Paediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0) was used for evaluating the quality of life in children. Pearson correlation, univariate and logistic regression analyses were condcuted to evaluate the influencing factors of quality of life in children undergoing tonsillectomy. A total of 118 children undergoing tonsillectomy were included. The total score of PedsQL™ 4.0 in children undergoing tonsillectomy was (70.28 ± 13.15). Pearson correlation analyses indicated that age(r = 0.586), courses of tonsillitis(r = 0.595), parental education level(r = 0.612) and monthly family income(r = 0.608) were associated with the PedsQL™ 4.0 total score in children undergoing tonsillectomy (all P < 0.05). Logistic regression analyses indicated that age ≤ 5y (OR = 2.009,95%CI: 1.826 ~ 2.401), courses of tonsillitis ≥ 3years (OR = 2.167,95%CI: 1.688 ~ 2.547), high school of parental education level (OR = 1.807,95%CI: 1.224 ~ 2.181) and monthly family income ≤ 5000 RMB(OR = 2.624,95%CI:2.092 ~ 3.077) were the independent influencing factors of quality of life in children with undergoing tonsillectomy (all P < 0.05). The quality of life of children after tonsillectomy is not high, and the quality of life of children is affected by many factors. Medical staff should take early targeted nursing countermeasures tageted on those influencing factors to improve the quality of life of children.


Clear subretinal fluid in a case of non-neovascular early-onset drusen: Swept-source imaging evaluation.
A 50-year-old male presented with recent metamorphopsia in the right eye. Fundus examination revealed bilateral multiple cuticular drusen along with few large colloid drusen (phenotype 3 cuticular drusen). No vitelliform material was evident in the macula in either eye. Fluorescein angiography (FA), indocyanine green angiography (ICGA) did not demonstrate a macular neovascularization (MNV) in either eye. Swept-source optical coherence tomography (SS-OCT) revealed sub-retinal pigment epithelial (RPE) drusen and a clear space beneath the inter-digitation zone and above the RPE-Bruch's complex. SS-OCTA did not reveal MNV in either eye. The patient was kept under observation, and follow-up at 3 months did not reveal any structural change. Among patients with early-onset drusen, vitelliform detachments may occur due to accumulation of yellow pseudo-vitelliform material. However, serous detachments with an "optically clear" subretinal space can occur by the same mechanism without MNV. Such patients do not merit therapy with anti-vascular endothelial growth factor agents.


Current Perspectives of Urology Involvement in Renal Transplantation: A Survey of Canadian Senior Residents.
The role of urology in renal transplantation has become increasingly variable with the growth of multiorgan transplant programs. We examined the involvement of urology in renal transplantation across Canada and the perceptions of urology residents. An anonymous questionnaire was administered to all final year Canadian urology residents. The survey was devised to assess urological involvement and resident exposure to renal transplant. Responses were closed-ended and used a validated 5-point Likert scale. Descriptive statistics and Pearson's chi-square test were used to analyze the responses. Urologists were involved in renal transplants at 77.4% of training centers in Canada. Most residents believed that urology should remain highly involved with transplantation (77.4%) and that it should be a mandatory component of residency (64.5%). However, only half of the residents (51.6%) believed they had sufficient exposure to transplantation. Only 41.9% would be comfortable performing a transplant after residency. A minority of residents had plans for fellowship training (9.7%) or future careers (12.9%) involving renal transplant. There was a positive correlation between the involvement of urology in transplantation at a resident's training center and the opinion that urology should have an important role in this field (r=0.51, p=0.003). Renal transplantation remains a limited component of the majority of residency programs in Canada. However, only a small number of residents intend to pursue fellowship training or a future career that involves transplantation. Consequently, a strong exposure to transplantation during residency is vital to ensuring that urology remains highly involved in renal transplantation.