Thinking Outside of Outpatient: Underutilized Settings for Psychotherapy Education.
Although psychiatry residents are expected to achieve competency in conducting psychotherapy during their training, it is unclear how psychotherapy teaching is integrated across diverse clinical settings. Between January and March 2015, 177 psychiatry residency training directors were sent a survey asking about psychotherapy training practices in their programs, as well as perceived barriers to psychotherapy teaching. Eighty-two training directors (44%) completed the survey. While 95% indicated that psychotherapy was a formal learning objective for outpatient clinic rotations, fifty percent or fewer noted psychotherapy was a learning objective in other settings. Most program directors would like to see psychotherapy training included (particularly supportive psychotherapy and cognitive behavioral therapy) on inpatient (82%) and consultation-liaison settings (57%). The most common barriers identified to teaching psychotherapy in these settings were time and perceived inadequate staff training and interest. Non-outpatient rotations appear to be an underutilized setting for psychotherapy teaching.


Family environment and premarital intercourse in Bandjoun (West Cameroon).
Family environment is one of the most influential factors on youth sexual behavior but has received little investigation in sub-Saharan Africa. Yet, a comprehensive understanding of family influences could improve the efficiency of reproductive health (RH) interventions. Using retrospective data from a population-based survey, life-table analysis was utilized to compute the median age at premarital intercourse among 1,182 youth aged 12-24 years. Discrete-time hazard models were used in multivariate analysis to estimate the effects of family structures and parent-child interactions on premarital intercourse. Overall, 42% of participants had a premarital intercourse, and the median age at first sex was 16.9 years. Participants in nuclear two-parent families had the highest median (17.7) compared with those in nuclear one-(16.7), extended one-(16.5), extended two-parent families (16.9) or other relatives (16.8). Youth from monogamous families had the highest median (16.9) compared to those from polygamous (16.3) and other families (16.0). Orphans and youth reporting family transitions were more likely to initiate first sex at an earlier age compared with non-orphans and non-movers, with a median of 16.1 and 16.9 years, respectively. Multivariate results showed that living in extended families, being orphaned, and family transitions significantly increased the risk of premarital intercourse. Polygamy showed marginal effects. Stronger parent-child relationships and higher levels of parental control decreased the risk of premarital intercourse. Unexpectedly, parent-child communication was significantly associated with a higher risk of sexual debut. Programmatically, family environment is an important resource that needs to be promoted when designing RH interventions in sub-Saharan Africa.


Changes in sexual activity of male patients with ankylosing spondylitis undergoing total hip arthroplasty.
Sexual activity is often an important component of life. To date, no studies have examined sexual activity before and after total hip arthroplasty (THA) in male patients with ankylosing spondylitis (AS). The purpose of the current study was to evaluate the effect of THA on sexual activity and to explore the most commonly reported and comfortable coital position for male AS patients with hip involvement. Data from 31 male AS patients who underwent THA for hip involvement were retrospectively reviewed. Information from the International Index of Erectile Function (IIEF), the Harris Hip Score (HHS) and other clinical parameters was collected and monitored over time. We compared the above-mentioned parameters before surgery and 2 years after surgery and analysed the correlation between changes on the IIEF and changes in clinical parameters. The domain and total scores of the IIEF, except EF, were significantly higher after surgery than were those before surgery ( p < 0.05). There was a significant positive correlation between changes on the IIEF and improvement in flexion-extension range of motion (ROM), adduction-abduction ROM and HHS ( p < 0.05). Most patients (26/31, 83.9%) resumed sexual activity 5-12 weeks after surgery. The pre- and postoperative distributions of the most commonly reported and comfortable position were not significantly different (p > 0.05). Successful THA may improve sexual activity in male AS patients with hip involvement. Changes in hip ROM show the most significant correlation with improvement in sexual activity. Resumption of sexual activity occurs within 5-12 postoperative weeks.


Purification of Thiobacillus denitrificans siroheme sulfite reductase and investigation of some molecular and catalytic properties.
A siroheme-containing sulfite reductase was isolated from Thiobacillus denitrificans, purified to an electrophoretically homogenous state, and investigated with regard to some of its molecular and catalytic properties. The enzyme was a tetramer with a molecular weight of 160 000, consisting of two types of subunits arranged to an alpha 2 beta 2-structure. The molecular weight of the alpha-subunit was 38 000, that of the beta-subunit 43 000. As prosthetic groups siroheme and Fe/S groupings could be detected. The absorption spectrum showed maxima at 273 nm, 393 nm, and 594 nm; the molar extinction coefficient at these wavelengths were 280, 181, and 60 . 10(3) cm2 . mmol-1, respectively. With reduced viologen dyes the enzyme reduced sulfite to sulfide, thiosulfate and trithionate. In many properties T. denitrificans sulfite reductase closely resembled desulfoviridin, the dissimilatory sulfite reductase of Dssulfovibrio species. It is proposed that the physiological function of this enzyme is not to reduce but rather to form sulfite from reduced sulfur compounds in the course of dissimilatory sulfur oxidation in T. denitrificans.


Haemodynamic and endocrine responses of the kidney to frusemide in mild essential hypertension.
Prostaglandin-dependent, frusemide-induced changes in renal plasma flow, glomerular filtration rate and plasma renin activity were measured in 14 patients with mild essential hypertension. The renal haemodynamic responses to frusemide were the same as in 10 normal subjects. Frusemide-induced changes in urinary PGE and kallikrein excretion were also the same as in normal subjects. Impaired renal release of vasodilator prostaglandins in essential hypertension is likely to be secondary to the hypertension rather than an underlying factor in its development.


Calcium supplementation in patients with essential hypertension: assessment by office, home and ambulatory blood pressure.
To study the effects of a high calcium intake in hypertensive patients by blood pressure monitoring. In a randomized crossover study, patients were assigned to an 8-week calcium supplementation period and an 8-week control period. The subjects were given 25 mmol/day (1 g/day) of calcium as calcium carbonate during the intervention period. A hypertension clinic in a tertiary teaching hospital. Sixty untreated or treated hypertensive patients (35 men and 25 women, mean age 58 years) with office systolic/diastolic blood pressure > or = 140/90 mmHg. Office blood pressure, home blood pressure (last 7 days), and ambulatory 24 h blood pressure (every 30 min using TM-2421). The serum calcium concentration and urinary calcium excretion increased significantly with calcium supplementation. Office, home and 24 h blood pressure were lower in the calcium period than in the control period, although the differences were small (mean +/- SEM office blood pressure: 1.2+/-1.2/1.1+/-0.7 mmHg; home blood pressure: 1.9+/-0.7/1.3+/-0.6 mmHg; 24 h blood pressure: 1.2+/-0.8/0.9+/-0.5 mmHg,), and significant only for home systolic and diastolic blood pressures. The difference in home systolic blood pressure was inversely correlated with the level of home blood pressure in the control period and with the difference in urinary calcium. The difference in 24 h systolic blood pressure was positively correlated with the control level of urinary calcium. Age, sex, antihypertensive medication, drinking habit, sodium intake or order of treatment did not significantly influence the effects of calcium supplementation. An increase in calcium intake tends to lower office, home and ambulatory blood pressure in hypertensive patients. However, the antihypertensive effect is too small to support the general application of a high calcium intake in the treatment of hypertension.


Contribution of retinal neurons to d-wave of primate photopic electroretinograms.
The purpose of this study was to determine the contribution of different types of retinal neurons to the d-wave of the primate electroretinogram using pharmacological agents. NMDA + TTX was used to suppress inner retinal activity, and APB and PDA to block the activity of the ON- and OFF-pathways, respectively. Results indicated that the inner retinal neurons had a small but certain contribution to the d-wave. The initial rapid phase of the d-wave originates from the activity of the cone OFF-pathway nearly exclusively, and the later slow phase is shaped by the cone photoreceptors. The cone ON-pathway acts in a direction opposite to that of the other components.


ACL double bundle linked cortical-aperture tibial fixation: a technical note.
The purpose of this technical note is to describe the tibial fixation characteristics for an all-inside anatomic anterior cruciate ligament (ACL) reconstruction method that links extra-cortical button suspensory and aperture fixation replicating double bundle soft tissue graft function in single femoral and tibial sockets. A 55° drill guide aligned guidewires in the ACL footprint center of 8 porcine tibiae (mean apparent bone mineral density = 1.15 g/cm(2)). A Flipcutter created 27 mm sockets and 15 mm guidewire channels. Advancement sutures seated porcine soft tissue graft-PEEK implants to achieve both socket aperture and extra-cortical button suspensory fixation. Potted specimens were loaded into a 6º of freedom clamp with the servohydraulic loading vector in direct socket alignment. Constructs were pre-loaded to 25 N, underwent 10 pre-conditioning cycles (0-50 N, 0.5 Hz), and 500 submaximal loading cycles (50-250 N, 1 Hz) prior to load to failure testing (20 mm/min). Mode of failure was recorded. Descriptive statistical analysis was performed. All specimens survived the biomechanical test protocol. Displacement during cyclic loading was 2.8 ± 0.9 mm, yield load was 475.2 ± 36 N, ultimate load at failure was 671.4 ± 98 N, stiffness was 127.5 ± 15 N/mm. The most common failure mode was suture pulling through the soft tissue graft. This ACL reconstruction method combines the high ultimate load to failure and low graft slippage of extra-cortical button suspensory fixation with the high stiffness of aperture fixation. Biomechanical test findings were comparable or better to previous reports for displacement during submaximal loading, ultimate failure load, and construct stiffness. Based on current understanding of soft tissue graft ACL reconstruction biomechanics, this fixation method should enhance graft-bone socket integration during healing, facilitate long-term graft survival, and improve patient outcomes. Clinical studies are needed to confirm in vivo efficacy.


A beta-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus.
In the course of screening for anti-dementia agents from natural products, a beta-secretase (BACE1) inhibitor was isolated from the culture broth of Phellinus linteus and identified as hispidin. It showed an IC (50) value of 4.9 x 10 (-6) M and a Ki value of 8.4 x 10 (-6) M. The compound was a non-competitive inhibitor. Hispidin also inhibited a prolyl endopeptidase (IC (50) = 1.6 x 10 (-5) M, Ki = 2.4 x 10 (-5) M), but it was less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase.


Shaker K+ channel subunits from heteromultimeric channels with novel functional properties.
A large number of related genes (the Sh gene family) encode potassium channel subunits which form voltage-dependent K+ channels by aggregating into homomulitimers. One of these genes, the Shaker gene in Drosophila, generates several products by alternative splicing. These products encode proteins with a constant central region flanked by variable amino and carboxyl domains. Coinjection of two Shaker RNAs with different amino or different carboxyl ends into Xenopus oocytes produces K+ currents that display functional properties distinct from those observed when each RNA is injected separately, indicating the formation of heteromultimeric channels. The analysis of Shaker heteromultimers suggests certain rules regarding the roles of variable amino and carboxyl domains in determining kinetic properties of heteromultimeric channels. Heteromultimers with different amino ends produce currents in which the amino end that produces more inactivation dominates the kinetics. In contrast, heteromultimers with different carboxyl ends recover from inactivation at a rate closer to that observed in homomultimers of the subunit which results in faster recovery. While this and other recent reports demonstrate that closely related Sh family proteins form functional heteromultimers, we show here that two less closely related Sh proteins do not seem to form functional heteromultimeric channels. The data suggest that sites for subunit recognition may be found in sequences within a core region, starting about 130 residues before the first membrane spanning domain of Shaker and ending after the last membrane spanning domain, which are not conserved between Sh Class I and Class III genes.


The Prognostic Relevance of the Number and Location of Positive Lymph Nodes for Ampulla of Vater Carcinoma.
Lymph node metastasis (LNM) has been regarded as one of the prognostic factors in patients with ampulla of Vater carcinoma (AC). However, the consensus about an optimal cutoff value of the number of LNMs and the definition of the regional lymph nodes (RLNs) has not been achieved. This study included 114 consecutive patients who underwent pancreatoduodenectomy for AC between January 2002 and March 2019. The minimum p value approach for the greatest difference in the overall survival classified the number of LNM into none (N0, n = 66), from 1 to 2 (N1, n = 32), and ≥3 LNM (N2, n = 11) (p = 0.004). Distant LNM was defined as M1 (n = 5). Significant differences in relapse-free survival (RFS) were found between N0 and N1 (p < 0.001), N1 and N2 (p = 0.047), and N1 and M1 (p = 0.044) but not between N2 and M1 (p = 0.683). Moreover, the patients with regional LNM were classified into two groups: Np group (n = 35, LNM only in pancreatic head region) and Nd group (n = 8, LNM in other regional location). Significant differences in the RFS were found between N0 and Np (p < 0.001), Np and Nd (p = 0.004), and Np and M1 (p = 0.033) but not between Nd and M1 (p = 0.883). A Cox proportional hazards analysis for RFS revealed that ≥ 3 LNMs (hazards ratio [HR], 3.22) and LNM except for pancreatic head region (HR, 4.27) were individually independent worse prognostic factors. ≥3 LNMs and regional LNM except for pancreatic head region were associated with poor prognosis comparable to that of the patients with M1.


1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induced Parkinson's Disease in Mouse: Potential Association between Neurotransmitter Disturbance and Gut Microbiota Dysbiosis.
Recent studies have revealed significant roles of neurotransmitters and gut microbiota along the gut-brain axis in Parkinson's disease (PD); however, the potential mechanisms remain poorly understood. In the current study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced characteristic PD neurobehavior changes accompanied by increased α-synuclein, apoptotic protein Bim, and cleaved caspase-3 and decreased expression of tyrosine hydroxylase (TH). Meanwhile, the tryptophan (Trp) and tyrosine (Tyr) neurotransmitter metabolites involving kynurenine (KYN), serotonin (5-HT), and dopamine (DA) pathways were significantly changed in serum. Furthermore, the step-limited enzymes, which are responsible for the key metabolic pathways of these neurotransmitters, were obviously dysregulated. The 16S rRNA gene sequence results indicated that the abundance and diversity of the microbiota were obviously decreased in MPTP-treated mice, the presence of Ruminococcus, Parabacteroides and Parasutterella genera were obviously increased, while Coriobacteriaceae, Flavonifractor, Lachnospiraceae, Lactobacillaceae, and Rikenellaceae abundance was markedly decreased. The connectivity between the gut microbiota and neurotransmitter metabolism revealed that the gut microbiota dysbiosis was associated with disturbance of the DA, KYN, and 5-HT metabolic pathways. Therefore, our results provide evidence that gut-microbiota-brain axis disturbance may play an important role in PD development and targeting this axis might provide a promising therapeutic strategy for PD.


Proteolysis as a probe of ligand-associated conformational changes in rat carbamyl phosphate synthetase I.
Elastase, V8 protease, subtilisin, trypsin, and chymotrypsin all cleaved the 1462-residue polypeptide of rat carbamyl phosphate synthetase I in segment C 160-180 residues from the COOH-end. Its activator N-acetylglutamate (AcGlu) increased the rate of cleavage approximately ninefold, presumably by binding preferentially to the conformation in which C is exposed. ATP/Mg2+ prevented proteolysis both +/- AcGlu. Kd,app for AcGlu (66 microM) and ATP (4.2 microM with AcGlu and 5 mM Mg2+) was estimated from the pseudo-first-order rate constants for inactivation caused by cleavage with elastase at C. Chymotrypsin and trypsin also hydrolyzed the enzyme, independent of AcGlu, at site D within less than 20 residues of the COOH-end. D was protected by ATP only in the presence of AcGlu and K+, and enzyme hydrolyzed exclusively at D had greater than 30-fold higher Km's for AcGlu and ATP. Digestion by trypsin at a third site (B) approximately 530 residues upstream from C appeared to occur subsequent to hydrolysis at C. Slow cleavage by elastase at an additional site (A) to give 360- and 1100-residue peptides was unaffected by AcGlu and ATP, and caused only modest loss of activity. These peptides were isolated by chromatography on DEAE-cellulose. Assignment of the smaller one to the NH2-end on the basis of its cysteine content places site A in the junction between the segments homologous to the small glutaminase and large synthetase subunits of Escherichia coli carbamyl phosphate synthetase II. Neither peptide alone was active; maximal regain of activity (approximately 25%) occurred on combining them in equimolar proportions. The sizes of the peptides produced by further digestion of the site A digest gave the approximate locations of the other sites. Sites A (Ala-417) and B (Arg-787) have recently been identified by NH2-terminal sequencing (S. G. Powers-Lee and K. Corina (1986) J. Biol. Chem. 261, 15349-15352). Reasons for the low value of KAcGlu,app are examined, and protection by ATP is discussed in relation to previous models for the conformational equilibria of the enzyme.


Prognostic significance of alpha-methylacyl-coA racemase among men with high grade prostatic intraepithelial neoplasia in prostate biopsies.
Serum prostate specific antigen screening has increased the number of prostate biopsies performed increasing the number of patients with high grade prostatic intraepithelial neoplasia. The criteria for re-biopsy are not standardized but may be refined by the identification of novel biomarkers demonstrating prognostic significance. Alpha-methylacyl-CoA racemase is a robust marker of prostate cancer and is expressed in a subset of high grade prostatic intraepithelial neoplasia. This study evaluates the prognostic significance of alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia glands in prostate biopsies. Immunohistochemical staining with alpha-methylacyl-coA racemase and p63 was examined in a selected group of 62 patients with a diagnosis of high grade prostatic intraepithelial neoplasia on initial prostate biopsy, of which on repeat biopsy 32 had no carcinoma and 30 had prostate cancer. There was no significant difference in age, number of cores sampled or prostate specific antigen history between the 2 outcome groups (ANOVA p >0.9). High grade prostatic intraepithelial neoplasia glands in each case were evaluated for alpha-methylacyl-coA racemase and p63. Reactivity for alpha-methylacyl-coA racemase was found in 27 of the 62 cases examined. Fisher's exact analysis revealed that patients with at least 1 alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia gland were 5.2 times more likely to have a subsequent diagnosis of prostate cancer on repeat biopsy than those without any alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia glands (p = 0.0044). No correlation was found between alpha-methylacyl-coA racemase positivity and any other clinical variable. This is the first study to our knowledge to illustrate that alpha-methylacyl-coA racemase reactivity in high grade prostatic intraepithelial neoplasia may be useful to refine re-biopsy criteria and assist in clinical management decisions.


Description of a new species of Sternocoelis from Morocco with proposal of the Sternocoelis marseulii species group (Coleoptera, Histeridae).
TheSternocoelis marseulii species group is proposed based on antennal and prosternal characters. Five species are included in the group:Sternocoelis marseulii (Brisout de Barneville, 1866)(Spain), Sternocoelis viaticus Lewis, 1892 (Algeria), Sternocoelis vaucheri Lewis, 1896 (Morocco), Sternocoelis berberus Lackner & Yélamos, 2001 (Morocco)and Sternocoelis yelamosisp. n. (Morocco). The external morphology of Sternocoelis yelamosisp. n. is described and illustrated, the illustrations of genitalia of all species of the group (except for Sternocoelis vaucheri) are provided and a key to the species of the group is given.


Human Milk Fortification: A Practical Analysis of Current Evidence.
Human milk (HM) with appropriate fortification is the recommended nutrition for very low birth weight (VLBW) infants. Fortification provides additional nutrients, vitamins, and minerals to support the growing preterm infant during critical periods of development. This article discusses the variability of HM including differences between maternal and pasteurized donor human milk (DHM), fortification of HM through the use of single- and multi-nutrient fortifiers, and clinical controversies including the timing of fortification, volume of feedings, and future innovations in HM fortification.


Pro-thyrotropin-releasing hormone concentrations in the brain of ataxic mice.
Concentrations of pro-thyrotropin-releasing hormone (pro-TRH) were studied in the brain of the Weaver ataxic mouse, the Purkinje cell degenerative mouse (pcd-ataxic mouse), the Staggerer ataxic mouse and the C3H mouse. The brain tissue was dissected into 7 parts, e.g., hypothalamus, cerebrum, thalamus, striatum, brain stem, cerebellum and cervical spinal cord. Pro-TRH concentrations in each part of the brain were measured by radioimmunoassay. Pro-TRH concentrations in the brain of Weaver ataxic mice, pcd-ataxic mice and Staggerer ataxic mice were significantly higher in the thalamus, brain stem, cerebellum and cervical spinal cord. Pro-TRH concentrations in the hypothalamus, striatum and cerebrum of ataxic mice did not differ from those of controls. The elution profile of acetic acid extracted cerebellum of ataxic mice on Sephadex G-50 was identical to that of synthetic pro-TRH. These findings suggest that changes in pro-TRH concentrations in the brain may play a pathophysiological role in ataxic mice.


Factors determining acute normal tissue reactions during postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases.
Acute radiotherapy reactions are commonly underestimated and under-reported in the literature. Our aim was to evaluate the incidence and risk factors for acute reactions during postoperative radiotherapy in endometrial cancer patients. Performed was detailed retrospective analysis of 317 endometrial cancer patients given postoperative radiotherapy. Two hundred forty seven patients (78%) received both intracavitary (BRT) and external beam irradiation (EBRT), 49 patients (15%) received only BRT and 21 patients (7%) - only EBRT. BRT included radium (Ra) or cesium (Cs). The mean total dose at 0.5 cm for Ra and Cs was 50.5+/-10.3 Gy and 48.4+/-15.0 Gy, respectively, and the mean dose rate - 0.47+/-0.06 Gy/h and 1.42+/-0.41 Gy/h, respectively. Mean EBRT dose in the ICRU reference point was 49.0+/-3.7 Gy given in fractions of 1.54-2.49 Gy (mean 2.0+/-0.17 Gy). Radiotherapy and Oncology Group classification system was employed to score acute reactions. The impact of patient- and treatment-related factors on the risk of acute bowel and urinary bladder reactions was assessed with uni- and multivariate tests. Acute radiotherapy reactions of any grade occurred in 265 patients (84%) including bowel complications in 66% and urinary bladder complications in 36%. There were 21 severe (grade 3 or 4) reactions, all but one seen in the patients treated with combined EBRT and BRT. Higher total dose (P=0.024), higher EBRT dose (P=0.022) and higher age (P=0.026) were correlated with increased acute bowel toxicity in univariate analysis. Multivariate analysis showed that higher EBRT dose (P=0.015) and older age (P=0.016) were independently correlated with the risk of acute bowel events. Higher total dose (P=0.009), BRT dose (P=0.029), BRT dose rate (P=0.004), EBRT fraction size (P=0.007), the use of Cs BRT (P=0.001) and lower parity (P=0.041) were correlated with increased risk of acute bladder toxicity in univariate test. Multivariate analysis demonstrated that the independent risk factors for acute bladder events were BRT dose rate (P=0.002) and low parity (P=0.042) and there was a trend for EBRT dose (P=0.076). In multivariate analysis there was no impact of other clinical factors (FIGO stage, diabetes mellitus, hypertension, prior abdominal surgery) on the risk of acute bowel and/or bladder reactions nor was the impact of surgery-to-radiotherapy interval, overall radiotherapy time and overall treatment time. The risk of acute reactions depends both on treatment-related (BRT dose rate, EBRT dose) and patient-related factors (age, parity). Precise treatment prescription, planning and verification are of paramount concern. Further studies are warranted to evaluate the impact of extrinsic and intrinsic factors associated with acute normal tissue injury.


Species specificity of immunity to malignant transformed cultured insect cells.
The specificity of malignantly transformed cultured cells of the German cockroach was assayed by injecting the cells into eight additional species of cockroaches in three families. All species but the most advanced one were susceptible. The range of lethal times for the different species reflected their relationship to the species from which the cells originated. The abilities of the injected hosts to encapsulate implants of embryo fragments of the German cockroach and microcarrier beads paralleled their resistance against the malignant cells. The order of susceptibility of the cockroach species to a pathogenic amoeba paralleled their susceptibility to the malignant cells, but death from the amoeba occurred in a much shorter time. Hematocrit values were higher in the more resistant species.


Misdiagnoses and delay of diagnoses in Moyamoya angiopathy-a large Caucasian case series.
The lacking awareness of healthcare providers bears the risk of delayed or false diagnoses in rare diseases. No systematic data about misdiagnoses of Moyamoya angiopathy (MMA) are available. To evaluate the rate and pattern of missed diagnoses in MMA. Retrospective analysis of a consecutive case series from a single German referral center. Rates of missed or delayed diagnoses in Caucasian MMA patients were calculated based on discharge letters from other hospitals and systematic chart review. Out of 192 Caucasian patients eventually diagnosed with MMA at our center, an initial misdiagnosis was identified in 119 patients (62%). The time between onset and diagnosis was 1 year in 24 patients, 2 years in 23 patients, 3 years in 10 patients, and > 3 years in 49 patients (mean 5.28, median 3, standard deviation 5.11, and range 4-26 years). The most common misdiagnoses were cerebral vasculitis (31%), etiologically ill-defined stroke diagnoses (30.2%), and MS (3.6%). This is the first systematic report which shows that patients with MMA are at high risk to be falsely diagnosed and treated. Depiction of typical vascular abnormalities in angiopathy is essential. Normal CSF cell counts, negative oligoclonal bands, and lack of infratentorial lesions as well as gadolinium-positive T1 lesions on MRI may be red flags differentiating this vasculopathy from vasculitis and MS.


Ruptured pseudoaneurysm of the external iliac artery in an advanced cervical cancer patient treated by endovascular covered stent placement.
The formation of pseudoaneurysms in patients with gynecologic malignancies is rare. We describe a patient with locally advanced cervical cancer who had life-threatening rectal bleeding due to a ruptured pseudoaneurysm of the right external iliac artery, which was successfully treated by emergent endovascular covered stent placement. This 56-year-old woman had received concurrent chemoradiation, salvage hysterectomy and systemic chemotherapy for advanced cervical cancer. About 25 months after her diagnosis of cervical cancer, she suffered from acute life-threatening rectal bleeding. Angiography revealed active extravasation from a pseudoaneurysm of the right external iliac artery. A covered stent was placed across the pseudoaneurysm via an endovascular approach to stop the bleeding. The patient recovered well without any sequelae. We believe that this technique might also be useful in other irradiated gynecologic cancer patients, especially when direct surgical repair is difficult to perform due to pelvic irradiation or tumor recurrence.


Deciphering RNA m6 A regulation in aging: Perspectives on current advances and future directions.
N6 -methyladenosine (m6 A) is a dynamic and reversible RNA modification that has emerged as a crucial player in the life cycle of RNA, thus playing a pivotal role in various biological processes. In recent years, the potential involvement of RNA m6 A modification in aging and age-related diseases has gained increasing attention, making it a promising target for understanding the molecular mechanisms underlying aging and developing new therapeutic strategies. This Perspective article will summarize the current advances in aging-related m6 A regulation, highlighting the most significant findings and their implications for our understanding of cellular senescence and aging, and the potential for targeting RNA m6 A regulation as a therapeutic strategy. We will also discuss the limitations and challenges in this field and provide insights into future research directions. By providing a comprehensive overview of the current state of the field, this Perspective article aims to facilitate further advances in our understanding of the molecular mechanisms underlying aging and to identify new therapeutic targets for aging-related diseases.


[The clinical manifestation and linkage analysis in one Chinese family with congenital fibrosis of extraocular muscles].
To describe the clinical phenotype in a Chinese family with congenital fibrosis of extraocular muscles and to identify the location of candidate gene of the disease in chromosome. The clinical feature of all affected members in this family were examined. A genome-wide linkage screening was conducted. Direct genomic sequencing was used to evaluate the candidate gene KIf21A. Four affected members in the pedigree were born with classic phenotype of CFEOM. By linkage analysis the disease gene was mapped to chromosomal region 12p11.2-q12 defined by microsatellite markers D12S1648 and D12S1668. The maximum Lod Score was 2.12 (D12S1090). Direct sequence showed no mutation in all exons and exon-intron boundaries of the candidate gene KIF21A, a polymorphism substitution occurred in the exon 21. The disorder in this family should be referred as CFEOM1 which was inherited as an autosomal dominant trait. The candidate gene was linked to CFEOM1 locus on chromosome 12p11.2-q12, between marker D12S1648 and D12S1668. It's more likely that KIf21A is not the disease causing gene in this family.


Six months of omeprazole 20 mg daily, 20 mg every other day or 40 mg at weekends in duodenal ulcer patients: a multicenter, prospective, comparative study. Interdisciplinary Group for Ulcer Study.
We performed an open, prospective, randomized, three-cell, 6-month clinical trial on the prevention of duodenal ulcer (DU) relapse, comparing three omeprazole schedules, i.e. 20 mg daily, 20 mg every other day (e.o.d.) and 40 mg on Saturdays and Sundays (S/S). Diagnosis of either healed or relapsed DU was on an endoscopic basis. Follow-up visits were performed at 3-monthly intervals with endoscopy at the baseline, after 6 months and at every symptomatic relapse. chi 2 test with standardized deviates, Yates' corrected chi 2 test and analysis of variance (one-way). One hundred and fifteen patients were randomized to receive omeprazole 20 mg/day, 123 omeprazole 20 mg e.o.d. and 115 40 mg S/S. Twenty-eight dropped out (11, 8 and 9, respectively). Demonstrated ulcer relapse rates were 5.7% with omeprazole 20 mg/day, 18.1% with 20 mg e.o.d. and 17.6% with 40 mg S/S (p = 0.0124, 'per-protocol' analysis). No clinically significant adverse effects were recorded. In conclusion, of the three schedules studied, omeprazole 20 mg/day proved the most effective maintenance treatment for healed DU.


Transport routes of metalloids into and out of the cell: a review of the current knowledge.
Except for their extra- and intra-cellular interfaces, cell membranes are hydrophobic and inhibit the transport of hydrophilic molecules. Metalloids in aqueous solutions form chemical species with oxygen and hydroxyl groups and, therefore, exist as hydrophilic neutral polar solutes or as hydrophilic anions. This characteristic of metalloids introduces a large barrier for their passage through the cell membrane via unaided diffusion. The necessity for an uptake mechanism for metalloids arises from the requirement of these species for the maintenance of life, such as the need of boron for plant cells. Conversely, the transport of these species out of the cell is necessary because some metalloids are toxic, such as arsenic and antimony, and their entrance into the cell is undesirable. The undesired uptake of these toxic species is possible via pathways designed for the uptake of other structurally and chemically similar essential compounds. Therefore, the extrusion of arsenic and antimony out of the cell is an example of a detoxification mechanism. As a consequence of the hydrophobic character of the cell membrane in all living systems, the main route for the uptake and efflux of metalloids is facilitated by transmembrane proteins, driven either by concentration gradients or by energy-fueled pumps. However, metalloids forming or embedded in nano-sized particles escape the need to cross the cell membrane because these particles can be taken into the cell by endocytosis. Here, we review the uptake and efflux pathways of boron, silicon, arsenic, and antimony through the cell membranes of different organisms and the protein channels involved in these processes. In particular, passive diffusion via aquaglyceroporins, active transport via primary and secondary ion pumps, extrusion into vacuoles of metalloid-thiol conjugates via ATP-binding cassette, the efflux of methylated metalloids, and endocytosis are summarized.


An analysis of the responses of rat striatal neurones to scrotal skin temperature.
The responses of neurones in the caudate-putamen complex of anaesthetised rats to different scrotal skin temperatures were examined, together with the electroencephalogram (EEG). Caudate neuronal firing patterns did not change independently of rate, unlike the thermo-responsive cells of the hypothalamus previously reported. The scrotal skin temperature threshold for the caudate neuronal response corresponds precisely with the temperature which provokes desynchronisation of the EEG.


Innovative video capsule endoscopy for detection of ubiquitously elongated small intestinal villi in Cronkhite-Canada syndrome.
Cronkhite-Canada syndrome (CCS) is a rare non-familial disorder with multiple gastrointestinal polyps and ectodermal changes. Adenomatous and carcinomatous changes have been reported. Video capsule endoscopy is a useful non-invasive tool to reveal polypoid lesions of the gastrointestinal tract suspicious for malignancy. We report a case of a patient with CCS with excessively elongated intestinal villi resembling dense sea grass under water as well as multiple polyps of the intestinal mucosa revealed by video capsule endoscopy. This report presents for the first time small bowel video sequences of CCS qualifying video capsule endoscopy for screening purposes and early detection of malignancy.


A small region of porcine hemagglutinating encephalomyelitis virus spike protein interacts with the neural cell adhesion molecule.
The spike (S) protein of porcine hemagglutinating encephalomyelitis virus (PHEV) may mediate infection by binding to a cellular neural cell adhesion molecule (NCAM). This study aimed to identify the crucial domain of the S1 subunit of the S protein that interacts with NCAM. Three truncated segments (S(1-291), S(277-794) and S(548-868)) of the S gene of PHEV and the NCAM gene were cloned individually into the Escherichia coli expression vectors and yeast two-hybrid expression vectors. The interaction between S(1-291), S(277-794), S(548-868) and NCAM were detected by a GST pull-down experiment and yeast two-hybrid assay. Three fusion proteins (S(1-291), S(277-794) and S(548-868)) were screened for their interactions with NCAM by protein-protein interaction assays. The results of these assays clarified that S(277-794) interacted with NCAM, while S(1-291) and S(548-868) did not. A small fragment (258-amino-acid fragment, residues 291-548) on the PHEV S protein was posited to be the minimum number of amino acids necessary to interact with NCAM. This fragment may be the receptor-binding domain that mediates PHEV binding to NCAM.


Validation of an rpoB gene PCR assay for detection of Tropheryma whipplei: 10 years' experience in a National Reference Laboratory.
The performance of a real-time PCR assay targeting the Tropheryma whipplei rpoB gene was evaluated using test strains and 1,236 clinical specimens in a national reference laboratory. The novel rpoB-PCR assay proved to be specific, revealed improved analytical sensitivity, and substantially accelerated detection of T. whipplei DNA in clinical specimens.


Pill counts and pill rental: unintended entrepreneurial opportunities.
Prescription opioid diversion and abuse are becoming increasingly prevalent in many regions of the world, particularly the United States. One method advocated to assess compliance with opioid prescriptions is occasional "pill counts." Shortly before a scheduled appointment, a patient is notified that they must bring in the unused portion of their opioid prescription. It has been assumed that if a patient has the correct number and strength of pills that should be present for that point in a prescription interval that they are unlikely to be selling or abusing their opioids. Two cases are presented where patients describe short term rental of opioids from illicit opioid dealers in order to circumvent pill counts. Pill renting appears to be an established method of circumventing pill counts. Pill counts do not assure non-diversion of opioids and provide additional cash flow to illicit opioid dealers.


Assessment of "silent" restenosis and long-term follow-up after successful angioplasty in single vessel coronary artery disease: the value of quantitative exercise electrocardiography and quantitative coronary angiography.
Exercise electrocardiographic (ECG) testing during follow-up after coronary angioplasty is widely applied to evaluate the efficacy of angioplasty, even in asymptomatic patients. One hundred forty-one asymptomatic patients without previous myocardial infarction underwent quantitative exercise ECG testing and quantitative coronary angiography 1 to 6 months after successful angioplasty in single vessel coronary artery disease to 1) determine the value of exercise ECG testing to detect "silent" restenosis, and 2) assess the long-term prognostic value of exercise ECG testing and coronary angiography. The prevalence of restenosis (defined as greater than or equal to 50% luminal narrowing at the dilation site) was 12% in this selected study group. Of 26 patients with an abnormal exercise ECG (ST segment depression greater than or equal to 0.1 mV), only 4 (15%) showed recurrence of stenosis. Sensitivity and specificity for detection of restenosis were 24% and 82%, respectively. One hundred thirty-four patients (95%) were followed up 1 to 64 months (mean 35) after exercise ECG testing and coronary angiography. Thirty-two patients (24%) experienced a cardiac event: in 25 patients (78%) the initial event was recurrent angina pectoris (New York Heart Association class III or IV) and in 7 patients (22%) it was myocardial infarction, although cardiac death did not occur. The mean interval between exercise ECG testing and the initial cardiac events was 14 months (range 1 to 55), whereas 47% of the initial events took place less than or equal to 6 months after exercise ECG testing.(ABSTRACT TRUNCATED AT 250 WORDS)


Application of four dyes in gene expression analyses by microarrays.
DNA microarrays are widely used in gene expression analyses. To increase throughput and minimize costs without reducing gene expression data obtained, we investigated whether four mRNA samples can be analyzed simultaneously by applying four different fluorescent dyes. Following tests for cross-talk of fluorescence signals, Alexa 488, Alexa 594, Cyanine 3 and Cyanine 5 were selected for hybridizations. For self-hybridizations, a single RNA sample was labelled with all dyes and hybridized on commercial cDNA arrays or on in-house spotted oligonucleotide arrays. Correlation coefficients for all combinations of dyes were above 0.9 on the cDNA array. On the oligonucleotide array they were above 0.8, except combinations with Alexa 488, which were approximately 0.5. Standard deviation of expression differences for replicate spots were similar on the cDNA array for all dye combinations, but on the oligonucleotide array combinations with Alexa 488 showed a higher variation. In conclusion, the four dyes can be used simultaneously for gene expression experiments on the tested cDNA array, but only three dyes can be used on the tested oligonucleotide array. This was confirmed by hybridizations of control with test samples, as all combinations returned similar numbers of differentially expressed genes with comparable effects on gene expression.


Predictors of cardiac sarcoidosis using commonly available cardiac studies.
Cardiac involvement affects ≤40% of patients with sarcoidosis and accounts for ≤25% of deaths. The diagnosis of cardiac sarcoidosis is challenging using the existing screening tests and often relies on expensive cardiac magnetic resonance imaging (cMRI) and cardiac 18-fluorodeoxuyglucose positron emission tomography (FDG-cPET). We developed a scoring system using common clinical tests to predict positive imaging findings using cMRI or FDG-cPET. A retrospective chart review of subjects undergoing cMRI or FDG-cPET was performed. The data were extracted and scored using a predetermined system. Our cohort was predominantly white, with a mean age of 55 years, and 60% were women. The scoring system was compared with the findings from cMRI and FDG-cPET to determine the ability to predict the imaging results that define cardiac sarcoidosis. The scoring system for the patients who had undergone both FDG-cPET and cMRI suggested predictability, but the differences were not statistically significant. However, the positive results from just 1 study were as predictive as having positive findings from both studies. A 1-point increase in the total score increased the probability of positive findings from cMRI or FDG-cPET by 14% (95% confidence interval 3% to 25% increase; p = 0.01). The scoring system seemed to be driven more by the findings from cMRI than by those from FDG-cPET. In patients who had undergone cMRI alone, for each 1-point increase in the total score, the probability of positive cMRI findings increased 11% (95% confidence interval 1% decrease to 25% increase, p = 0.08). All screening modalities were analyzed. No modality was sensitive or specific, although major findings (defined in our scoring system) were most predictive of positive imaging findings. In conclusion, commonly available cardiac screening tools used together in a composite score provide reasonable results to predict positive cardiac sarcoidosis findings on imaging, but the system needs refinement. Our data suggest that major findings from screening studies are more likely to correlate with cMRI findings than with findings from FDG-cPET.


Effects of Weaning Age on Plasma Biomarkers and Growth Performance in Simmental Calves.
Weaning plays a key role in health status and future performance of calves. The aim of this study was to investigate the effects of weaning age (Wa), early (45 d, EW) or conventional (60 d, CW), on growth performance and metabolic profile of ten Simmental calves (5 EW and 5 CW calves). Daily intake of milk and calf starter was recorded. Blood samples and measurements of body weight (BW), heart girth (HG), and wither height (WH) were collected at −25, −15, 0, 6, and 20 days relative to weaning. Growth performances (BW, HG, WH) were affected by Wa, resulting lower in EW calves compared with CW calves (p < 0.05). Average daily gain was affected by overall Wa and Time but also by the interaction Wa × Time (p < 0.05). EW calves had lower paraoxonase and higher oxidation protein products levels, lower glucose levels in the post-weaning period, lower Ca and cholesterol levels at 20 d after weaning, and higher GGT activity at −25 d from weaning (p < 0.05). A significant interaction effect between Wa and Time was reached for glucose, Ca, cholesterol. In conclusion, weaning Simmental calves at approximately six weeks of age might not affect inflammatory status and liver functionality after weaning. As secondary outcome, even though the low number of animals could represent a limitation, the average daily gain obtained by Simmental calves weaned at 45 d supported this strategy (despite the lower body weight at weaning and after was due only to the age difference of 15 days). Hence, in order to reduce rearing costs, early weaning for Simmental calves (dual-purpose breed, milk and beef) might not jeopardize calf development, as long as calves can reach body gains as reported in the present study.


Evoked potential correlates of human information processing.
The late positive component (P3) of the feedback evoked potential was investigated in two tasks: the detection of near-threshold auditory stimuli, and the estimation of 1 s time intervals. When the intensity or probability of the threshold stimuli was varied in the detection task, it became apparent that the feedback P3 was related to the 'contingent probability' of confirming or disconfirming feedback given a particular response. In the time-estimation task the relative probabiliti-s of confirming and disconfirming feedback were altered by changing the time-window wherein a response was judged correct. In these experiments it was found that the feedback P3 component was highly dependent upon the probability of the feedback, and relatively independent of its confirming or disconfirming meaning. With decreasing probability of the feedback stimuli, the P3 component became larger, later, and somewhat more frontal.


Lernaea cyprinacea infection in a new host Puntius pulchellus in intensive culture system and its control by doramectin.
The present study explored the susceptibility of Puntius pulchellus subadults to Lernaea cyprinacea infection subsequent upon their first introduction to an intensive culture system that had a previous history of Lernaea infection and evaluated the efficacy of doramectin against the parasite. All the P. pulchellus introduced to the culture pond got infected demonstrating 100 % susceptibility of this species to Lernaea infection. Pathological changes caused by the parasite as evidenced by the extensive hemorrhage and tissue necrosis of the host at the point of parasite attachment was most severe in P. pulchellus. On the contrary, among the fish species already present in the pond and were previously exposed to the infection before the start of the present study, only Labeo fimbriatus developed mild to moderate infection. Cirrhinus mrigala, Ctenopharyngodon idella and Cyprinus carpio from the same culture pond did not develop Lernaea infection. Doramectin administration at 1 mg/kg b.wt. of fish incorporated in feed and given orally for 10 days or by a single intramuscular injection at 200 μg/kg b.wt. was found to be effective in controlling L. cyprinacea adult parasite infection in P. pulchellus. Doramectin hastened healing of the wounds caused by L. cyprinacea and did not cause any noticeable adverse reactions or toxicity to the fish host during the present study. In conclusion, P. pulchellus was observed to be highly susceptible to L. cyprinacea upon its first exposure to the infective stages of the parasite and a single intramuscular injection of doramectin at 200 μg/kg b.wt. was more effective than oral administration of the drug in controlling L. cyprinacea infection.


Connecting science with industry: lessons learned transferring a novel plasmonic mercury sensor from the bench to the field.
Mercury is a pollutant of pressing global concern. National and international efforts are focused on reducing mercury in the environment to prevent its adverse health impacts. Better sensors would aid in these efforts. This paper details ongoing efforts to deploy novel plasmonic mercury sensors. The authors describe the research efforts to develop the fundamental technology in a research lab and the experience translating that fundamental research into a viable field-ready sensor. Lessons learned along the way are explored.


Phospholipid bilayers made from monolayers on patch-clamp pipettes.
Phospholipid bilayers were made from phospholipid monolayers at the air/water interface on patch-clamp pipettes. Lipid bilayers were characterized using the K+ carrier nonactin and the channel formers gramicidin and alamethicin. Bilayers were also formed from monolayers spontaneously assembled in a suspension of native vesicles from cardiac sarcolemma and lobster axonal membranes and an excess of lipids. In these types of bilayers we observed several different channels including one contained in the axonal membrane that shows delayed rectifier behavior. This technique permits the study of reconstituted channels on a time scale and noise comparable to cellular patch-clamp standards.


Hospital staff 'frustrated' at lack of progress on delayed discharge.
Leading nurses have expressed their frustration at the latest figures revealing the scale of delays in discharging older people from hospital.


Robust complementary hierarchical clustering for gene expression data analysis by β-divergence.
A hierarchical clustering (HC) algorithm is one of the most widely used unsupervised statistical techniques for analyzing microarray gene expression data. When applying the HC algorithm to the gene expression data to cluster individuals, most of the HC algorithms generate clusters based on the highly differentially expressed (DE) genes that have very similar expression patterns. These highly DE genes may sometimes be irrelevant in biological processes. The serious problem is that those irrelevant genes with high expressions potentially drown out the low expressed genes that have important biological functions. To overcome the problem, Nowak and Tibshirani proposed the complementary hierarchical clustering (CHC) (Biostatistics, 9, 467-483, 2008). However, it is not robust against outlying expression and often produces misleading results if there exist some contaminations in the gene expression data. Thus, we propose the robust CHC (RCHC) method to robustify the CHC with respect to outliers by maximizing the β-likelihood function for sequential extraction of a gene-set with proper groups of individuals. Note that the proposed method reduces to the CHC with the tuning parameter β → 0. A value of β plays a key role in the performance of the RCHC method, which controls the tradeoff between the robustness and efficiency of the estimators. Using simulation and real gene expression analysis, the RCHC method shows robust properties to gene expression clustering with respect to data contaminations, overcomes the problem of the CHC, and predicts critically important genes from breast cancer data.


Exploratory toxicology studies of 2,3-substituted imidazo[1,2-a]pyridines with antiparasitic and anti-inflammatory properties.
Trichomoniasis and amoebiasis are neglected diseases and still remain as a global health burden not only for developing countries, from where are endemic, but also for the developed world. Previously, we tested the antiparasitic activity of a number of imidazo[1,2-a]pyridine derivatives (IMPYs) on metronidazole-resistant strains of Entamoeba Hystolitica (HM1:IMSS), and Trichomonas Vaginalis (GT3). Their anti-inflammatory activity was also evaluated. The present work is a part of a project whose aim is to find new alternatives to standard treatments for these maladies, and to address the current concern of emerging resistant parasite strains. Here we report a non-clinical study focused on exploratory toxicology assays of seven IMPYs that showed the best antiparasitic and/or anti-inflammatory properties. Acute, and subacute toxicity tests were carried out. After 14-day oral treatment, liver and kidney functionality assays in combination with chemometric methods were implemented to detect hepatic and/or kidney damage. Some compounds produced off-target effects. Vehicle effects were also detected. However, no signs of hepatic or renal toxicity were observed for any IMPY. These compounds can continue non-clinical evaluations, and if possible, clinical trials as new candidates to treat trichomoniasis and amoebiasis, and inflammatory diseases. Further studies are also needed to fully elucidate a proposed dual effect that may exert these molecules against trichomoniasis and amoebiasis, which may also signify a novel mechanism of action to treat these infections.


Inhibition of human brain dihydropteridine reductase [E.C.184.108.40.206] by the oxidation products of catecholamines, the aminochromes.
Dihydropteridine reductase from human brain has been purified to homogeneity using a naphthaquinone affinity column followed by chromatography on a 5'-AMP-Sepharose column. Contrary to earlier findings, dopamine (I), noradrenaline (II), and adrenaline (III) do not inhibit this enzyme at concentrations below 200 microM, but their oxidation products, the respective aminochromes (IV, V and VI) are inhibitors. The Ki values for adrenochrome (VI) are reported.


Transcriptomic analysis reveals the role of Glycolysis pathway in Litopenaeus vannamei during DIV1 infection.
In recent years, shrimp farming has experienced significant losses due to the emergence of DIV1 (Decapod iridescent virus 1), an infectious virus with a high fatality rate among shrimp. In this study, we conducted transcriptomic analyses on shrimp Litopenaeus vannamei hemocytes following DIV1 infection and focused on the function of genes in the Glycolysis pathway during DIV1 infection. A total of 2197 differentially expressed genes (DEGs) were identified, comprising 1506 up-regulated genes and 691 down-regulated genes. These genes were primarily associated with Phagosome, ECM-Receptor Interaction, Drug Metabolism-Other Enzymes, and the AGE-RAGE signaling pathway in diabetic complications. KEGG pathway enrichment analysis of the DEGs revealed a noteworthy correlation with metabolic pathways, with a specific focus on glucose metabolism. Specifically, the Glycolysis/Gluconeogenesis pathway exhibited significant upregulation following DIV1 infection. In line with this, we observed an augmented accumulation of glycolytic-related metabolites in the hemolymph following DIV1 challenge along with upregulation of the relative mRNA expression of several glycolytic-related genes. Moreover, we found that the inhibition of lactate dehydrogenase (LDH) activity through RNAi or the use of an inhibitor resulted in reduced lactate production, effectively safeguarding shrimp from DIV1 infection. These findings not only provide a comprehensive dataset for further investigation into DIV1 pathogenesis but also offer valuable insights into the immunometabolism mechanisms that govern shrimp responses to DIV1 infection.


Parental intentions to vaccinate children against COVID-19: Findings from a U.S. National Survey.
We examined parents' COVID-19 vaccination intentions for their children, reasons for not vaccinating, and the potential impact of a school/daycare vaccination requirement or pediatrician's recommendation on vaccination intentions. Two online surveys were conducted in June-July and September-October 2021, before pediatric COVID-19 vaccines were authorized for emergency use in children age < 12 years, with an internet-based, non-probability sample of U.S. adults. Respondents with children (age < 18 years) in the household were asked about their intention (likelihood) of vaccinating these children against COVID-19. Weighted Chi-square tests using a Rao-Scott correction were performed. Vaccinated (45.7 %) versus unvaccinated (6.9 %) parents were almost seven times more likely to have vaccinated their 12-17-year-old children against COVID-19. Approximately 58.4 % of respondents with unvaccinated children ages 2-11 years and 42.4 % of those with children < 2 years said they are "very" or "extremely likely" to vaccinate these children against COVID-19. Female parents were significantly more likely (p < .01 to p < .001) to express lower levels of COVID-19 vaccine intentions. Across all age groups of children unvaccinated against COVID-19, parental vaccine intentions increased with increased household income and education levels. COVID-19 vaccine side effects and safety concerns were primary reasons for not vaccinating children. Strategies including school vaccination requirements and recommendations from pediatricians were shown to increase parental COVID-19 vaccination intentions for some. More research is needed on factors that increase/hinder COVID-19 pediatric vaccine uptake.


The use of biologic response modifiers in polyarticular-course juvenile idiopathic arthritis: a systematic review.
To systematically review the clinical efficacy and safety evidence of biologic drugs used to treat the polyarticular category of juvenile idiopathic arthritis (JIA). The literature was searched between 2000 and September 2012 for randomized controlled trials (RCTs), non-randomized comparative studies, and non-comparative observational cohort studies. The drugs evaluated included etanercept, infliximab, adalimumab, abatacept, anakinra, and ritixumab. Eligible studies included 20 or more patients with JIA, the majority of whom had polyarticular course disease. Outcomes of interest were disease improvement defined by the American College of Rheumatology criteria for Pediatrics, disease flares, rates of inactive disease, remissions, discontinuations, and adverse events (severe and non-severe). Thirty-seven studies were included, the majority focused on etanercept. Seven RCTs were identified, including one each for etanercept, infliximab, adalimumab, abatacept, and anakinra, and one each looking at etanercept or infliximab as first-line therapies. There was strong evidence to support the efficacy and safety of biologics over the short-term, but a lack of long-term data for treatments other than etanercept. Several high-quality patient registries confirmed the efficacy and safety of etanercept over the long-term. Current evidence shows that a short-term improvement in treatment response is achieved when patients with polyarticular JIA with an inadequate response to conventional treatment are treated with biologics. Long-term effectiveness data, however, are sparse leaving many questions regarding switches between biologics, handling patients that achieve disease remission, and long-term safety. Study designs other than RCTs may be important in understanding the role of biologics in JIA over the long-term.


Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.
Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.


Comparative study of vascularized and nonvascularized tendon grafts for reconstruction of flexor tendons in zone 2: an experimental study in primates.
Vascularized tendon grafts were compared with nonvascularized tendon grafts in a primate experimental model. In four monkeys, seven vascularized extensor hallucis longus grafts were placed in the foot's digital fibroosseous canal and these were compared with eight nonvascularized tendon grafts similarly placed in the opposite extremities. The juncture techniques and postoperative protocols were identical for both tendon groups. All tendons were explored 5 months after insertion. The vascular pedicle was patent in all vascularized tendons. Three tendon ruptures occurred in nonvascularized tendons and only one rupture occurred in a vascularized tendon. The digits with vascularized tendons demonstrated a significantly better simulated total active motion (117 degrees versus 128 degrees, p less than 0.05) than digits with nonvascularized tendons. The difference was even more significant when a localized tenolysis of the proximal juncture of the tendon graft was performed (215 degrees versus 138 degrees, p less than 0.01). This study supports the concept that vascularized tendon grafts may be advantageous in scarred tendon beds.


Development of Down Syndrome Research Over the Last Decades-What Healthcare and Education Professionals Need to Know.
Down syndrome (DS) is the most prevalent neurodevelopmental disorder, with a known genetic cause. Besides facial dysmorphologies and congenital and/or acquired medical conditions, the syndrome is characterized by intellectual disability, accelerated aging, and an increased likelihood of an early onset Alzheimer's disease in adulthood. These common patterns of DS are derived from the long-held standard in the field of DS research, that describes individuals with DS as a homogeneous group and compares phenotypic outcomes with either neurotypical controls or other neurodevelopmental disorders. This traditional view has changed, as modern research pinpoints a broad variability in both the occurrence and severity of symptoms across DS, arguing for DS heterogeneity and against a single "DS profile." Nevertheless, prenatal counseling does not often prioritize the awareness of potential within-group variations of DS, portraying only a vague picture of the developmental outcomes of children with DS to expectant parents. This mini-review provides a concise update on existent information about the heterogeneity of DS from a full-spectrum developmental perspective, within an interdisciplinary context. Knowledge on DS heterogeneity will not only enable professionals to enhance the quality of prenatal counseling, but also help parents to set targeted early interventions, to further optimize daily functions and the quality of life of their children.


Maternal Renovascular Hypertensive Rats Treatment With Hydrogen Sulfide Increased the Methylation of AT1b Gene in Offspring.
A large number of studies have shown hypertension of offspring in adulthood is related to parental health during pregnancy. Hydrogen sulfide (H2S) could relax placental vasculature and improve intrauterine growth restriction. In the present study, we want to observe the effect of H2S on the fetal programming of renovascular hypertension, a rat model of secondary hypertension. Renovascular hypertension was induced by 2-kidney-1-clip, their adult pups were used to evaluate basal blood pressure. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively by tail-cuff plethysmography in conscious offspring; HE staining was used to observe morphology of kidney; the protein expression of angiotensin II receptor 1 (AT1R) tested by western blot; methylation of angiotensin II receptor 1b (AT1b) gene used pBLUE-T-cloning to check. The SBP and DBP in the offspring of renovascular hypertensive dams were higher than those in control group. Moreover, interstitial inflammatory infiltration was significant in the kidney and the protein expression of AT1R was also increased in the offspring of renovascular hypertensive dams. Conversely, methylation of AT1b promoter (U01033 277-1611) decreased in the first 3 CG sites. Either prenatal or postnatal treatment with H2S could increase the methylation of AT1b and downregulate AT1R expression then improve the blood pressure. These results suggested that parental secondary hypertension-induced kidney damage that elevated basal blood pressure in adult offspring. Prenatal or postnatal administration with H2S induced improved effect accompanied by an increased methylation of AT1b gene then downregulated protein of AT1R in offspring.


Muscle satellite cells are impaired in type 2 diabetic mice by elevated extracellular adenosine.
Muscle regeneration is known to be defective under diabetic conditions. However, the underlying mechanisms remain less clear. Adult quiescent muscle satellite cells (MuSCs) from leptin-receptor-deficient (i.e., db/db) diabetic mice are defective in early activation in vivo, but not in culture, suggesting the involvement of pathogenic niche factors. Elevated extracellular adenosine (eAdo) and AMP (eAMP) are detected under diabetic conditions. eAdo and eAMP potently inhibit cell cycle re-entry of quiescent MuSCs and injury-induced muscle regeneration. Mechanistically, eAdo and eAMP engage the equilibrative Ado transporters (ENTs)-Ado kinase (ADK)-AMPK signaling axis in MuSCs to inhibit the mTORC1-dependent cell growth checkpoint. eAdo and eAMP also inhibit early activation of quiescent fibroadipogenic progenitors and human MuSCs by the same mechanism. Treatment of db/db diabetic mice with an ADK inhibitor partially rescues the activation defects of MuSCs in vivo. Thus, both ADK and ENTs represent potential therapeutic targets for restoring the regenerative functions of tissue stem cells in patients with diabetes.


Characterisation of the discriminative stimulus properties of flumazenil.
Rats were trained to discriminate flumazenil (15 mg/kg i.p.) from vehicle in a two-lever, food-reinforced, operant conditioning procedure. Substitution tests were performed with a wide dose range of flumazenil and of several benzodiazepines and non-benzodiazepine compounds possessing behavioural effects similar to or opposite to those of benzodiazepine agonists. The results indicate that low doses of flumazenil have behavioural effects, that the flumazenil cue has a low degree of specificity and is most strongly related to the stimulus properties of benzodiazepines.


Effect of volatile organic compounds from bacteria on nematodes.
The five studied bacterial strains could produce volatile organic compounds (VOCs) that kill nematodes. Based on their 16S rRNA sequences, these strains were identified as Pseudochrobactrum saccharolyticum, Wautersiella falsenii, Proteus hauseri, Arthrobacter nicotianae, and Achromobacter xylosoxidans. The bacterial VOCs were extracted using solid-phase micro-extraction (SPME) and subsequently identified by GC/MS analysis. The VOCs covered a wide range of aldehydes, ketones, alkyls, alcohols, alkenes, esters, alkynes, acids, ethers, as well as heterocyclic and phenolic compounds. Among the 53 VOCs identified, 19 candidates, produced by different bacteria, were selected to test their nematicidal activity (NA) against Caenorhabditis elegans and Meloidogyne incognita. The seven compounds with the highest NAs were acetophenone, S-methyl thiobutyrate, dimethyl disulfide, ethyl 3,3-dimethylacrylate, nonan-2-one, 1-methoxy-4-methylbenzene, and butyl isovalerate. Among them, S-methyl thiobutyrate showed a stronger NA than the commercial insecticide dimethyl disulfide. It was reported for the first time here that the five bacterial strains as well as S-methyl thiobutyrate, ethyl 3,3-dimethylacrylate, 1-methoxy-4-methylbenzene, and butyl isovalerate possess NA. These strains and compounds might provide new insights in the search for novel nematicides.


The Critical Role of Imaging in the Management of Multiple Myeloma.
Multiple myeloma (MM) is characterized by abnormal proliferation of plasma cells in the bone marrow leading to symptoms of anemia, renal failure, hypercalcemia, and bone lesions. Bone imaging is critical for the diagnosis, staging, assessment for the presence and extent of bone lesions, and initial treatment of MM. Skeletal survey is the preferred initial imaging modality due to its availability and low cost. However, it has poor sensitivity and patients with occult myeloma may escape detection, delaying their diagnosis and treatment. New cross-sectional imaging modalities such as low-dose whole body CT, MRI, and PET-CT have high sensitivity and specificity for detecting lytic lesions and extramedullary relapse in MM. The combined use of cross-sectional imaging may provide complimentary information for staging, prognosis, and disease monitoring. In this review, we will discuss commonly used imaging modalities and their advantages and disadvantages in the management of MM.


Neurological sequel of chronic kidney disease: From diminished Acetylcholinesterase activity to mitochondrial dysfunctions, oxidative stress and inflammation in mice brain.
With increasing prevalence, chronic kidney disease (CKD) has become a global health problem. Due to the retention of uremic toxins, electrolytes and water, and the resultant metabolic disturbances, CKD affects several organs, including the nervous system. Thus, CKD patients suffer from several neurological complications, including dementia, cognitive impairment, motor abnormalities, depression, and mood and sleep disturbances. However, the mechanisms underlying the neurological complications are least elucidated. We have recently reported a highly reproducible mice model of CKD induced by high adenine diet, which exhibited psychomotor behavioral abnormalities and blood-brain barrier disruption. In the present study, using the mice model, we have investigated psycho-motor and cognitive behaviour, and the neurochemical and histopathological alterations in brain relevant to the observed behavioural abnormalities. The results demonstrate global loss of Acetylcholinesterase activity, and decrease in neuronal arborisation and dendritic spine density in discrete brain regions, of the CKD mice. Oxidative stress, inflammation, and mitochondrial dysfunctions were found in specific brain regions of the mice, which have been regarded as the underlying causes of the observed neurochemical and histopathological alterations. Thus, the present study is of immense importance, and has therapeutic implications in the management of CKD-associated neurological complications.


Malaria: new vaccines for old?
Detailed analyses of the 5500 genes revealed by the complete Plasmodium genome sequence are yielding new candidate parasite antigens and strategies that may contribute to a successful vaccine against malaria in the coming decade.


Density-dependent growth adaptation kinetics in 3T3 cell populations following sudden [Ca2+] and temperature changes. A comparison with SV40-3T3 cells.
Lowered extracellular [Ca2+] cause low growth rates and low stationary cell densities in 3T3 cell cultures as compared to physiological [Ca2%]. Under otherwise constant conditions the extracellular [Ca2+] determines a stable stationary cell density, which can be reached by increase of net cell number or decrease of net cell number, depending on cell density at the time of [Ca2+] adjustment. SV40-3T3 cells do not show this [Ca2+] dependency. At 39 degrees C 3T3 and SV40-3T3 cell populations show an increased growth rate at low cell densities as compared to cell populations at 35 degrees C. Approaching the stationary density the growth rate of both cell sorts is reduced faster at 39 degrees C than at 35 degrees C, leading to lower stationary cell densities at 39 degrees C than at 35 degrees C. A temperature change from 39 degrees C to 35 degrees C or in the opposite direction can affect the stationary cell density of 3T3 cell populations only if applied before reduction of growth rate by density-dependent growth-inhibiting principles has taken place.


Smoking cessation as a dental intervention--views of the profession.
To undertake a questionnaire-based survey to determine the attitudes and activities of dental professionals in primary care in the Northern Deanery of the UK in relation to providing smoking cessation advice. Questionnaires for dentists, hygienists and dental nurses were sent to hygienists to distribute to other members of the team. The information collected included: smoking status of the professionals and the practice; roles of the dental team in giving smoking cessation advice; levels of training received; and potential barriers to giving this brief intervention. Over 90% of practices were smoke-free environments and significantly more dental nurses (23%) were smokers compared to dentists (10%) and hygienists (7%) (p<0.01). The majority of dentists and hygienists enquired about smoking status of their patients and all three groups believed that hygienists and dentists should offer brief smoking cessation advice. Potential barriers to delivering smoking cessation advice were identified: lack of remuneration; lack of time; and lack of training. Dental teams in primary care are aware of the importance of offering smoking cessation advice and, with further training and appropriate remuneration, could guide many of their patients who smoke to successful quit attempts.


Soluble sugars in the mycelium of the basidiomycete Oudemansiella mucida.
Quantitative gas chromatography was used to determine soluble neutral sugars in an extract of the fungus Oudemansiella mucida grown on a synthetic glucose medium. Apart from the usual fungal sugar components, viz. trehalose, D-glucose, D-mannitol, D-arabinitol, glycerol and inositol, the 6-day-old mycelium contained D-arabino-2-hexosulose (D-glucosone). In the period of maximum growth, this aldoketose was the predominant monosaccharide (3.4% mycelial dry weight).


High efficient removal of fluoride from aqueous solution by a novel hydroxyl aluminum oxalate adsorbent.
A novel adsorbent, hydroxyl aluminum oxalate (HAO), for the high efficient removal of fluoride from aqueous solution was successfully synthesized. The adsorbent was characterized and its performance in fluoride (F(-)) removal was evaluated for the first time. Kinetic data reveal that the F(-) adsorption is rapid in the beginning followed by a slower adsorption process; 75.9% adsorption can be achieved within 1min and only 16% additional removal occurred in the following 239min. The F(-) adsorption kinetics was well described by the pseudo second-order kinetic model. The calculated adsorption capacity of this adsorbent for F(-) by Langmuir model was 400mgg(-1) at pH 6.5, which is one of the highest capabilities of today's materials. The thermodynamic parameters calculated from the temperature-dependent isotherms indicate that the adsorption reaction of F(-) on the HAO is a spontaneous process. The FT-IR spectra of HAO before and after adsorbing F(-) show adsorption mechanism should be hydroxyl and oxalate interchange with F(-).


Catalytic subunit of cAMP-dependent protein kinase from bovine heart: several isoforms demonstrated by high resolution focusing in immobilized pH gradient.
The catalytic subunit (C) of cAMP-dependent protein kinase holoenzyme type II from bovine cardiac muscle was separated by isoelectric focusing in Immobiline polyacrylamide gels into 9 protein forms. The major forms (i) appeared at pH 7.1, 7.4, 7.5, and 7.7, (ii) exhibited protein kinase activity and were inhibited by heat and acid stable inhibitor, (iii) represented approx. 30%, 4%, 64%, and 1% of the protein respectively, (iv) refocused in the same position from which they had been eluted from the first gel. Antibodies against C detected additional proteins at approx. pH 7.55, 7.75, and 7.8. Two more bands became detectable at approx. pH 7.3 and 7.45 by application of antibody against C beta (Uhler, M.D. & McKnight G.S. 1987, J.Biol.Chem. 262, 15202-15207). The relation of the different forms of C to the fractions CA and CB (Kinzel V. et al. 1987 Arch. Biochem. Biophys. 253, 341-349) is demonstrated.


Facilitation by pyrimidine deoxyribonucleosides and hypoxanthine of mutagenic and cytotoxic effects of monofunctional alkylating agents in Chinese hamster cells.
Hypoxanthine (Hx), thymidine (TdR) and deoxycytidine (CdR), at concentrations of 10(-5) M increased the yield of 8-azaguanine-resistant (AzGr) mutants induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in cultured Chinese hamster V79 cells. The cytotoxicity of MNNG was increased 2-fold in the presence of Hx, and more than 10-fold in the presence of TdR. This cytotoxic effect of TdR was abolished by equal concentrations of CdR, which by itself did not increase the cytotoxicity of MNNG. However, the yield of MNNG-induced AzGr colonies was increased 2--10-fold in the presence of both CdR and TdR. The AzGr colonies displayed phenotypes characteristic of hypoxanthine: guaninephosphoribosyltransferase-deficient (HGPRT-) mutants, or indicative of mutant HGPRT with altered substrate affinities. The nucleosides did not affect the growth or expression time of the HGPRT- mutants; the same extent of alkali-labile DNA damage occurred in cells treated with alkylating agents in the presence and absence of TdR and CdR; and the increase in mutation frequency in the presence of these nucleosides occurred not only with MNNG, but also with ethylating agents. Nucleosides treated with MNNG were not mutagenic, and treatment of the cells with TdR and CdR only prior to treatment with MNNG or only during selection with AzG did not increase the induced mutation frequency. Therefore, the interpretation is proposed that CdR, TdR and Hx produce nucleotide-pool imbalances that increase lethal and mutagenic errors of replication of alkylated DNA.


Self-Efficacy Intervention Programs in Patients with Chronic Obstructive Pulmonary Disease: Narrative Review.
Chronic obstructive pulmonary disease (COPD) is a common chronic disease whose development is irreversible, which leads to more than six million deaths each year. There is no treatment confirmed effective for the improvement of impaired lung function, but the combination of drug therapy with non-drug therapy such as pulmonary rehabilitation training has demonstrated a great potential in reducing the occurrence of complications and delaying the progression of COPD. Self-efficacy is the core of cognitive theory, which is crucial for chronic disease management. It has been proposed as an important component of disease management to help people develop skills to manage diseases more effectively. This study reviewed the development of self-efficacy and its application in patients with COPD, with the purpose of providing a better clinical reference for the treatments of COPD.


Structure-activity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanling male C57BL/6J x C3H/HeJ F1 mice.
Further information on the structure-activity relationships among the synthetic and naturally occurring alkenylbenzene derivatives was obtained by examining their hepatocarcinogenicities for mice following administration of one or a few doses prior to weaning. Under these conditions preweanling male C3H/HeJ mice were more susceptible than male C57BL/6J mice or females of either strain to liver tumor induction by 1'-hydroxyestragole (1'-hydroxy-1-allyl-4-methoxybenzene) and 1'-hydroxysafrole (1'-hydroxy-1-allyl-3,4-methylenedioxybenzene). Male C57BL/6J X C3H/HeJ F1 mice given a single dose of 1'-hydroxyestragole at 12 days of age developed approximately twice as many hepatomas per liver as did those given the same dose per g of body weight at 1 day of age. The acetylenic compounds 1'-hydroxy-2',3'-dehydroestragole and 1'-hydroxy-2',3'-dehydrosafrole were the most potent derivatives studied; they were 5- and 10-fold more potent (based on the average numbers of hepatomas per liver) than the corresponding allylic benzene derivatives. 1'-Acetoxyestragole and 1'-acetoxysafrole had activities similar to those of their respective 1'-hydroxy derivatives; estragole derivatives were consistently 2- to 3-fold more potent than the related safrole derivatives. 1'-Hydroxyelemicin (1'-hydroxy-1-allyl-3,4,5-trimethoxybenzene), its acetic acid ester 1'-oxoestragole, and 3'-bromo-trans-anethole (3'-bromo-1-trans-propenyl-4-methoxybenzene) each had very weak, but statistically significant, hepatocarcinogenic activity. The propenylic derivatives cis-anethole, trans-isosafrole, 1:1 cis,trans-isosafrole, 3'-hydroxy-trans-anethole, piperine, and trans-cinnamaldehyde showed no hepatocarcinogenic activity at the levels examined. In contrast, the propenylic derivatives cis- and trans-asarone (1-propenyl-2,4,5-trimethoxybenzene) were each active; the hepatocarcinogenicities of the asarones were not inhibited by prior administration of pentachlorophenol, a sulfotransferase inhibitor that abolished the hepatocarcinogenicity of estragole under the same conditions. Furthermore, precocene II (6,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran), a cyclic propenylic plant metabolite and asarone analogue, showed strong hepatocarcinogenic activity similar to that of 1'-hydroxy-2',3'-dehydroestragole and 1'-hydroxy-2',3'-dehydrosafrole; precocene I (the 7-methoxy analogue of precocene II) was less active than precocene II but more active than cis-asarone.


Effects of nitric oxide synthase inhibition on diethylstilbestrol-induced hyperprolactinaemia and pituitary tumourigenesis in rats.
The overexpression of nitric oxide synthase (NOS) has been found in tumours, including pituitary adenomas. It has also been found that NOS is overexpressed in human spontaneous pituitary adenomas. The question arises whether NOS and its product, nitric oxide (NO), are involved in pituitary tumourigenesis. To investigate this question, in the present paper we examine the effects of NOS inhibition on the development of diethylstilbestrol (DES)-induced prolactin-secreting pituitary tumours in rats. Thirty male Fisher 344 rats, four weeks old, were submitted to subcutaneous implantation of a silastic capsule containing DES (10 mg/capsule) or of an empty capsule. Six weeks after implantation, some of the DES-treated animals received a NOS inhibitor, N-nitro-l-arginine methyl ester (NAME), 1 mg/mL, in their drinking water, for the subsequent 14 days. Eight weeks after the implantation, all the animals were sacrificed, their pituitaries were weighed, and samples of heart blood were collected for prolactin (PRL) and vascular endothelial growth factor (VEGF) measurements. It was found that DES implantation significantly increased pituitary mass, as well as PRL and VEGF concentrations in blood serum. On the other hand, the administration of NAME did not affect significantly either VEGF concentration or pituitary mass. On the other hand, it did induce a further increase in PRL levels. These findings indicate that NO is involved in oestrogen-induced hyperprolactinaemia, but does not play a crucial role in oestrogen-induced pituitary tumourigenesis.


The role of physical fitness as risk indicator of increased low back pain intensity among people working with physically and mentally disabled persons: a 30-month prospective study.
A prospective cohort study. To study if low level of physical fitness was associated with increased low back pain (LBP) intensity at 30-month follow-up. The evidence of low physical fitness as a risk factor for LBP is inconclusive due to contradictory results. Study participants were 327 employees (women = 271, men = 56) at institutions for physically and mentally disabled persons. Physical fitness was measured by tests of: back extension and flexion endurance, flexibility and balance; and by self-assessed aerobic fitness, muscle strength, endurance, flexibility and balance, using visual analogue scales. Low back pain, lifestyle parameters, and physical and psychosocial work factors were assessed by questionnaires at baseline and at follow-up. Outcome was defined as an increase above 2 steps in average LBP intensity during the previous year (0-10). Persons with low level back endurance showed an insignificantly higher risk of increased LBP intensity (OR = 2.4, P = 0.076), whereas persons with medium level back endurance were at significantly higher risk (OR = 2.7, P = 0.034) compared with those with high level back endurance. The general association between isometric back extension endurance and increased LBP intensity was insignificant (P = 0.067). Persons with medium level self-assessed aerobic fitness were at lower risk of increased LBP intensity compared with those with high level (OR = 0.37, P = 0.02), although the general association of aerobic fitness was insignificant (0.066). Performance-based back flexion endurance, flexibility, and balance; and self-assessed muscle strength, endurance, flexibility, and balance were not associated with increased LBP intensity. The significant association between medium level back extension endurance and increased LBP intensity supports the finding of other studies that particularly back extension endurance is an important physical fitness component in preventing LBP and that the subcomponents of physical fitness are related in different ways to LBP.


A rapid and comprehensive quality assessing method of Yin-Qiao-Jie-Du tablets using UHPLC-QTOF-MS in combination with multivariate statistical analysis.
Yin-Qiao-Jie-Du (YQJD) tablet is a well-known non-prescription Chinese patent drug widely used for the prevention and treatment of diseases in China. However, documented studies for assessing and controlling the quality of YQJD tablet are limited. In this article, a rapid and comprehensive method for the quality assessment and control of YQJD tablets was developed, via qualitative and quantitative analysis of the major active ingredients of YQJD tablets by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) in combination with multivariate statistical analysis. The samples of YQJD tablets were triturated and then extracted with methanol, and the extracts were analyzed by UHPLC-QTOF-MS. A good separation was achieved within 30 min by using an Agilent RRHD SB-C18 (150 mm × 2.1mm I.D., 1.8 μm) column with a gradient elution of water (0.5% formic acid) and acetonitrile. Forty-one major chromatographic peaks were obtained, and 31 of them were identified according to the obtained data from the measurements of accurate mass, isotopic composition, and collision-induced dissociation. Among them, 21 were confirmed by the comparison of retention times, MS, and MS/MS information with those of their references. Quantitative analysis was performed based on the peak areas of extracted ion chromatograms of the exact pseudo-molecular ions (with a 0.01 Da window), and the result of method validation demonstrated that the proposed method possessed desirable specificity, linearity, precision, and accuracy. Subsequently, the method was utilized to analyze the major constituents in YQJD tablets of 18 batches produced by different manufacturers. The obtained contents of the 21 confirmed ingredients were applied for orthogonal partial-least squares to latent structures discriminant analysis (OPLS-DA). An assessment of the quality consistency and stability as well as tracing the origins of the investigated YQJD tablets were successfully achieved by OPLS-DA. All of these results demonstrated that the UHPLC-QTOF-MS method developed in this study was a rapid and desirable approach for differentiating the origin, discriminating the authenticity, and assessing and controlling the quality of YQJD tablets.


Case presentation: nephrolithiasis in a patient treated with atazanavir.
Of the recently approved antiretroviral protease inhibitors, atazanavir has become a popular medication for the treatment of HIV infection. The advantages of an atazanavir-based regimen include a favorable side effect profile, low impact on lipids, low pill burden, and daily dosing. These have made it a favorable choice for antiretroviral treatment. As more experience is gained with newer antiretroviral medications, additional side effects become apparent. Recent reports have highlighted occurrences of nephrolithiasis in patients using atazanavir-based regimens. The authors present a case of a patient who experienced nephrolithiasis while taking combination antiretroviral therapy that included atazanavir.


Renal artery stenting with two simultaneous protection devices.
To describe a new technique for distal protection during stenting of a bifurcated renal artery using two simultaneous filter devices. A 70-year-old patient underwent angiography of a single functional kidney. Severe proximal, nonostial narrowing of an early bifurcated renal artery was found. Two AngioGuard filter protection devices were placed, one in each branch. A balloon mounted stent was advanced over both wires simultaneously till they reached divergence point, expanded fully, and the protection devices were retrieved. No complications were observed and the final result was good. The concomitant use of two protection devices is feasible in a particular anatomy context.


Exploring spatial feedbacks between adaptation policies and internal migration patterns due to sea-level rise.
Climate change-induced sea-level rise will lead to an increase in internal migration, whose intensity and spatial patterns will depend on the amount of sea-level rise; future socioeconomic development; and adaptation strategies pursued to reduce exposure and vulnerability to sea-level rise. To explore spatial feedbacks between these drivers, we combine sea-level rise projections, socioeconomic projections, and assumptions on adaptation policies in a spatially-explicit model ('CONCLUDE'). Using the Mediterranean region as a case study, we find up to 20 million sea-level rise-related internal migrants by 2100 if no adaptation policies are implemented, with approximately three times higher migration in southern and eastern Mediterranean countries compared to northern Mediterranean countries. We show that adaptation policies can reduce the number of internal migrants by a factor of 1.4 to 9, depending on the type of strategies pursued; the implementation of hard protection measures may even lead to migration towards protected coastlines. Overall, spatial migration patterns are robust across all scenarios, with out-migration from a narrow coastal strip and in-migration widely spread across urban settings. However, the type of migration (e.g. proactive/reactive, managed/autonomous) depends on future socioeconomic developments that drive adaptive capacity, calling for decision-making that goes well beyond coastal issues.


Knowledge translation tools for parents on child health topics: a scoping review.
An emerging field of knowledge translation (KT) research has begun to focus on health consumers, particularly in child health. KT tools provide health consumers with research knowledge to inform health decision-making and may foster 'effective consumers'. Thus, the purpose of this scoping review was to describe the state of the field of previously published effectiveness research on child health-related KT tools for parents/caregivers to understand the evidence-base, identify gaps, and guide future research efforts. A health research librarian developed and implemented search strategies in 8 databases. One reviewer conducted screening using pre-determined criteria. A second reviewer verified 10% of screening decisions. Data extraction was performed by one reviewer. A descriptive analysis was conducted and included patient-important outcome classification, WIDER Recommendation checklist, and methodological quality assessment. Seven thousand nine hundred fifty two independent titles and abstracts were reviewed, 2267 full-text studies were retrieved and reviewed, and 18 articles were included in the final data set. A variety of KT tools, including single- (n = 10) and multi-component tools (n = 10), were evaluated spanning acute (n = 4), chronic (n = 5) and public/population health (n = 9) child health topics. Study designs included: cross-sectional (n = 4), before-after (n = 1), controlled before-after (n = 2), cohort (n = 1), and RCTs (n = 10). The KT tools were evaluated via single primary outcome category (n = 11) and multiple primary outcome categories (n = 7). Two studies demonstrated significant positive effects on primary outcome categories; the remaining studies demonstrated mixed effects (n = 9) and no effect (n = 3). Overall, methodological quality was poor; studies lacked a priori protocols (n = 18) and sample size calculations (n = 13). Overall, intervention reporting was also poor; KT tools lacked description of theoretical underpinnings (n = 14), end-user engagement (n = 13), and preliminary research (n = 9) to inform the current effectiveness evaluation. A number of child health-related knowledge translation tools have been developed for parents/caregivers. However, numerous outcomes were used to assess impact and there is limited evidence demonstrating their effectiveness. Moreover, the methodological rigor and reporting of effectiveness studies is limited. Careful tool development involving end-users and preliminary research, including usability testing and mixed methods, prior to large-scale studies may be important to advance the science of KT for health consumers.


Fine structural aspects of silk secretion in a spider. II. Conduction in the pyriform glands.
The excretory duct of pyriform glands in Araneus diadematus is connected to the secretory sac through an intermediary cell ring. Apices of these cells bear thick, long microvilli and cytoplasmic extensions containing microtubules in bundles, some of which are derived from normal basal bodies. These finger-like extensions lie between the cuticular intima and the secretory product; they are thought to protect the intima and to initiate moulding of the silk thread. Structural features of the duct cells suggest that the latter play a role in the control of the water content of the silk glue which is restricted to the last portion of the duct where numerous nerve endings are inserted between cells. It is evident that duct structure and chemical and physical characteristics of silk are correlated in all spider silk glands.


Mice transgenic for equine cyclin T1 and ELR1 are susceptible to equine infectious anemia virus infection.
As a member of the tumor necrosis factor receptor (TNFR) protein superfamily, equine lentivirus receptor 1 (ELR1) has been shown to be expressed in various equine cells that are permissive for equine infectious anemia virus (EIAV) replication. The EIAV Tat protein (eTat) activates transcription initiated at the viral long terminal repeat (LTR) promoter through a unique mechanism that requires the recruitment of the equine cyclin T1 (eCT1) cofactor into the viral TAR RNA target element. In vitro studies have demonstrated that mouse fibroblast cell lines (e.g., NIH 3T3 cells) that express the EIAV receptor ELR1 and eCT1 support the productive replication of EIAV. Therefore, we constructed transgenic eCT1- and ELR1-expressing mice to examine whether they support in vivo EIAV replication. For the first time, we constructed mice transgenic for ELR1 and eCT1. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis confirmed that ELR1 and eCT1 were expressed in the transgenic mouse tissues, particularly in the intestines, spleen and lymph nodes. Consistent with the results of EIAV infection in NIH 3T3 cells expressing ELR1 and eCT1, mouse embryonic fibroblasts (MEFs) from the transgenic mice could support EIAV replication. More importantly, this virus could infect and replicate in mouse blood monocyte-derived macrophages (mMDMs). Macrophages are the principle target cell of EIAV in its natural hosts. Furthermore, after the transgenic mice were inoculated with EIAV, the virus could be detected not only in the plasma of the circulating blood but also in multiple organs, among which, the spleen and lymph nodes were the predominant sites of EIAV replication. Finally, we found that consistent with high viral replication levels, the relevant pathological changes occurred in the spleen and lymph nodes. Our results show that mice transgenic for ELR1 and eCT1 are susceptible to EIAV infection and replication. Further, EIAV infection can cause lesions on the spleen and lymph nodes, similar to those frequently observed in horses, the natural hosts. Therefore, ELR1 and eCT1 are essential in vivo for EIAV invasion and replication.