Modulation by endothelium of contractile responses in rat aorta in absence and presence of flunarizine.
The possible modulation by endothelium of phenylephrine- and prostaglandin F2 alpha-induced mobilization of calcium for contraction in the rat aorta has been investigated. Contractions elicited by these and other agonists are inhibited in the presence of endothelium. For any single concentration of phenylephrine in the presence of endothelium, the initial phasic components of contractions were significantly greater, the maximal contractions were achieved sooner and were less well maintained as compared to contractions elicited in the absence of endothelium. The kinetic characteristics of contractions stimulated by single concentrations of PGF2 alpha were similar in the presence and absence of endothelium and did not exhibit initial phasic components of contraction. Sub-maximal contractions-elicited by both PGF2 alpha and phenylephrine in the absence of endothelium were inhibited to a greater extent by flunarizine 3 microM than equieffective contractions elicited in the presence of endothelium. Maximal contractions elicited by phenylephrine (1 microM) were inhibited to a similar extent by flunarizine in the presence and absence of endothelium, but maximal contractions elicited by PGF2 alpha (30 microM) were inhibited by flunarizine to a greater extent in the presence than in the absence of endothelium. It is concluded that an endothelium-derived factor, perhaps distinct from endothelium-derived relaxing factor, can modulate the ability of both phenylephrine and PGF2 alpha to mobilize calcium for contraction. This modulatory effect is associated with an enhanced mobilization of intracellular calcium. Thus, submaximal concentrations of both agonists were less dependent on extracellular calcium than on intracellular calcium to elicit contractions in the presence of endothelium, as compared to contractions elicited in the absence of endothelium.


The activation, by antigen, of naïve TCR transgenic CD4 T cells cultured at physiological, rather than artificially high, frequencies more accurately reflects the in vivo activation of normal numbers of naïve CD4(+) T cells.
The majority of in vitro studies investigating the activation of naïve TCR transgenic T cells routinely employ an artificially high frequency of such cells. To assess whether employing high frequencies of TCR transgenic cells in vitro accurately reflects the in vivo activation of a normal number of T cells, we cultured between 300 and 3×10(6) Rag2(-/-) DO11.10 T cells per well under otherwise identical conditions. We find that those T cells cultured at low frequencies proliferate more and are more potently activated, as assessed by the expression of CD44 and CD62L, each giving rise to a much larger number of cytokine producing cells, comparable to the number generated in vivo when a normal number of CD4(+) T cells are activated. The effect of T cell frequency on the level of their activation was not due to differences in MHCII or CD80/86 expression by B cells, the major APC population present, nor to increased death of B cells in high frequency cultures. Taken together, our observations illustrate the necessity of culturing naïve TCR transgenic CD4(+) T cells at a physiological frequency if one is to more accurately recapitulate the in vivo activation of naïve CD4(+) T cells.


Dosimetric impact of interfraction catheter movement and organ motion on MRI/CT guided HDR interstitial brachytherapy for gynecologic cancer.
To determine the dosimetric impact of catheter movement for MRI/CT image guided high dose rate (HDR) interstitial brachytherapy (ISBT) for gynecologic cancers. Ten patients were treated with HDR ISBT. The CTV and organs at risk were contoured using a postimplant MRI and CT. 5 fractions were delivered twice daily on 3 consecutive days. The first fraction was delivered on day 1 (d1), fraction 2-3 on d2 and fraction 4-5 on d3. MRI/CT was acquired prior to the second and fourth fractions. Four scenarios were modeled. (1) The d1 plan was applied to the d2 and d3 CT, using the updated catheter positions. (2) Replanning was performed for d2 and d3. (3) We applied the dwell positions/times from the d2 replan over the d3 CT and compared with a d3 CT replan. (4) Based on daily MRI, target volumes were recontoured and replanned. Dosimetry was analyzed for each plan and compared to the d1 dose distribution. (1) When using the d1 plan on the d2 and d3 CT with the updated catheter positions, the mean CTV D90 was reduced from 93.4% on d1 to 89.3% (p=0.08) on d2 and to 87.7% (p=0.005) on d3. (2) Replanning on d2 and d3 compensated for catheter movement, mean CTV D90 of 95.4% on d2 and 94.6% (p=0.36) on d3. (3) When compared to the replan of d2 applied on the d3 CT vs the d3 replan, there was no significant difference in coverage, mean CTV D90 of 90.9% (p=0.09). (4) Reoptimization based on daily MRI, significantly improved the CTV coverage for each day. The mean D2cc for the rectum was significantly higher with model 1 vs model 3 59.1±4.7 vs 60.9±4.8 (p=0.04) Gy EQD2. There were no significant differences in D2cc of bladder and sigmoid between models. Interfraction dosimetric changes significantly decreased the CTV coverage of the third day. Rather than replanning on each day, replanning on the day 2 CT before the second or third fraction would give an optimal solution that would compensate for interfraction catheter displacement.


Impact of prior abdominal surgery on short-term outcomes following laparoscopic colorectal cancer surgery: a propensity score-matched analysis.
Whether laparoscopic surgery after prior abdominal surgery (PAS) is safe and feasible for colorectal cancer (CRC) remains controversial. The present study aimed to evaluate the impact of PAS on short-term outcomes following laparoscopic CRC surgery. We performed retrospective analysis used propensity score-matched analysis to reduce the possibility of selection bias. Participants comprised 1284 consecutive patients who underwent elective laparoscopic CRC surgery between 2010 and 2020. Patients were divided into two groups according to PAS. Patients with PAS were then matched to patients without these conditions. Short-term outcomes were evaluated between groups in the overall cohort and matched cohort, and risk factors for conversion to laparotomy and severe postoperative complications were analyzed. After propensity score matching, we enrolled 762 patients (n = 381 in each group). Before matching, significant group-dependent differences were observed in sex, age, primary tumor site, pathological (p) T stage, and type of procedure. No significant difference was found between groups in terms of rate of conversion to laparotomy, estimated blood loss, rate of extended resection, length of postoperative stay, and postoperative complications. After matching, estimated operative time was significantly longer in the PAS group (p = 0.01). Significant differences were found between groups in terms of reason for conversion to laparotomy. Multivariate analyses identified significant risk factors for conversion to laparotomy as pT stage ≥ 3 (odds ratio [OR] 2.36; 95% confidence interval [CI] 1.05-5.26) and body mass index ≥ 25 kg/m2 (OR 3.56; 95% CI 1.07-11.7). Multivariate analyses identified rectum in the primary tumor site as the only significant risk factor for severe postoperative complications (OR 2.37; 95% CI 1.08-5.20). Laparoscopic CRC surgery after PAS showed acceptable short-term outcomes compared to Non-PAS. The laparoscopic approach appears safe and feasible for CRC regardless of whether the patient has a history of PAS.


The clinical value and risks of lung biopsy in children with congenital heart disease.
A retrospective review was made of 59 open lung biopsy specimens taken between 1984 and 1988 from children with congenital heart disease who were at risk for pulmonary vascular disease. Thirty-seven patients (ranging in age from 3.5 months to 23 years; median age, 14 months) had a primary left-to-right shunt (group A) and 22 patients (ages 1 to 15 years) had palliated cyanotic heart disease (group B). Forty-five of the lung biopsy specimens were requested as frozen sections. In both groups lung biopsy specimens were graded by the Heath-Edwards classification and correlated against preoperative hemodynamic data and outcome. In group A patients, carefully measured pulmonary vascular resistance and pulmonary/systemic vascular resistance ratio were reliable indicators of the structural state of the pulmonary vascular bed, obviating the need for routine lung biopsy. Pulmonary/systemic vascular resistance ratios greater than 0.45 accurately predicted all patients with irreversible pulmonary vascular disease, and pulmonary vascular resistance greater than 7 units.m2 accurately predicted all but one case of disease. Reversibility of pulmonary vascular changes is not synonymous with immediate postoperative survival: Fatal postoperative pulmonary hypertensive crises occurred in the presence of reversible pulmonary disease. Of those considered for the Fontan procedure, a mean pulmonary artery pressure less than 30 mm Hg and pulmonary vascular resistance less than 3 units.m2 correlated with Heath-Edwards grade I or normal lung biopsy results. In 36% of group B patients, reliable assessment of pulmonary vascular resistance could not be made, indicating a possible need for open lung biopsy procedures. When lung biopsy procedures were used as an isolated procedure, they were more dangerous (20% mortality, 13% morbidity) than previously reported. Intraoperative frozen sections are not adequate to accurately assess pulmonary vascular changes (9% error); serial paraffin sections are required.


Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review.
Allergic and non-allergic rhinorrhea in the forms of acute or chronic rhinosinusitis can mean a watery nasal discharge that is disabling. Primary objective was to review the evidence supporting the hypothesis that rhinorrhea is due to increased chloride secretion through the CFTR chloride channel. The structure of the evidence review followed the EQUATOR Reporting Guidelines. Databases searched from inception to February 2022 included Pubmed, EMBASE and the Cochrane library using keywords "Rhinorrhea", "chloride", "chloride channel", "CFTR" and "randomized controlled trial". Quality assessment was according to the Oxford Centre for Evidence-based Medicine. 49 articles were included. They included randomized controlled trials out of which subsets of data with the outcome of rhinorrhea on 6038 participants were analysed and in vitro and animal studies. The review revealed that drugs, which activate CFTR are associated with rhinorrhea. Viruses, which cause rhinorrhea like rhinovirus were found to activate CFTR. The chloride concentration in nasal fluid showed an increase in patients with viral upper respiratory tract infection. Increased hydrostatic tissue pressure, which is an activator of CFTR was observed in allergic upper airway inflammation. In this condition exhaled breath condensate chlorine concentration was found to be significantly increased. Drugs, which can reduce CFTR function including steroids, anti-histamines, sympathomimetic and anticholinergic drugs reduced rhinorrhea in randomized controlled trials. A model of CFTR activation-mediated rhinorrhea explains the effectiveness of anticholinergic, sympathomimetic, anti-histamine and steroid drugs in reducing rhinorrhea and opens up avenues for further improvement of treatment by already known specific CFTR inhibitors.


Maximum Phonation Time and Body Mass Index in Nondysphonic Eutrophic Children.
Literature presents controversial maximum phonation time values in children. Verify and correlate the maximum phonation time of vowels /a, i, u/ and the body mass index of children. Evaluation of 484 children, eutrophic and without dysphonia, aged from 4:00 to 7:11 years. questionnaire, audiometric screening, auditory-perceptual evaluation of voice, and assessment of the body mass index. measurement of the maximum phonation time of /a, i, u/. Descriptive statistics, t test, and multiple regression at 5% significance. /a:/ = 3.77 seconds at age 4:00 years, 5 seconds at 5:00, 5.85 seconds at 6:00, and 7.5 seconds at 7:00 for boys, and 3.89 seconds, 4.89 seconds, 5.61 seconds, and 6.61 seconds for girls, respectively; /i:/ = 3.49 seconds at age 4:00 years, 4.96 seconds at 5:00, 5.72 seconds at 6:00, and 6.88 seconds at 7:00 for boys, and 3.49 seconds, 4.73 seconds, 5.41 seconds, and 6.63 seconds for girls, respectively; /u:/ = 3.64 seconds at age 4:00 years, 4.85 seconds at 5:00, 5.76 seconds at 6:00, and 7.08 seconds at 7:00 for boys, and 3.54 seconds, 4.73 seconds, 5.64 seconds, and 6.47 seconds for girls, respectively. There were no significant differences between genders, except for /a:/ at age 7:00 years. The correlations were not significant. Maximum phonation time of /a, i, u/ increased with age and its value in seconds was approximately equal to the age in years. At the age 7:00 years, /a:/ from boys was longer. The body mass index did not show influence on the maximum phonation times.


Effect of testosterone supplementation on leptin release in rats after castration and/or unilateral surrenalectomy.
The objective of this study was to examine the effect of testosterone supplementation on leptin release in rats which underwent castration and unilateral surrenalectomy. The study was conducted on 80 adult male Wistar albino rats. Animals were divided into eight groups, with ten animals in each group. Group 1 was the Control group, Group 2 the Testosterone group, Group 3 the Castration group, Group 4 the Surrenalectomy group, Group 5 the Castration and Surrenalectomy group, Group 6 the Castration and Testosterone group, Group 7 the Surrenalectomy and Testosterone group, and Group 8 the Castration, Surrenalectomy and Testosterone group. The animals in Groups 2, 6, 7 and 8 were administered 5 mg/kg/day intramuscular testosterone propionate for four weeks. Blood samples were collected for analyses of leptin, LH, FSH and free and total testosterone levels in plasma. Groups 3 and 5 had the highest leptin and LH levels of all the groups (p < 0.01). Leptin and LH levels in Groups 1 and 4 were higher than those in Groups 2, 6, 7 and 8 (p < 0.01). A comparison of groups with regard to plasma FSH levels showed that the concerned parameter was significantly higher in Groups 3 and 5 than in the other groups (p < 0.01). FSH levels in Groups 1 and 4 were lower than those in all other groups (p < 0.01). The highest testosterone levels were obtained in Groups 2, 6, 7 and 8 (p < 0.01). Testosterone levels in Groups 1 and 4 were higher than those in Groups 3 and 5 (p < 0.01). This study demonstrates that unilateral surrenalectomy in rats does not have a significant effect on leptin release, while plasma LH levels, rather than testosterone, may be more effective on plasma leptin.


Modulation of intracellular formation of reactive oxygen intermediates in peritoneal macrophages and microglia/brain macrophages by propentofylline.
Ischemia-induced nerve cell death can partly be prevented by propentofylline, a pharmacon structurally related to xanthine derivates that interacts with the neuromodulatory function of endogenous adenosine. To evaluate a possible mechanism of neuroprotection by propentofylline, we studied its effect on the cellular production of reactive oxygen intermediates in microglial cells, which under pathological conditions can differentiate into brain macrophages, in comparison to peritoneal macrophages. Using a flow cytometric assay, we determined the intracellular formation of reactive oxygen intermediates by measuring the oxidation of the membrane-permeable and nonfluorescent dihydrorhodamine 123 to the cationic and intracellularly trapped, green fluorescent rhodamine 123 in single viable cells. Propentofylline at the therapeutic concentration of 50 microM completely inhibited the Ca(2+)-dependent Con A-induced increase in the production of reactive oxygen intermediates in peritoneal macrophages. In isolated and cultured microglial cells, which have a high spontaneous respiratory burst activity, the spontaneous production of reactive oxygen intermediates was reduced by approximately 30%. A phorbol 12-myristate 13-acetate-induced rise in the respiratory burst activity could not be inhibited by propentofylline in either cell type. An increased generation of reactive oxygen intermediates is thought to contribute to nerve cell death after brain ischemia, edema, and neurodegenerative diseases like Alzheimer's disease. These pathological conditions are all accompanied by an activation of microglial cells. We therefore suggest that the neuroprotective properties of propentofylline might in part be due to a modulation of the microglial production of potentially harmful reactive oxygen intermediates.


Application of e-PTFE Frontalis Suspension in the Treatment of Congenital Ptosis in Children.
Analysis of the value of expanded polytetrafluoroethylene (e-PTFE) frontalis suspension applied to children with congenital ptosis. Eighty clinical cases of children with congenital ptosis from October 2019 to October 2021 were randomly selected from our hospital. All children were divided into the observation group (n = 44) treated with e-PTFE frontalis suspension and the control group (n = 36) treated with frontalis flap suspension according to the treatment procedure. Comparison of eyelid condition [palpebral fissure height, margin reflex distance (MRD), eyelid closure time], ocular surface status [corneal fluorescein staining (CFS) score, tear film breakup time (TBUT), surgical eye lacrimal river height (LRH), sehirmer test I (STI)], frontal muscle strength of affected side, cosmetic results and complications in both groups at 1, 6 and 12 months postoperative follow-up. At 1, 6 and 12 months after surgery, there was no significant difference in terms of palpebral fissure height and MRD between both groups (p > 0.05); After surgery, the eyelid closure time was shorter in the observation group than in the control group (p < 0.05). At 1, 6 and 12 months after surgery, the CFS scores were lower in the observation group than in the control group (p < 0.05); At 6 and 12 months after surgery, the TBUT was longer and the surgical eye LRH was higher in the observation group than in the control group (p < 0.05); At 1, 6, and 12 months after surgery, there was no significant difference in STI between both groups (p < 0.05). At 1, 6 and 12 months after surgery, the frontal muscle strength of affected side was higher in the observation group than in the control group (p < 0.05). At 1, 6, and 12 months after surgery, there was no significant difference in cosmetic results between both groups (p > 0.05). The overall complication rate in the observation group (6.82%) was lower than that in the control group (25.00%) (p < 0.05). The surgical and cosmetic results of e-PTFE frontalis suspension and frontalis flap suspension applied to congenital ptosis are comparable, but the former has the advantage of faster postoperative recovery, better ocular surface status, less frontali muscle strength damage and fewer complications.


Polydopamine functionalized graphene sheets decorated with magnetic metal oxide nanoparticles as efficient nanozyme for the detection and degradation of harmful triazine pesticides.
A facile and an eco-friendly reduction and functionalization of reduced graphene oxide (rGO) sheets is carried out using dopamine and decorated with magnetic Fe3O4 nanoparticles with an average size of 12 nm by a simple co-precipitation method which is established as an artificial nanozyme. Here, functionalization of graphene using dopamine has introduced several advantages and insights into this study. The Fe3O4 nanoparticles decorated functionalized rGO sheets (FDGs) nanozymes are characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, atomic force microscopy (AFM), thermogravimetric (TGA) and vibrating sample magnetometer (VSM) analysis. FDGs nanozymes exhibits dual characteristics towards detection and degradation of harmful simazine pesticide. The hydrogen bonding interactions between pesticide molecules and 3,3',5,5'-tetramethylbenzidine (TMB) causes inhibition of the catalytic activity of the FDGs towards oxidation of TMB molecule. Based on that, the presence of simazine pesticide in an aqueous medium can be easily determined and a certain value (2.24 μM) of detection limit was achieved. The photocatalytic degradation of simazine is also executed and excellent photocatalytic activity was observed under irradiation of direct natural sunlight. The FDGs nanozyme is also reusable up to several times with insignificant loss in its catalytic activity towards simazine degradation.


Comparative investigations of the effects of the neodymium:YAG laser at 1.06 microns and 1.32 microns on tissue.
The beneficial deep homogeneous coagulation of neodymium (Nd):YAG laser radiation at 1.06 microns owing to low absorption and high scattering in tissue has been documented widely. For another Nd:YAG laser wavelength at 1.32 microns the absorption coefficient of water and saline is approximately ten times higher than at 1.06 microns. This results in more efficient energy conversion into heat in tissue at 1.32 microns. The extinction coefficient in blood at 1.32 microns is only one-third of that at 1.06 microns. We would expect this to result in less heat dissipation by blood and deeper penetration in tissue at 1.32 microns. Nevertheless, at this wavelength scattering also contributes to an effective, uniform distribution of the laser light in the tissue. Animal experiments have been done to examine the effect of wavelength, irradiation time, and beam geometry on tissue damage and to assess its possible clinical uses. The results imply that the 1.32 microns wavelength will produce further indications for the use of the Nd:YAG laser in surgery.


Association between socioeconomic factors and urinary sodium-to-potassium ratio: the Nagahama Study.
High sodium intake is a simple modifiable risk factor for hypertension. Although not confirmed, lower socioeconomic status may be a factor that increases sodium intake. We aimed to clarify the association between socioeconomic status and urinary sodium-to-potassium ratio by cross-sectional and longitudinal analyses. The study included 9410 community residents. Spot urine sodium-to-potassium ratios were measured twice with a 5-year interval. Socioeconomic status was investigated using a self-administered questionnaire. Cross-sectional analysis revealed that educational attainment was inversely associated with urinary sodium-to-potassium ratio (years of education ≤ 9: 3.0 ± 1.8, ≤ 12: 2.9 ± 1.6, ≥ 13: 2.8 ± 1.6; P < 0.001), whereas no significant association was observed with household income. Men, particularly individuals living alone, exhibited markedly high sodium-to-potassium ratios (3.6 ± 2.3). Although frequent intake of vegetables, fruits, and dairy products was also inversely associated with the ratio, the associations with educational attainment ( ≤ 9: reference, ≤ 12: β = -0.032, P = 0.026, ≥ 13: β = -0.059, P < 0.001), marital status (β = -0.040, P < 0.001), and sex*marital status interaction (β = 0.054, P = 0.001) were independent of these covariates. Educational attainment was also inversely associated with differences in the urinary sodium-to-potassium ratio during the follow-up period (odds ratio, 0.70; P < 0.001). Lower educational attainment was an independent determinant for urinary sodium-to-potassium ratio. Health literacy education, particularly in men living alone, may be a factor for reducing salt intake even in high-income countries where equal educational opportunity is assured.


A new nucleosomic-based model to identify and diagnose SSc-ILD.
Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the evolution of the lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. Nucleosomes are stable DNA/protein complexes that are shed into the blood stream making them ideal candidates for biomarkers. We studied circulating cell-free nucleosomes (cf-nucleosomes) in SSc patients, 31 with ILD (SSc-ILD) and 67 without ILD. We analyzed plasma levels for cf-nucleosomes and investigated whether global circulating nucleosome levels in association with or without other biomarkers of interest for systemic sclerosis or lung fibrosis (e.g., serum growth factors: IGFBP-1 and the MMP enzyme: MMP-9), could be suitable potential biomarkers for the correct identification of SSc-ILD disease. We found that H3.1 nucleosome levels were significantly higher in patients with SSc-ILD compared SSc patients without ILD (p < 0.05) and levels of MMP-9 were significantly increased in patients with SSc-ILD compared to SSc patients without ILD (p < 0.05). Conversely, IGFBP-1 was significantly reduced in patients with SSc-ILD compared to SSc without ILD (p < 0.001). The combination of cf-nucleosomes H3.1 coupled to MMP-9 and IGFBP-1 increased the sensitivity for the differential detection of SSc-ILD. High levels of accuracy were reached with this combined model: its performances are strong with 68.4% of positive predictive value and 77.2% of negative predictive value for 90% of specificity. With our model, we identified a significant negative correlation with FVC % pred (r = -0.22) and TLC % pred (r = -0.31). The value of our model at T1 (baseline) has a predictive power over the Rodnan score at T2 (after 6-18 months), showed by a significant linear regression with R2 = 19% (p = 0.013). We identified in the sole group of SSc-ILD patients a significant linear regression with a R2 = 54.4% with the variation of DLCO between T1 and T2 (p < 0.05). In our study, we identified a new blood-based model with nucleosomic biomarker in order to diagnose SSc-ILD in a SSc cohort. This model is correlated with TLC and FVC at baseline and predictive of the skin evolution and the DLCO. Further longitudinal exploration studies should be performed in order to evaluate the potential of such diagnostic and predictive model.


Foot shock stress decreases chloride efflux from rat brain synaptoneurosomes.
Foot shock stress delivered continuously for 20 min decreased the 36Cl- efflux from cerebral cortex synaptoneurosomes of handling-habituated (unstressed) rats but failed to have the same effect on the synaptoneurosomes of naive (stressed) rats. The presence of pentobarbital (500 microM), GABA (100 microM) or muscimol (50 microM in the dilution buffer reversed the stress-induced decrease of 36Cl- efflux from synaptoneurosomes of unstressed rats. Moreover, these drugs also stimulated 36Cl- efflux from cortical synaptoneurosomes of naive stressed rats. The results indicate that stress decreases the function of Cl- channels coupled to the GABA/barbiturate receptor complex.


Corrigendum: Comparison of surgical outcome between conventional open thyroidectomy and endoscopic thyroidectomy through axillo-breast approach.
[This corrects the article on p. 286 in vol. 32.].


Opportunities for human resources for health and rehabilitation: a response to Jesus et al.
We welcome Jesus et al.'s paper, which makes an important contribution to the under-researched area of the physical rehabilitation workforce. The authors present recommendations to "advance a policy and research agenda for ensuring that an adequate rehabilitation workforce can meet the current and future rehabilitation health needs" (p. 1). We argue that their perspective could however be strengthened by adopting a stronger global perspective, including consideration of the needs of low-resource settings. In particular, we highlight the integral role of more effective sector and inter-sectoral governance, the opportunity to support the development of community-based rehabilitation (CBR), the lessons that can be learnt from human resources for health (HRH) research and practice more generally, and the recent developments in the global provision of assistive technologies. Each of these issues has important implications and contributions to make to advance the policy and research agenda for the global rehabilitation workforce.


Left bundle branch area pacing for heart failure patients requiring cardiac resynchronization therapy: A meta-analysis.
Left bundle branch area pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure with reduced ejection fraction (HFrEF). We conduted this meta-analysis and systemic review to review current data comparing BVP and LBBP in patients with HFrEF and indications for CRT. We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel-Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity. Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49-14.87, I2 = 95%, p < .01, minutes) as well as a shorter procedural time (MD 33.68, 95% CI: 17.80-49.55, I2 = 73%, p < .01, minutes) during the implantation of LBBP CRT compared to conventional BVP CRT. LBBP was shown to have a greater reduction in QRS duration (MD 25.13, 95% CI: 20.06-30.20, I2 = 51%, p < .01, milliseconds), a greater left ventricular ejection fraction improvement (MD: 5.80, 95% CI: 4.81-6.78, I2 = 0%, p < .01, percentage), and a greater left ventricular end-diastolic diameter reduction (MD: 2.11, 95% CI: 0.12-4.10, I2 = 18%, p = .04, millimeter). There was a greater improvement in New York Heart Association function class with LBBP (MD: 0.37, 95% CI: 0.05-0.68, I2 = 61%, p = .02). LBBP was also associated with a lower risk of a composite of heart failure hospitalizations (HFH) and all-cause mortality (RR: 0.48, 95% CI: 0.25-0.90, I2 = 0%, p = .02) driven by reduced HFH (RR: 0.39, 95% CI: 0.19-0.82, I2 = 0%, p = .01). However, all-cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR: 0.98, 95% CI: 0.21-4.68, I2 = 0%, p = .87). This meta-analysis of primarily nonrandomized studies suggests that LBBP is associated with a greater improvement in left ventricular systolic function and a lower rate of HFH compared to BVP. There was uniformity of these findings in all of the included studies. However, it would be premature to conclude based solely on the current meta-analysis alone, given the limitations stated. Dedicated, well-designed, randomized controlled trials and observational studies are needed to elucidate better the comparative long-term efficacy and safety of LBBP CRT versus BIV CRT.


Hypomethylation of CD30 CpG islands with aberrant JunB expression drives CD30 induction in Hodgkin lymphoma and anaplastic large cell lymphoma.
High expression of CD30 and JunB is the hallmark of malignant cells in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Ligand-independent signaling by CD30 induces JunB, which activates the CD30 promoter, stabilizing CD30 expression and supporting the survival of Hodgkin-Reed-Sternberg (H-RS) and ALCL cells. Here we show for the first time CpG islands encompassing 60 CpG dinucleotides, located in the core promoter, exon 1 and intron 1 of CD30 gene. Analysis of the methylation status of CD30 CpG islands in H-RS, ALCL and unrelated cell lines reveals an inverse relationship between the extent of CD30 CpG methylation and CD30 expression. CD30 CpG islands of H-RS and ALCL cell lines are rarely methylated. Methylation of the CD30 promoter decreases CD30 induction and JunB action on the demethylated CD30 promoter enhances CD30 induction. CD30 and JunB are strongly expressed in H-RS and ALCL cells, whereas they are not expressed in nonmalignant lymphocytes in which CD30 CpG islands are rarely methylated. We conclude that constitutive action of aberrantly expressed JunB on hypomethylated CD30 CpG islands of lymphocytes triggers CD30 induction and initiates activation of the JunB-CD30-JunB loop, essential to the pathogenesis of HL and ALCL.


Mitochondrial and nuclear DNA analysis revealed a cryptic species and genetic introgression in Littorina sitkana (Mollusca, Gastropoda).
We investigated mitochondrial and nuclear DNA genotypes in nominal Littorina sitkana samples from 2 localities in Eastern Hokkaido, northern Japan. Our results indicated the existence of cryptic species. In the analysis of partial mitochondrial Cytchrome b gene sequences, haplotypes of L. sitkana samples were monophyletic in a phylogenetic tree with orthologous sequences from other Littorina species, but were apparently separated in 2 clades. One included typical L. sitkana (CBa clade) samples, which formed a clade with an allopatric species, L. horikawai. The other, CBb, was independent from CBa and L. horikawai. Haplotypes of the mitochondrial 16S rRNA gene also separated into 2 clades. We additionally examined intron sequence of the heat shock cognate 70 (HSC70) nuclear gene and identified 17 haplotypes. These were also separated into 2 clades, HSCa and HSCb. Among the examined Hokkaido samples, 60% of individuals were heterozygotes. However, each heterozygote consisted of haplotypes from the same clade, HSCa or HSCb, and no admixture of HSCa and HSCb haplotypes was observed. These results indicate reproductive isolation between the 2 clades. Among the genotyped Hokkaido samples, 93% of individuals had CBa + HSCa or CBb + HSCb genotypes, and 7% had CBb + HSCa genotypes. The discrepancy between the mtDNA and nuclear DNA haplotypes in a few individuals may have been caused by genetic introgression due to past hybridization.


Microplastic pollution and its relationship with the bacterial community in coastal sediments near Guangdong Province, South China.
The ecological stress caused by microplastic (MP) pollution in marine environments has attracted global attention. However, few studies have investigated the relationship between MP pollution and the microbial community in natural sediments. This study was the first to systematically characterize MP pollution (i.e., its abundance, shape, size and color) and investigate its relationship with the bacterial community in coastal sediments from Guangdong, South China, by microscopic observation and Illumina sequencing. The results of this study indicated that the abundance of microplastics (MPs), which was 344 ± 24 items/kg in 33 coastal sediments from 11 sites from South China, represented a relatively high level of MP pollution. MPs with sizes of <0.5 m, 0.5-1.0 mm and 1-2 mm accounted for the highest proportion (75%) in the sediments. Fiber/film (82%) and white/blue (91%) were the dominant shapes and colors, respectively, in all MP samples. Furthermore, the abundances, three shapes (fiber, film and fragment), three sizes (<0.5 mm, 0.5-1.0 mm and 1-2 mm), and two colors (blue and white) of MPs displayed positive correlations with some potential pathogens, including Vibrio, Pseudomonas, Bacillus and Streptococcus, but exhibited negative correlations with an environmentally friendly bacterial genus, Sphingomonas (which degrades various hazardous organic compounds), indicating that MPs might increase the potential ecological risks of coastal sediments. Our results may help to elucidate the relationship between MP pollution and the microbial community in coastal sediments.


Correlates of quality of life in South Korean patients undergoing hematopoietic stem cell transplantation based on the symptom management model.
While hematopoietic stem cell transplantation (HSCT) has led to higher survival rates, the number of patients experiencing adverse reactions is also increasing. Based on the symptom management model, we aimed to analyze the relationships between symptom experience, symptom management strategies, self-management behavior, and quality of life among patients undergoing HSCT in South Korea and to identify the factors affecting their quality of life. The data of 67 conveniently sampled patients undergoing HSCT at a university-affiliated hospital, for the period from March 23 to June 7, 2016, were collected using a self-reported structured questionnaire. Data were analyzed using Pearson's correlations and multiple regression analysis. Quality of life showed a significant negative correlation with symptom experience and significant positive correlations with symptom management strategies. Factors influencing quality of life included symptom distress, symptom management strategies, and self-management behavior; these explained 39.4% of the variance. To improve quality of life in patients undergoing HSCT, the efficient management of multiple co-existing symptoms is important. There is a need for tailored nursing interventions based on a patient-focused and person-centered approach for patients undergoing HSCT.


Successful Surgical Resection of Spinal Artery Aneurysms: Report of 3 Cases.
Spinal artery aneurysms (SAAs) are extremely rare lesions that can occur in isolation or associated with vascular malformations. Herein, we present 3 unusual cases of SAAs and discuss imaging, diagnosis, and surgical management strategies. The first patient was a 57-year-old woman who presented with sudden onset of severe headache. Spinal angiography demonstrated an isolated anterior spinal artery (ASA) aneurysm at the level of the craniocervical junction. The second patient was a 27-year-old woman who presented with progressive bilateral pain of her lower limbs. The result of spinal angiography was consistent with an aneurysm at the level of L1. The third patient was a 26-year-old man who presented with bilateral weakness and numbness of the lower limbs. Spinal angiography revealed a conus medullaris aneurysm associated with an arteriovenous malformation (AVM). All these lesions were successfully managed with clipping or resection, and good outcomes were achieved. Spinal artery aneurysms are rare lesions. Herein, we report 3 such cases and emphasize the importance of surgical management.


Lions, tigers, and bears, oh sh!t: Semantics versus tabooness in speech production.
While both semantic and highly emotional (i.e., taboo) words can interfere with speech production, different theoretical mechanisms have been proposed to explain why interference occurs. Two experiments investigated these theoretical approaches by comparing the magnitude of these two types of interference and the stages at which they occur during picture naming. Participants named target pictures superimposed with semantic, taboo, or unrelated distractor words that were presented at three different stimulus-onset asynchronies (SOA): -150 ms, 0 ms, or +150 ms. In addition, the duration of distractor presentation was manipulated across experiments, with distractors appearing for the duration of the picture (Experiment 1) or for 350 ms (Experiment 2). Taboo distractors interfered more than semantic distractors, i.e., slowed target naming times, at all SOAs. While distractor duration had no effect on type of interference at -150 or 0 SOAs, briefly presented distractors eliminated semantic interference but not taboo interference at +150 SOA. Discussion focuses on how existing speech production theories can explain interference from emotional distractors and the unique role that attention may play in taboo interference.


Governance and functionality of community water schemes in rural Ethiopia.
A key challenge for achieving universal water access in Sub-Saharan Africa is poor sustainability of water schemes. Previous studies have posited factors that may lead to failed schemes; however, empirical data are lacking. We conducted direct observations of water sources and interviewed water committee members about governance in two regions of Ethiopia. Based on direct observation at each water point, and harmonizing previous research in the sector, we developed an ordinal measure of functionality. Among functional systems, linear regression models were used to assess changes in score or level of functionality against governance characteristics. Of 89 water schemes over 5 years old, 82 had sufficient data to receive a score. Higher functionality scores were associated with having good records, meeting regularly, financial audits, higher monthly fees, a paid caretaker and water committees with capacity to perform minor repairs. Our continuous measure of functionality was simple to derive, objective and may be widely applicable for further studies assessing key indicators of sustainability.


Transmembrane electrical characteristics of cultured human skeletal muscle cells.
Skeletal muscle explants from normal subjects were established from biopsy material on collagen. Cellular outgrowth appeared within 3-4 days, and fusion of myoblasts was observed in 5-10 days. Multinucleated myotubes were impaled under high optical magnification, at 37 degrees C, with conventional glass microelectrodes. The mean resting potential was -44.4 mV +/- 2.4 (n = 399); -33 +/- 2.3 mV at 9 days (n = 10) vs -48 +/- 2.5 mV (n = 15) at 27 days. The average input resistance (Rin) was 9.7 M omega (n = 83). Action potentials could be elicited by electrical stimulation and had a mean amplitude of 55.9 +/- 2.1 mV with a mean maximum rate of rise (Vmax) of 72.1 +/- 7.5 V/s. The mean overshoot was 13.9 +/- 2.3 mV, and the action potential duration determined at 50% of repolarization (APD50) was 8.0 msec (n = 7). The resting membrane potential showed a depolarization of 23 mV/decade for extracellular potassium ion concentration ([K]o) between 4.5-100 mM. Thus, we have established the normal resting potential and maximum rate of rise of the action potential for human myotubes in culture. We have shown that the values for these are less than those previously reported in cultured avian and rodent cells. In addition, we have shown that the response in our system of the resting potential to change in extracellular potassium concentration is blunted compared to studies using isolated muscle, suggesting an increase in ratio of sodium to potassium permeability. Cultured human muscle cells depolarized in the presence of ouabain.


Preterm birth and fetal growth restriction in HIV-infected Brazilian pregnant women.
Maternal HIV infection and related co-morbidities may have two outstanding consequences to fetal health: mother-to-child transmission (MTCT) and adverse perinatal outcomes. After Brazilian success in reducing MTCT, the attention must now be diverted to the potentially increased risk for preterm birth (PTB) and intrauterine fetal growth restriction (IUGR). To determine the prevalence of PTB and IUGR in low income, antiretroviral users, publicly assisted, HIV-infected women and to verify its relation to the HIV infection stage. Out of 250 deliveries from HIV-infected mothers that delivered at a tertiary public university hospital in the city of Vitória, state of Espírito Santo, Southeastern Brazil, from November 2001 to May 2012, 74 single pregnancies were selected for study, with ultrasound validated gestational age (GA) and data on birth dimensions: fetal weight (FW), birth length (BL), head and abdominal circumferences (HC, AC). The data were extracted from clinical and pathological records, and the outcomes summarized as proportions of preterm birth (PTB, < 37 weeks), low birth weight (LBW, < 2500 g) and small (SGA), adequate (AGA) and large (LGA) for GA, defined as having a value below, between or beyond the ± 1.28 z/GA score, the usual clinical cut-off to demarcate the 10th and 90th percentiles. PTB was observed in 17.5%, LBW in 20.2% and SGA FW, BL, HC and AC in 16.2%, 19.1%, 13.8%, and 17.4% respectively. The proportions in HIV-only and AIDS cases were: PTB: 5.9 versus 27.5%, LBW: 14.7% versus 25.0%, SGA BW: 17.6% versus 15.0%, BL: 6.0% versus 30.0%, HC: 9.0% versus 17.9%, and AC: 13.3% versus 21.2%; only SGA BL attained a significant difference. Out of 15 cases of LBW, eight (53.3%) were preterm only, four (26.7%) were SGA only, and three (20.0%) were both PTB and SGA cases. A concomitant presence of, at least, two SGA dimensions in the same fetus was frequent. The proportions of preterm birth and low birth weight were higher than the local and Brazilian prevalence and a trend was observed for higher proportions of SGA fetal dimensions than the expected population distribution in this small casuistry of newborn from the HIV-infected, low income, antiretroviral users, and publicly assisted pregnant women. A trend for higher prevalence of PTB, LBW and SGA fetal dimensions was also observed in infants born to mothers with AIDS compared to HIV-infected mothers without AIDS.


Multinuclear magnetic resonance analysis of 2-(trifluoromethyl)-2-oxazoline.
(1)H, (19)F, (13)C, (15)N, and (17)O NMR chemical shifts and (1)H-(1)H, (1)H-(19)F, (1)H-(13)C, (19)F-(13)C, and (19)F-(15)N coupling constants are reported for 2-(trifluoromethyl)-2-oxazoline.


Perforating Barrett's ulcer resulting in a life-threatening esophagobronchial fistula.
Perforating benign ulcer is a very rare complication of Barrett's esophagus. This report presents the management of a patient with a Barrett's ulcer that penetrated into the left mainstem bronchus resulting in a life-threatening bronchial esophageal fistula. This rare complication was successfully managed by using a staged surgical approach, which combined the principles used for treating benign esophagorespiratory fistulas and perforating Barrett's ulcers.


Impact of chitosan administration on titanium dioxide nanoparticles induced testicular dysfunction.
The potential reproductive toxic effects of oral TiO2 NPs in adult male rats as well as the possible alleviation of chitosan administration was investigated. Animals were allocated to four groups; the first group received deionized water and was assigned as a control group. In the second group, rats received chitosan at a dose of 5 mg/kg BW/day. The third group was designed for administration of TiO2 NPs at a dose of 150 mg/kg BW/day (1/80 LD50). Rats in the fourth group received both TiO2 NPs and chitosan. After 14 days, TiO2 NPs induced testicular lipid peroxidation as well as oxidative stress. Nano-titanium significantly upregulated genes that encode apoptosis and inflammation in testicular tissue. Moreover, it induced histological alteration in the testicular structure with impairment in spermatogenesis via reduction of PCNA immune-staining. Chitosan administration significantly improved the activities of testicular GPx, SOD, and CAT enzymes. In addition, it significantly down-regulated the relative expressions of pro-apoptotic and pro-inflammatory testicular genes. Chitosan was able to improve the testicular architecture as well as spermatogenesis. The current study revealed the capability of chitosan to ameliorate nano-titanium induced testicular toxicity. Thus, attention should be given to the extensive consumption of nano-titanium particles.


Transepithelial permeability of myricitrin and its degradation by simulated digestion in human intestinal Caco-2 cell monolayer.
Myricitrin permeated the human intestinal Caco-2 cell monolayer via the paracellular pathway in a time- and concentration-dependent manner. Myricitrin was not conjugated by Caco-2 cells. Myricitrin was degraded by simulated intestinal digestion, but permeability did not change significantly.


Changes in behavior in free-ranging Lemur catta following release in a natural habitat.
The adjustment of captive-reared and developmentally deprived ringtailed lemurs (Lemur catta) to supported release on St. Catherine's Island, Georgia, was studied over 7 years to examine if these animals developed behavior comparable to wild populations. Initial changes after release included decreased obesity and increased agility as well as foraging for appropriate novel plants. Ranging, daily behavior cycles, and vocalizations developed more slowly over 1-3 years, but eventually the behavior resembled that of wild groups. Group composition and social structure changed through conflict to resemble wild and captive troops in social organization, including the emergence of matrilineal dominance and male emigration. Since behavior eventually resembled that seen in the wild, some resilience of species-typical wild behavior in captivity is supported.


Starnes procedure in a neonate with pulmonary atresia and intact ventricular septum.
We describe the case of 7-day-old neonate with pulmonary atresia, intact ventricular septum, and severe tricuspid valve (TV) dysplasia who underwent a Starnes right ventricular exclusion procedure (RVEP). The patient had severe tricuspid stenosis and regurgitation and right ventricular dysfunction after perforation and balloon dilation of the pulmonary valve.


The ubiquitin-proteasome pathway regulates claudin 5 degradation.
The tight junctions (TJs) form continuous intracellular contacts, which help create selective barriers in epithelial and endothelial cell layers. The structures created by the TJs are very dynamic and can be rapidly remodeled in response to physiological and pathological signals. Claudin 5 is a membranal TJ protein which plays a critical role in determining the permeability of endothelial barriers. We describe the regulation of claudin 5 degradation by the ubiquitin-proteasome system (UPS). Our results indicate that claudin 5 has a relatively short half-life and can be polyubiquitinated on lysine 199. This ubiquitination appears to trigger the proteasome-dependent degradation of claudin 5. Other mechanisms also seem to be involved in the post-translational regulation of claudin 5, including a ubiquitin-independent and probably indirect lysosomal-dependent pathway. These findings provide evidence for the involvement of the UPS in the regulation of claudin 5 levels, and set the stage for further research to determine the involvement of this pathway in the modulation of the properties of TJs and cell-layer barriers.


[Combined hamartoma of the retinal pigment epithelium and retina: case report].
We report the case of a 19-year-old woman with a combined hamartoma of the retinal pigment epithelium and retina incidentally discovered during her first eye exam. By way of this case, we describe and illustrate the epidemiological and clinical characteristics of the condition and its potential complications.


Inactivation of the BSE agent by the heat and pressure process for manufacturing gelatine.
Dietary exposure to the bovine spongiform encephalopathy (BSE) agent is the probable cause of variant Creutzfeldt-Jakob disease in people. The industrial manufacturing process for the production of gelatine and colloidal protein by the heat and pressure process was downscaled accurately and its capacity to remove or inactivate bse infectivity was investigated. Gelatine was made from bones experimentally contaminated with mouse brain infected with the 301V strain of mouse-passaged bse agent in which the infective titre was 10(8.7) ID50/g. No infectivity was detected in the extracted protein (> or =10(0.45) ID50/g), and the calculated clearance factor was 10(6.5) ID50 or more.


Predefined gene transfer for expression of a glycosphingolipid antigen by transfection with a cosmid genomic library prepared from a cell line in which the specific glycosphingolipid is highly expressed.
The deliberate transfer of globotriaosylceramide (Gb3) expression in mouse lymphoma L5178 cells was achieved by transfection with a cosmid DNA library prepared from human Burkitt lymphoma Ramos cells in which Gb3 was highly expressed. The recipient mouse lymphoma cells did not contain Gb3 but did contain its direct precursor, lactosylceramide. The transfected cells expressed Gb3, detected both chemically and immunologically, and contained human DNA detected by an Alu sequence probe. This model demonstrates a general method for studying glycosyltransferase genes and other factors necessary for the expression of glycosphingolipid antigens.


Stereotactic body radiation therapy for the primary treatment of localized prostate cancer.
The low alpha/beta ratio of prostate cancer suggests that hypofractionated schemes of dose-escalated radiotherapy should be advantageous. We report our experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer to assess efficacy and toxicity. From 2007 to 2010, 70 patients (51 % low risk, 31 % intermediate risk, and 17 % high risk) with localized prostate cancer were treated with SBRT using the CyberKnife system. One-third of patients received androgen deprivation therapy. Doses of 37.5 Gy (n = 29), 36.25 Gy (n = 36), and 35 Gy (n = 5) were administered in five fractions and analyzed as high dose (37.5 Gy) vs. low dose (36.25 and 35 Gy). At a median 27 and 37 months follow-up, the low and high dose groups' median PSA nadir to date was 0.3 and 0.2 ng/ml, respectively. The 3-year freedom from biochemical failure (FFBF) was 100 %, 95.0 % and 77.1 % for the low-, intermediate- and high-risk patients. A dose response was observed in intermediate- and high-risk patients with 72 % vs. 100 % 3-year FFBF for the low and high dose groups, respectively (p = 0.0363). Grade III genitourinary toxicities included 4 % acute and 3 % late (all high dose). Potency was preserved in 83 % of hormone naïve patients. CyberKnife dose escalated SBRT for low-, intermediate- and high-risk prostate cancer exhibits favorable efficacy with acceptable toxicity.


Nocturnal sleep, cardiovascular function, and adrenal activity following maximum-capacity exercise.
Eight subjects performed a treadmill test of their maximal aerobic capacity (VO2max) to determine whether exercise which is maximally stressful but relatively low in total energy expenditure may affect nocturnal sleep. The test was performed at 16.00 h on day 3 of the study, with day 1 as adaptation, day 2 as baseline and day 4 as a carryover night. Changes observed after exercise included a decrease in the duration of the first REM sleep period, an elevation of heart rate in the first 2 h of sleep, a reduction in norepinephrine excretion and an increased excretion of dopamine. Comparisons of sleep alterations in 4 subjects who exercised regularly (active group) with 4 subjects who took no regular exercise revealed differences in the first sleep cycle. Active subjects displayed an increased duration of SWS coupled with an increased latency to first REM onset. Non-active subjects, by contrast, displayed a shortened REM latency and duration of SWS. These results indicate that short-term maximum exercise may induce significant alteration of the temporal distribution of SWS with differences in response seen between regular exercisers and non-exercisers.


Fear of childbirth and its determinants in pregnant women in the third trimester: a cross-sectional study.
Fear of childbirth (FOC) is a prevalent issue among pregnant women and significantly relates to adverse outcomes for the mother and child. However, it is not clear the prevalence and risk factors of FOC among pregnant women in a region with a moderate level of economic development in China. The aim of this study was to investigate the prevalence and risk factors of FOC among pregnant women in the third trimester of pregnancy in Lianyungang city, Eastern China. A cross-sectional survey was conducted from December 2022 to February 2023 among pregnant women in the third trimester who met the inclusion criteria and visited Lianyungang Maternal and Child Health Hospital in Jiangsu Province, Eastern China. A structured questionnaire including sociodemographic characteristics, clinical characteristics, FOC, family function, doctor-patient communication, social support, general self-efficacy, anxiety, depression, insomnia symptoms, and quality of life was used to collect data. A multiple linear regression model was used to identify predictors of FOC. This study included 535 pregnant women in the third trimester. The mean score of FOC was 30.67 ± 10.18, and the median score was 29.00. The prevalence of FOC was 56.64%. Multiple linear regression analysis revealed that pregnant women with electronic screen exposure time more than 5 h per day (β = 2.02, 95%CI: 0.50-3.53, P < 0.05), no history of cesarean section (β = 2.66, 95%CI: 0.61-4.71, P < 0.05), likes sour food or hates greasy food (β = 1.75, 95%CI: 0.00-3.50, P < 0.05), anxiety (β = 0.50, 95%CI: 0.21-0.80, P < 0.05) and depression (β = 0.30, 95%CI: 0.04-0.57, P < 0.05) were more likely to have a greater level of FOC than their counterparts. However, a significantly lower level of FOC was observed in pregnant women who were multipara (β=-1.64, 95%CI: -3.27-0.01, P < 0.05), not worrying about delivery without family members (β=-3.75, 95%CI: -5.26-2.25, P < 0.001), had good family function (β=-0.32, 95%CI: -0.64-0.00, P < 0.05) and doctor-patient communication (β=-0.33, 95%CI: -0.64-0.02, P < 0.05). The prevalence of FOC was high in Lianyungang city, Eastern China. FOC is influenced by multiple factors. There is an urgent need to develop interventions to reduce the prevalence of FOC in the third trimester of pregnancy, and to pay attention to pregnant women with risk factors for FOC.


Effect of soman on N-methyl-D-aspartate-stimulated [3H]norepinephrine release from rat cortical slices.
Effects of soman on N-methyl-D-aspartate (NMDA) evoked [3H]norepinephrine (NE) release were examined in rat brain cortical slices. NMDA increased [3H]NE release in a concentration-dependent manner. Soman could inhibit the increase evoked by NMDA, but carbachol, an agonist of cholinergic receptor, could potentiate the increase evoked by NMDA. Atropine (a selective muscarinic antagonist) attenuated the release of [3H]NE induced by NMDA in the presence of carbachol or acetylcholine (ACh), but had no effect on the release of [3H]NE induced by NMDA alone. Both d-tubocurarine (an antagonist of nicotinic receptor) and atropine had no effect on the release of [3H]NE induced by NMDA in the presence of soman. These results suggested that soman has a direct action at non-cholinergic sites, probably at NMDA receptors.


Postural responses without versus with acute external cervical spine fixation: a comparative study in healthy subjects and patients with acute unilateral vestibular loss.
Using a diagnostic prospective cohort single center study design, the influence of a cervical collar on standing balance during dynamic postural perturbations in healthy adults and patients with acute unilateral vestibular dysfunction was measured in 31 healthy subjects and 27 patients with acute unilateral vestibular loss. The main outcome measures were completed standard protocols on the Sensory Organization Test (SOT) and Motor Control Test (MCT) of the NeuroCom Equitest(®) computerized posturography platform measured without and with acute cervical fixation, respectively. Paired t test showed no significant difference during the six conditions of neither the SOT scores nor analyzing the SOT strategies or during the MCT between the non-fixed and fixed neck in healthy subjects and in the patients (all p > 0.05). Older healthy subjects showed decreased SOT scores but equal MCT results. The age effect was more dominant in the patients when wearing the collar. Gender had no influence whether in healthy individuals nor in patients. In almost all conditions of the SOT but only in some MCT subtests patients had significantly lower scores than healthy subjects without collar and with collar (all p < 0.05). In conclusion, the SOT but only some subtest of the MCT could clearly distinguish between healthy adults and patient with acute unilateral vestibular loss. Equilibrium scores did not change significantly when the cervical spine was fixed with a collar. Acute fixation of the neck with a collar seems not to affect standing balance, even not when vestibular, visual and/or somatosensory input are also reduced.


Signs and symptoms of parotid gland carcinoma and their prognostic value.
The aim of this study was to analyse signs and symptoms present in patients with parotid gland carcinoma and to assess their prognostic value. A retrospective study of data from 131 patients who were treated surgically was performed. Evaluation of prognostic factors was possible in 109 patients who completed a minimum 5 year follow up. The most common sign and symptoms were parotid mass (96.9%), pain (40.4%), enlarged cervical lymph nodes (32.0%), facial nerve palsy (20.6%) and overlying skin infiltration (19.8%). In 20% of all cases there were no symptoms of tumour malignancy. The average duration of symptoms suggesting malignancy was 4 months. In univariate analysis, the strongest prognostic value was found for facial nerve palsy; it reduced nearly tenfold (9.7) the 5-year disease-free survival. The subsequent poor prognostic factors were: skin infiltration, enlarged cervical lymph nodes, tumour fixation and tumour size (>4 cm). Pain and the dynamics of tumour growth were not statistically significant for survival rate. Significant difference in 5-year disease free survival rate was found between the groups of patients, according to the number of symptoms suggesting malignancy. The multivariate analysis showed that only facial nerve palsy and skin infiltration were independent prognostic factors.


Formation of inositol 1,3,4,6-tetrakisphosphate during angiotensin II action in bovine adrenal glomerulosa cells.
Angiotensin II stimulates the formation of several inositol polyphosphates in cultured bovine adrenal glomerulosa cells prelabelled with [3H] inositol. Analysis by high performance anion exchange chromatography of the inositol-phosphate compounds revealed the existence of two additional inositol tetrakisphosphate (InsP4) isomers in proximity to Ins-1,3,4,5-P4, the known phosphorylation product of Ins-1,4,5-trisphosphate and precursor of Ins-1,3,4-trisphosphate. Both of these new compounds showed a slow increase after stimulation with angiotensin II. The structure of one of these new InsP4 isomers, which is a phosphorylation product of Ins-1,3,4-P3, was deduced by its resistance to periodate oxidation to be Ins-1,3,4,6-P4. The existence of multiple cycles of phosphorylation-dephosphorylation reactions for the processing of Ins-1,4,5-P4 may represent a new aspect of the inositol-lipid related signalling mechanism in agonist-activated target cells.


Social cognition in patients with schizophrenia, their unaffected first degree relatives and healthy controls. Comparison between groups and analysis of associated clinical and sociodemographic variables.
To evaluate and compare the social cognition in patients with schizophrenia, healthy first-degree relatives and controls, by studying the relationship between social cognition and nonsocial cognition, psychopathology, and other clinical and sociodemographic variables. The total sample was comprised of patients diagnosed with paranoid schizophrenia (N = 29), healthy first-degree relatives (N = 21) and controls (N = 28). All groups were assessed with an ad hoc questionnaire and a Social Cognition Scale, which assessed the domains: emotional processing, social perception and attributional style in a Spanish population. The patient group was also assessed with the Scale for the Positive and Negative Syndrome Scale and the Mini-mental state examination. Statistical analyses were performed with SPSS version 15.0. Patients scored significantly worse in all domains of social cognition assessed, compared with controls, and mastery attributional style, compared with relatives. The type of psychopathology correlated negatively and statistically significantly with different domains of social cognition: negative symptoms with emotional processing and attributional style, and positive symptoms with social perception. Basic cognition scores correlated positively and statistically significantly with the domains social perception and attributional style. Social cognition has become an interesting object of study, especially in how it relates to non-social cognition, psychopathology and global functioning of patients, bringing new elements to be considered in the early detection, comprehensive treatment and psychosocial rehabilitation of patients. Its conceptualization as trait variable, the consideration of the existence of a continuum between patients and relatives are plausible hypotheses that require further research.


Ovulation and follicular development associated with three low-dose oral contraceptives: a randomized controlled trial.
To address the hypothesis that multiphasic oral contraceptives (OCs) increase rather than decrease the risk of functional ovarian cysts. In this single-center, randomized controlled study, women were assigned to a multiphasic pill, a lower-dose monophasic pill, a higher-dose monophasic pill, or nonsteroidal contraception. Forty volunteers were randomized (ten each) to three different pill regimens or to nonsteroidal contraception. During 6 months of treatment, follicular development was measured by vaginal ultrasonography and ovulation was indicated by serum progesterone levels. The relative risk (RR) of developing a follicular structure greater than 30 mm in diameter during a cycle with the higher-dose monophasic pill was 0.5 (95% confidence interval [CI] 0.1-1.9; P = .49) compared with the multiphasic pill. The risk with the lower-dose monophasic pill was comparable to that with the multiphasic pill (RR 1.3, 95% CI 0.5-3.6; P = .56). With the multiphasic pill, the maximum ovulation rate over 60 cycles was 1.7 per 100 cycles (95% CI 0.0-8.9). This multiphasic pill more closely resembled the lower-dose monophasic pill than the higher-dose monophasic pill in its suppression of follicular development.


Applications of Platelet Rich Plasma in Urology.
Platelet rich plasma is a product obtained from vein whole blood sample, with a high concentration of growth factors, which have been reported to be beneficial for tissue regeneration. In the last few years, several assays that pretend to demonstrate the efficacy of platelet rich plasma in many disciplines, including urology, have been published. The aim of this assay is to develop a bibliographic review of the publications available about platelet rich plasma and urology. The search was based on PubMed database. Platelet rich plasma has demonstrated to be a safe and easy to obtain product, and it has also shown promising results in terms of efficacy in urology. However, it is necessary to conduct large, placebo-controlled, studies that can confirm or deny the effectiveness of platelet rich plasma before it can be used on urological conditions.


Retirement as a predictor of physical functioning trajectories among older businessmen.
Associations between retirement characteristics and consequent physical functioning (PF) are poorly understood, particularly in higher socioeconomic groups, where postponing retirement has had both positive and negative implications for PF. Multiple assessments of PF, the first of which at the mean age of 73.3 years, were performed on 1709 men who were retired business executives and managers, using the RAND-36/SF-36 instrument, between 2000 and 2010. Questionnaire data on retirement age and type of pension was gathered in 2000. Five distinct PF trajectories were created using latent growth mixture modelling. Mortality- and covariate-adjusted multinomial regression models were used to estimate multinomial Odds Ratios (mOR) on the association between retirement characteristics and PF trajectories. A one-year increase in retirement age was associated with decreased likelihood of being classified in the 'consistently low' (fully adjusted mOR = 0.82; 95%CI = 0.70, 0.97; P = 0.007), 'intermediate and declining' (mOR = 0.89; 95%CI = 0.83, 0.96; P = 0.002), and 'high and declining' (mOR = 0.92; 95%CI = 0.87, 0.98; P = 0.006) trajectories, relative to the 'intact' PF trajectory. Compared to old age pensioners, disability pensioners were more likely to be classified in the 'consistently low' (mOR = 23.77; 95% CI 2.13, 265.04; P = 0.010), 'intermediate and declining' (mOR = 8.24; 95%CI = 2.58, 26.35; P < 0.001), and 'high and declining' (mOR = 2.71; 95%CI = 1.17, 6.28; P = 0.020) PF trajectories, relative to the 'intact' PF trajectory. Among executives and managers, older age at retirement was associated with better trajectories of PF in old age. Compared to old age pensioners, those transitioning into disability and early old age pensions were at risk of having consistently lower PF in old age.


Maternal left ventricular mass and diastolic function during pregnancy.
To evaluate changes in left ventricular mass and diastolic function during normal pregnancy. This was a cross-sectional study of 125 pregnant women at 9-42 weeks of gestation and 19 non-pregnant female controls. Two-dimensional and M-mode echocardiography of the maternal left ventricle and left atrium was performed. During pregnancy left ventricular mass increased by 52%. There was an increase in left ventricular end-diastolic and end-systolic diameters (12% and 20%, respectively), left ventricular posterior wall diameter during diastole and systole (22% and 13%, respectively) and left intraventricular septum during diastole and systole (15% and 19%, respectively). Mitral valve A-wave maximum velocity increased during pregnancy by 19%, while mitral valve E-wave maximum velocity and the ratio of E-wave/A-wave velocities increased early in pregnancy by about 14% and 6%, respectively, with a subsequent decline to 4% and 10%, respectively, below non-pregnant levels. Left ventricular mass increases during pregnancy, while left ventricular diastolic function, as demonstrated by the changes in mitral valve flow velocities, increases in the first two trimesters but declines in the third trimester.


Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine.
Aging-related bradykinesia affects ∼ 15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacologic therapeutics, noninvasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month-old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial, and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate that initiation of CR at middle age may reduce aging-related bradykinesia, and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral dopamine neurotransmission may be one component of preserving locomotor capabilities during aging.


Long-time dynamics of Met-enkephalin: comparison of theory with Brownian dynamics simulations.
A recent theory for the long time dynamics of flexible chain molecules is applied for the first time to a peptide of biological importance, the neurotransmitter met-enkephalin. The dynamics of met-enkephalin is considerably more complicated than that of the previously studied glycine oligomers; met-enkephalin contains the interesting motions of phenyl groups and of side chains relative to the backbone, motions that are present in general flexible peptides. The theory extends the generalized Rouse (GR) model used to study the dynamics of polymers by providing a systematic procedure for including the contributions from the memory function matrices neglected in the GR theory. The new method describes the dynamics by time correlation functions instead of individual trajectories. These correlation functions are analytically expressed in terms of a set of equilibrium averages and the eigenvalues and eigenfunctions of the diffusion operator. The predictions of the theory are compared with Brownian dynamics (BD) simulations, so that both theory and simulation use identical potential functions and solvent models. The theory thus contains no adjustable parameters. Inclusion of the memory function contributions profoundly affects the dynamics. The theory produces very good agreement with the BD simulations for the global motions of met-enkephalin. It also correctly predicts the long-time relaxation rate for local motions.


Cancer stem cell plasticity and its implications in the development of new clinical approaches for oral squamous cell carcinoma.
Oral squamous cell carcinoma (SCC) represents a major worldwide disease burden, with high rates of recurrence and metastatic spread following existing treatment methods. Populations of treatment resistant cancer stem cells (CSCs) are well characterised in oral SCC. These populations of CSCs engage the cellular programme known as epithelial mesenchymal transition (EMT) to enhance metastatic spread and therapeutic resistance. EMT is characterised by specific morphological changes and the expression of certain cell surface markers that represent a transition from an epithelial phenotype to a mesenchymal phenotype. This process is regulated by several cellular pathways that interact both horizontally and hierarchically. The cellular changes in EMT occur along a spectrum, with sub-populations of cells displaying both epithelial and mesenchymal features. The unique features of these CSCs in terms of their EMT state, cell surface markers and metabolism may offer new druggable targets. In addition, these features could be used to identify more aggressive disease states and the opportunity to personalise therapy depending on the presence of certain CSC sub-populations.


Phylogenetic diversity of bacterial communities in bovine rumen as affected by diets and microenvironments.
Phylogenetic analysis was conducted to examine ruminal bacteria in two ruminal fractions (adherent fraction vs. liquid fraction) collected from cattle fed with two different diets: forage alone vs. forage plus concentrate. One hundred forty-four 16S rRNA gene (rrs) sequences were obtained from clone libraries constructed from the four samples. These rrs sequences were assigned to 116 different operational taxonomic units (OTUs) defined at 0.03 phylogenetic distance. Most of these OTUs could not be assigned to any known genus. The phylum Firmicutes was represented by approximately 70% of all the sequences. By comparing to the OTUs already documented in the rumen, 52 new OTUs were identified. UniFrac, SONS, and denaturing gradient gel electrophoresis analyses revealed difference in diversity between the two fractions and between the two diets. This study showed that rrs sequences recovered from small clone libraries can still help identify novel species-level OTUs.


Determination of a potential antitumor quassinoid in rat plasma by UPLC-MS/MS and its application in a pharmacokinetic study.
A sensitive UPLC-MS/MS method was developed and validated for the determination of brusatol in rat plasma. Chromatographic separation was carried out on a C18 column using methanol and 10mM ammonium acetate containing 0.1% (v/v) formic acid (55:45, v/v). The lower limit of quantification (LLOQ) was 1.0 ng/mL for brusatol in plasma. The intra- and inter-day precision for the analyte ranged from 3.2% to 9.2% and 1.3% to 7.8%, and the accuracy was between 97.3% and 108.5%. The method was successfully applied in a pharmacokinetic study of brusatol following intravenous injection (0.5, 1.0, and 2.0mg/kg) of brusatol.


Contralateral necrotizing fascitis after left nephrectomy for emphysematous pyelonephritis.
Emphysematous pyelonephritis is an acute necrotizing infection of the renal parenchyma. The management is variable, extending to total nephrectomy in severe or refractory cases. Post-nephrectomy complications are numerous and common, necrotizing fasciitis, and sepsis being among them. We present a case of a 37-year-old woman with obesity and a previous left emphysematous pyelonephritis episode managed conservatively. The patient presented with a second left emphysematous pyelonephritis and underwent a left total nephrectomy. Two weeks later, the patient presented with a contralateral necrotizing fasciitis of the abdominal wall. Subsequently, the patient required several surgical debridement procedures and a vacuum-assisted closure system treatment. Emphysematous pyelonephritis is an aggressive infectious disease that requires high suspicion in patients at risk.


Multisession radiosurgery for grade 2 (WHO), high risk meningiomas. A phase II clinical trial.
Patients suffering from recurrent and residual grade 2 (WHO) meningiomas after subtotal excision should be considered as high-risk groups with an uncertain prognosis. Adjuvant radiotherapy seems to be the best approach to reduce disease progression. The primary aim of this phase II explorative, monocentric, single arm study was to evaluate the safety of adjuvant multisession radiosurgery (mRS) in this group of patients; the efficacy in terms of tumour local control was the secondary endpoint. Patients recruited from April 2017 to May 2019 were over 18 years old, had a histologically-documented intracranial recurrent or residual Grade 2 meningioma (WHO 2016) and a KPS > 70. Patients with NF2, concomitant neoplasm or pregnancy were excluded. Descriptive statistics were provided for categorical variables. Progression free survival (PFS) was modelled using the Kaplan-Meier method. Twenty-four patients were enrolled. All 24 patients underwent mRS: twenty-two patients received 28 Gy in 4 fractions, 2 patients received 24 Gy in 4 Treatment related adverse events (CTCAE 4.3) were limited to grade 2 in 1 patient (4.1%). At a median follow-up of 28 months, 8 patients (33.3%) had disease progression, either out-of-field or infield, compared with the planning target volume. Considering both infield and out-of-field progressions, 3-year PFS was 47% (95% confidence interval, CI, 22-69%); considering only the infield ones, 3-year PFS was 86% (95% CI 55-96%), and local control at last follow-up was 92%. mRS provides good local control of the tumour volume (TV) and is associated with a low rate of toxicity. These results call for further investigation to confirm favourable outcomes in patients with high-risk meningioma. NCT05081908, October 18, 2021, retrospectively registered.


Racial/Ethnic Differences in Insulin Resistance and Beta Cell Function: Relationship to Racial Disparities in Type 2 Diabetes among African Americans versus Caucasians.
Both biological and sociocultural factors have been implicated in the well-documented racial disparity in incidence and prevalence of type 2 diabetes (T2D) between African Americans (AA) and non-Hispanic whites (NHW). This review examines the extent to which biological differences in glucose metabolism, specifically insulin resistance and beta cell function (BCF), contribute to this disparity. The majority of available data suggests that AA are more insulin resistant and have upregulated BCF compared to NHW. Increasing evidence implicates high insulin secretion as a cause rather than consequence of T2D; therefore, upregulated BCF in AA may specifically confer increased risk of T2D in this cohort. Racial disparities in the metabolic characteristics of T2D have direct implications for the treatment and health consequences of this disease; therefore, future research is needed to determine whether strategies to reduce insulin secretion in AA may prevent or delay T2D and lessen racial health disparities.


Developmental dyscalculia.
Developmental dyscalculia (DD) is a learning disorder affecting the acquisition of school level arithmetic skills present in approximately 3-6% of the population. At the behavioral level DD is characterized by poor retrieval of arithmetic facts from memory, the use of immature calculation procedures and counting strategies, and the atypical representation and processing of numerical magnitude. At the neural level emerging evidence suggests DD is associated with atypical structure and function in brain regions associated with the representation of numerical magnitude. The current state of knowledge points to a core deficit in numerical magnitude representation in DD, but further work is required to elucidate causal mechanisms underlying the disorder.


Proteome analysis of ventral midbrain in MPTP-treated normal and L1cam transgenic mice.
Treatment of mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridene hydrochloride (MPTP) is a well established animal model for Parkinson's disease (PD), while overexpression of L1 cell adhesion molecule (L1cam) has been proposed to attenuate the degeneration of dopaminergic neurons induced by MPTP. To gain insight into the role of L1cam in the pathomechanism of PD, we investigated protein expression patterns after MPTP-treatment in both C57BL/6 (wild-type) and transgenic mice overexpressing L1cam in astrocytes. Our results showed that during the acute phase, proteins in functional complexes responsible for mitochondrial, glycolysis, and cytoskeletal function were down-regulated in MPTP-treated wild-type mice. After a recovery phase, proteins that were down-regulated in the acute phase reverted to normal levels. In L1cam transgenic mice, a much higher number of proteins was altered during the acute phase and this number even increased after the recovery phase. Many proteins involved in oxidative phosphorylation were still down-regulated and glycolysis related protein were still up-regulated. This pattern indicates a lasting severely impaired energy production in L1cam mice after MPTP treatment.


A validated prediction score for having two or more embryos for cryopreservation following freeze-all IVF cycles: an analysis utilizing SART CORS database.
To develop and validate a prediction score for having 2 or more embryos cryopreserved following an IVF cycle without a fresh transfer such that an embryo selection method may be applicable. We also developed a counseling tool on the probability of not having any embryos following an IVF cycle without a fresh transfer. We split the data into a development set and a validation set by region within the USA using a coin flip approach and subsequently performed a logistic regression model to identify factors most predictive of cryopreservation of 2 or more embryos in the development set. This model was validated in the validation set. Subsequently, a clinical prediction score was derived using the model coefficients and the predictive accuracy measured with the concordance (c) statistic. A total of 31,537 potential freeze-all cycles were reported to the Society for Assisted Reproductive Technology in 2014. Of these, 57.87% produced and cryopreserved two or more embryos. We identified that age, AMH, and the number of eggs retrieved were the most significant predictors of having 2 or more embryos cryopreserved with a validated c-statistic of 0.84 (95% CI: 0.83 to 0.85). A clinical prediction score was derived from the model. 28.9% of freeze-all cycles had no embryos created from the IVF cycle despite a cycle start and an egg retrieval. The number of eggs retrieved was the most significant predictor of having no embryos available for a transfer, with a c-statistic of 0.80 when modeled as the only predictor variable. We derived counseling tools with acceptable discrimination for use in clinical practice (c-statistics > 0.7). Our study further suggests that the number of eggs retrieved from an IVF cycle is most predictive of having 2 or more embryos cryopreserved and not having any embryos after an IVF cycle, suggesting that clinicians should strive to optimize oocyte yield especially in poor prognosis patients. The probability of having two more embryos cryopreserved in a freeze-all IVF cycle such that an embryo selection method is applicable can be predicted with acceptable precision prior to the IVF cycle and excellent precision following egg retrieval using the prediction score.


Relationship between proliferative activity and estrogen receptors in breast cancer.
The proliferative activity of breast cancer has been analyzed in relation to the hormonal characteristics of the host and of the tumor for 199 patients. The analyses of labeling index frequency distributions of estrogen receptor positive (ER+) and negative (ER-) cancers from premenopausal and postmenopausal patients have allowed us to identify three different kinetic groups. A first group, with a very low proliferative activity, includes ER+ cancers from postmenopausal patients; a second group, with an intermediate proliferative activity, includes ER+ cancers from premenopausal and ER- cancers from postmenopausal patients; and a third group, with a very high proliferative activity, includes ER- cancers from premenopausal patients. Generally, the amount of estrogen receptors in ER+ cancers is inversely correlated with the proliferative activity. Lower levels of ER in premenopausal in comparison to postmenopausal patients were found in low proliferative activity tumors.


Effect of long-term feeding of graded levels of deoxynivalenol (DON) on growth performance, nutrient utilization, and organ health in finishing pigs and DON content in biological samples.
The prevalence of deoxynivalenol (DON) is a concern for swine producers, and although there has been extensive research into the effects of DON in pigs, focus has been in young pigs and/or in short-term studies. The objective of the study was to determine the effect of long-term exposure to DON-contaminated diets in finisher pigs. A total of 200 pigs (76.6 ± 3.9 kg initial weight) were group housed (five pigs per pen; n = 10 pens/treatment) in a 6-wk trial. Pigs were fed a wheat-barley-soybean meal-based control (CONT) diet with no DON or the basal diet in which clean wheat was replaced by DON-contaminated wheat and wheat screenings to provide DON content of 1, 3, or 5 ppm (DON1, DON3, and DON5, respectively). Individual BW and pen feed intake were recorded weekly to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F). Blood was collected on days 0, 14, and 43 and analyzed for indicators of liver and kidney health. Nitrogen (N)-balance was conducted immediately following the growth performance period to determine the effect of DON on nutrient utilization. Blood and urine samples collected during N balance were analyzed for DON content. Feeding DON reduced (P < 0.05) ADFI and ADG from days 0 to 28 compared with CONT, after which there was no effect of diet on ADFI and ADG. The G:F was lower (P < 0.05) in DON5 fed pigs compared with all treatments during days 0 to 7; however, no treatment effects on G:F was observed from days 8 to 42. Nitrogen retention was lower (P < 0.05) in DON3 and DON5 compared with DON1-fed pigs. Nitrogen retention efficiency was higher (P < 0.05) in DON1 compared with DON3 and DON5 and protein deposition for DON1 pigs was higher (P < 0.05) than all treatments. There were no treatment effects on indicators of liver and kidney health. As dietary DON intake increased, concentration of DON in blood and urine increased. Overall, although there was an initial decrease in ADG and ADFI in pigs receiving diets containing >1 ppm DON, pig performance recovered after a period of time, whereas nutrient utilization continued to be affected after recovery of performance. Moreover, the lack of DON on G:F indicates that the negative effects of DON on growth performance are largely due to reduced feed intake. Overall, although pigs maybe capable of adapting to intake of DON-contaminated diets, their final body weight will be reduced when fed diets containing >1 ppm DON.


[Stress tolerance of the patient in abdominal surgery: stomach cancer].
Patients with gastric cancer undergoing surgery have much to endure and are accompanied by many risks. These risks depend on localization and extent of the tumor, the patients' general condition (nutritional and immune status), age, coexistent diseases and the extent of the required operation. In view of these facts, the principle of radical surgery must be weighed against the tolerance capability of the patient, especially in old people. Extensive diagnostic procedures are necessary to explore those risks. The preoperative treatment (hyperalimentation), the well considered indication for surgery, the choice of operation with lowest risk and the perioperative measurements are of great importance in limiting the risk for the patient.


Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer.
Perineural invasion (PNI) is a typical poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking PNI to poor prognosis remain unclear. This study aimed to clarify what changes occurred alongside PNI in PDAC. A 128-patient cohort undergoing surgery for early-stage PDAC was evaluated. Subdivided into two groups, according to pathological state, a pancreatic nerve invasion (ne) score of less than three (from none to moderate invasion) was designated as the low-grade ne group. The high-grade (marked invasion) ne group (74 cases, 57.8%) showed a higher incidence of lymphatic metastasis (P = 0.002), a higher incidence of early recurrence (P = 0.004), decreased RFS (P < 0.001), and decreased DSS (P < 0.001). The severity of lymphatic (r = 0.440, P = 0.042) and venous (r = 0.610, P = 0.002) invasions was positively correlated with the ne score. Tumors having abundant stroma often displayed severe ne. Proteomics identified eukaryotic initiation factor 2 (EIF2) signaling as the most significantly enriched pathway in high-grade ne PDAC. Additionally, EIF2 signaling-related ribosome proteins decreased according to severity. Results showed that PNI is linked with lymphatic and vascular invasion in early-stage PDAC. Furthermore, the dysregulation of proteostasis and ribosome biogenesis can yield a difference in PNI severity.


Substitution Phalloplasty in Patients With Bladder Exstrophy-Epispadias Complex: A Systematic Review of Techniques, Complications and Outcomes.
Males born with bladder exstrophy-epispadias complex generally have a shorter phallus, split corpora with dorsal curvature, and a scarred and flattened glans, so substitution phalloplasty is often required. The aim of this study was to review the techniques, complications, and outcomes of substitution phalloplasty in bladder exstrophy-epispadias complex patients to determine the ideal surgical procedure and gauge the risks and benefits for the patient. A systematic review of the literature was performed using PubMed/MEDLINE and the Cochrane Library with the following terms: ("phalloplasty"); (("epispadias") OR ("bladder exstrophy") OR ("cloacal exstrophy")). We included only full-text articles reporting data about techniques and outcomes of substitution phalloplasty in patients with bladder exstrophy-epispadias complex. To determine whether patients with bladder exstrophy-epispadias complex might benefit from substitution phalloplasty. We selected 7 studies involving 47 patients. All the studies were characterized by a low level of evidence and a heterogeneous approach during treatment and outcome assessment. The free radial forearm flap was the most commonly performed technique (89%) with an overall complication rate of 15%. Urethroplasty was performed in 22 of 47 (47%) patients, and in most cases (20/22) a "tube-within-the-tube" technique was performed simultaneously with the phalloplasty (20/47). Urethroplasty complications were recorded in 12 of 22 (54%) patients with 6 fistulae and 6 stenoses. A penile prosthesis was implanted in 32 of 47 (68%) patients and complications occurred in 8 of 32 (25%) patients with 6 erosion. Aesthetic, sexual, and psychological outcomes were satisfactory, but none of the studies used validated instruments for the final assessment. It was not possible to formulate any recommendations based on a high level of evidence regarding substitution phalloplasty in patients with bladder exstrophy-epispadias complex. To our knowledge, this is the first review to address bladder exstrophy-epispadias complex patients only. The limitations are mainly represented by the small number of cases because of the rarity of this disease and by the fact that no studies used validated instruments. Substitution phalloplasty in patients with bladder exstrophy-epispadias complex can achieve good functional, aesthetic, psychological, and sexual outcomes. It requires multiple procedures and carries a high complication rate. Multicentric studies including the assessment of patients by means of a validated questionnaire which investigates both sexual function and psychosexual satisfaction are required. Berrettini A, Sampogna G, Gnech M, et al. Substitution Phalloplasty in Patients With Bladder Exstrophy-Epispadias Complex: A Systematic Review of Techniques, Complications, and Outcomes. J Sex Med 2021;18:400-409.


Oxidative stress and dystrophy Facioscapulohumeral: Effects of vitamin C, vitamin E, zinc gluconate and selenomethionine supplementation.
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. Despite major progress in the understanding of the genetic basis of FSHD, the exact mechanisms that lead to FSHD defects are not completely understood and no curative treatment is available. However, there is growing evidence that oxidative stress may contribute to FSHD pathology. We recently reported that reduced physical performance in patients with FSHD is associated with important redox unbalance and oxidative stress in blood. Hence, we hypothesized that insufficient intake of antioxidant vitamins and minerals may reduce the body capacity to regulate free radical insults, leading to a condition known as oxidative stress that could affect muscle function performance in patients with FSHD. We thus conducted a pilot randomized double-blind placebo-controlled study to test whether oral administration of vitamins and minerals could improve the physical performance of patients with FSHD. The results of this randomized double-blind placebo-controlled trial show that supplementation with vitamin C, vitamin E (as alpha tocopherol), zinc gluconate and selenomethionine in patients with FSHD significantly improves the maximal voluntary contraction and endurance of both quadriceps by enhancing the antioxidants defences and reducing oxidative stress.


Long noncoding RNA study: Genome-wide approaches.
Long noncoding RNAs (lncRNAs) have been confirmed to play a crucial role in various biological processes across several species. Though many efforts have been devoted to the expansion of the lncRNAs landscape, much about lncRNAs is still unknown due to their great complexity. The development of high-throughput technologies and the constantly improved bioinformatic methods have resulted in a rapid expansion of lncRNA research and relevant databases. In this review, we introduced genome-wide research of lncRNAs in three parts: (i) novel lncRNA identification by high-throughput sequencing and computational pipelines; (ii) functional characterization of lncRNAs by expression atlas profiling, genome-scale screening, and the research of cancer-related lncRNAs; (iii) mechanism research by large-scale experimental technologies and computational analysis. Besides, primary experimental methods and bioinformatic pipelines related to these three parts are summarized. This review aimed to provide a comprehensive and systemic overview of lncRNA genome-wide research strategies and indicate a genome-wide lncRNA research system.


Thyroid hormones in rats during long-term cold exposure and hypometabolic effect of reverse triiodothyronine on adrenaline induced thermogenesis.
One-day cold exposure to 5 degrees C induced temporal increase of reverse-triiodothyronine (rT3), triiodothyronine (T3) and thyroxine (T4) concentrations in the blood of rats (by 151%, 91% and 107%, respectively). The levels of all thyroid hormones remain elevated for at least 10 days of cold exposure. The injection of rT3 (330 micrograms kg-1 s.c.) inhibited the resting and adrenaline stimulated metabolism 1-3 days after application independently from the thyroid status of the animals. Since the hypothermic effect of rT3 occurred in thyroidectomized rats, it was concluded that rT3 acted primarily on peripheral, tissues, rather than on the thyroid.