Pain, disability, and lifestyle: Patients with complex regional pain syndrome compared to chronic musculoskeletal pain-A retrospective analysis.
Complex regional pain syndrome (CRPS) is an orphan disease occurring as a complication after trauma. Due to its acute onset and the typical clinical presentation of the inflammatory and autonomous signs, it is an eye-catching chronic pain disease affecting also young and working people. In social media and the internet, high pain severity and the unfavourable prognosis are often empathized. Here, we compared epidemiological, pain and lifestyle factors of 223 CPRS patients from the "ncRNAPain" cohort with 255 patients with chronic musculoskeletal pain (MSK). MSK patients were recruited at the beginning of a multimodal pain therapy programme. We searched for factors predicting pain intensity. Both chronic pain diseases affected women in middle age. Patients with MSK were more obese, drank more alcohol, and were less educated (Pearson chi-square Test or Mann-Whitney/U-Test). Both groups smoked more than healthy people in the OECD (Organization for Economic Cooperation and Development). Mann-Whitney/U-Test confirmed that CRPS patients did not have more severe pain and did not suffer more from pain-related disability than patients with MSK. CRPS patients also had less psychiatric comorbidities. Multiple linear regression analysis revealed that group assignment, depressive characteristics, body mass index, average alcohol consumption and smoking predicted higher pain ratings, while disease duration, anxiety symptoms or gender had no influence on pain intensity. In summary, our study supports a more optimistic view on pain in CRPS patients in comparison to MSK and identifies lifestyle factors that might contribute to the pathophysiology like smoking and drinking. Important next steps are the identification of CRPS patients at risk for chronification or-vice versa-with protective factors for pain resolution. This study compares complex regional pain syndrome (CRPS) and chronic musculoskeletal pain and questions previously reported pain, disability and lifestyle factors associated with CRPS.


Visual performance in preterm infants with brain injuries compared with low-risk preterm infants.
Neonatal brain injuries are the main cause of visual deficit produced by damage to posterior visual pathways. While there are several studies of visual function in low-risk preterm infants or older children with brain injuries, research in children of early age is lacking. To assess several aspects of visual function in preterm infants with brain injuries and to compare them with another group of low-risk preterm infants of the same age. Forty-eight preterm infants with brain injuries and 56 low-risk preterm infants. The ML Leonhardt Battery of Optotypes was used to assess visual functions. This test was previously validated at a post-menstrual age of 40 weeks in newborns and at 30-plus weeks in preterm infants. The group of preterm infants with brain lesions showed a delayed pattern of visual functions in alertness, fixation, visual attention and tracking behavior compared to infants in the healthy preterm group. The differences between both groups, in the visual behaviors analyzed were around 30%. These visual functions could be identified from the first weeks of life. Our results confirm the importance of using a straightforward screening test with preterm infants in order to assess altered visual function, especially in infants with brain injuries. The findings also highlight the need to provide visual stimulation very early on in life.


Between paradigms: Comparing experiences for adolescents treated at pediatric and adult trauma centres.
Injured adolescents may be treated at pediatric trauma centres (PTCs) or adult trauma centres (ATCs). Patient and parent experiences are an integral component of high-quality health care and can influence patient clinical trajectory. Despite this knowledge, there is little research on differences between PTCs and ATCs with respect to patient and caregiver-reported experience. We sought to identify differences in patient and parent-reported experiences between the regional PTC and ATC using a recently developed Patient and Parent-Reported Experience Measure. We prospectively enrolled patients (caregivers) aged 15-17 (inclusive), admitted to the local PTC and ATC for injury management (01/01/2020 - 31/05/2021) We provided a survey 8-weeks post-discharge to query acute care and follow-up experience. Patient and parent experiences were compared between the PTC and ATC using descriptive statistics, chi-square tests for categorical and independent t-tests for continuous variables. We identified 90 patients for inclusion (51 PTC, and 39 ATC). From this population, we had 77 surveys (32 patient and 35 caregiver) completed at the PTC, and 41 (20 patient and 21 caregiver) at the ATC. ATC patients tended to be more severely injured. We identified few differences in reported experience on the patient measure but identified lower ratings from caregivers of adolescents treated in ATCs for the domains of information and communication, follow-up care, and overall hospital scores. Patients and parents reported poorer family accommodation at the ATC. Patient experiences were similar between centres. However, caregivers report poorer experiences at the ATC in several domains. These differences are multifaceted, and may reflect differing patient volumes, effects of COVID-19, and healthcare paradigms. However, further work should target information and communication improvement in adult paradigms given its impact on other domains of care.


Effective treatment of high-voltage pulsed radiofrequency combined with oxygen-ozone injection in acute zoster neuralgia.
Postherpetic neuralgia (PHN) is the most common and severe complication of acute herpes zoster. Early treatment of herpes zoster neuralgia is of great significance to reduce the incidence of PHN. This retrospective study evaluated the efficacy and safety of the combination of high-voltage pulsed radiofrequency (PRF) and oxygen-ozone(O2-O3) injection in patients with acute zoster neuralgia (AZN) who failed to respond to conservative treatment. One-hundred patients diagnosed with AZN were classified into two groups (high-voltage PRF group [HP group, n = 50] and high-voltage PRF combined with O2-O3 injection group [HPO group, n = 50]) based on different treatment methods. Therapeutic effectiveness was assessed using a numerical rating scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI). The dosages of gabapentin and tramadol (mg/d) before treatment and after 1 week and 1, 3, and 6 months of treatment were measured. The incidence of clinically meaningful PHN after treatment was also recorded. Pain intensity and sleep quality in both groups at all time points improved after treatment compared to before treatment (P < 0.05). After 1 week and 1 month of treatment, NRS and PSQI scores in both groups decreased, but the differences were not statistically significant (P > 0.05). NRS, PSQI scores, and the dosages of gabapentin and tramadol decreased more significantly in the HPO group than those in the HP group after 3 months (P < 0.05). The incidence of PHN was significantly lower in the HPO group than in the HP group (P < 0.05). There were no significant differences in adverse events between the groups. High-voltage PRF is a safe and effective method for treating AZN. The combination of high-voltage PRF and O2-O3 injection is superior to high-voltage PRF alone for treating late-stage AZN. This approach could be recommended as an alternative treatment for patients with refractory AZN and could significantly reduce the risk of PHN.


Immunohistochemical PGP 9.5 positivity in human osteoblasts may indicate that compensatory and dysplastic craniofacial growth are under control by peripheral nerves.
The purpose was to examine human osteoblasts immunohistochemically in order to clarify the significance of the innervation for alveolar bone growth. Unstained sections available from 21 normal human mandibles (foetal gestational ages: 14-22 weeks). Before sectioning in 1980-1990, the mandibular tissue had been fixed in 4% neutral-buffered formaldehyde for 5 days. Tissue blocks were then decalcified in equal parts of 2% citric acid and 20% sodium citrate for 7-15 days, dehydrated, embedded in paraffin, and sagittally cut into 4-mum-thick serial sections and mounted on Superfrost Plus microscope slides. Sections were dried overnight at 40 degrees C. In the present study, paraffin sections were deparaffinized and treated with Tris-EDTA (Merck, Germany), pH 9.0, and immunohistochemically tested with polyclonal rabbit anti-PGP 9.5, and the EnVision +/HRP dual link (K4065; DAKO Denmark A/S, Denmark) method. A pronounced protein gene product (PGP) 9.5 activity was registered in osteoblasts from alveolar bone in all specimens. In all cases, the activity was intense at the top of and labially to the alveolar bone, while less or no activity was observed on the inner lingual aspects of the alveolar processes. Osteoclasts and osteocytes reacted vaguely or negatively. As the present study has demonstrated that human osteoblast activity in the alveolar bone seemingly responds to innervation, it is suggested that the peripheral nervous system via the trigeminal ganglion regulates compensatory and dysplastic alveolar bone formation.


Pyruvate dehydrogenase, lipoamide dehydrogenase and citrate synthase activity in fibroblasts from patients with Friedreich's and Charlevoix-Saguenay ataxia.
The activity of lipoamide dehydrogenase and two closely related enzymes was studied simultaneously in early, mild, and late passage fibroblast cultures. Friedreich's ataxia fibroblasts tended to lose pyruvate dehydrogenase and citrate synthase activities, while lipoamide dehydrogenase activity remained constant with aging of the cells. Mean pyruvate dehydrogenase activity was lower over-all in fibroblasts from ataxics. Mean citrate synthase activity was higher in ataxic fibroblasts. Present tissue culture media do not represent the best conditions in which to reproduce cofactor binding defects such as those found in other genetic diseases with structural enzyme mutations.


Gastric Fistula After Sleeve Gastrectomy: Clinical Features and Treatment Options.
To trace the clinical profile of fistula cases after sleeve gastrectomy (SG) and evaluate the efficacy and safety of endoscopic treatments and the admission costs of these patients. This is a retrospective study of patients who developed gastric fistulas after SG. All patients were submitted to surgical and/or endoscopic interventions (self-expandable stent, septotomy, and balloon dilation). The main studied variables were need for reoperation, number of endoscopic procedures, endoscopic complications, time until fistula diagnosis, fistula location, time until resolution, length of hospital stay, and health costs. The sample was mainly female (76.2%) with a mean age of 39.5 years and a BMI of 39.6 kg/m2. In 90.5% of cases, the fistula occurred in the topography of the His angle. Thirteen patients required surgical intervention. Of the patients who underwent endoscopic interventions, it was necessary to place more than one self-expandable stent of a maximum duration of 4 weeks. Six patients underwent more than two sessions of septotomy. There was one case of bleeding after septotomy. Dilatation was required in 71.4% of patients and an average of two sessions (1-5) per patient. The diagnosis of fistula occurred 14.4 days after surgery. The average time to resolve fistulas was 50.6 days. The average hospital stay was 75.8 days. The total cost of hospitalization was on average US$ 75,180.00. The surgical and endoscopic treatment of gastric fistulas after SG was safe and effective. There was a very low rate of complications. The time of onset of fistulas was not decisive for patient improvement.


A comparative study of Taxol production in liquid and solid-state fermentation with Nigrospora sp. a fungus isolated from Taxus globosa.
To determine in liquid (LF) and solid-state fermentation (SSF) the effect of medium concentration on growth and Taxol produced by Nigrospora sp., a fungus isolated from the Mexican yew. Nigrospora sp. was grown at different concentrations of the base culture medium M1D, i.e. two (2×), four (4×), six (6×) and eight times (8×) the base concentration. The titres of Taxol determined by competitive inhibition enzyme immunoassay increased with increasing medium concentration in LF and SSF but were higher in SSF in every medium concentration. The Taxol produced in SSF and LF with 8× medium was 221 and 142 ng l(-1) . The SSF gave also higher biomass, growth and sugar utilization than LF in every medium. The growth and sugar consumption were modelled by the logistic and the Pirt models, respectively. However, the Luedeking-Piret model was unsuitable for Taxol. The SSF surpassed LF in terms of Taxol, growth and sugar utilization; thus, it has significant advantages over LF. This is the first report on Taxol production by SSF and the first contribution to evaluate the influence of the medium on Taxol production in LF and SSF.


Relative affinity of Ca(II) and Mg(II) ions for human and bovine prothrombin and fragment 1.
Equilibrium dialysis results are presented for Ca(II) and Mg(II) ion binding to human and bovine prothrombin and fragment 1. Ca(II) ions bind cooperatively, Mg(II) does not.


Seed Infection Rate, but Not Pathogen Titer, Positively Correlates with Disease Index of Cephalosporium Stripe in Winter Wheat.
Cephalosporium gramineum survives primarily in colonized plant residue but is also transmitted by seed at a low frequency. The purpose of this study was to correlate disease intensity in the field with percentage of infected seed and amount of pathogen DNA using a high-throughput PCR method. Field-grown seed of three wheat cultivars was collected over 4 years from plots with a known disease index. The culture-based seed infection rate was determined by isolation of C. gramineum from 2,016 seeds per seed lot. DNA of 380 seeds from each seed lot was extracted individually, and a PCR assay with a fluorescent-labeled forward primer for detecting C. gramineum was performed on each seed. C. gramineum was isolated from 0.12% of the seed on average (range 0 to 0.74%), whereas it was detected in 3.7% on average (range 1.3 to 7.6%) using PCR detection. The single-seed PCR assay was more sensitive than either the culture-based method or conventional PCR. DNA of 674 seeds that tested positive by this PCR was quantified using a real-time PCR with newly designed primers for the amount of pathogen per seed. Seed contained 0.017 to 77.1 pg/seed of C. gramineum DNA (mean 3.0 pg/seed). Disease index was positively correlated with seed infection rate but not with pathogen titer in seed. This fluorescent-labeled PCR, along with quantitative PCR, improved our understanding of seed transmission of C. gramineum in wheat.


A generalized algorithm for determining category size.
A revision and extension of Vandermeer's algorithm for choosing size categories from demographic data is presented along with an example of its use. The extension permits an exact consideration of sample populations which may have different underlying transition probabilities at different census periods and/or within different subpopulations. Once categories are chosen transition matrices may be computed to investigate the dynamics of the population.


Tobacco industry attempts to counter the World Bank report Curbing the Epidemic and obstruct the WHO framework convention on tobacco control.
In 1999 the World Bank published a landmark study on the economics of tobacco control, Curbing the Epidemic: Governments and the Economics of Tobacco Control (CTE), which concluded that tobacco control brings unprecedented health benefits without harming economies, threatening the transnational tobacco companies' ability to use economic arguments to dissuade governments from enacting tobacco control policies and supporting the WHO Framework Convention on Tobacco Control (FCTC). We used tobacco industry documents to analyze how tobacco companies worked to discredit CTE. They hired public relations firms, had academics critique CTE, hired consultants to produce "independent" estimates of the importance of tobacco to national economies, and worked through front groups, particularly the International Tobacco Growers' Association, to question CTE's findings. These efforts failed, and the report remains an authoritative economic analysis of global tobacco control during the ongoing FCTC negotiations. The industry's failure suggests that the World Bank should continue their analytic work on the economics of tobacco control and make tobacco control part of its development agenda.


Functional roles of orexin in obstructive sleep apnea: From clinical observation to mechanistic insights.
Obstructive sleep apnea is the most common sleep-related breathing disorder. Repetitive episodes of the obstructive respiratory events lead to arousal, sleep fragmentation, and excessive daytime sleepiness. Orexin, also known as hypocretin, is one of the most important neurotransmitters responsible for sleep and arousal regulation. Deficiency of orexin has been shown to be involved in the pathogenesis of narcolepsy, which shares cardinal symptoms of sleep apnea and excessive daytime sleep with obstructive sleep apnea. However, the relationship between orexin and obstructive sleep apnea is not well defined. In this review, we summarize the current evidence, from in vitro, in vivo, and clinical data, regarding the association between orexin and obstructive sleep apnea. The effects of orexin on sleep apnea, as well as how the consequences of obstructive sleep apnea affect the orexin system function are also discussed. Additionally, the contrary findings are also included and discussed.


Surgical Management of Shoulder Heterotopic Ossification.
The formation of heterotopic ossification around the shoulder is a rare but potentially debilitating condition. It is found most commonly around the hip and is usually associated with an inciting event such as trauma, burn, previous surgery, or traumatic brain/spinal cord injury. The formation of shoulder heterotopic ossification following arthroscopic surgery is very uncommon, with few data pertaining to it in the current literature. Formation of heterotopic ossification in the shoulder after arthroscopic surgery typically occurs around the acromioclavicular joint and in the subacromial space. This location may lead to chronic pain and decreased mobility. The purpose of this article is to describe an arthroscopic technique for excision of heterotopic ossification.


(E)-2-Cyano-3-(substituted phenyl)acrylamide analogs as potent inhibitors of tyrosinase: A linear β-phenyl-α,β-unsaturated carbonyl scaffold.
In this study, we synthesized (E)-2-cyano-3-(substituted phenyl)acrylamide (CPA) derivatives which possess a linear β-phenyl-α,β-unsaturated carbonyl scaffold and examined their inhibitory activities against tyrosinase. CPA analogs exerted inhibitory activity against mushroom tyrosinase. Results from the docking simulation indicated that CPA2 could bind directly to the active site of mushroom tyrosinase and the binding affinity of CPA2 for tyrosinase might be higher than that of kojic acid, a well-known potent tyrosinase inhibitor. In B16F10 cells, CPA2 significantly suppressed tyrosinase activity and melanogenesis in a dose-dependent manner. At the concentration of 25μM, CPA2 exhibited tyrosinase inhibitory activity comparable to that of kojic acid with no cytotoxic effect. Results from the present study suggest that CPA2 bearing a linear β-phenyl-α,β-unsaturated carbonyl scaffold may be the potential candidate for treatment of diseases associated with hyperpigmentation and that a linear β-phenyl-α,β-unsaturated carbonyl scaffold might be closely related to potent tyrosinase inhibition.


Polychlorinated dibenzo-p-dioxins/furans and polychlorinated biphenyls in sediments and aquatic organisms from the Taihu Lake, China.
Sediments at 16 sites and muscles of four aquatic species collected in Taihu Lake were analyzed for polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) by HRGC/HRMS. The concentrations of total PCDD/Fs, PCBs and WHO-TEQ were 120.1-1315.1pg/gdw, 889.7-29747.8pg/gdw, and 0.83-17.72pgTEQ/gdw, respectively in sediments; and those in muscles were 5.49-35.84pg/gww, 1517.10-27647.98pg/gww, and 0.52-3.83pgTEQ/gww respectively. The concentrations of PCDD/Fs and PCBs in the sediments were decreasing gradually along the water flow. The pollution levels were compared with other studies and the possible sources were discussed.


The common sense of the community.
Maternal and childhood mortality are health indicators that show very wide gaps between rich and poor, and between countries. The 2022 John Dirks Global Health Award recognizes Zulfiqar Bhutta "for the development and evaluation of evidenced-based interventions in child and maternal health for marginalized populations, focusing on outcomes for the 'first thousand days' of life." Cell editor Nicole Neuman caught up with Zulfiqar to discuss how he became passionate about maternal and child health, how mentors have shaped his career, and the lessons of his work for high-income countries. Excerpts of the conversation are presented below and have been edited for clarity and conciseness.


Clinical Significance and Prognostic Value of the Expression of LAG-3 and FGL1 in Esophageal Squamous Cell Carcinoma.
In this retrospective study, we analyzed the expression of lymphocyte activating gene 3 (LAG-3) and fibrinogen-like protein 1 (FGP1) mRNA and the corresponding proteins in 78 patients with esophageal squamous cell carcinoma (ESCC) to evaluate the clinical significance and prognostic value. mRNA and protein expression were analyzed by reverse transcription PCR and Western blotting, respectively. The expression of LAG-3 and FGL1 mRNA and the corresponding proteins in tumor tissues were significantly increased in comparison with the normal esophageal mucosa. The overexpression of LAG-3 significantly correlated with the content of tumor-infiltrating lymphocytes (TILs), tumor differentiation, and TNM stage. The overexpression of FGL1 also significantly correlated with TILs, TNM stage, and lymph node metastasis. Kaplan-Meier survival analysis showed that tumor diameter, TNM stage, lymph node metastasis, LAG-3 and FGL1 protein expression were related to the progression-free survival (p<0.05). Multivariate Cox regression showed that the level of FGL1 and TNM stage were independent prognostic factors of progression-free survival. We speculated that the tumor microenvironment of ESCC induces immunosuppression due to up-regulated expression of LAG-3 and FGL1 in the tumor tissues, which promotes tumor growth.


Evaluation of chromium, cobalt and manganese in biological samples (scalp hair, blood, and urine) of Pakistani viral hepatitis (A-E) patients and controls.
The aim of the present study was to compare the level of chromium (Cr), cobalt (Co), and manganese (Mn) in biological samples (blood, urine, and scalp hair) of patients suffering from different types of viral hepatitis (A, B, C, D, and E; n = 521) of both genders, ages ranging from 31 - 45 years. For comparative study, 255 age-matched control subjects of both genders residing in the same city were selected as referents. The digests of all biological samples were analysed for Cr, Co, and Mn by electrothermal atomic absorption spectrometry (ETAAS). The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and compared with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cr, Co, and Mn were higher in blood and scalp hair samples of hepatitis patients than in age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p <0.001). These results are consistent with literature-reported data, confirming that the overload of these trace elements can directly cause lipid peroxidation and eventually hepatic damage.


Platelet-Rich Plasma and the Knee-Applications in Orthopedic Surgery.
To consolidate and synthesize the most recent evidence on the effects of platelet-rich plasma (PRP) in the knee with respect to osteoarthritis, meniscal injuries, ACL reconstruction, total knee arthroplasty (TKA), and high tibial osteotomy. PRP has been shown to be more beneficial in the context of knee osteoarthritis compared to both placebo and hyaluronic acid. Direct comparison with corticosteroid injections has been sparsely studied. It has also been shown to improve the clinical postoperative course in meniscal injuries and to a lesser extent TKA. Radiographic improvements without clinically significant benefits have been observed with ACL reconstructions treated with PRP. PRP injections may be more beneficial than other current non-surgical management options for specific knee pathologies. Further research should broaden the knowledge of PRP effects on the knee, and identify the type of PRP, growth factor distribution, and route of administration associated with the most benefit.


Down-regulation of beta1-adrenoceptors gene expression by short interfering RNA impairs the memory retrieval in the basolateral amygdala of rats.
The influence of basolateral amygdala (BLA) on memory is known to depend critically on adrenergic neurotransmission. However, the roles of noradrenergic receptors on memory retrieval have been elusive and controversial. Here, we investigated the effect of beta(1)-adrenoceptor (beta(1)-AR) on auditory fear memory in the rat BLA. We attenuated the expression of beta(1)-AR by RNA interference, a popular means to specific suppress gene expression. Bilaterally microinjection of beta(1)-AR short interfering RNA (siRNA) could reach a satisfying transfection in the BLA: beta(1)-AR protein expression was reduced transiently by siRNA in vivo at day 3. The behavioral tests indicated that memory retrieval was impaired as beta(1)-AR protein expression was prevented, and the memory was restored when the beta(1)-AR protein got back to normal level. The results suggested that beta(1)-AR might be critical for the retrieval of auditory fear memory.


Effect of vitamin E on 24(S)-hydroxycholesterol-induced necroptosis-like cell death and apoptosis.
24(S)-Hydroxycholesterol (24S-OHC) has diverse physiological and pathological functions. In particular, cytotoxic effects of 24S-OHC in neuronal cells are important in development of neurodegenerative diseases. 24S-OHC induces necroptosis-like cell death in SH-SY5Y cells expressing little caspase-8. In the present study, 24S-OHC was found to induce apoptosis as determined by caspase-3 activation in all-trans-retinoic acid (atRA)-treated SH-SY5Y cells in which expression of caspase-8 was induced. 24S-OHC-induced cell death was inhibited by α-tocopherol (α-Toc) but not by α-tocotrienol (α-Toc3) in SH-SY5Y cells regardless of whether cells were treated with atRA. In contrast, cumene hydroperoxide (CumOOH)-induced cell death was significantly inhibited by α-Toc and α-Toc3. In atRA-treated SH-SY5Y cells, generation of reactive oxygen species (ROS) was induced by stimulation with CumOOH but was not induced by stimulation with 24S-OHC. These results suggest that inhibition of 24S-OHC-induced cell death by α-Toc cannot be explained by its radical scavenging antioxidant activity. Esterification of 24S-OHC followed by lipid droplet (LD) formation due to acyl-CoA:cholesterol acyltransferase 1 (ACAT1) are key events in 24S-OHC-induced cell death in atRA-treated SH-SY5Y cells as demonstrated by inhibition of cell death by ACAT1 inhibitor. LD number was not changed by treatment with either α-Toc or α-Toc3. The different physical properties of α-Toc and α-Toc3 may account for their different inhibitory effects on 24S-OHC-induced cell death.


Characteristics of resonance in heart rate variability stimulated by biofeedback.
As we previously reported, resonant frequency heart rate variability biofeedback increases baroreflex gain and peak expiratory flow in healthy individuals and has positive effects in treatment of asthma patients. Biofeedback readily produces large oscillations in heart rate, blood pressure, vascular tone, and pulse amplitude via paced breathing at the specific natural resonant frequency of the cardiovascular system for each individual. This paper describes how resonance properties of the cardiovascular system mediate the effects of heart rate variability biofeedback. There is evidence that resonant oscillations can train autonomic reflexes to provide therapeutic effect. The paper is based on studies described in previous papers. Here, we discuss the origin of the resonance phenomenon, describe our procedure for determining an individual's resonant frequency, and report data from 32 adult asthma patients and 24 healthy adult subjects, showing a negative relationship between resonant frequency and height, and a lower resonant frequency in men than women, but no relationship between resonant frequency and age, weight, or presence of asthma. Resonant frequency remains constant across 10 sessions of biofeedback training. It appears to be related to blood volume.


Molecular Signatures for Combined Targeted Treatments in Diffuse Malignant Peritoneal Mesothelioma.
Background-There are currently no effective therapies for diffuse malignant peritoneal mesothelioma (DMPM) patients with disease recurrence. In this study, we investigated the biology of DMPM by analyzing the EGFR family, Axl, and MET, in order to assess the presence of cross-talk between these receptors, suggesting the effectiveness of combined targeted treatments in DMPM. Method-We analyzed a series of 22 naïve epithelioid DMPM samples from a single institute, two of which showed higher-grade malignancy ("progressed"). EGFR, HER2, HER3, Axl, and MET activation and expression were investigated by biochemical analysis, real-time PCR immunofluorescence, immunohistochemistry, next-generation sequencing, miRNA, and mRNA in situ hybridization. Results-In most DMPMs, a strong EGFR activation was associated with HER2, HER3, Axl, and MET co-activation, mediated mainly by receptor heterodimerization and autocrine-paracrine loops induced by the expression of their cognate ligands. Axl expression was downregulated by miRNA34a. Mutations in MET Sema domain were exclusively found in two "progressed" DMPMs, and the combined Axl and MET inhibition reduced cellular motility in a DMPM cell line obtained from a "progressed" DMPM. Conclusion-The results indicate that the coordinated activity of multiple cross-talks between RTKs is directly involved in the biology of DMPM, suggesting the combined inhibition of PIK3 and mTOR as an effective strategy that may be easily implemented in clinical practice, and indicating that the combined inhibition of EGFR/HER2 and HER3 and of Axl and MET deserves further investigation.


Achieving partial denitrification using organic matter in brewery wastewater as carbon source.
To find a cost-effective carbon source for partial denitrification (PD), brewery wastewater was utilized to test the viability of initiating PD. The Sbre (sludge from the biological treatment tank of Tsingtao Brewery Plant sewage treatment station) and Slab (sludge from laboratory) were fed with brewery wastewater at CODCr/NO3--N (C/N) ratios of 8.0-10.0 and 5.0 for 95 days at 25 ± 1 °C, respectively. The mean NO3--N to NO2--N transformation ratio (NTR) in long-term operation was 40.0% in the Sbre system and 83.2% in the Slab system. Batch tests with C/N ratio of 2.2-4.4 were conducted after 95 days incubation and the result suggested that C/N ratio of 4.3 ± 0.1 contributed more to NO2--N accumulation in both systems. Thauera bacteria, known to be beneficial for NO2--N accumulation, became the dominant community. The relative abundances of Thauera on day 95 in the Sbre and Slab system were 83.36% and 79.11%, respectively.


Evaluating drug toxicity signals: is a hierarchical classification of evidence useful or a hindrance?
Only randomized clinical trials (RCTs) are deemed suitable to determine causality, as epidemiological studies are considered not 'robust'. The objective of this study was to evaluate whether causality should remain the only consideration with drug toxicity signals. Cyclooxygenase-2 (Cox-2) inhibitors provided an example. Our study population included patients aged 40+ years prescribed Cox-2 inhibitors in the General Practice Research Database (GPRD) (N = 150 000). We estimated the risks of upper gastrointestinal (GI) events and myocardial infarction (MI). Attributable risks were estimated using simulation methodology based on various hypothetical scenarios. The risk-benefit profile was strongly related to the rate of GI events. With a RCT incidence, the GI benefits would exceed MI risks. With a 'real-life' GI incidence, the benefits did not exceed the risks substantially. The onset and offset of drug effects also predicted the magnitude of both risks and benefits. If risks and benefits occurred in different sub-groups, the risk-benefit profile varied substantially. Also, it was found that any restriction of use to patients at high risk of drug toxicity may not improve the risk-benefit profile when this restriction affected patients who would benefit most. We conclude that rigid classification of evidence is not appropriate in the monitoring of risks and benefits and all valid study evidence--not only that derived from a RCT--needs to be included. The first priority should be to consider the potential impact of a drug toxicity signal.


Sensory deprivation during development decreases the responsiveness of cricket giant interneurones.
1. The effect sensory deprivation, early in development, has on the adult response properties of identified neurones was studied in the abdominal nervous system of the cricket Acheta domesticus.2. Neural activity in the cercal-to-giant interneurone system was lowered by blocking the movement of the mechanosensitive hairs, located on each cercus, with a facial cleansing cream.3. When specimens were treated unilaterally one of a pair of homologous neurones exhibited drastically altered response properties. The neurone which received its afferent input from the treated receptors was much less sensitive to tones. Its threshold was increased approximately 20 db with respect to its untreated homologue.4. Bilateral treatment lowered the responsiveness of both of the bilaterally homologous neurones.5. Increased levels of inhibition impinging on the treated neurones accounts for part of the altered responsiveness. The inhibitory pathway is activated by the untreated mechanoreceptors.6. Control experiments demonstrate that the sensory apparatus is not injured or modified by the treatment.7. The results suggest that normal development of some invertebrate neural pathways may be more dependent on experience during ontogeny than has previously been assumed.


Progression-free and overall survival in patients with recurrent Glioblastoma multiforme treated with last-line bevacizumab versus bevacizumab/lomustine.
Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma multiforme (GBM). 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU, lomustine) monotherapy is an approved chemotherapeutical option for recurrent GBM. Recent evidence demonstrated a survival benefit of combined treatment with BEV and CCNU in patients with a first recurrence of GBM. We examined the outcome of recurrent GBM patients with BEV monotherapy versus BEV/CCNU therapy when used as last-line therapy. 35 patients with recurrent GBM treated between 2010 and 2014 were included in this retrospective study. Progression-free and overall survival was determined with reference to the beginning of BEV or BEV/CCNU therapy and initial diagnosis. 17 patients received BEV monotherapy, 18 patients received combined BEV and CCNU therapy. The impact of parameters such as IDH mutation, MGMT promoter methylation, tumor localization, histology and the number of surgeries were included in a multivariate ANOVA analysis. Furthermore, Karnofsky performance score (KPS), neurological function and toxicity were assessed. BEV/CCNU treatment led to an extension of PFS (6.11 months; 95% CL 3.41-12.98 months; log-rank p = 0.00241) and OS (6.59 months; 95% CL 5.51-16.3 months; log-rank p = 0.0238) of 2 months compared to BEV monotherapy. This survival advantage was independent of histology, IDH mutation status or the number of previous surgeries. Neurological function, KPS and toxicity were not significantly different between both treatment groups. Last-line therapy with BEV/CCNU results in a longer PFS and OS compared to BEV monotherapy and is well-tolerated. These findings confirm the role of these agents in the treatment of recurrent GBM and are in line with other studies.


Pomegranate seed oil prevents bone loss in a mice model of osteoporosis, through osteoblastic stimulation, osteoclastic inhibition and decreased inflammatory status.
In the current context of longer life expectancy, the prevalence of osteoporosis is increasingly important. This is why development of new strategies of prevention is highly suitable. Pomegranate seed oil (PSO) and its major component, punicic acid (a conjugated linolenic acid), have potent anti-inflammatory and anti-oxidative properties both in vitro and in vivo, two processes strongly involved in osteoporosis establishment. In this study, we demonstrated that PSO consumption (5% of the diet) improved significantly bone mineral density (240.24±11.85 vs. 203.04±34.19 mg/cm(3)) and prevented trabecular microarchitecture impairment in ovariectomized (OVX) mice C57BL/6J, compared to OVX control animals. Those findings are associated with transcriptional changes in bone tissue, suggesting involvement of both osteoclastogenesis inhibition and osteoblastogenesis improvement. In addition, thanks to an ex vivo experiment, we provided evidence that serum from mice fed PSO (5% by gavage) had the ability to significantly down-regulate the expression of specific osteoclast differentiation markers and RANK-RANKL downstream signaling targets in osteoclast-like cells (RAW264.7) (RANK: negative 0.49-fold vs. control conditions). Moreover, in osteoblast-like cells (MC3T3-E1), it elicited significant increase in alkaline phosphatase activity (+159% at day 7), matrix mineralization (+271% on day 21) and transcriptional levels of major osteoblast lineage markers involving the Wnt/β-catenin signaling pathways. Our data also reveal that PSO inhibited pro-inflammatory factors expression while stimulating anti-inflammatory ones. These results demonstrate that PSO is highly relevant regarding osteoporosis. Indeed, it offers promising alternatives in the design of new strategies in nutritional management of age-related bone complications.


Transcriptional Profiling Identifies the Signaling Axes of IGF and Transforming Growth Factor-b as Involved in the Pathogenesis of Osteosarcoma.
Osteosarcoma is the most common primary bone tumor in adolescents associated with skeletal development. The molecular pathogenesis of osteosarcoma has not been completely determined, although many molecular alterations have been found in human osteosarcomas and cell lines. We questioned whether (1) we could identify gene expression in osteosarcoma specimens that differs from normal osteoblasts and mesenchymal stem cells and (2) this would provide clues to the molecular pathogenesis of osteosarcoma? The whole-genome transcriptional profiles of osteosarcomas, including two primary biopsy specimens, two cell lines, two xenografts derived from patient specimens, and one from normal osteoblasts and from mesenchymal stem cells, respectively, were quantitatively measured using serial analysis of gene expression. A statistical enrichment was performed, which selects the common genes altered in each of the osteosarcomas compared with each of the normal counterparts independently. Sixty (92%) of 65 total genes that were at least twofold downregulated in osteosarcoma compared with osteoblasts and mesenchymal stem cells, could be classified in four categories: (1) seven genes in the insulin–like growth factor (IGF) signaling axis, including three of the IGF-binding proteins (IGFBP) and three of the IGFBPrelated proteins (IGFBPrP); (2) eight genes in the transforming growth factor-b (TGF-b)/bone morphogenetic protein (BMP) signaling cascade; (3) 39 genes encoding cytoskeleton and extracellular matrix proteins that are regulated by TGF-b/BMPs; and (4) six genes involved in cell cycle regulation, including tumor suppressors TP63 and p21. Based on these transcriptional profiles, a coordinated theme of clustered gene deregulation in osteosarcoma has emerged. Cell proliferation driven by the IGF axes during bone growth is unrestrained owing to downregulation of IGFBPs and cell cycle regulators. Tumor cells may be maintained in an undifferentiated state secondary to impaired TGF-b/BMP signaling. This wellpreserved pattern suggests that the alterations in the signaling axes of IGF-1 and TGF-b, in concert with cell cycle regulators, may be an important pathogenic basis of osteosarcoma. CLINIC RELEVANCE: This study provides a possible molecular basis of pathogenesis of osteosarcoma. This may help to develop new therapeutic targets and strategy for this disease. Preclinical and subsequently clinical testing of inhibitors of the IGF-1 and TGF pathways would be warranted.


Experiences of children treating functional bladder disturbances on schooldays.
After clinical urotherapeutic guidance, schoolchildren suffering from functional bladder disturbances are expected to manage treatment at school. To comply with treatment instructions the children have to visit the toilet at least every 3 h, find the sitting position facilitating relaxation of the pelvic floor, and then empty the bladder as completely as possible. They often blame failing to comply on their experiences of the school toilet. We describe the experiences of children treating functional bladder disturbances on schooldays. The study consisted of open-ended interviews of 20 schoolchildren aged 8-14 years undergoing treatment for functional bladder disturbances, and qualitative content analysis was performed. Conflicting rules, a risky toilet environment and uncertainty concerning social support at school were experienced. The children had difficulty in reconciling treatment compliance with their psychological needs. They used various tricks to avoid disclosing their bladder disturbances and enabling postponement of toilet visits. Most children gave their psychological needs priority over carrying out treatment. The physical and social school environment was not adapted to these children's needs.


Environmental controls of allergies.
Environmental controls of allergy remain a cornerstone in the management of patients who have allergic rhinitis. In the past, recommendations for environmental controls were based on common sense and the demonstration that certain methods of environmental control reduce antigen quantity. Reduction of antigen quantity is, however, only an indirect measure of whether an environmental control strategy actually reduces allergic symptoms. This article details current recommendations for reducing antigen exposure based on specific antigen sensitivities. Strategies for reduction of indoor inhalant allergens-dust mites, cockroach, molds, and house pet danders-are presented, as well as techniques for reducing exposure to outdoor inhalant allergens.


Decreased binding of polymyxin by polymyxin-resistant mutants of Salmonella typhimurium.
Polymyxin-resistant pmrA strains were shown to absorb only about 25% of the amount of polymyxin absorbed by the corresponding polymyxin-sensitive parent strains. The lipopolysaccharide from the pmrA strains bound less polymyxin than the lipopolysaccharide from the parent strains.


How and when EEG reflects changes in neuronal connectivity due to time awake.
Being awake means forming new memories, primarily by strengthening neuronal synapses. The increase in synaptic strength results in increasing neuronal synchronicity, which should result in higher amplitude electroencephalography (EEG) oscillations. This is observed for slow waves during sleep but has not been found for wake oscillations. We hypothesized that this was due to a limitation of spectral power analysis, which does not distinguish between changes in amplitudes from changes in number of occurrences of oscillations. By using cycle-by-cycle analysis instead, we found that theta and alpha oscillation amplitudes increase as much as 30% following 24 h of extended wake. These increases were interrupted during the wake maintenance zone (WMZ), a window just before bedtime when it is difficult to fall asleep. We found that pupil diameter increased during this window, suggesting the ascending arousal system is responsible. In conclusion, wake oscillation amplitudes reflect increased synaptic strength, except during the WMZ.


Translocation and metabolism of the chiral neonicotinoid cycloxaprid in oilseed rape (Brassica napus L.).
Neonicotinoids have been banned in some countries because of increased nontarget resistance and ecological toxicity. Cycloxaprid is a potentially promising substitute, but its metabolism in plants is still poorly understood. The study aims to clarify the translocation of cycloxaprid, identify its metabolites, propose possible metabolic pathways and compare differences between enantiomers in oilseed rape via 14C tracing technology and HPLC-QTOF-MS. The results showed that most cycloxaprid remained in the treated leaves, and only a small amount translocated to the anthers. Seven metabolites were identified, and the possible metabolic pathway was divided into two phases. Phase Ⅰ metabolism included two metabolites obtained via cleavage of the oxa-bridged seven-membered ring. Phase II metabolism was responsible for glucose conjugate formation. The possible metabolic pathways revealed that the proportion of phase I metabolites gradually decreased over time, and the phase II metabolites transformed from monosaccharide and disaccharide conjugates to trisaccharide and tetrasaccharide conjugates. The levels of metabolites were significantly different between the enantiomers. In particular, the main metabolite was M4, which has confirmed biological toxicity. M2 was the only metabolite detected in rapeseed. The results will promote the scientific application of cycloxaprid in agriculture and could have implications for assessing environmental risk.


A great misfortune: second traumatic spinal cord injury.
A second and a separate traumatic spinal cord injury, which results in neurological deterioration, is very rare. In this report we describe a patient who became tetraplegic after sustaining a second spinal trauma. A 27-year-old female had a C(7)-T(1) dislocation after a motor vehicle accident. She was neurologically intact and she had undergone a posterior fusion between C(6)-T(2). She made a complete recovery. Eight months after her initial trauma, she sustained a second motor vehicle accident causing a C(5) burst fracture. Second traumatic spinal cord injury is a rare entity. Motor vehicle accidents are the most common cause of this type of injury. Whatever the treatment strategy is, the best treatment modality for traumatic spinal cord injury is prevention.


The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Breast Carcinoma: A Retrospective Study.
If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy. We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327). Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.


Lonely in a Crowd: Social Isolation Profiles and Caregiver Burden Among Family Caregivers of Community-Dwelling Older Adults With Cognitive Impairment.
This study identified distinct social isolation profiles among caregivers, each formed by varied combinations of social disconnectedness and loneliness, and examined if and how the profiles were associated with caregiver burden. Latent class analysis and multivariable regression were applied to data from 266 caregivers of community-dwelling older Singaporeans with cognitive impairment. Two caregiver social isolation profiles were identified: strongly connected, not lonely (86%), and moderately connected, lonely (14%). Moderately connected and lonely caregivers tended to perceive a higher level of burden than strongly connected and not lonely caregivers. Moderately connected and lonely caregivers were also more likely to be burdened by their care recipients' poor health than their connected and not lonely counterparts. Caregivers who feel "lonely in a crowd" are vulnerable to caregiving stress and burden. Tailored interventions, such as cognitive behavioral therapy, are needed to reduce the loneliness of moderately connected caregivers.


Impact of diagnosis-related groups on the quality of postoperative care of patients with neck dissections.
Two hundred eighty patients underwent neck dissection over a 10-year period: 138 during the 5-year period before the institution of Diagnosis-Related Group (DRG) reimbursement and 142 during the 5 years after DRG regulations. A comparison of these two groups by site of tumor, stage of disease, histopathology, previous treatment, type of neck dissection, whether neck dissection was carried out alone or in combination with another procedure, presence of preexisting disease, postoperative complications, and mortality revealed no significant differences. A 35% reduction in the length of hospital stay from 16 to 10 days was identified in the post-DRG group with no detrimental effects on patient care. The variables found to have the greatest impact on length of hospital stay were the extent of operation and postoperative complications.


The detection and measurement of D-norgestrel in human milk using Sephadex LH 20 chromatography and radioimmunoassay.
An accurate sensitive method for the assay of D-norgestrel in human milk is described. The steroid is isolated from an ether extract of milk by Sephadex LH 20 chromatography in the system iso-octane-benzene-methanol (70:20:10 v/v). The radioimmunoassay utilises a specific antibody produced in rabbits against D-'norgestrel 3-(O-carboxymethyl) - oxime coupled to bovine serum albumin with D-norgestrel 3-(0-carboxymethyl) -oxime/ [125I]-iodohistamine conjugate as radioligand. Accuracy, sensitivity and blank value are satisfactory. Milk samples were obtained from three subjects treated with 30 microgram/day D-norgestrel, treatment commencing two weeks following parturition. Significant amounts of D-norgestrel were found, ranging between 92-135 pg/ml milk at the end of the first two-week treatment regimen. In two of three subjects, lower, but significant concentrations (53 pg and 35 pg/ml respectively) of steroid were found at the end of four weeks treatment. In the third subject, D-norgestrel could not be detected at this time. As a check on the specificity of the assay, three samples were submitted to additional chromatographic purification on alumina thin layer in the system benzene-cyclohexane-ethanol (70:27:3 v/v). Although this additional chromatographic step yielded somewhat lower values, agreement between the respective sets of results was good. The significance and implications of these findings are discussed.


A comparison of mezlocillin versus clindamycin/gentamicin for the treatment of postcesarean endomyometritis.
In a prospective, randomized study of 96 patients after cesarean section who had endomyometritis, there was a therapeutic cure in 35 of 47 (74.5%) patients who received mezlocillin, in comparison with 42 of 49 (85.7%) patients who received clindamycin and gentamicin (p = 0.17). Only wound infections in the study population were predictive for therapeutic outcome. Four of the five patients who received mezlocillin and none of the three patients who received clindamycin and gentamicin with wound infections were associated with therapeutic failures. This suggests mezlocillin may not be as effective as clindamycin and gentamicin in successfully treating wound infections. The number of vaginal examinations in patients sectioned for cephalopelvic disproportion was associated with increased febrile morbidity, suggesting that an excessive number of vaginal examinations should be avoided in the laboring patient.


A facile Fmoc solid phase synthesis strategy to access epimerization-prone biosynthetic intermediates of glycopeptide antibiotics.
A rapid protocol based on Fmoc-chemistry for the solid phase peptide synthesis of vancomycin- and teicoplanin-type peptides is described. Epimerization of highly racemization-prone arlyglycine derivatives is suppressed through optimized Fmoc-deprotection and coupling conditions. Starting from easily accessible Fmoc-protected amino acids, this strategy enables the enantioselective synthesis of peptides corresponding to intermediates found in vancomycin and teicoplanin biosynthesis with excellent purity and in high yields (38%-71%).


Discovery and SAR of a novel series of 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles as N-type calcium channel inhibitors.
A novel series of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles were investigated as N-type calcium channel blockers (Cav2.2 channels), a chronic pain target. One compound was active in vivo in the rat CFA pain model.


Pharmacokinetics of intravenously administered moxifloxacin in eye compartments: an experimental study.
The purpose of this study was to evaluate the pharmacokinetics of intravenously administered moxifloxacin, a fourth-generation fluoroquinolone, in different parts of the non-inflamed eye. Moxifloxacin was administered intravenously at a dose of 20mg/kg moxifloxacin over 30min. Sampling of peripheral blood, aqueous humour and vitreous was performed at standard time intervals post infusion once in each animal. Moxifloxacin levels were estimated by high-performance liquid chromatography with fluorescence detection. Mean serum concentrations were 3.43, 2.74, 1.48 and 1.12microg/mL at 0.5, 3, 6 and 24h after the end of drug infusion, respectively. Respective concentrations in aqueous humour were 2.44, 2.03, 1.30 and 1.09microg/mL and in vitreous body they were 1.68, 1.87, 1.78 and 1.15microg/mL. It is concluded that systemic administration of moxifloxacin in rabbits was accompanied by efficient penetration into both the aqueous humour and the vitreous body at concentrations well above the minimum inhibitory concentration for most causative pathogens of endophthalmitis. Further research is mandatory to clarify the clinical significance of these findings.


Icariside II protects against cerebral ischemia-reperfusion injury in rats via nuclear factor-κB inhibition and peroxisome proliferator-activated receptor up-regulation.
Icariside II (IRS) is a metabolite of icariin, which is derived from Herba Epimedii. Although the potential therapeutic effects of icariin on ischemic brain injury were well-investigated; the role of IRS in ischemic stroke is still not addressed clearly. Therefore, the current study aimed to evaluate the effects of IRS on cerebral ischemia-reperfusion injury in rats. The rats were pre-treated by IRS (10 or 30 mg kg(-1), twice a day) for 3 days. After pre-treatment, a MCAO (middle cerebral artery occlusion) for 2 h followed by reperfusion for 24 h was applied on the rats to induce the cerebral ischemia injury model. The neurological deficit scores were assessed at 24 h after reperfusion, then animals were sacrificed, infarct volumes were determined by 2,3,5-triphenyltetrazolium chlorid (TTC) staining and protein expression levels of interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), inhibitory κB (IκB), nuclear factor κB (NF-κB) p65, peroxisome proliferator-activated receptor α (PPARα), and peroxisome proliferator-activated receptor γ (PPARγ) were assayed by using Western blot. IRS pretreatment markedly improved the neurological dysfunction and decreased infarct volume in MCAO rats. In addition, IRS inhibited IL-1β and TGF-β1 protein expression, and resulted in beneficial effects such as inhibition of IκB-α degradation and NF-κB activation induced by MCAO, in a dose-dependent manner. Furthermore, IRS increased the protein expression levels of PPARα and PPARγ in the ischemic brain. In conclusion, pretreatment with IRS protects against cerebral ischemic/reperfusion injury via up-regulation of PPARα and PPARγ and inhibition of NF-κB activation.


Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. I. Stimulus intensity.
Paired pulse stimulation of the perforant path provides a measure of inhibition of dentate granule cell field potentials that is reflected in the depression of the second (test) population spike (PS) relative to the first (conditioning) PS. The assumption that the strength of paired pulse depression is dependent upon the amplitude of the conditioning PS was investigated by increasing the stimulus intensity of both pulses (5-100% of maximum, Experiment 1), or by increasing the stimulus intensity of the conditioning pulse (5-100%) while maintaining a constant stimulus intensity of the test pulse (50%, Experiment 2). In both experiments, the threshold for early paired pulse depression (20 ms interpulse interval, IPI) was reached with moderate stimulation (30-40% of maximum). Above threshold, the test PS was depressed to a relatively constant amplitude in Experiment 1, in contrast to a nearly linear decrease observed in Experiment 2 with increasing strength of early paired pulse, relative to the conditioning reflects the lower stimulus intensity of the test pulse, relative to the conditioning pulse, in the second study, thereby allowing the increasing strength of early paired pulse depression to be detected more easily. The threshold for late paired pulse depression was reached near (20%, Experiment 1) or below (5%, Experiment 2) the PS threshold of dentate granule cells, and a paradoxical decrease in late paired pulse depression was detected with maximal stimulation in both studies. Together, these results suggest that early paired pulse depression exhibits a strong dependence upon the amplitude of the conditioning PS, whereas late paired pulse depression is marginally affected by the conditioning PS amplitude and is influenced by additional processes at both extremes of the stimulus intensity continuum.


The Impact of Chronic Repetitive Leg Ischemia on Left Ventricular Function and Severity of Coronary Atherosclerosis in Patients with Acute Coronary Syndrome.
The purpose of this study was to assess the impact of the presence of peripheral arterial disease (PAD) on left ventricular (LV) function in patients with coronary artery disease (CAD) presenting with acute coronary syndrome (ACS). The medical records of the patients who were referred to Ankara Bayindir Hospital, Ankara, Turkey, due to a first episode of ACS were reviewed. Patients with concomitant PAD and CAD (group 1) were compared with those who had CAD only (group 2). The Mann-Whitney U and χ2 tests were used to compare continuous and categorical variables, respectively. Baseline demographic data of 53 patients with PAD + CAD (42 men and 11 women; mean age 62.5 ± 9.5 years) and a group of 60 patients with CAD only (41 men and 19 women; mean age 59.9 ± 9.8 years) were similar, except for the serum creatinine level which was higher in group 1 than in group 2 (1.32 ± 0.34 vs. 1.03 ± 0.22 mg/dL, p < 0.001). Patients with CAD + PAD had significantly higher Gensini scores (62.6 ± 19.7 vs. 41.4 ± 26.8, p = 0.004) and more 3-vessel disease than patients with CAD alone (62.2 vs. 31.6%, p < 0.045). There was a significant difference between the 2 groups regarding the LV ejection fraction at the time of the diagnosis (52.0 ± 8.2% in the CAD + PAD group and 43.7 ± 13.3% in the CAD-alone group; p = 0.017). CAD concomitant with PAD was associated with preserved LV function at early stages of diagnosis in patients with ACS.


Risk factors associated with physical therapist burnout: a systematic review.
Studies consistently suggest that work as a physical therapist is associated with burnout, yet no review of the contributing factors has been conducted. To identify and examine the risk factors associated with physical therapist burnout. PubMed, Embase, CINAHL, and the Cochrane Library were searched from inception to May 2020. Quantitative studies of physical therapists in clinical practice who experience burnout symptoms or syndrome. Risk factors such as characteristics of the participant, environment, structures, and experiences that demonstrate a significant predisposition to burnout were extracted. The modified Downs and Black checklist was used to identify risk of bias. Forty-six studies (8717 participants) were included. The risk of bias assessment determined all were of fair or poor quality. Fifty-three risk factors were identified, with four being classified as unavoidable and forty-nine determined as avoidable. The avoidable risk factors were further categorized as either structural/organizational (32%), psychological/emotional (19%), environmental (19%), or sociodemographic (13%). A risk factor's importance may not correlate with its prevalence, and the low-quality studies limit the ability to make definitive conclusions. A significant amount of literature has identified a wide variety of risk factors. The majority are avoidable, and the effect and degree to which each risk factor contributes to burnout varies. The identified risk factors can help develop targeted prevention and intervention strategies for the benefit of physical therapists, organizations, and policymakers. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. PROSPERO CRD42020136356.


Korkormicins, novel depsipeptide antitumor antibiotics from Micromonospora sp C39500: fermentation, precursor directed biosynthesis and biological activities.
Micromonospora sp C39500, isolated in our laboratory from a soil sample, produced a complex of seven novel depsipeptide antitumor antibiotics, designated korkormicins. The major component of the complex, korkormicin A, has a MW of 1452 and a molecular formula of C66H84N16O22. Korkormicin A exhibits potent in vivo antitumor activity against P388 leukemia and M109 lung carcinoma implanted intraperitoneally (ip) in mice, with effective doses of 0.05-0.20 mg kg-1 injection-1, for five or three ip injections, respectively. It is also active against Gram-positive bacteria but inactive against Gram-negative bacteria. The production of korkormicin A was enhanced by 3-fold when 0.1% L-valine was added to the production culture at 48 h. A titer of 401.0 micrograms ml-1 was achieved in the fermenter culture supplemented with 0.1% L-valine.


Apoptosis of primary sensory neurons in GD1b-induced sensory ataxic neuropathy.
Experimental autoimmune sensory ataxic neuropathy was induced in three of six rabbits sensitized with GD1b ganglioside (GD1b-SAN). TUNEL assay was performed on sections of dorsal root ganglia in the cauda equina. The results showed the presence of TUNEL-positive neurons in all three rabbits affected with GD1b-SAN. In contrast, no such neurons were observed in any of the sections from the unaffected rabbits that had been inoculated with GD1b, rabbits inoculated with adjuvant alone or those without inoculation. These data support that an apoptotic mechanism is involved in the pathogenesis of GD1b-SAN.


How to prevent the retiring brain from degenerating.
In organs other than the brain, cell activation seems to increase "wear and tear", e.g. by increased free-radical formation, and so to cause an increased rate of aging. However, activation of nerve cells within the physiological range seems to lead to maintenance of neurons during aging, possibly by preferentially stimulating the action of protective mechanisms such as DNA repair. This "use it or lose it" principle might explain why in aging and neurodegenerative diseases certain neurons degenerate while others do not, and why recovery of various neuronal systems during aging has been obtained by restoration of the missing stimulus. Consequently, neuronal activation might provide a means of prolonging its optimal function for the full length of our natural life span, also following retirement.


Microbial community response to ammonia levels in hydrogen assisted biogas production and upgrading process.
Biological conversion of carbon dioxide into methane using hydrogen derived from surplus renewable energy (wind power) as reducing power is a novel technology for biogas upgrading. High ammonia concentrations are toxic to the biogas upgrading process, however the mechanisms behind the inhibition as well as the microbial stress response in such unique upgrading system have never been reported. Thus, the effect of high ammonia concentrations on microbial community during hydrogen induced biogas upgrading process was evaluated here. The results showed that a change from aceticlastic pathway to hydrogenotrophic pathway occurred when ammonia level increased (1-7 g NH4+-N L-1). In addition, the bacteria, potentially syntrophic associated with hydrogenotrophic methanogens, were enriched at high ammonia concentrations. Moreover, growth of some bacteria (e.g., Halanaerobiaceaeen and Leucobacter) which were vulnerable to ammonia toxicity was restored upon hydrogen injection. Furthermore, hydrogen injection under high ammonia concentration could promote growth of some hydrolytic and fermentative bacteria.


Endoscopic treatment of vesicoureteral reflux: 11 to 17 years of followup.
We review our 17-experience with endoscopic subureteral polytetrafluoroethylene injection for the treatment of primary vesicoureteral reflux in children. We retrospectively reviewed the charts of 258 patients with primary vesicoureteral reflux who were treated with subureteral polytetrafluoroethylene injection from 1984 to 1990. The study included 205 girls and 53 boys between 3 months and 14 years old (median age 6 years). Of the patients 92 had unilateral vesicoureteral reflux, 129 had bilateral reflux and 37 had a refluxing duplex system including 6 with bilateral duplex systems. Endoscopic treatment by subureteral polytetrafluoroethylene injection was performed in 393 ureters. Reflux was corrected in 302 ureters (76.8%) after a single injection. Injection failed to stop reflux in 7 ureters (7 patients) and reimplantation was required. Patients were followed from 11 to 17 years with a mean followup plus or minus standard deviation of 13.5 +/- 3.4 years. Four patients were either lost to followup or parents refused to let them undergo voiding cystourethrography. Voiding cystourethrography in 247 patients with 379 ureters revealed that 360 ureters (95%) remain free of reflux whereas reflux recurred in 19 ureters (5%). Of these 19 ureters reflux was grade I or II in 13 for which no treatment was given and reflux was grade III or IV in 6, which required repeat injection. No untoward effects were seen in any of these patients with use of polytetrafluoroethylene as an injectable biomaterial. Endoscopic subureteral polytetrafluoroethylene injection is a simple and effective outpatient procedure for in the treatment of vesicoureteral reflux. No long-term morbidity was observed in our patients with small amounts of injectable polytetrafluoroethylene.


PUBG-related suicides during the COVID-19 pandemic: Three cases from Pakistan.
The present case report presents the most extreme negative aspects of gaming, namely PUBG-related suicide during the coronavirus disease-2019 pandemic in Pakistan. Three suicide cases of extreme gamers occurred within a few days of each other in Lahore, Pakistan. All three were young males aged 16-20 years and their suicides appear to be related to PUBG addiction. It is likely that all three individuals experienced other predisposing factors relating to psychological instability. For vulnerable groups such as adolescents and emerging adults who have psychological predispositions and/or other comorbidities, engrossing videogames which take up many hours a day such as PUBG may pose a risk which in the most extreme cases may be fatal.


Hypoxia-inducible factor 1α mediates the down-regulation of superoxide dismutase 2 in von Hippel-Lindau deficient renal clear cell carcinoma.
Hypoxia-inducible factor 1α (HIF-1α) is an oxygen-sensitive subunit of HIF-1, the master transcription factor for cellular response to hypoxia. Down-regulation of the mitochondrial enzyme superoxide dismutase 2 (SOD2) contributes to the stabilization of HIF-1α under hypoxia due to the decreased dismutation of superoxide radical. Here we report that HIF-1α could also regulate the expression of SOD2. We found that both stabilization of HIF-1α expression under nomoxia caused by pVHL deficiency and hypoxia treatment significantly reduced SOD2 expression, and shRNAs specifically against HIF-1α restored SOD2 expression in both circumstances. Further analyses with luciferase reporter assay and chromatin immunoprecipitation assay revealed that HIF-1α inhibited and directly bound to the hypoxia-responsive element in SOD2 promoter. These findings indicated the existence of a positive feedback between HIF-1α and SOD2 and provided new clues for understanding the molecular mechanisms of hypoxia adaptation.


The role of sophisticated radiological testing in the assessment and management of epiphora.
In the management of a patient with epiphora, appropriate investigation is important in arriving at the cause of obstruction, and in helping to outline a plan for management. Standard dacryocystography has been modified by utilizing the techniques of intubation, distension, macrography, and subtraction to produce optimal anatomical information. Lacrimal nuclear scanning with the addition of rapid sequence display and computer interfacings produce the most sophisticated functional information regarding tear drainage. The role of plain films and computerized tomography in lacrimal drainage pathway disease is outlined.


Effects of cooling methods on silver-palladium castings.
Cast metal specimens for three ceramic metals were subjected to two different types of cooling procedures after casting. One method involved the rapid cooling of the casting as soon as the red glow of the button disappeared. The other method allowed the castings to bench cool to room temperature. Hardness, bond strength, and microstructural determinations lead to the following conclusions. 1. Vickers hardness values for W-1 and Rx-91 alloys for each cooling regimen were not significantly different. Statistically higher hardness values were obtained for the quenched specimens of JP-5 alloys compared with the bench-cooled specimens. 2. Cooling of W-1 and JP-5 alloy specimens by quenching resulted in higher bond strengths than for specimens that were bench-cooled to room temperature. However, bench-cooling Rx-91 alloy lead to higher bond strengths than did quenching. 3. For all of the alloys examined, quenching produced a smaller grain structure than did bench-cooling. 4. From the standpoint of the parameters tested and the saving of processing time, quenching of the silver-palladium ceramic alloys examined is the cooling procedure of choice for W-1 and JP-5 alloys.


Emotion Analysis of COVID-19 Vaccines Based on a Fuzzy Convolutional Neural Network.
COVID-19 created immense global challenges in 2020, and the world will live under its threat indefinitely. Much of the information on social media supported the government in addressing this major public health event. On January 9, to control the virus, the Chinese government announced universal vaccinations. However, due to a range of varied interpretations, people held different attitudes towards vaccination. Therefore, the success of the mass immunization strategy greatly depended on the public perception of the COVID-19 vaccine. This article explores the changes in people's emotional attitudes towards vaccines and the reasons behind them in the context of the global pandemic in an effort to help mankind overcome this ongoing crisis. For this article, microblogs from January to September containing Chinese people's responses to the COVID-19 vaccines were collected. Based on fuzzy logic and deep learning, we advance the hypothesis that fuzzy vector adaptive improvements will make it possible to better express language emotion and that fuzzy emotion vectors can be integrated into deep learning models, thus making these models more interpretable. Based on this assumption, we design a deep learning model with a fuzzy emotion vector. The experimental results show the positive effect of this model. By applying the model in analyses of people's attitudes towards vaccines, we can obtain people's attitudes towards vaccines in different time periods. We discovered that the most negative emotions about the vaccine appeared in April and that the most positive emotions about the vaccine appeared in February. Combined with word cloud technology and the LDA model, we can effectively explore the reasons for the changes in vaccine attitudes. Our findings show that people's negative emotions about the vaccine are always higher than their positive emotions about the vaccine and that people's attitudes towards the vaccine are closely related to the progress of the epidemic. There is also a certain relationship between people's attitudes towards the vaccine and those towards the vaccination.


The NADPH-cytochrome P450 reductase family in Trypanosoma cruzi is involved in the sterol biosynthesis pathway.
Trypanosoma cruzi flavoproteins TcCPR-A, TcCPR-B and TcCPR-C are members of the NADPH-dependent cytochrome P-450 reductase family expressed in the parasite. Epimastigotes over-expressing TcCPR-B and TcCPR-C showed enhanced ergosterol biosynthesis and increased NADP(+)/NADPH ratio. Transgenic parasites with augmented ergosterol content presented a higher membrane order with a corresponding diminished bulk-phase endocytosis. These results support a significant role for TcCPR-B and TcCPR-C in the sterol biosynthetic pathway and to our knowledge for the first time reveals the participation of more than one CPR in this metabolic route. Notably, TcCPR-B was found in reservosomes while TcCPR-C localised in the endoplasmic reticulum. In addition, we suggest a different role for TcCPR-A, since its over-expression is lethal, displaying cells with an increased DNA content, aberrant morphology and severe ultrastructural alterations.


Thyroid V40 is a good predictor for subclinical hypothyroidism in patients with nasopharyngeal carcinoma after intensity modulated radiation therapy: a randomized clinical trial.
Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of life. The percentage of thyroid volume receiving more than 40 Gy (V40) ≤ 85% was reported to be a useful dose constraint to adopt during intensity-modulated radiation therapy (IMRT) planning. This study aims to verify whether V40 ≤ 85% can be used as an effective dose constraint in IMRT planning in a randomized clinical trial. This single-center 1:1 randomized clinical trial was conducted in Fujian province hospital between March 2018 and September 2022. All patients were treated with IMRT and randomized to induction chemo followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Ninety-two clinically NPC patients were included in this study. The thyroid function tests were performed for all patients before and after radiation at regular intervals. Thyroid dose-constraint was defined as V40 ≤ 85%. The primary outcome in this study was subclinical HT. Median follow up was 34 months. Significant difference in the incidence of subclinical HT between the thyroid dose-constraint group and unrestricted group was observed (P = 0.023). The risk of subclinical HT in the thyroid dose-constraint group was lower than that in the unrestricted group (P = 0.022). Univariate and multivariate cox regression analysis indicated that thyroid dose-constraint was a protective effect of subclinical HT (HR = 0.408, 95% CI 0.184-0.904; HRadjusted = 0.361, 95% CI 0.155-0.841). V40 ≤ 85% can be used as an effective dose constraint in IMRT planning to prevent radiation-induced subclinical HT.


A pupillometric correlate of scotopic visual acuity.
While not easily fit into the classic descriptions of the pupillary light reflex, previous studies reported that changes in the spatial composition of the retinal image can evoke a pupillary response. The present study extends this observation by showing that the pupil constricts in response to scotopic as well as photopic spatial patterns. Moreover, the amplitude of the scotopic response decreases with increasing spatial frequencies suggesting a pupillary spatial acuity of about 3 c/deg. The scotopic pupil acuity is similar to the scotopic perceptual visual acuity measured in the same observers.


The collaborative monitored natural attenuation (CMNA) of soil and groundwater pollution in large petrochemical enterprises: A case study.
A large in-service petrochemical enterprises in Northeast China was taken as the research object, and the Collaborative Monitored Natural Attenuation (CMNA) for soil and groundwater pollution was carried out to remedy combined pollution and reduce environmental risks. The pollutants distributions were obtained based on detailed regional investigation (Mar. 2019), and feature pollutants in soil and groundwater were then screened. The spatiotemporal variations of feature pollutants and relative microbial responses were explored during the CMNA process. Furthermore, the CMNA efficiency of the contaminated site at initial stage was evaluated by calculation of natural attenuation rate constant. The results showed that the feature pollutants in soil were 2,2',5,5'-tetrachlorobiphenyl (2,2',5,5'-TCB) and petroleum hydrocarbons (C10∼C40), and the feature pollutant in groundwater was 1,2-dichloroethane (1,2-DCA). The concentrations of all feature pollutants decreased continuously during four years of monitoring. Feature pollutants played a dominant role in the variability of microbial species both in soil and groundwater, increasing the relative abundance of petroleum tolerant/biodegradation bacteria, such as Actinobacteria, Proteobacteria and Acidobacteriota. The average natural attenuation rate constant of 2,2',5,5'-TCB and C10∼C40 in soil was 0.0012 d-1 and 0.0010 d-1, respectively, meeting the screening value after four years' attenuation. The average natural attenuation rate constant of 1,2-DCA was 0.0004 d-1, which need strengthening measures to improve the attenuation efficiency.


Expression of gap-junctional protein (connexin 43 or alpha 1 gap junction) is down-regulated at the transcriptional level during adipocyte differentiation of H-1/A marrow stromal cells.
Bone marrow stromal cells are requisite for the proliferation of hematopoietic cells and communicate with each other via gap junctions. Marrow stromal cells expressed connexin 43, but not connexin 32. H-1/A, a murine marrow stromal cell line, underwent adipocyte differentiation at confluence, and expressed the 3.0 kilobase mRNA species of connexin 43 before differentiation. H-1/A cells studied with the dye-transfer method showed gap-junctional communication with adjacent cells but lost this communication during differentiation. The connexin 43 transcripts in H-1/A cells were down-regulated before the expression of glycero-monophosphate dehydrogenase was induced. Loss of gap-junctional communication was regulated at the mRNA level of connexin 43. Connexin 43 expression was down-regulated at the transcriptional level.


A complex response element in intron 1 of the androgen-regulated 20-kDa protein gene displays cell type-dependent androgen receptor specificity.
The androgen-regulated 20-kDa protein gene consists of four exons that code for a major secretory protein of rat ventral prostate. Analysis of its potential cis-acting transcriptional regulatory elements revealed that a large intron 1 region (In-1) had stronger androgen response element (ARE) activity than did the 5'-flanking DNA. In cotransfected CV1 cells, In-1 and its most active subfragment In-1c functioned as AREs but not glucocorticoid response elements (GRE). Nevertheless several ARE/GRE-like partial palindromic sequences are present in In-1c, and it bound both androgen receptors and glucocorticoid receptors in mobility shift assays. A cluster of three ARE/GRE-like sequences contained within a 39-base pair sequence of In-1c had both ARE and GRE activities when analyzed as an isolated oligonucleotide, suggesting that other elements within In-1c determined its ARE specificity. In addition to ARE/GRE-like sequences, In-1c contains putative response elements for the transcription factors AP1, CREB, AP2, OCT-1, C/EBP, and a number of inverted and direct repeats. The ARE specificity of In-1c observed in CV1 cells was diminished in PC3 and HeLa cells transiently cotransfected with an androgen receptor or glucocorticoid receptor expression vector together with an In-1c reporter vector; however, the ARE activity of In-1c was greater than its GRE activity in these cell lines. Interestingly, a 131-base pair subfragment of In-1c retained ARE specificity in all three cell lines.


Reconstruction of Wassel IV-D radial polydactyly with a boot-shaped neurovascular island flap: A Consecutive series of 91 thumbs.
Reconstruction of Wassel IV-D radial polydactyly is challenging and requires a custom strategy dependent on the relative size and shape of the radial and ulnar duplicates. Herein, we describe a technique using a boot-shaped neurovascular island flap and review our outcomes. Ninety-one consecutive patients had reconstruction with a boot-shaped neurovascular island flap. The flap was dissected out from the thumb to be removed. Specific flap modifications were inclusion of the lateral nail fold, Bruner incisions dorsally and volarly to reduce scarring at the interphalangeal (IP) joint and also complete mobilization of the island flap on its pedicle to allow easier inset. A flexor pollicis longus and extensor tendon rebalancing technique was used to correct the deviation of the reconstructed thumb IP joint. All boot-shaped neurovascular island flaps survived with good contour, shape, and symmetry. The average follow-up period was 25 months (range 6-60 months). Using the Japanese Society for Surgery of the Hand (JSSH) score for classification of outcomes, seven cases were classified as excellent and 84 cases as good. The median JSSH score was 18. The median Kapandji score for opposition was 9 (range 8-10). Using a boot-shaped neurovascular island flap completely mobilized on its pedicle with a custom strategy for each radial duplicate, good outcomes can be achieved in reconstruction of Wassel IV-D radial polydactyly. Therapeutic Level IV.


Microscopic insights into the variations of antibiotics sorption to clay minerals.
Understanding the adsorption behavior of antibiotic molecules on minerals is crucial for determining the environmental fate and transport of antibiotics in soils and waters. However, the microscopic mechanisms that govern the adsorption of common antibiotics, such as the molecular orientation during the adsorption process and the conformation of sorbate species, are not well understood. To address this gap, we conducted a series of molecular dynamics (MD) simulations and thermodynamics analyses to investigate the adsorption of two typical antibiotics, tetracycline (TET) and sulfathiazole (ST), on the surface of montmorillonite. The simulation results indicated that the adsorption free energy ranged from - 23 to - 32 kJ·mol-1, and - 9 to - 18 kJ·mol-1 for TET and ST, respectively, which was consistent with the measured difference of sorption coefficient (Kd) for TET-montmorillonite of 11.7 L·g-1 and ST-montmorillonite of 0.014 L·g-1. The simulations also found that TET was adsorbed through dimethylamino groups (85% in probability) with a molecular conformation vertical to the montmorillonite's surface, while ST was adsorbed through sulfonyl amide group (95% in probability) with vertical, tilted and parallel conformations on the surface. The results confirmed that molecular spatial orientations could affect the adsorption capacity between antibiotics and minerals. Overall, the microscopic adsorption mechanisms revealed in this study provide critical insights into the complexities of antibiotics adsorption to soil and facilitate the prediction of adsorption capacity of antibiotics on minerals and their environmental transport and fate. This study contributes to our understanding of the environmental impacts of antibiotic usage and highlights the importance of considering molecular-level processes when assessing the fate and transport of antibiotics in the environment.


Waldenström macroglobulinemia whole genome reveals prolonged germinal center activity and late copy number aberrations.
The genomic landscape of Waldenström macroglobulinemia (WM) is characterized by somatic mutations in MYD88, present from the precursor stages. Using the comprehensive resolution of whole genome sequencing (WGS) in 14 CD19-selected primary WM samples; comparing clonal and subclonal mutations revealed that germinal center (GC) mutational signatures SBS9 (poly-eta) and SBS84 (AID) have sustained activity, suggesting that the interaction between WM and the GC continues over time. Expanding our cohort size with 33 targeted sequencing samples, we interrogated the WM copy number aberration (CNA) landscape and chronology. Of interest, CNA prevalence progressively increased in symptomatic WM and relapsed disease when compared with stable precursor stages, with stable precursors lacking genomic complexity. Two MYD88 wild-type WGS contained a clonal gain affecting chromosome 12, which is typically an early event in chronic lymphocytic leukemia. Molecular time analysis demonstrated that both chromosomal 12 gain events occurred early in cancer development whereas other CNA changes tend to occur later in the disease course and are often subclonal. In summary, WGS analysis in WM allows the demonstration of sustained GC activity over time and allows the reconstruction of the temporal evolution of specific genomic features. In addition, our data suggest that, although MYD88-mutations are central to WM clone establishment and can be observed in precursor disease, CNA may contribute to later phases, and may be used as a biomarker for progression risk from precursor conditions to symptomatic disease.


Self-narrative reconstruction after dilemma-focused therapy for depression: A comparison of good and poor outcome cases.
The aim of this study is to improve the understanding of self-changes after an intervention for depression focused on implicative dilemmas, a type of cognitive conflict related to identity. As recent research has highlighted the relevance of identity-related dilemmas in clients with depression, we sought to assess the way in which clients resolve such inner conflicts after a tailored dilemma-focused intervention and how this is reflected in the clients' self-narratives. We used three instruments to observe differences between good (n = 5) and poor (n = 5) outcome cases: (i) the Repertory Grid Technique to track the resolution of dilemmas, (ii) the Change Interview to compile clients' accounts of changes at posttreatment, and (iii) the Innovative Moments Coding System to examine the emergence of clients' novelties at the Change Interview. Groups did not differ in terms of the number and relevance of client-identified significantly helpful events. However, between-group differences were found for the resolution of dilemmas and for the proportion of high-level innovative moment (IM) types. Furthermore, a greater self-narrative reconstruction was associated with higher levels of symptom improvement. Good outcome cases seem to be associated with the resolution of conflicts and high-level IMs.


Tertiary structure of RNase Pch1 predicted from the model structure of RNase Ms and the crystal structure of RNase T1. Comparison among the model structures--testing the limits of modelling by homology.
In this paper we predict the structure of RNase Pch1 as modelled from the previously predicted structure of RNase Ms and the crystal structure of RNase T1 in the complex with 2'GMP. The predicted structures and their initial energy minimized structural RNase T1 template are compared. The predicted structures of RNase Pch1 show, independent of their prediction form RNase Ms or T1, a higher structural similarity to RNase T1 than to RNase Ms, in agreement with higher sequence similarity and specificity - RNases T1 and Pch1 are specific for guanine whereas RNase Ms is base-unspecific with preference for guanine.


Halide coordinated homoleptic [Fe4S4X4](2-) and heteroleptic [Fe4S4X2Y2](2-) clusters (X, Y = Cl, Br, I)--alternative preparations, structural analogies and spectroscopic properties in solution and solid state.
New facile methods to prepare iron sulphur halide clusters [Fe4S4X4](2-) from [Fe(CO)5] and elemental sulphur were elaborated. Reactions of ferrous precursors like tetrahalidoferrates(ii) or simple ferrous halides with [Fe(CO)5] and sulphur turned out to be efficient methods to prepare homoleptic [Fe4S4X4](2-) (X = Cl, Br) and heteroleptic clusters [Fe4S4X4-nYn](2-) (X = Cl, Br; Y = Br, I). Solid materials were obtained as salts of BTMA(+) (= benzyltrimethylammonium); the new compounds containing [Fe4S4Br4](2-) and [Fe4S4X2Y2](2-) (X, Y = Cl, Br, I) were all isostructural to (BTMA)2[Fe4S4I4] (monoclinic, Cc) as inferred from synchrotron X-ray powder diffraction. While the solid materials contain defined heteroleptic clusters with a halide X : Y ratio of 2 : 2, dissolving these compounds leads to rapid scrambling of the halide ligands forming mixtures of all five possible [Fe4S4X4-nYn](2-) clusters as could be shown by UHR-ESI MS. The variation of X and Y allowed assignment of the absorption bands in the visible and NIR; the long-wavelength bands around 1100 nm were tentatively assigned to intervalence charge transfer (IVCT) transitions.


Rapid detection and differentiation of Clonorchis sinensis and Opisthorchis viverrini eggs in human fecal samples using a duplex real-time fluorescence resonance energy transfer PCR and melting curve analysis.
We developed a single step duplex real-time fluorescence resonance energy transfer (FRET) PCR merged with melting curve analysis for the fast detection and differentiation of Clonorchis sinensis and Opisthorchis viverrini eggs in human fecal samples. Two species of mitochondrial NADH dehydrogenase subunit 2 (nad2) DNA elements, the 165-bp nad2 product of C. sinensis and the 209-bp nad2 product of O. viverrini, were amplified by species-specific primers, and the fluorescence melting curve analyses were generated from hybrid of amplicons and two pairs of species-specific fluorophore-labeled probes. By their different fluorescence channels and melting temperatures, both C. sinensis and O. viverrini eggs in infected human fecal samples were detected and differentiated with high (100%) sensitivity and specificity. Detection limit was as little as a single C. sinensis egg and two O. viverrini eggs in 100 mg of fecal sample. The assay could distinguish the DNA of both parasites from the DNA of negative fecal samples and fecal samples with other parasitosis, as well as from the well-defined genomic DNA of human leukocytes and other parasites. It can reduce labor time of microscopic examination and is not prone to carry over contamination of agarose electrophoresis. Our duplex real-time FRET PCR method would be useful to determine the accurate range of endemic areas and/or to discover the co-endemic areas of two liver flukes, C. sinensis and O. viverrini, in Asia. This method also would be helpful for the differential diagnosis of the suspected cases of liver fluke infections among travelers who had visited the endemic countries of those parasites.


Gel electrophoretic analysis of proteins in human milk and colostrum.
Protein patterns of skim milk and fat globule phases were relatively unchanging throughout 9 months lactation, the only notable differences being a rise in lysozyme and a decline up to 6 months with increase thereafter in lactoferrin. Profound changes in protein patterns of the breast secretion were observed during the first week postpartum. True colostrum, in which peptides of sIgA dominate the protein patterns, exists for at most the 2 initial days of secretion. Proteins of mature milk are not coordinated to appear in the colostral secretion simultaneously. A band corresponding to alpha-lactalbumin is present from the initial secretion; that for beta-casein emerges approximately 2 days layer.


Validation of stationary phases in (111)In-pentetreotide planar chromatography.
Since Pall-German stopped manufacturing ITLC-SG, it has become necessary to validate alternative stationary phases. To validate different stationary phases versus ITLC-SG Pall-Gelman in the determination of the radiochemical purity (RCP) of (111)In-pentetreotide ((111)In-Octreoscan) by planar chromatography. We conducted a case-control study, which included 66 (111)In-pentetreotide preparations. We determined the RCP by planar chromatography, using a freshly prepared solution of 0,1M sodium citrate (pH 5) and the following stationary phases: ITLC-SG (Pall-Gelman) (reference method), iTLC-SG (Varian), HPTLC silica gel 60 (Merck), Whatman 1, Whatman 3MM and Whatman 17. For each of the methods, we calculated: PRQ, relative front values (RF) of the radiopharmaceutical and free (111)In, chromatographic development time, resolution between peaks. We compared the results obtained with the reference method. The statistical analysis was performed using the SPSS program. The p value was calculated for the study of statistical significance. The highest resolution is obtained with HPTLC silica gel 60 (Merck). However, the chromatographic development time is too long (mean=33.62minutes). Greater resolution is obtained with iTLC-SG (Varian) than with the reference method, with lower chromatographic development time (mean=3.61minutes). Very low resolutions are obtained with Whatman paper, essentially with Whatman 1 and 3MM. Therefore, we do not recommend their use. Although iTLC-SG (Varian) and HPTLC silica gel 60 (Merck) are suitable alternatives to ITLC-SG (Pall-Gelman) in determining the RCP of (111)In-pentetreotide, iTLC-SG (Varian) is the method of choice due to its lower chromatographic development time.


A quantitative assay for measuring the induction of mutations in human peripheral blood T-lymphocytes.
We optimized conditions for propagating freshly-isolated human peripheral blood T-lymphocytes and cells that had been stored in liquid nitrogen on Day 5 post-isolation, exposing them to mutagens in exponential growth, and measuring the cytotoxicity of the agent from the loss of colony-forming ability, and its mutagenicity from the increase in frequency of 6-thioguanine-resistant cells. Supernatant containing T-cell growth factor, from 60Co-irradiated peripheral mononuclear cells cultured in the presence of 60Co-irradiated B-lymphoblastoid human cells as allogeneic stimulators, supplied at a concentration of 10% along with 10% serum and 10(5) allogeneic stimulator cells/ml, supported exponential growth (population doubling times of 22 h) for extended periods (greater than 30 d). It gave cloning efficiencies of greater than or equal to 40%. T-lymphocytes stored in liquid nitrogen and returned to culture shortly before mutagen exposure exhibited the same sensitivity as freshly-isolated T-cells to killing by the agents tested, i.e., UV radiation, ethyl-nitrosourea, and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,19 alpha,epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene. We showed that if mutagenized populations frozen during the expression period were thawed and assayed, they exhibited the same cloning efficiencies and frequencies of 6-thioguanine-resistant cells as did the corresponding populations that had been assayed directly without freezing. Use of these procedures should facilitate investigation of the frequency and kinds of mutations induced in the HPRT gene of peripheral blood T-lymphocytes in vivo and in vitro.


[Comparative assessment of clinical features and imaging findings for patients with vascular parkinsonism and idiopathic Parkinson's disease].
To compare the differences of clinical features and imaging findings between vascular parkinsonism (VP) and idiopathic Parkinson's disease (PD). The clinical features and imaging findings from 54 patients with VP and 53 patients with PD were compared. The main clinical manifestations of patients with VP were hemiplegia, rigidity and bulbar palsy with obviously pyramidal tract system damage and less rest tremor. Patients with PD showed remarkable tremor-cogwheel rigidity. In the aspect of imageology, there were obvious imaging changes in patients with VP, mainly manifested lacunar infarction located in unilateral or bilateral basal ganglia and white matter of frontal lobe. Furthermore, some ischemic changes could be seen in the cerebral peduncle and lateral cerebral ventricle. In patients with PD, ischemic changes were invisible. As to the therapeutic effect to the anti-Parkinson's disease, patients with PD showed better effect than VP patients. As a self-sustaining clinical syndrome, the clinical manifestations and imaging findings in patients with VP are different from those with PD.


Avoiding Potential Pitfalls in Qualitative Research Methods.
The Associate Editor provides strategies for authors to use when they prepare reports of qualitative studies.