The ReadFree tool for the identification of poor readers: a validation study based on a machine learning approach in monolingual and minority-language children.
In this study, we validated the "ReadFree tool", a computerised battery of 12 visual and auditory tasks developed to identify poor readers also in minority-language children (MLC). We tested the task-specific discriminant power on 142 Italian-monolingual participants (8-13 years old) divided into monolingual poor readers (N = 37) and good readers (N = 105) according to standardised Italian reading tests. The performances at the discriminant tasks of the "ReadFree tool" were entered into a classification and regression tree (CART) model to identify monolingual poor and good readers. The set of classification rules extracted from the CART model were applied to the MLC's performance and the ensuing classification was compared to the one based on standardised Italian reading tests. According to the CART model, auditory go-no/go (regular), RAN and Entrainment100bpm were the most discriminant tasks. When compared with the clinical classification, the CART model accuracy was 86% for the monolinguals and 76% for the MLC. Executive functions and timing skills turned out to have a relevant role in reading. Results of the CART model on MLC support the idea that ad hoc standardised tasks that go beyond reading are needed.


Road to the elimination of schistosomiasis from Asia: the journey is far from over.
Schistosomiasis is a neglected tropical disease with a very long endemic history in Asia. Great strides have been made to control the disease in China and the Philippines but the road to elimination is far from over, given the zoonotic nature of the schistosome parasites in both countries.


Bargaining models of depression and evolution of cooperation.
This paper presents a model for evolutionary origins of unipolar depressive disorders and reviews empirical evidence in support of the "nonparticipation hypothesis of depression" suggested by the model. In line with previous theory, depression is interpreted to provide means for not participating in joint enterprises that would otherwise be difficult to avoid ('bargaining' model); therefore, it provides an additional alternative strategy to social-imitation dynamics occurring in Public Good Games. Average income from joint enterprises modeled with a Public Good Game is interpreted to drive group-level genetic selection. Based on these assumptions, it is shown that if a joint enterprise is sufficiently important for both the between-individual and the between-groups competition, then a nonparticipation strategy (or gene for depression vulnerability) will be present in total population almost surely (i.e., with probability one). The modeling framework serves to explain several other seemingly unrelated empirical observations, such as association between income inequality and depression, co-morbidity and proximal biological mechanisms for negative emotions, and mechanisms for the social network-dynamics of emotion.


Metabolic and histologic investigation of the nature of nephrocalcinosis in children with hypophosphatemic rickets and in the Hyp mouse.
To investigate the biochemical nature of nephrocalcinosis in children with hypophosphatemic rickets treated with orally administered phosphate and vitamin D, we studied five such patients, aged 3.7 to 12.3 years, during treatment and again 3 days after it had been discontinued. Treatment was associated with significant increases in mean serum phosphate concentration and urine phosphate/creatinine ratio, from 0.71 to 1.03 mmol/L and from 3.61 to 9.42 mmol/mmol, respectively. Significant correlation was found between urine phosphate/creatinine and oxalate/creatinine ratios (r = 0.670; p less than 0.01); however, the mean urine oxalate/creatinine ratio of 65.0 mumol/mmol while patients were taking phosphate orally was not significantly different from the ratio of 59.0 mumol/mmol when treatment was discontinued. Kidney biopsy specimens from three of the patients showed that the renal calcifications were located mainly intratubularly and were composed exclusively of calcium phosphate. In a further investigation of the nature of phosphate-induced nephrocalcinosis, six 6-week-old male Hyp mice, the murine analog of the human disease, received oral phosphate therapy with drinking water for 48 days; six others served as control animals. Mice in the experimental group excreted more phosphate (p less than 0.001) and less calcium (p less than 0.01) than control mice did, and medullary nephrocalcinosis, with a high kidney calcium content, developed (p less than 0.001). Histologic sections showed that the renal calcifications were located intratubularly and were composed of calcium phosphate. We conclude that, both in children with hypophosphatemic rickets and in the Hyp mouse, the development of nephrocalcinosis is associated with high oral phosphate intake and subsequent deposition of calcium phosphate precipitates in the kidney.


Expression levels and patterns of B-cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent.
Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell-surface protein B-cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR-T cell and monoclonal-antibody therapies in MM. However, the knowledge of the BCMA expression-pattern in myeloma patients from the Indian subcontinent is still not available. We present an in-depth study of BCMA expression-pattern on abnormal plasma cells (aPC) in Indian MM patients. We studied BM samples from 217 MM patients (211-new and 6-relapsed) with a median age of 56 years (range, 30-78 years & M:F-2.29) and 20 control samples. Expression levels/patterns of CD269 (clone-19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression-level of CD269 was determined as a ratio of mean fluorescent intensity (MFI-R) of CD269 in PCs to that of non-B-lymphocytes and expression-pattern (homogenous/heterogeneous) as coefficient-of-variation of immunofluorescence (CVIF). Median (range) percentage of CD269-positive abnormal-PCs in total PCs was 71.6% (0.49-99.29%). The MFI-R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12-26.88) than nPCs (3.33, 1.23-12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77-9.57) and 2.66 (2.15-3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529. We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.


Castleman's Disease Presenting as Peri - Pancreatic Neoplasm.
Castleman's disease (CD) is a relatively singular disorder. Usually presenting as a mediastinal mass, peri pancreatic localization of CD is even rarer. Diagnosis is seldom established pre-operatively. We report two such cases of CD in which peri pancreatic region was involved and were diagnosed on biopsy, hence avoiding complex and high risk surgery.


Etiological agents of viral meningitis in children from a dengue-endemic area, Southeast region of Brazil.
Meningitis is a disease with a global distribution that constitutes a worldwide burden, with viruses as the primary etiologic agents. The range of viral meningitis severity depends mainly on age, immune status and etiological agent. The aim of this work was to investigate the suspected cases of viral meningitis using molecular techniques to confirm the viral infection. The diagnosed virus was correlated with clinical findings and cytochemical parameters in cerebrospinal liquid (CSF) of patients. CSF of 70 children with the presumptive diagnosis of viral meningitis was analyzed by real time PCR (qPCR). Viruses were identified by qPCR in 44 CSF samples (62.9%). Among them, 31 were identified as Enterovirus (ENTV) (70.4%), six as Human herpes virus 3 (HHV-3) (13.6%), five as Dengue virus (DENV) (11.7%), one as Human herpes virus 1-2 (2.3%) and one as Human herpes virus 5 (2.3%). Patients in the HHV-positive groups had increased percentage of polymorphonuclear neutrophils (PMN) (mean of 81%) while the groups of patients with DENV and ENTV had a mean of 30.9%. This study contributes to the knowledge of the epidemiological distribution of viral agents in CNS infections in children. In addition, it raises the relevance of DENV as an agent of CNS infection, and reinforces the importance for molecular in the cases of CNV infection.


Paretic knee extensor strength, gait velocity, and fat mass are major determinants of peak aerobic capacity in subacute stroke: observational cohort study.
The purpose of this study is to investigate major determinants of peak aerobic capacity in subacute stroke patients among body composition, balance function, walking capacity, and lower limb muscular strength. This was a retrospective observational cohort study. Eighty-three subacute stroke patients were enrolled and their medical records were retrospectively reviewed in the study (47 males; mean age: 62.95 ± 13.9 years). Gait capacity was assessed by gait velocity (10 m walk velocity:10MWV) and gait endurance (6 min walk distance:6MWD). Balance function was evaluated with Berg Balance Scale (BBS). The isometric muscular strengths of bilateral knee extensors were measured with an isokinetic dynamometer. Cardiovascular fitness was evaluated with an expired gas analyzer. In backward linear regression analyses, paretic isometric extensor strength (p < 0.001), fat mass (p = 0.005) and 10MWV (p < 0.001) are significantly correlated with peak aerobic capacity (adjusted R2 = 0.499) in all patients. Our results confirmed that paretic knee extensor strength, gait velocity, and fat mass were major determinants of peak aerobic capacity in subacute stroke. Therefore, therapeutic approaches should focus on improving gait velocity and paretic knee extensor strength in the early stages of recovery from stroke.


Interferon alpha antagonizes STAT3 and SOCS3 signaling triggered by hepatitis C virus.
We aimed to investigate regulation of signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) by interferon alpha (IFN-α) and to analyze the relationship between STAT3 and SOCS3 during hepatitis C virus (HCV) infection. Changes in STAT3 and SOCS3 were analyzed at both mRNA and protein levels in human hepatoma cells infected with HCV (J6/JFH1). At 72h of HCV infection, STAT3 expression was decreased with sustained phosphorylation, and IFN-α increased such decrease and phosphorylation. HCV increased SOCS3 expression, while IFN-α impaired such increase, indicating different regulation of STAT3 and SOCS3 by IFN-α. IFN-α-induced expression and phosphorylation of upstream kinases of the JAK/STAT pathway, Tyk2 and Jak1, were suppressed by HCV. Moreover, knockdown of STAT3 by RNA interference led to decreases in HCV RNA replication and viral protein expression, without affecting either the expression of Tyk2 and Jak1 or the SOCS3 induction in response to IFN-α. These results show that IFN-α antagonizes STAT3 and SOCS3 signaling triggered by HCV and that STAT3 regulation correlates inversely with SOCS3 induction by IFN-α, which may be important in better understanding the complex interplay between IFN-α and signal molecules during HCV infection.


Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report.
To describe a case of left vagal nerve stimulation (VNS) resulting in immediate cessation of status epilepticus (SE) with good neurological outcome. A 30-year-old man with medically intractable seizures including episodes of SE was successfully treated using left VNS. After requiring discontinuation of phenytoin, valproic acid, carbamazepine, and topiramate because of severe allergic reactions resembling Stevens-Johnson syndrome, the patient required pentobarbital coma along with phenobarbital, tiagabine, and levetiracetam for seizure frequency reduction. He underwent left vagal nerve stimulator placement after nearly 9 days of barbiturate-induced coma, with stimulation initiated in the operating room. On the following day, electroencephalography revealed resolution of previously observed periodic lateral epileptiform discharges and the patient was free of seizures. Prestimulation seizure frequency was recorded at 59 times a day, with some seizures enduring 45 minutes despite barbiturate coma. Poststimulation, the patient has been free of seizures for 19 days and is presently taking only levetiracetam and phenobarbital, from which he continues to be successfully weaned without seizures. He is awake, alert, and can recall events leading up to his seizures, with good long-term memory and residual left upper extremity and lower extremity weakness. This case illustrates the role of left vagal stimulation in the treatment of SE and otherwise medically intractable seizures caused by allergic reactions. To our knowledge, this is the first case in the world literature for adults reporting cessation of SE after VNS. Another case with a similar improvement has been reported in the pediatric population.


Transforming sustainable plant proteins into high performance lubricating microgels.
With the resource-intensive meat industry accounting for over 50% of food-linked emissions, plant protein consumption is an inevitable need of the hour. Despite its significance, the key barrier to adoption of plant proteins is their astringent off-sensation, typically associated with high friction and consequently poor lubrication performance. Herein, we demonstrate that by transforming plant proteins into physically cross-linked microgels, it is possible to improve their lubricity remarkably, dependent on their volume fractions, as evidenced by combining tribology using biomimetic tongue-like surface with atomic force microscopy, dynamic light scattering, rheology and adsorption measurements. Experimental findings which are fully supported by numerical modelling reveal that these non-lipidic microgels not only decrease boundary friction by an order of magnitude as compared to native protein but also replicate the lubrication performance of a 20:80 oil/water emulsion. These plant protein microgels offer a much-needed platform to design the next-generation of healthy, palatable and sustainable foods.


Cardiovascular effects of benzquinamide in man.
Benzquinamide HCl, a new antiemetic agent, was studied in twelve healthy volunteers. Each subject received intravenously both benzquinamide (0.7 mg/kg) and placebo in a randomized, double-blind crossover manner. Cardiac output and arterial pressure, arterial blood gases, respiration (tidal volume and rate), and oxygen consumption were measured twice before drug administration and at 5, 10, 20 and 30 min after injection. Intra-arterial pressure increased significantly (P less than 0.005) at 5 min (12.6%) and 10 min (8.6%) following benzquinamide. Likewise, peripheral vascular resistance increased significantly (P less than 0.005) at 5 min (14.3%) and 10 min (8.8%) post-injection. Cardiac output, stroke volume and heart rate remained essentially unchanged. A significant increase (P less than 0.025) in respiratory rate was observed at 10 min (8.7%) and 20 min (12.6%) following benzquinamide. Values for the arterial Po2, Pco2, and pH showed no significant changes. It is considered that the effect of benzquinamide in increasing intra-arterial pressure is due to the increased peripheral vascular resistance.


The prognostic significance of histological grading and pathological staging in carcinoma of the prostate.
Histological grading and pathological staging are relevant factors in the prognosis of patients with prostatic cancer. Of 115 consecutive patients with carcinoma of the prostate that was staged fully before treatment 16 had stage A2 disease. Low grade neoplasms were present in 6 of these patients and evidence of nodal metastases was documented at lymphadenectomy in 2. Similarly, 4 of 35 patients with low grade stage B1 disease had nodal metastases. With the enzymatic and/or radioimmunoassay techniques for acid phosphatase determination we were unable to select those patients with nodal metastases. From these studies we believe that low grade, low stage carcinoma of the prostate retains a potential for metastatic disease and that acid phosphatase determinations are unreliable in detecting bulky regional nodal involvement.


Efficacy of periodontal treatment on glycaemic control in diabetic patients: A meta-analysis of interventional studies.
There is growing evidence that periodontal disease may favour the incidence or aggravation of diabetes and its complications. To investigate the issue, we conducted a meta-analysis of the effect of periodontal therapy on glycaemic control in diabetic patients. A literature search was carried out using seven databases (Medline, EMBASE, LILACS, The Cochrane Library, Pascal, IADR Abstracts and Current Contents), with no language restrictions. We followed the QUOROM-recommended standards for improving the quality of reporting meta-analyses of interventional studies. Twenty-five studies, involving 976 subjects altogether, were included in the present systematic review. Of these, nine studies, involving a total of 485 patients, were controlled trials and were included in the meta-analysis. The standardized mean difference in HbA(1c) with the treatment of periodontal disease was 0.46 (95% CI: 0.11, 0.82). These findings suggest that periodontal treatment could lead to a significant 0.79% (95% CI: 0.19, 1.40) reduction in HbA(1c) level. The present meta-analysis represents the best information available to date that addresses this issue, and suggests that periodontal treatment could improve glycaemic control. Nevertheless, these results need to be viewed with caution because of a lack of robustness, and deficiencies in the design of some of the studies included. A randomized controlled trial with sufficient statistical power would help to confirm the results of this meta-analysis.


Quality of Life in Elderly Cancer Patients Undergoing Chemotherapy.
As life expectancy increases, it is expected that 60% of all cases of cancer will be detected in elderly patients in the next two decades. Cancer treatment for older persons is complicated by a number of factors, thus negatively affecting patients' quality of life. The purpose of this study is to investigate quality of life in elderly cancer patients undergoing chemotherapy. This study was descriptive and non-experimental. It was conducted in one large hospital in a major city of Northern Greece. The sample was convenience comprising 53 elderly cancer patients undergoing cycle 3 chemotherapy. The data was collected using the Functional Assessment of Cancer Therapy scale and included questions related to demographic and clinical characteristics. The majority of participants were men (n = 27, 50.9%) who were married (n = 32, 79.5%). Their mean age was 70.07 ± 3.60. Almost half of the sample (n = 30, 56.6%) had colon cancer. There was a statistical significant difference between men and women pertaining to physical wellbeing (p = 0.004) and overall quality of life (p < 0.001). When comparing each subscale with the patients' marital status it was found that there was a statistical difference with respect to social/family wellbeing (p = 0.029), functional wellbeing (p = 0.09) and overall quality of life (p < 0.001). Moreover, the type of cancer affected overall quality of life (p < 0.001) and social/family wellbeing (p = 0.029). These findings call attention to quality of life and its related factors in elderly cancer patients. It is highly recommended to envisage measures for improving quality of life in this group of cancer patients.


Uterine macrophages as treatment targets for therapy of premature rupture of membranes by modified ADSC-EVs through a circRNA/miRNA/NF-κB pathway.
Circular RNA (circRNA) is a type of stable non-coding RNA that modifies macrophage inflammation by sponging micro RNAs (miRNAs), binding to RNA-binding proteins, and undergoing translation into peptides. Activated M1 phenotype macrophages secrete matrix metalloproteinases to participate in softening of the cervix uteri to promote vaginal delivery. In this study, the premature rupture of membranes (PROM) mouse model was used to analyze the role of macrophages in this process. Profiling of circRNAs was performed using a competing endogenous RNA microarray, and their functions were elucidated in vitro. Meanwhile, adipose tissue-derived stem cell-secreted extracellular vesicles (EVs) were applied as a vehicle to transport small interfering RNAs (siRNAs) targeting the circRNAs to demonstrate their biological function in vivo. The miRNA miR-1931 is dependent on the nuclear factor kappa-B (NF-κB) pathway but negatively regulates its activation by targeting the NF-κB signaling transducer TRAF6 to prevent polarization of M1 macrophages and inhibit matrix metalloproteinase (MMP) secretion. The host gene of circRNA B4GALNT1, also an NF-κB pathway-dependent gene, circularizes to form circRNA_0002047, which sponges miR-1931 to maintain NF-κB pathway activation and MMP secretion in vitro. In the PROM model, EVs loaded with siRNAs targeting circRNAs demonstrated that the circRNAs reduced miR-1931 expression to maintain NF-κB pathway activation and MMP secretion for accelerating PROM in vivo. Our data provide insights into understanding PROM pathogenesis and improving PROM treatment.


Treatment Seeking for Alcohol Use Disorders: Treatment Gap or Adequate Self-Selection?
This study examines whether it is harmful that subjects with an alcohol use disorder (AUD) in the general population rarely seek treatment. Baseline and 3-year follow-up data from the Netherlands Mental Health Survey and Incidence Study-2 were used. Treatment utilization covered a 4-year period. The Composite International Diagnostic Interview 3.0 assessed AUD and other psychiatric disorders. Of 154 subjects with baseline 12-month DSM-5 AUD, 35.4% used only general treatment (GenTx) for mental problems or alcohol/drugs problems; 10.3% used specialized AUD treatment (AUDTx); and 54.3% used no treatment at all. Of these 3 groups, AUDTx users had the highest severity on AUD characteristics, comorbid psychopathology and mental functioning. Compared to non-treatment (NonTx), GenTx users more often had 12-month emotional disorders at follow-up, but AUD remission rates and functioning were similar. NonTx users functioned similarly at follow-up as people in the general population without lifetime AUD or other psychopathology. Adequate treatment seeking often occurs in the general population: the most severe AUD subjects use AUDTx, and most NonTx users have a mild AUD and a favorable course. Current findings suggest a smaller treatment gap than previously reported, but still one-quarter of the people with AUD do not seek AUDTx but could benefit from this, as they have a persistent AUD.


Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile In Vitro.
Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68+/FXIII-A- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α+ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.


Lifestyle and nutrition related to male longevity in Sardinia: an ecological study.
A demographic analysis in the Mediterranean island of Sardinia revealed marked differences in extreme longevity across the 377 municipalities and particularly identified a mountain inner area where the proportion of oldest subjects among male population has one of the highest validated value worldwide. The cause(s) of this unequal distribution of male longevity may be attributed to a concurrence of environmental, lifestyle and genetic factors. In this study we focussed on some lifestyle and nutrition variables recorded in the island's population in early decades of 20th century, when agricultural and pastoral economy was still prevalent, and try to verify through ecological spatial models if they may account for the variability in male longevity. By computing the Extreme Longevity Index (the proportion of newborns in a given municipality who reach age 100) the island's territory was divided in two areas with relatively higher and lower level of population longevity. Most nutritional variables do not show any significant difference between these two areas whereas a significant difference was found with respect to pastoralism (P = 0.0001), physical activity estimated by the average slope of the territory in each municipality (P = 0.0001), and average daily distance required by the active population to reach the usual workplace (P = 0.0001). Overall, these findings suggest that factors affecting the average energy expenditure of male population such as occupational activity and geographic characteristics of the area where the population mainly resides, are important in explaining the spatial variation of Sardinian extreme longevity.


Sesquiterpenes and other constituents from the aerial parts of Inula japonica.
Three new sesquiterpenes, 1beta-hydroxy-8beta-acetoxycostic acid methyl ester, 1beta-hydroxy-8beta-acetoxyisocostic acid methyl ester and 1beta-hydroxy-4alpha,11alpha-eudesma-5-en-12,8beta-olide, along with fourteen known compounds were isolated from the aerial parts of Inula japonica. The structures of these new compounds were elucidated by spectroscopic methods (IR, EIMS, HRMS, 1D and 2D NMR). 1,6alpha-dihydroxy-4alphaH-1,10-secoeudesma-5(10),11(13)-dien-12,8beta-olide exhibited appreciable cytotoxic activity against cultured SMMC-7721 (human hepatoma cell) and HO-8910 (human ovarian carcinoma cell) with IC 50 values of 52.22 and 21.32 microg/mL, while 5alphaH-eudesma-4(15),11(13)-dien-12,8beta-olide showed remarkable cytotoxic activity against cultured SMMC-7721 and HO-8910 with IC 50 values of 6.21 and 5.28 microg/mL, respectively.


Triptolidenol, isolated from Tripterygium wilfordii, disrupted NF-κB/COX-2 pathway by targeting ATP-binding sites of IKKβ in clear cell renal cell carcinoma.
Triptolidenol (TPD) is an epoxy diterpene lactone from Tripterygium wilfordii, which has been used for chronic nephritis in China,and possessed various pharmacological properties, such as anti-inflammatory and anti-cancer activities. However, the precise molecular antitumor mechanism of TPD remains to be elucidated. In this study, we investigated the effects of TPD on human clear cell renal cell carcinoma (ccRCC) and investigated its precise anti-tumor mechanisms. It was showed that TPD significantly suppressed ccRCC cell proliferation, cell migration, and induced cell cycle arrest at S phase. Furthermore, TPD also induced apoptosis by activating the cytochrome c (cyt c)/caspase cascade signaling pathway. Moreover, using confocal immunofluorescence, a dual-luciferase reporter assay and molecular docking study, the results showed that TPD obviously reduced the expression of COX-2 by inhibiting the kinase activity of IKKβ via targeting its ATP-binding domain, and then attenuating the transactivation of NF-κB. Collectively, our study demonstrated that TPD suppressed renal cell carcinoma growth through disrupting NF-κB/COX-2 pathway by targeting ATP-binding sites of IKKβ, and provided pharmacological evidence that TPD exhibits potential use in the treatment of COX-2-mediated diseases such as ccRCC.


Comparison of Design, Eligibility, and Outcomes of Neuroendocrine Neoplasm Trials Initiated From 2000 to 2009 vs 2010 to 2020.
Neuroendocrine neoplasms (NENs) have historically been grouped homogenously in clinical trials, despite their heterogeneity. Given the adoption of a more advanced pathologic classification system and drug licensure of several targeted therapies over the last decade, information is needed on whether study characteristics of NEN studies have evolved. To assess changes in study design, eligibility, accrual, sponsorship, and outcomes between phase II or III NEN clinical trials that began enrollment from 2000 to 2009 vs 2010 to 2020. This quality improvement study used a systematic survey of completed studies published between January 1, 2000, and December 31, 2020. Therapeutic phase II and III NEN studies were identified through a database search of Medline (via PubMed), EMBASE (OvidSP), Cumulative Index of Nursing and Allied Health Literature (EBSCOhost), Web of Science (Clarivate), Cochrane Database of Systematic Reviews (Wiley), ClinicalTrials.gov (National Institutes of Health), EU Clinical Trials Register, and National Cancer Institute Clinical Trials. Data were analyzed between March and June 2021. Study characteristic proportions between the 2 enrollment periods. Of 3243 identified studies, 119 studies met criteria for inclusion, of which 117 studies (54 studies that began enrollment between 2000-2009 and 63 studies that began enrollment between 2010-2020) included exact dates of enrollment and were compared. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were less likely to include all NENs (13 studies [21%] vs 34 studies [63%]; P < .001) and more likely to include select NENs (eg, gastrointestinal neuroendocrine tumors, 25 studies [40%] vs 11 studies [20%]; P = .02; pancreatic neuroendocrine tumors, 32 studies [51%] vs 16 studies [30%]; P = .02). Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to specify tumor differentiation (59 studies [98%] vs 34 studies [63%]; P < .001) or Ki-67 index (23 studies [38%] vs 5 studies [9%]; P < .001) in inclusion criteria. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to use progression-free survival (22 studies [35%] vs 9 studies [18%]; P = .04) rather than objective response rate (19 studies [30%] vs 27 studies [53%]; P = .01) as a primary or coprimary end point. These findings suggest that NEN trials enrolling over the last decade were more focused on select tumor populations, compared with studies that began enrollment before 2010. Despite this shift, more than 20% of studies still included all NENs. Studying novel agents in specific disease populations may enhance drug development in the field.


Foraminal cervical herniated disc treated by anterior discoforaminotomy.
The authors report their experience with cervical foraminal disc herniation. The importance of the computed tomographic scan in its diagnosis is emphasized, and discoforaminotomy is described.


Percutaneous kyphoplasty with or without temporary unipedicle screw reduction : A retrospective comparative study of osteoporotic vertebral fractures.
Temporary unipedicle screw reduction with percutaneous kyphoplasty (TUSR-PKP) is a relatively new method for managing osteoporotic vertebral compression fractures (OVCFs). A clinical retrospective comparative study was conducted to verify whether TUSR-PKP was noninferior to simple PKP regarding the management of OVCFs. A total of 38 consecutive patients who sustained OVCFs without neurological deficits and had undergone surgeries in our hospital from June 2012 to January 2014 were included in the study: 24 patients underwent simple PKP (control group) and the other 14 patients underwent TUSR-PKP (treatment group). All 38 patients were asked to participate in a long-term (>1 year) follow-up. Visual analog scale (VAS) pain scores and Oswestry Disability Index (ODI) were recorded, and the Cobb angles and the vertebral body heights were measured on the lateral radiographs before surgery and on day 1, as well as 1, 3, 6, and 12 months after surgery. The patients in the treatment group had better vertebral height gain and greater improvement on ODI compared with the control group (p < 0.05). The VAS scores of the two groups were similar at all points until the end of the 1‑year follow-up period. Two patients from the treatment group and 5 patients from the control group had cement leakage. In the control group, 3 patients suffered adjacent or nonadjacent vertebra fractures. TUSR-PKP is a safe and effective surgical option for OVCFs. Compared with simple PKP, TUSR-PKP provided at least equal results for OVCFs. Moreover, during the postsurgery observations, TUSR-PKP showed potential advantages including vertebral height gain, ODI improvement, and fewer subsequent refractures.


Histamine release induced by dextran: the nature of the dextran receptor.
Dextrans of molecular weight 10(4) to 2 x 10(6) induced histamine release from rat peritoneal mast cells in the presence of calcium (1 mM) and phosphatidyl serine (10 micrograms/ml). Glucose and low molecular weight dextrans inhibited the histamine release induced by high molecular weight dextrans but the inhibition could not be explained in terms of a simple competitive model. Structure-activity relationships for the inhibition of dextran-induced histamine release by a number of saccharides demonstrated that substitution at the C-3, C-4, and C-6 positions of glucose were most important for activity. Inhibition of histamine release by glucose was specific for the dextran stimulus. Soluble IgE and IgG antibodies failed to interfere with histamine release induced by dextran. Phlorizin specifically inhibited the histamine release induced by dextran. Purification of mast cells on albumin or ficoll gradients produced a selective loss of response to dextran which was not due to the removal of non-mast cells but to some change in the mast cells themselves. The possible nature of the dextran receptor is discussed.


The Effect of Minimally Invasive Thoracoscopic Left Atrial Appendage Excision on Cardiac Dynamic and Endocrine Function.
Left atrial appendage (LAA) isolation is an effective surgical treatment for decreasing thromboembolic risk. We sought to evaluate the short-term effect of minimally invasive surgery with LAA excision on left atrial dynamic and endocrine function in atrial fibrillation (AF) patients. A total of 52 patients with paroxysmal AF undergoing minimally invasive surgery with LAA excision in Anzhen Hospital from October 2012 to June 2014 were enrolled in the study. The natriuretic peptide plasma level was determined by enzyme-linked immunosorbent assay (ELISA), and left atrial dynamic function was measured preprocedure by real-time three-dimensional echocardiography and postprocedure after 7 days and 3 months. With the exception of six recurrences, 88.5% (46/52) of the patients were prospectively followed over 3 months in terms of their sinus rhythm postprocedure. No severe operative complications or embolism events occurred within those 3 months. Echocardiography showed a 3-6% decrease in left atrial volume postprocedure, and dynamic function was largely restored by 3 months. There was no significant change in natriuretic peptide levels, although a slight decrease was detected 7 days postprocedure, which gradually recovered by 3 months (P = 0.350). There are no significant differences in left atrial dynamics and natriuretic peptide secretion in AF patients after minimally invasive surgery with LAA excision.


Polyamines and the development of isolated neurons in cell culture.
The possible role of polyamines in the development of isolated neuroblasts from the cerebral cortex of embryonic chick brain was studied by means of three enzyme activated irreversible inhibitors of ornithine decarboxylase. alpha-Difluoromethylornithine (MDL 71782) showed no effects on development at doses which depleted dramatically neuronal putrescine and spermidine levels. In contrast, the two other inhibitors, (E)-alpha-(fluoromethyl)dehydroputrescine (MDL 72197) and 6-heptyne-2,5-diamine (MDL 72175) blocked the formation of neuronal outgrowths completely at 100 microM and higher concentrations. Their effects on neuronal polyamines differed at this concentration considerably. The growth inhibitory effect of the ornithine decarboxylase inhibitors was in all cases reversible: cells which were grown after 3 days of exposure to the drugs in normal medium produced neuronal networks. The presence of putrescine at 10 microM concentration in the culture medium prevented the growth inhibitory effect of 100 microM concentrations of the drugs. This concentration of putrescine was not only capable of preventing, but also of reversing growth inhibition by the ornithine decarboxylase inhibitors. Although the cellular polyamine levels were not correlated with the morphological development of chick embryo cortical neurons, the present study leaves no doubt that putrescine plays an essential role in neuronal differentiation.


Inhibitory signaling in collective social insect networks, is it indeed uncommon?
Individual entities across levels of biological organization interact to reach collective decisions. In centralized neuronal networks, competing neural populations commonly accumulate information over time while increasing their own activity, and cross-inhibiting other populations until one group passes a given threshold. In social insects, there is good evidence for decisions mediated by positive feedbacks, but we found evidence for similar inhibitory signals only in honey bee (Apis mellifera) stop signals, and Pharaoh's ant- (Monomorium pharaonic) repellent pheromones, with only the former occasionally being used as cross-inhibition. We discuss whether these differences stem from insufficient research effort or represent genuine differences across levels of biological organization.


Pyruvate prevents poly-ADP ribose polymerase (PARP) activation, oxidative damage, and pyruvate dehydrogenase deactivation during hemorrhagic shock in swine.
The inadequate availability of fuel substrates and sharp decline in cellular ATP have been implicated in a cascade of events associated with cell death and organ failure during hemorrhagic shock (HS). In this in vivo swine model of severe prolonged HS, the effect of exogenous pyruvate administration on various markers of cell damage in brain and liver was examined. Thirty minutes after the start of controlled arterial hemorrhage, 30% sodium pyruvate, 10% saline, or 0.9% saline was administered via jugular vein. Four hours after the initiation of hemorrhage, tissue samples from brain and liver were obtained and examined for the cellular and molecular markers of cellular damage. Results of our study suggest that pyruvate prevents loss of total NAD content, cleavage of poly-ADP ribose polymerase (PARP), and inhibits lipid peroxidation in both the brain and liver of swine during prolonged severe HS. We conclude that there are multiple mechanisms by which pyruvate can possibly prevent cell damage caused during HS.


Assessing the effects of meteorological factors on daily children's respiratory disease hospitalizations: A retrospective study.
Respiratory disease symptoms in children are aggravated by frequent changes in meteorological conditions. The net effective temperature (NET) integrates temperature, relative humidity, and wind speed as a cooling indicator. This study aims to assess the effect of daily changes in meteorological factors and corresponding NET data on children's hospitalizations for different ages, genders and subtypes of respiratory infections in Baotou, China. Distributed lag non-linear models were constructed to simultaneously assess the exposure-response associations between daily admission counts of children with respiratory diseases and daily NET and other meteorological factors, as well as their lag dependencies. As air pollution significantly affects the respiratory tract, it was considered as confounding factor. In general, the cumulative meteorological factors had greater effects on lower respiratory tract infections than upper respiratory tract infections (RR: temperature [5.21 vs. 2.33], wind speed [4.89 vs. 3.12], and humidity [1.77 vs. 0.97]). The effects of cumulative meteorological factors on female children were greater than those on male children (RR: temperature [2.14 vs. 1.82], wind speed [5.46 vs. 1.90], and humidity [1.60 vs. 1.55]). Temperature and wind speed showed an influence on 4-7-year-old children, but these factors had no influence on other age groups; humidity only showed an influence on the 0-3-year-old group. The NET value had a large effect on lower respiratory infections, in the 4-7-year-old group and female children. In conclusion, a complex non-linear relationship exists between climate variability and children's respiratory diseases. The results of the study can be used to support the development of important meteorological information tools for early warnings of respiratory disease events in children. Concurrently, the NET values can be used for comprehensive assessments of climate change in the future, which will help the government and health authorities better minimize the impacts of children's respiratory diseases.


Validation of a High-Sensitivity Assay for Detection of Chimeric Antigen Receptor T-Cell Vectors Using Low-Partition Digital PCR Technology.
Although in vivo engraftment, expansion, and persistence of chimeric antigen receptor (CAR) T cells are pivotal components of treatment efficacy, quantitative monitoring has not been implemented in routine clinical practice. We describe the development and analytical validation of a digital PCR assay for ultrasensitive detection of CAR constructs after treatment, circumventing known technical limitations of low-partitioning platforms. Primers and probes, designed for detection of axicabtagene, brexucabtagene, and Memorial Sloan Kettering CAR constructs, were employed to validate testing on the Bio-Rad digital PCR low-partitioning platform; results were compared with Raindrop, a high-partitioning system, as reference method. Bio-Rad protocols were modified to enable testing of DNA inputs as high as 500 ng. Using dual-input reactions (20 and 500 ng) and a combined analysis approach, the assay demonstrated consistent target detection around 1 × 10-5 (0.001%) with excellent specificity and reproducibility and 100% accuracy compared with the reference method. Dedicated analysis of 53 clinical samples received during validation/implementation phases showed the assay effectively enabled monitoring across multiple time points of early expansion (day 6 to 28) and long-term persistence (up to 479 days). CAR vectors were detected at levels ranging from 0.005% to 74% (vector versus reference gene copies). The highest levels observed in our cohort correlated strongly with the temporal diagnosis of grade 2 and 3 cytokine release syndrome diagnosis (P < 0.005). Only three patients with undetectable constructs had disease progression at the time of sampling.


LENTICULE discs provide a homogenous format for external quality assessment samples: a comparison with freeze-dried samples for shellfish microbiology.
The aim was to compare the variability in Escherichia coli enumeration data and detection of Salmonella spp. between four samples of LENTICULE discs and freeze-dried samples for the Health Protection Agency's External Quality Assessment (EQA) scheme for shellfish microbiology. Four samples of known but undisclosed microbiological content were dispatched in both freeze-dried and LENTICULE disc formats to 57 participating laboratories in 20 countries. Participants examined samples using their routine methods for the most probable number (MPN) of E. coli per 100 g and the presence/absence of Salmonella spp. There was no significant difference between the Food and Environmental Proficiency Testing Unit and participating laboratories for E. coli and Salmonella spp. results. There were significantly less outlying results using the LENTICULE discs than freeze-dried sample format and equivalent or less variance for the former for E. coli MPN. There was no significant difference between LENTICULE discs and freeze-dried samples for the presence/absence of Salmonella spp. Overall the results indicated that there was equivalent or less variance in results for the LENTICULE discs than for freeze-dried samples, therefore LENTICULE discs are a homogenous and stable matrix for EQA samples. This study provides validation data for the replacement of freeze-dried samples by LENTICULE discs for the Health Protection Agency Shellfish EQA Scheme.


Adolescent otolaryngology.
To determine the pattern of disease amongst ambulatory adolescents referred to a pediatric otolaryngology outpatient department. Retrospective chart review of adolescents newly referred to a tertiary pediatric otolaryngology outpatient department over a 12-month period. One hundred and fifteen patients were included (male 56, female 59) mean age 14.9 years. There were 36 (31%) patients who had previously required otolaryngology management for another condition, and 29 patients with complex medical conditions. Investigations, including audiology and medical imaging, were performed in 35 patients. The patients were managed surgically 34 (30%), medically 28 (24%), referred to other departments 10 (9%) had no intervention 21 (18%), while 22 (19%) failed to attend for follow up. Ambulatory adolescent patients present with a comparable spectrum of otolaryngological problems to other pediatric age groups. These patients appear to be well managed by pediatric otolaryngologists, and there does not seem to be a need to develop a free standing adolescent otolaryngology subspecialty within tertiary pediatric otolaryngology at this time.


Urinary trypsin inhibitor reduced inflammatory response after stent injury in minipig.
This study investigated whether urinary trypsin inhibitor (UTI) inhibits neointimal formation by reducing inflammatory response after stent injury. Twenty minipigs having undergone oversized bare material stent implantation in the left anterior descending artery were randomly subdivided into two groups: a UTI group (n=10) and a control group (n=10). Two systemic markers of inflammation (serum macrophage chemoattractant protein-1 and interleukin-6 levels measured by ELISA) were increased after stent implantation, and two days after stem implantation, their levels were positively correlated with the maximal percentage of area stenosis on day 28 (r(2)=0.889 and 0.743, respectively). This effect was abolished by UTI administration. Twenty-eight days after implantation, morphometric analysis of the stented arteries revealed significantly reduced luminal stenosis (38±6% vs. 64±12%, P<0.05), a neointimal area (3.22±0.57 mm(2) vs. 5.21±1.04 mm(2), P<0.05), neointimal thickness (0.31±0.13 mm vs. 0.46±0.16 mm, P<0.05), and an inflammatory score of 1.02±0.05 vs. 1.30±0.08 in UTI-treated animals as compared with controls. Twenty-eight days after stenting, arterial nuclear factor-κB expression was 36.93±7.16% in all of the cells in controls and 23.32±4.54% in UTI-treated minipigs. UTI could reduce neointimal formation after stenting by inhibiting the local and the systemic inflammatory response. Percutaneous coronary intervention could benefit from precocious anti-inflammatory treatment.


Bronchial inflammation in corticosteroid-sensitive and corticosteroid-resistant asthma at baseline and on oral corticosteroid treatment.
Pathophysiology of corticosteroid (CS)-resistant asthma remains incompletely understood. To determine if failure of asthma to clinically improve with CS is due to a defective response of airway bronchial inflammation to these drugs. Twenty-one asthmatics having a decreased baseline FEV1 that improved >or= 30% with inhaled beta2 agonist got bronchial biopsies before and at the end of an oral CS treatment (methylprednisolone 40 mg daily for 14 days). They were arbitrarily divided into two groups according to baseline FEV1 improvement following this treatment: >or= 23% designated as CS-sensitive (CSS) (n = 10) and < 15% as CS-resistant (CSR) (n = 11). Before oral CS, counts of bronchial mucosa inflammatory cells identified by immunohistochemistry (CD3, MBP, tryptase, CD68, neutrophil elastase and CD25 for lymphocytes, eosinophils, mast cells, macrophages, neutrophils and IL-2 receptors, respectively) were similar in CSS and CSR subjects. Oral CS decreased CD3+ cell counts (medians: 60-20 cells/mm(2); P = 0.014) and MBP+ cell counts (medians: 19-4 cells/mm(2); P = 0.03) in CSS asthmatics, but only tryptase+ cell counts in CSR asthmatics (medians: 30-18 cells/mm(2); P = 0.05). Few bronchial neutrophil elastase+ cells were observed and their counts were similar in the two groups of asthmatics before and when on oral CS (all medians: = 2 cells/mm(2)). These data show that, in these subjects with moderate to severe asthma, lymphocytes and eosinophils constitute most of the inflammatory cells infiltrating the bronchial mucosa. They also demonstrated that clinical impaired response to CS is associated with a persistent bronchial mucosa cellular infiltrate despite oral CS treatment. Additional studies are required to determine the role of this CS-resistant bronchial inflammation in the impaired asthma clinical response to these drugs.


Erythrocyte adherence to the marginal zone of mouse spleen follicle mediated by receptor(s) for neuraminic acid.
Erythrocytes of different species (chicken, sheep, man, mouse, rat, guinea pig) except rabbit erythrocytes strongly adhere to the marginal zone of mouse spleen follicles in frozen sections. This adherence reaction (AR) is not restricted to red blood cells but is also observed with human lymphocytes. Pretreatment of the tissue sections with trypsin, mercaptoethanol, periodate, chloroform/methanol, acetone, and heating the sections abolishes AR whereas neuraminidase (VCN) treatment of the sections has an amplifying effect. AR is inhibited by preincubation of the neuraminidase- or untreated sections with neuraminic acid (NA). Treatment of the erythrocytes with VCN completely abolishes AR whereas treatment with other enzymes (hyaluronidase, collagenase) is ineffective in this respect. Determination of NA in the erythrocyte membrane before and after VCN treatment reveals a positive correlation between the amount of NA and AR. Rabbit red blood cells have the lowest NA content in their membranes and, in addition, there is little effect of VCN treatment in further reducing it. It is possible that a lectin-like substance is responsible for AR. The biologic significance of AR is hypothetical, but since AR occurs in an area of the spleen playing a role in antigen trapping it is conceivable that this trapping may be mediated by interaction of NA and NA receptor(s).


A new cestode Raillietina (Skrjabinia) doggaddaensis n. sp. from Gallus gallus domesticus (L.) from India.
Anew poultry cestode Raillietina(Skrjabinia) doggaddaensis n.sp.has been described from the domestic fowl Gallus gallus domesticus (L.). The new species has been compared with R.(S.) dhuncheta Sharma (1943) and R.(S.) magnicoronata(Fuhrmann, 1908).


Fiber optic sensing in rapidly rotating mechanical structures.
A novel, generic approach for fiber-optical sensing in rapidly rotating structures is presented. This approach does not require optical ingress via the central rotation axis. In this work, strain sensing at rotation speeds of up to 5000 rpm is demonstrated, and higher speeds should be possible. We demonstrate measurement of the rotation-induced strain in a rotating body at 500 rpm intervals up to 5000 rpm, and results agree very well with predictions.


Immunoperoxidase stains of ganglion cells and abnormal mucosal nerve proliferations in Hirschsprung's disease.
Hirschsprung's disease is congenital aganglionosis of the distal colon. The affected bowel shows an abnormal proliferation of mucosal nerve fibers by acetylcholinesterase stains. We retrospectively reviewed biopsy specimens from patients with suspected and proven Hirschsprung's disease, performed immunoperoxidase stains for S-100 protein and neuron-specific enolase (NSE), and compared these results to routine histologic findings and acetylcholinesterase stains. Ganglion cells were demonstrated by immunoperoxidase in 63 of 69 specimens containing ganglion cells and in 1 specimen interpreted as aganglionic by hematoxylin-eosin staining. Increased numbers of nerve fibers in the muscularis mucosae and deep lamina propria by S-100 staining were detected in 8 of 8 specimens diagnostic for Hirschsprung's disease by hematoxylin-eosin and acetylcholinesterase stains and in 1 specimen diagnostic for colonic neuronal dysplasia (a disorder related to Hirschsprung's disease). Whereas 45 of 67 specimens from unaffected bowel showed a normal number and distribution of nerve fibers by S-100 staining, in 22 the pattern resembled that of Hirschsprung's disease. Specimens from affected colon also showed hypertrophied submucosal nerve trunks by S-100 stain (average nerve trunk thickness, 29.8 micron in affected bowel, 16.1 micron in unaffected segments--p less than 0.03). We conclude that NSE and S-100 stains are of value in demonstrating ganglion cells in suspected cases of Hirschsprung's disease and colonic neuronal dysplasia. The acetylcholinesterase stain is preferred over S-100 stain for detecting mucosal nerve proliferations in affected bowel. Submucosal nerve trunk thickness, although significantly different in affected and unaffected colon, is not of diagnostic value because of the wide variation in the measurements in the two groups.


Clinicopathology of soft tissue lesions associated with extracted teeth.
The study assessed the prevalence and the clinical and histologic pattern of soft tissue lesions associated with extracted teeth and determined the validity of clinical diagnoses in comparison with histologic diagnosis. Soft tissue from the apices of 100 teeth extracted by the intra-alveolar approach and from the follicle of 50 teeth extracted by the transalveolar approach was examined histologically subsequent to clinical diagnosis. The subjects were seen within a 2-year period at the Oral Surgery unit of a Nigerian teaching hospital. Association between age, gender, and the histopathologic diagnosis was assessed, and the clinical presumptive diagnoses were compared with the histopathologic diagnoses using the epidemiologic parameters of sensitivity, specificity, and positive and negative predictive values. There were 76 (50.7%) males and 74 (49.3%) females, with age range of 17 to 77 years (33 +/- 14 years). Although clinical diagnosis indicated that all the cases were inflammatory in origin, histopathologic diagnosis reported 84% to be of inflammatory origin, 10% to be normal tissue, and 6% to be noninflammatory in nature. The noninflammatory lesions included dentigerous cyst (4%), central giant cell granuloma (1.3%), and ameloblastoma (0.7%). Gender and age were not associated statistically with type and frequency of pathology. Inflammatory conditions showed the highest sensitivity (98%). The study showed that the probability of clinical misdiagnosis of pathologically significant lesions associated with extracted teeth is lowest with inflammation and highest with cysts and neoplasms. Thus, routine histopathologic examination of all recoverable soft tissues associated with extracted teeth would contribute to improve management of cases although the cost and related implications of this need to be investigated further.


Heterogeneous fate of perfusion and contraction after anterior wall acute myocardial infarction and effects on left ventricular remodeling.
After acute myocardial infarction, patency of infarct vessel and extent of left venticular (LV) dysfunction are major determinants of ventricular remodeling. Spontaneous, delayed reperfusion in the infarct zone occurs in a sizeable number of patients well after the subacute phase. The aim of this study was to determine the relation between the occurrence of this spontaneous, delayed reperfusion and LV remodeling. In 84 patients, resting LV volumes, topography, regional function, and perfusion were quantitatively evaluated by 2-dimensional echocardiography and sestamibi tomography 5 weeks (study 1) and 7 months (study 2) after anterior Q-wave infarction. At study 2, LV end-diastolic volume increased by > 15% in 17 patients (20%, LV remodeling); they had already had at study 1 significantly larger LV volumes, more severe hypoperfusion and wall motion abnormalities, and greater regional dilation than patients with stable LV volumes. Delayed reperfusion occurred in 8 of 17 patients with and in 42 of 67 patients without LV remodeling (47% vs 63%; p=NS). At study 2, LV regional dilation and end-diastolic volumes were stable in patients with, but increased in patients without, spontaneous reperfusion (from 25+/-24% to 29+/-26% at study 2 [p<0.05] and from 65+/-14 to 68+/-18 ml/m2 [p <0.05]). At multivariate analysis, however, regional ventricular dilation at study 1 was the sole predictor of further LV remodeling. Thus, after acute myocardial infarction, spontaneous reperfusion occurring after 5 weeks plays only a minor role in influencing LV remodeling. Benefits from delayed reperfusion seem limited to patients with preserved LV volumes; patients with an enlarged left ventricle 5 weeks after acute infarction are prone to further LV remodeling, irrespective of delayed reperfusion.


The current status of β-thalassemia major in Mainland China.
β-Thalassemia (β-thal) is caused by a decrease in the production of β-globin chains that is a genetic disorder worldwide. The diagnosis of β-thal major (β-TM) depends on clinical manifestations, laboratory investigations, family history and genetic analysis. Patients with β-TM require long-term blood transfusion and chelation therapy. Hematopoietic stem cell transplantation is the only strategy for curing this disease. Many patients with β-TM cannot get regular diagnosis and treatment in developing countries. With economic improvement and medical technology development, a great progress has been made in Mainland China. In this study, we describe the current status of diagnosis and treatment of β-thal in Mainland China.


Progress of Research on Exosomes in the Protection Against Ischemic Brain Injury.
Exosomes, as a type of extracellular vesicle (EV), are lipid bilayer vesicles 20-100 nm in diameter that can cross the blood-brain barrier. Exosomes are important transport vesicles in the human body that participate in many conduction pathways and play an important physiological role. Because of their high biocompatibility and low immunogenicity and toxicity, exosomes have attracted increasing attention as an attractive drug delivery system. This article reviews the relevant studies that have shown that exosomes play an important role in protective mechanisms against ischemic brain injury.


Valproate robustly enhances AP-1 mediated gene expression.
Valproic acid (VPA) is a potent broad spectrum anticonvulsant with demonstrated efficacy in the treatment of Bipolar Affective Disorder, but the biochemical basis for VPA's antimanic or mood-stabilizing actions have not been fully elucidated. It has been demonstrated that VPA, at therapeutically relevant concentrations, increases AP-1 DNA binding activity in cultured cells in vitro. These findings raise the possibility that VPA may produce its mood-stabilizing effects by regulating the expression of subsets of genes via its effects on the AP-1 family of transcription factors. To determine if VPA does, in fact, enhance AP-1 mediated gene expression, the effects of VPA on the expression of a luciferase reporter gene were studied in transiently transfected rat C6 glioma and human SH-SY5Y neuroblastoma cells using the pGL2-control vector. The luciferase gene in the vector is driven by an SV40 promoter which contains well characterized AP-1 sites. VPA produced a greater than doubling of luciferase activity in a time- and concentration-dependent manner in both cell lines. Furthermore, mutations of the AP-1 sites in the SV40 promoter markedly attenuated the VPA-induced increases in luciferase activity. These effects of VPA on AP-1 mediated gene expression are very similar to the effects observed with lithium, and suggest that the temporal regulation of AP-1 mediated gene expression in critical neuronal circuits may play a role in the long-term therapeutic efficacy of these agents.


LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and suppressing Hippo signaling.
In this research, we aimed to investigate the biological functions of LIM domain only 3 (LMO3) in hepatocellular carcinoma (HCC) and uncover the underlying molecular mechanism in it. HCC tissue microarray (n = 180) was used to analyze the correlation between LMO3 expression and clinicopathological findings. In vitro transwell matrigel invasion assay and annexin V anoikis assay in HCC cells were conducted to investigate LMO3 related biological functions. In vivo intrahepatic and lung metastasis models were used to determine the role of LMO3 in HCC metastasis. Quantitative real-time PCR, western blotting and immunohistochemical staining were performed to investigate the expression and mechanism of LMO3 in HCC. We found that the expression of LMO3 was significantly upregulated in HCC tissues, and it was closely related to clinicopathological findings and patient prognoses. Knockdown of LMO3 suppressed the invasion and anoikis inhibition of HCC cells in vitro. Meanwhile, the metastasis of SMMC-7721 cells was also suppressed by LMO3 knockdown in vivo. Furthermore, we found that LMO3 knockdown increased the phosphorylation of YAP and LATS1, and decrease Rho GTPases activities. LMO3 directly interacted with LATS1, and thus suppressed Hippo signaling. Recombinant LMO3 (rLMO3) protein administration decreased the phosphorylation of YAP and LATS1, and increased Rho GTPases activities. The inhibitors of the Hippo pathway abrogated rLMO3 protein-induced HCC cell invasion and anoikis inhibition. These results suggest that LMO3 promotes HCC cell invasion and anoikis inhibition by interacting with LATS1 and suppressing Hippo signaling. LMO3 may serve as a potential therapeutic target for HCC in future.


Use of integrated landscape indicators to evaluate the health of linked watersheds and coral reef environments in the Hawaiian islands.
A linkage between the condition of watersheds and adjacent nearshore coral reef communities is an assumed paradigm in the concept of integrated coastal management. However, quantitative evidence for this "catchment to sea" or "ridge to reef" relationship on oceanic islands is lacking and would benefit from the use of appropriate marine and terrestrial landscape indicators to quantify and evaluate ecological status on a large spatial scale. To address this need, our study compared the Hawai'i Watershed Health Index (HI-WHI) and Reef Health Index (HI-RHI) derived independently of each other over the past decade. Comparisons were made across 170 coral reef stations at 52 reef sites adjacent to 42 watersheds throughout the main Hawaiian Islands. A significant positive relationship was shown between the health of watersheds and that of adjacent reef environments when all sites and depths were considered. This relationship was strongest for sites facing in a southerly direction, but diminished for north facing coasts exposed to persistent high surf. High surf conditions along the north shore increase local wave driven currents and flush watershed-derived materials away from nearshore waters. Consequently, reefs in these locales are less vulnerable to the deposition of land derived sediments, nutrients and pollutants transported from watersheds to ocean. Use of integrated landscape health indices can be applied to improve regional-scale conservation and resource management.


Dual-specificity phosphatase DUSP1 protects overactivation of hypoxia-inducible factor 1 through inactivating ERK MAPK.
Hypoxia-inducible factor 1 (HIF-1) plays a critical role in controlling oxygen delivery and metabolic adaptation to hypoxic conditions in hypoxic tumor cells. HIF-1 activation is initiated by several factors including mitogen-activated protein kinase (MAPK) superfamily. We have previously reported that mitogen-activated protein kinase phosphatase DUSP1 (MKP-1) was implicated in the negative regulation of HIF-1alpha subunit phosphorylation and HIF-1 activity. However, the molecular basis by which MKP-1 influences HIF-1 activity is not clarified. In this paper, we show that hypoxia transcriptionally induces MKP-1 expression in a time-dependent manner. Meanwhile, hypoxia also activates extracellular signal-regulated kinase (ERK) whose activity is enhanced or reduced by MKP-1 suppression or MKP-1 overexpression, respectively. We also show that suppression of MKP-1 expression facilitates the interaction between HIF-1alpha subunit and p300, a co-activator of HIF-1. Moreover, MKP-1 suppression leads to enhanced HIF-1 activity, which can be counteracted by PD98059, an ERK kinase inhibitor. Taken together, the results presented here suggest that hypoxia-induced MKP-1 protects overactivation of HIF-1 activation through inhibiting ERK kinase activity.


Inhibition of glucuronomannan hexamer on the proliferation of lung cancer through binding with immunoglobulin G.
The anti-lung cancer activity of oligosaccharides derived from glucuronomannan was investigated. The inhibition of A549 cell proliferation by glucuronomannan (Gn) and its oligomers (dimer (G2), tetramer (G4) and hexamer (G6)) were concentration dependent. In vivo activities on the A549-derived tumor xenografts showed the tumor inhibition of G2, G4 and G6 were 17 %, 40 % and 46 %, respectively. Organ coefficients in nude mice showed an increase in the kidney with G4, the brain with G6, and the spleen with G6. An advanced tandem mass tag labeled proteomics approach was performed. A significant differential expression was found in 59 out of the 4371 proteins, which involved the immune system. Surface plasmon resonance (SPR) studies revealed G6 was strongly bound to immunoglobulin G. This suggests that glucuronomannan hexamer inhibits the proliferation of lung cancer through its binding to immunoglobulin.


Dinuclear lanthanide complexes supported by a hybrid salicylaldiminato/calix[4]arene-ligand: synthesis, structure, and magnetic and luminescence properties of (HNEt3)[Ln2(HL)(L)] (Ln = SmIII, EuIII, GdIII, TbIII).
The synthesis, structures, and properties of a new calix[4]arene ligand with an appended salicylaldimine unit (H4L = 25-[2-((2-methylphenol)imino)ethoxy]-26,27,28-trihydroxy-calix[4]arene) and four lanthanide complexes (HNEt3)[Ln2(HL)(L)] (Ln = SmIII (4), EuIII (5), GdIII (6), and TbIII (7)) are reported. X-ray crystallographic analysis (for 4 and 6) reveals an isostructural series of dimeric complexes with a triply-bridged NO3Ln(μ-O)2(OHO)LnO3N core and two seven coordinated lanthanide ions. According to UV-vis spectrometric titrations in MeCN and ESI-MS the dimeric nature is maintained in solution. The apparent stability constants range between log K = 5.8 and 6.3. The appended salicylaldimines sensitize EuIII and TbIII emission (λexc 311 nm) in the solid state or immersed in a polycarbonate glass at 77 K (for 5, 7) and at 295 K (for 7).


Short-term immobilization influences use-dependent cortical plasticity and fine motor performance.
Short-term immobilization that reduces muscle use for 8-10h is known to influence cortical excitability and motor performance. However, the mechanisms through which this is achieved, and whether these changes can be used to modify cortical plasticity and motor skill learning, are not known. The purpose of this study was to investigate the influence of short-term immobilization on use-dependent cortical plasticity, motor learning and retention. Twenty-one adults were divided into control and immobilized groups, both of which underwent two experimental sessions on consecutive days. Within each session, transcranial magnetic stimulation (TMS) was used to assess motor-evoked potential (MEP) amplitudes, short- (SICI) and long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF) before and after a grooved pegboard task. Prior to the second training session, the immobilized group underwent 8h of left hand immobilization targeting the index finger, while control subjects were allowed normal limb use. Immobilization produced a reduction in MEP amplitudes, but no change in SICI, LICI or ICF. While motor performance improved for both groups in each session, the level of performance was greater 24-h later in control, but not immobilized subjects. Furthermore, training-related MEP facilitation was greater after, compared with before, immobilization. These results indicate that immobilization can modulate use-dependent plasticity and the retention of motor skills. They also suggest that changes in intracortical excitability are unlikely to contribute to the immobilization-induced modification of cortical excitability.


Being in the moment and shifting self-perspectives.
Being in the moment can either heighten self-awareness through observation and interpretation or result in temporary loss of self through experiences of flow. Patients who can flexibly shift between these self-perspectives benefit the most from treatment. When patients risk breaking away from their fixed patterns, they experience a greater sense of aliveness and engagement. Patients who focus too much on the past or too little on the present have problems being centered. Case studies and Antonioni's film Blowup (1966) illustrate how our lives take on renewed meaning through sustaining a present focus.


Bio-detoxification of Jatropha curcas L. cake by a soil-borne Mucor circinelloides strain using a zebrafish survival model and solid-state fermentation.
The aims of the study were to (i) improve the evaluation criteria of detoxifying Jatropha curcas L. cake (JCC), (ii) isolate and characterize a JCC tolerant strain, (iii) explore its JCC detoxifying potential. The zebrafish was employed as a survival model to screen the strains capable of detoxifying JCC. A strain identified as Mucor circinelloides SCYA25, which is highly capable of degrading all toxic components, was isolated from soil. Different solid-state fermentation parameters were optimized by response surface methodology. The optimal values for inoculation amount, moisture content, temperature, and time were found to be 18% (1·8 × 106 spores g-1 cake), 66%, 26, and 36 days, respectively, to achieve maximum detoxification of the JCC (92%). Under optimal fermentation conditions, the protein content of JCC was increased, while the concentrations of ether extract, crude fiber, toxins, and anti-nutritional substances were all degraded considerably (P < 0·05). Scanning electron microscopy and Fourier transform infrared spectrometer analysis revealed that the fermentation process could disrupt the surface structure and improve the ratio of α-helix to β-folding in the JCC protein, which may improve the digestibility when the detoxified JCC is used as a feedstuff. Our results indicate that M. circinelloides SCYA25 is able to detoxify JCC and improve its nutritional profile, which is beneficial to the safe utilization of JCC as a protein feedstuff. The newly identified M. circinelloides SCYA25 detoxified JCC in a safe manner to provide a potential alternative to soybean meal for the feed industry. These results also provide a new perspective and method for the toxicity evaluation and utilization of JCC and similar toxic agricultural by-products.


Prevalence of Merkel Cell Polyomavirus (MCPyV) in the Oral Cavity Biopsies in Northern Iran.
Infection with human tumor viruses is one of the hypothesized causes of cancer. The current investigation aimed to explore the presence and quantitative analysis of a new human tumor virus, Merkel cell polyomavirus (MCPyV) in tissue samples of 114 patients with oral cavity lesions including oral squamous cell carcinoma (OSCC), oral lichen planus (OLP), Dysplasia and oral irritation fibroma (OIF) in Northern Iran. From 114 formalin fixed paraffin embedded samples; 35 with SCC, 29 with OLP, 14 with dysplasia and 36 with OIF were cut, deparaffinized and DNA was extracted. Quantitative detection of MCPyV large T antigen was performed by absolute quantitative Real-Time PCR. MCPyV DNA was detected in 30.6% (n: 11/36) of IF, 24.1% (n; 7/29) of OLP, 21.4% (n:3/14) of dysplasia and 20% (n;7/35) of OSCC samples. The mean MCPyV DNA copy number was 2.32×10-2 ± 3.97 ×10-2, 2.02×10-2 (SD=3.13×10-2), 2.69×10-4 (SD=2.51×10-4), and 2.56×10-4 (SD=6.73×10-4) per cell in OSCC, dysplasia and both of OLP and OIF samples, respectively (P=0.76). This study provides the first data from Iran regarding the presence of MCPyV genome in oral cavity lesions and oral cancer. These results also emphasize that MCPyV has an active role in the occurrence of oral lesions and progression to cancer. Further studies should be carried out to clarify the role of MCPyV in oral cavity lesions.


Disposition and antimuscarinic effects of the urinary bladder spasmolytics propiverine: influence of dosage forms and circadian-time rhythms.
Propiverine extended release is expected to be better tolerated compared to immediate release tablets because of slower drug release and reduced formation of active metabolites in the colon. CYP3A4 and ABCC2, the major variables in pharmacokinetics of propiverine, are less expressed in the colon. Therefore, disposition and pharmacodynamics of propiverine were measured in a double-blind, double-dummy, crossover study with administration of 15 mg immediate release 3 times daily for 7 days compared to 45 mg extended release once daily for 7 days in 24 healthy subjects. Twelve subjects also received 15 mg propiverine intravenously. Serum and urine propiverine levels were measured repeatedly following oral administration on day 7 for up to 72 hours and correlated to duodenal expression of CYP3A4, ABCB1, and ABCC2. Propiverine immediate release 3 times daily was not different to extended release once daily in areas under the serum concentration-time curve (0-24 hours) and peak-trough fluctuation. The areas under the serum concentration-time curve of propiverine immediate release was circadian-time-dependent, with the lowest values during the night. Disposition of intravenous propiverine and propiverine immediate release administered in the night was influenced by intestinal expression of ABCC2. We concluded that oral absorption of propiverine is site-dependent and influenced by dosage form and circadian-time-dependent elimination processes.


Cellulose Nanowhisker/Silver Nanoparticle Hybrids Sterically Stabilized by Surface Poly(ethylene glycol) Grafting.
Sterically stabilized hybrids of cellulose nanowhiskers (CNWs) and silver nanoparticles (AgNPs) were prepared via poly(ethylene glycol) (PEG) grafting and subsequent reduction of Ag+ counterions by sodium borohydride (NaBH4) for improved dispersion stability after hybridization. The preparation scheme includes surface carboxylation of CNWs using a 2,2,6,6-tetramethyl-1-pyperidinyloxy radical (TEMPO), grafting of monomethoxy PEG (mPEG) via amidation mediated by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride or 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, exchange of countercation of residual carboxyls to Ag+, and deposition of AgNPs via reduction with NaBH4. UV-vis spectroscopy and electron microscopy analyses confirmed the successful deposition of AgNPs. Most of the mPEG-grafted hybrids were stable under the presence of an electrolyte, although some of them were precipitated by the addition of 0.1 M CaCl2. The addition of CaCl2 was also found to trigger discoloration of the hybrids, suggesting the partial dissolution of AgNPs and the formation of water-insoluble AgCl.


Ventilation in the trauma and surgical patient.
Changes in the understanding of the pathophysiology of ARDS and effects of mechanical ventilation with high pressures have led to treatment strategies that resulted in improved survival rates. The central principle in these strategies is to avoid ventilation induced lung injury by allowing the lungs to rest. A number of promising new treatments emphasizing this principle are under investigation. Physicians caring for patients who develop ARDS should make every effort to avoid alveolar overdistention by ventilating patients in the compliant portion of pressure-flow loop and avoid peak inspiratory pressures in excess of 40 cm H2O.


Effect of specific growth limitations on cell wall composition of Staphylococcus aureus H.
Conditions are described for the continuous culture of a derivative of Staphylococcus aureus H in a fully defined minimal medium in which cysteine is the sole amino acid. The effects of growth under various nutrient limitations on the composition and properties of the cell wall have been studied. The proportion of ribitol teichoic acid present in the wall, and the extent to which it is substituted with N-acetylglucosamine, varies in bacteria grown under different conditions as does the composition and extent of cross-linking of the peptidoglycan. Neither the derivative nor the original strain H produced teichuronic acid when grown under phosphate limitation.


Protecting the stars of tomorrow: do international cardiovascular preparticipation screening policies account for the paediatric athlete? A systematic review and quality appraisal.
(1) Identify and review current policies for the cardiovascular screening of athletes to assess their applicability to the paediatric population and (2) evaluate the quality of these policy documents using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool. Systematic review and quality appraisal of policy documents. A systematic search of PubMed, MEDLINE, Scopus, Web of Science, SportDiscus and CINAHL. An article was included if it was a policy/position statement/guideline/consensus or recommendation paper relating to athletes and cardiovascular preparticipation screening. Of the 1630 articles screened, 13 met the inclusion criteria. Relevance to paediatric athletes was found to be high in 3 (23%), moderate in 6 (46%) and low in 4 (31%), and only 2 provide tailored guidance for the athlete aged 12-18 years. A median 5 related citations per policy investigated solely paediatric athletes, with study designs most commonly being retrospective (72%). AGREEII overall quality scores ranged from 25% to 92%, with a median of 75%. The lowest scoring domains were rigour of development; (median 32%) stakeholder involvement (median 47%) and Applicability (median 52%). Cardiac screening policies for athletes predominantly focus on adults, with few providing specific recommendations for paediatric athletes. The overall quality of the policies was moderate, with more recent documents scoring higher. Future research is needed in paediatric athletes to inform and develop cardiac screening guidelines, to improve the cardiac care of youth athletes.


Motility of Vibrio spp.: regulation and controlling strategies.
Flagellar motility in bacteria is a highly regulated and complex cellular process that requires high energy investment for movement and host colonization. Motility plays an important role in the lifestyle of Vibrio spp. in the aquatic environment and during host colonization. Flagellar motility in vibrios is associated with several cellular processes, such as movement, colonization, adhesion, biofilm formation, and virulence. The transcription of all flagella-related genes occurs hierarchically and is regulated positively or negatively by several transcription factors and regulatory proteins. The flagellar regulatory hierarchy is well studied in Vibrio cholerae and Vibrio parahaemolyticus. Here, we compared the regulatory cascade and molecules involved in the flagellar motility of V. cholerae and V. parahaemolyticus in detail. The evolutionary relatedness of the master regulator of the polar and lateral flagella in different Vibrio species is also discussed. Although they can form symbiotic associations of some Vibrio species with humans and aquatic organisms can be harmed by several species of Vibrio as a result of surface contact, characterized by flagellar movement. Thus, targeting flagellar motility in pathogenic Vibrio species is considered a promising approach to control Vibrio infections. This approach, along with the strategies for controlling flagellar motility in different species of Vibrio using naturally derived and chemically synthesized compounds, is discussed in this review. KEY POINTS: • Vibrio species are ubiquitous and distributed across the aquatic environments. • The flagellar motility is responsible for the chemotactic movement and initial colonization to the host. • The transition from the motile into the biofilm stage is one of the crucial events in the infection. • Several signaling pathways are involved in the motility and formation of biofilm. • Attenuation of motility by naturally derived or chemically synthesized compounds could be a potential treatment for preventing Vibrio biofilm-associated infections.


Magnetic Resonance Imaging Study of the Pericranial Flap and Its Local Effects Following Endoscopic Craniofacial Resection.
To describe the magnetic resonance imaging (MRI) characteristics of the pericranial flap, changes in the pericranial flap thickness over time, presence of frontal sinus opacification, and presence of frontal lobe herniation into the nasal cavity. Retrospective case series. Seventeen consecutive endoscopic craniofacial resections with pericranial flap reconstruction performed at a tertiary hospital from 2010 to 2019 were reviewed. Sixty-eight serial MRI scans were evaluated. All pericranial flaps consistently featured a homogenous appearance on T1-weighted sequence and enhanced with contrast. On T2-weighted sequence, the skull base reconstruction demonstrated four layers of alternating hypo- and hyperintensity, which corresponded with the inlay synthetic graft or neodura (hypointense), loose areolar tissue (hyperintense), fibrous pericranium (hypointense), and nasal mucosa or granulation tissue (hyperintense). The mean pericranial flap thickness was 9.9 mm. In thicker flaps, the loose areolar layer contributed the bulk of the thickness. Of 13 patients who underwent three or more serial MRI scans, 11 flaps (84.6%) were stable and two (15.4%) had >50% reduction in their original thickness over time. Thirteen of 17 (76.5%) patients had frontal sinus opacification on follow-up. None developed frontal sinus mucoceles or frontal lobe herniation. The pericranial flap has a distinctive MRI appearance, especially on T2-weighted sequence. The thickness of the flap remains relatively stable over time for most patients even following radiotherapy. It is a sturdy flap that is able to support the frontal lobe. Frontal sinus obstruction is common, although complications from this appear to be rare. 4 Laryngoscope, 131:E90-E97, 2021.


Symptom concerns and quality of life in hepatobiliary cancers.
To describe the symptom concerns of patients with hepatocellular carcinoma (HCC) and pancreatic cancer and explore the effect of symptoms on patients' quality of life (QOL). Descriptive, longitudinal study. Ambulatory clinics of a comprehensive cancer center. 45 patients actively receiving treatment for either HCC or pancreatic cancer. Patients were followed from baseline for three months, with outcome measures repeated monthly. Outcome measures included the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and the Functional Assessment of Chronic Illness Therapy-Spirituality Subscale (FACIT-Sp-12). Descriptive analysis of demographic, treatment, and symptom data was conducted, followed by two-way repeated measures analysis of variance of FACT-Hep and FACIT-Sp-12 scale scores by diagnosis and treatment type. Symptoms, QOL. Overall QOL is poor in patients with hepatobiliary cancer, and this trend continues over time. Symptoms such as abdominal pain, fatigue, weight loss, and poor appetite commonly are reported in this population. Patients with hepatobiliary cancer suffer from multiple symptoms that may have a negative affect on overall QOL. Specific QOL domains, such as physical and functional well-being, are of particular concern for patients. The identification of specific symptom and QOL concerns in hepatobiliary cancers will enhance clinical care and aid in the future development of multidisciplinary interventions for this understudied cancer population.


Can you be cured if the doctor disagrees? A case study of 27 prayer healing reports evaluated by a medical assessment team in the Netherlands.
THE SETTING: between 2015 and 2020 a medical assessment team evaluated 27 reports of prayer healing in the Netherlands. Three research questions were formulated. What are the medical and experiential findings? Are there medically remarkable and/or unexplained healings? Which explanatory frameworks can help us understand the findings? The reported healings were analyzed using both medical files and patient narratives, as part of a case study research design compiled by a multidisciplinary research team. An independent team of five medical consultants, representing different fields of expertise, evaluated the 27 case files. According to criteria these were selected from a larger group of 83 received reports. Experiential data was obtained by in-depth interviews and analyzed. Instances of healing could be classified as 'medically remarkable' or 'medically unexplained'. Subsequent analysis was transdisciplinary. Eleven of the 27 healings assessed were evaluated as 'medically remarkable', none were labelled as 'medically unexplained'. Recurring characteristics were common to some degree in all healings, whether 'medically remarkable' or not: a temporal connection with prayer, instantaneity and unexpectedness of healing, strong emotional and physical manifestations, and a sense of 'being overwhelmed' and transformed. The healings were invariably interpreted as acts of God. Positive effects have persisted for 5 to 33 years, with 2 relapses. Our findings on remarkable healings do not fit well in the traditional biomedical conceptual framework. All healings exhibited important non-medical aspects, whether or not they were assessed as medically remarkable. We need a broader multi-perspective approach in which all relevant data is considered to be valuable, both experiential and objective. This so-called horizontal epistemology may be helpful when trying to understand the findings, and it may bring about mutual understanding between patients, health practitioners and relevant disciplines.


Infective endocarditis associated with a scorpion sting.
We report the successful surgical intervention in two cases of aortic valve bacterial endocarditis after scorpion stings. Infective endocarditis developed in both patients several weeks after they suffered repeated scorpion stings. Both patients had similar, but uncommon features: (1) the isolated organisms were unusual causes of infective endocarditis (streptococcus group G and Streptococcus milleri), (2) annular abscesses developed that required either aortic root replacement with a homograft or annular patch repair with pericardium, and (3) complete heart block developed postoperatively, requiring permanent pacemaker implantation. Both patients completed a 6-week postoperative course of antibiotic therapy and are without recurrent infection.


Adult living donor liver transplantation from donors with Gilbert's syndrome: Is it safe?
We evaluate whether it is safe to accept donors with Gilbert's syndrome (GS) for a living donor liver transplantation (LDLT) or not. This study is the first controlled study to be conducted. Between January 2004 and May 2014, 600 LDLTs which used right lobe liver grafts were performed in our center. Forty-five of the 600 donors had a GS diagnosis. For a control group, 99 donors without GS who had completed 1 year or more of follow-up were selected retrospectively and consecutively. The clinical results of the donors and recipients were then analyzed. A total of 45 donors with GS and 99 donors without GS were included. There were no significant differences in patient demographics, actual graft weight, remnant ratio, portal and ductal variations, pre-peri-post-operative liver enzymes. The donors with GS had significantly higher bilirubin levels compared with the control group at first reading, at maximal peak, and post-operative 1-7 days, 1st and 6th months (P < .001 for all readings). Post-operative complication ratio was 40% in GS, 34.3% in non-GS group. In GS and non-GS group, hospitalization period was 10.2 and 9.2 days, respectively. The 1-year donor survival rate was 100% for both groups and 1-year recipient survival was similar who have donors with GS and non-GS (93.3%; 92.9%, P = .93). The use of right lobe grafts from donors with GS appears to be safe for donor health.


Circulating microRNAs: a novel potential biomarker for diagnosing acute aortic dissection.
Acute aortic dissection (AAD) is a catastrophic emergency with high mortality and misdiagnosis rate. We aimed to determine whether circulating microRNAs allow to distinguish AAD from healthy controls and chest pain patients without AAD (CP). Plasma microRNAs expression were determined in 103 participants, including 37 AAD patients, 26 chronic aortic dissection patients, 17 healthy volunteers, 23 patients without AAD. We selected 16 microRNAs from microarray screening as candidates for further testing via qRT-PCR. The results showed that plasma miR-15a in patients with AAD (n = 37) had significantly higher expression levels than it from control group (n = 40; P = 0.008). By receiver operating characteristic curve analysis, the sensitivity was 75.7%; the specificity was 82.5%; and the AUC was 0.761 for detection of AAD. Furthermore, 37 patients with AAD had significantly higher plasma expression levels of let-7b, miR-15a, miR-23a and hcmv-miR-US33-5p compared with 14 CP patients of 40 controls (P = 0.000, 0.000, 0.026 and 0.011, respectively). The corresponding sensitivity were 79.4%, 75.7%, 91.9% and 73.5%, respectively; the specificity were 92.9%, 100%, 85.7% and 85.7%, respectively; and the AUCs of these microRNAs were 0.887, 0.855, 0.925 and 0.815, respectively. These data indicate that plasma miR-15a and miR-23a have promising clinical value in diagnosing AAD.


The biliary tree--a reservoir of multipotent stem cells.
The biliary tree is composed of intrahepatic and extrahepatic bile ducts, lined by mature epithelial cells called cholangiocytes, and contains peribiliary glands deep within the duct walls. Branch points, such as the cystic duct, perihilar and periampullar regions, contain high numbers of these glands. Peribiliary glands contain multipotent stem cells, which self-replicate and can differentiate into hepatocytes, cholangiocytes or pancreatic islets, depending on the microenvironment. Similar cells-presumably committed progenitor cells-are found in the gallbladder (which lacks peribiliary glands). The stem and progenitor cell characteristics indicate a common embryological origin for the liver, biliary tree and pancreas, which has implications for regenerative medicine as well as the pathophysiology and oncogenesis of midgut organs. This Perspectives article describes a hypothetical model of cell lineages starting in the duodenum and extending to the liver and pancreas, and thought to contribute to ongoing organogenesis throughout life.


Beyond Meaning: Globalization and the Icons of Power.
As the nature of symbolic mechanisms has been reconsidered, shared meaning in healing rituals can no longer be unproblematically assumed. Globalization processes challenge the idea of local worlds of meaning as foundational for healing. Discussing two episodes of healing in 'global assemblages', the paper questions the centrality of meaning in the healing encounter. In search for alternatives, it turns to the ethical phenomenology of Levinas. It is suggested that in the core of healing encounter lies 'the healing gesture' of the Other seen as an icon of power.


Munc18 - Munc13-dependent pathway of SNARE complex assembly is resistant to NSF and α-SNAP.
Synaptic exocytosis requires efficient SNARE complex assembly that is precisely regulated by multiple regulatory proteins. Increasing evidence suggests that Munc18-1 and Munc13-1 protect SNARE complex assembly in a manner resistant to NSF and α-SNAP. However, the protective mechanisms of Munc18-1 and Munc13-1 are not fully understood. Here, by analyzing two pathways of SNARE complex assembly (i.e., the Munc18 - Munc13-dependent pathway and the Munc18 - Munc13-independent pathway), we found that the Munc18 - Munc13-dependent pathway of SNARE complex assembly is resistant to NSF - α-SNAP. In this pathway, Munc18-1 and Munc13-1 each, independently, have protective effects. The protective effect of Munc18-1 relies on the interaction with the C-terminal part of Syb2 during the transition from the Munc18-1/Syx1 complex to the SNARE complex. Moreover, the protective effect of Munc13-1 is most likely attributed to its ability in templating the assembling SNAREs. In addition, we found that the Munc18 - Munc13-dependent pathway opposes the association of α-SNAP with the SNARE bundle, thus explaining how this pathway is resistant to NSF - α-SNAP disassembly. Although the above results were derived from the studies on SNARE complex in solution or in cis-configurations, instead of trans-configurations residing on the opposite membrane, our data could still help to understand the protective mechanism of Munc18-1 and Munc13-1 in SNARE-mediated synaptic exocytosis.


Chronic obstructive pulmonary diseases related health resources allocation in hunan province of china.
Information about Chronic obstructive pulmonary diseases (COPD)-related health resources allocation in China is very limited. The aim of the study was to explore the distribution of COPD-related health resources allocation among different levels public hospitals (PHs) in Hunan Province of central south China. We randomly collected data from 57 Public Hospitals (PHs) at 3 different levels in Hunan province as well as 893 pulmonary physicians (PPs) who worked there in 2009. Questionnaires based on the recommendations of COPD guideline were designed, including availability of spirometers, inhaled agents for COPD and COPD-related health education for local residents, as well as PPs' educational levels. Spirometers equipped ratio in 3(rd) level PHs was much higher than 1(st), 2(nd) PHs. The disparity varied vastly form 0% to 100%. The inhaled agents equipped ratio was 5.56%, 70.85% and 100% respectively for the 1(st), 2(nd) and 3(rd) levels PHs. No 1(st) level PHs launched COPD-related healthcare education for local residents, only 10 of 24 for the 2(nd) level PHs and 10 of 15 for the 3(rd) level PHs. PPs of high educational levels concentrate in 3(rd) levels PHs, however, PPs working in 1(st) levels PHs and 2(nd) levels PHs were mainly low and median educational levels PPs' knowledge of COPD of 3(rd) levels PHs was much better than of 1(st) levels PHs and 2(nd) levels PHs. The extreme imbalance and disparity existed in COPD-related health resources allocation at three levels PHs in central south China. Inequity and insufficient in COPD-related health resources in 1(st) and 2(nd) levels PHs should be improved.


Effects of voltage on the emergence and spread of antibiotic resistance genes in microbial electrolysis cells: From mutation to horizontal gene transfer.
Microbial electrolysis cells (MECs) are widely considered as promising alternatives for degrading antibiotics. As one of the major operating parameters in MECs, voltage might affect the spread of antibiotic resistance genes (ARGs) given it can affect the physiological characteristics of bacteria. However, little is known about the impacts of voltage on the acceleration of bacterial mutation and the promotion of ARG dissemination via horizontal transfer in MECs. In this study, two voltages (0.9 V and 1.5 V) were applied to identify if electrical stimulation could increase bacterial mutation frequency. Three voltages (0.9 V, 1.5 V, and 2.5 V) were used to evaluate the conjugative transfer frequency of plasmid-encoded the ARGs from the donor (E. coli K-12) to the recipient (E. coli HB101) in MECs. After repeating subculture in MECs for 10 days, the mutation frequency of E. coli K-12 was promoted, consequently, the generated mutants became more resistant against tetracycline. When the voltage was higher than 0.9 V, conjugative ARG transfer frequency was significantly increased in the anode chamber (p < 0.05). The over-production of reactive oxygen species (ROS) (voltage >0.9 V) and cell membrane permeability (voltage >1.5 V) were significantly enhanced under electrical stimulations (p < 0.05). Genome-wide RNA sequencing indicated that the expressions of genes related to oxidative stress and cell membrane were upregulated with exposure to electrical stimulation. Electrical stimulations induced oxidative reactions, which triggered ROS over-production, SOS response, and enhancement of cell membrane permeability for both donor and recipient in the MECs. These findings provide insights into the potential role of voltage in the generation and spread of ARGs in MECs.