Wearable tubing assistive walking device immediately enhances gait parameters in subjects with stroke: A randomized controlled study.
Stroke patients develop compensatory movements due to limitations of ankle dorsiflexion and knee flexion. To solve the limitations, there are many adjustable walking assistive devices such as robotic devices, ankle-foot orthoses, and functional electric stimulation in rehabilitation session. However, these assistive devices have some disadvantages, including expense and discomforts. Therefore, the development of a new assistive device for stroke patients is needed to assist ankle dorsiflexion and knee flexion. This study investigated the effects of a wearable tubing assistive walking device (WTAWD) on gait parameters (gait speed, cadence, and step length and stride length on affected and less affected sides) in patients with stroke. Gait parameters were measured using the GAITRite system. One-way repeated measures analysis of variance was used to determine gait differences under three conditions (WTAWD, barefoot, and conventional elastic band orthosis). Gait speed, cadence, and step length and stride length on both affected and less affected sides were significantly greater with WTAWD, compared to barefoot and conventional elastic band orthosis conditions. WTAWD could be effective for patients with stroke.


Pharmacological treatment of delayed cerebral ischemia and vasospasm in subarachnoid hemorrhage.
Subarachnoid hemorrhage after the rupture of a cerebral aneurysm is the cause of 6% to 8% of all cerebrovascular accidents involving 10 of 100,000 people each year. Despite effective treatment of the aneurysm, delayed cerebral ischemia (DCI) is observed in 30% of patients, with a peak on the tenth day, resulting in significant infirmity and mortality. Cerebral vasospasm occurs in more than half of all patients and is recognized as the main cause of delayed cerebral ischemia after subarachnoid hemorrhage. Its treatment comprises hemodynamic management and endovascular procedures. To date, the only drug shown to be efficacious on both the incidence of vasospasm and poor outcome is nimodipine. Given its modest effects, new pharmacological treatments are being developed to prevent and treat DCI. We review the different drugs currently being tested.


The Efficacy of Psychoeducational Family Intervention for Major Depression: Study Protocol of a Randomized Controlled Trial.
This study aims to assess the efficacy of a psychoeducational family intervention (PFI) to reduce the severity of depressive symptoms and to improve psychosocial functioning and to increase social contacts in a sample of patients with major depressive disorder (MDD). The degree to which PFI will reduce patients' relapses, hospitalizations, and self-stigmatization and will improve their quality of life will also be assessed. Other secondary outcomes include the improvement of relatives' coping strategies, family burden, expressed emotions and quality of life. This non-profit, unfunded, national, multicentric randomized controlled trial with blinded outcome assessments will be carried out in 24 Italian university outpatient units. Families will be assessed at baseline and at 6, 12, and 24 months post-randomization. Our working hypothesis is that the PFIs will reduce the patients' severity of depressive symptoms, their relapses, and their hospitalizations, and that they will improve their psychosocial functioning and quality of life. We expect these results to be maintained after 12 and 24 months, albeit with a reduction in magnitude. The sample will consist of 384 patients randomized at a 1:1 ratio and stratified according to center, age, gender, and educational level.


Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis.
Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA. The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches. The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome. This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy.


Human RNase3 immune modulation by catalytic-dependent and independent modes in a macrophage-cell line infection model.
The human RNase3 is a member of the RNaseA superfamily involved in host immunity. RNase3 is expressed by leukocytes and shows broad-spectrum antimicrobial activity. Together with a direct antimicrobial action, RNase3 exhibits immunomodulatory properties. Here, we have analysed the transcriptome of macrophages exposed to the wild-type protein and a catalytic-defective mutant (RNase3-H15A). The analysis of differently expressed genes (DEGs) in treated THP1-derived macrophages highlighted a common pro-inflammatory "core-response" independent of the protein ribonucleolytic activity. Network analysis identified the epidermal growth factor receptor (EGFR) as the main central regulatory protein. Expression of selected DEGs and MAPK phosphorylation were inhibited by an anti-EGFR antibody. Structural analysis suggested that RNase3 activates the EGFR pathway by direct interaction with the receptor. Besides, we identified a subset of DEGs related to the protein ribonucleolytic activity, characteristic of virus infection response. Transcriptome analysis revealed an early pro-inflammatory response, not associated to the protein catalytic activity, followed by a late activation in a ribonucleolytic-dependent manner. Next, we demonstrated that overexpression of macrophage endogenous RNase3 protects the cells against infection by Mycobacterium aurum and the human respiratory syncytial virus. Comparison of cell infection profiles in the presence of Erlotinib, an EGFR inhibitor, revealed that the receptor activation is required for the antibacterial but not for the antiviral protein action. Moreover, the DEGs related and unrelated to the protein catalytic activity are associated to the immune response to bacterial and viral infection, respectively. We conclude that RNase3 modulates the macrophage defence against infection in both catalytic-dependent and independent manners.


Extent of thyroidectomy: When should hemithyroidectomy be performed? Recommendations from the Francophone Association for Endocrine Surgery, the French Society of Endocrinology and the French Society of Nuclear Medicine.
These recommendations, drawn from current data in the medical literature, incorporate the risks of hemithyroidectomy (HT) and total thyroidectomy (TT) and clarify the place of these two procedures in clinical settings. Discussions leading to a consensus were then assessed by the Francophone Association for Endocrine Surgery (Association francophone de chirurgie endocrinienne [AFCE]), along with the French Society of Endocrinology (Société française d'endocrinologie [SFE]), and the French Society of Nuclear Medicine (Société française de médecine nucléaire [SFMN]). The complication rate was twice as high after TT compared to HT. Total thyroidectomy requires life-long thyroid hormone supplementation, whereas such supplementation is required in only 30% of patients after HT. When surgery is indicated for Bethesda category II nodules, and in the absence of any indication for surgery on the contralateral lobe, HT is recommended. In patients with thyroid cancer (TC)≤1cm requiring surgical management or TC≤2cm, in the absence of risk factors for TC and in the absence of pre- or intraoperative detection of extrathyroidal extension, lymph node metastases (cN0) and/or suspected contra-lateral disease, HT is the preferred technique as long as the patient accepts the possibility of TT which might be required when aggressive forms of cancer are detected on definitive cytohistology (extrathyroidal extension, lymphovascular invasion, high-grade histology). For TC measuring between 2 and 4cm, the debate between HT and TT remains open today, although some surgeons tend to prefer TT. In patients with TC>4cm, macroscopic lymph node involvement (cN1), signs of extrathyroidal extension or predisposing factors for TC, TT is the treatment of choice.


Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma.
Regulatory T cells (T(regs)) may inhibit immunity against cancer. Induction and expansion of T(regs) in the immunosuppressive microenvironment created by a growing tumour appear to be one of the mechanisms by which it can evade host defence. We studied the impact of CD25+ T(regs) in a B cell lymphoma model in which Rag2-/- mice received adoptive transfer of wild-type spleen cells with or without CD25+ cells, and concurrently subcutaneous inoculation of the B cell lymphoma cell line A20. We also examined the effect of engaging the glucocorticoid-induced tumour necrosis factor receptor (GITR) - an approach reported previously to abrogate the suppressive effects of T(regs). Mice that received spleen cells depleted of CD25+ T(regs) showed significantly slower tumour growth and increased survival compared with mice that received unsorted spleen cells. The T(reg)-depleted group also had significantly more CD8+ T cells infiltrating the tumours and higher levels of serum immunoglobulin G subclasses. The anti-GITR treatment had no significant effect on tumour growth, survival or immunoglobulin production. In the CD25-depleted group four of 10 mice developed clinical signs of autoimmunity, in contrast to none in the non-depleted group. Forkhead box P3+ T cells were found in tumour-draining lymph nodes in mice in the CD25-depleted group, suggesting an in vivo induction or expansion of rare transferred donor T(regs). Thus, our study showed that removal of CD25+ T(regs) enhanced anti-tumour immunity against local growth of a B cell lymphoma and that induction or expansion of T(regs) could be one mechanism by which the growing tumour evades immune surveillance.


Concussion among soccer players in the 2017 Brazilian championship - the gap between protocol and medical practice.
The present study aims to report traumatic brain injury (TBI) among soccer players in the 2017 Brazilian Soccer Championship and discuss the protocols for concussion evaluation. This is an observational study utilizing video analysis of 380 matches. TBI was considered as any event in which one or more soccer player(s) had a head trauma. For potential concussion diagnosis, we analyzed players with one of the following signs: slowness to get up, disorientation, motor incoordination, loss of consciousness, head clutching and impact seizure. There were 374 TBIs in total. The average time for medical assessment was 1'35". 13 players had concussion with an average time of 3'19″ for medical evaluation. Four players were replaced after having a concussion. There is a gap between concussion protocols and medical practices in Brazilian elite soccer. Further discussion about soccer replacement rules are imperative.


Annotation matters: validating the discovery of cancer drivers.
Advanced sequencing techniques have helped unveil numerous new, potential cancer driver mutations. However, manual curation and analysis of gene and protein annotation are essential to verify such discoveries. Our recent study of STK19 (Serine Threonine Kinase 19), a previously identified melanoma driver, is a clear example of the importance of such detailed analysis, with both STK19 gene and protein annotations in frequently used databases having been proven incorrect.


Emotion regulation, emotionality, and expression of emotions: A link between social skills, behavior, and emotion problems in children with ASD and their peers.
This study aimed to investigate differences between emotion regulation (ER), emotionality, and expression of emotions in children with Autism Spectrum Disorder (ASD) and their typically developing (TD) peers; and to examine the potential links between these areas of development with social skills in both groups, as well as with behavioral, emotional, and social problems in ASD. Forty-four children (40 males and 4 females, ages 3 to 7 years) with ASD (n = 22) and their TD peers (n = 22) were included in this study. Mothers reported about their children's ASD symptoms, social, emotional, and behavioral functioning. As predicted, children with ASD were described as showing decreased ER, increased emotionality, and decreased expression of emotions when compared to their TD peers. Moreover, in the ASD group, increased social skills were associated with enhanced ER and increased expression of emotions; and in the TD group, increased social skills were correlated with decreased emotionality. Finally, enhanced ER was linked to decreased peer problems, and increased prosocial behaviors; and decreased emotionality was linked to decreased behavior and emotional problems in the ASD group. Implications for further research are discussed.


Threat induces cardiac and metabolic changes that negatively impact survival in flies.
Adjusting to a dynamic environment involves fast changes in the body's internal state, characterized by coordinated alterations in brain activity and physiological and motor responses. Threat-induced defensive states are a classic case of coordinated adjustment of bodily responses, cardiac regulation being one of the best characterized examples in vertebrates. A great deal is known regarding the neural basis of invertebrate defensive behaviors, mainly in Drosophila melanogaster. However, whether physiological changes accompany these remains unknown. Here, we set out to describe the internal bodily state of fruit flies upon an inescapable threat and found cardiac acceleration during running and deceleration during freezing. In addition, we found that freezing leads to increased cardiac pumping from the abdomen toward the head-thorax, suggesting mobilization of energy resources. Concordantly, threat-triggered freezing reduces sugar levels in the hemolymph and renders flies less resistant to starvation. The cardiac responses observed during freezing were absent during spontaneous immobility, underscoring the active nature of freezing response. Finally, we show that baseline cardiac activity predicts the amount of freezing upon threat. This work reveals a remarkable similarity with the cardiac responses of vertebrates, suggesting an evolutionarily convergent defensive state in flies. Our findings are at odds with the widespread view that cardiac deceleration while freezing has first evolved in vertebrates and that it is energy sparing. Investigating the physiological changes coupled to defensive behaviors in the fruit fly has revealed that freezing is costly yet accompanied by cardiac deceleration and points to heart activity as a key modulator of defensive behaviors.


Accuracy of acetabular component alignment with surgical guidance systems during hip arthroplasty.
Navigation in total hip arthroplasty has been shown to improve acetabular positioning and can decrease the incidence of mal-positioned acetabular components. This study aimed to assess two surgical guidance systems by comparing intra-operative measurements of acetabular component inclination and anteversion with a post-operative CT scan. We prospectively collected intra-operative navigation data from 102 hips receiving conventional THA or hip resurfacing arthroplasty through either a direct anterior or posterior approach. Two guidance systems were used simultaneously: an inertial navigation system (INS) and an optical navigation system (ONS). Acetabular component anteversion and inclination were measured on a post-operative CT. The average age of the patients was 64 years (range: 24-92) and the average BMI was 27 kg/m2 (range 19-38). 52% had hip surgery through an anterior approach. 98% of the INS measurements and 88% of the ONS measurements were within 10° of the CT measurements. The mean (and standard deviation) of the absolute difference between the postoperative CT and the intra-operative measurements for inclination and anteversion were 3.0° (2.8) and 4.5° (3.2) respectively for the ONS, along with 2.1° (2.3) and 2.4° (2.1) respectively for the INS. There was a significantly lower mean absolute difference to CT for the INS when compared to ONS in both anteversions (p < 0.001) and inclination (p = 0.02). We found that both inertial and optical navigation systems allowed for adequate acetabular positioning as measured on postoperative CT, and thus provide reliable intraoperative feedback for optimal acetabular component placement. Therapeutic Level II.


Chemotherapy-induced amenorrhea in patients with breast cancer with a BRCA1 or BRCA2 mutation.
To determine the likelihood of long-term amenorrhea after treatment with chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation. We conducted a multicenter survey of 1,954 young women with a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included premenopausal women who were diagnosed with invasive breast cancer between 26 and 47 years of age. We determined the age of onset of amenorrhea after breast cancer for women who were and were not treated with chemotherapy, alone or with tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when the patient experienced ≥ 2 years of amenorrhea, commencing within 2 years of initiating chemotherapy, with no resumption of menses. Of the 1,426 women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed before age 30 years, 33% for women age 31 to 44 years, and 79% for women diagnosed after age 45 years (P trend < .001). The probability of induced amenorrhea was higher for women who received tamoxifen than for those who did not (52% v 29%; P < .001). Age at treatment and use of tamoxifen are important predictors of chemotherapy-induced amenorrhea in women who carry a BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem to be greater among mutation carriers than among women who do not carry a mutation.


Synthesis and antimalarial activities of a diverse set of triazole-containing furamidine analogues.
Four different series of triazole diamidines have been prepared by the Pinner method from the corresponding triazole dinitriles. Copper-catalyzed "click chemistry" was used for the synthesis of 1,4- and 4,5-substituted triazoles, aryl magnesium acetylide reagents for the 1,5-substituted triazoles, with a thermal dipolar addition reaction employed for the 2,4-substituted triazoles. In vitro antimalarial activity against two different PfCRT-modified parasite lines (Science 2002, 298, 210-213) of Plasmodium falciparum and inhibition of hemozoin formation were determined for each compound. Several diamidines with potent nanomolar antimalarial activities were identified, and selected molecules were resynthesized as their diamidoxime triazole prodrugs. One of these prodrugs, OB216, proved to be highly potent in vivo with an ED50 value of 5 mg kg(-1) (po) and an observed 100 % cure rate (CD100) of just 10 mg kg(-1) by oral (po) administration in mice infected with P. vinckei.


Preventative and Therapeutic Effects of Low-dose Ionizing Radiation on the Allergic Response of Rat Basophilic Leukemia Cells.
The prevalence of allergies has increased over the last four decades. In allergic reactions, mast cells induce a hypersensitive immune response to a substance that is normally harmless. Ionizing radiation has different biological effects depending on the dose and dose rate. In this study, we investigated whether low-dose irradiation before (preventative effect) or after (therapeutic effect) an antigen-antibody reaction has an anti-allergic effect. To test this, we activated rat basophilic leukemia (RBL-2H3) mast cells with anti-2,4-dinitrophenyl IgE (antibody) and 2,4-dinitrophenyl human serum albumin, which served as an antigen. To test for both the potential of a preventative effect and a therapeutic effect, we irradiated mast cells both before and after mast cell activation, and we measured mediator release and signaling pathway activity. Low-dose ionizing radiation suppressed mediator release from RBL-2H3 mast cells activated by the antigen-antibody reaction regardless of when the mast cells were irradiated. These results were due to the suppression of FcεRI expression. Therefore, we suggest that low-dose ionizing radiation has a preventative and therapeutic effect in allergic reactions via the FcεRI-mediated RBL-2H3 mast cell activation system.


Surfactant-facilitated remediation of metal-contaminated soils: efficacy and toxicological consequences to earthworms.
The effectiveness of surfactant formulations to remove aged metals from a field soil and their influence on soil toxicity was investigated. Batch studies were conducted to evaluate the efficacy of cationic (1-dodecylpyridinium chloride; DPC), nonionic (oleyl dimethyl benzyl ammonium chloride; trade name Ammonyx KP), and anionic (rhamnolipid biosurfactant blend; trade name JBR-425) surfactants for extracting Zn, Cu, Pb, and Cd from a soil subjected to more than 80 years of metal deposition. All three surfactants enhanced removal of the target metals. The anionic biosurfactant JBR-425 was most effective, reducing Zn, Cu, Pb, and Cd in the soil by 39, 56, 68, and 43%, respectively, compared with less than 6% removal by water alone. Progressive acidification of the surfactants with citric acid buffer or addition of ethylenediaminetetra-acetic acid (EDTA) further improved extraction efficiency, with more than 95% extraction of all four metals by surfactants acidified to pH 3.6 and generally greater than 90% removal of all metals with addition of 0.1 M EDTA. In two species of earthworm, Eisenia fetida and Lumbricus terrestris, metal bioaccumulation was reduced by approximately 30 to 80%, total biomass was enhanced by approximately threefold to sixfold, and survival was increased to greater than 75% in surfactant-remediated soil compared with untreated soil. The data indicate that surfactant washing may be a feasible approach to treat surface soils contaminated with a variety of metals, even if those metals have been present for nearly a century, and that the toxicity and potential for metal accumulation in biota from the treated soils may be significantly reduced.


[Familial asymmetrical septal hypertrophy with and without obstruction: clinical findings in patients with echocardiographically confirmed diagnosis (author's transl)].
Obstructive and non-obstructive asymmetrical septal hypertrophy (ASH) is a relatively common disease which has no characteristic clinical symptoms. In only 14 of 71 patients in whom the diagnosis had been confirmed echocardiographically had it been possible to make the diagnosis by clinical means alone. Most of the patients had no specific clinical symptoms (angina, dyspnoea, systolic murmur, non-specific ECG changes) indicating a cardiomyopathy. Every patient with such uncharacteristic signs should therefore be studied by echocardiography in order to exclude ASH. In 17 patients there were no clinical symptoms at all, the diagnosis being made entirely by echocardiography.


Four plus one: vacuoles serve in photorespiration.
Photorespiration is inevitable for oxygenic photosynthesis. It has fascinated researchers over decades because of its multicompartmental organization. Recently, Lin and Tsay identified a vacuole glycerate transporter contributing to photorespiratory metabolism under short-term nitrogen depletion. This key finding adds a fifth interacting subcellular compartment and extends the photorespiratory metabolic repair module.


Association of Neutrophil-to-lymphocyte Ratio with Contrast-induced Nephropathy in Patients with Non-ST-elevation Acute Coronary Syndrome Treated with Percutaneous Coronary Intervention.
A higher neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical outcomes in various cardiovascular diseases, including acute coronary syndromes. However, the relationship between NLR and contrast-induced nephropathy (CIN) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) has not been known. Hence, we investigated whether admission NLR is associated with CIN after PCI in patients with NSTE-ACS. A total of 478 patients (mean age 62.8±12.6 years, and 64.2% men), who were admitted to our hospital for NSTEACS and underwent PCI with stent, were recruited. Neutrophil-to-lymphocyte ratio was calculated via dividing neutrophil count by lymphocyte count. The patients were divided into two groups: CIN (+) and CIN (-). Contrast-induced nephropathy was defined as a ≥0.5mg/dL and/or a ≥25% increase in serum creatinine within 48-72hours post-PCI. Admission NLR was significantly higher in patients with CIN than in patients without CIN (median 5.43, interquartile range 3.23-7.73 vs. median 2.59, interquartile range 1.83-3.88, P<0.001). On multivariate analysis, NLR ≥ 3.46 value (OR=2.631, 95%CI 1.146-6.060, P=0.022), estimated glomerular filtration rate (OR=0.963, P=0.004), high sensitivity C-reactive protein (OR=1.028, P=0.016) were independent factors of CIN. Increased NLR is independently associated with risk of CIN in NSTE-ACS patients treated by PCI.


Expression of colony-stimulating factor 1 and interleukin-34 in gingival tissue and gingival fibroblasts from periodontitis patients and controls.
Colony-stimulating factor 1 (CSF-1) and interleukin (IL)-34 are important for the functions of myeloid lineage cells and are involved in several chronic inflammatory conditions associated with tissue degeneration. The aim of this study is to evaluate the expression of CSF-1 and IL-34 in gingival tissue and gingival fibroblasts (GF) from patients with periodontitis and controls. Gingival biopsies were obtained from 19 periodontitis patients and 15 controls. Expression of CSF-1 and IL-34 in gingival tissue was assessed by western blot and localization by immunohistochemistry. Expression of CSF1 and IL34 mRNA in GF was analyzed by real-time polymerase chain reaction and protein expression visualized by immunofluorescence stainings. CSF-1 and IL-34 secretion from GF was evaluated in response to tumor necrosis factor-alpha (TNF-α), IL-1β, Escherichia coli lipopolysaccharide (Ec-LPS) and Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) stimulation, using enzyme-linked immunosorbent assays. CSF-1 was increased in gingival tissue from periodontitis patients compared with controls (P < 0.05) whereas IL-34 expression was similar. In GF from a non-periodontitis donor, stimulation with either TNF-α, IL-1β, Ec-LPS, or Pg-LPS, increased the secretion of CSF-1 (P < 0.05) and Ec-LPS stimulation increased IL-34 (P < 0.05). CSF-1 and IL-34 were expressed and secreted constitutively from GF, with comparable levels in GF from periodontitis patients and controls. Inflammatory stimuli increased the secretion of CSF-1 and IL-34 with comparable levels measured from GF from periodontitis patients and controls (P < 0.05). The expression of CSF-1 and IL-34 in gingival tissue and fibroblasts suggests involvement in myeloid cell functions during periodontal inflammation.


The supraspinatus footprint: an anatomic study of the supraspinatus insertion.
Management of articular sided partial-thickness rotator cuff tears is controversial. Most management decisions rest on determining the thickness of tendon loss and location of tendon involvement, without any clear guidelines offered on how to make this determination. This study attempts to confirm the normal cuff thickness at its humeral head attachment and correlate the amount of exposed bone at the "footprint" attachment of the supraspinatus as an accurate measurement of the amount of tendon loss. Anatomic study. Forty-eight cadaver shoulders with an average age of 71.5 years were examined. Specimens with full- or partial-thickness rotator cuff tears were not measured, leaving 17 specimens with an average age of 70 for analysis. The anterior to posterior width of the supraspinatus was measured with a caliper, as well as the medial to lateral width at the rotator interval, at midtendon, and at the posterior limit determined by the spine of the scapula raphe. The distance from the articular cartilage margin to the supraspinatus tendon insertion was also measured. The mean anteroposterior dimension of the supraspinatus insertion was 25 mm. The mean superior to inferior tendon thickness at the rotator interval was 11.6 mm, 12.1 mm at midtendon, and 12 mm at the posterior edge. The distance from the articular cartilage margin to the bony tendon insertion was 1.5 to 1.9 mm, with a mean of 1.7 mm. Articular partial-thickness tears with > 7 mm of exposed bone lateral to the articular margin should be considered significant tears approximating 50% of the tendon substance. Arthroscopic measurement of the exposed bone between the articular margin and the supraspinatus tendon insertion (footprint) is an accurate way to estimate tear depth and provide a rational, reproducible guideline for treatment.


Adenocarcinoma in an ileal conduit: a late recurrence of urethral adenocarcinoma.
We report a case of recurrent adenocarcinoma in an ileal loop 13 years after cystectomy for adenocarcinoma of the urethra. The method of diagnosis is discussed.


Brachytherapy for the Conservative Treatment of Female Peri-Urethral Carcinoma.
Introduction: Peri-urethral cancers (PUC) are rare tumors. Brachytherapy (BT), either monotherapy or combined with radiation therapy, is a preferred treatment option to spare the morbidity of surgery and achieve organ preservation. We report, to the best of our knowledge, the largest experience of brachytherapy among women with PUC. Patients and Methods: This is a retrospective review of the medical records of female patients with PUC who underwent low- or pulse-dose-rate BT with or without external beam radiotherapy at Gustave Roussy between 1990 and 2018. Patients were categorized according to the treatment intention into a primary and recurrent group. The Kaplan-Meier method was used for survival analysis, and the Cox proportional-hazard model was used for univariate analysis. Brachythewharapy-related adverse events were reported according to Common Terminology Criteria for Adverse Events version 4. Results: We identified 44 patients with PUC who underwent BT. Of the 44 patients, 22 had primary tumors and 22 had recurrent tumors. Histologies were mainly adenocarcinoma (n = 20) and squamous cell carcinoma (n = 14). The median prescribed dose was 60 Gy for the 24 patients treated with BT alone and 20 Gy (IQ range: 15-56.25 Gy) for the 20 patients treated with BT in combination with EBRT. With a median follow-up of 21.5 months (range 7.5-60.8), a total of six patients experienced local relapse (17.5%). The 2-year overall survival probability was 63% (95%CI: 49.2-81.4%). The most common toxicities were acute genito-urinary grade 1-2 toxicities. At the last follow-up, four patients experienced focal necrosis. Conclusions: In this cohort of women with PUC undergoing BT, we observed an 80% probability of local control with acceptable morbidity. Though survival was poor, with high metastatic relapse probability, BT was useful to focally escalate the dose and optimize local control in the context of an organ sparing strategy.


Overexpression of blaGES-1 due to a strong promoter in the class 1 integron contributes to decreased ceftazidime-avibactam susceptibility in carbapenem-resistant Pseudomonas aeruginosa ST235.
Sequence type 235 (ST235) Pseudomonas aeruginosa, harboring so-called international, high-risk, or widespread clones, is associated with relatively high morbidity and mortality, partly due to multiantibiotic and high-level antibiotic resistance. Treatment of infections caused by such strains with ceftazidime-avibactam (CZA) is often successful. However, CZA resistance in carbapenem-resistant P. aeruginosa (CRPA) strains has been consistently reported with the increasing use of this drug. Likewise, we identified thirty-seven CZA-resistant ST235 P. aeruginosa strains from among 872 CRPA isolates. A total of 10.8% of the ST235 CRPA strains were resistant to CZA. Site-directed mutagenesis, cloning, expression, and whole-genome sequencing analysis revealed that overexpression of blaGES-1, which was carried in a class 1 integron of the complex transposon Tn6584, occurred due to a strong promoter, contributing to CZA resistance. Moreover, such overexpression of blaGES-1 combined with an efflux pump resulted in high-level resistance to CZA, considerably reducing the therapeutic options available for treating infections caused by ST235 CRPA. Considering the widespread presence of ST235 P. aeruginosa strains, clinicians should be aware of the risk of CZA resistance development in high-risk ST235 P. aeruginosa. Surveillance initiatives for preventing further dissemination of high-risk ST235 CRPA isolates with CZA resistance are essential.


Seasonality and Ecological Suitability Modelling for Anthrax (Bacillus anthracis) in Western Africa.
Anthrax is hyper-endemic in West Africa affecting wildlife, livestock and humans. Prediction is difficult due to the lack of accurate outbreak data. However, predicting the risk of infection is important for public health, wildlife conservation and livestock economies. In this study, the seasonality of anthrax outbreaks in West Africa was investigated using climate time series and ecological niche modeling to identify environmental factors related to anthrax occurrence, develop geospatial risk maps and identify seasonal patterns. Outbreak data in livestock, wildlife and humans between 2010 and 2018 were compiled from different sources and analyzed against monthly rates of change in precipitation, normalized difference vegetation index (NDVI) and land surface temperature. Maximum Entropy was used to predict and map the environmental suitability of anthrax occurrence. The findings showed that: (i) Anthrax outbreaks significantly (99%) increased with incremental changes in monthly precipitation and vegetation growth and decremental changes in monthly temperature during January-June. This explains the occurrence of the anthrax peak during the early wet season in West Africa. (ii) Livestock density, precipitation seasonality, NDVI and alkaline soils were the main predictors of anthrax suitability. (iii) Our approach optimized the use of limited and heterogeneous datasets and ecological niche modeling, demonstrating the value of integrated disease notification data and outbreak reports to generate risk maps. Our findings can inform public, animal and environmental health and enhance national and regional One Health disease control strategies.


A Quantitative Method for Evaluating Phragmoplast Morphology.
Phragmoplasts are plant-specific microtubule structures that form cell plates at the cell division plane. During late anaphase, phragmoplasts emerge between daughter nuclei as the derivative of spindle microtubules, and centrifugally expand toward the cell cortex to build cell plates during telophase. Phragmoplasts are composed of short antiparallel microtubules decorated with various microtubule-associated proteins. Mutants of these microtubule-associated proteins exhibit defects in phragmoplast morphology. Quantification of phragmoplast morphology is indispensable for assessing the phenotypes of these mutants. Here, we describe a method to quantify the width of phragmoplasts.


The myelination of the cerebellar cortex in the cat.
The myelination of the cerebellar cortex of the cat was investigated in 61 cats aged from 3 hrs post partum to two and a half years. The first myelinated fibers appear at the time of birth in the central medullary ray. Before the onset of myelination, all fibers reach a critical diameter of about 1 micrometer. About the 14th day of life the number of oligodendrocytes in the prospective while matter increases markedly. Thereafter, the oligodendrocytes invade the inner granular layer. It therefore seems that the myelination of the cerebellar cortex proceeds from the central medullary ray towards the granular layer. At the 60th day of postnatal life, most of the afferent and efferent fiber systems are myelinated. These findings are discussed in relation to the development of function and the maturation of the electrical activity of the cerebellar circuit.


Editorial for the Special Issue "Detoxification Mechanisms in Insects".
Insects are faced with numerous toxins (xenobiotics) as they go through life, some produced naturally by plants (sometimes called allelochemicals) and some produced by humans (insecticides) [...].


Spatial calibration of structured illumination fluorescence microscopy using capillary tissue phantoms.
Quantitative assessment of microvascular structure is relevant to the investigations of ischemic injury, reparative angiogenesis and tumor revascularization. In light microscopy applications, thick tissue specimens are necessary to characterize microvascular networks; however, thick tissue leads to image distortions due to out-of-focus light. Structured illumination confocal microscopy is an optical sectioning technique that improves contrast and resolution by using a grid pattern to identify the plane-of-focus within the specimen. Because structured illumination can be applied to wide-field (nonscanning) microscopes, the microcirculation can be studied by sequential intravital and confocal microscopy. To assess the application of structured illumination confocal microscopy to microvessel imaging, we studied cell-sized microspheres and fused silica microcapillary tissue phantoms. As expected, structured illumination produced highly accurate images in the lateral (X-Y) plane, but demonstrated a loss of resolution in the Z-Y plane. Because the magnitude of Z-axis distortion was variable in complex tissues, the silica microcapillaries were used as spatial calibration standards. Morphometric parameters, such as shape factor, were used to empirically optimize Z-axis software compression. We conclude that the silica microcapillaries provide a useful tissue phantom for in vitro studies as well as spatial calibration standard for in vivo morphometry of the microcirculation.


Zap1-dependent transcription from an alternative upstream promoter controls translation of RTC4 mRNA in zinc-deficient Saccharomyces cerevisiae.
Maintaining zinc homeostasis is an important property of all organisms. In the yeast Saccharomyces cerevisiae, the Zap1 transcriptional activator is a central player in this process. In response to zinc deficiency, Zap1 activates transcription of many genes and consequently increases accumulation of their encoded proteins. In this report, we describe a new mechanism of Zap1-mediated regulation whereby increased transcription of certain target genes results in reduced protein expression. Transcription of the Zap1-responsive genes RTC4 and RAD27 increases markedly in zinc-deficient cells but, surprisingly, their protein levels decrease. We examined the underlying mechanism further for RTC4 and found that this unusual regulation results from altered transcription start site selection. In zinc-replete cells, RTC4 transcription begins near the protein-coding region and the resulting short transcript leader allows for efficient translation. In zinc-deficient cells, RTC4 RNA with longer transcript leaders are expressed that are not efficiently translated due to the presence of multiple small open reading frames upstream of the coding region. This regulation requires a potential Zap1 binding site located farther upstream of the promoter. Thus, we present evidence for a new mechanism of Zap1-mediated gene regulation and another way that this activator protein can repress protein expression.


Identification of the cAMP-dependent protein kinase and protein kinase C phosphorylation sites within the major intracellular domains of the beta 1, gamma 2S, and gamma 2L subunits of the gamma-aminobutyric acid type A receptor.
Gamma-aminobutyric acid Type A (GABAA) receptors are the major sites of synaptic inhibition in the central nervous system. These receptors are thought to be pentameric complexes of homologous transmembrane glycoproteins. Molecular cloning has revealed a multiplicity of different GABAA receptor subunits divided into five classes, alpha, beta, gamma, delta, and rho, based on sequence homology. Within the proposed major intracellular domain of these subunits, there are numerous potential consensus sites for protein phosphorylation by a variety of protein kinases. We have used purified fusion proteins of the major intracellular domain of GABAA receptor subunits produced in Escherichia coli to examine the phosphorylation of these subunits by cAMP-dependent protein kinase (PKA) and protein kinase C (PKC). The purified fusion protein of the intracellular domain of the beta 1 subunit was an excellent substrate for both PKA and PKC. PKA and PKC phosphorylated the beta 1 subunit fusion protein on serine residues on a single tryptic phosphopeptide. Site-directed mutagenesis of serine 409 in the intracellular domain of the beta 1 subunit to an alanine residue eliminated the phosphorylation of the beta 1 subunit fusion protein by both protein kinases. The purified fusion proteins of the major intracellular domain of the gamma 2S and gamma 2L subunits of the GABAA receptor were rapidly and stoichiometrically phosphorylated by PKC but not by PKA. The phosphorylation of the gamma 2S subunit occurred on serine residues on a single tryptic phosphopeptide. Site-directed mutagenesis of serine 327 of the gamma 2S subunit fusion protein to an alanine residue eliminated the phosphorylation of the gamma 2S fusion protein by PKC. The gamma 2L subunit is an alternatively spliced form of the gamma 2S subunit that differs by the insertion of 8 amino acids (LLRMFSFK) within the major intracellular domain of the gamma 2S subunit. The PKC phosphorylation of the gamma 2L subunit occurred on serine residues on two tryptic phosphopeptides. Site-specific mutagenesis of serine 343 within the 8-amino acid insert to an alanine residue eliminated the PKC phosphorylation of the novel site in the gamma 2L subunit. No phosphorylation of a purified fusion protein of the major intracellular loop of the alpha 1 subunit was observed with either PKA or PKC. These results identify the specific amino acid residues within GABAA receptor subunits that are phosphorylated by PKA and PKC and suggest that protein phosphorylation of these sites may be important in regulating GABAA receptor function.(ABSTRACT TRUNCATED AT 400 WORDS)


Pituitary gland and beta-catenin signaling: from ontogeny to oncogenesis.
Although pituitary tumors are mostly benign, they share certain molecular events with more malignant neoplasia, although their precise pathogenesis is far from established. The acquisition of new functional characteristics during their evolution suggests a multistep process that leads to tumor transformation. Mutations in classical tumor suppressor genes or oncogenes are infrequently associated with pituitary tumorigenesis. However, alterations in different signaling pathways, especially those involved in pituitary gland development, have emerged as significant features in pituitary adenomas. In particular, changes in inhibitory components of the beta-catenin pathway and its relationship to the cadherin family of peptides may well play an important role in tumorigenesis. We review and assess the role of the beta-catenin signaling pathway in the pathogenesis of pituitary adenomas.


Inhibiting or antagonizing glucagon: making progress in diabetes care.
Absolute or relative hyperglucagonaemia has been recognized for years in all experimental or clinical forms of diabetes. It has been suggested that excess secretion of glucagon by the islet α cells is a direct consequence of intra-islet insulin secretory defects. Recent studies have shown that knockout of the glucagon receptor or administration of a monoclonal specific glucagon receptor antibody make insulin-deficient type 1 diabetic rodents thrive without insulin. These observations suggest that glucagon plays an essential role in the pathophysiology of diabetes and that targeting the α cell and glucagon are innovative approaches in the management of diabetes. Despite active research and identification of promising compounds, no one selective glucagon antagonist is presently used in the treatment of diabetes. Interestingly, besides insulin, several drugs used today in the management of diabetes appear to exert their effects, in part, by inhibiting glucagon secretion (glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors and, possibly, sulphonylureas) or glucagon action (metformin). The potential risks associated with total glucagon suppression include α-cell hyperplasia, increased mass of the pancreas, increased susceptibility to hepatosteatosis and hepatocellular injury and increased risk of hypoglycaemia, and these should be considered in the search and development of new compounds reducing glucagon receptor signalling. More than 40 years after its initial description, hyperglucagonaemia in diabetes can no longer be ignored or minimized, and its correction represents an attractive way to improve diabetes management.


Effect modification of body mass index and body fat percentage on fatty liver disease in a Japanese population.
No previous study has performed multivariate analysis of the risk factors of fatty liver disease (FL), focusing on the effect of weight gain of ≥ 10 kg since the age of 20, and no analysis model exists that simultaneously evaluates body mass index (BMI) and body fat percentage (BFP) as adjustment variables. To investigate these, we collected anthropometric data from health checkups, and conducted a cross-sectional study (targeting 1851 males and 1259 females aged 30 years or over). Regardless of sex, weight gain of ≥10 kg since the age of 20 was positively associated with FL. Our stratified analysis of BFP into two categories, to evaluate the interaction between BMI and BFP in FL, indicated an approximately fivefold increase in the odds ratio in the male group with high BMI and BFP values compared to those with low BMI and BFP values, with a synergy index of 1.77 > 1. On the other hand, females demonstrated no significant additive interaction, with a synergy index of 0.49 < 1. We revealed that weight gain ≥ 10 kg since the age of 20 is significantly associated with FL regardless of sex. In addition, by performing a synergy index (S), we showed that the additive interaction between BMI and BFP in FL differs according to gender.


Animal-assisted therapy at a University Centre for Palliative Medicine - a qualitative content analysis of patient records.
Animal-assisted therapy (AAT) is a therapeutic concept, which has only recently been explored in more detail within the palliative care setting. A programme of AAT was begun in June 2014 at the Interdisciplinary Centre for Palliative Medicine of the University Hospital Dusseldorf, Germany. The AAT sessions were performed by two trained and certified dog assistant therapy teams (DATT). To date only very limited scientific data are available with regard to feasibility, therapeutic indications and efficacy of AAT in palliative care. The present qualitative study aims to describe the first year's practice and experience of AAT after implementation as an integral part of adjunctive therapy options offered within an academic palliative care centre. This study is a qualitative content analysis of all post-encounter protocols of AAT interventions recorded by the dog handlers from June 2014 through May 2015. Qualitative content analysis was conducted according to Mayring's approach; the report followed the recommendations of the Standards for Reporting Qualitative Research (SRQR). Fifty-two patients received 84 AAT interventions, with only 18 patients receiving more than one intervention due to discharge or death. In 19 cases relatives also participated in the AAT session. The inductive coding process yielded four main categories. One hundred and fifty-three codes related to the content and structure of the AAT sessions, with physical contact with the dog taking considerable precedence. The AAT sessions included conversations with the dog handler, 10.5% of which related to the current health state as well as to discussions around death and dying. Eighty-nine codes related to perceived emotional responses, with pleasure being the most often observed response. Two hundred and seventeen codes related to the effects of the AAT sessions, identifying the dog as a catalyst of communication and observing patients' physical activation or relaxation. AAT may constitute a valuable and practicable adjunct to the interdisciplinary therapeutic repertoire of palliative care in the hospital setting. The results of this study suggest that patients may potentially benefit from AAT in terms of facilitated communication, positive emotional responses, enhanced physical relaxation or motivation for physical activation. These early stage results will need to be followed-up by more robust study designs.


Neural affective mechanisms associated with treatment responsiveness in veterans with PTSD and comorbid alcohol use disorder.
Post-traumatic stress disorder (PTSD) is associated with neuro-physiological abnormalities reflecting increased anticipatory anxiety and reactivity to traumatic cues. It remains unclear whether neural mechanisms associated with PTSD treatment responsiveness, i.e. hyperactivation of the affective salience network in the brain, extend to a comorbid PTSD and substance use disorder population. Thirty-one Veterans with PTSD and co-occurring alcohol use disorder (AUD) were randomly assigned to either prolonged exposure or a non-exposure based treatment. They completed an affective anticipation task while undergoing fMRI, immediately prior and after completing treatment. After controlling for type and length of treatment, larger reduction of PTSD symptoms was associated with decreased anticipatory activation to negative trauma-related cues in the right pre-Supplementary Motor Area (pre-SMA), a region associated with emotion regulation. Smaller reduction in PTSD severity was associated with enhanced anticipatory activation to those cues within the right para-hippocampal region, an affective processing region. Our findings suggest that post-treatment reductions in anticipatory reactivity to trauma-related cues in the pre-SMA and para-hippocampal area are associated with larger PTSD symptom reduction in individuals with co-occurring PTSD and AUD. These results may offer neurofeedback training targets as an alternative to or enhancement of other PTSD treatment modalities in this population.


Effect of diphosphonate on crystallization of calcium oxalate in vitro.
Reliable techniques for the calculation of activity product (state of saturation), formation product (limit of metastability) and crystal growth of calcium oxalate were devised. The activity product at saturation was 2.53 times 10 minus 9 M2, and was independent of duration of incubation, solid-to-solution ratio, pH, calcium concentration or ionic strength. These tehcniques were utilized to assess the effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on crystallization of calcium oxalate in an aqueous salt solution in vitro. EHDP increased the formation product of calcium oxalate, indicating an inhibition of nucleation of calcium oxalate. Further, it inhibited the crystal growth of calcium oxalate.


A semi-supervised multi-task learning framework for cancer classification with weak annotation in whole-slide images.
Cancer region detection (CRD) and subtyping are two fundamental tasks in digital pathology image analysis. The development of data-driven models for CRD and subtyping on whole-slide images (WSIs) would mitigate the burden of pathologists and improve their accuracy in diagnosis. However, the existing models are facing two major limitations. Firstly, they typically require large-scale datasets with precise annotations, which contradicts with the original intention of reducing labor effort. Secondly, for the subtyping task, the non-cancerous regions are treated as the same as cancerous regions within a WSI, which confuses a subtyping model in its training process. To tackle the latter limitation, the previous research proposed to perform CRD first for ruling out the non-cancerous region, then train a subtyping model based on the remaining cancerous patches. However, separately training ignores the interaction of these two tasks, also leads to propagating the error of the CRD task to the subtyping task. To address these issues and concurrently improve the performance on both CRD and subtyping tasks, we propose a semi-supervised multi-task learning (MTL) framework for cancer classification. Our framework consists of a backbone feature extractor, two task-specific classifiers, and a weight control mechanism. The backbone feature extractor is shared by two task-specific classifiers, such that the interaction of CRD and subtyping tasks can be captured. The weight control mechanism preserves the sequential relationship of these two tasks and guarantees the error back-propagation from the subtyping task to the CRD task under the MTL framework. We train the overall framework in a semi-supervised setting, where datasets only involve small quantities of annotations produced by our minimal point-based (min-point) annotation strategy. Extensive experiments on four large datasets with different cancer types demonstrate the effectiveness of the proposed framework in both accuracy and generalization.


Entropy analysis of neuronal spike train synchrony.
Although vector strength (VS) and the Rayleigh tests are widely used to quantify neuronal firing synchrony to cyclic events, their use is valid only for singly peaked, unimodal distributions. In this report, we propose a new method to quantify synchrony, applicable to both unimodal and multimodal distributions. We also propose a statistical test to examine temporal structure under a null hypothesis of no synchrony.


Accuracy of a fixed value nasion relator in facebow design.
This study examined whether a fixed value nasion relator accurately locates the orbitale in a patient population. The mean value for the vertical distance between soft tissue nasion and orbitale was determined through the analysis of cephalometric radiographs of 114 adult patients. This value was then compared to a facebow design, which uses a fixed value of 25.4 mm. In this study, the mean distance between the orbitale and nasion was found to be 26.8 mm. The values ranged from 15.9 to 39.4 mm with a standard deviation of 3.87 mm. The difference between the calculated mean and the 25.4 mm fixed value was less than 2.0 mm and presumed to be clinically irrelevant; however, an accumulation of design errors combined with the variation within the patient population was asserted to be clinically relevant and makes the use of a fixed value nasion relator impractical.


Evaluation of a scale of patient-reported outcomes for the assessment of myasthenia gravis patients in China.
To evaluate a scale of patient-reported outcomes for the assessment of myasthenia gravis patients (MG-PRO) in China. A total of 100 MG patients were interviewed for the field testing. Another 56 MG patients were selected and assessed with the MG-PRO scale before treatment and at 1, 2 and 4 weeks after treatment. The classical test theory and item response theory (IRT) were used to assess the psychometric characteristics of the MG-PRO scale. The MG-PRO scale included 4 dimensions: physical, psychological, social environment, and treatment. Confirmatory factor analysis showed that each dimension was consistent with the theoretical construct. The scores of the physical and psychological dimensions increased significantly at 1 week after treatment (P<0.05). All the dimension scores and the MG-PRO score increased significantly at 2 and 4 weeks after treatment (P<0.05). IRT showed that person separation indices were greater than 0.8, most of the item fit residual statistics were within ± 2.5, and no item had uniform or non-uniform differential item functioning (DIF) between gender and age (<40, [Symbol: see text]40). The MG-PRO scale is valid for measuring the quality of life (QOL) of MG patients, with good reliability, validity, responsiveness, and good psychometric characteristics from IRT. It can be applied to evaluate the QOL of MG patients and to assess treatment effects in clinical trials.


Formation of noncanonical high molecular weight caspase-3 and -6 complexes and activation of caspase-12 during serum starvation induced apoptosis in AKR-2B mouse fibroblasts.
Apoptosis is mainly brought about by the activation of caspases, a protease family with unique substrate selectivity. In mammals, different complexes like the DISC complex or the apoptosome complexes have been delineated leading to the cleavage and thus activation of the executioner caspases. Although caspase-3 is the main executioner caspase in apoptosis induced by serum starvation in AKR-2B fibroblasts as demonstrated by affinity labeling with YVK(-bio)D.aomk and partial purification of cytosolic extracts by high performance ion exchange chromatography, its activation is apparently caused by a noncanonical pathway: (1) Expression of CrmA, an inhibitor of caspase-8, failed to suppress apoptosis; (2) There was no formation of high molecular weight complexes of Apaf-1 indicative for its activation. Furthermore no cleavage of caspase-9 was observed. But surprisingly, gelfiltration experiments revealed the distribution of caspase-3 and -6 into differently sized high molecular weight complexes during apoptosis. Though the apparent molecular weights of the complexes containing caspase-3 (600 kD for apoptosome and 250 kD for microapoptosome) are in accordance with recently published data, the activity profiles differ strikingly. In AKR-2B cells caspase-3 is mainly recovered as uncomplexed enzyme and in much lower levels in the apoptosomes. Remarkably, the 600 kD and 250 kD complexes containing activated caspase-3 were devoid of Apaf-1 and cytochrome c. In addition a new 450 kD complex containing activated caspase-6 was found that is clearly separated from the caspase-3 containing complexes. Furthermore, we disclose for the first time the activation of caspase-12 in response to serum starvation. Activated caspase-12 is detectable as non-complexed free enzyme in the cytosol.


Rare earth elements in tea garden soils and their bioavailability to tea buds in Taiwan.
Tea (Camellia sinensis) is a widespread beverage plant that prefers aluminum-enriched acidic soils. However, rare earth elements (REEs) might be highly phyto-available in these soils. With the increasing demands for REEs in high-technology industries, understanding the dynamics of REEs in the environment is essential. Thus, this study identified the total concentration of REEs in the root-zone soils and corresponding tea buds (n = 35) collected from tea gardens in Taiwan. Additionally, the labile REEs in the soils were extracted with 1 M KCl, 0.1 M HCl, and 0.05 M ethylenediaminetetraacetic acid (EDTA) to elucidate the fractionation tendency of REEs in the soil-plant system and the relationships between REEs and Al in the tea buds. The concentration of light REEs (LREEs) was higher than those of medium REEs (MREEs) and heavy REEs (HREEs) in all soil and tea bud samples. According to the upper continental crust (UCC) normalization, MREEs and HREEs were more abundant than LREEs in the tea buds. Furthermore, REEs remarkably increased with increasing Al in the tea buds, whereas the linear correlations between Al and MREEs and HREEs were stronger than between LREEs. Compared with LREEs, the extractabilities of MREEs and HREEs by all single extractants in the soils were higher, coinciding with their higher UCC-normalization-based enrichments in the tea buds. Moreover, the 0.1 M HCl- and 0.05 M EDTA-extractable REEs were affected by soil properties and significantly correlated with the total REEs in the tea buds. The concentration of REEs in the tea buds was successfully predicted by empirical equations of extractable REEs with 0.1 M HCl and 0.05 M EDTA, as well as general soil properties including pH, organic carbon, dithionite-citrate-bicarbonate-extractable iron, aluminum, and phosphorus. However, this prediction should be further verified using many soil and tea types in the future.


Selected low-cohesion variants of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus lack distinct antigens recognized by human antibodies.
Actinobacillus actinomycetemcomitans OMZ 346 A and Haemophilus aphrophilus OMZ 384 A, isolated on a synthetic selective and differentiating agar, show the highly cohesive and wall adherent growth in liquid medium which is typical for all primary oral isolates of these species. From each of them a low cohesion variant, OMZ 346 F and OMZ 384 F, respectively, was obtained by selection for cells growing in suspension. Screening of Western blots of these four strains with several human sera revealed the loss of a 4000 Mr antigen in both F strains. Human antibodies bound to the 4000 Mr band material on preparative Western blots of the A strains were eluted with 4 M magnesium chloride. These antibodies showed no cross-reaction between the 4000 Mr material of the two closely related species.


Hormone relationships in breast cancer: the role of receptor-binding proteins.
The introduction of receptor protein studies as markers for hormone dependence of breast carcinomas has had a profound effect on the management of advanced disease. All breast carcinomas, regardless of stage, should have receptor binding protein studies for estrogen and progesterone by the sucrose gradient method or by the dextran-coated charcoal method as a good alternative. A simpler test is needed. In cases of primary advanced disease or in recurrent disease, receptor binding protein studies effectively identify the subgroup of hormone-dependent tumors that should be managed by surgical hormone ablation or endocrine manipulation. These tests are even more effective in identifying patients that should not receive hormone therapy and respond better to chemotherapy. In primary, potentially surgically curable disease, receptor studies may serve as a therapeutic guide to adjuvant hormone or chemotherapy. In all breast cancers, ER and PgR receptor studies should be performed and the information should be stored for possible future use. If possible, tisssue should be stored in a freezer in anticipation of future tests and for confirmation of hormone dependence in the event of recurrence.


Clinical, radiological, and audiological relationships in hemifacial microsomia.
Hemifacial microsomia is a craniofacial disorder involving structures derived from the first and second brachial arches. Bony structures, soft tissue, and the facial nerve can all be hypoplastic or absent. In this retrospective study of 70 patients at the Children's Hospital Los Angeles, craniofacial dysmorphology, temporal bone computed tomography, and audiological evaluations were examined. The purpose of this study was to identify further relationships between clinical findings, temporal bone anatomy, and audiological findings in these patients. Significant relationships were identified between total radiographic score and overall clinical findings (p<0.001). Clinical measurements of mandibular hypoplasia were also predictive of temporal computed tomographic findings (p<0.001), whereas clinical ear findings were related specifically to specific temporal bone abnormalities such as hypoplasia of the middle ear (p=0.008) and fusion or absence of ossicles (p<0.001). Interestingly, neither clinical findings nor temporal bone computed tomographic findings were related to either hearing loss type or degree. Audiology should not be deferred on the basis of relatively mild clinical findings.


Semiclosed iliac recanalisation by an inguinal approach--modified surgical techniques integrating interventional procedures.
Technical success and early outcome of modified surgical techniques integrating interventional procedures for iliac recanalisation performed through an incision in the groin. Sixty-one consecutive iliac arteries in 59 patients with long occlusions in 16, occlusions of the common iliac in 11, occlusions of the external iliac in 24 and multiple stenoses of the iliac in 10 cases underwent semiclosed recanalisation through a groin incision. Passage of the lesion by guidewire permits retrograde ring-stripper endarterectomy over the wire as a guiding splint or thrombectomy with a double lumen balloon catheter. Residual lesions are corrected by balloon or stent angioplasty. Adequate outflow is established by femoral patch plasty. Conversion to a standard operation was required in 10 limbs (failure to recanalise the lesion in nine, rupture after angioplasty in one). Initial technical success was achieved in the remaining 51 limbs (recanalisation by ring stripper endarterectomy in 36, thrombectomy in 14, both in six, additional intraoperative angioplasty in 42). Five postoperative thromboses were successfully treated by a combined surgical and interventional approach accounting for a 1-month 100% secondary patency. Iliac recanalisation through the groin by modified ring stripper endarterectomy or modified thrombectomy in combination with intraoperative angioplasty is a safe and effective procedure. Long-term results are required to evaluate the procedure.


Calpain cleaves RhoA generating a dominant-negative form that inhibits integrin-induced actin filament assembly and cell spreading.
Integrin-induced cell adhesion results in transmission of signals that induce cytoskeletal reorganizations and resulting changes in cell behavior. The cytoskeletal reorganizations are regulated by transient activation and inactivation of Rho GTPases. Previously, we identified mu-calpain as an enzyme that is activated by signaling across beta1 and beta3 integrins. We showed that it mediates cytoskeletal reorganizations in bovine aortic endothelial (BAE) and Chinese hamster ovary (CHO) cells and does so by acting upstream of Rac1 activation. Here we show that mu-calpain is also involved in inactivating RhoA during integrin-induced signaling. Cleavage of RhoA was detectable in BAE cells plated on an integrin substrate; it did not occur in cells plated on poly-l-lysine. Cleavage was inhibited by calpain inhibitors. In vitro, mu-calpain cleaved RhoA generating a fragment of the same size as in intact cells. The cleavage site was identified, an HA-tagged construct expressing calpain-cleaved RhoA generated, and the construct expressed in BAE and CHO cells. Calpain-cleaved RhoA inhibited integrin-induced stress fiber assembly and decreased cell spreading. Together, our data show that calpain cleaves RhoA and generates a form that inhibits integrin-induced stress fiber assembly and cell spreading.


Efficient production of n-caproate from syngas by a co-culture of Clostridium aceticum and Clostridium kluyveri.
In recent years, the possibility of merging technologies for waste recovery such as those based on syngas fermentation and chain elongation has been studied for the production of medium chain fatty acids (MCFAs) and bioalcohols, in an attempt to integrate the concept of circular economy in the industry. Nevertheless, one of the main issues of this approach is the pH mismatch between acetogens and chain elongating microorganisms. This work reports, for the first time, the suitability of a co-culture of C. aceticum and C. kluyveri metabolizing syngas at near neutral pH in stirred tank bioreactors. For this purpose, bioreactor studies were carried out with continuous syngas supply. In the first experiment, maximum concentrations of n-butyrate and n-caproate of 7.0 and 8.2 g/L, respectively, were obtained. In the second experiment, considerable amounts of n-butanol were produced as a result of the reduction, by C. aceticum, of the carboxylates already formed in the broth. In both experiments, ethanol was used as an exogenous electron agent at some point. Finally, batch bottle assays were performed with a pure culture of C. aceticum grown on CO in presence of n-butyrate to assess and confirm its ability to produce n-butanol, reaching concentrations up to 951 mg/L, with a n-butyrate conversion efficiency of 96%, which had never been reported before in this species. Therefore, this work contributes to the state of the art, presenting a novel system for the bioproduction of MCFAs by combining syngas fermentation and chain elongation at near neutral pH, as opposed to the acidic pH range used in all previously reported literature.


Refractory hypertension: definition, prevalence, and patient characteristics.
Among patients with resistant hypertension (RHTN), there are those whose blood pressure (BP) remains uncontrolled in spite of maximal medical therapy. This retrospective analysis aims to characterize these patients with refractory hypertension. Refractory hypertension was defined as BP that remained uncontrolled after ≥3 visits to a hypertension clinic within a minimum 6-month follow-up period. Of the 304 patients referred for RHTN, 29 (9.5%) remained refractory to treatment. Patients with refractory hypertension and those with controlled RHTN had similar aldosterone levels and plasma renin activity (PRA). Patients with refractory hypertension had higher baseline BP (175±23/97±15 mm Hg vs 158±25/89±15 mm Hg; P=.001/.005) and heart rate, and higher rates of prior stroke and congestive heart failure. During follow-up, the BP of patients with refractory hypertension remained uncontrolled (168.4±14.8/93.8±17.7 mm Hg) in spite of use of an average of 6 antihypertensive medications, while those of patients with controlled RHTN decreased to 129.3±11.2/77.6±10.8 mm Hg. Spironolactone reduced the BP by 12.9±17.8/6.6±13.7 mm Hg in patients with refractory hypertension and by 24.1±16.7/9.2±12.0 mm Hg in patients with controlled RHTN. In patients with RHTN, approximately 10% remain refractory to treatment. Similar aldosterone and PRA levels and a diminished response to spironolactone suggest that aldosterone excess does not explain the treatment failure.


Efficacy and safety of stereotactic body radiotherapy for painful bone metastases: Evidence from randomized controlled trials.
Pain relief is one of the main objectives of radiotherapy for cancer patients with bone metastases. Stereotactic body radiotherapy (SBRT) enables precise delivery of a higher dosage to the target area. Several trials have reported comparisons between SBRT and conventional radiotherapy (cRT) in patients with painful bone metastasis. However, the results of those investigations were inconsistent, and no systematic review or meta-analysis has been done till now. We systematically searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov up to May 1, 2022 for relevant studies. Patients with painful bone metastasis who received SBRT or cRT were included. The primary outcome was the patients' pain response rate at three months. The secondary outcomes included the rate of pain responders at one month and six months, oral morphine equivalent dose (OMED) use, and any adverse events. STATA software 12.0 was used for the statistical analysis. We collected 533 patients' data from 4 randomized controlled trials (RCTs), there was a significant difference of pain response rate at 3 months between two groups (RR = 1.41, 95% CI: 1.12-1.77, I2 = 0.0%, P = 0.003). However, no significant difference was found in pain response rate at 1 month (RR = 1.19, 95% CI: 0.91-1.54, I2 = 31.5%, P = 0.201) and 6 months (RR = 1.25, 95% CI: 0.93-1.69, I2 = 0.0%, P = 0.140). OMED consumption was not significantly different in patients treated with SBRT compared with control group (WMD = -1.11, 95% CI: -17.51-15.28, I2 = 0.0%, P = 0.894). For safety outcome, no statistical difference was found between SBRT and cRT (RR = 0.72, 95% CI: 0.46-1.14, I2=20.1%, P = 0.162). This study shows that for painful bone metastases, patients with SBRT experienced better pain relief 3 months after radiation than patients with cRT, and SBRT did not increase the incidence of adverse events. https://inplasy.com/inplasy-2022-6-0099/, identifier INPLASY202260099.


Treatment of eosinophilic esophagitis in children.
Eosinophilic esophagitis (EE) is an increasingly recognized disease of the esophagus with distinct clinicopathologic features. Adult and pediatric patients experience upper intestinal symptoms including food impaction, vomiting, abdominal pain, or dysphagia. Histopathologic analysis of the distal and proximal esophageal mucosa demonstrates dense eosinophilic infiltration despite proton pump inhibition. Few studies document the long-term outcomes of EE but current evidence suggests that EE is a chronic condition that can sometimes lead to esophageal strictures. Although the incidence of this complication is not yet known, it has sparked significant interest in defining safe, effective treatments. Once a diagnosis of EE is made, patients should seek the consultation of the allergist in an effort to identify possible food sensitivities. This is particularly important because the etiologic agent(s) that drive the eosinophilia are likely different for each patient. If the allergic evaluation identifies a specific food, this food should be strictly avoided as a first-line treatment. If a food is not identified, an elemental formula should be used to induce a remission. If an elemental diet cannot be used, topical steroids are effective in inducing a remission. The side effects associated with long-term steroid administration limit their use as a maintenance medication. Given the lack of prognostic data, the use of systemic corticosteroids should be reserved for severe cases when dietary elimination or topical steroids are ineffective. Most importantly, patients should remain under the care of a physician so that long-term outcomes can be identified. To date, diet restriction has been identified as the only effective maintenance treatment, but montelukast and topical cromolyn may also offer benefit. Anti-interleukin-5 antibody represents an emerging form of targeted therapy.


Otdbase.
This article describes the rationale behind the development of an "only occupational therapy" computerized literature search service. OTDBASE, the clinically-oriented index and data base, contains all relevant information about all articles from eight occupational therapy (OT) journals from 1970 to the present and includes up to 10 lines of abstract per article. The service was developed for purposes of contributing to continuing education and research efforts in occupational therapy.


Genetic determinants of adiponectin regulation revealed by pregnancy.
This study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. A genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome Study with adiponectin measured at ∼28 weeks of gestation. Variants reaching P < 5×10-5 for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N = 522; ECOGENE-21 N = 174) were selected. In the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (β ± standard error [SE] = -0.18 ± 0.03 standard deviation [SD] of adiponectin per risk allele; P = 1.5 ×10-8 ; N = 2,004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of nonpregnant women (β ± SE = -0.012 ± 0.006; P = 0.05; N = 16,678 women from the ADIPOgen consortium). The offspring rs900400 T risk allele was associated with greater neonatal skinfold thickness (β ±SE = 0.19 ± 0.04 SD per risk allele; P = 4.1×10-8 ; N = 1,489) and higher cord blood leptin (β ± SE = 0.28 ± 0.05 log-leptin per risk allele; P = 8.2 ×10-9 ; N = 502), but not with cord blood adiponectin (P = 0.23; N = 495). The T allele of rs900400 was associated with higher expression of TIPARP in adipocytes. These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.


Forced Unfolding of Proteins Directs Biochemical Cascades.
Many proteins in cells and in the extracellular matrix assemble into force-bearing networks, and some proteins clearly transduce mechanical stimuli into biochemical signals. Although structural mechanisms remain poorly understood, the designs of such proteins enable mechanical forces to either inhibit or facilitate interactions of protein domains with other proteins, including small molecules and enzymes, including proteases and kinases. Here, we review some of the structural proteins and processes that exhibit distinct modes of force-dependent signal conversion.


Effects of the superoxide dismutase-mimetic compound tempol on endothelial dysfunction in streptozotocin-induced diabetic rats.
Evidence exists to support the beneficial effects of superoxide dismutase on endothelial dysfunction induced by hyperglycemia in vitro. In vivo, however, studies of the effects of native superoxide dismutase preparations on the vascular complications accompanying diabetes are limited, and their therapeutic application potential has so far been disappointing. The objective of this study was to evaluate, for the first time in vivo, the effects of long-term administration of tempol, a stable superoxide dismutase-mimic compound, on diabetes-induced endothelial dysfunction in rats. Diabetes was induced by streptozotocin and rats were monitored for 8 weeks with or without treatment with tempol (100 mg/kg, s.c., b.i.d). Diabetic rats showed increased vascular levels of superoxide, which was accompanied by increased levels of the oxidative stress markers malondialdehyde and 8-epi-prostaglandin F(2alpha). In addition, the vasorelaxant as well as the cGMP-producing effects of acetylcholine and glyceryl trinitrate were reduced in diabetic rats. Treatment with tempol abolished not only the differences in the vascular content of superoxide, malondialdehyde and 8-epi-prostaglandin F(2alpha), but also the differences in the relaxation and cGMP responses of aortic rings to both acetylcholine and glyceryl trinitrate between control and diabetic rats. These results support the involvement of reactive oxygen species in mediation of hyperglycemia-induced endothelial dysfunction in vivo, and provide the rationale for potential utilization of stable superoxide dismutase-mimic nitroxides for the prevention of the vascular complications accompanying diabetes.


Midterm Results for Robotic Thymectomy for Malignant Disease.
There are limited reports on robotic thymectomy for malignant disease. Our objectives are to review our experience and midterm outcomes. We reviewed a single-surgeon prospective database for patients who underwent planned robotic resection for malignancy from January 2010 to June 2019. Two hundred thirteen patients underwent resection of an anterior mediastinal mass, all of which were planned for a robotic approach. Of these, 84 (39%) underwent robotic thymectomy for malignant disease. Thymoma was the most common pathology resected (68%). Median tumor size was 4.7 cm (interquartile range, 2.9-6.3), and median operative time was 81.5 minutes (interquartile range, 64-104). All except 1 patient had a complete (R0) resection (98.8%). There were 2 (2.3%) unplanned but elective conversions to open surgery, 1 of which required cardiopulmonary bypass. Median length of stay was 1 day (range, 0-9) with 1 readmission (1.2%). Major morbidity occurred in 3 patients (3.5%), and there were no 30- or 90-day mortalities. In patients with thymoma, follow-up was complete at a median of 32 months (range, 1-98), and 1 patient (1.8%) had an ipsilateral chest recurrence. To date there have been no patient deaths. Robotic thymectomy for patients with malignant disease is safe with excellent perioperative outcomes. A robotic approach achieves a high rate of complete R0 resection, even for larger tumors. For patients with thymoma local recurrence is low after midterm follow-up, but longer-term analysis is needed to determine oncologic durability.


Evaluation of the motion of lung tumors during stereotactic body radiation therapy (SBRT) with four-dimensional computed tomography (4DCT) using real-time tumor-tracking radiotherapy system (RTRT).
We investigated the usefulness of four-dimensional computed tomography (4DCT) performed before stereotactic body radiation therapy (SBRT) in determining the internal margins for peripheral lung tumors. The amplitude of the movement of a fiducial marker near a lung tumor measured using the maximum intensity projection (MIP) method in 4DCT imaging was acquired before the SBRT (AmpCT) and compared with the mean amplitude of the marker movement during SBRT (Ampmean) and with the maximum amplitude of the marker movement during SBRT (Ampmax) using a real-time tumor-tracking radiotherapy (RTRT) system with 22 patients. There were no significant differences between the means of the Ampmean and the means of the AmpCT in all directions (LR, P = 0.45; CC, P = 0.80; AP, P = 0.65). The means of the Ampmax were significantly larger than the means of the AmpCT in all directions (LR, P < 0.01; CC, P = 0.03; AP, P < 0.01). In the lower lobe, the mean difference of the AmpCT from the mean of the Ampmax was 5.7 ± 8.0 mm, 12.5 ± 16.7 mm, and 6.8 ± 8.5 mm in the LR, CC, and AP directions, respectively. Acquiring 4DCT MIP images before the SBRT treatment is useful to establish the mean amplitude for a patient during SBRT but it underestimates the maximum amplitude during actual SBRT. Caution must be paid to determine the margin with the 4DCT especially for tumors at the lower lobe where it is of the potentially greatest benefit.


Object play in the everyday home environment generates rich opportunities for infant learning.
Infants everywhere engage with objects throughout the day, even if the objects of play differ across cultures. Indeed, object play is a universal context for learning. Yet, the characteristics of object play at home remain largely unexamined, especially in infants from non-English-speaking backgrounds. Through frame-by-frame video coding, we documented Hispanic infants' object interactions based on 1-2 h of naturalistic home observations. Infants interacted with a wide variety of toys and household objects in brief bouts that summed to ~60% of their time. As infants transition among objects, they serendipitously generate opportunities for learning that support development across domains.


Detection of occult thymoma during exercise thallium 201, technetium 99m tetrofosmin imaging for coronary artery disease.
Thallium (Tl) 201 and technetium (Tc) 99m tetrofosmin single-photon emission CT are routinely used in the evaluation of coronary artery disease. Mediastinal tumors demonstrate Tl 201 and Tc 99m tetrofosmin uptake. We report a 56-year-old man who developed chest pain after a previously successful angioplasty and stent of the left anterior descending coronary artery. He underwent a Tl 201, Tc 99m tetrofosmin exercise study. Abnormal mediastinal activity was visualized in both the Tl 201 and Tc 99m tetrofosmin images. Subsequently, the patient underwent resection of a stage II thymoma. Unanticipated focal extracardiac accumulation during myocardial scintiscanning should lead to further investigation to exclude mediastinal tumor.


Short fibre-reinforced composite for extensive direct restorations: a laboratory and computational assessment.
The objective of the study was to evaluate the effectiveness of a short fibre-reinforced composite (FRC) applied in combination with a conventional filler composite (CFC) on the fatigue resistance, fracture strength, failure mode and stress distribution, for restorations of premolars under two loading angles. Thirty-two inferior premolars received extensive cavities with removal of the lingual cusp. Teeth were restored directly using 'FRC (EverX Posterior, GC) + CFC (G-aenial, GC)' or 'CFC only' and received two fatigue/fracture loadings at two different angles (0°/45°) (n = 8). Data were submitted to two-way ANOVA (α = 5 %) and Tukey test. Failure mode was analysed using SEM. Four 3D finite element (FE) models were constructed and static, linear and elastic analyses were performed. Maximum principal and von Mises stresses were evaluated. All specimens survived the mechanical fatigue simulation. No statistical difference in fracture resistance was recorded between FRC + CFC and CFC only, considering both loading angles (p = 0.115). However, the 0° loading showed a statistical significant higher strength than the 45° loading (p = 0.000). Failure mode analysis revealed more repairable fractures upon 0° loading, versus more root fractures (unrepairable) upon 45° loading. FE revealed a higher amount of stress upon 45° loading, with tensile stress being imposed to the lingual cervical area. The fracture strength was not increased using the FRC. Loading at a 45° decreased significantly the fracture resistance. The restoration of extensive cavities in posterior tooth is a challenge for the clinicians and the choice of the material that increases the fracture strength of tooth-restoration complex is required.


Mutated fukutin-related protein (FKRP) localises as wild type in differentiated muscle cells.
The mechanism of disease in forms of congenital and limb girdle muscular dystrophy linked to mutations in the gene encoding for Fukutin-related protein (FKRP) has previously been associated with the mis-localisation of FKRP from the Golgi apparatus. In the present report, we have transfected V5-tagged Fukutin-related protein expression constructs into differentiated C2C12 myotubes and the tibialis anterior of normal mice. The transfection of either wild type (WT) or several mutant constructs (P448L, C318Y, L276I) into myotubes consistently showed clear co-localisation with GM130, a Golgi marker. In contrast, whilst WT and the L276I localised to the Golgi of Cos-7 cells, the P448L and C318Y was mis-localised in the majority of these undifferentiated cells. The injection of the same constructs into the tibialis anterior of mice resulted in similar localisation of both the WT and all the mutants. Immunolabelling of FKRP in the muscle of MDC1C and LGMD2I patients was found to be indistinguishable from normal controls. Overall, these data suggest that retention in the endoplasmic reticulum of FKRP is not the main mechanism of disease but that this may instead relate to a disruption of the functional activity of this putative enzyme with its substrate(s) in the Golgi.


Phenol degradation catalyzed by a peroxidase mimic constructed through the grafting of heme onto metal-organic frameworks.
The aim of this work was to construct a peroxidase mimic for achieving the phenol degradation through Fenton reaction. The enzyme mimic was synthesized through the conjugation of heme with the amino group of 2-amino-1,4-benzene dicarboxylate in UiO-66-NH2 (ZrMOF), namely Heme-ZrMOF. Compared to free heme, the composite Heme-ZrMOF exhibited an obviously enhanced ability for phenol degradation with up to 97.3% of phenol removal after 2h. Meanwhile, it could achieve the easy separation of catalyst from the system and the elimination of iron residues in the process of phenol degradation. Finally, the catalyst Heme-ZrMOF was observed to possess good recyclability in the phenol degradation with still 76.2% of phenol removal after 4 cycles.


Mechanism of formation of polychlorinated dibenzo-p-dioxins produced on municipal incinerator flyash from reactions of chlorinated phenols.
All incinerators burning municipal waste produce chlorinated dioxins. The mechanism by which these compounds are formed is unknown. Experiments were performed that show these compounds can be produced from known precursors by surface catalysed reactions on the flyash particulates present in the incineration process. A full range of the tetra- through octachlorinated dibenzo-p-dioxins were produced from 13C-labelled pentachlorophenol and two trichlorophenols on the surface of flyash from an Ontario municipal incinerator that had been previously freed from organic material. A simple flow-tube apparatus at 300 degrees C under a 10-ml/min nitrogen flow was used for the experiments. The use of 13C-labelled pentachlorophenol gave a direct measure of the extent of the catalytic reactivity of the flyash surface. Much lower amounts of chlorinated dioxins were produced in similar experiments with flyash from a modern Japanese incinerator whose effluents are normally extremely low in these compounds. Only small amounts of octachlorodioxin, the thermal condensation product expected, were formed using ground firebrick or an empty flow-tube for the reactive surface. These results indicate that the flyash surface has constituents and properties that promote the production of chlorinated dioxins from chlorinated phenols and support the catalyzed surface reaction mechanism previously proposed.


Uncemented Porous Tantalum Acetabular Components: Early Follow-Up and Failures in 599 Revision Total Hip Arthroplasties.
The purpose of this study was to determine the early outcomes of 599 cases of revision THA performed using a porous tantalum cup. Clinical and radiographic data was sought in all patients at a minimum two years follow-up, after acetabular revision performed with a porous tantalum cup. Of the 599 cases identified, there were 51 re-operations in 47 patients (7.8 percent). Cup removal was required in 14 of these cases (2.3 percent). The most common cause for cup removal was a septic joint (12). No cups were revised for aseptic loosening during the study period. There was one case of early cup migration. There were 17 incomplete lucencies not initially seen on post-operative films, but identified later, all were non-progressive on subsequent x-rays. Early results of porous tantalum acetabular components in the revision setting demonstrate good initial stability and low re-operation rates at two years follow-up. Level 4: Case series.


Deoxycytidine kinase is phosphorylated in vitro by protein kinase C alpha.
Deoxycytidine (dCyd) kinase was effectively phosphorylated by protein kinase C. The reaction was rapid, occurring at 4 degrees C as well as at 37 degrees C and approximately 0.7 mol of phosphate could be incorporated per mol of deoxycytidine kinase. Phosphoserine was the primary amino acid to be phosphorylated. Phosphorylation of deoxycytidine kinase resulted in a 100% increase in the Vmax using dCyd as a substrate (52.16 +/- 1.3 versus 104.47 +/- 11.4 nmol/min/mg protein), and an increase in the apparent Km (2.0 +/- 0.2 microM versus 6.9 +/- 1.2 microM). The inactive antimetabolite, ara-C, is activated within a cell by deoxycytidine kinase phosphorylation of the prodrug. Recent studies have shown that ara-C activates protein kinase C in vivo [1]. Furthermore, ara-C has been shown to be metabolized to ara-CDP-choline via reversal of the cholinephosphotransferase [2] producing diglyceride, a cellular activator of protein kinase C. Thus, in situ, deoxycytidine kinase may be phosphorylated by protein kinase C with the result that self-potentiation of ara-C toxicity may occur via increased activity of deoxycytidine kinase.


Re-Irradiation of Locoregional NSCLC Recurrence Using Robotic Stereotactic Body Radiotherapy.
We evaluated the efficacy, toxicity, and dose responses of re-irradiation with stereotactic body radiotherapy (SBRT) in patients with recurrent non- small cell lung cancer (NSCLC) after previous irradiation. 28 patients were included. Previous median radiation doses were 54 and 66 Gy. The median interval time between previous radiotherapy and SBRT was 14 months. The median follow-up time after SBRT was 9 months (range 3-93 months). To evaluate the effectiveness of SBRT, local control, overall survival, and treatment-related toxicity were reported. SBRT doses and fractionation ranged from 60 to 30 Gy and from 3 to 8, respectively, according to previous doses, location of the recurrence, and interval time. 65% of tumor recurrences overlapped with previous treatment, while 35% of tumors recurred outside of the previous treatment. 4 patients had local progression after SBRT at their first follow-up. The Kaplan-Meier estimates of the 1- and 2-year actuarial overall survival were 71 and 42%, respectively. The mean survival following SBRT was 32.8 months, and the median survival was 21 months. No grade 3 or higher toxicities were observed. Robotic SBRT is a tolerable treatment option with manageable toxicity which can be used with radical or palliative intent in carefully selected patients with locally recurrent tumors after previous irradiation.


A Novel Optical Scanning Technique with an Inclined Focusing Plane.
We propose a novel technique for fully automated optical scanning of thin samples. We analyze its performance and estimate the achievable scanning speed to compare it with conventional techniques. It paves the way to the next generation of highspeed scalable scanning systems, at least one order of magnitude faster than existing ones. We show that the efficiency and the accuracy of this new technique are comparable to those of the conventional ones, while the scanning speed scales proportionally with the number of cameras installed, hence the large expected improvement.


Development of virtual reality stimuli for force platform posturography.
People relying much on vision in the control of posture are known to have an elevated risk of falling. Dependence on visual control is an important parameter in the diagnosis of balance disorders. We have previously shown that virtual reality (VR) methods can be used to produce visual stimuli that affect balance, but suitable stimuli need to be found. In this study, the effect of six different VR stimuli on the balance of 22 healthy test subjects was evaluated using force platform posturography. We report in more detail and expand the results published earlier. According to the tests two of the stimuli have a significant destabilizing effect on balance. In addition a significant displacement effect on the subject's center of pressure (COP) was found. Thus it is shown that the design of VR stimuli to cause different effects on the control of balance is possible.


Studies on organomercury(II) complexes of isoniazid.
A number of organomercury(II) complexes involving isoniazid (I), of the type RHgCl(L)(II) [R = phenyl(C6H5), o-hydroxyphenyl (o-HOC6H4), p-hydroxyphenyl (p-HOC6H4), p-acetoxyphenyl (p-AcOC6H4), 2-furyl (2-C4H3O); L = isoniazid] have been synthesized and characterized. Conductance measurements indicate that the complexes are nonelectrolytes. From IR and UV studies, it is concluded that isoniazid acts as a bidentate ligand, coordinating through hydrazinic nitrogen and carbonyl oxygen. 1H and 13C NMR support the stoichiometry of the complexes. From fluoroscence studies a number of photochemical parameters have been elucidated. For the C6H5HgCl(L), p-HOC6H4HgCl(L), and p-AcOC6H4HgCl(L) complexes, thermogravimetric studies have been carried out and relevant kinetic and thermodynamic parameters for thermal degradation have been enumerated. In addition, the fragmentation pattern of the complexes has been analyzed on the basis of mass spectra. The C6H5HgCl(L) and p-HOC6H4HgCl(L) complexes have been screened for tuberculosis activity.


Gestational nicotine exposure reduces nicotinic cholinergic receptor (nAChR) expression in dopaminergic brain regions of adolescent rats.
Children of women who smoked during pregnancy are at increased risk of dependence when smoking is initiated during adolescence. We previously reported that gestational nicotine exposure attenuated dopamine release induced by nicotine delivered during adolescence. In this study, we determined the effects of gestational nicotine exposure on nicotinic cholinergic receptor (nAChR) expression. Timed pregnant rats received nicotine (2 mg/kg/day) or vehicle via mini-osmotic pumps during gestation. Treatments continued in pups via maternal nursing during postnatal days (PN) 2-14 (equivalent to the human in utero third trimester). On PN35, 125I-epibatidine binding to nAChR was measured. The Bmax values (fmol/mg) in prefrontal cortex (PFC), nucleus accumbens (NAcc), substantia nigra (SN) and ventral tegmental area (VTA) were reduced by 26.6% (P<0.05), 32.6% (P<0.01), 23.0% (P<0.01) and 27.6% (P<0.05), respectively. In addition, gender differences were found in vehicle-treated groups; in SN and VTA, females were 79.3% (P<0.005) and 82.9% (P=0.08) of males, respectively. The expression of nAChR subunit mRNAs was measured using real-time RT-PCR on laser-capture microdissected tissues. In adolescent VTA, gestational nicotine exposure reduced (P<0.05) nAChR subunit mRNAs encoding alpha3 (53.0%), alpha4 (23.9%), alpha5 (46.7%) and beta4 (61.4%). In NAcc core, the treatment increased alpha3 mRNA (75.8%). In addition, the number of neurons in VTA was reduced by 15.0% (P<0.001). These studies indicate that gestational exposure to nicotine induces long-lasting changes in nAChR expression that may underlie the vulnerability of adolescents to dependence on nicotine.