Vitamin D Levels and Associations in Indian Patients with Primary Sjögren's Syndrome.
Vitamin D is a steroid hormone belonging to the class of secosteroids with myriad immune functions and has been implicated in aetiopathogenesis of various autoimmune diseases. Although, there have been various studies showing the association of vitamin D in rheumatoid arthritis and lupus in different populations, there have been limited studies on vitamin D and primary Sjögren's Syndrome (pSS). There are no studies on association of vitamin D and pSS from any tropical country including Indian subcontinent. The purpose of the study was to look for any association between 25-hydroxyvitamin D (25(OH)D) levels and disease manifestations in Indian patients with pSS. This is a retrospective cross-sectional study done at a tertiary teaching hospital in southern India in 235 patients with pSS. Patients satisfying the American European Consensus Group (AECG) or American College of Rheumatology (ACR) 2012 for pSS between 2008 and 2015 were included if baseline 25(OH)D levels using electrochemiluminescence were available in hospital's laboratory record, 25(OH)D <20 ng/ml,20-30 ng/ml and >30 ng/ml was defined as deficiency, insufficiency and normal, respectively. Clinical laboratory data and disease activity scoring by EULAR Sjögren's syndrome disease activity index (ESSDAI) were retrieved retrospectively. Latitude corresponding to residence of each patient and the season of performing the assay were recorded. Chi-square statistics was done to find associations between categorized 25(OH)D and outcomes and was reported as odds ratio(95% confidence interval). Mean 25(OH)D for 235 patients with pSS was 19.98(12.55)ng/ml. A vitamin D deficiency, insufficiency and sufficiency was seen in 141(60%), 60(25.5%) and 34.0(14.5%), respectively. No association was noted between latitude or season of performing assay and the levels. pSS with 25(OH)D ≤30ng/ml had more than two fold risk of higher grading on lip biopsy as well as Rheumatoid Factor (RF) positivity. However, low 25(OH)D seemed to be associated with lower ESSDAI and less pulmonary involvement. Prevalence of 25(OH)D deficiency in Indian patients with pSS was comparable to that of general Indian population. Low 25(OH)D level ≤30ng/ml was associated with higher odds for RF positivity and positive grading on lip biopsy. Surprisingly, low 25(OH)D was associated with lower ESSDAI score.


Reelin, an extracellular matrix protein linked to early onset psychiatric diseases, drives postnatal development of the prefrontal cortex via GluN2B-NMDARs and the mTOR pathway.
Defective brain extracellular matrix (ECM) is a factor of vulnerability in various psychiatric diseases such as schizophrenia, depression and autism. The glycoprotein reelin is an essential building block of the brain ECM that modulates neuronal development and participates to the functions of adult central synapses. The reelin gene (RELN) is a strong candidate in psychiatric diseases of early onset, but its synaptic and behavioral functions in juvenile brain circuits remain unresolved. Here, we found that in juvenile reelin-haploinsufficient heterozygous reeler mice (HRM), abnormal fear memory erasure is concomitant to reduced dendritic spine density and anomalous long-term potentiation in the prefrontal cortex. In juvenile HRM, a single in vivo injection with ketamine or Ro25-6981 to inhibit GluN2B-N-methyl-D-aspartate receptors (NMDARs) restored normal spine density, synaptic plasticity and converted fear memory to an erasure-resilient state typical of adult rodents. The functional and behavioral rescue by ketamine was prevented by rapamycin, an inhibitor of the mammalian target of rapamycin pathway. Finally, we show that fear memory erasure persists until adolescence in HRM and that a single exposure to ketamine during the juvenile period reinstates normal fear memory in adolescent mice. Our results show that reelin is essential for successful structural, functional and behavioral development of juvenile prefrontal circuits and that this developmental period provides a critical window for therapeutic rehabilitation with GluN2B-NMDAR antagonists.


Impact of electronic medical record on physician practice in office settings: a systematic review.
Increased investments are being made for electronic medical records (EMRs) in Canada. There is a need to learn from earlier EMR studies on their impact on physician practice in office settings. To address this need, we conducted a systematic review to examine the impact of EMRs in the physician office, factors that influenced their success, and the lessons learned. For this review we included publications cited in Medline and CINAHL between 2000 and 2009 on physician office EMRs. Studies were included if they evaluated the impact of EMR on physician practice in office settings. The Clinical Adoption Framework provided a conceptual scheme to make sense of the findings and allow for future comparison/alignment to other Canadian eHealth initiatives.In the final selection, we included 27 controlled and 16 descriptive studies. We examined six areas: prescribing support, disease management, clinical documentation, work practice, preventive care, and patient-physician interaction. Overall, 22/43 studies (51.2%) and 50/109 individual measures (45.9%) showed positive impacts, 18.6% studies and 18.3% measures had negative impacts, while the remaining had no effect. Forty-eight distinct factors were identified that influenced EMR success. Several lessons learned were repeated across studies: (a) having robust EMR features that support clinical use; (b) redesigning EMR-supported work practices for optimal fit; (c) demonstrating value for money; (d) having realistic expectations on implementation; and (e) engaging patients in the process. Currently there is limited positive EMR impact in the physician office. To improve EMR success one needs to draw on the lessons from previous studies such as those in this review.


Evaluation of antitumor effects following tumor necrosis factor-α gene delivery using nanobubbles and ultrasound.
The antitumor effects of tumor necrosis factor (TNF-α) were evaluated following transfection of TNF-α plasmid DNA into solid mouse tumors using the nanobubbles (NBs) and ultrasound (US) gene delivery system. Murine breast carcinoma (EMT6) cells expressing luciferase (1 × 10(6) cells) were injected intradermally into the flanks of 6-7-week-old male SCID mice on day 0. Ten microliters of TNF-α (5 μg/μL) or TNF-α mock plasmid DNA (5 μg/μL) with/without NBs (15 μL) and saline was injected intratumorally in a total volume of 30 μL, and tumors were exposed to US (frequency, 1 MHz; intensity, 3.0 W/cm(2); duty cycle, 20%; number of pulses, 200; and exposure time, 60 s) on days 2, 4, 7, and 9. Changes in tumor size were measured with an in vivo bioluminescent imaging system and a mechanical caliper. Changes in tumor vessel area were quantified using contrast-enhanced US imaging with Sonazoid and a high frequency US imaging system (40 MHz) and immunohistochemistry (CD31). At the mRNA level, expression of TNF-α, caspase-3, and p53 were quantified using real-time quantitative RT-PCR. At the protein level, expression of caspase-3 and p53 were confirmed by immunohistochemistry. We show that repeated TNF-α gene delivery using NBs and US can lead to the local production of TNF-α. This results in antitumor effects, including activation of p53-dependent apoptosis, decrease in tumor vessel density, and suppression of tumor size. In this study, we showed the effectiveness of using NBs and US for TNF-α gene delivery into tumor cells.


MRI-based delta-radiomics predicts pathologic complete response in high-grade soft-tissue sarcoma patients treated with neoadjuvant therapy.
In high-grade soft-tissue sarcomas (STS) the standard of care encompasses multimodal therapy regimens. While there is a growing body of evidence for prognostic pretreatment radiomic models, we hypothesized that temporal changes in radiomic features following neoadjuvant treatment ("delta-radiomics") may be able to predict the pathological complete response (pCR). MRI scans (T1-weighted with fat-saturation and contrast-enhancement (T1FSGd) and T2-weighted with fat-saturation (T2FS)) of patients with STS of the extremities and trunk treated with neoadjuvant therapy were gathered from two independent institutions (training: 103, external testing: 53 patients). pCR was defined as <5% viable cells. After segmentation and preprocessing, 105 radiomic features were extracted. Delta-radiomic features were calculated by subtraction of features derived from MRI scans obtained before and after neoadjuvant therapy. After feature reduction, machine learning modeling was performed in 100 iterations of 3-fold nested cross-validation. Delta-radiomic models were compared with single timepoint models in the testing cohort. The combined delta-radiomic models achieved the best area under the receiver operating characteristic curve (AUC) of 0.75. Pre-therapeutic tumor volume was the best conventional predictor (AUC 0.70). The T2FS-based delta-radiomic model had the most balanced classification performance with a balanced accuracy of 0.69. Delta-radiomic models achieved better reproducibility than single timepoint radiomic models, RECIST or the peri-therapeutic volume change. Delta-radiomic models were significantly associated with survival in multivariate Cox regression. This exploratory analysis demonstrated that MRI-based delta-radiomics improves prediction of pCR over tumor volume and RECIST. Delta-radiomics may one day function as a biomarker for personalized treatment adaptations.


Resonance Raman spectra of the heme in leghemoglobin. Evidence for the absence of ruffling and the influence of the vinyl groups.
Resonance Raman spectra of deoxy and carbonmonoxy leghemoglobin (Lb) are compared to the corresponding forms of human adult hemoglobin (HbA). It is found that the heme "core size" indicator line has nearly the same frequency for the two deoxyhemoglobins and the pi-electron density-sensitive line also falls at the same frequency. However, several other modes occur at very different frequencies in the spectra of the two proteins. From an examination of the spectrum of an HbA derivative in which the beta-carbon atoms of the heme vinyl groups were deuterated, it appears that the major differences between deoxy-HbA and -Lb may result from conformational changes in the vinyl groups. No evidence for the suggested ruffling (Irwin, M. J., Armstrong, R. S., and Wright, P. E. (1981) FEBS Lett. 133, 239-243) in deoxy-Lb was found. The spectra of carbonmonoxy-Lb and -HbA were also found to be very different. As in the deoxy case, some of these frequency differences could be attributed to vinyl group conformational differences. However, from the large difference in the pi-electron density-sensitive line, it appears that the vinyl pi-conjugation into the porphyrin in Lb(CO) may be different than it is in HbA(CO). The vinyl conformational differences may be a consequence of the looser heme pocket in Lb than in HbA. The difference in pi-conjugation could make a significant contribution to the difference in ligand binding affinity for these two globins.


Coccidioidomycosis in renal dialysis and transplant patients: radiologic findings in 30 patients.
Asymptomatic primary coccidioidal infection is common. After the initial infection is contained, the organism can remain dormant in the body for years. Immunosuppression related to renal transplantation or dialysis may reactivate dormant disease. Thus, symptomatic disease may be seen in those with no known history of previous coccidioidomycosis who have visited endemic areas only briefly. To determine if coccidioidomycosis produces characteristic radiographic findings in renal transplant and dialysis patients, we reviewed the records and radiographs of all patients in either of these two categories who are known to have developed active coccidioidal infection in southern Arizona since 1965. Thirty patients (12 undergoing dialysis and 18 transplant recipients) were identified. We conclude that the radiographic manifestations of pulmonary coccidioidomycosis in renal transplant and dialysis patients are highly variable. Interstitial and alveolar patterns of disease are equally likely to occur. Extrathoracic infection without evidence of pulmonary disease occurred in 11 patients (37%), but was radiographically demonstrable only as septic arthritis or perinephric abscess.


STAT5 promotes multilineage hematolymphoid development in vivo through effects on early hematopoietic progenitor cells.
The transcription factor signal transducers and activators of transcription 5 (STAT5) is activated by numerous cytokines that orchestrate blood cell development. Multilineage peripheral blood cytopenias were observed in adult mice lacking both isoforms of STAT5 (STAT5A and STAT5B) as well as accelerated rates of apoptosis in the bone marrow. Although the hematopoietic stem cell (HSC) population was preserved in a number of these mice, the post-HSC progenitor populations were diminished and a marked reduction in functional progenitors (spleen colony-forming units) was detected. Competitive bone marrow transplantation studies in vivo revealed a profound impairment of repopulation potential of STAT5-null HSCs, leading to complete lack of contribution to the myeloid, erythroid, and lymphoid lineages. These abnormalities were associated with heightened proliferation activity in the HSC fraction, suggesting the action of homeostatic mechanisms to maintain sufficient levels of diverse blood cell types for viability. Thus, STAT5 normally sustains the robust hematopoietic reserve that contributes to host viability through crucial survival effects on early progenitor cells.


The epilepsy phenotypic spectrum associated with a recurrent CUX2 variant.
Cut homeodomain transcription factor CUX2 plays an important role in dendrite branching, spine development, and synapse formation in layer II to III neurons of the cerebral cortex. We identify a recurrent de novo CUX2 p.Glu590Lys as a novel genetic cause for developmental and epileptic encephalopathy (DEE). The de novo p.Glu590Lys variant was identified by whole-exome sequencing (n = 5) or targeted gene panel (n = 4). We performed electroclinical and imaging phenotyping on all patients. The cohort comprised 7 males and 2 females. Mean age at study was 13 years (0.5-21.0). Median age at seizure onset was 6 months (2 months to 9 years). Seizure types at onset were myoclonic, atypical absence with myoclonic components, and focal seizures. Epileptiform activity on electroencephalogram was seen in 8 cases: generalized polyspike-wave (6) or multifocal discharges (2). Seizures were drug resistant in 7 or controlled with valproate (2). Six patients had a DEE: myoclonic DEE (3), Lennox-Gastaut syndrome (2), and West syndrome (1). Two had a static encephalopathy and genetic generalized epilepsy, including absence epilepsy in 1. One infant had multifocal epilepsy. Eight had severe cognitive impairment, with autistic features in 6. The p.Glu590Lys variant affects a highly conserved glutamine residue in the CUT domain predicted to interfere with CUX2 binding to DNA targets during neuronal development. Patients with CUX2 p.Glu590Lys display a distinctive phenotypic spectrum, which is predominantly generalized epilepsy, with infantile-onset myoclonic DEE at the severe end and generalized epilepsy with severe static developmental encephalopathy at the milder end of the spectrum. Ann Neurol 2018;83:926-934.


Current Strategies to Enhance Anti-Tumour Immunity.
The interaction of the immune system with cancer is complex, but new approaches are resulting in exciting therapeutic benefits. In order to enhance the immune response to cancer, immune therapies seek to either induce high avidity immune responses to tumour specific antigens or to convert the tumour to a more pro-inflammatory microenvironment. Strategies, including vaccination, oncolytic viruses, and adoptive cell transfer all seek to induce anti-tumour immunity. To overcome the suppressive tumour microenvironment checkpoint inhibitors and modulators of regulatory cell populations have been investigated. This review summarizes the recent advances in immune therapies and discusses the importance of combination therapies in the treatment of cancers.


Chief nursing officer turnover: chief nursing officers and healthcare recruiters tell their stories.
Chief nursing officers (CNOs) develop environments in which quality patient care is delivered and nurses enjoy professional practice. Because of the growing turbulence in this vital role, the American Organization of Nurse Executives conducted a study to examine CNO turnover as described in interviews with CNOs and healthcare recruiters to inform the development of strategies to improve CNO recruitment and retention and ease transition for those who turn over. The authors present the findings from this research and describe American Organization of Nurse Executives' initiatives to address the identified needs.


AVURT: aspirin versus placebo for the treatment of venous leg ulcers - a Phase II pilot randomised controlled trial.
Venous leg ulcers (VLUs) are the most common cause of leg ulceration, affecting 1 in 100 adults. VLUs may take many months to heal (25% fail to heal). Estimated prevalence is between 1% and 3% of the elderly population. Compression is the mainstay of treatment and few additional therapies exist to improve healing. Two previous trials have indicated that low-dose aspirin, as an adjunct to standard care, may improve healing time, but these trials were insufficiently robust. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. Primary objective - to assess the effects of 300 mg of aspirin (daily) versus placebo on the time to healing of the reference VLU. Secondary objectives - to assess the feasibility of leading into a larger pragmatic Phase III trial and the safety of aspirin in this population. A multicentred, pilot, Phase II randomised double-blind, parallel-group, placebo-controlled efficacy trial. Community leg ulcer clinics or services, hospital outpatient clinics, leg ulcer clinics, tissue viability clinics and wound clinics in England, Wales and Scotland. Patients aged ≥ 18 years with a chronic VLU (i.e. the VLU is > 6 weeks in duration or the patient has a history of VLU) and who are not regularly taking aspirin. 300 mg of daily oral aspirin versus placebo. All patients were offered care in accordance with Scottish Intercollegiate Guidelines Network (SIGN) guidance with multicomponent compression therapy aiming to deliver 40 mmHg at the ankle when possible. Participants were allocated in a 1 : 1 (aspirin : placebo) ratio by the Research Pharmacy, St George's University Hospitals NHS Foundation Trust, using a randomisation schedule generated in advance by the investigational medicinal product manufacturer. Randomisation was stratified according to ulcer size (≤ 5cm2 or > 5cm2). The primary outcome was time to healing of the largest eligible ulcer (reference ulcer). 27 patients were recruited from eight sites over a period of 8 months. The target of 100 patients was not achieved and two sites did not recruit. Barriers to recruitment included a short recruitment window and a large proportion of participants failing to meet the eligibility criteria. The average age of the 27 randomised participants (placebo, n = 13; aspirin, n = 14) was 62 years (standard deviation 13 years), and two-thirds were male (n = 18). Participants had their reference ulcer for a median of 15 months, and the median size of ulcer was 17.1 cm2. There was no evidence of a difference in time to healing of the reference ulcer between groups in an adjusted analysis for log-ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p = 0.357). One expected, related serious adverse event was recorded for a participant in the aspirin group. The trial under-recruited because many patients did not meet the eligibility criteria. There was no evidence that aspirin was efficacious in hastening the healing of chronic VLUs. It can be concluded that a larger Phase III (effectiveness) trial would not be feasible. Clinical Trials.gov NCT02333123; European Clinical Trials Database (EudraCT) 2014-003979-39. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 55. See the NIHR Journals Library website for further project information.


Metformin use in renal dysfunction: is a serum creatinine threshold appropriate?
The relationship among metformin use, plasma lactate levels, and lactic acidosis in patients with type 2 diabetes mellitus and the appropriateness of metformin use in patients with renal dysfunction are discussed. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes recommends metformin therapy as first-line therapy along with lifestyle modification to treat type 2 diabetes mellitus. Despite this recommendation, metformin may be underutilized due to the fear of metformin-associated lactic acidosis and because its use is contraindicated in patients with renal dysfunction. Several studies have attempted to characterize the relationship among plasma metformin levels, plasma lactate levels, and lactic acidosis. However, a causal relationship between metformin and lactic acidosis has not been definitively established. In the United States, the estimated rate of lactic acidosis among diabetic patients treated with metformin is similar to that of diabetic patients not taking metformin. Despite specific guidelines advising against prescribing metformin in renal dysfunction, published reports indicate that metformin is continued in 25% of patients after the contraindication is discovered. Individual studies point to a possible correlation between metformin levels and plasma lactate levels, but mortality does not appear to correlate with plasma metformin levels. These results indicate that there may not be a direct relationship between plasma lactate and metformin levels. Current studies point to a weak causal relationship between metformin and lactic acidosis. In patients without comorbid conditions that would predispose them to lactic acidosis, elevated serum creatinine levels should be considered a risk factor for the development of lactic acidosis but not an absolute contraindication.


Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers as a possible medical treatment of the overactive bladder and urge incontinence.
Urinary incontinence affects millions of people worldwide and also represents a social problem. People of all ages suffer from urinary incontinence. The disease is found in about 30% of women aged 30 to 60 years. There are different types of incontinence. Urge incontinence is the most often pharmacologically treated type. The mainly used substances belong to the class of antimuscarinic drugs. Their use is limited by several side effects. Furthermore, in some patients anticholinergic medication is ineffective and antimuscarinics used as single medication do not lead to a sufficient therapeutic effect. Other possible pharmacological substances for treatment of overactive bladder (detrusor instability) associated with urge and urge incontinence are the selective beta-adrenoceptor-agonists which are mainly responsible for the adrenergic mediated relaxation. It depends on the species, which beta-adrenoceptor-subtype (the beta2- and/or beta3-adrenoceptor) mainly mediates the relaxation. Non selective beta-adrenoceptor-agonists exhibit serious cardiovascular side effects like tachycardia or decrease of blood pressure by stimulating beta1- and beta2-adrenoceptors. These side effects should be decreased when using selective agonists. Additionally, substances whose targets are membrane channels of muscle cells could be interesting for treatment of overactive bladder. This group includes L-type calcium antagonists and potassium channel openers of ATP-sensitive potassium channels or BK channels. Especially the local use of the pharmacologically very potent calcium antagonists could be an interesting therapeutic approach, since systemic cardiovascular side effects were avoided. After chronic oral treatment with different calcium antagonists effects on the detrusor muscle were reduced or could not be detected, possibly due to an upregulation of 1,4-dihydropyridine-sensitive potassium channels. A very interesting approach is the use of potassium channel openers said to be selective for the urinary bladder. If there is a selectivity for the detrusor muscle, cardiovascular side effects were reduced. Possibly, the local use is a useful application form. Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers are pharmacological approaches, which are not yet available for clinical use.


Remote sensing in development.
Remote sensing is used to acquire statistics on crops in developing countries and to locate petroleum and mineral deposits. It has increasing potential for forest monitoring and subsurface water location. Problems related to Third World use of the technology include sensitivity about the dissemination of data with high spatial resolution, exploitation by multinational companies, absorptive capacity of countries for advanced technology, autonomy in acquiring resource information, and competing foreign policy interests of the industrialized world in the global search for raw materials. The attitude of Third World countries toward use of remote sensing tends to depend on the development model they adopt.


A randomized crossover study comparing two mandibular repositioning appliances for treatment of obstructive sleep apnea.
The purpose of this study was to determine whether treatment outcomes vary according to the design of the mandibular repositioning appliance (MRA). Two titratable MRA's were compared. The designs differ in advancement hardware and configuration of acrylic both in bulk and interocclusal contact. The primary treatment outcome was the Respiratory Disturbance Index (RDI). Other outcomes that were compared included Sleep Apnea Quality of Life Index (SAQLI), Epworth Sleepiness Scale, oxygen saturation, and subjective feedback regarding experiences with the appliances. Twenty-four subjects were recruited from consecutive referrals for MRA therapy following diagnosis of obstructive sleep apnea (OSA) by polysomnography. Subjects were randomly assigned to a treatment arm of the crossover study. Each subject underwent an initial sleep study with a type III home monitor to establish a baseline RDI. Subjects were then treated with one of the two MRAs determined by random assignment. The MRA self-titration phase was monitored until a treatment position was determined, and the home sleep study was repeated. After a 2-week period without any OSA treatment, subjects received the second MRA and the self-titration treatment protocol was repeated. At completion of treatment with each appliance, subjects answered questionnaires and underwent a sleep study with the type III monitor. The outcome data for each appliance were compared using analysis of variance. Eighteen subjects completed the treatment protocol. There were no significant statistical differences in treatment outcomes between the two appliances. There was a statistically significant (p ≤ 0.05) preference for a MRA design with minimal coverage of teeth and palate. The subjects' appliance selection was consistent with a corresponding reduction in SAQLI score for the selected appliance. Although no statistically significant difference was observed between the two appliances in the outcomes measured, there was a trend toward greater improvement with the appliance with less acrylic resin bulk and less interocclusal contact. MRA selection should favor titratable, unobtrusive designs with appropriate construction to promote acceptance and adherence to MRA therapy.


Intra-thoracic Impedance and the Onset of Atrial and Ventricular Tachyarrhythmias: A Meta-analysis.
Advances of implantable cardioverter-defibrillator (ICD) devices allow correlating changes in the intra-thoracic impedance (TI), an indicator of fluid overload, with the onset of arrhythmic events. In an attempt to attain a better understanding of this relationship, we conducted a meta-analysis of studies that investigated the association between TI changes and the onset of AT/AF and/or VT/VF in patients with ICD devices. We performed a meta-analysis of studies published through January 2017 that reported an association between a decrease in the TI measured by the OptiVol fluid index (OI) and occurrence of AT/AF and VT/VF. We searched four databases: PubMed, Embase, CINAHL and Cochrane. Effect estimates were extracted from each study in the form of odds ratio (OR) and 95% confidence intervals. We identified 8 articles with results of the original research, allowing us to extract data for the OR calculation. Our pooled sample included 94,666 patients from 4 studies for AT/AF and 23,601 patients from 6 studies for VT/VF. Two studies were included in both analyses. The pooled OR for fluid index threshold crossing of 60Ω-days was 1.56 (95% CI 1.35, 1.81) for VT/VF and 1.8 (95% CI 1.43, 2.27) for AT/AF. The findings of our meta-analysis based on the large pooled population of >110,000 patients, reveal that decreased TI (measured by OI threshold crossing of 60Ω-days) is a significant risk factor for the onset of AT/AF and VT/VF.


Giant-cell tumor of bone around the knee.
In most of the reported series, almost half of the giant-cell tumors involved the knee region. The characteristics of the lesions were usually benign but often locally aggressive and easily recurrent neoplasms. Some surgeons performed intralesional excision combined with local adjunctive chemical coagulant, and bone grafting or methylmethacrylate cement packing. These methods could both decrease local recurrence and retain the function of joint. From January, 1984 to December, 1994, a review was made of the results for eighteen patients who had been managed consecutively at the Veterans General Hospital-Taipei for giant-cell tumor of bone around the knee. Fourteen instances had occurred in the proximal tibia and four, in the distal femur. According to the classification of Campanacci, nine lesions were Stage II and nine, Stage III. Eleven patients had been managed with intralesional excision of the tumor with local adjunctive application; the other seven had en bloc resection and reconstructive procedures. All patients had been followed for a mean of fifty-six months (range 22 to 125 months). The overall recurrence rate was 11% (2/18). The intralesional excision had 18% (2/11) recurrence; there was no recurrence in the en bloc resection (0/7). The complication rate was 16% (4/18); 9% (1/11) for intralesional excision and 42% (3/7) for en bloc resection, respectively. The mean functional score was 28 points (range, 22 to 30) in the intralesional excision group and 21 points (range, 11 to 30) in the en bloc resection group. En bloc resection with reconstruction had a lower rate of recurrence, but a higher rate of complication and poor functional results. Intralesional excision, combined with a local adjunctive application and packed with bone grafting or methylmethacrylate cement, was an acceptably good method with satisfactory results, which either decreased local recurrence or retained the function of the joint.


Arrangement of elastic fibres in the integument of domesticated mammals.
The hairy skin of important domesticated mammals (12 species) was studied with scanning electron microscopy, transmission electron microscopy, laser scanning microscopy, and several light microscopical methods, to obtain more information about three-dimensional elastic fibre arrangement. It was obvious that there is a basic construction scheme of the elastic fibre meshwork as present in the upper and mid-dermis, with special regard to the size, number, and grouping of hair follicles. In the densely-haired species, in particular, a typical elastic mat with horizontal fibres is formed. In many of the sparsely-haired animals, the upper and mid-dermis show a sponge-like elastic system. In the rather massive, collagen-rich skin of large species, the lower two thirds of the dermis without hair follicles only possess a loosely-structured elastic network, but thick elastic sheets are found at the border zone with the hypodermis. Specific features appear with regard to the type of mechanical strain exerted, different body regions, varying hair follicle density, or as connected with the anchoring of the hair follicle complex, blood vessels, and nerves.


Nonlinear effects of radiation dose on donor-cell reconstitution by limited numbers of purified stem cells.
Despite the increasing use of bone marrow transplantation (BMT) as a treatment for a wide variety of diseases, the numbers and types of cells required for both rapid and sustained recovery of hematopoiesis are not well defined. To investigate further the potential of transplants consisting of highly enriched populations of long-term repopulating cells, we transplanted a series of Ly-5.2 mice given various doses (750, 800, 850, 900, or 950 cGy) of total-body irradiation (TBI) with 30 or 90 Sca-1+Lin-WGA+ marrow cells isolated from congenic Ly-5.1 donors. As expected, mature progeny derived from these cells, belonging to both myeloid and lymphoid compartments, could be detected with increasing case in recipients given radiation doses from 750 to 900 cGy TBI. Surprisingly, expression of this potential was significantly reduced in mice that had received 950 cGy TBI. This contrasts with the capacity of the same number of purified Sca-1+Lin-WGA+ cells to generate readily detectable progeny in 950 cGy treated mice given a simultaneous transplant of 10(5) normal marrow cells or 2 x 10(5) serially passaged marrow cells. We suggest that this variable behavior of purified stem cells in differently treated recipients may reflect radiation dose-dependent differences in the types or levels of expression of factors that regulate transplanted stem cell proliferation and differentiation in vivo and that above a certain threshold radiation dose, this may result in an irreversible loss of long-term reconstituting potential. Regardless of the nature of the underlying mechanism, this study shows that the extent of donor repopulation after BMT can be a function not only of the number of stem cells transplanted but also of the conditioning of the recipient and whether other cell types are also injected.


Dynamic in vivo quantification of rod photoreceptor degeneration using fluorescent reporter mouse models of retinitis pigmentosa.
Imaging techniques have revolutionised the assessment of retinal disease in humans and animal models. Here we describe a novel technique for the in vivo visualisation of rod photoreceptors which permits semiquantitative assessment of outer retinal degeneration, and validate this approach in two mouse models of retinitis pigmentosa (RP). Transgenic mice carrying an Nrl-EGFP allele and homozygous for either knock-out of rhodopsin (Nrl-EGFP, Rho-/-) or heterozygous for knock-in of P23H mutant rhodopsin (Nrl-EGFP, RhoP23H/+) were used in this study. These novel strains have green fluorescent rods which undergo a progressive degeneration. Fundus imaging was performed at three-weekly intervals by near infrared reflectance (NIR) and blue light autofluorescence (BAF) confocal scanning laser ophthalmoscopy (cSLO). Mean grey values (mGV), which quantify fluorescence levels within such images, were compared for degenerate and age-matched non-degenerate (Nrl-EGFP, Rho+/+) controls. Mean grey value significantly decreased over time in the Rho-/- and RhoP23H/+ groups but was maintained in Rho+/+ mice (P < 0.001, two-way ANOVA). This corresponded to outer nuclear layer (ONL) thinning as observed by histology. The mGV of superior retina was significantly greater than that of inferior retina in RhoP23H/+ (P = 0.0024) but not in age-matched Rho+/+ (P = 0.45) or Rho-/- (P = 0.65) mice reflecting histological findings. Focal loss of rods could be visualised and mapped in vivo with this technique following a toxic insult, with thinning of the ONL being confirmed in hypofluorescent regions by spectral domain ocular coherence tomography (OCT). Fluorescence labelling of rods permits in vivo characterisation of models of RP and may provide new insights into patterns of degeneration, or rescue effect after treatment. mGV can be used in such cases as a semiquantitative metric of ONL degeneration, and can be used to identify regional variations in photoreceptor loss.


Differential DNA recognition and cleavage by EcoRI dependent on the dynamic equilibrium between the two forms of the malondialdehyde-deoxyguanosine adduct.
DNA damage may alter the outcome of protein-nucleic acid interactions. The malondialdehyde-deoxyguanosine adduct, 3-(2'-deoxy-beta-d-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10-(3H)-one (M(1)dG), miscodes in vivo and in vitro. M(1)dG is an exocyclic adduct that undergoes ring-opening in duplex DNA to form the acyclic adduct, N(2)-(3-oxo-1-propenyl)-deoxyguanosine (N(2)-OPdG). These two adducts have different effects on DNA polymerase bypass and may affect other DNA processing enzymes. We employed the EcoRI restriction endonuclease as a model for the interaction of DNA binding proteins with adducted DNA substrates. The presence of M(1)dG in the EcoRI recognition sequence impaired the ability of the enzyme to cleave DNA, resulting in only 60% cleavage of the adducted strand and 75% cleavage of the complementary strand. Three adducts of similar structure to M(1)dG that are unable to ring-open were cleaved poorly, or not at all, by EcoRI. None of the adducts appeared to inactivate or sequester EcoRI. Additional studies with BssHII and PauI confirmed these results and demonstrated a positional effect of M(1)dG on cleavage efficiency. These data suggest dissimilar modes of protein-nucleic acid interactions based on differences in adduct structure. Comparison of the solution structures of DNA adducts and the crystal structure of EcoRI complexed to substrate suggest a model to explain the functional differences.


Level-set-based inverse lithography for photomask synthesis.
Inverse lithography technology (ILT) treats photomask design for microlithography as an inverse mathematical problem. We show how the inverse lithography problem can be addressed as an obstacle reconstruction problem or an extended nonlinear image restoration problem, and then solved by a level set time-dependent model with finite difference schemes. We present explicit detailed formulation of the problem together with the first-order temporal and second-order spatial accurate discretization scheme. Experimental results show the superiority of the proposed level set-based ILT over the mainstream gradient methods.


Genetic diversity of nontuberculous mycobacteria among symptomatic tuberculosis negative patients in Kenya.
Non-Tuberculous Mycobacteria (NTM) transmission to humans occurs through inhalation of dust particles or vaporized water containing NTM leading to pulmonary manifestations. NTM infections are often misdiagnosed for tuberculosis (TB) due to their similar clinical and radiological manifestations. We, therefore, performed a species-level identification of NTM in symptomatic TB negative patients through sequencing of the hsp65 gene. We conducted a cross-sectional study at the National Tuberculosis Reference Laboratory in the period between January to November 2020. One hundred and sixty-six mycobacterial culture-positive samples that tested negative for TB using capilia underwent Polymerase Chain Reaction targeting the hsp65 gene. Isolates showing a band with gel electrophoresis at 441 bp position were sequenced using Sanger technology. Geneious software was used to analyze the obtained sequences, and the National Center for Biotechnology Information gene database identified NTM species for each isolate. A phylogenetic tree was constructed from the DNA sequences and evolutionary distances computed using the general time-reversible method. Pearson chi-square was used to determine the association between NTM infection and participants' characteristics. Our study identified 43 different NTM species. The dominant NTM belonged to Mycobacterium avium complex 37 (31%). Slow-growing NTM were the majority at 86 (71%) while rapid-growing NTM were 36 (29%). A significant association (P<0.05) was observed for regions and age, while patient type had a weak likelihood of NTM infection. Our study characterized the diversity of NTM in Kenya for the first time and showed that species belonging to M. Avium Complex are the most prevalent in the country.


Maternal pre-pregnancy obesity and health care utilization and costs in the offspring.
The association between maternal pre-pregnancy obesity and adverse child health outcomes is well described, but there are few data on the relationship with offspring health service use. We examined the influence of maternal pre-pregnancy obesity on offspring health care utilization and costs over the first 18 years of life. This was a population-based retrospective cohort study of children (n = 35,090) born between 1989 and 1993 and their mothers, who were identified using the Nova Scotia Atlee Perinatal Database and linked to provincial administrative health data from birth through 2014. The primary outcome was health care utilization as determined by the number and cost of physician visits, hospital admissions and days, and high utilizer status (>95th percentile of physician visits). The secondary outcome was health care utilization by ICD chapter. Maternal pre-pregnancy weight was categorized as normal weight, overweight, or obese. Multivariable-adjusted regression models were used to examine the association between maternal weight status and offspring health care use. Children of mothers with pre-pregnancy obesity had more physician visits (10%), hospital admissions (16%), and hospital days (10%) than children from mothers of normal weight over the first 18 years of life. Offspring of mothers with obesity had C$356 higher physician costs and C$1415 hospital costs over 18 years than offspring of normal weight mothers. Children of mothers with obesity were 1.74 times more likely to be a high utilizer of health care and had higher rates of physician visits and hospital stays for nervous system and sense organ disorders, respiratory disorders, and gastrointestinal disorders compared to children of normal weight mothers. Our findings suggest that maternal pre-pregnancy overweight and obesity are associated with slightly higher offspring health care utilization and costs in the first 18 years of life.


Primary appendiceal diffuse large B-cell lymphoma initially presenting as acute appendicitis: A case report.
Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 25% of all NHL cases. Primary appendiceal lymphomas (PAL) presenting as acute appendicitis are very rare, occurring in only 0.015% of all cases of gastrointestinal lymphoma. A 57-year-old man who was initially presented as acute appendicitis and subsequently underwent interval laparoscopic appendectomy. Pathological examination revealed diffuse large B cell lymphoma with cut end involvement. Whole-body positron emission tomography (PET) scan revealed enlarged right palatine tonsil and raised a suspicion of lymphoma involvement in two right cervical lymph nodes (level II and III); biopsy, however, showed that the lymph nodes were benign, with non-specific cellular changes. Bone marrow biopsy of the iliac crest also did not show lymphoma involvement. Subsequently, a diagnosis of primary appendiceal diffuse large B cell lymphoma (Ann Arbor Stage II) was established. After six courses of definite chemotherapy with cyclophosphamide, doxorubicin HCl, vincristine, and rituximab (R-CHOP), PET/CT showed complete remission of the prior FDG-avid malignancy of appendiceal DLBCL. The patient continued to be stable with no recurrence for fifteen months of regular outpatient department follow-ups. PAL is rare, and it clinically manifests the signs and symptoms of acute appendicitis. Specific characteristics of lymphoma in CT scans may lead to a more confirmative diagnosis. PET/CT is important for staging the lymphoma. Patients with PAL should be managed with surgical resection followed by R-CHOP-21 for 6 cycles regardless of whether they have localized disease or disseminated disease.


[Clinical application of three-dimensional spiral CT in skeletal disorders].
Three-dimensional (3D) computed tomographic reformations are used as an adjunct to standard axial computed tomography (CT) in the evaluation of disorders affecting areas of complex anatomy such as the skull, the spine, the pelvis, hands and feet. 3D-CT can provide a clear impression of lesion extent, pattern, shape and proximity to adjacent structures. This unique spatial information potentially has a significant impact on decisions regarding resectability, surgical approach and repair. The basic requirements for high-quality 3D-reformations are an absence of patient movement and narrow-width transaxial sections. Spiral CT significantly contributes to fulfilling these requirements. In addition, spiral CT scan data can be used to produce the ultimate representation of the third dimension: a life-size palpable medical model. In this review we describe the process of three-dimensional reconstruction and highlight potential problems arising during 3D-imaging processing. Useful clinical applications of spiral CT for 3D-visualization of skeletal pathology are discussed.


Effect of Initial Periodontal Therapy on Serum Nitric Oxide Levels in Chronic Periodontitis Patients with or without Type 2 Diabetes Mellitus.
To evaluate the effect of initial periodontal therapy on serum NO levels in chronic periodontitis (CP) patients with or without type2 diabetes mellitus (T2DM) Materials and methods: A total of 90 subjects (group I-30 healthy controls, group I-30 CP and group III-30 CP with T2DM) participated in this study. Groups II and III subjects received initial periodontal therapy. Clinical periodontal parameters (OHI-S, GI, PPD, and CAL) and serum NO levels were evaluated at baseline and 4 weeks after initial periodontal therapy. Serum NO levels were determined by the Spectrophotometric assay based on the Griess colorimetric reaction. Four weeks after initial periodontal therapy both groups II and III exhibited improvement in clinical periodontal parameters (OHI-S, GI, PPD, CAL) and reduction in serum levels of NO from its baseline values (Baseline-Group II: 3.64 ± 0.53, 1.93 ± 0.30, 3.29 ± 0.42, 3.60 ± 0.42, 89.21 ± 1.46 respectively, group III: 3.66 ± 0.44, 2.03 ± 1.32, 3.57 ± 0.40, 3.65 ± 0.45, 85.54 ± 1.54 respectively. Post-treatment-Group II: 1.73 ± 0.42, 1.27 ± 0.23, 3.16 ± 0.46, 3.47 ± 0.58, 70.91 ± 1.68 respectively, group III: 2.39 ± 0.49, 1.71 ± 0.33, 3.44 ± 0.42, 3.61 ± 0.48, 68.69 ± 1.17 respectively). However, statistically significant differences were observed only with OHI-(S) and serum NO values in both groups II and III (p < 0.05). When the baseline values of groups II and III were compared the differences were non-significant except for GI (p < 0.05). However, when the post-treatment clinical periodontal parameters and serum NO level of groups II and III were compared, statistically significant differences (p < 0.05) were observed except for PPD and CAL between the groups. NO can be utilized as a good indicator of the inflammatory status of the periodontium. Initial periodontal therapy is effective in reducing serum levels of NO in CP patients with or without T2DM. A bidirectional relationship exists between periodontal disease and diabetes mellitus. NO is found to play a significant role in the pathobiology of both CP and T2DM. Initial periodontal therapy seems to be beneficial in reducing serum NO levels along with periodontal parameters in CP patients with or without T2DM. However further studies are warranted to enhance our knowledge about the role of NO in periodontal diseases in the course of diabetes.


[Cellular composition of hemopoietic tissue of the liver and spleen in the human fetus].
Cell composition has been studied in hepatic reprints of 76 human fetuses between 6-27 weeks of development. Erythropoiesis predominates during the whole period of hepatic hemopoiesis. During 6-7 weeks primary erythroblasts make 1/4 of all erythroid cells, and by the 22d-27th weeks their content does not even reach 1.5%. Content of neutrophilic leucocytes is 1-1.5%. Nondifferentiated blast cells make 2.9 +/- 0.5-1 +/- 0.1%. Their greatest amount is observed between 6-8 and 18 and more weeks. The cell composition of the fetal spleen has been studied in 10 fetuses 19-25-week-old. Lymphoid forms make 85%, of all cells of the organ's hemopoietic tissue, of them 2.9 +/- 0.4% are lymphoblasts, 0.3 +/- 0.1%--nondifferentiated blasts. The investigations studying colonyforming properties of the hematopoietic cells confirmed that the highest content of myeloid precursers in the fetal liver and spleen is noted between 9-21 weeks of age. Therefore, it is possible to expect the greatest effect of these organs' transplantation during this time.


Identification of cis-acting elements that can obviate a requirement for the C-terminal domain of RNA polymerase II.
We have used an in vitro RNA polymerase II (RNAP II) inhibition-restimulation assay to investigate the inability of a form of RNAP II (RNAP IIB) that lacks the conserved, C-terminal heptapeptide repeat domain (CTD) to transcribe the dihydrofolate reductase (dhfr) promoter. Our previous studies demonstrated promoter-specific responses to RNAP IIB in the inhibition-restimulation assay and suggested the existence of cis-acting elements that alleviate the requirement for the CTD. We have now identified elements from two different classes of promoters that can convert dhfr to a CTD-independent promoter. First, addition of a consensus TATA box to the dhfr promoter resulted in a promoter capable of CTD-independent transcription and increased the promoter's affinity for the general transcription factor TFIID. These results suggest that high affinity for TFIID correlates with an ability to be transcribed by RNAP IIB, supporting a proposed interaction between the CTD and TFIID. Second, transfer of a combination of two elements (located at -25 and +1) from the rep-3b promoter, which does not contain a consensus TATA box but can nonetheless be transcribed by RNAP IIB, into the dhfr promoter also allowed CTD-independent transcription. These elements do not constitute a high affinity binding site for TFIID, indicating that an additional mechanism exists to allow CTD-independent transcription. Thus, elements from two classes of CTD-independent promoters that can obviate a requirement for the CTD appear to function via distinct mechanisms. Our finding that a change in a basal element can affect a requirement for the CTD is consistent with a role for the CTD during the formation of the transcriptional preinitiation complex.


Additional hemodynamic measurements with an esophageal Doppler monitor: a preliminary report of compliance, force, kinetic energy, and afterload in the clinical setting.
The esophageal Doppler monitor (EDM) is a minimally-invasive hemodynamic device which evaluates both cardiac output (CO), and fluid status, by estimating stroke volume (SV) and calculating heart rate (HR). The measurement of these parameters is based upon a continuous and accurate approximation of distal thoracic aortic blood flow. Furthermore, the peak velocity (PV) and mean acceleration (MA), of aortic blood flow at this anatomic location, are also determined by the EDM. The purpose of this preliminary report is to examine additional clinical hemodynamic calculations of: compliance (C), kinetic energy (KE), force (F), and afterload (TSVR(i)). These data were derived using both velocity-based measurements, provided by the EDM, as well as other contemporaneous physiologic parameters. Data were obtained from anesthetized patients undergoing surgery or who were in a critical care unit. A graphical inspection of these measurements is presented and discussed with respect to each patient's clinical situation. When normalized to each of their initial values, F and KE both consistently demonstrated more discriminative power than either PV or MA. The EDM offers additional applications for hemodynamic monitoring. Further research regarding the accuracy, utility, and limitations of these parameters is therefore indicated.


A Data Mining-Based Analysis of Core Herbs on Different Patterns (Zheng) of Non-Small Cell Lung Cancer.
To explore the role of Chinese prescriptions in non-small cell lung cancer (NSCLC) and provide references for the application of herbs and prescriptions. Randomized and quasirandomized controlled clinical trials on Chinese herbal medicine in the treatment of NSCLC were collected from seven databases to establish a database of prescriptions on NSCLC. Data-mining analyses were performed by RStudio (v4.0.3) software. A total of 970 prescriptions were obtained from 945 included studies, involving 7 syndromes and 428 herbs. The main patterns of NSCLC included qi deficiency pattern, yin deficiency pattern, blood deficiency pattern, kidney deficiency pattern, heat toxin pattern, phlegm-dampness pattern, and blood stasis pattern. High-frequency herbs on NSCLC were Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizome (Baizhu), Glycyrrhizae Radix Rhizome (Gancao), Poria (Fuling), Ophiopogonis Radix (Maidong), Hedyotidis Diffusae Herba (Baihuasheshecao), Codonopsis Radix (Dangshen), and Glehniae Radix (Beishashen). The properties of the herbs were mainly cold, warm, and mild. The flavors of the herbs were mainly sweet, bitter, and pungent. The main meridian tropisms were Lung Meridian of Hand-Taiyin, Spleen Meridian of Foot-Taiyin, and Stomach Meridian of Foot-Yangming. Applying clearing and tonifying method by targeting the lung and spleen was the most frequently used therapy in the treatment of NSCLC. This study offered a glimpse of unique views of traditional Chinese medicine on NSCLC and may benefit the treatment of NSCLC.


Grief, depressive symptoms, and inflammation in the spousally bereaved.
Grief is conceptualized by strong negative emotions, which include longing, sadness, and preoccupations with thoughts, recollections, and images of the spouse. In the initial months after the loss of a spouse, those who are widowed are at risk for cardiovascular problems and premature mortality. In the general population, depression is characterized by chronic low-grade inflammation, a key predictor of cardiovascular problems, morbidity, and mortality. Although depression and grief share similarities, they are distinct constructs. We aimed to identify if grief was related to inflammation among those who had a spouse recently die. We also sought to determine if those who are widowed and already experience elevated levels of depressive symptoms compared with the general population had higher levels of inflammation compared with those who are widowed who report fewer depressive symptoms. Ninety-nine recently bereaved individuals (M = 84.74 days since passing, SD = 18.17) completed a blood draw and psychological assessments. Proinflammatory T cell-derived cytokines were assessed, which included interferon gamma (IFN-γ), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL17-A, and IL-2. Bereaved individuals with a higher grief severity (using an established cut-score) had higher levels of the proinflammatory cytokines IFN-γ, IL-6, and TNF-α than those with less grief severity. Those who experienced higher levels of depression exhibited elevated levels of proinflammatory cytokines compared with those who had lower levels of depression (using a continuous measure of depressive symptoms, as well as an established cut score). This is the first study to demonstrate that inflammatory markers can distinguish those who are widowed based on grief severity such that those who are higher on grief severity have higher levels of inflammation compared with those who are lower on grief severity. These findings also add to the broader literature on depression and inflammation by showing that even in a population with high levels of depressive symptoms, there is a positive relationship between depression and inflammation.


Mechanistic Understanding of Water Oxidation in the Presence of a Copper Complex by In Situ Electrochemical Liquid Transmission Electron Microscopy.
The design of molecular oxygen-evolution reaction (OER) catalysts requires fundamental mechanistic studies on their widely unknown mechanisms of action. To this end, copper complexes keep attracting interest as good catalysts for the OER, and metal complexes with TMC (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) stand out as active OER catalysts. A mononuclear copper complex, [Cu(TMC)(H2O)](NO3)2 (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), combined both key features and was previously reported to be one of the most active copper-complex-based catalysts for electrocatalytic OER in neutral aqueous solutions. However, the functionalities and mechanisms of the catalyst are still not fully understood and need to be clarified with advanced analytical studies to enable further informed molecular catalyst design on a larger scale. Herein, the role of nanosized Cu oxide particles, ions, or clusters in the electrochemical OER with a mononuclear copper(II) complex with TMC was investigated by operando methods, including in situ vis-spectroelectrochemistry, in situ electrochemical liquid transmission electron microscopy (EC-LTEM), and extended X-ray absorption fine structure (EXAFS) analysis. These combined experiments showed that Cu oxide-based nanoparticles, rather than a molecular structure, are formed at a significantly lower potential than required for OER and are candidates for being the true OER catalysts. Our results indicate that for the OER in the presence of a homogeneous metal complex-based (pre)catalyst, careful analyses and new in situ protocols for ruling out the participation of metal oxides or clusters are critical for catalyst development. This approach could be a roadmap for progress in the field of sustainable catalysis via informed molecular catalyst design. Our combined approach of in situ TEM monitoring and a wide range of complementary spectroscopic techniques will open up new perspectives to track the transformation pathways and true active species for a wide range of molecular catalysts.


Treatment of thoracic actinomycosis: A retrospective analysis of 40 patients.
The aim of this study was to evaluate treatment outcomes in patients with thoracic actinomycosis and identify patient characteristics associated with unfavorable responses to antibiotic therapy. A retrospective analysis was performed on 40 patients with pathologically confirmed thoracic actinomycosis. Initial surgical treatment was performed on 17 patients to control severe symptoms such as hemoptysis or rule out lung cancer. Sixteen (94%) patients were successfully treated, including three patients who did not receive postoperative antibiotics, and one patient died of a postoperative complication. The median duration of oral antibiotic therapy after surgery was 3 months. After the diagnosis of actinomycosis, 23 patients began antibiotic therapy. The median duration of oral antibiotic therapy was 5 months. Favorable treatment outcomes were achieved in 18 of these 23 patients (78%), while five (22%) showed unfavorable responses to antibiotic therapy. Surgery was successfully performed in these five patients. The patients with unfavorable responses to antibiotic therapy had a longer duration of symptoms prior to treatment (median, 10 months) as compared to patients with favorable responses (median, 2 months; P = 0.012). Medical treatment failure is possible in patients with thoracic actinomycosis, and close monitoring is necessary in those who begin antibiotic therapy. In addition, surgical resection may be a valid option for patients who do not respond to antibiotic therapy, with the consideration of the age and comorbid conditions.


Physiochemical and optical study of chitosan-terephthaldehyde derivative for biomedical applications.
The chitosan-terephthaldehyde derivative was prepared by conversion of the chitosan gels through the extraction of the solvent, filtration and drying, a greener technique used for processing the materials. The identity of Schiff base was confirmed by UV-vis and Fourier-transform infrared (FTIR) spectroscopy. The chitosan-terephthaldehyde derivative was evaluated by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photoluminescence (PL) and rheological study. Photoluminescence (PL) spectrum had shown red shifted at excitation wavelength 254 nm. The rheological study revealed satisfactory behaviour which demonstrates better fluidity as well as moderate viscoelastic strength of the prepared gel. These results suggest that the chitosan-terephthaldehyde derivative material may open a new perspective in biomedical applications.


Analysis of algebraic weighted least-squares estimators for enzyme parameters.
An algorithm for the least-squares estimation of enzyme parameters Km and Vmax. is proposed and its performance analysed. The problem is non-linear, but the algorithm is algebraic and does not require initial parameter estimates. On a spreadsheet program such as MINITAB, it may be coded in as few as ten instructions. The algorithm derives an intermediate estimate of Km and Vmax. appropriate to data with a constant coefficient of variation and then applies a single reweighting. Its performance using simulated data with a variety of error structures is compared with that of the classical reciprocal transforms and to both appropriately and inappropriately weighted direct least-squares estimators. Three approaches to estimating the standard errors of the parameter estimates are discussed, and one suitable for spreadsheet implementation is illustrated.


Quantification of the Selective Advantage of Driver Mutations Is Dependent on the Underlying Model and Stage of Tumor Evolution.
Measuring the selective fitness advantages provided by driver mutations has the potential to facilitate a precise quantitative understanding of cancer evolution. However, accurately measuring the selective advantage of driver mutations has remained a challenge in the field. Early studies reported small selective advantages of drivers, on the order of 1%, whereas newer studies report much larger selective advantages, as high as 1,200%. In this article, we argue that the calculated selective advantages of cancer drivers are dependent on the underlying mathematical model and stage of cancer evolution and that comparisons of numerical values of selective advantage without regard for the underlying model and stage can lead to spurious conclusions.


Simulated annealing study of asymmetric diblock copolymer thin films.
We report a simulated annealing study of the morphology of asymmetric diblock copolymer thin films confined between two homogeneous and identical surfaces. We have focused on copolymers that form a gyroidal morphology in the bulk. The morphological dependence of the confined films on the film thickness and the surface-polymer interaction has been systematically investigated. From the simulations it is found that much richer morphologies can form for the gyroid-forming asymmetric diblock copolymer thin films, in contrast to the lamella-forming symmetric and cylinder-forming asymmetric diblock copolymer films. Multiple morphological transitions induced by changing the film thickness and polymer-surface interactions are observed.


Characteristics of water absorption in amine-cured epoxy networks: a molecular simulation and experimental study.
Moisture corrosion of cured epoxy resins seriously affects the durability of epoxy products and has been a serious issue in scientific and engineering fields. In this study, a series of cured epoxy resins with different structures were prepared by tuning their curing conversion in both experimental and simulation methods. In experiments, the equilibrium water content and the diffusion coefficient of amine-cured epoxy resins were measured by gravimetric measurement. The interaction between water molecules and epoxy network was investigated by time-resolved FTIR, difference spectroscopy and 2D correlation spectroscopy. In simulation, the hydrogen bonds, the mobility of hydroxypropyl ether groups and water molecules, and the free volume with its distributions were analyzed. Five types of water molecules were intuitively observed in this study; free volume had a stronger influence on equilibrium water content than polarity in the bifunctional epoxy/amine system, and the increase in the diffusion coefficient was considered as the result of reduction in motion resistance and an increase in channels for the motion of water molecules.


Accuracy and artifact: reexamining the intensity bias in affective forecasting.
Research on affective forecasting shows that people have a robust tendency to overestimate the intensity of future emotion. We hypothesized that (a) people can accurately predict the intensity of their feelings about events and (b) a procedural artifact contributes to people's tendency to overestimate the intensity of their feelings in general. People may misinterpret the forecasting question as asking how they will feel about a focal event, but they are later asked to report their feelings in general without reference to that event. In the current investigation, participants predicted and reported both their feelings in general and their feelings about an election outcome (Study 1) and an exam grade (Study 3). We also assessed how participants interpreted forecasting questions (Studies 2 and 4) and conducted a meta-analysis of affective forecasting research (Study 5). The results showed that participants accurately predicted the intensity of their feelings about events. They overestimated only when asked to predict how they would feel in general and later report their feelings without reference to the focal event. Most participants, however, misinterpreted requests to predict their feelings in general as asking how they would feel when they were thinking about the focal event. Clarifying the meaning of the forecasting question significantly reduced overestimation. These findings reveal that people have more sophisticated self-knowledge than is commonly portrayed in the affective forecasting literature. Overestimation of future emotion is partly due to a procedure in which people predict one thing but are later asked to report another.


Effect of pravastatin on blood pressure in people with cardiovascular disease.
Experimental evidence and several small studies in humans suggest that HMG-CoA (3-hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) reduce blood pressure, perhaps through effects on endothelial function or by reducing inflammation. We tested the hypothesis that pravastatin would reduce blood pressure at 3 months and the risk of developing new hypertension over a follow-up period of 5 years. This was a post hoc subgroup analysis of a randomized double-blind placebo-controlled trial of pravastatin 40 mg daily vs placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol <240 mg/dl (6.2 mmol/l). The primary outcome was the unadjusted change in mean arterial pressure (MAP) from baseline to 3 months. We also considered systolic and diastolic blood pressure (SBP and DBP) and pulse pressure. Analysis of covariance was used to calculate the adjusted effect of treatment on change in these outcomes at 3, 6, 12 and 24 months postrandomization, after controlling for potential confounders. Logistic regression was used to calculate the adjusted effect of treatment on incident hypertension (blood pressure > or =140/90 in those without known hypertension at baseline). This analysis included 4126/4159 (99.2%) participants for whom blood pressure was measured at baseline and during at least one follow-up visit. Median duration of follow-up was 57.8 months. The unadjusted and adjusted change in MAP, SBP, DBP or pulse pressure from baseline was not significantly different for pravastatin or placebo recipients at 3, 6, 12 or 24 months after randomization, or at last follow-up. Pravastatin did not reduce the adjusted risk of incident systolic hypertension (odds ratio 0.99, 95% CI 0.80-1.23), or incident diastolic hypertension (odds ratio 0.97, 95% CI 0.73-1.27). In summary, pravastatin 40 mg daily did not reduce blood pressure in survivors of myocardial infarction without overt hypercholesterolaemia.


Impact of Anticoagulation and Circuit Technology on Complications During Extracorporeal Membrane Oxygenation.
The objective of this study is to evaluate the impact a change in anticoagulation protocol and circuit technology had on bleeding and thrombotic complications in patients supported on extracorporeal membrane oxygenation (ECMO). A retrospective review at a tertiary, academic pediatric intensive care unit was undertaken. The anticoagulation protocol changed from targeting an activated clotting time (ACT) to anti-Xa level. Significant changes in the ECMO circuit were undertaken concurrently. One-hundred and fifty-two ECMO runs in 129 patients in the ACT target group were compared with 122 ECMO runs in 101 patients in the anti-Xa target group. Improved probability of survival by ECMO duration, decreased rate of surgical exploration, increased time to first surgical exploration, decreased incidence of intracranial hemorrhage, increased time to identification of intracranial hemorrhage, decreased blood loss and transfused product volumes, decreased rate of circuit changes, and increased time to first circuit change were all observed in the anti-Xa targeted group. Heparin dosing was similar in both groups with fewer bolus doses of heparin and fewer changes in the infusion rate in the anti-Xa targeted group. The change in anticoagulation protocol and circuit technology was associated with an improvement in survival, a decrease in hemorrhagic complications, and a decrease in circuit changes.


Sugar binding polymers showing high anomeric and epimeric discrimination obtained by noncovalent molecular imprinting.
Noncovalent molecular imprinting of sugar compounds in ethylene glycol dimethacrylate-methacrylic acid copolymers yielded materials containing highly selective sugar binding sites. Investigation of a range of polymers demonstrated that the resulting polymer imprints have a high degree of both anomeric and epimeric selectivity favoring the original print molecule. In HPLC assays, a polymer imprinted using p-nitrophenyl-alpha-D-galactoside could separate the alpha and beta anomers of the same compound with near baseline resolution. A polymer imprinted using p-nitrophenyl-beta-D-galactoside showed similar results but with the beta anomers retained longer as expected. Anomeric discrimination of closely related sugars was also possible, with the degree of separation depending on the structural resemblance to the print molecule. Similarly, a polymer imprinted with p-nitrophenyl-alpha-L-fucoside could separate alpha/beta mixtures of p-nitrophenyl-L-fucoside with baseline resolution. Using radioligand displacement assays a polymer imprinted using octyl-alpha-D-glucoside was shown to bind methyl-alpha-D-glucoside with a 40-fold higher affinity than that for the beta-anomer. The epimeric selectivity was even more impressive: methyl-alpha-D-mannoside and methyl-alpha-D-galactoside had 130- and 240-fold lower affinity, respectively, than methyl-alpha-D-glucoside. The results are discussed in relation to possible uses of such polymers in separation and analysis.


The effect of visual similarity on short-term memory for spatial location: implications for the capacity of visual short-term memory.
Evidence from the recency effect suggests that visual short-term memory is limited to preserving information about a single pattern. Three experiments explored the capacity of visual short-term memory using a task which involved presenting a series of patterns in a random spatio-temporal sequence and probing memory for the spatial location of one of them. Experiment 1 used sequences of quasi-random block patterns which were either visually similar or dissimilar. Serial position curves showed a single-item recency effect. However, there was also a deleterious effect of visual similarity for the earlier patterns, indicating that visual short-term memory was supporting their retention. Experiment 2 showed that performance was unaffected by articulatory suppression, confirming that phonological coding is not an important factor in the localisation task. Experiment 3 switched to letter stimuli and, because of the known tendency for this type of stimulus to be phonologically recoded, required articulatory suppression. Letters were shown in a customised form in sequences which were either visually similar or visually dissimilar. The results replicated experiment 1 in showing restricted recency combined with an effect of visual similarity extending across earlier list items. When the same letters were shown in standard form, the recency effect remained but the similarity effect disappeared, ruling out possible interpretations in terms of semantic as well as phonological coding. It is concluded that the recency effect gives a misleading indication of the capacity of visual short-term memory. The visual similarity effect suggests that it is capable of supporting the retention of several patterns.


Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum.
Purpose: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer-specific gene panel to detect DNA methylation in sputum and plasma.Experimental Design: This is a case-control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained preoperatively. Cases (n = 150) had pathologic confirmation of node-negative (stages I and IIA) non-small cell lung cancer. Controls (n = 60) had non-cancer diagnoses. We detected promoter methylation using quantitative methylation-specific real-time PCR and methylation-on-beads for cancer-specific genes (SOX17, TAC1, HOXA7, CDO1, HOXA9, and ZFP42).Results: DNA methylation was detected in plasma and sputum more frequently in people with cancer compared with controls (P < 0.001) for five of six genes. The sensitivity and specificity for lung cancer diagnosis using the best individual genes was 63% to 86% and 75% to 92% in sputum, respectively, and 65% to 76% and 74% to 84% in plasma, respectively. A three-gene combination of the best individual genes has sensitivity and specificity of 98% and 71% using sputum and 93% and 62% using plasma. Area under the receiver operating curve for this panel was 0.89 [95% confidence interval (CI), 0.80-0.98] in sputum and 0.77 (95% CI, 0.68-0.86) in plasma. Independent blinded random forest prediction models combining gene methylation with clinical information correctly predicted lung cancer in 91% of subjects using sputum detection and 85% of subjects using plasma detection.Conclusions: High diagnostic accuracy for early-stage lung cancer can be obtained using methylated promoter detection in sputum or plasma. Clin Cancer Res; 23(8); 1998-2005. ©2016 AACR.


Transfection of mammalian cells by the methods of receptor mediated gene transfer and particle bombardment.
The efficacy of currently developed methods for gene transfer into mammalian cells depends primarily on the transfection technique, and also on the type of targeted cells. Considering the importance of gene transfer in the creation of gene therapies, our study was aimed at the assessment of transfection capacity of receptor mediated gene transfer method (RMGT), and method of particle bombardment (helios gene gun system--HGG) in different normal and malignant mammalian cells ex vivo. In addition, the HGG was also assessed for its ability to transfect tumor cells of subcutaneous (s.c.) tumors in C57Bl/6 mice in vivo. Using RMGT an average ex vivo transfection rate of 35.7%, and 20.4% was achieved in malignant melanoma B-16, and human breast adenocarcinoma MCF7, respectively. However, in normal fibroblast L929 cells the transfection by RMGT succeeded only in 2.1% of the cells. On the other hand, the transfection efficacy of HGG was comparable in both malignant cell lines resulting in an average gene transfer to 9.6% of B-16 and 10.5% of MCF7 cells, while only 3.9% of normal fibroblasts were successfully transfected. Application of HGG for an in vivo gene transfer into s.c. B-16 melanoma tumors in C57Bl/6 mice resulted in a successful but limited transfection of the epithelium as well as of the superficially sited tumor cells. Taking into consideration both methods, RMGT is more appropriate for ex vivo transfection of cells, under the condition that target cells express a specific receptor for the molecule attached to the carrier. On the other hand, HGG is not complicated to use, no requirements for specific structures on target cells are necessary (potentially usable in different cells), and it has applicability in direct in vivo transfection processes.


Infection prevention in long-term care: re-evaluating the system using a human factors engineering approach.
The emergence and spread of extensively multidrug-resistant organisms is a public health crisis, and long-term care settings have been identified as a reservoir for the cultivation of these organisms. Long-term care settings are now taking on increasingly ill residents with complicated medical problems, indwelling devices, and significant healthcare exposure, all of which are considered risk factors selecting for resistant organisms. Despite this, guidelines addressing infection prevention procedures in long-term care remain vague, and implementation of these guidelines is challenging, largely due to staff turnover, limited resources, knowledge gaps, and lack of organizational support. Human factors engineering approaches have emerged as an important innovation to address patient safety issues and develop interventions in the healthcare work system (ie, tools and technologies, tasks, organization, physical environment) that support human performance, which, in turn, lead to improvements in processes (eg, compliance with infection prevention guidelines) and outcomes (eg, reduced infection rates). We propose the concept of using the methods and approaches from the scientific field of human factors engineering to address the unique challenges of implementing infection prevention in the long-term care setting.


Performance improvement of optical RZ-receiver by utilizing an all-optical waveform converter.
A practical receiver scheme with all-optical waveform conversion is proposed and demonstrated. To mitigate influence of the timing jitter of the received signal, the proposed receiver employs a semiconductor optical amplifier (SOA)-based waveform converter, which can generate signal pulses with a rectangular-like profile. We have evaluated the receiver performances of the conventional and proposed schemes. The receiver sensitivity improvement of 0.7 dB and the phase-margin enlargement of 60 % were simultaneously achieved in comparison with the conventional receiver scheme.


Antioxidant effect of astragalin isolated from the leaves of Morus alba L. against free radical-induced oxidative hemolysis of human red blood cells.
We evaluated the antioxidant properties of mulberry leaves extract (MLE) and flavonoids isolated from MLE. MLE was prepared by extraction with methanol. Flavonoids were analyzed by high-performance liquid chromatography. Oxidative hemolysis of normal human red blood cells (RBCs) was induced by the aqueous peroxyl radical [2,2'-Azobis (2-amidinopropane) dihydrochloride, AAPH]. MLE contained three flavonoids in the order quercetin (QC) > kaempferol (KF) > astragalin (AG). Oxidative hemolysis of RBCs induced by AAPH was suppressed by MLE, AG, KF, and QC in a time- and dose-dependent manner. MLE and these three flavonoids prevented the depletion of cystosolic antioxidant glutathione (GSH) in RBCs. AG had the greatest protective effect against AAPH-induced oxidative hemolysis and GSH depletion in RBCs.


Response of the IGF-I system to prolonged undernutrition and its involvement in somatic and skeletal muscle growth retardation in rats.
We examined the response of the IGF-I system to prolonged undernutrition and its involvement in somatic and skeletal muscle growth retardation. Male rats were food-restricted to 50% of freely-fed controls (C) from birth to 120 days postpartum. Serum and tissues were collected at d 50 and d 120 postpartum. Somatic growth of food-restricted animals (R) was proportional to food intake while organ and tissue growth was disproportionate. Skeletal muscle DNA content and synthesis rates were depressed by undernutrition and DNA synthesis decreased with age. Food-restriction abated serum IGF-I concentrations, serum IGFBP-3 expression and hepatic IGF-I mRNA levels at d 50. Conversely, at d 120, hepatic IGF-I mRNA levels in R were similar to C despite decreased serum IGF-I concentrations and serum IGFBP-3 expression. Hepatic IGFBP-1 and -2 mRNA expression in R was increased at both d 50 and 120, and hepatic IGFBP-4 mRNA expression was elevated on d 120 compared to C. Gastrocnemius IGF-I mRNA levels in R were not different from C at either d 50 or 120. These results suggest that hepatic IGF-I sensitivity to undernutrition decreases with increasing age, and endocrine regulation of IGF-I following adaptation to chronic undernutrition occurs post-transcriptionally. Further, local production of IGF-I in skeletal muscle does not appear to be responsible for the marked decline in muscle DNA synthesis, for skeletal muscle IGF-I mRNA expression was not altered by undernutrition.


Use of ultraportable vacuum therapy systems in the treatment of venous leg ulcer.
The high incidence of venous leg ulcers and the difficult to give a complete healing involves in an increase of costs for National Health System. Main therapies to obtain a fast healing are compressive bandages, treatment of abnormal venous flow and in-situ-strategies of wound care. Negative pressure therapy does not conventionally used, because these systems not allow the use of compression bandages. Recently the development of ultraportable devices has improved the compliance and the results. Ten patients with venous chronic ulcer on the lower extremities were recruited for this study: all patients had venous leg ulcers from at least one year. We treated the patients with autologous partial thickness skin graft and subsequently we applied NANOVA device included in compressive bandage. We used NANOVA for fourteen days and after we made traditional medications. We submitted a questionnaire to evaluate the impact of dressing and NANOVA device in the quality of life of patients. The device contributed to the formation of granulation tissue and increased the success rate of autologous skin graft without limiting mobility of patient. In addition to this, we have been able to perform compression bandages thanks to small size of this device. Eight ulcers healed within 90 days of medication. We believe that ultraportable negative pressure systems are useful devices for treatment of venous leg ulcers because them allows to realize a compressive bandage without mobility limitations.


Blastema from rabbit ear contains progenitor cells comparable to marrow derived mesenchymal stem cells.
Rabbits have the capacity to regenerate holes in their ears by forming a blastema, a tissue that is made up of a group of undifferentiated cells. The purpose of the present study was to isolate and characterize blastema progenitor cells and compare them with marrow mesenchymal stem cells (MSCs). Five New Zealand white male rabbits were used in the present study. A 2-mm hole was created in the animal ears. After 4 days, the blastema ring formed in the periphery of the hole was removed and cultivated. The cells were expanded through several subcultures and compared with the MSCs derived from the marrow of same animal in terms of in vitro differentiation capacity, growth kinetics and culture requirements for optimal proliferation. The primary cultures from both cells tended to be heterogeneous. Fibroblastic cells became progressively dominant with advancing passages. Similar to MSCs blastema passaged-3 cells succeeded to differentiate into bone, cartilage and adipose cell lineages. Even lineage specific genes tended to express in higher level in blastema cells compared to MSCs (p < 0.05). Moreover blastema cells appeared more proliferative; producing more colonies (p < 0.05). While blastema cells showed extensive proliferation in 15% fetal bovine serum (FBS), MSCs displayed higher expansion rate at 10% FBS. In conclusion, blastema from rabbit ear contains a population of fibroblastic cells much similar in characteristic to bone marrow mesenchymal stem cells. However, the two cells were different in the level of lineage-specific gene expression, the growth curve characteristics and the culture requirements.


Cross-resistance between dieldrin and fipronil in German cockroach (Dictyoptera: Blattellidae).
The toxicity of fipronil and dieldrin was determined in one susceptible laboratory strain and seven insecticide-resistant field-collected strains of Blattella germanica (L). The Zo960302 and Ga021001 strains were 1,270- and 2,030-fold resistant to dieldrin and 15- and 14-fold resistant to fipronil. The Su960304 and Od010803 strains were 15- and 13-fold resistant to dieldrin and two- and four-fold resistant to fipronil. Three strains showed no or a low level of resistance to dieldrin and fipronil. Crosses were performed between the susceptible strain Danish Pest Infestation Laboratory (DPIL)-SUS and the resistant strains Zo960302 and Su960304 and resistance to dieldrin and fipronil were intermediate compared with the susceptible and the resistant strains. Backcrosses to both of the parental strains showed cosegregation of dieldrin and fipronil resistance. The toxicity of dieldrin and fipronil was correlated when compared at LD50, and 93% of the observed variation in LD50 of fipronil can be ascribed to variation among predictions based on the value of LD50 of dieldrin. The frequency of the A302S substitution in the resistance to dieldrin (Rdl) gene in the highly dieldrin- and fipronil-resistant strains Zo960302 and Ga021001 and the moderately resistant Su960304 was 0.97, 1.0, and 0.38, respectively. We consider the connection between the frequency of the Rdl mutation and dieldrin and fipronil resistance a causal connection and not merely a coincidence.


ALLOOCIMENE: ABSENCE IN CIGARETTE SMOKE.
Alloocimene was not found to be a constituent of cigarette smoke under test conditions that allowed 86 percent recovery when authentic alloocimene was added to the smoke. In the same experiments dipentene was found to the extent of 0.2 percent of the smoke condensate.


Food Behavior in Emergency Time: Wild Plant Use for Human Nutrition during the Conflict in Syria.
Wild food plants (WFPs) have been an important source of human nutrition since ancient times, and it particularly revives when conventional food is not available due to emergency situations, such as natural disasters and conflicts. The war in Syria has entered 10 years since it started in 2011, and it has caused the largest war-related crises since World War II. Nearly 60% of the Syrian population (12.4 million people) are food-insecure. WFPs are already culturally important in the region, and may be supplementing local diets during this conflict. Our study aimed to uncover the conflict's effect on the use of WFPs and to know what species are consumed by local people during the current crisis. The fieldwork was carried out between March 2020 and March 2021 in the Tartus governorate located in the coastal region of Syria. Semi-structured interviews were conducted with 50 participants (26 women and 24 men) distributed in 26 villages along the study area. We recorded the vernacular names, uses, plant parts used, modes of preparation and consumption, change in WFP use before and during the conflict, and informants' perceptions towards WFPs. We documented 75 wild food plant species used for food and drink. Almost two-thirds (64%) of informants reported an increase in their reliance on wild plants as a food source during the conflict. The species of Origanum syriacum, Rhus coriaria, Eryngium creticum, and Cichorium intybus were among the most quoted species by informants. Sleeq (steamed leafy vegetables), Zaatar (breakfast/dinner food), and Louf (soup) were the most popular wild plant-based dishes.


Changes in the centrin and microtubule cytoskeletons after metaphase arrest of the Chlamydomonas reinhardtii met1 mutant.
The temperature-sensitive conditional met1 Chlamydomonas reinhardtii mutant arrests in metaphase at the restrictive temperature (33 degrees C) with an intact spindle and high cell division kinase levels. In this study, met1 was investigated with respect to changes in the microtubule and centrin-based cytoskeletons after arrest at 33 degrees C. Immunofluorescence microscopy revealed that, initially on arrest, the microtubule spindle and centrin-based cytoskeleton appeared as previously reported for wild-type metaphase cells; crescent-shaped spindles were seen with two brightly labelled centrin foci at each spindle pole in the basal body region at the cell surface. Observation of met1 held at the restrictive temperature reveals spindles can detach from one spindle pole and chromosomes eventually detach from the spindles. Moreover, a pseudo-anaphase event of spindle and nucleus elongation occurs in the absence of chromosome separation. Electron microscopy confirms that cytokinesis is initiated, the nuclei maintain a crescent shape but are distended and multiple pyrenoids are detected, suggesting chloroplast division also continues. Interestingly, prolamellar-like bodies usually present in etioplasts of dark-grown plants appear at the nuclear envelope. These results are discussed in relation to the coordination of division events in Chlamydomonas reinhardtii and the loss of viability in arrested cells of this mutant.


Detecting space-time disease clusters with arbitrary shapes and sizes using a co-clustering approach.
Ability to detect potential space-time clusters in spatio-temporal data on disease occurrences is necessary for conducting surveillance and implementing disease prevention policies. Most existing techniques use geometrically shaped (circular, elliptical or square) scanning windows to discover disease clusters. In certain situations, where the disease occurrences tend to cluster in very irregularly shaped areas, these algorithms are not feasible in practise for the detection of space-time clusters. To address this problem, a new algorithm is proposed, which uses a co-clustering strategy to detect prospective and retrospective space-time disease clusters with no restriction on shape and size. The proposed method detects space-time disease clusters by tracking the changes in space-time occurrence structure instead of an in-depth search over space. This method was utilised to detect potential clusters in the annual and monthly malaria data in Khyber Pakhtunkhwa Province, Pakistan from 2012 to 2016 visualising the results on a heat map. The results of the annual data analysis showed that the most likely hotspot emerged in three sub-regions in the years 2013-2014. The most likely hotspots in monthly data appeared in the month of July to October in each year and showed a strong periodic trend. A Correction has been published: https://doi.org/10.4081/gh.2023.1232


Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.
The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales.


Modulation of in vitro murine B-lymphocyte response by curcumin.
Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (tumeric). It was previously described that curcumin had a potent anti-inflammatory effect and inhibited the proliferation of a variety of tumor cells. In the present study, we investigated the inhibitory effects of curcumin on the response of normal murine splenic B cells. Curcumin inhibited the proliferative response of purified splenic B cells from BALB/c mice stimulated with the Toll-like receptor ligands LPS and CpG oligodeoxynucleotides. LPS-induced IgM secretion was also inhibited by curcumin. The proliferative response induced by either the T-independent type 2 stimuli anti-delta-dextran or anti-IgM antibodies was relatively resistant to the effect of curcumin. We investigated the intracellular signaling events involved in the inhibitory effects of curcumin on murine B cells. Curcumin did not inhibit the increase in calcium levels induced by anti-IgM antibody. Western blotting analysis showed that curcumin inhibited TLR ligands and anti-IgM-induced phosphorylation of ERK, IkappaB and p38. Curcumin also decreased the nuclear levels of NFkappaB. Our results suggested that curcumin is an important inhibitor of signaling pathways activated upon B cell stimulation by TLR ligands. These data indicate that curcumin could be a potent pharmacological inhibitor of B cell activation.


Palliative care for vulnerable populations.
The purpose of this article is to identify how inclusive and accessible palliative care can be achieved for all, including those labelled as vulnerable populations. Drawing on a review of existing literature as well the research of the Vulnerable Persons and End-of-Life New Emerging Team (VP-NET), this article reflects on what changes can be made within palliative care to make it more inclusive. Experiences of marginalization often result, intentionally or unintentionally, in differential treatment in healthcare. This increased vulnerability may result from attitudes of healthcare providers or from barriers as a result of "normal" care practices and policies that may exclude or stigmatize certain populations. This may include identifying when palliative care is necessary, who receives palliative care and where, and what is necessary to complement palliative care. Inclusive and accessible palliative care can become possible through building on the existing strengths in palliative care, as well as addressing existing barriers. This may include treating the whole person and that person's support team, including paid support workers, as part of the unit of care. It involves ensuring physically accessible hospice and palliative care locations, as well as thinking creatively about how to include those excluded in traditional locations. Inclusive palliative care also ensures coordination with other care services. Addressing the barriers to access, and inclusion of those who have been excluded within existing palliative care services, will ensure better palliative and end-of-life care for everyone.