The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus.
West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (CNS) infection in humans and animals. Although commercial vaccines are available for horses, none is currently approved for human use. In this study, we evaluated the efficacy and mechanism of immune protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV vaccine induced higher levels of specific and neutralizing antibodies compared to a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial and almost complete protection against a highly stringent lethal intracranial WNV challenge were observed in mice 60 days after single dose immunization with the DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with a single dose of DNA plasmid or inactivated vaccine, antigen-specific CD8(+) T cells were induced and contributed to protective immunity as acquired or genetic deficiencies of CD8(+) T cells lowered the survival rates. In contrast, in boosted animals, WNV-specific antibody titers were higher, survival rates after challenge were greater, and an absence of CD8(+) T cells did not appreciably affect mortality. Overall, our experiments suggest that in mice, both inactivated WNV and DNA plasmid vaccines are protective after two doses, and the specific contribution of antibody and CD8(+) T cells to vaccine immunity against WNV is modulated by the prime-boost strategy.


Intrapleural instillation of quinacrine for treatment of recurrent spontaneous pneumothorax.
We used intrapleural instillation of quinacrine hydrochloride in 20 patients (Group A) with recurrent spontaneous pneumothorax (one bilateral) and compared their clinical course with 19 patients who underwent thoracotomy and scarification or pleurectomy (Group B) and 63 patients treated by tube thoracostomy alone (Group C). In Group A, there was one complication of treatment, a pneumothorax immediately following tube removal, which necessitated repeat tube thoracostomy, and there was one late ipsilateral recurrence 2 years after treatment. These 20 patients with 21 recurrent spontaneous pneumothoraces treated with intrapleurally administered quinacrine have been followed for from 6 months to more than 4 years with only one late recurrence on the treated side. Eight patients in Group B had postoperative complications: 2 patients who had had pleurectomy required reoperation for postoperative bleeding; lobar pneumonia developed in 3; 1 had lack of total expansion of the lung; an intrathoracic hematoma developed in 1; and an ipsilateral pneumothorax necessitating tube thoracostomy developed in 1. In Group C, the rate of recurrence of pneumothorax was 23% during the first year following treatment. Intrapleural instillation of quinacrine is a simple, low-risk, reliable, and effective treatment for recurrent spontaneous pneumothorax, and is equally as effective as thoracotomy and scarification.


The underutilization of preventive cardiovascular measures in patients with cancer: an analysis of the Behavioural Risk Factor Surveillance System, 2011-22.
This study aimed to characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD). Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011-22) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation. Among 5 012 721 respondents, 579 114 reported a history of CVD (coronary disease or stroke), and 842 221 reported a diagnosis of cancer. The association between cancer and the use of pharmacological therapies varied between those with vs. without CVD (P-value for interaction: <0.001). Among patients with CVD, a cancer diagnosis was associated with a lower use of blood pressure-lowering medications {AME: -1.46% [95% confidence interval (CI): -2.19% to -0.73%]}, lipid-lowering medications [AME: -2.34% (95% CI: -4.03% to -0.66%)], and aspirin [AME: -6.05% (95% CI: -8.88% to -3.23%)]. Among patients without CVD, there were no statistically significant differences between patients with and without cancer regarding pharmacological therapies. Additionally, cancer was associated with a significantly lower likelihood of engaging in physical activity in the overall cohort and in using post-CVD rehabilitation regimens, particularly post-stroke rehabilitation. Preventive pharmacological agents are underutilized in those with cancer and concomitant CVD, and physical activity is underutilized in patients with cancer in those with or without CVD. •This paper compared the use of preventive cardiovascular measures, both pharmaceutical and non-pharmaceutical, in patients with and without cancer.•In patients with cardiovascular disease and cancer, there is a lower use of preventive cardiovascular medications compared with those with cardiovascular disease but without cancer. This includes a lower utilization of blood pressure-lowering medications, cholesterol-lowering medications, and aspirin.•Patients with cancer reported lower levels of exercise but higher levels of smoking cessation compared with those without cancer.


Effect of Training on Qualitative Mammographic Density Assessment.
The aim of this study was to evaluate the accuracy of visual mammographic breast density assessment and determine if training can improve this assessment, to compare the accuracy of qualitative density assessment before and after training with a quantitative assessment tool, and to evaluate agreement between qualitative and quantitative density assessment methods. Consecutive screening mammograms performed over a 4-month period were visually assessed by two study breast radiologists (the leads), who selected 200 cases equally distributed among the four BI-RADS density categories. These 200 cases were shown to 20 other breast radiologists (the readers) before and after viewing a training module on visual density assessment. Agreement between reader assessment and lead radiologist assessment was calculated for both reading sessions. Quantitative volumetric density of the 200 mammograms, determined using a commercially available tool, was compared with both sets of reader assessment and with lead radiologist assessment. Compared with lead radiologist assessment, reader accuracy of breast density assessment increased from 65% before training to 72% after training (odds ratio, 1.41; P < .0001). Training specifically improved assignment to BI-RADS categories 1 (P < .0001) and 4 (P < .10). Compared with quantitative assessment, reader accuracy showed statistically nonsignificant improvement with training (odds ratio, 1.1; P = .26). Substantial agreement between qualitative and quantitative breast density assessment was demonstrated (κ = 0.78). Training may improve the accuracy of mammographic breast density assessment. Substantial agreement between qualitative and quantitative breast density assessment exists.


Aorta wall quantitative alterations due to different long-term high-fat diet in rats.
Twenty Wistar male rats, with ages varying from 21 days to 12 months, were fed with diets supplemented by soybean oil (S group), canola oil (CA group), lard and egg yolk (LE group), and canola plus lard and egg yolk (CA+LE group). The LE group presented the highest heart mass/body mass ratio and the highest blood pressure as well. The aortic structure suffered a number of alterations, from CA rats group (minor alterations) to LE and CA+LE rats group (major alterations). The CA group showed the smallest aorta thickness. No significant differences among groups were found concerning the number of aortic lamellae and the density of tunica media smooth muscle nuclei. Surface density of the aortic lamellae was greater in the CA group and smaller in the LE group. These results suggest that the dietary intake of canola oil could attenuate the aorta structure aging process with a favorable BP maintenance.


Investigating the efficacy of amnion-derived compared with bone marrow-derived mesenchymal stromal cells in equine tendon and ligament injuries.
This is the first study to compare the treatment of horse tendon and ligament injuries with the use of mesenchymal stromal cells (MSCs) obtained from two different sources: amniotic membrane (AMSCs) and bone marrow (BM-MSCs). The objective was to prove the ability of AMSCs to exert beneficial effects in vivo. Five million allogeneic frozen-thawed AMSCs or autologous fresh BM-MSCs were injected intralesionally in horses belonging to group A (51 horses) and group B (44 horses). The interval lesion/implantation was of 6-15 days for the AMSCs and 16-35 days for the BM-MSCs. Healing was assessed clinically and ultrasonographically. Follow-up was monitored for 2 further years from return to full work. No significant adverse effects after MSCs treatment were seen in any of the horses studied, independent of the type of stromal cell implanted. All animals belonging to group A resumed their activities between 4-5 months after treatment, whereas animals of group B resumed their activities after 4-12 months. The rate of re-injury in horses treated with AMSCs is lower (4.00%) compared with the average observed when horses were treated with BM-MSCs (23.08%). The possibility to inject allogeneic AMSCs in real time, before any ultrasonographic change occurs within the injured tendon and ligament, together with the higher plasticity and proliferative capacity of these cells compared with BM-MSCs, represents the main features of interest for this novel approach for the treatment of equine tendon diseases. An obvious active proliferative healing in the area injected with AMSCs makes these cells more effective than BM-MSCs.


Techniques to Control Microbial Contaminants in Nonsterile Microalgae Cultivation.
The aim of this mini-review with own results was an identification of techniques to suppress the growth of microbial contaminants under photo- and mixotrophic conditions. Techniques identified are the modification of environmental conditions, such as pH, oxygen, and nutrient concentrations, as well as the application of pulsed electric field, ultrasonication, and surfactants. In phototrophic cultivations, the mentioned techniques result in a decrease of number of predatory cells, but not in a complete removal. Measures to suppress the growth of contaminations (e.g., bacteria and fungi) in mixotrophic cultivations could not be identified. The co-cultivation of algae and fungi, however, was found to be beneficial for the utilization of unusual carbon compounds (e.g., phenolic compounds).


Laparoscopic Double Discoid Resection With a Circular Stapler for Bowel Endometriosis.
To demonstrate the technique of laparoscopic double discoid resection with a circular stapler for bowel endometriosis. Case report (Canadian Task Force classification III). Private hospital in Curitiba, Paraná, Brazil. A 33-year-old woman was referred to our service complaining about cyclic dysmenorrhea, dyspareunia, chronic pelvic pain, and cyclic dyschezia. Transvaginal ultrasound with bowel preparation showed a 6-cm endometriotic nodule at the retrocervical area, uterosacral ligaments, posterior vaginal fornix, and anterior rectal wall, infiltrating up to the submucosa, 5 cm far from the anal verge. Under general anesthesia, the patient was placed in the dorsal decubitus position with her arms alongside her body and her lower limbs in abduction. Pneumoperitoneum was achieved using a Veres needle placed at the umbilicus. Four trocars were placed: a 10-mm trocar at the umbilicus for the zero-degree laparoscope; a 5-mm trocar at the right anterosuperior iliac spine; a 5-mm trocar in the midline between the umbilicus and the pubic symphysis, approximately 8 to 10 cm inferior to the umbilical trocar; and a 5-mm trocar at the left anterosuperior iliac spine. The entire pelvis was inspected for endometriotic lesions, and all implants in the anterior compartment of the pelvis were resected. The lesions located at the ovarian fossae were completely removed. The ureters were identified bilaterally, and both para-rectal fossae were dissected. The right hypogastric nerve was released from the disease laterally. The lesion was separated from the retrocervical area, and the posterior vaginal fornix was resected (reverse technique), leaving the disease attached to the anterior surface of the rectum. The lesion was shaved off the anterior rectal wall using a harmonic scalpel. A x-shaped stitch was placed at the anterior rectal wall using 2-0 mononylon suture. A 33-mm circular stapler was placed transanally under laparoscopic control, and once it reached the area to be resected, it was opened. A gap was created between the envil and the stapler. The anterior rectal wall was placed inside this gap with the aid of the stitch at the anterior rectal wall. The stapler was fired, and a piece of the anterior rectal wall was resected. The same procedure was performed using a 29-mm circular stapler, which allowed for the complete removal of the lesion. We usually perform the second discoid resection using a 29-mm circular stapler to allow an easy progression of the stapler through the rectum beyond the first stapler line, so not to put too much pressure on it. In our experience, the first discoid resection removes most of the disease, and the second discoid resection is only needed to remove a small amount of residual disease, along with the first staple line. The procedure took 177 min, and the estimated blood loss was 100 mL. The patient started clear liquids 6 hours after the procedure, and was discharged 19 hours after that [1]. Pathological examination of the 2 strips of the anterior rectal wall revealed infiltration of the bowel wall by endometriotic tissue. She had an uneventful postoperative course, and was able to re-start sexual intercourse 50 days after surgery. Between January 2010 and January 2015, 315 women underwent laparoscopic surgery for the treatment of bowel endometriosis in our service. Among them, 16 (5.1%) were operated on by using the double discoid resection technique. Median age of the patients was 34 years, and median body mass index was 25.9 kg/m(2). Median preoperative cancer antigen-125 level was 26.5 U/mL (normal value is <35 U/mL). Median size of the rectosigmoid nodule was 35 mm (range: 30-60), and median distance from the anal verge was 10.5 cm (range: 5-15 cm). Median surgical time was 160 min (range: 54-210 min). Concomitant procedures included hysterectyomy (n = 5), partial cystectomy (n = 3), resection of the posterior vaginal fornix (n = 4), and appendectomy (n = 1). Median estimated intraoperative bleeding was 32.5 mL (range: 30-100), and median time of hospitalization was 19 hours (range: 10-41). Median American Fertility Society score was 46 (10-102). Two minor complications (12.5%) occurred in this initial series: 1 patient required bladder catheterization for urinary retention; and 1 patient developed a urinary tract infection that required oral antibiotic treatment. One major complication (6.2%) was observed; the patient developed fever and abdominal pain on the fourth postoperative day. She was re-operated, and the intraoperative diagnosis was pelviperitonitis. The abdominal cavity was inspected for any dehiscence of the bowel and then washed. She was discharged on the second day after re-operation with oral antibiotic therapy. In our daily practice, we are used to discharging our patients soon in the postoperative setting (19 hours for rectal shaving or discoid resection and 28 hours for segmental bowel resection) [1] because the rate of postoperative fistula seems to be low [2]. Because we still have not seen any fistulas after conservative surgery (rectal shaving, discoid resection, and double discoid resection), we usually prefer to perform this type of surgery compared with segmental bowel resection, when possible. Laparoscopic double discoid resection with circular stapler may be an alternative to segmental bowel resection in selected patients with bowel endometriosis.


Protein modification and its biological role.
The modifications present on a polypeptide play an important role in determining its eventual fate. Modifications, particularly proteolysis, are important in the generation of biological activity. Modifications are used to "target" particular polypeptides to specific cellular locations. Protein modification also plays a role in determining the rate of polypeptide degradation. Cells have developed elaborate systems for the modification of their proteins because these modifications serve important biological functions.


Role of phospholipase A2 activation in histamine release from human basophils.
The present experiments were undertaken to investigate the role of phospholipase A2 (PLA2) activation in histamine release from human basophils. A PLA2 inhibitor, P-bromophenacyl bromide (BPB), inhibited IgE-mediated anti-IgE-induced histamine release from human basophils with a concentration of drug required to produce 50% inhibition (IC50) of 1.5 x 10(-6) M when leukocytes were preincubated with this agent for 15 min. Histamine release induced by calcium ionophore A23187 and formyl-L-methionyl-L-leucyl-L-phenylalanine was also blocked by BPB with IC50 of 4.1 x 10(-6) M, and 3.5 x 10(-6) M, respectively. A PLA2 activator, 12-0-tetradecanoylphorbol-13-acetate (TPA) caused basophil histamine release with a dose-dependent fashion. BPB inhibited TPA-induced histamine release (IC50: 2.5 x 10(-6) M). However, another PLA2 activator, melittin, and PLA2 did not release histamine through non-cytotoxic mechanisms. Collectively, these results suggest that PLA2 activation plays a central role in histamine release from human basophils via generation of lysophosphatidylcholine or products of the lipoxygenase pathway of arachidonic acid metabolism.


Decrease of PECAM-1-gene-expression induced by proinflammatory cytokines IFN-gamma and IFN-alpha is reversed by TGF-beta in sinusoidal endothelial cells and hepatic mononuclear phagocytes.
The mechanisms of transmigration of inflammatory cells through the sinusoids are still poorly understood. This study aims to identify in vitro conditions (cytokine treatment) which may allow a better understanding of the changes in PECAM (platelet endothelial cell adhesion molecule)-1-gene-expression observed in vivo. In this study we show by immunohistochemistry, that there is an accumulation of ICAM-1 (intercellular cell adhesion molecule-1) and ED1 positive cells in necrotic areas of livers of CCl4-treated rats, whereas there are few PECAM-1 positive cells observable. After the administration of CCl4, we could detect an early rise of levels of IFN-gamma followed by an enhanced TGF-beta protein level. As shown by Northern blot analysis and surface protein expression analysed by flow cytometry, IFN-gamma-treatment decreased PECAM-1-gene-expression in isolated SECs (sinusoidal endothelial cells) and mononuclear phagocytes (MNPs) in parallel with an increase in ICAM-1-gene-expression in a dose and time dependent manner. In contrast, TGF-beta-treatment increased PECAM-1-expression. Additional administration of IFN-gamma to CCl4-treated rats and observations in IFN-gamma-/- mice confirmed the effect of IFN-gamma on PECAM-1 and ICAM-1-expression observed in vitro and increased the number of ED1-expressing cells 12 h after administration of the toxin. The early decrease of PECAM-1-expression and the parallel increase of ICAM-1-expression following CCl4-treatment is induced by elevated levels of IFN-gamma in livers and may facilitate adhesion and transmigration of inflammatory cells. The up-regulation of PECAM-1-expression in SECs and MNPs after TGF-beta-treatment suggests the involvement of PECAM-1 during the recovery after liver damage.


Production of antibodies and development of a radioimmunoassay for okadaic acid.
An okadaic acid immunogen, prepared by conjugation of okadaic acid to bovine albumin with carbodiimide, was used to immunize two rabbits. The rabbits responded by producing antibodies that neutralized okadaic acid's stimulation of arachidonic acid metabolism and this neutralization increased during the course of immunization. The immune sera bound 3H-okadaic acid and this binding also increased with repeated immunization. After absorption of the rabbit IgG with a goat anti-rabbit IgG, binding was reduced greater than 99%. The binding of okadaic acid to the antibodies in one antiserum was inhibited by as little as 0.2 pmoles of unlabelled okadaic acid. The apparent association constant for binding with this antiserum was 4.17 x 10(9) M-1 (35 degrees C). Maitotoxin, teleocidin, 12-O-tetradecanoylphorbol-13-acetate, aplysiatoxin, palytoxin and brevetoxin B when tested at 29, 228, 168, 169, 3.7 and 112 pmole levels, respectively, did not inhibit binding. The serologic and biological activities of okadaic acid after incubation for 60 min in 0.01 N HCl at 35 degrees C or at 100 degrees C at pH 7.2 were unaffected.


Client-centred assessment and the identification of meaningful treatment goals for individuals with a spinal cord injury.
Retrospective analysis. (1) Describe the self-care, productivity and leisure problems identified by individuals with a spinal cord injury (SCI) during rehabilitation, (2) describe the perceived level of satisfaction and performance with self-care, productivity and leisure activities following an SCI, (3) quantify the relationship between the Canadian occupational performance measure (COPM), a client-centred, individualized measure of function, and the functional independence measure (FIM). Tertiary rehabilitation centre, spinal cord injury unit, GF Strong Rehabilitation Centre, Vancouver, Canada. Health records from 41 individuals with an SCI admitted between 2000 and 2002 were reviewed. Information was obtained from assessments performed on admission and discharge. Self-care, productivity and leisure problems identified by individuals with an SCI were described and their perceived level of performance and satisfaction was calculated. The relationship between the COPM and the FIM was measured by the Pearson product correlation. Self-care goals were identified most frequently (79%) followed by productivity (12%) and leisure (9%) goals. The top three problems identified by individuals with an SCI were functional mobility (including transfers and wheelchair use), dressing and grooming. A fair relationship was found between the COPM and the FIM (r between 0.351 and 0.514, P<0.05). The results highlight the importance of including a client-centred outcome measure in the assessment of individuals with an SCI. Initial support is provided for use of the COPM in individuals with an SCI.


The learning curve for safety and success of precut sphincterotomy for therapeutic ERCP: a single endoscopist's experience.
The aims of this study were to evaluate the efficacy and safety of precut sphincterotomy in relation to the experience of a single endoscopist, and to establish the number of procedures required before achieving an effective and safe precut sphincterotomy. A total of 200 consecutive patients underwent precut sphincterotomy carried out by a single endoscopist (T.A.) between January 2003 and December 2005. All of the procedures were divided into four chronological groups of 50 (Group I, II, III, and IV). Medical records and patient data were retrospectively reviewed and included procedure indications, outcomes, and complications. All patients were admitted for observation after the procedure in case of complications. A total of 200 patients (23.3%) (mean age 58.5 years; 101 men) underwent precut sphincterotomy (161 with needle-knife technique, 32 with septotomy technique, and seven with Erlangen technique). There was no mortality. The success rates of prompt bile duct cannulation after precut sphincterotomy were 88%, 86%, 94%, and 82%, respectively ( P > 0.05). Immediate bleeding requiring a submucosal adrenaline injection was observed in combined group I - II (28%) and combined group III - IV (7%) ( P < 0.05). One patient (2%) from each of group I, III, and IV required further endoscopic treatment for rebleeding. Duodenal perforation (2%) was detected and conservatively treated in one patient from group II. Mild pancreatitis was found in one patient (2%) in group III. The success rates of bile duct cannulation by precut sphincterotomy were not associated with the experience of the endoscopist. The postprocedural complications significantly decreased after the first 100 procedures. An experience of at least 100 procedures is suggested to achieve a safe precut sphincterotomy.


SOAP Notes During APPEs: Assessment of Student Performance.
To evaluate and compare students' ability to perform in each area of the subjective, objective, assessment, and plan (SOAP) note during advanced pharmacy practice experiences (APPEs) within an academic year. This study also aimed to compare the quality of SOAP notes between semesters: summer (1-3 rotation blocks), fall (4-6 rotation blocks), and spring (7-9 rotation blocks). During internal medicine and acute-care APPEs, students were required to submit a minimum of 2 SOAP notes. Each SOAP note was assessed by a full-time faculty member at a College of Pharmacy. Students were rated on the ability to perform in each area of the SOAP note using a rubric with a scale of 1 to 5 (1 = unacceptable/needs significant improvement, 5 = exemplary). This study was granted exempt approval by the Long Island University institutional review board. Quality of the SOAP note summer versus fall versus spring rotations: Thirty-four SOAP notes were assessed during the summer, 48 SOAP notes were assessed during the fall, and 46 SOAP notes were assessed during the spring. Students performed similarly regardless of the semester they took for "subjective/objective, assess, and plan." All P values were nonstatistically significant. Performance on SOAP note #1 versus SOAP note # 2: On overall rubrics for SOAP notes 1 versus SOAP notes 2, students did better on SOAP notes 2 after feedback, and an opportunity to improve was provided. There were statistically significant differences on all areas of SOAP note "subjective/objective, assess, and plan." Conclusion: Overall, students performed adequately on the SOAP note activity during APPE rotations. Students performed similarly regardless of the semester/time when students took the APPEs during an academic year.


A Population-based Study of Grade 12 Academic Performance in Adolescents With Childhood-onset Chronic Rheumatic Diseases.
The aims of this study were (1) to compare grade 12 standardized test results of patients diagnosed with childhood-onset chronic rheumatic diseases (ChildCRD) and unaffected peers; and (2) to identify factors associated with test results of patients with ChildCRD and unaffected peers. This was a population-based retrospective cohort study. All patients with ChildCRD (juvenile arthritis and systemic autoimmune rheumatic diseases) from the only pediatric rheumatology center in Manitoba for birth cohorts January 1979 to December 1998 were linked to the provincial administrative databases containing records of healthcare use and education outcomes. Patients were matched by age, sex, and postal codes to their peers who did not have ChildCRD. The primary outcomes were the grade 12 Language Arts Achievement Index (LAI) and the Math Achievement Index (MAI) scores. ChildCRD, sociodemographic, and mental health factors were tested for their associations with LAI and MAI scores using multivariable linear regression. Five hundred and forty-one patients with ChildCRD were matched to 2713 unaffected peers. Patients with ChildCRD had lower LAI and MAI scores compared to their peers. More patients with ChildCRD failed or did not take the language arts (51% vs 41%, P < 0.001) and math (61% vs 55%, P = 0.02) tests. On multivariable analysis, ChildCRD, lower socioeconomic status, younger maternal age at first childbirth, family income assistance, involvement with child welfare services, and mental health morbidities (between ChildCRD diagnosis and standardized testing), were associated with worse LAI and MAI results. This population-based study showed that patients with ChildCRD performed less well than their peers on grade 12 standardized testing, independent of sociodemographic and mental health comorbidities.


Critical review of solid phase extraction for multiresidue clean-up and pre-concentration of antibiotics from livestock and poultry manure.
The release of antibiotics into the environment from agricultural industries has received tremendous attention in recent years. Nonpoint source contamination of the terrestrial environment by these compounds can result from fertilisation of agricultural soils with manure. The presence of antibiotics and their metabolites in manure may pose a threat to agro-ecosystems. This may result in the emergence of antibiotic resistance bacteria in humans through the food chain and this is a major concern globally at the moment. Therefore, monitoring of manure for antibiotic residues is of vital importance in order to assess the risks of environmental pollution to human health by these drugs. Several sample pre-treatment techniques have been developed for the extraction of antibiotic residues from complex matrices including manure over the years. Despite new developments in recent years in separation science where the common trend is miniaturisation and green approaches, solid-phase extraction is still the most widely used technique in the extraction of antibiotics from agricultural wastes such as manure. In view of this, the aim of this review was to give a critical overview of studies that have been conducted in the past 6 years on the extraction of antibiotic residues from manure employing solid-phase extraction based on Oasis HLB and Strata-X. Adsorption mechanisms of these sorbents were also briefly discussed.


Review on Comfort Nursing Interventions for Patients Undergoing Neurosurgery and General Surgery.
To summarize the commonalities and particularities of comfort care interventions for neurology and general surgery patients. The development of comfort care and its practical application in neurology and general surgery were discussed and summarized by searching the current literature on comfort care interventions for neurology and general surgery patients, including case reports, clinical studies, and systematic reviews. Comfort nursing intervention is a kind of nursing intervention with integrity and creativity. In addition to its uniqueness, the comfort nursing model also has strong effectiveness. Clinical holistic nursing has been significantly improved through the application of comfort nursing intervention theory, and its nursing mode has enhanced the connotation of clinical nursing. Comfort nursing intervention for neurology and general surgery patients can help patients recover and deserves further promotion.


The effects of zinc deficiency on homeostasis of twelve minerals and trace elements in the serum, feces, urine and liver of rats.
Zinc deficiency can change the concentrations of minerals and trace elements in the body. However, previous studies still had many limitations. To reveal the effects of zinc deficiency on homeostasis of 16 minerals and trace elements. Forty-five rats were divided randomly into three groups: normal zinc diet (30 mg/kg), low zinc diet (10 mg/kg), and pair-fed diet(30 mg/kg). The concentrations of 16 minerals and trace elements in serum, feces, urine, and liver were measured by inductively coupled plasma mass spectrometry. The excretion of 16 elements in urine and feces were calculated and compared. Zinc-deficient rats exhibited significant changes in up to 12 minerals and trace elements. The low zinc diet induced decreased excretion of zinc and concentrations of zinc in serum, feces, urine, and liver. Zinc deficiency increased feces concentrations of Mg, Cu, Se, K, Ag, Fe and Mn; decreased the concentrations of Mg, Cu, Se, K in liver and urine, and a diminished amount of Ag was observed in serum. Decreased urinary concentrations of Zn Ca, Mg, Cu, Se, K, Na, As and Cr, suggested that zinc-deficient rats increased the 9 elements' renal reabsorption. Decreased concentrations of Ca in liver, urine, and feces, decreased excretion in urine and feces and increased serum total Ca suggested that zinc deficiency increased the redistribution of Ca in serum or other tissues. Zinc deficiency increased excretion of Cu, Se, Fe; and decreased the excretion of other 8 elements except for Ag. Zinc deficiency changed the excretion, reabsorption and redistribution of 12 minerals and trace elements in rats. Our findings are the first to show that zinc deficiency alters the concentrations of Ag, Cr, and As. Supplementary information accompanies this paper at 10.1186/s12986-019-0395-y.


Risk of hepatocellular carcinoma in relation to ABO blood type.
Mortality and incidence rates of hepatocellular carcinoma (HCC) parallel the geographical distribution of hepatitis B and C viruses among the general population, however genetic factors modulate individual cancer risk. ABO blood type, as a genetic marker, has previously been associated with the risk of several malignancies; we aimed to evaluate whether an association exists with HCC. This is a retrospective case-control study based on ABO distribution in 194 patients with HCC, compared with 215 decompensated cirrhotics without HCC listed for liver transplantation, and 90,322 healthy blood donors. In patients with HCC, prevalence of blood type O was 35%, vs. 44% in cirrhotics (OR: 0.67, 95% CI 0.45-0.99; p=0.046) and 45% in blood donors (OR: 0.65, 95% CI 0.48-0.88; p=0.004). ABO blood type non-O is associated with higher risk of hepatocellular carcinoma, compared to cirrhotics without HCC and healthy subjects.


Transaction costs and community-based natural resource management in Nepal.
Transaction costs in community-based resource management are incurred by households attempting to enforce property right rules over common resources similar to those inherent in private property rights. Despite their importance, transaction costs of community-based management of common pool resources (CPRs) are often not incorporated into the economic analysis of participatory resource management. This paper examines the transaction costs incurred by forest users in community forestry (CF) based on a survey of 309 households belonging to eight different forest user groups (FUGs) in the mid hills of Nepal. The analysis reveals that the average 'poor' household incurred Nepalese rupees (NRS) 1265 in transaction costs annually, while wealthier 'rich' households incurred an average of NRS 2312 per year. Although richer households bear higher proportions of such costs, transaction costs for CF management as a percentage of resource appropriation costs are higher for poorer households (26%) than those of middle-wealth (24%) or rich households (14%). There are also village differences in the level of transaction costs. The results show that transaction costs are a major component of resource management costs and vary according to socio-economic status of resource users and characteristics of the community.


Excessive sleepiness and associated symptoms in the U.S. adult population: prevalence, correlates, and comorbidity.
This study examined the prevalence, sociodemographic features, patterns of comorbidity, and impact on functional impairment of excessive sleepiness (Ex.S) and associated symptoms in a nationally representative sample of adults using the National Comorbidity Survey Replication (NCS-R) dataset. Participants ≥18 years (n = 5,962) were queried about their sleep using the Composite International Diagnostic Interview (CIDI). Specifically, respondents were questioned about feeling sleepy during the day and falling asleep in permissive situations, feelings of insufficient sleep despite adequate time in bed, and/or difficulty waking up. Those endorsing daytime sleepiness and at least one additional symptom were considered to have Ex.S plus associated symptoms. Associations between Ex.S plus associated symptoms and sociodemographics, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) mental disorders, chronic physical conditions, and functional impairment were examined. The prevalence of Ex.S plus associated symptoms in U.S. adults was 23.34% (standard error [SE] = 0.88) and significantly co-occurred with insomnia-related symptoms after adjusting for confounders (Odds ratio [OR] = 5.65; 95% confidence interval [CI] = 4.55-7.02). The presence of Ex.S and associated symptoms was more common in women, particularly younger women, those with lower family income, and the unemployed (all P<.001). After controlling for demographic characteristics and other confounders, Ex.S plus associated symptoms was associated with having a DSM-IV mental disorder (OR = 4.25; 95% CI = 3.53-5.10), a chronic physical condition (OR = 2.57; 95% CI = 1.94-3.42) and greater disability (P<.001). Ex. S with associated symptoms was common, frequently co-occurred with other mental and physical conditions, and was associated with substantial disability. Dissipation of some associations after controlling for insomnia-related symptoms indicated that physical-mental comorbidity and disability were greater among individuals with more pervasive sleep disturbances.


Colonic obstruction secondary to impaction of a large calcified fecolith. Report of a case.
The case of a patient with colonic obstruction secondary to impaction of a large calcified fecolith is presented. Clinical features, radiographic findings and treatment are described and the literature is reviewed.


Perillyl alcohol, a pleiotropic natural compound suitable for brain tumor therapy, targets free radicals.
Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis. When cells are subjected to oxidative stress conditions, there is an accumulation of ROS that can lead to irreversible cell injury caused primarily by lipid peroxidation, protein aggregation and/or DNA damage. Malignant tumors, such as glioblastoma multiforme, display elevated rates of oxygen consumption, necrosis and abnormal structural microvasculature. Alterations in the tumor microenvironment are tightly linked to tumor progression and occur as a result of activation of complex signaling networks involving inter-clonal cooperation, cell-matrix interactions and an ongoing inflammatory response leading to genetic and epigenetic alterations. This review will focus on the pro- and anti-oxidant activities of POH, which are greatly dependent on the respective ROS levels within the tumor microenvironment and involve the ER stress response system. As well, some critical aspects of tumor-associated metabolic changes and the consequences of endogenous ROS production for tumor progression will be discussed.


Identification of a novel HLA-DRB1 allele, DRB1*09:20, by sequence-based typing in an unrelated bone marrow donor.
The novel allele HLA-DRB1*09:20 differs from HLA-DRB1*09:01:02 by one nucleotide substitution at codon 9 (AAG->CAG) and differs from HLA-DRB1*09:07 by one nucleotide substitution at codon 13 (TAT->TTT).


Primary health care nurses implement and evaluate a community outreach approach to health care in the South African agricultural sector.
Early detection and effective case management of tuberculosis (TB) among a high-risk group of materially poor farm workers in an area of the Cape Winelands, South Africa, presents special challenges to the health community, where resource constraints lead to service reduction. In order to address this problem, local nurses established a collaborative partnership between permanent farm workers and their families, their employers, selected non-governmental organizations and the public health sector. In consultation with stakeholders, they developed an intervention primarily focusing on having peer selected trained lay health workers (LHWs) on farms, mentored and managed by nurses. To describe the complex process of implementation and evaluation of the LHW project, and provide a summary of a number of discrete studies evaluating the effectiveness, cost implications, and the perceptions and experiences of key stakeholders of the intervention. Quantitative and qualitative research methods conducted within the context of a pragmatic unblinded community cluster randomized control trial were used. Emphasis was placed on an iterative participatory interaction between the researchers and key stakeholders. The intervention contributed to significantly better successful treatment completion rates among adult new smear-positive TB cases. The process implemented proved cost-effective and was pivotal in initiating a community-based social development programme. The use of peer-selected LHWs within a wider programme of integrated care designed to merge technical biomedical approaches to disease management with more holistic social development activities, appears essential to meet the complex health needs in conjunction with public health of the rural poor.


Delirium in the first days of acute stroke.
Delirium is an acute, transient disorder of cognition and consciousness with fluctuating intensity. The aim of this study was to investigate the presence and the risk factors for delirium in the first days after stroke onset. We assessed delirium prospectively in a sample of 218 consecutive patients (mean age 57 years) with an acute (</= 4 days) stroke (28 subarachnoid haemorrhages, 48 intracerebral haemorrhages, 142 cerebral infarcts) and in a control group of 50 patients with acute coronary syndromes with the Delirium Rating Scale (DRS) (cut-off score >/= 10). 29 (13%) acute stroke patients (mean DRS score = 13.2, SD = 2.3) and only one (2 %) acute coronary patient had delirium (chi(2) = 5.2, p = 0.02). In nine patients delirium was secondary to stroke without any additional cause, in 10 patients there were also medical complications and in the remaining 10 there were multiple potential causes for delirium. Delirium was more frequent after hemispherical than after brainstem/cerebellum strokes (p = 0.02). No other statistically significant associations with stroke locations were found. Medical complications (OR = 4.3; 95% CI = 1.8 to 10.2), neglect (OR = 3.5; 95% CI = 1.3 to 9.2), intracerebral haemorrhage (OR = 3.1; 95% CI = 1.3 to 7.5) and age >/= 65 (OR = 2.4; 95% CI = 1.0 to 5.8) were independent factors to the development of delirium in stroke patients. Delirium was more frequent in stroke than in coronary acute patients. Among stroke patients, delirium was most frequent in older patients, in those with neglect, with medical complications and with intracerebral haemorrhages. These findings indicated that delirium in acute stroke patients 1) is not a non-specific consequence of acute disease and hospitalisation and 2) is secondary to hemisphere brain damage and to metabolic disturbances due to medical complications.


Protective effect of Polygonatum sibiricum against cadmium-induced testicular injury in mice through inhibiting oxidative stress and mitochondria-mediated apoptosis.
Polygonatum sibiricum (PS), the dried rhizome of the liliaceous plant including P. sibiricum Red., P. cyrtonema Hua. and P. kingianum Coll. et Hemsl., is a widely used Chinese herbal medicines. It was first published in "Special Records of Famous Doctors", in which is described to replenished Qi and nourish Yin, strengthening the spleen and nourishing the lungs and kidney. Based on the principle of kidney controlling the reproduction, kidney-tonifying therapy has traditionally been seen as most applicable to the treatment of infertility. The current investigation has focused on the protective effect of PS against cadmium-induced testicular injury in mice. To investigate the protective effect of PS against cadmium-induced testicular injury in mice via the TXNIP-NLRP3-Caspase-1 and CytC-Caspase-9-Caspase-3 pathways. PS was processed into Polygonatum sibiricum aqueous extract (PSAE). A mouse testicular injury model was established by a single intraperitoneal (i.p.) injection of cadmium chloride (CdCl2) (2.5 mg/kg b.w.), and the mice were treated intragastrically with PSAE (10 g/kg b.w.) once daily for 35 consecutive days. At the end of the experiment blood and testicular tissue samples were collected to analyze sperm survival rate and sperm deformity rate, serum testosterone T content, testicular oxidation related indicators levels (SOD, MDA, GSH, CAT) in testicular tissue, and histopathological changes of testicular tissues. The testicular cell cycle and reactive oxygen species (ROS) levels were measured by flow cytometry, the expression levels of thioredoxin-interacting protein (TXNIP), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, interleukin (IL)-1β, Cyctochrome C (CytC), Caspase-3, and Caspase-9 mRNA in testicular tissue were detected by qRT-PCR and the protein expression levels of TXNIP, NLRP3, Caspase-1, CytC, Caspase-3, and Caspase-9 were detected by Western blot and immunohistochemical method. The results indicated that compared with the model group, PSAE brought testicular weight to a near-normal range, improved sperm survival rate and reduced sperm abnormality rate, elevated the level of testosterone, made the damaged testis tissue recover to near normal, reduced the level of ROS, and inhibited testicular cell apoptosis. Further study showed that PSAE significantly decreased the levels of relative genes and proteins in testicular cells, such as TXNIP, NLRP3, Caspase-1, IL-1β, CytC, Caspase-3, and Caspase-9, which suggested that PSAE could regulate oxidative stress through the TXNIP-NLRP3-Caspase-1 signaling pathway, and inhibit apoptosis in the mitochondrial pathway via CytC-Caspase-9-Caspase-3 pathway. In summary, we have confirmed that PSAE exerted a powerful protective effect on CdCl2-induced testicular injury in mice through inhibiting oxidative stress and mitochondria-mediated apoptosis.


Fermi surface reconstruction in electron-doped cuprates without antiferromagnetic long-range order.
Fermi surface (FS) topology is a fundamental property of metals and superconductors. In electron-doped cuprate Nd2-x Ce x CuO4 (NCCO), an unexpected FS reconstruction has been observed in optimal- and overdoped regime (x = 0.15-0.17) by quantum oscillation measurements (QOM). This is all the more puzzling because neutron scattering suggests that the antiferromagnetic (AFM) long-range order, which is believed to reconstruct the FS, vanishes before x = 0.14. To reconcile the conflict, a widely discussed external magnetic-field-induced AFM long-range order in QOM explains the FS reconstruction as an extrinsic property. Here, we report angle-resolved photoemission (ARPES) evidence of FS reconstruction in optimal- and overdoped NCCO. The observed FSs are in quantitative agreement with QOM, suggesting an intrinsic FS reconstruction without field. This reconstructed FS, despite its importance as a basis to understand electron-doped cuprates, cannot be explained under the traditional scheme. Furthermore, the energy gap of the reconstruction decreases rapidly near x = 0.17 like an order parameter, echoing the quantum critical doping in transport. The totality of the data points to a mysterious order between x = 0.14 and 0.17, whose appearance favors the FS reconstruction and disappearance defines the quantum critical doping. A recent topological proposal provides an ansatz for its origin.


[Radiological diagnostics of malignant tumors of the musculoskeletal system in childhood and adolescence].
Rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma are the most common malignant tumors of the musculoskeletal system in childhood and adolescence representing about 10% of newly diagnosed cancers in children and adolescents.In the last two decades the prognosis of patients with such malignancies improved significantly. On the one hand because of the advances in chemotherapy and orthopedic surgery, on the other hand also because of the innovations in radiological diagnostics. The precise pre-therapeutical staging of tumors of the musculoskeletal system provides important prognostic information and has impact on the entire therapy management. During respectively after therapy, imaging is extremely important in the follow-up and in diagnosing a possible recurrent disease.Modern imaging diagnostics of musculoskeletal tumors basically consist of conventional X-ray, of computed tomography (CT) and magnetic resonance imaging (MRI), and of modalities of nuclear medicine such as szintigraphy, positron emission tomography (PET) and PET CT.


Performance and ethanol oxidation kinetics of a sulfate-reducing fluidized-bed reactor treating acidic metal-containing wastewater.
The treatment of simulated acidic wastewater (pH 2.5-5) containing sulfate (1.0-2.2 g l(-1)), zinc (15-340 mg l(-1)) and iron (57 mg l(-1)) was studied in a sulfate-reducing fluidized-bed reactor (FBR) at 35 degrees C. The original lactate feed for enrichment and maintenance of the FBR culture was replaced stepwise with ethanol over 50 days. The robustness of the process was studied by increasing stepwise the Zn, sulfate and ethanol feed concentrations and decreasing the feed pH. The following precipitation rates were obtained: 360 mg l(-1) d(-1) for Zn and 86 mg l(-1) d(-1) for Fe, with over 99.8% Zn and Fe removal, with a hydraulic retention time of 16 h. Under these conditions, 77-95% of the electrons were accepted by sulfate reduction. The alkalinity produced from ethanol oxidation increased the wastewater pH from 2.5 to 7.5-8.5. Michaelis-Menten constants (Km) determined in batch FBR experiments, were 4.3-7.1 mg l(-1) and 2.7-3.5 mg l(-1) for ethanol and acetate oxidation, respectively. The maximum oxidation velocities (Vmax) were 0.19-0.22 mg gVS(-1) min(-1) and 0.033-0.035 mg gVS(-1) min(-1), for ethanol and acetate, respectively. In summary, the FBR process produced a good quality effluent as indicated by its low organic content and Zn and Fe concentrations below 0.1 mg l(-1).


Quantifying Changes in Chromosome Position to Assess Chromokinesin Activity.
The chromokinesin KIF22 (Kid, kinesin-10 family) is the primary generator of polar ejection forces, which contribute to chromosome positioning and alignment in mitotic cells. Assessment of KIF22 function requires quantitative comparison of relative polar ejection forces between experimental conditions. This is facilitated by the generation of monopolar spindles to reduce the impact of bioriented microtubule attachment at kinetochores on chromosome positions and increase the dependence of chromosome positions on chromokinesin activity. Radial profile plots measure the intensity of chromatin signal in concentric circles around the poles of monopolar cells and represent an expedient quantitative measure of relative polar ejection forces. As such, this assay can be used to measure changes in polar ejection forces resulting from chromokinesin depletion or perturbation.


Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances.
Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.


Demographic shift in COVID-19 patients in Singapore from an aged, at-risk population to young migrant workers with reduced risk of severe disease.
The vast majority of COVID-19 cases in Singapore have occurred amongst migrant workers. This paper examined trends in the hospitalised cases and tested the assumption that the low severity of disease was related to the relatively young affected population. All patients with PCR-positive SARS-CoV-2 admitted from February to April 2020 were divided into: (i) imported cases, (ii) locally-transmitted cases outside migrant worker dormitories and (iii) migrant worker dormitory cases. They were examined for underlying comorbidities, clinical progress and outcomes. Imported cases (n = 29) peaked in mid-March 2020, followed by local cases (n = 100) in mid-April 2020; migrant worker cases (n = 425) continued to increase in late April 2020. Migrant worker cases were younger, had few medical comorbidities and less severe disease. As the migrant worker cases increased, the proportion of patients with pneumonia decreased, whilst patients presenting earlier in their illness and asymptomatic disease became more common. Singapore experienced a substantial shift in the population at risk of severe COVID-19. Successful control in the community protected an aging population. Large migrant worker dormitory outbreaks occurred, but the disease incurred was less severe, resulting in Singapore having one of the lowest case fatality rates in the world.


CO2 transport in agnathan blood: evidence of erythrocyte Cl-/HCO3- exchange limitations.
CO2 transport properties of blood were examined in the lamprey Petromyzon marinus and the hagfish Myxine glutinosa. In order to evaluate possible chloride/bicarbonate exchange limitations, experiments were conducted under control conditions and in the presence of an ionophore to permit equilibrium distribution of chloride, bicarbonate, and protons across the erythrocyte membrane. The ionophore, tri-n-propyl tin chloride, markedly altered the CO2 transport properties and apparent nonbicarbonate buffering characteristics of the blood of Petromyzon marinus. In addition, the distributions of protons, bicarbonate and chloride ions across the erythrocyte membrane were very different from each other under control conditions, but became very similar in the presence of the anionic ionophore. The CO2 transport properties of the blood of Myxine glutinosa were not significantly different in the presence of the ionophore. Small but significant changes were observed, however, in erythrocyte pH, chloride concentration and water content in the presence of tri-n-propyl tin chloride. These results demonstrate that chloride/bicarbonate exchange limitations and possibly active transport of protons contribute to the unique CO2 transport properties in the blood of the lamprey, Petromyzon marinus. In the hagfish, Myxine glutinosa, the importance of anion exchange limitations or active proton transport with regard to the CO2 carrying properties of the blood are clearly much less than in the lamprey under the in vitro conditions of this study.


Blended pulp mill, forest humus and mine residual material Technosols for mine reclamation: A growth-chamber study to explore the role of physiochemical properties of substrates and microbial inoculation on plant growth.
A growth chamber trial was conducted to investigate the effects of blends of pulp and paper mill residuals and forest humus on soil properties, microbial communities and germination rate and biomass production of annual ryegrass (Lolium multiflorum) in both acid-producing and neutral to mildly alkaline mine tailings in a mine reclamation context. The organic residual amendments improved the nutritional status of the tailings substrates, and increased pH in acid-generating tailings, leading to higher germination rates and improved plant growth. A trace addition (<0.02% of sludge by dry weight) of natural forest floor material as a microbial inoculum to the sludge could increase plant biomass up to four-fold. The effects of sludge application on bioavailability of metals were variable, with the concentration of soluble copper (Cu) and nickel (Ni) increasing in some of the substrates following organic amendments. Addition of paper mill residuals to mine tailings modified the microbial communities observed in the oligotrophic tailings with the majority of DNA sequences in the sludge amended substrates being found to be closely related to heterotrophic bacterial species rather than the chemolithotrophic communities that dominate tailings environments.


[Evaluation of molecular biology reagents used in plcR-tergeted RSI-PCR assay for B. anthracis identification and their influence on time necessary for obtaining results].
Fast and reliable identification of B. anthracis is crucial for a successful therapy of persons exposed to anthrax spores. Use of molecular biology techniques significantly reduces time necessary for obtaining results. However, the molecular identification is hampered by the high genetic similarity of the B. cereus group bacteria. A lot of published B. antharcis identification approaches turned out to be non-specific. Nevertheless, theplcR-targeted RSI-PCR assay described in 2007 is still regarded as highly specific for anthrax identification. In this paper possibility of significant reduction of time necessary for obtaining results by the use of modern, "fast" polymerases and restriction enzymes will be presented. The use of a such reagents enable to reduce time of the plcR-targeted RSI-PCR assay to about two hours.


Comparison of pro B-natriuretic peptide in hypertensive patients with and without diastolic dysfunction.
to evaluate whether pro BNP can be used for detection of diastolic dysfunction. thirty nine hypertensive patients with normal systolic function, consecutively referred for echocardiography examination between October and December 2004 were recruited in the study. Diastolic dysfunction was diagnosed when echocardiographic mitral flow pattern demonstrated impaired relaxation, pseudonormalization or restrictive like patterns. NT-pro BNP levels were assessed using electro chemiluminescence Immunoassay (ECLIA) method. Unpaired t test was used to analyze the results. twelve out of thirty nine subjects had normal diastolic function. All base line characteristics, except for uric acid, were equally distributed between normal and abnormal diastolic function group. NT-pro BNP levels were nearly significantly higher in the diastolic dysfunction group (P=0.053). NT-pro BNP levels trends to be higher in hypertensive subjects with diastolic dysfunction.


Apoptosis, angiogenesis, inflammation, and oxidative stress: basic interactions in patients with early and metastatic breast cancer.
Breast cancer (BC) is a complex, multi-stage disease involving deregulation of different signaling cascades. The present study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with different stages of BC as an approach to disease biological behavior. Therefore, plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; interleukin (IL)-8, tumor necrosis factor (TNF)-α as apoptotic, inflammatory, angiogenic indices; lipid peroxides (LPO), nitric oxide (NO) as oxidative stress and angiogenic indices were measured in patients with BC. Thirty-seven newly diagnosed patients with BC, 30 patients with benign breast masses, and 30 healthy controls were recruited. Plasma levels of sFas, bcl-2, IL-8, and TNF-α were measured by immunosorbent assay kits and LPO and NO by chemical methods. Plasma sFas and LPO were significantly higher in BC patients versus benign breast masses and healthy controls (P < 0.0001). Bcl-2, IL-8, TNF-α, and NO were significantly higher in benign breast masses (P < 0.0001, P < 0.037, P < 0.0001, P < 0.001) and BC (P < 0.0001) versus controls and in BC versus benign breast masses (P < 0.0001). sFas, bcl-2, IL-8, TNF-α, LPO, and NO were increased with advanced tumor stages. There were positive correlations between sFas, bcl-2, IL-8 TNF-α, LPO, and NO. BC tumor cells overexpress bcl-2 and sFas to secure their outgrowth and survival. However, this coincides with activation of physiologic regulatory mechanisms, as increased IL-8, TNF-α, LPO, and NO, which try to stop tumor cells by inducing apoptosis. Outcompeting of these mechanisms result in tumor progression as IL-8, TNF-α, and NO are also angiogenic stimulators.


Surgical treatment of invasive renal aspergillosis after chemotherapy.
The treatment of hematological malignancies with intensive chemotherapy results in prolonged periods of immunosuppression. This is associated with an increased incidence of Aspergillus infections of the upper respiratory tract with high mortality. We present a case of a 4-year-old girl with acute lymphoblastic leukemia who developed disseminated pulmonary and renal aspergillosis. To our knowledge, this is the first reported case of aspergillosis affecting a kidney after chemotherapy.


Expression of RANTES and MCP-1 in epithelial cells is regulated via LMP1 and CD40.
Epstein-Barr virus (EBV)-associated undifferentiated nasopharyngeal carcinoma (NPC) is characterized by a prominent nonneoplastic lymphoid stroma. The functional role of these inflammatory cells and the mechanism of their recruitment are not fully understood. In B-cells, the EBV-encoded latent membrane protein 1 (LMP1) can induce the expression of chemokines in an NF-kappaB dependent manner. We now show that LMP1 can induce the expression of RANTES and MCP-1 in an epithelial cell line, and that this effect is partially reversible by an inhibitor of NF-kappaB. Since tumor cells of virtually all NPCs show CD40 expression while many cases are LMP1-negative at the protein level, we also investigated the effect of CD40 signaling and demonstrate that CD40 stimulation can transiently induce RANTES and MCP-1 expression in LMP1-negative epithelial cells. In in situ hybridization only rare tumor cells showed expression of these chemokines unrelated to LMP1 expression, a pattern consistent with transient induction through CD40 signaling. Since RANTES and MCP-1 were also detected in the neoplastic cells of oral squamous cell carcinomas lacking a lymphoid stroma it remains uncertain to what extent these CC chemokines contribute to the attraction of inflammatory cells into the NPC microenvironment.


Catastrophic progression of the disassembly of a modular acetabular component.
Disassembly of a metal-backed modular acetabular component used for total hip arthroplasty is becoming more common. If the acetabular disassembly is detected early, the revision procedures are relatively simple. In the case of long-term sustained disassembly, however, there are more complicated problems, and more difficult revision procedures are needed. We report a case of long-term sustained disassembly of a modular acetabular component in order to alert orthopaedic surgeons of the catastrophic progression to more severe complications, such as the loosening of the metal-acetabular component and severe acetabular osteolysis.


Chromomycin staining of vertebrate chromosomes: enhancement of banding patterns by NaOH.
A simple technique is described for staining vertebrate chromosomes with the GC-base pair specific DNA fluorochrome, chromomycin A3. Addition of NaOH crystals to a glycerol mounting medium resulted in good differentiation of chromosome bands and eliminated the need for counterstaining.


[Biological characteristics of culture 6734-21 and the conditions for isolating the antiviral antibiotic it produces].
An actinomyceteous strain No. 6734-21 was isolated from a soil sample of Central Asia and classified as Actinomyces bottropensis. It inhibited the development of the phage of the lysogenic culture of Micrococcus lysodeicticus 53-40 (No. 5) and the variolovaccine DNA-containing virus. Actinomyces bottropensis, strain No. 6734-21 produced an antiviral antibiotic classified as one belonging to the actinorodine group.


Experimental Study on Bead on Plate (BOP) Welding of 6 mm Thick 9% Nickel Steel by Fiber Laser Welding.
Nine percent nickel steel has excellent properties in a cryogenic environment, so it has recently been used as a tank material for most LNG fuel-powered ships. However, 9% nickel steel causes arc deflection due to its tendency of magnetization during manual FCAW welding and the currently used filler metal is 10-25 times more expensive as a base metal compared to other materials, depending on manufacturers. Furthermore, the properties of its filler metal cause limitation in the welding position. To overcome these disadvantages, in this study, the tendency of penetration shape was analyzed through a fiber laser Bead on Plate (BOP) welding for 9% nickel steel with a thickness of 6 mm and a range of welding conditions for 1-pass laser butt welding of 6 mm thick 9% nickel steel with I-Groove were derived. Through this study, basic data capable of deriving optimal conditions for laser butt welding of 9% nickel steel with a thickness of 6 mm were obtained.


Fiber-aligned polymer scaffolds for rotator cuff repair in a rat model.
Repair techniques of rotator cuff tendon tears have improved in recent years; nonetheless, the failure rate remains high. Despite the availability of various graft materials for repair augmentation, there has yet to be a biomechanical study using fiber-aligned scaffolds in vivo. The objective of this study was to evaluate the efficacy of fiber-aligned nanofibrous polymer scaffolds as a potential treatment-delivery vehicle in a rat rotator cuff injury model. Scaffolds with and without sacrificial fibers were fabricated via electrospinning and implanted to augment supraspinatus repair in rats. Repairs without scaffold augmentation were also performed to serve as controls. Rats were sacrificed at 4 and 8 weeks postoperatively, and repairs were evaluated histologically and biomechanically. Both scaffold formulations remained in place, with more noticeable cellular infiltration and colonization at 4 and 8 weeks after injury and repair for scaffolds lacking sacrificial fibers. Specimens with scaffolds were larger in cross-sectional area compared with controls. Biomechanical testing revealed no significant differences in structural properties between the groups. Some apparent material properties were significantly reduced in the scaffold groups. These reductions were due to increases in cross-sectional area, most likely caused by the extra thickness of the implanted scaffold material. No differences were observed between the 2 scaffold groups. No adverse effect of surgical implantation of overlaid fiber-aligned scaffolds on structural properties of supraspinatus tendons in rat rotator cuff repair was demonstrated, validating this model as a platform for targeted delivery.


Treatment of the Lennox syndrome with ACTH: a clinical and electroencephalographic study.
In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became "seizure free" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.


Chediak-Higashi syndrome in a Chinese infant.
Chediak-Higashi syndrome in Chinese has not been previously reported in the English literature. A 14-month Chinese girl who presented with partial oculocutaneous albinism and Pseudomonas infection was found to have the classical intracytoplasmic inclusion bodies in the leucocytes by light and electron microscopy. Other characteristic features typical of this syndrome included hepatosplenomegaly, defective chemotaxis, and coarse but sparse melanin granules in hair shaft. She was also found to have hypertriglyceridaemia, a rare lipid abnormality occasionally reported in children suffering from this syndrome. Despite vigorous therapy with high dose ascorbate, corticosteroid and intravenous antibiotics, she died in the accelerated phase of Pseudomonas septicaemia.


Pertussis toxin induces parallel loss of neuropeptide Y Y1 receptor dimers and Gi alpha subunit function in CHO cells.
Treatment with pertussis toxin in addition to a stable inhibition of G(i)alpha subunits of G-proteins also strongly reduced human neuropeptide Y Y(1) receptors expressed in Chinese hamster ovary (CHO) cells. This was reflected in abolition of the inhibition by Y(1) agonists of forskolin-stimulated adenylyl cyclase in intact cells, and of Y(1) agonist stimulation of GTPgammaS binding to particulates from disrupted cells. The loss of both receptor and G(i)alpha subunit function was attenuated by ammonium chloride, an inhibitor of acid proteinases, pointing to a chaperoning co-protection of active pertussis toxin-sensitive Galpha subunits and Y(1) receptors. The surface complement of the Y(1) receptor was changed a little in conditions of approximately 85% decrease of the Y(1) population, but the rate of the Y(1) receptor-linked internalization of agonist peptides was reduced about 70%. The preserved receptor fraction consisted of monomers significantly coupled to G(q)alpha subunits. The persistent pertussis toxin-insensitive internalization of agonists with the Y(1) receptor may reflect a rescue or alternative switching that could be important for cell functioning in neuropeptide Y-rich environments. The results are compatible with a loss, due to G(i)alpha subunit inactivation by the toxin, of a large Y(1) receptor reserve constituted of oligomers associating with heterotrimeric G-proteins.


Effect of conjugated linoleic acid on bovine mammary cell growth, apoptosis and stearoyl Co-A desaturase gene expression.
The effects of the primary biologically active conjugated linoleic acid (CLA) isomers (cis-9, trans-11 and trans-10, cis-12; 15-150microM) on growth and survival of the bovine mammary cell-line, Mac-T, were evaluated using cell enumeration and TUNEL assay. Previous studies have shown that high concentrations of CLA induced severe milk fat depression and have had negative effects on milk yield and composition whereas the impact of lower doses has been a modest depression in milk fat percent. In this study, we show that increasing concentrations of both CLA isomers had negative impacts on cell growth, including reduced cell number at concentrations of 35microM and above (P<0.05) and a two-fold increase in induction of apoptosis in the mammary cells. Changes in cell morphology occurred with large vacuole-like structures in the cytoplasm, nuclear shrinkage and changes of nuclear shape to kidney shape. Insulin did not significantly affect apoptosis in CLA-treated cells. In addition, the effect of increased doses of CLA and the interaction of CLA and insulin on the bovine stearoyl Co-A desaturase (Scd) gene promoter was also analyzed. While a significant difference in the Scd promoter transcriptional activity was not observed in cells treated with different concentrations of CLA, insulin significantly enhanced Scd promoter activity in CLA-treated cells. Our in vitro data support the hypothesis that high levels of CLA may induce in vivo apoptosis in the mammary gland.


Mechanisms of contextual control when contexts are informative to solve the task.
An experiment was conducted using a human instrumental learning task with the goal of evaluating the mechanisms underlying the deleterious effect of context-switching on responding to an unambiguous stimulus when contexts are informative to solve the task. Participants were trained in a context-based reversal discrimination in which two discriminative stimuli (X and Y) interchange their meaning across contexts A and B. In context A, discriminative stimulus Z consistently announced that the relationship between a specific instrumental response (RI) and a specific outcome (O1) was in effect. Performance in the presence of stimulus Z was equally deteriorated when the test was conducted outside the training context, regardless of whether the test context was familiar (context B) or new (context C). This result is consistent with the idea that participants code all the information presented in an informative context as context-specific with the context playing a role akin to an occasion setter.


Genomic loci with pleiotropic effects on coronary artery calcification.
We measured 381 genomewide markers and performed genetic linkage analyses in search of loci influencing coronary artery calcification (CAC), a measure of atherosclerosis determined by electron beam computed tomography, in 948 non-Hispanic white siblings (mean age [+/-standard deviation] = 59.6 +/- 9.9 years; 73.7% hypertensive). Measured risk factors for atherosclerosis included body mass index, pulse pressure, and high-density lipoprotein (HDL)-cholesterol. After adjustment for sex and age, the logarithm transformed measure of CAC was heritable (0.40 +/- 0.08, P < 0.0001) and genetically correlated with body mass index (0.28, P < 0.001), pulse pressure (0.36, P < 0.001), and HDL-cholesterol (-0.19, P < 0.001). Univariate linkage analysis demonstrated evidence of linkage for CAC, defined by maximum LOD scores (MLS) >or= 1.30, on chromosomes 1p, 4p, 5q, 7p, 13q, and 14q. Bivariate linkage analyses of CAC with each risk factor provided evidence of two regions with pleiotropic effects on CAC and HDL-cholesterol on chromosomes 4p16 (MLS=3.03, P = 0.00084) and 9q12 (MLS = 3.21, P = 0.00056), and of a region with pleiotropic effects on CAC and body mass index on chromosome 17p11 (MLS = 3.04, P = 0.00082). Inasmuch as the chromosome 9 and 17 regions were not detected in the univariate linkage analysis for CAC, multivariate linkage analyses of CAC and genetically correlated risk factors may help localize genes for coronary atherosclerosis.


Trichostrongylus colubriformis larvae induce necrosis and release of IL33 from intestinal epithelial cells in vitro: implications for gastrointestinal nematode vaccine design.
Gastrointestinal nematodes represent a major production problem for ruminant livestock. Enhancing immunity to gastrointestinal nematodes through vaccination is desirable but mechanistic understanding of initial host responses that facilitate gastrointestinal nematode protective immunity is limited. We hypothesise that gastrointestinal nematode invasion induces mucosal epithelium damage and alarmin (e.g. IL33) release, thereby contributing to initiation of protective gastrointestinal nematode immunity. To test this, an in vitro air-liquid interface human HT-29 epithelial cell-Trichostrongylus colubriformis co-culture system was developed. Exsheathed L3 T. colubriformis exhibited both sinusoidal and burrowing motions in the co-culture system. Burrowing parasites, but not ivermectin-paralysed larvae, induced necrotic death of epithelial cells (annexin V(+)/propidium iodide(+)/caspase 3/7(-)). Microscopy confirmed that larvae consumed labelled necrotic epithelial cell contents. Trichostrongylus colubriformis larvae and their post-exsheathment antigens (excretory/secretory products) significantly induced IL33 mRNA expression in the epithelial cells. Immunoblot confirmed that IL33 was released from epithelial cells due to the damage caused by motile larvae. Exposure of HT-29 cells to alum or Sigma proprietary adjuvants induced significant epithelial cell IL33 mRNA expression without inducing cellular necrosis. Hence, the intracellular contents were not released externally where they might exert alarmin activity and this may limit their ability to trigger a protective anti-gastrointestinal nematode response. We conclude that T. colubriformis motion at the infection site induces intestinal epithelial cell necrosis which facilitates the release of intracellular contents, including IL33, and may be fundamental to the initiation of an appropriate host response to gastrointestinal nematodes. Our co-culture model is useful for studying initial epithelial cell-parasite interactions without conducting expensive animal trials.


Historical trends of neuroendoscopic surgical techniques in the treatment of hydrocephalus.
The treatment of hydrocephalus nowadays is still a challenge for neurosurgery. Neuroendoscopy is a valuable alternative of the CSF shunts in hydrocephalus management. Because of the complicated and always changeable pathophysiology of hydrocephalus, the history of the endoscopic treatment of hydrocephalus is also a history of severe frustrations, great expectations, and significant achievements. The historical milestones and state of the art of neuroendoscopic treatment of hydrocephalus are reviewed for each of its surgical techniques: choroid plexus coagulation, third ventriculostomy, aqueductoplasty, septostomy, foraminal plasty of the foramen of Monro, and foraminal plasty of the foramen of Magendie. The future trends of neuroendoscopic treatment of hydrocephalus such as robotics, image-guided neuroendoscopic surgical techniques, treatment "in utero", application of stem cell therapy, implementation of new technological solutions, and so on are discussed in the light of the approaching end of the century of neuroendoscopy.


Effect of opposition quality and match location on the positional demands of the 4-2-3-1 formation in elite soccer.
The present study examined the influence of match location, quality of opposition team, and playing position on physical performance indicators of the 4-2-3-1 formation. Twenty-six (n = 26) games (with 184 player-observations; n = 17 players, played full 90 min games) were recorded with a video system and the physical demands of the players were analyzed according to their specific playing position (classified into central and wide defenders, central and wide midfielders and forwards). Match performance variables analyzed included total distance (TD), high-intensity running (HIR), very-high-intensity running (VHIR) and sprinting (SPR). There was a main effect of position for TD (F = 37.84, p < 0.001), HIR (F = 41.19, p < 0.001), VHIR (F = 27.89, p < 0.001) and SPR (F = 22.25, p < 0.001). Wide defenders covered the most SPR and -along with the central midfielders-the most VHIR. Central midfielders covered the most TD and HIR. Match location and opposition quality had interactive effects on TD (F = 12.96, p < 0.001), HIR (F = 8.33 p = 0.004) and VHIR (F = 8.17 p = 0.005). Competing against "weak" opponents, more TD, HIR and VHIR covered during home games compared to away games (p < 0.05). However, more TD was covered during away games against "strong" opponents compared to away games against "weak" opponents (p < 0.05). The current study supports more intense-based drills (i.e. repeated sprint training) for wide defenders and more volume-based drills (i.e. long interval training) for central midfielders, whilst total weekly training load can be adjusted based on match location and quality of oppositions on the anticipated game-load.


A randomised controlled trial of a nutrition and a decision support intervention to enable partnerships with families of critically ill patients.
The aim of the study was to investigate the effect of supporting family members to partner with health professionals on nutrition intakes and decision-making and to evaluate intervention and study feasibility. Family partnerships can improve outcomes for critically ill patients and family members. Interventions that support families to engage with health professionals require evaluation. A multi-centre, randomised, parallel group superiority Phase II randomised controlled trial. In nine intensive care units (ICUs) across three countries, critically ill patients ≥60 years, or those 55-59 years with advanced chronic diseases and expected ICU length of stay >72 h and their family member were enrolled between 9 May 2017 and 31 March 2020. Participants were randomised (1:1:1) to either a decision support or nutrition optimisation family-centred intervention, or usual care. Primary outcomes included protein and energy intake during ICU and hospital stay (nutrition intervention) and family satisfaction (decision support). Study feasibility was assessed as a composite of consent rate, intervention adherence, contamination and physician awareness of intervention assignment. We randomised 135 patients/family members (consent rate 51.7%). The average rate of randomisation was 0.5 (0.13-1.53) per month. Unavailability (staff/family) was the major contributor to families not being approached for consent. Declined consent was attributed to families feeling overwhelmed (58/126, 46%). Pandemic visitor restrictions contributed to early study cessation. Intervention adherence for the decision support intervention was 76.9%-100.0% and for the nutrition intervention was 44.8%-100.0%. Nutritional adequacy, decisional conflict, satisfaction with decision-making and overall family satisfaction with ICU were similar for all groups. Active partnerships between family members and health professionals are important but can be challenging to achieve in critical care contexts. We were unable to demonstrate the efficacy of either intervention. Feasibility outcomes suggest further refinement of interventions and study protocol may be warranted. Interventions to promote family partnerships in critical illness are needed but require a greater understanding of the extent to which families want and are able to engage and the activities in which they have most impact. This study has been reported following the Consolidated Standards of Reporting Trials (CONSORT) and the Template for Intervention Description and Replication (TIDieR) guidelines. Patients and caregivers were engaged in and contributed to the development and subsequent iterations of the two family-centred interventions use in this study. Trial registration. gov, ID: NCT02920086. Registered on 30 September 2016. First patient enrolled on 9 May 2017 https://clinicaltrials.gov/ct2/results?cond=&term=NCT02920086&cntry=&state=&city=&dist=.


On-line measurement of muscle fibre conduction velocity: analysis and optimization of performance.
Measurement of the average muscle fibre conduction velocity from surface electromyographic signals has important applications in the study of muscle fatigue and in ergonomics. In this paper, a two-channel hardware polarity correlator (which estimates 256 correlation coefficients per channel at a sampling rate of 18.58 kHz) and a specially designed surface electrode unit, are used to investigate various factors affecting the measurement reliability: electrode dimensions; EMG preprocessing to make the estimated correlation function more suitable for time delay measurement; and the manner in which velocity estimates, measured simultaneously from two different sections of the same muscle, are related. All the tests were performed on the biceps brachii when under medium tension; some tests involved tensions which led to muscle fatigue. Results showed that smaller electrode dimensions (i.e. smaller electrode units) and EMG preprocessing to increase its effective bandwidth, give more reliable measurements. Further, it was found that the estimated mean velocity is dependent on the location of the electrode unit on the muscle, and that at certain locations no reliable estimates can be obtained. The preliminary results obtained with muscle fatigue indicate that the estimated conduction velocity decreases, but not uniformly, across the muscle.


Benzodiazepines and their antagonists interfere with opioid-dependent stress-induced analgesia.
Timing or intensity of shocks significantly modify the characteristics of the analgesia induced by footshock, and conditioning to footshock induces analgesia, independently from the time and shock parameters used for conditioning. However, whatever the parameters of shock, and the presence of conditioning or not, the stress has to be inescapable in order to produce an increase in pain thresholds. This observation suggests that anxiety plays a major role in the development of stress-induced analgesia. In order to test this hypothesis we investigated the effects of the benzodiazepine agonists diazepam and clonazepam, the antagonists RO 15-1788, CGS 8216, CGS 9896, and the inverse agonists FG 7142 and FG 7041 on the development and maintenance of stress-induced analgesia. Benzodiazepine receptor agonists decreased the analgesic effect of inescapable footshock, benzodiazepine receptor antagonists increased the footshock induced analgesia, whereas inverse agonists did not modify the analgesia induced by the shock. All the benzodiazepine receptor ligands blocked the antagonism of the footshock analgesia induced by naloxone.


Pharmacological options for Candida albicans Endocarditis at the roadblock with irrecoverable prosthetics and drug interactions: a case report and review of literature.
Candidemia is the fourth most common nosocomial bloodstream infection. Endocarditis from candidemia is a rare but possibly fatal complication. The efficacy of amphotericin and echinocandins for induction and azoles for suppression has been well studied. Source control of infection, including removal of foreign bodies, remains the cornerstone for the success of any antifungal therapy. We are describing a case of a 63-years old patient with multiple comorbidities who developed candidemia secondary to Candida albicans. The prospect of curing the fungemia was made difficult by prosthetic devices, including prosthetic heart valves, intracardiac defibrillator, and inferior vena filter, which could not be extracted due to poor cardiovascular status and higher postoperative mortality risk. Combination therapy with amphotericin and 5-Flucytosine (5FC) was used with the first recurrence. Suppression with fluconazole was contraindicated due to prolonged corrected QT (QTc) interval. Isavuconazole was employed for chronic lifelong suppression. Retaining prosthetics in higher surgical risk patients presents us with unique clinical and pharmacological challenges regarding breakthrough infections, drug interaction, and side effects from prolonged suppressive therapies.


Ethical soundness of health technology assessment reports in Islamic Republic of Iran.
Health technology assessment (HTA) is a conventional method for evaluating reasonable use of health technologies in many countries. To investigate the ethical soundness of HTA studies in Islamic Republic of Iran. All HTA reports published by the HTA office until 2020 were reviewed using the HTA Core Model and the Q-SEA questionnaires. We evaluated 91 reports for ethical soundness. The research question, literature search and inclusion/exclusion criteria were included in 91.2%, 83.5% and 82.4% of the HTA reports, respectively. Only 13.2% of the reports explicitly stated the objective of the analysis and 6.6% stated the ethics framework. Only 2.2%, 4.4%, 9.9%, 9.9%, 14.3%, and 2.2%, respectively, of the reports, complied with the completeness, bias, policy implications, other implications, conceptual clarification, and conflicting values. HTA reports in the Islamic Republic of Iran require coordinated and integrated framework acceptable to all stakeholders to ensure their compliance with sound ethical requirements.


Assessment of a customised immobilisation system for head and neck IMRT using electronic portal imaging.
To evaluate set-up reproducibility of a cabulite shell and determine CTV-PTV margins for head and neck intensity-modulated-radiotherapy. Twenty patients were entered into the study. A total of 354 anterior and lateral isocentric electronic portal images (EPIs) were compared to simulator reference images. About 94% of all translational displacements were < or =3 mm, and 99% < or =5 mm. The overall systematic error was 0.9 mm (+/-1.0SD) in the Right-Left, 0.7 mm (+/-0.9SD) in the Superior-Inferior and -0.02 mm (+/-1.1SD) in the Anterior-Posterior directions. The corresponding SDs of the random errors were +/-0.4, +/-0.6 and +/-0.7 mm. The estimated margins required from CTV-PTV were calculated according to the Van Herk formula was 2.9, 2.6 and 3.3 mm, respectively. This head and neck immobilisation system is of sufficient accuracy for its use with IMRT treatments and a 3 mm CTV-PTV margin has been adopted.


Neutralization of excessive levels of active TGF-β1 reduces MSC recruitment and differentiation to mitigate peritendinous adhesion.
Peritendinous adhesion formation (PAF) can substantially limit the range of motion of digits. However, the origin of myofibroblasts in PAF tissues is still unclear. In this study, we found that the concentration of active TGF-β1 and the numbers of macrophages, mesenchymal stromal cells (MSCs), and myofibroblasts in human and mouse adhesion tissues were increased. Furthermore, knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagen I and III deposition, respectively. Moreover, we found that MSCs differentiated into myofibroblasts to form adhesion tissues. Systemic injection of the TGF-β-neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and, subsequently, PAF. These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions. An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.


Poly(N,N-dimethylacrylamide)-coated upconverting NaYF4:Yb,Er@NaYF4:Nd core-shell nanoparticles for fluorescent labeling of carcinoma cells.
Upconverting luminescent lanthanide-doped nanoparticles (UCNP) belong to promising new materials that absorb infrared light able to penetrate in the deep tissue level, while emitting photons in the visible or ultraviolet region, which makes them favorable for bioimaging and cell labeling. Here, we have prepared upconverting NaYF4:Yb,Er@NaYF4:Nd core-shell nanoparticles, which were coated with copolymers of N,N-dimethylacrylamide (DMA) and 2-(acryloylamino)-2-methylpropane-1-sulfonic acid (AMPS) or tert-butyl [2-(acryloylamino)ethyl]carbamate (AEC-Boc) with negative or positive charges, respectively. The copolymers were synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization, reaching Mn ~ 11 kDa and containing ~ 5 mol% of reactive groups. All copolymers contained bisphosphonate end-groups to be firmly anchored on the surface of NaYF4:Yb,Er@NaYF4:Nd core-shell nanoparticles. To compare properties of polymer coatings, poly(ethylene glycol)-coated and neat UCNP were used as a control. UCNP with various charges were then studied as labels of carcinoma cells, including human hepatocellular carcinoma HepG2, human cervical cancer HeLa, and rat insulinoma INS-1E cells. All the particles proved to be biocompatible (nontoxic); depending on their ξ-potential, the ability to penetrate the cells differed. This ability together with the upconversion luminescence are basic prerequisites for application of particles in photodynamic therapy (PDT) of various tumors, where emission of nanoparticles in visible light range at ~ 650 nm excites photosensitizer.


Effect of 2-ethylhexyl salicylate incorporation on the color stability of different maxillofacial silicone elastomers after outdoor weathering.
Silicone elastomers are considered the most favorable materials for the prosthetic rehabilitation of facial defects. However, color change, because of the ultraviolet (UV) light, limits the life of facial prostheses. The addition of 2-ethylhexyl salicylate as a UV-protective may improve the color stability of different maxillofacial silicone elastomers. The purpose of this in vitro study was to evaluate the effect of 2-ethylhexyl salicylate on the color stability of 3 different maxillofacial silicone elastomers after outdoor weathering. Three different ratios of UV-protective 2-ethylhexyl salicylate (UV-ES) were incorporated into 3 different types of maxillofacial silicones (M511, TechSil S25, and A-2000) in 1%, 2%, and 5% ratios, and a control group for each silicone was generated. A total of 120 Ø15×2-mm disk-shaped specimens were prepared from 3 different silicone elastomers according to the 4 different UV-ES ratio groups (n=10). The specimens were subjected to outdoor weathering in Ankara, Türkiye, from June 2021 to June 2022. Color differences in the specimens were measured at 3 months and 1 year of weathering. The color change values (ΔE) were statistically analyzed by using repeated measures of 3-way ANOVA. The differences were compared by using the Tukey honest significant difference test (α=.05). No interaction was found among the factors (silicone type, UV-ES ratio, and aging) (P=.29). The highest ΔE values were found in TechSil S-25 (P<.001), while the results were not significantly different between the M511 and A2000 groups (P=.324) The higher ΔE values were found in the control group when compared with those of the UV-ES added group of each material, while the results were not significantly different among the 1%, 2%, and 5% groups (P>.05). Incorporating 2-ethylhexyl salicylate into the tested maxillofacial silicones reduced color change.


The role of parent-offspring interactions during and after fledging in the Black-legged Kittiwake.
Most bird species endure a high mortality at fledging, and selection should favour parental behaviour diminishing these costs. Post-fledging parental care varies greatly among species and is often linked to parent-offspring recognition. In the Black-legged Kittiwake (Rissa tridactyla), fledglings need to return to the natal nest to be fed by their parents until independence. Rejections of fledglings by non-parent adults may be fairly violent, and parents are expected to recognize and help their chicks at the time of first return. However, previous cross-fostering experiments pointed out that parents are not able to recognize their chicks up to 15 days before fledging. In this paper, we study the behaviour of both parents and juveniles at fledging. We found that parents answered significantly more to their fledgling's calls than to those of others. Compared to silent juveniles, juveniles that called before landing were more likely to be accepted by their parents. No such pattern was observed with foreign juveniles, indicating that fledglings' voice may carry individual identity. Furthermore, fledglings found their way back to the natal nest faster when parents attended the natal nest and reacted to their offspring's calls than when they were absent or inactive. Such interactions may therefore diminish juvenile mortality at fledging.


Monitoring the performance of a dedicated weaning unit using risk-adjusted control charts for the weaning rate in prolonged mechanical ventilation.
Weaning rate is an important quality indicator of care for patients with prolonged mechanical ventilation (PMV). However, diverse clinical characteristics often affect the measured rate. A risk-adjusted control chart may be beneficial for assessing the quality of care. We analyzed patients with PMV who were discharged between 2018 and 2020 from a dedicated weaning unit at a medical center. We generated a formula to estimate monthly weaning rates using multivariate logistic regression for the clinical, laboratory, and physiologic characteristics upon weaning unit admission in the first two years (Phase I). We then applied both multiplicative and additive models for adjusted p-charts, displayed in both non-segmented and segmented formats, to assess whether special cause variation existed. A total of 737 patients were analyzed, including 503 in Phase I and 234 in Phase II, with average weaning rates of 59.4% and 60.3%, respectively. The p-chart of crude weaning rates did not show special cause variation. Ten variables from the regression analysis were selected for the formula to predict individual weaning probability and generate estimated weaning rates in Phases I and II. For risk-adjusted p-charts, both multiplicative and additive models showed similar findings and no special cause variation. Risk-adjusted control charts generated using a combination of multivariate logistic regression and control chart-adjustment models may provide a feasible method to assess the quality of care in the setting of PMV with standard care protocols.


Travel Less. Make It Worthwhile.
Academic travel has a substantial carbon footprint. The ongoing pandemic has propelled the development and adoption of technologies for online delivery of seminars and remote attendance at scientific conferences. This should not lead to the complete elimination of in-person events, but the scientific community must seize the opportunity to permanently change its modus operandi and reduce the impact of its activities on the environment.