A tri-enzyme co-immobilized magnetic complex: Process details, kinetics, thermodynamics and applications.
A tri-enzyme mixture of cellulase, pectinase and xylanase present in fermentation broth of Aspergillus niger culture was directly recovered by solvent precipitation and co-immobilized on magnetic nanoparticles (MNPs) by cross linking with glutaraldehyde. A 2:1 ratio of isopropanol:total protein in the fermentation broth gave a precipitate with maximal activity recovery of the three enzymes. The co-immobilization on MNPs was optimized at 30 mM glutaraldehyde for 3 h incubation, and 3:1 MNPs:enzyme ratio, yielding a maximum activity recovery of cellulase (80.25 ± 1.03%), pectinase (84.76 ± 1.71%) and xylanase (75.62 ± 0.76%), respectively. The tri-enzyme co-immobilized MNPs were characterized by particle size analysis, FTIR, XRD, VSM and SEM studies, and showed enhanced thermal stability as evident from lower kd, higher t1/2 and D-value in the range of 55-75 °C. The tri-enzyme co-immobilized MNPs showed a shift in optimum temperature from 55 to 60 °C with improved pH tolerance along with a slender rise in kinetic constants and enhanced thermodynamic parameters. It was stable for 36 days at 5 °C, and retained >90% activity up to 4 cycles. The tri-enzyme co-immobilized MNPs were successfully utilized for extraction of piperine from black pepper, preparation of sugarcane cell protoplasts, and clarification of papaya juice with prominent yield and reusability vis-à-vis traditional methods.


Impact of minimally invasive/bariatric surgery fellowship on perioperative complications and outcomes in the first year of practice.
Several reports have described worse perioperative outcomes of laparoscopic gastric bypass procedure during learning curve, which improved after completion of one-year fellowship training. The aim of this study was to evaluate the immediate impact of fellowship training on perioperative complications and outcomes of various bariatric procedures. One hundred initial patients who underwent laparoscopic gastric banding, laparoscopic Roux-en-Y gastric bypass, laparoscopic vertical sleeve gastrectomy, and robotically-assisted laparoscopic biliopancreatic diversion with duodenal switch by a single fellowship trained surgeon were analyzed. Overall average Body Mass Index (BMI) of the patients was 45.9 kg/m(2), age was 47.5 years, and the American Society of Anesthesiologist Score was 2.89. There were no intraoperative, major 30-day complications, or open conversions. Average operative time was 62 minutes in gastric banding, 160 minutes in gastric bypass, 119 minutes in vertical sleeve gastrectomy, and 320 minutes in biliopancreatic diversion. Length of stay ranged from 0.5 day after gastric banding to 3.9 days after biliopancreatic diversion. The perioperative complications and outcomes are comparable with those reported by experienced surgeons. No mortality occurred in this series. Bariatric fellowship ensured skills acquisition for new surgeons to safely and effectively perform various types of bariatric operations, with minimal perioperative complications and excellent outcomes.


The vascular disrupting activity of OXi8006 in endothelial cells and its phosphate prodrug OXi8007 in breast tumor xenografts.
This study describes the vascular disrupting ability and the mechanism of action of the indole-based tubulin-binding compound, OXi8006, and its water-soluble phosphate prodrug OXi8007. Treatment of rapidly proliferating human umbilical vein endothelial cells (HUVECs), used as a model for the tumor vasculature, with OXi8006 or OXi8007, caused potent microtubule disruption followed by extensive reorganization of the cytoskeletal network. The mechanism of action involved an increase in focal adhesion formation associated with an increase in phosphorylation of both non-muscle myosin light chain and focal adhesion kinase. These effects were dramatically diminished by an inhibitor of RhoA kinase, a downstream effector of RhoA. Cell cycle blockade at G2/M and cytotoxicity toward rapidly proliferating HUVECs were also observed. Capillary-like networks of HUVECs were disrupted by the action of both OXi8006 and OXi8007. The prodrug OXi8007 exhibited potent and rapid dose-dependent antivascular activity assessed by dynamic bioluminescence imaging (BLI) in an MDA-MB-231-luc breast cancer xenograft mouse model. By 6 hours post treatment, over 93% of the BLI signal was abolished with only a slight recovery at 24 hours. These findings were confirmed by histology. The results from this study demonstrate that OXi8007 is a potent vascular disrupting agent acting through an anti-microtubule mechanism involving RhoA.


MicroRNA 146-5p, miR-let-7c-5p, miR-221 and miR-345-5p are differentially expressed in Respiratory Syncytial Virus (RSV) persistently infected HEp-2 cells.
Many viruses can establish non-cytolytic, chronic infections in host cells. Beyond the intrinsically interesting questions of how this long-term parasitism is achieved, persistently infected cells can be useful to study virus-host interactions. MicroRNAs (miRNAs) are a class of noncoding RNAs transcribed from the genomes of all multicellular organisms and some viruses. Individual miRNAs may regulate several hundred genes. In this research we have studied the expression of a selective group of host-cell encoded miRNAs, as expressed in a Respiratory Syncytial Virus (RSV) persistently infected HEp-2 cell line (HEp-2 + RSV-GFP). The RSV is a virus that does not encode miRNAs in its genome. Our study shows that Dicer is down regulated, miRNA's 146a-5p is strongly up-regulated and miRNAs 345-5p, let-7c-5p and miRNA's-221 are down-regulated in HEp-2 + RSV-GFP cells. Correspondingly, changes in the miRNA 146a-5p and he sequences of the reference genes are miRNA 345-5p respective miRNAs target proteins: HSP-70 and p21, were observed. Thus, RSV persistent viral infection induces unique patterns of miRNA's expression with relevance to how the virus regulates the host cell response to infection.


Development of a highly efficient ion-ozone cavitation technology for accelerated bread production.
The bakery market is one of the most capacious in Kazakhstan. Manufacturers of bread products are in dire need of the introduction of intensive technologies for improving product quality and safety. This article presents the results of research to develop technology for accelerated production of bread with ion-ozone cavitation treatment. The influence of various modes of exposure to ion-ozone cavitation has been investigated. After baking, bread samples were examined for organoleptic, physicochemical, rheological and microbiological indicators. The optimal method is treatment with ion-ozone at a concentration of 0.0025 units/mg, at a pressure of 1.0 atm for 1 min. As a result, it was proved that this mode accelerates the process of obtaining dough and shortens the fermentation time, and baking bread increases the qualitative and quantitative indicators according to the control method. The results showed that the ion-ozone technology reduces the length of the process of making dough and bread by three times compared to traditional technologies. The developed products with existing analogues in the Kazakhstan market will differ due to their high taste and consumer properties, product safety, long shelf life and low cost.


Mechanism of a redox coupling of seleninic acid with thiol.
Equimolar quantities of 2-ethoxyethaneseleninic acid and p-thiocresol react rapidly in dichloromethane solution to give the selenosulfide along with disulfide, diselenide, and two products oxidized at sulfur, the thiosulfonate and the selenosulfonate. The latter two are new for this sort of coupling; their formation may be the result of an early thioseleninate to selenosulfinate isomerization. A radical chain mechanism is proposed to account for all five products, as well as their relative amounts.


Node status algorithm for load balancing in distributed service architectures at paperless medical institutions.
Service architectures are necessary for providing value-added services in telecommunications networks, including those in medical institutions. Separation of service logic and control from the actual call switching is the main idea of these service architectures, examples include Intelligent Network (IN), Telecommunications Information Network Architectures (TINA), and Open Service Access (OSA). In the Distributed Service Architectures (DSA), instances of the same object type can be placed on different physical nodes. Hence, the network performance can be enhanced by introducing load balancing algorithms to efficiently distribute the traffic between object instances, such that the overall throughput and network performance can be optimised. In this paper, we propose a new load balancing algorithm called "Node Status Algorithm" for DSA infrastructure applicable to electronic-based medical institutions. The simulation results illustrate that this proposed algorithm is able to outperform the benchmark load balancing algorithms-Random Algorithm and Shortest Queue Algorithm, especially under medium and heavily loaded network conditions, which are typical of the increasing bandwidth utilization and processing requirements at paperless hospitals and in the telemedicine environment.


Inverse energy cascade in forced two-dimensional quantum turbulence.
We demonstrate an inverse energy cascade in a minimal model of forced 2D quantum vortex turbulence. We simulate the Gross-Pitaevskii equation for a moving superfluid subject to forcing by a stationary grid of obstacle potentials, and damping by a stationary thermal cloud. The forcing injects large amounts of vortex energy into the system at the scale of a few healing lengths. A regime of forcing and damping is identified where vortex energy is efficiently transported to large length scales via an inverse energy cascade associated with the growth of clusters of same-circulation vortices, a Kolmogorov scaling law in the kinetic energy spectrum over a substantial inertial range, and spectral condensation of kinetic energy at the scale of the system size. Our results provide clear evidence that the inverse energy cascade phenomenon, previously observed in a diverse range of classical systems, can also occur in quantum fluids.


Training with a three-dimensional multiple object-tracking (3D-MOT) paradigm improves attention in students with a neurodevelopmental condition: a randomized controlled trial.
The efficacy of attention training paradigms is influenced by many factors, including the specificity of targeted cognitive processes, accuracy of outcome measures, accessibility to specialized populations, and adaptability to user capability. These issues are increasingly significant when working with children diagnosed with neurodevelopmental conditions that are characterized by attentional difficulties. This study investigated the efficacy of training attention in students with neurodevelopmental conditions using a novel three-dimensional Multiple Object-Tracking (3D-MOT) task. All students (ages 6-18 years) performed the Conners Continuous Performance Task (CPT-3) as a baseline measure of attention. They were then equally and randomly assigned to one of three groups: a treatment group, (3D-MOT); an active control group (visual strategy/math-based game, 2048); and a treatment as usual group. Students were trained on their respective tasks for a total of 15 training sessions over a five-week period and then reassessed on the CPT-3. Results showed that post-training CPT-3 performance significantly improved from baseline for participants in the treatment group only. This improvement indicates that training with 3D-MOT increased attentional abilities in students with neurodevelopmental conditions. These results suggest that training attention with a non-verbal, visual-based task is feasible in a school setting and accessible to atypically developing students with attentional difficulties.


Oblique radiographs compared favorably with computed tomography images in assessing cervical foraminal area.
Oblique radiographs are often ordered to evaluate the patency of cervical intervertebral foramina. Previous studies have shown that computed tomography (CT) provides accurate measurements of foraminal dimensions. Up until now, no study has directly compared the diagnostic utility of oblique radiographs and CT. We conducted a study to quantify the correlation between cervical foramina dimensions measured on oblique radiographs and on CT scans. Heights, widths, and cross-sectional areas were evaluated at every level from C2-C3 through C7-T1 using both oblique radiographs and oblique CT reconstructions. Both measurements were performed at a 50% oblique angle. Interreliability and intrareliability statistics for radiographs and CT were 0.91 and 0.99 for height, 0.90 and 0.97 for width, and 0.84 and 0.92 for area. Pearson correlation coefficients for height, width, and area were 0.439, 0.871, and 0.899, respectively. Oblique radiographs of the cervical spine provide accurate estimates of intervertebral foraminal dimensions--estimates similar to those generated from CT reconstructions. Thus, these radiographs may serve as an acceptable first-line imaging study for initial assessment of patients suspected of having nerve root compression that precludes the higher cost and radiation exposure associated with CT scans.


In vivo studies on the function of cardiac beta-adrenoceptors in man.
The original Lands classification considered cardiac beta-adrenoceptors to be predominantly beta 1 in type and to respond to both noradrenaline and adrenaline. Radioligand binding studies subsequently identified substantial numbers of beta 2-adrenoceptors in cardiac tissue. Studies in man employing intensive exercise, isoprenaline testing and a variety of selective and non-selective beta-adrenoceptor antagonists would now suggest that under certain circumstances these receptors may be functionally active. Severe exercise, as a sympathetic stimulus, is associated with high circulating noradrenaline concentrations, and appears to produce tachycardia predominantly by cardiac beta 1-adrenoceptor activity. In contrast, isoprenaline testing increases heart rate by a number of mechanisms: it stimulates beta 1-adrenoceptor activity in the sinoatrial node; it may result in reflex vagal withdrawal; and it appears to stimulate cardiac beta 2-adrenoceptors directly. In addition, isoprenaline also facilitates noradrenaline release by presynaptic beta 2-adrenoceptors. Thus the effects of isoprenaline would appear to mimic stress in man with the subsequent release of adrenaline from the adrenal medulla and its complex interaction directly and indirectly with both cardiac beta 1 and beta 2-adrenoceptors. These differing circumstances may also influence the relative efficacy of beta 1-selective and non-selective beta-adrenoceptor agonists and antagonists.


[Experimental acute pancreatitis induced by L-arginine: a histological and biochemical evaluation].
Excessive doses of basic amino acids such as L-arginine are able to injure the pancreas of rats. To describe and evaluate the biochemical and histological characteristics of acute pancreatitis in rats induced by L-arginine during the installation, development and repair stages of the pancreatic inflammatory process. MATERIAL AND METHODS - The study group consisted of 105 male Wistar rats. The rats in the experimental group (n = 70) received 500 mg/100 g of corporal weight L-arginine injection intraperitoneally. In the control group (n = 35), isotonic saline solution was injected. Ten rats in the experiment group and five in the control group were analyzed after 6, 12, 24, 48, and 72 hours, on the 7th and 14th days. During those times, blood samples were collected for laboratory testing and samples from the pancreas were collected for an optical microscopy analysis. From 12 to 24 hours after the injection of L-arginine, the amylase serum levels raised to their peak values when compared to the rats in the control group, decreasing gradually, reaching an equal level after the 48th hour and being significantly lower after 72 hours and 7 days. The enzymatic activity returned to its basal level after 14 days. The amylase values were normal in all the times evaluated in the control group. In optical microscopy, after the injection of L-arginine, a pancreatic architecture histologically preserved was observed after 6 hours, evidencing an important interstitial edema in 24 hours. After 48 hours, the acinar architecture was partially destroyed with focal cellular necrosis, reaching its maximum severity after 72 hours. On the 7th, the tissue necrosis and the edema had diminished, and the regeneration of the acinar architecture initiated. The pancreatic structural reconstruction could be observed after 14 days. Pancreatic histological changes were not found in the control group. - Experimental acute pancreatitis induced by L-arginine leads to pancreatic necrosis showing self-limited evolution with pancreas regeneration in 2 weeks.


Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures.
There is controversy surrounding the relative effectiveness of local irradiation and oral indomethacin for prophylaxis against heterotopic ossification following surgical treatment of acetabular fractures. The purpose of this study was to compare the efficacy of these two commonly used methods in a prospective, randomized trial. From July 1992 to June 1999, 166 patients in whom a fracture of the acetabulum was treated surgically through a posterior, extensile, or combination approach were randomized to receive either indomethacin or radiation therapy postoperatively. Seventy-eight patients received 800 cGy of local radiation therapy within seventy-two hours after surgery, and seventy-two patients received a six-week course of indomethacin (25 mg three times a day) beginning within twenty-four hours after surgery. Sixteen additional patients were randomized but did not receive treatment with either prophylactic regimen. At an average of fourteen months, the extent of heterotopic ossification was assessed on plain radiographs with use of the classification of Brooker et al. The grade of ossification was correlated with hip motion. There was no significant difference between treatment groups with regard to patient age, gender, Glasgow Coma Scale, operative time, estimated operative blood loss, duration of follow-up, or presence of closed head injury. The Injury Severity Score appeared to be the only covariate that was significantly different between the groups (p = 0.019). Grade-III or IV ossification developed in eight (11%) of the patients in the indomethacin group and three (4%) in the radiation therapy group. The difference was not significant (p = 0.22; 95% confidence interval, -1.1%, +15.7%). No complications related to the prophylaxis were noted in either group. Heterotopic ossification developed in all sixteen patients who did not receive prophylaxis, with six demonstrating grade-III or IV changes. The overall prevalence of grade-III or IV heterotopic ossification was 7% (eleven of 150) in the treated groups and 38% (six of sixteen) in the untreated group. We did not find any association between the prevalence of heterotopic ossification and fracture type (p = 0.296) or posterior hip dislocation (p = 0.306). Grade-I, II, and III heterotopic ossification did not decrease the range of motion of the hip except in flexion. Both local radiation therapy and indomethacin were found to provide effective prophylaxis against heterotopic ossification following surgical treatment of acetabular fractures through a posterior or extensile approach. We detected no significant difference in efficacy between the two prophylactic regimens.


Circulating Tumor Cells: Diagnostic and Therapeutic Applications.
Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.


A computer assisted approach for monitoring and planning biological reconstructions in orthopaedic oncology: preliminary results and future perspectives.
The evaluation of the mechanical strength of a reconstructed bone, and its evolution during the follow-up is, at present, almost impossible. This information, however, may prove extremely useful in clinical practice, both in the surgical planning and in the management of the rehabilitation therapy. In this work, a non-invasive technique, based on the use of finite element modelling, is presented that allows the simulation of the mechanical behaviour of a skeletal reconstructions starting from Computed Tomography data. This method was applied to study the evolution, during the first year of follow-up, of the strength of the reconstructed femur of a ten year-old child if a short, slow, level walk were allowed. The preliminary results indicate that the window sculpted by the surgeon to allow the anastomosis of the vascular pedicle acts as a stress concentrator and that the reduced bone mineral density, induced in the child's bone by the absence of load during the post-operative period, increases the stress level in the proximal femur.


Human antibody responses to the Anopheles salivary gSG6-P1 peptide: a novel tool for evaluating the efficacy of ITNs in malaria vector control.
To optimize malaria control, WHO has prioritised the need for new indicators to evaluate the efficacy of malaria vector control strategies. The gSG6-P1 peptide from gSG6 protein of Anopheles gambiae salivary glands was previously designed as a specific salivary sequence of malaria vector species. It was shown that the quantification of human antibody (Ab) responses to Anopheles salivary proteins in general and especially to the gSG6-P1 peptide was a pertinent biomarker of human exposure to Anopheles. The present objective was to validate this indicator in the evaluation of the efficacy of Insecticide Treated Nets (ITNs). A longitudinal evaluation, including parasitological, entomological and immunological assessments, was conducted on children and adults from a malaria-endemic area before and after the introduction of ITNs. Significant decrease of anti-gSG6-P1 IgG response was observed just after the efficient ITNs use. Interestingly, specific IgG Ab level was especially pertinent to evaluate a short-time period of ITNs efficacy and at individual level. However, specific IgG rose back up within four months as correct ITN use waned. IgG responses to one salivary peptide could constitute a reliable biomarker for the evaluation of ITN efficacy, at short- and long-term use, and provide a valuable tool in malaria vector control based on a real measurement of human-vector contact.


Modeling the expenditure and reconstitution of work capacity above critical power.
The critical power (CP) model includes two constants: the CP and the W' [P = (W' / t) + CP]. The W' is the finite work capacity available above CP. Power output above CP results in depletion of the W' complete depletion of the W' results in exhaustion. Monitoring the W' may be valuable to athletes during training and competition. Our purpose was to develop a function describing the dynamic state of the W' during intermittent exercise. After determination of V˙O(2max), CP, and W', seven subjects completed four separate exercise tests on a cycle ergometer on different days. Each protocol comprised a set of intervals: 60 s at a severe power output, followed by 30-s recovery at a lower prescribed power output. The intervals were repeated until exhaustion. These data were entered into a continuous equation predicting balance of W' remaining, assuming exponential reconstitution of the W'. The time constant was varied by an iterative process until the remaining modeled W' = 0 at the point of exhaustion. The time constants of W' recharge were negatively correlated with the difference between sub-CP recovery power and CP. The relationship was best fit by an exponential (r = 0.77). The model-predicted W' balance correlated with the temporal course of the rise in V˙O(2) (r = 0.82-0.96). The model accurately predicted exhaustion of the W' in a competitive cyclist during a road race. We have developed a function to track the dynamic state of the W' during intermittent exercise. This may have important implications for the planning and real-time monitoring of athletic performance.


Evaluation of left ventricular functional status using thermodynamic indices.
Conventional methods to assess cardiac contractility have been focused on the mechanical properties of the myocardium. Many of these have suffered from theoretical and practical drawbacks. In this study, we have attempted to evaluate the left ventricular contractile status using the thermodynamic principle and compared these indices with the conventional index (dP/dt). A total of 8 mongrel dogs were anesthetized and artificially ventilated. A Millar catheter with high-fidelity multiple sensors was inserted into the aorta to record the simultaneous changes in aortic flow and pressure waves. Cardiac inotropy was increased by graded doses (2-32 micrograms/kg/min) of dobutamine. Angiotensin injection (100-300 micrograms) to achieve a blood pressure elevation of 30 mmHg was employed for afterload augmentation. Preload was increased by rapid infusion of 6% dextran solution (20 ml/kg). Several thermodynamic parameters were calculated at steady state during the control period and after drug interventions. These included power-averaged rate of power density generation (ARPD), peak ejection rate of change of power (PREP), energy-averaged power density (APD) and frequency-normalized ARPD (FARPD). PREP and APD were unchanged by afterload increment while FARPD, ARPD and dP/dt decreased significantly with an increase in afterload, ARPD was highly sensitive to an increased preload (p < 0.001), and PREP was also changed significantly by an increase in preload. dP/dt was boarderlinely affected by Dextran infusion (p = 0.05), and APD was independent of preload (P > 0.05). Inotropic stimulation increased ARPD, PREP, APD, FARPD and dP/dt by 139.0 +/- 48.0%, 98.0 +/- 51.4%, 74.0 +/- 49.7%, 60.0 +/- 30.4% and 44.6 +/- 10.4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of nutritious meals on the nutritional status of the tribal students: A comparison between centralized kitchens (Annapurna) and regular kitchens in government tribal residential schools from two Districts of Maharashtra, India.
Tackling undernutrition is a global priority. It is the single largest risk factor influencing the burden of disease estimates at the global level. The Annapurna Project was undertaken by Government of Maharashtra to provide nutritious meals to Ashram/residential tribal school students through a centralized kitchen for achieving optimal growth and development and to prevent morbidity. The primary objective of our work was to ascertain whether the provision of nutritious meals through centralized kitchens improves the proportion of underweight and stunted children. We used a cluster trial with parallel intervention and control arms. The allocation ratio was 1:1 for participants in the intervention and control areas. The pilot was undertaken between 2015 and 2017. Tribal dominant Nashik and Palghar districts in Maharashtra were selected by the state government to implement the centralized kitchen plan. At the baseline, the percentage of underweight children in the intervention group was 36.9% and 31.9% in the control groups. The percentage of stunting in the intervention group was 30.0% and 38.2% in the control group. At the endline, 21.9% and 26.3% of the children were underweight. Both groups showed an improvement as compared to the baseline. However, the difference in reduction between the intervention and the control group was insignificant. Similarly, stunting also reduced to 12.9% and 14.6% in the intervention and control groups, respectively. The provision of regular nutritious meals, through centralized and local kitchen in government tribal residential schools of Maharashtra is effective and important in tackling undernutrition in Tribal children.


What studies are appropriate and necessary for staging gastric adenocarcinoma? Results of an international RAND/UCLA expert panel.
The approach for staging gastric adenocarcinoma (GC) has not been well defined, with heterogeneity in the application of staging modalities. Utilizing a RAND/UCLA appropriateness methodology (RAM), a multidisciplinary expert panel of 16 physicians scored 84 GC staging scenarios. Appropriateness was scored from 1 to 9. Median appropriateness scores from 1 to 3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 or more of 16 panelists scored the scenario similarly. Appropriate scenarios were subsequently scored for necessity. Pretreatment TNM stage determination is necessary. Necessary staging maneuvers include esophagogastroduodenoscopy (EGD); biopsy of the tumor; documentation of tumor size, description, location, distance from gastroesophageal junction (GEJ), and any GEJ, esophageal, or duodenal involvement; if an EGD report is unclear, surgeons should repeat it to confirm tumor location. Pretreatment radiologic assessment should include computed tomography (CT)-abdomen and CT-pelvis, performed with multidetector CT scanners with 5-mm slices. Laparoscopy should be performed before resection of cT3-cT4 lesions or multivisceral resections. Laparoscopy should include inspection of the stomach, diaphragm, liver, and ovaries. Using a RAM, we describe appropriate and necessary staging tests for the pretreatment staging evaluation of GC, as well as how some of these staging maneuvers should be conducted.


A review of nevus-associated melanoma: What is the evidence?
Cutaneous melanoma may have an adjacent nevus remnant on histological examination in 30% of cases (nevus-associated melanoma, NAM), while it may appear de novo, without a precursor lesion, in the remaining 70% of cases. Nevus-associated melanoma and the concept of acquired melanocytic nevi serving as precursors of melanoma has long been considered as a controversial topic. This controversy is, in part, due to their overall low rate of transformation to melanoma and scarce data on the natural history of progression. Another matter of debate regarded the possibility that the reported differences in NAM vs. de novo melanoma were due to an underestimation of NAM in thicker lesions due to obliteration of the nevus component by the tumour. During the last few years, several evidence has accumulated in order to address these controversies. In this review, we present a comprehensive synthesis of the epidemiological, clinical, dermoscopic and genetic findings in NAM, including thin NAM, compared to de novo melanoma. Answering the questions on nevus-associated melanoma may provide further insight into the classification of these tumours and disentangle their biology and route of development from that of de novo melanoma.


TECRL deficiency results in aberrant mitochondrial function in cardiomyocytes.
Sudden cardiac death (SCD) caused by ventricular arrhythmias is the leading cause of mortality of cardiovascular disease. Mutation in TECRL, an endoplasmic reticulum protein, was first reported in catecholaminergic polymorphic ventricular tachycardia during which a patient succumbed to SCD. Using loss- and gain-of-function approaches, we investigated the role of TECRL in murine and human cardiomyocytes. Tecrl (knockout, KO) mouse shows significantly aggravated cardiac dysfunction, evidenced by the decrease of ejection fraction and fractional shortening. Mechanistically, TECRL deficiency impairs mitochondrial respiration, which is characterized by reduced adenosine triphosphate production, increased fatty acid synthase (FAS) and reactive oxygen species production, along with decreased MFN2, p-AKT (Ser473), and NRF2 expressions. Overexpression of TECRL induces mitochondrial respiration, in PI3K/AKT dependent manner. TECRL regulates mitochondrial function mainly through PI3K/AKT signaling and the mitochondrial fusion protein MFN2. Apoptosis inducing factor (AIF) and cytochrome C (Cyc) is released from the mitochondria into the cytoplasm after siTECRL infection, as demonstrated by immunofluorescent staining and western blotting. Herein, we propose a previously unrecognized TECRL mechanism in regulating CPVT and may provide possible support for therapeutic target in CPVT.


Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis.
Helios, a member of the Ikaros family of DNA-binding proteins, is expressed in multipotential lymphoid progenitors and throughout the T lineage. However, in most B lineage cells, Helios is not expressed, suggesting that its absence may be critical for B cell development and function. To test this possibility, transgenic mice were generated that express Helios under the control of an Ig mu enhancer. Commitment to the B cell lineage was unaltered in Helios transgenic mice, and numbers of surface IgM(+) B cells were normal in the bone marrow and spleen. However, both bone marrow and splenic B cells exhibited prolonged survival and enhanced proliferation. B cells in Helios transgenic mice were also hyperresponsive to Ag stimulation. These alterations were observed even though the concentration of ectopic Helios in B lineage cells, like that of endogenous Helios in thymocytes, was well below the concentration of Ikaros. Further evidence that ectopic Helios expression contributes to B cell abnormalities was provided by the observation that Helios transgenic mice developed metastatic lymphoma as they aged. Taken together, these results demonstrate that silencing of Helios is critical for normal B cell function.


Investigation of the physical-mechanical properties of Eudragit(®) RS PO/RL PO and their mixtures with common pharmaceutical excipients.
Ammonio methacrylate copolymers Eudragit(®) RS PO and Eudragit® RL PO have found widespread use as key components in various types of extended release solid dosage forms. The deformation behavior of neat polymers and binary mixes was evaluated using Heckel Analysis, strain rate sensitivity, work of compaction and elastic recovery index. Additionally, the compact forming ability of neat materials and binary mixes were evaluated by analyzing their tabletability, compressibility and compactibility profiles. The Heckel analysis of both polymers exhibited a speed-sensitive deformation behavior typical to plastic materials. The yield values of the binary mixes of the polymers with microcrystalline cellulose revealed a linear relationship with the weight fractions of individual components. The yield values of binary mixes of both the polymers with dibasic calcium phosphate exhibited slight negative deviations from linearity. Both polymers exhibited axial relaxation after ejection typical of viscoelastic materials, as measured by the elastic recovery index values. The work of compaction and the elastic recovery index values of the binary mixtures were found to be linearly related to the weight fractions of the individual components thus, confirming ideal mixing behavior based on the composition. Addition of microcrystalline cellulose to both polymers significantly improved their tabletability and compactibility. The tensile strengths of the compacts prepared with neat materials and binary mixes with microcrystalline cellulose, dibasic calcium phosphate and lactose were the function of their solid fraction and independent of the tableting speeds tested; thus, validating compactibility as a reliable parameter in predicting acceptable tablet properties.


Comparison of Zidovudine and Tenofovir Based Regimens With Regard to Health-Related Quality of Life and Prevalence of Symptoms in HIV Patients in a Kenyan Referral Hospital.
Aim: Zidovudine and tenofovir form the backbone of antiretroviral therapy in Kenya. However, their side-effects may affect the quality of life (QoL) of patients. The aim was to compare the health-related quality of life (HRQoL) of adult patients on tenofovir versus zidovudine based regimens in a referral hospital in Kenya to provide future guidance. Methods: A comparative cross sectional study among 501 adult out-patients on either tenofovir or zidovudine was undertaken in Kenyatta National Hospital between 2015 and 2016. The Medical Outcome Study HIV Health Survey (MOS-HIV) was administered along with other key aspects of treatment. Linear regression analysis was performed to identify determinants of HRQoL. Results: Patients on zidovudine had a higher Physical Health Summary Score (PHSS) and Mental Health Summary Score (MHSS) compared to those on tenofovir. The presence of any symptom of the disease and a stated inability to cope were negatively associated with PHSS, whilst having a regular source of income improved PHSS. Being on tenofovir, symptom of illness [β = -1.24; 95% CI (-2.253, -0.226)], absence of pain [β=0.413; 95% CI (0.152, 0.674)] and patient stated inability to cope with HIV [β = -1.029; 95% CI (-1.441, -0.617)] affected the MHSS. Patients on tenofovir and second line regimens had more signs and symptoms of illness. Conclusion: Participants on zidovudine based regimens showed a better performance across all aspects of HRQoL. These are considerations for the future.


Noise control for molecular computing.
Synthetic biology is a growing interdisciplinary field, with far-reaching applications, which aims to design biochemical systems that behave in a desired manner. With the advancement in nucleic-acid-based technology in general, and strand-displacement DNA computing in particular, a large class of abstract biochemical networks may be physically realized using nucleic acids. Methods for systematic design of the abstract systems with prescribed behaviours have been predominantly developed at the (less-detailed) deterministic level. However, stochastic effects, neglected at the deterministic level, are increasingly found to play an important role in biochemistry. In such circumstances, methods for controlling the intrinsic noise in the system are necessary for a successful network design at the (more-detailed) stochastic level. To bridge the gap, the noise-control algorithm for designing biochemical networks is developed in this paper. The algorithm structurally modifies any given reaction network under mass-action kinetics, in such a way that (i) controllable state-dependent noise is introduced into the stochastic dynamics, while (ii) the deterministic dynamics are preserved. The capabilities of the algorithm are demonstrated on a production-decay reaction system, and on an exotic system displaying bistability. For the production-decay system, it is shown that the algorithm may be used to redesign the network to achieve noise-induced multistability. For the exotic system, the algorithm is used to redesign the network to control the stochastic switching, and achieve noise-induced oscillations.


Triggers and appropriateness of red blood cell transfusions in the postpartum patient--a retrospective audit.
Despite published guidelines, a proportion of red blood cell (RBC) transfusions seem unnecessary. To evaluate the indications for and the appropriateness of RBC transfusions in the postpartum patient, we performed a retrospective audit over a 1-year period in two Dutch hospitals. Observational study of transfused obstetric patients, admitted in 2006 to the Departments of Obstetrics of a university and a general hospital, was carried out. Relevant clinical and laboratory data were recorded. The appropriateness of RBC transfusions was assessed using the national and age-based transfusion guidelines for the general population; for the studied group the transfusion threshold haemoglobin (Hb) value was 6.4 g/dl for non-massive and 8.1 g/dl for massive blood loss. From these we derived target Hb levels. Ninety patients received one or more RBC units within 48 h of delivery. Mean pretransfusion Hb level was 6.9 [SD 1.2] g/dl. Median number of transfusions was 2. Mean Hb level at discharge was 9.7 [SD 1.1] g/dl. Taking threshold Hb and the derived target Hb level into account, 68% (n = 61) of the patients may have received one or more RBC units inappropriately. Of 311 RBC units transfused, 143 units (46%) were possibly inappropriate, partly due to over-transfusion. A significant proportion of postpartum RBC transfusions are possibly inappropriate, partly due to over-transfusion. If current guidelines would be more specific, in particular, with respect to the target Hb levels, the total amount of RBC transfusions may be considerably decreased.


Geographical disparities in access to cancer management and treatment services in England.
This study seeks to examine the extent to which cancer services are geographically located according to cancer incidence, and assess the association with cancer survival. We identified hospital sites serving English PCTs (Primary Care Trusts) with the management and treatment of breast, lung and colorectal cancer. Geographical access was estimated as travel time in minutes from LSOAs (Lower Super Output Areas) to the nearest hospital site and aggregated to PCT level. Correlations between PCT level mean travel times and cancer cases were estimated using Spearman's rank correlation. Associations between PCT level mean travel times and cancer relative survival rates were estimated using linear regression with adjustment for area deprivation and for a PCT level measure of the reported ease of obtaining a doctor's appointment. We found that cancer services tended to be located farther from areas with more cancer cases, and longer average travel times are associated with worse survival after adjustment for age, sex, year and area deprivation. This suggests that geographical access to cancer services remains a concern in England.


Marking of metabolites in the diagnostics of metabolic diseases and in the investigation of xenobiotics metabolism using NMR spectroscopy.
There are currently no sound estimates of the number of children born with a serious congenital disorder attributable to genetic or environmental causes (World Health Organization) but there is a supposed number of babies born with birth defects per year: in the world approximately 7.9 million children (6% of births). There is conducted population-based screening by the individual countries. The specialised methods are used when it is not possible to diagnose disease in screening. In recent years in the diagnostics of these disorders the methods of Magnetic Resonance Spectroscopy of the brain (in vivo1H-MRS) and high resolution NMR spectroscopy gain in importance. The manuscript focused on developing the method of marking the metabolic diseases markers of various origins using NMR spectroscopy (including synthesis of markers). Considering the disorders occurring among children, according to Hoffman, Zschocke, Nyhan, there are three following groups of inherited metabolic diseases: disorders of intermediary metabolism, disorders of the biosynthesis and breakdown of complex molecules and neurotransmitter defects and related disorders. The presented investigation is focused on: a study of selected compounds that cause disorders of intermediary metabolism, a study of compounds that cause disorders of the biosynthesis and breakdown of complex molecules and a study of compounds that cause neurotransmitter defects and related disorders. In the subsequent chapter of manuscript there are presented the results of investigation concerning the metabolism of xenobiotics that could potentially be used in therapy of inherited metabolic diseases, basing on stilbene derivatives. In the last chapter there are presented the results of experiments with creatinine- the metabolite produced in muscles.


[A technical device for the percutaneous extraction in monobloc of various renal calculi larger than 10 mm].
The authors present a technical device consisting of a modification of the operating channel for stone extraction by percutaneous nephrostomy. For selected stones, widening of the lips of the operating channel allows the stone to be rapidly and entirely removed without the need for ultrasound or hydroelectric fragmentation, which is always associated with a risk of leaving residual fragments. The aim of this technical device is to ensure complete absence of residual fragments with a minimum of risks for the renal parenchyma.


Study on potential role of apolipoprotein E in recurrent pregnancy loss.
The role of apolipoprotein E (Apo E) gene polymorphisms in the etiology of recurrent pregnancy loss (RPL) is not clearly understood. We evaluated this polymorphism in unexplained pregnancy losses in a group of Turkish women. In our prospective case-control study, 45 well-characterized RPL cases were examined for their Apo E genotypes, based on restriction fragment length polymorphism analysis of polymerase chain reaction (PCR)-amplified fragments. The observed genotypes were compared with those obtained from equal number matched controls. We observed similar Apo E genotypes and E2, E3 and E4 allele frequency distribution among RPL patients and controls. The allele frequencies obtained in patients and controls, respectively, were as follows: E2=8 (9%) and 12 (13.4%) (P=0.342), E3=66 (73.3%) and 60 (66.6%) (P=0.328) and E4=16 (17.7%) and 18 (20%) (P=0.703). Our data did not support the association of Apo E gene polymorphisms with RPL as reported by previous studies. We endorse adequate characterization of RPL cases and adequate sample size prior to addressing such studies.


CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway.
Interleukin-17 (IL-17)-producing T cells (Th17 cells) play critical roles in the pathogenesis of immune-related diseases, including systemic lupus erythematosus. However, the fundamental mechanism regulating Th17 cell differentiation is not fully understood. Recently, we demonstrated that plasma levels of CD147/basigin (Bsg) in patients with lupus nephritis (LN) were closely associated with disease activity. but the molecular mechanism involving Bsg has been elusive. Here, we addressed the role of Bsg in the pathogenesis of LN. Injections of pristane (2,6,10,14-tetramethylpentadecane [TMPD]) were administered to Bsg(-/-) or Bsg(+/+) mice to induce LN. The mice were killed 6 months after being injected, for histologic and biochemical analyses of the kidneys and spleens. Pristane induced LN more strikingly in Bsg(-/-) mice than in Bsg(+/+) mice, even though humoral autoimmunity was similarly increased in both genotypes. The increased number of Th17, but not Th1, Treg cells, was augmented in Bsg(-/-) mice. The expression of IL-17 was also increased in the kidneys of Bsg(-/-) mice, in proportion to LN disease activity. Furthermore, treatment with anti-IL-17 antibody reduced LN disease activity in Bsg(-/-) mice. Complementary to these phenotypes of Bsg(-/-) mice, Bsg expression was enhanced in activated CD4+ T cells in vivo and in vitro. Bsg deficiency selectively augmented in vitro differentiation of naive CD4+ T cells to Th17 cells and STAT-3 phosphorylation during this differentiation. Moreover, STAT-3 phosphorylation was suppressed by crosslinking of Bsg with its antibody. Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway.


Simultaneous employment and depressive symptom trajectories around retirement age in Chile.
Objectives: Over the last decade, an increasing number of empirical studies have examined long-term patterns of depression among adults around retirement age and identified employment status as a crucial determinant. However, most research has examined associations between cross-sectional measures of employment and prospective depression patterns, overlooking the changing nature of employment statuses, particularly close to retirement age. Furthermore, most knowledge in this field comes from studies conducted in developed countries in Western Europe and North America. To address these gaps, this study examined simultaneous trajectories in the employment and depressive symptom domains among two age groups of Chileans before and after the standard retirement age. Method: Using population-representative data and longitudinal statistical methods, we identified different trajectory types among two age groups (one aged 56-65 and another aged 66-75, at baseline) and characterized them according to social and health characteristics.Results: We found that trajectories defined by permanent employment were accompanied by lower depressive symptoms than trajectories indicating either retirement or inactivity. However, trajectories combining employment and the absence of depressive symptoms were primarily followed by individuals with advantaged health and social statuses at the baseline. Conclusion: Public policies aimed at promoting the mental health of older adults through their labor market integration risk forcing individuals who have accumulated social and health disadvantages across the life course to work longer.


The influence of cyclosporin on lipid peroxidation and superoxide dismutase in adriamycin nephropathy in rats.
Cyclosporin A (CsA) was shown to reduce proteinuria in nephrotic syndrome, but its potential to increase lipid peroxidation may play a role in cyclosporin nephrotoxicity. The influence of cyclosporin treatment on the lipid peroxidation (assessed as malondialdehyde (MDA) in plasma and kidney homogenates using HPLC and reaction with thiobarbituric acid) and the activity of superoxide dismutase (SOD) in erythrocytes was studied in rats with nephrotic syndrome induced by single intravenous injection of adriamycin. Rats with nephrotic syndrome treated from the beginning with cyclosporin had lower proteinuria than untreated nephrotic rats. Free MDA in blood and kidney homogenates was significantly elevated in untreated nephrotic rats in comparison with controls. Activity of SOD in erythrocytes was significantly elevated in nephrotic rats treated with cyclosporin (113.40 +/- 34.31 mU/10(6) erythrocytes) in comparison with the control group (55.63 +/- 9.90 mU/10(6) erythrocytes, p < 0.001), rats treated with cyclosporin (65.7 +/- 17.49 mU/10(6) erythrocytes, p < 0.01) and untreated nephrotic rats (65.07 +/- 17.49 mU/10(6) erythrocytes, p < 0.001). In conclusion, cyclosporin reduced proteinuria in rats with mild adriamycin nephropathy (similar to human minimal change disease). Cyclosporin also partially counteracted adriamycin-induced lipid peroxidation probably due to the stimulation of antioxidant enzyme SOD. The possible contribution of decreased lipid peroxidation to the antiproteinuric effect of cyclosporin deserves further study.


Ab initio investigation of structure and cohesive energy of crystalline urea.
The structure and cohesive energy of crystalline urea have been investigated at the ab initio level of calculation. The performance of different Hamiltonians in dealing with a hydrogen-bonded molecular crystal as crystalline urea is assessed. Detailed calculations carried out by adopting both HF and some of the most popular DFT methods in solid-state chemistry are reported. Local, gradient-corrected, and hybrid functionals have been adopted: SVWN, PW91, PBE, B3LYP, and PBE0. First, a 6-31G(d,p) basis set has been adopted, and then the basis set dependence of computed results has been investigated at the B3LYP level. All calculations were carried out by using a development version of the periodic ab initio code CRYSTAL06, which allows full optimization of lattice parameters and atomic coordinates. With the 6-31G(d,p) basis set, structural features are well reproduced by hybrid methods and GGA. LDA gives lattice parameters and hydrogen-bond distances that are too small relative to experiment, while at the HF level the opposite trend is observed. Results show that hybrid methods are more accurate than HF and both LDA and GGA functionals, with a trend in the computed properties similar to that of hydrogen-bonded molecular complexes. When BSSE and ZPE are taken into account, all methods, except LDA, give computed cohesive energies that are underestimated with respect to the experimental sublimation enthalpy. Dispersion energy, not properly taken into account by DFT methods, plays a crucial role. Such a deficiency also affects dramatically the computed crystalline structure, especially when large basis sets are adopted. We show that this is an artifact due to the BSSE. Indeed, with small basis sets the BSSE gives an extra-binding that compensates for the missing dispersion forces, thus yielding structures in fortuitous agreement with experiment.


Estimation of Pubertal Growth Spurt Parameters in Children and Adolescents Living at Moderate Altitude in Colombia.
Knowledge of the biological parameters of pubertal growth spurt allows verification of secular changes and exploration of the timing of puberty. The aim of the study was to estimate final height, age at peak height velocity (APHV), and peak height velocity PHV (cm/y) in children and adolescents living at moderate altitude in Colombia. A cross-sectional study was designed in 2.295 schoolchildren from Bogotá (Colombia) with an age range from 5.0 to 18.9 years. Height (cm) was assessed. Preece-Baines model 1 (1PB) was used to make inferences about mathematical and biological parameters. The five mathematical parameters estimated in general have reflected quality in the fit to the model, reflecting a small residual error. Final height was reached in boys at 170.8 ± 0.4 cm and in girls at 157.9 ± 0.2 cm. APHV was estimated at 12.71 ± 0.1 years in boys and 10.4 ± 0.2 years in girls. Girls reached APHV 2.2 years earlier than boys. In relation to PHV (cm/y), boys reached higher growth speed in height (7.4 ± 0.4 cm/y), and in girls it was (7.0 ± 0.2 cm/y). It was determined that final height was reached at 170.8 ± 0.4 cm in boys and 157.9 ± 0.2 cm in girls, and APHV (years) and PHV (cm/ye) were reached relatively early and with average peak velocity similar to Asian and Western populations. A large-scale longitudinal study is needed to confirm these findings.


Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis.
Epigenetic silencing of steroidogenic factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter transcription factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results indicate that SF1 directly contributes to the abnormal uterine gland morphogenesis, an inhibition of steroid hormone signaling and activation of an immune response, in addition to previously postulated estrogen production.


Analysis of Benzalkonium Chloride Resistance and Potential Virulence of Listeria monocytogenes Isolates Obtained from Different Stages of a Poultry Production Chain in Spain.
Listeria monocytogenes can survive in food production facilities and can be transmitted via contamination of food during the various stages of food production. This study was conducted to compile the results of three independent previous studies on the genetic diversity of L. monocytogenes in a poultry production company in Spain and to determine the potential virulence and sanitizer resistance of the strains by using both genotype and phenotype analyses. L. monocytogenes was detected at three production stages: a broiler abattoir, a processing plant, and retail stores marketing fresh poultry products from the same company. These three stages spanned three locations in three provinces of Spain. A set of 347 L. monocytogenes isolates representing 39 subtypes was obtained using pulsed-field gel electrophoresis (PFGE). A total of 28 subtypes (68%) had a full-length internalin A gene, and two subtypes had a phenotype with low potential for virulence because of a mutation in the prfA gene. A total of 32 subtypes (82%) were classified as benzalkonium chloride resistant (BAC-R) and contained the resistance determinant bcrABC (21 subtypes, 54%) or the resistance gene qacH (11 subtypes, 28%). A total of 13 persistent BAC-R subtypes (minimum of 3 months between the first and last sample from with the isolate was recovered) were identified at the abattoir and processing plant. The three production stages shared a unique subtype (PFGE type 1), which had the mutation in the prfA gene and the bcrABC resistance determinant. Whole genome sequencing revealed this subtype to be sequence type 31. Limited genetic diversity was noted in the isolates studied, including some subtypes that were persistent in the environment of the investigated facilities. Given the high prevalence of BAC-R subtypes, these results support the association between resistance to biocides and persistence of L. monocytogenes.


Menstruation, Myopia, and Marginalization: Advancing Menstrual Policies to "Keep Girls in School" at the Risk of Exacerbating Inequalities.
As countries across the world adopt policies addressing menstruation, it is imperative to identify who benefits from such policies and to understand the dynamics of inclusion and exclusion. We examine such policies through the lens of human rights, as a framework that demands addressing marginalization, ensuring substantive equality, and guaranteeing inclusive participation to ensure that the menstrual needs of everyone, everywhere are met. Our review is focused on four countries (India, Kenya, Senegal, and the United States) and is based on data from 34 policy documents and interviews with 85 participants. We show that girls, particularly school-going girls, are the main target group of policies. Due to this myopic view of menstrual needs, policies risk leaving the needs of adult menstruators, including those experiencing (peri)menopause, unaddressed. Moreover, the intersection between menstrual status and markers of identity such as disability and gender identity produces further policy gaps. These gaps can be attributed to the exclusion of marginalized menstruators from decision-making processes by creating barriers and failing to ensure meaningful inclusive participation. To address inequalities, policy makers need to make a concerted effort to understand and accommodate the needs of menstruators in all their diversity.


Comparison of outcomes between endoscopic surgery and conventional nasal packing for epistaxis in the posterior fornix of the inferior nasal meatus.
To investigate the clinical features of epistaxis in the posterior fornix of the inferior nasal meatus and compare the treatment outcomes of endoscopic surgery and conventional nasal packing for this intractable form of epistaxis. Between August 2011 and August 2014, the medical records of 53 adult patients with idiopathic epistaxis in the posterior fornix of the inferior nasal meatus diagnosed by nasal endoscopy were obtained from our department. Of these, 38 patients underwent endoscopic surgery (surgery group) and 15 received a nasal pack (packing group). The patients' background characteristics, incidence of re-bleeding, extent of discomfort after treatment as assessed using a 10-point visual analogue scale (VAS) and incidence of nasal cavity adhesion after treatment were analysed. There were no significant differences in background characteristics between the two groups. The incidence of re-bleeding (0/38 vs. 4/15, surgery vs. control, P = 0.001), VAS score for discomfort (2.4 ± 1.4 vs. 7.6 ± 1.0, surgery vs. control, P = 0.001) and incidence of nasal cavity adhesion after treatment (2/38 vs. 7/15, surgery vs. control, P = 0.007) were significantly lower in the surgery group than in the packing group. Endoscopic surgery is superior to conventional nasal packing for the management of epistaxis in the posterior fornix of the inferior nasal meatus. During surgery, it is crucial to expose the bleeding sites by shifting the inferior turbinate inward by fracture.


Single molecular level analysis and processing in nanochannels.
Recent advances in nanofluidic technologies have enabled devices to be fabricated that integrate nanochannels with at least one dimension smaller than several hundred nanometers. Since this dimension is close to the sizes of biomolecules such as DNA, proteins, and other biomolecules, it opens up new scientific and technological fields based on analysis and manipulation of single molecules. This paper reviews the current state of knowledge regarding single molecular level analysis and processing in nanochannels, particularly experimental findings in this area. While there have been many theoretical and molecular simulation studies, this paper surveys experimental studies. Following a brief survey of techniques for fabricating nanochannels, we review fundamental studies of single molecule behavior and manipulation in nanochannels. We then discuss important transport phenomena of single molecules in nanochannels. Finally, the emerging challenge of electrical single-molecule detection and its possible applications are highlighted.


Eye movements of human albinos.
Albino mammals are known to suffer from misrouted optic projections and there is a growing body of evidence suggesting that human albinos have similar aberrant anatomical pathways. The present study examined the possible consequences of such aberrant pathways on the oculomotor performance of five adult human albinos. Optokinetic nystagmus to drifting grating patterns and pursuit eye movements were measured. The subjects' congenital nystagmus was also measured under different conditions of gaze position and ambient room illumination. Two of the subjects showed clear instances of an inversion in the optokinetic response and there were probable inversions observed for a third subject. The magnitude of the optokinetic nystagmus was appropriate for the rate of pattern drift, but inverted in direction. In all cases smooth pursuit was severely impaired, but reversals of the appropriate direction of pursuit eye movements were not observed. Changes in the congenital nystagmus under conditions of light and darkness were found for four of the five subjects and varied greatly between subjects. The results suggest that human albinos share many of the oculomotor deficits found in other albino species.


Automatic sleep-wake and nap analysis with a new wrist worn online activity monitoring device vivago WristCare.
Vivago WristCare is a new activity monitoring device, which allows long-term online monitoring of the activity of the user. This study evaluates the ability of the device to discriminate sleep/wake patterns during nighttime and during napping. Participants spent one night in the sleep laboratory where signals from polysomnography, actigraphy and WristCare were acquired. In addition, actigraphy and WristCare were used for 3-6 days for nap-analysis. NA. Participants were 32 adults aged 26-89 years. The participants were studied in three study groups: all subjects, senior subjects (age > 65 years) and middle-aged subjects (age < 65 years). NA. Sleep/wake patterns were extracted from polysomnography, actigraphy and WristCare for the night slept in sleep laboratory. The agreement percents between the scorings of polysomnography and actigraphy, and between polysomnography and WristCare were about 80 % for all study groups. As total sleep time was estimated and the algorithm was optimized for this measure, the performance of the WristCare and actigraphy were similar. Both actigraphy and WristCare overestimated appreciably total sleep time (TST). Also in nap-analysis, actigraphy and WristCare performed similarly as the number of naps and the length of the naps were compared. The performance of the WristCare can be assumed to be well comparable to actigraphy in sleep/wake studies. The study suggests that the device may be used in long-term monitoring of sleep/wake patterns with similar performance to actigraphy.


Knowledge gains from a computer-based health risk appraisal.
During 1990, 83 patients seen for a general physical examination at a family practice clinic completed a computer-based health risk appraisal in one of two formats, batch or interactive. They also completed a written questionnaire on their health risks and knowledge before taking the appraisal, and 65 of them completed another health risk appraisal and questionnaire three months later. No difference in user evaluation of the appraisal regarding its helpfulness, their intent to change behavior based on the appraisal, or amount learned from the appraisal was found between batch and interactive formats. About half (48%) of the individuals correctly estimated their overall health risks before taking the health risk appraisal. Among those who initially misjudged their health risks, few women adjusted their health risk rating at followup. Men showed a tendency to adjust their rating to more closely agree with the health risk appraisal estimates although the differences are not statistically significant. Eighty percent of the men and 55% of the women accurately rated their overall risk at followup. Knowledge of specific causes of death did not improve at followup.


Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations.
Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder. In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales. Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p <0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p <0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination. Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.


Modulation of hair cell efferents.
Outer hair cells (OHCs) amplify the sound-evoked motion of the basilar membrane to enhance acoustic sensitivity and frequency selectivity. Medial olivocochlear (MOC) efferents inhibit OHCs to reduce the sound-evoked response of cochlear afferent neurons. OHC inhibition occurs through the activation of postsynaptic α9α10 nicotinic receptors tightly coupled to calcium-dependent SK2 channels that hyperpolarize the hair cell. MOC neurons are cholinergic but a number of other neurotransmitters and neuromodulators have been proposed to participate in efferent transmission, with emerging evidence for both pre- and postsynaptic effects. Cochlear inhibition in vivo is maximized by repetitive activation of the efferents, reflecting facilitation and summation of transmitter release onto outer hair cells. This review summarizes recent studies on cellular and molecular mechanisms of cholinergic inhibition and the regulation of those molecular components, in particular the involvement of intracellular calcium. Facilitation at the efferent synapse is compared in a variety of animals, as well as other possible mechanisms of modulation of ACh release. These results suggest that short-term plasticity contributes to effective cholinergic inhibition of hair cells.


Murine metapodophalangeal sesamoid bones: morphology and potential means of mineralization underlying function.
Normal murine metapodophalangeal sesamoid bones, closely associated with tendons, were examined in terms of their structure and mineralization with reference to their potential function following crystal deposition. This study utilized radiography, whole mount staining, histology, and conventional electron microscopy to establish a maturation timeline of mineral formation in 1- to 6-week-old metapodophalangeal sesamoids from CD-1 mice. An intimate cellular and structural relationship was documented in more detail than previously described between the sesamoid bone, tendon, and fibrocartilage enthesis at the metapodophalangeal joint. Sesamoid calcification began in 1-week lateral sesamoids of the murine metacarpophalangeal joint of the second digit. All sesamoids were completely calcified by 4 weeks. Transmission electron microscopy of 2-week metacarpophalangeal sesamoids revealed extensive Type I collagen in the associated tendon and fibrocartilage insertion sites and Type II collagen and proteoglycan networks in the interior of the sesamoid. No extracellular matrix vesicles were documented. The results demonstrate that murine sesamoid bones consist of cartilage elaborated by chondrocytes that predominantly synthesize and secrete Type II collagen and proteoglycan. Type II collagen and proteoglycans appear responsible for the onset and progression of mineral formation in this tissue. These data contribute to new understanding of the biochemistry, ultrastructure, and mineralization of sesamoids in relation to other bones and calcifying cartilage and tendon of vertebrates. They also reflect on the potentially important but currently uncertain function of sesamoids as serving as a fulcrum point along a tendon, foreshortening its length and altering advantageously its biomechanical properties with respect to tendon-muscle interaction.


[Surgical wound infection--a complication of mastectomy].
The present study contains a retrospective analysis of thirty medical reports of patients that were submitted to mastectomy at a school hospital, and has the objective of knowing the frequency of surgical injury infection, relating it to predisposed factors to infection. The frequency founded was 40%, a percentage above the level pointed in the literature, suggesting that can be included in it cases of seroma, due the indicators utilized to define infection and the absence of laboratory exams registers in the consulted medical reports.


Characterizing long-term contaminant mass discharge and the relationship between reductions in discharge and reductions in mass for DNAPL source areas.
The objective of this study was to characterize the temporal behavior of contaminant mass discharge, and the relationship between reductions in contaminant mass discharge and reductions in contaminant mass, for a very heterogeneous, highly contaminated source-zone field site. Trichloroethene is the primary contaminant of concern, and several lines of evidence indicate the presence of organic liquid in the subsurface. The site is undergoing groundwater extraction for source control, and contaminant mass discharge has been monitored since system startup. The results show a significant reduction in contaminant mass discharge with time, decreasing from approximately 1 to 0.15 kg/d over five years. Two methods were used to estimate the mass of contaminant present in the source area at the initiation of the remediation project. One was based on a comparison of two sets of core data, collected 3.5 years apart, which suggests that a significant (~80%) reduction in aggregate sediment-phase TCE concentrations occurred between sampling events. The second method was based on fitting the temporal contaminant mass discharge data with a simple exponential source-depletion function. Relatively similar estimates, 784 and 993 kg, respectively, were obtained with the two methods. These data were used to characterize the relationship between reductions in contaminant mass discharge (CMDR) and reductions in contaminant mass (MR). The observed curvilinear relationship exhibits a reduction in contaminant mass discharge essentially immediately upon the initiation of mass reduction. This behavior is consistent with a system wherein significant quantities of mass are present in hydraulically poorly accessible domains for which mass removal is influenced by rate-limited mass transfer. The results obtained from the present study are compared to those obtained from other field studies to evaluate the impact of system properties and conditions on mass-discharge and mass-removal behavior. The results indicate that factors such as domain scale, hydraulic-gradient status (induced or natural), and flushing-solution composition had insignificant impact on the CMDR-MR profiles and thus on underlying mass-removal behavior. Conversely, source-zone age, through its impact on contaminant distribution and accessibility, was implicated as a critical factor influencing the nature of the CMDR-MR relationship.


Nociceptive Cortical Activity Is Dissociated from Nociceptive Behavior in Newborn Human Infants under Stress.
Newborn infants display strong nociceptive behavior in response to tissue damaging stimuli, and this is accompanied by nociceptive activity generated in subcortical and cortical areas of the brain [1, 2]. In the absence of verbal report, these nociceptive responses are used as measures of pain sensation in newborn humans, as they are in animals [3, 4]. However, many infants are raised in a physiologically stressful environment, and little is known about the effect of background levels of stress upon their pain responses. In adults, acute physiological stress causes hyperalgesia [5-7], and increased background stress increases pain [8-10], but these data cannot necessarily be extrapolated to infants. Here we have simultaneously measured nociceptive behavior, brain activity, and levels of physiological stress in a sample of 56 newborn human infants aged 36-42 weeks. Salivary cortisol (hypothalamic pituitary axis), heart rate variability (sympathetic adrenal medullary system), EEG event-related potentials (nociceptive cortical activity), and facial expression (behavior) were acquired in individual infants following a clinically required heel lance. We show that infants with higher levels of stress exhibit larger amplitude cortical nociceptive responses, but this is not reflected in their behavior. Furthermore, while nociceptive behavior and cortical activity are normally correlated, this relationship is disrupted in infants with high levels of physiological stress. Brain activity evoked by noxious stimulation is therefore enhanced by stress, but this cannot be deduced from observation of pain behavior. This may be important in the prevention of adverse effects of early repetitive pain on brain development.


Development and in vitro characterization of floating sustained-release drug delivery systems of polyphenols.
The aim of this study was to develop and characterize floating stomach-retentive matrix tablets that will deliver polyphenols in a controlled release manner. The tablets were prepared by direct compression. A number of polymers were examined and egg albumin was chosen in light of a better performance in terms of floating behavior and decomposition time. Dissolution studies for three representative polyphenols loaded into a number of formulations were performed using the "f₂" factor in order to compare release profiles of different polyphenols and formulations. The release data showed a good fit into the power law equation and zero-order kinetics has been determined for some of the systems. Erosion and textural analysis studies revealed that higher concentration of egg albumin results in a higher gel strength that is less susceptible to erosion, potentially leading to a prolonged delivery time of drug. The ability of egg albumin-based tablets to resist high mechanical forces was also determined, while comparison to cellulose-derived polymers revealed that the latter have a much lower ability to resist the same forces. The developed delivery system has the potential to increase the efficacy of the therapy for various pathological stomach conditions and to improve patient compliance.


Borates: A Rich Source for Optical Materials.
The primary goal of this review is to present a clear chemical perspective of borates in order to stimulate and facilitate the discovery of new borate-based optical materials. These materials, which exhibit structures as varied as they are complex, are needed to meet the urgent technological milestones. In the current period of rapid sociotechnological breakthroughs, the need for the rational design and discovery of novel borates with superior performance is greater than ever before. Through the sustained efforts of chemists and material scientists, more than 3900 boron-containing compounds, including borate minerals and synthetic borates, have been documented in the scientific literature. This review provides a survey of all the reported anhydrous borates and an analysis of their complex structural chemistry. State-of-the-art progress related to technological advances in borate-based nonlinear optical, birefringent, and self-frequency-doubling materials is surveyed, with special emphasis on the relationships between structural architectures and optical properties. More importantly, this review serves both as a scientific introduction for graduates and post-doctoral researchers to the chemical richness of solid-state borates and as a comprehensive reference for researchers interested in borate-based optical materials.


Enhanced Fas-associated death domain recruitment by histone deacetylase inhibitors is critical for the sensitization of chronic lymphocytic leukemia cells to TRAIL-induced apoptosis.
Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by failure of mature lymphocytes to undergo apoptosis. CLL cells are inherently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment with histone deacetylase inhibitors (HDACi) sensitizes CLL cells to TRAIL-mediated apoptosis primarily via TRAIL-R1 and offers a novel approach for the therapy of CLL and other malignancies. Depsipeptide (romidepsin), a HDACi, did not enhance TRAIL binding to TRAIL-R1, TRAIL-R1 aggregation, or internalization of TRAIL-R1, but it enhanced Fas-associated death domain protein (FADD) recruitment to TRAIL-R1 in the death-inducing signaling complex. Cotreatment with phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, dramatically inhibited the HDACi-mediated increase in FADD recruitment and sensitization to TRAIL-induced apoptosis and both of these were reversed by PKC inhibitors. Thus, enhanced FADD recruitment is a critical step in HDACi-mediated sensitization of CLL cells to TRAIL-induced apoptosis and this step is differentially affected by HDACi and phorbol 12-myristate 13-acetate. Using biotinylated TRAIL and streptactin-tagged TRAIL, we have identified several novel TRAIL receptor interacting proteins, including PKCbeta, lymphocyte-specific protease-1, Lyn, and Syk. These molecules may play an as yet unappreciated role in TRAIL signaling in CLL cells and inhibition of one or more of these kinases/phosphatases may provide a novel target to overcome TRAIL resistance.


Proposals for funding graduate medical education: the Institute of Medicine report in context.
Federal support of graduate medical education (GME) has been accepted as an intrinsic ingredient of the Medicare program since that program's inception. Streams of clinical income generated by teaching hospitals, medical faculty practice plans, Medicaid, and other state and federal sources have also made important contributions to GME. Although it is difficult to ascribe legislative intent precisely, Medicare funding seems to have been based on a 2-fold assumption: that GME was socially beneficial and that there were legitimate costs to teaching hospitals associated with their educational missions, even though such costs were hard to identify specifically. The benefits and costs include the high quality generally ascribed to a teaching hospital environment; extra services and teaching costs; active, unsponsored research; a higher proportion of complex medical conditions and care; and technology development and introduction. The argument for Medicare support of GME is thus partly based on better service to all Medicare beneficiaries, and partly on a broader social investment in education and teaching hospitals, with benefits accruing to both present and future Medicare participants. Teaching hospitals and their young physicians in training are also important in providing care to underserved poor populations.


Association between nonsteroidal anti-inflammatory drugs and atrial fibrillation among a middle-aged population: a nationwide population-based cohort.
It remains inconclusive whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of atrial fibrillation (AF), especially in middle-aged Asian populations. In this study, we evaluated the association between NSAID use and the risk of AF in a nationwide population-based study of middle-aged individuals in Taiwan. A nested case-control study was conducted using the National Health Insurance Research Database (NHIRD) in Taiwan. We identified the cases with a diagnosis of AF (ICD-9-CM codes: 427.31) and the matched controls from three independent Longitudinal Health Insurance Databases (LHIDs) derived from the NHIRD from data collected from 2001 to 2013. Conditional logistic regression models with covariate adjustment were performed to evaluate the association between NSAID use and the risk of AF. A total of 57 058 participants (28 529 AF cases and 28 529 matched controls) were included. Participants with NSAID use had an elevated risk of AF compared to non-users [adjusted odds ratio (AOR) = 1.18, 95% confidence interval (CI): 1.14-1.23]. When further assessing the effects of different classes of NSAIDs on the risk of AF, the results showed that participants who used non-selective NSAIDs had a significantly elevated risk of AF (AOR = 1.18, 95% CI: 1.13-1.23), as did participants with a combined use of selective and non-selective NSAIDs (AOR = 1.30, 95% CI: 1.21-1.39). NSAID use was associated with an increased risk of AF occurrence among the participants included in our study cohort. Closely monitoring the adverse effects of NSAID treatment on the risk of AF will be important, particularly among individuals at high risk.


Food habits and anthropometric measurements in a group of independent and institutionalized elderly people in Spain.
Because of an increase in the number of elderly and the problems of nutrition associated with them, we considered it of interest to study the eating habits of 352 elderly persons (134 males and 218 females) 65 to 95 years of age in an urban area in the north of Spain (Oviedo). The purpose of this study was specifically to describe the differences in the eating habits of elderly institutionalized persons and those resident at home and to detect the nutritional status of 161 subjects living in institutions and 191 living at home. The weight, height, body mass index (BMI), and triceps skinfold (PTP) of each were recorded. To determine the eating habits, a questionnaire measuring the frequency of food consumption was distributed to the subjects. The mean age of the institutionalized elderly was greater than those living independently. The mean values of BMI indicated overweight in all cases, with values around those of obesity in independent females (BMI = 29.97). The value of PTP was found to be within normal limits, but a greater percentage of institutionalized subjects showed PTP values of less than P10 (males, 10.2%; females, 11%). Food habits showed that the consumption of fish and margarine/oil was greater in institutionalized subjects of both sexes. Independent males consumed more vegetables; females consumed more milk and greens. Milk, vegetables, fruit, and fish were the food groups with consumption frequencies less than those recommended. A greater percentage of noncompliance was seen among the institutionalized elderly.


The clinical course of COVID-19 in pregnant versus non-pregnant women requiring hospitalisation: results from the multicentre UK CA-COVID-19 study.
The impact of COVID-19 infection on pregnant women remains relatively unknown but the physiological changes of pregnancy and hypercoagulability of COVID-19 may further increase thrombotic risk. In this retrospective multicentre observational study, we report clinical characteristics and outcomes in 36 pregnant women requiring hospitalisation for COVID-19 compared to a propensity-matched cohort of non-pregnant women. Pregnant women had a lower haemoglobin and higher lymphocyte counts but no differences in other haematological or biochemical parameters on admission compared to non-pregnant women. There was no significant difference in the duration of hospitalisation; median two days (1-77) for pregnant versus eight days (1-49) for non-pregnant women. A higher proportion of non-pregnant women required mechanical ventilation [11/36 (31%) vs 3/36 (8%), P = 0·03] and received thromboprophylaxis with low-molecular-weight heparin (LMWH) within 24 h of admission [25/36 (69%) vs 15 /36(42%), P = 0·03] compared to pregnant women. One pregnant woman required extracorporeal membrane oxygenation. The rate of thrombosis was similar in both groups (one in each group). No women developed major bleeding or died. Data suggest that although non-pregnant women had a severe clinical course, overall outcomes were not different between women with or without pregnancy. The use of thromboprophylaxis was inconsistent, demonstrating a need for establishing evidence-based guidance for COVID-19 during pregnancy.


Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics.
Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (μ-ILEDs) with wireless control and power delivery strategies offer important functionality in such experiments, by eliminating the external tethers associated with traditional fiber optic approaches. Existing wireless μ-ILED embodiments allow, however, illumination only at a single targeted region of the brain with a single optical wavelength and over spatial ranges of operation that are constrained by the radio frequency power transmission hardware. Here we report stretchable, multiresonance antennas and battery-free schemes for multichannel wireless operation of independently addressable, multicolor μ-ILEDs with fully implantable, miniaturized platforms. This advance, as demonstrated through in vitro and in vivo studies using thin, mechanically soft systems that separately control as many as three different μ-ILEDs, relies on specially designed stretchable antennas in which parallel capacitive coupling circuits yield several independent, well-separated operating frequencies, as verified through experimental and modeling results. When used in combination with active motion-tracking antenna arrays, these devices enable multichannel optogenetic research on complex behavioral responses in groups of animals over large areas at low levels of radio frequency power (<1 W). Studies of the regions of the brain that are involved in sleep arousal (locus coeruleus) and preference/aversion (nucleus accumbens) demonstrate the unique capabilities of these technologies.


The child's active role in mother-child, father-child psychotherapy: a psychodynamic approach to the treatment of relational disturbances.
The short-term mother-child and father-child psychoanalytic psychotherapy assumes that children develop specific types of relationships with each parent, as well as with the parenting couple. The model integrates an intra-psychic, object-relational view with an interpersonal perspective to the treatment of relational disturbances in childhood. The same therapist meets with the mother-child, father-child dyads on a weekly basis, along with regular meetings with the parental dyad. The model focuses on the developmentally prelatency child's need for the active participation of both parents in the here-and-now shared experiences of the therapeutic process. The participants express, in interactions and in enactments, various contents and meanings of their specific patterns of relations. The therapist addresses the behaviours as well as the meanings of relations, thus promoting reflective understanding and experiential changes in self, other, and self-other relations. The child's active and different participation with each parent is the main change-promoting factor. The child uses mainly the medium of play to express his/her needs and to mobilize the therapist's help. The therapist's access to the different dyads is utilized to better understand the explicit and implicit relational themes. The therapist supports the co-construction of new and different behaviour patterns and the co-creation of additional meanings to representations. The setup fosters the child's active participation in each dyad's growth-promoting changes.


The Impact of Wildfires on Mental Health: A Scoping Review.
One of the many consequences of climate change is an increase in the frequency, severity, and, thus, impact of wildfires across the globe. The destruction and loss of one's home, belongings, and surrounding community, and the threat to personal safety and the safety of loved ones can have significant consequences on survivors' mental health, which persist for years after. The objective of this scoping review was to identify primary studies examining the impact of wildfires on mental health and to summarize findings for PTSD, depression, anxiety, and substance use. Literature searches on Pubmed and Embase were conducted in February and April of 2021, respectively, with no date restrictions. A total of 254 studies were found in the two database searches, with 60 studies meeting the inclusion criteria. Three other studies were identified and included based on relevant in-text citations during data abstraction. The results show an increased rate of PTSD, depression, and generalized anxiety at several times of follow-up post-wildfire, from the subacute phase, to years after. An increased rate of mental health disorders post-wildfire has been found in both the adult and pediatric population, with a number of associated risk factors, the most significant being characteristics of the wildfire trauma itself. Several new terms have arisen in the literature secondary to an increased awareness and understanding of the impact of natural disasters on mental health, including ecological grief, solastalgia, and eco-anxiety. There are a number of patient factors and systemic changes that have been identified post-wildfire that can contribute to resilience and recovery.


A review of protocols for the experimental release of kelp (Laminariales) zoospores.
Kelps (order Laminariales) are foundation species in temperate and arctic seas globally, but they are in decline in many places. Laminarian kelp have an alternation of generations and this poses challenges for experimental studies due to the difficulties in achieving zoospore release and gametophyte growth. Here, we review and synthesize the protocols that have been used to induce zoospore release in kelps to identify commonalities and provide guidance on best practices. We found 171 papers, where zoospore release was induced in four kelp families from 35 different ecoregions. The most commonly treated family was Laminariaceae, followed by Lessoniaceae and the most studied ecoregion was Central Chile, followed by the Southern California Bight. Zoospore release generally involved three steps: a pretreatment which included cleaning of the reproductive tissue to eliminate epiphytic organisms, followed by desiccation of the tissue, and finally a postdesiccation immersion of the reproductive material in a seawater medium for zoospore release. Despite these commonalities, there was a high degree of variation in the detail within each of these steps, even among studies within genera and from the same ecoregions. This suggests either that zoospore release may be relatively insensitive across the Laminariales or that little methods optimization has been undertaken. We suggest that greater attention to standardization of protocols and reporting of methodology and optimization would improve comparisons of kelp zoospore release across species and locations and facilitate a broader understanding of this key, but understudied life history stage. This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. The data is available at https://doi.org/10.5061/dryad.0kh1f8j.


The stage of seed development influences iron bioavailability in pea (Pisum sativum L.).
Pea seeds are widely consumed in their immature form, known as garden peas and petit pois, mostly after preservation by freezing or canning. Mature dry peas are rich in iron in the form of ferritin, but little is known about the content, form or bioavailability of iron in immature stages of seed development. Using specific antibodies and in-gel iron staining, we show that ferritin loaded with iron accumulated gradually during seed development. Immunolocalization and high-resolution secondary ion mass spectrometry (NanoSIMS) revealed that iron-loaded ferritin was located at the surface of starch-containing plastids. Standard cooking procedures destabilized monomeric ferritin and the iron-loaded form. Iron uptake studies using Caco-2 cells showed that the iron in microwaved immature peas was more bioavailable than in boiled mature peas, despite similar levels of soluble iron in the digestates. By manipulating the levels of phytic acid in the digestates we demonstrate that phytic acid is the main inhibitor of iron uptake from mature peas in vitro. Taken together, our data show that immature peas and mature dry peas contain similar levels of ferritin-iron, which is destabilized during cooking. However, iron from immature peas is more bioavailable because of lower phytic acid levels compared to mature peas.


Wheat-dependent exercise-induced anaphylaxis: subtypes, diagnosis, and management.
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is an IgE-mediated food allergy with allergic symptoms ranging from intermittent urticaria to severe anaphylaxis that occurs when wheat ingestion is combined with augmenting cofactors such as exercise, non-steroidal anti-inflammatory drugs, or alcohol. In most cases, patients are identified by sensitization to ω5-gliadins in the gluten fraction of wheat. ω5-gliadin-negative subtypes of WDEIA are often difficult to diagnose and may be caused by Tri a 14 (wheat lipid transfer protein), after percutaneous sensitization with hydrolyzed wheat proteins, or, in rare cases, by cross-reactivity to grass pollen. Diagnosis is established based on the patients' history in combination with serum IgE profile, skin testing, basophil activation tests, and challenge tests with cofactors. Individual dietary counselling remains the central pillar in the management of WDEIA patients. A completely wheat-free diet is a possible option. However, this appears to promote tolerance less than continued regular consumption of gluten-containing cereals in the absence of cofactors. All patients should have an emergency set for self-treatment including an adrenaline autoinjector and receive adequate instruction. More data are needed on sublingual immunotherapy for WDEIA, a potentially promising therapeutic prospect. This article provides an overview of current knowledge on the diagnosis and management of WDEIA including an optimized challenge protocol using wheat gluten and cofactors.