Mitochondrial DNA variation within and among populations of the mosquito Aedes albopictus.
A survey of restriction fragment polymorphism in mitochondrial DNA (mtDNA) of 17 populations of the mosquito Aedes albopictus was undertaken. The mtDNA size was estimated to be about 17.5 kbp. The level of polymorphism was low, with over 99% of the fragments being shared in common among the 17 populations. Three populations, Mauritius, Singapore, and Hong Kong, contained individuals with both the ancestral and novel mtDNA haplotypes. We conclude that the low level of mtDNA polymorphism in A. albopictus is a result of recent range expansion and that the mixture of haplotypes is a likely result of human-aided gene flow among populations.


Identification of metabolites from 2D (1)H-(13)C HSQC NMR using peak correlation plots.
Identification of individual components in complex mixtures is an important and sometimes daunting task in several research areas like metabolomics and natural product studies. NMR spectroscopy is an excellent technique for analysis of mixtures of organic compounds and gives a detailed chemical fingerprint of most individual components above the detection limit. For the identification of individual metabolites in metabolomics, correlation or covariance between peaks in (1)H NMR spectra has previously been successfully employed. Similar correlation of 2D (1)H-(13)C Heteronuclear Single Quantum Correlation spectra was recently applied to investigate the structure of heparine. In this paper, we demonstrate how a similar approach can be used to identify metabolites in human biofluids (post-prostatic palpation urine). From 50 (1)H-(13)C Heteronuclear Single Quantum Correlation spectra, 23 correlation plots resembling pure metabolites were constructed. The identities of these metabolites were confirmed by comparing the correlation plots with reported NMR data, mostly from the Human Metabolome Database. Correlation plots prepared by statistically correlating (1)H-(13)C Heteronuclear Single Quantum Correlation spectra from human biofluids provide unambiguous identification of metabolites. The correlation plots highlight cross-peaks belonging to each individual compound, not limited by long-range magnetization transfer as conventional NMR experiments.


THE 2016 ENVIRONMENTAL SCAN.
Every year, the American Hospital Association compiles the Environmental Scan to provide hospital leaders with insight and information about market forces that are likely to affect the health care field. One common theme this year is the pace of change.


Elevated daytime urinary excretion of testosterone glucuronide in men with the type A behavior pattern.
Urinary excretion of testosterone glucuronide was compared in 13 men with typical Type A behavior pattern (as determined by structured interviews) and 10 age-matched men with typical Type B behavior pattern. Twenty-four hour urine collections were divided into three periods: 9AM - 6PM , 6PM to bedtime, and bedtime to 9AM . Type A men showed a significantly higher excretion than Type B men in the daytime ( 9AM - 6PM ); the geometric mean value was 24 micrograms in Type A and 15 micrograms in Type B (P less than 0.05). There were no significant differences between Type A and Type B men for the other two time periods. Indicating an elevated daytime testosterone secretion in Type A men, this finding is consistent with a recent report that exposure to laboratory tests of reaction time causes an increase in plasma testosterone levels in Type A but not Type B men. Since a role for testosterone in the genesis of coronary heart disease (CHD) is suggested by the much higher incidence of CHD in men and the acceleration of murine atherogenesis by testosterone, the findings of this and the previous report may represent a mechanism for the elevated incidence of CHD in Type A men.


[Methodological problems in the determination of biological age].
It is reported on a new method of the establishment of the biological age. The test battery designed comprises 12 parameters, from which a so-called biological index can be calculated which on its part serves as basis for the establishment of biological age. The realisability of the methods is demonstrated by examinations carried out on 340 healthy persons. The method developed for the geriatric practice is regarded as supplementation of the general medical examination and for the clarification of certain, above all gerontologically orientated questions.


Janis Veliks.
"The most exciting thing about my research is turning theoretical ideas into useful synthetic methods and reagents … I am waiting for the day when someone will discover how to regrow a tooth." Find out more about Janis Veliks in his Introducing … Profile.


Bisphosphonate Use and Risk of Implant Revision after Total Hip/Knee Arthroplasty: A Meta-Analysis of Observational Studies.
Several studies investigated the association between bisphosphonate use and the risk of implant revision after total hip or knee arthroplasty (THA or TKA); However, the findings were inconsistent. We performed this meta-analysis to evaluate the overall relative risk of such an event. We searched the PubMed, EMBASE and Cochrane library databases to identify relevant publications on April 22, 2015. To calculate the pooled risk ratios (RRs) with 95% confidential intervals (CIs), a fixed- or random-effects model was applied based on the heterogeneity across studies. Three cohort studies and one case-control study were included in this meta-analysis. Compared with the bisphosphonate nonusers, the patients who used bisphosphonates for a long period of time had a significantly decreased risk of implant revision after THA/TKA (summary adjusted RR = 0.48, 95% CI: 0.38-0.61), and the summary adjusted RRs for the users who underwent THA and those who underwent TKA were 0.47 (95% CI: 0.36-0.61) and 0.45 (95% CI: 0.21-0.95), respectively. Long-term use of bisphosphonates is correlated with a significantly decreased risk of implant revision after THA/TKA. However, due to limited number of the included studies, the findings of the present study should be treated with caution. More well-designed studies are required to further confirm our findings.


Viral gastroenteritis.
As our ability to control many of the common infectious diseases has increased, attention has turned toward the less common or less severe infections. It is clear that worldwide, significant numbers of the cases of gastroenteritis in both adults and children are caused by viruses. Many of these viruses now are quite well understood and their control appears to be on the horizon. Many other etiologic agents are just being identified and will present a challenge to researchers and practitioners alike.


Expression of VEGF and its receptors and angiogenesis in bone and soft tissue tumors.
Tumor angiogenesis and vascularization are essential requirements for the growth and metastasis of tumors. There is evidence that overexpression of the vascular endothelial growth factor (VEGF) is correlated with an adverse prognosis in some tumors. The expression of VEGF, its receptors and microvessel density (MVD) of bone and soft tissue tumors was evaluated. Tissue specimens of 60 patients including 30 malignant and 30 benign tumors confirmed by biopsy were examined. Expression of VEGF and its receptors (flt-1 and KDR/flk-1) was observed by immunohistochemistry. Tumor angiogenesis was assessed morphologically by measuring intratumoral MVD. Semi-quantitative evaluation of immunoreactivity showed that VEGF was significantly higher in malignant tumors than in benign tumors. A correlation was found between the immunoreactivity of VEGF and KDR. Moreover, correlations were found either between MVD and VEGF or between MVD and KDR/flk-1. Signal transduction, in particular by VEGF and KDR, potentially contributes to the angiogenesis of bone and soft tissue tumor.


Comparison of transmission of Papaya leaf curl China virus among four cryptic species of the whitefly Bemisia tabaci complex.
Begomoviruses are transmitted by cryptic species of the whitefly Bemisia tabaci complex, often in a species-specific manner. Papaya leaf curl China virus (PaLCuCNV) has been recorded to infect several crops including papaya, tomato and tobacco in China. To help assess the risks of spread of this virus, we compared the acquisition, retention and transmission of PaLCuCNV among four species of whiteflies, Middle East-Asia Minor 1 (MEAM1), Mediterranean (MED), Asia 1 and Asia II 7. All four species of whiteflies are able to acquire, retain and transmit the virus, but with different levels of efficiency. Transmission tests using tomato as the host plant showed that MEAM1 transmitted PaLCuCNV with substantially higher efficiency than did MED, Asia 1 and Asia II 7. Furthermore, accumulation of PaLCuCNV in the whiteflies was positively associated with its efficiency of transmitting the virus. Altogether, these findings indicate that MEAM1 is the most efficient vector for PaLCuCNV in the four species of whiteflies, and suggest that risks of PaLCuCNV pandemics are high in regions where MEAM1 occurs.


Assessment of Patients Referred to Specialty Dental Hospitals for Dental Implant Procedure: A Retrospective Cohort Analysis.
One of the most common and effective ways of replacing missing teeth is by dental implants. Both quality and quantity of bone along with the area of implant placement govern the prognosis of the implant procedure. Certain risk factors predispose the implant treatment to high failure rate. Hence, we assessed the implant patients who were referred from private practitioners to the specialty hospitals from 2010 to 2014. All the patients being referred from private clinics to the specialty dental hospital for the purpose of prosthetic rehabilitation by dental implants from June 2010 to July 2014 were included in the present study. Skilled oral and maxillofacial surgeons were appointed for performing the implant surgical procedures. Prosthetic rehabilitation was done after 6 to 8 weeks and after 10 to 14 weeks in implant cases without and with bone augmentation procedures respectively. Distribution of dental implants based on the indications, location, dimension of augmentation procedure, and complication of implants was analyzed and assessed for the level of significance. Of the patients, 712 were females, while the remaining were males. Most of the patients were in the age group of 50 to 59 years. As compared with completely edentulous patients, most of the patients required rehabilitation by a single implant. Maximum dental implants were placed in maxillary premolar region and mandibular first molar region. Over 1,000 cases in this study required rehabilitation by augmentation procedure. Partially edentulous patients are most commonly referred to specialized dental hospitals for prosthetic rehabilitation by dental implants, mostly with the purpose of implant placement. Failure rate can be minimized by following strict patient selection protocols along with following a standard surgical criterion. Following standard surgical protocols and strict treatment planning, prognosis of the dental implant procedures can be improved to a greater extent, thereby increasing its clinical success rate.


Cost-effectiveness of population-based, community, workplace and individual policies for diabetes prevention in the UK.
To analyse the cost-effectiveness of different interventions for Type 2 diabetes prevention within a common framework. A micro-simulation model was developed to evaluate the cost-effectiveness of a range of diabetes prevention interventions including: (1) soft drinks taxation; (2) retail policy in socially deprived areas; (3) workplace intervention; (4) community-based intervention; and (5) screening and intensive lifestyle intervention in individuals with high diabetes risk. Within the model, individuals follow metabolic trajectories (for BMI, cholesterol, systolic blood pressure and glycaemia); individuals may develop diabetes, and some may exhibit complications of diabetes and related disorders, including cardiovascular disease, and eventually die. Lifetime healthcare costs, employment costs and quality-adjusted life-years are collected for each person. All interventions generate more life-years and lifetime quality-adjusted life-years and reduce healthcare spending compared with doing nothing. Screening and intensive lifestyle intervention generates greatest lifetime net benefit (£37) but is costly to implement. In comparison, soft drinks taxation or retail policy generate lower net benefit (£11 and £11) but are cost-saving in a shorter time period, preferentially benefit individuals from deprived backgrounds and reduce employer costs. The model enables a wide range of diabetes prevention interventions to be evaluated according to cost-effectiveness, employment and equity impacts over the short and long term, allowing decision-makers to prioritize policies that maximize the expected benefits, as well as fulfilling other policy targets, such as addressing social inequalities.


Increased body iron stores in elite road cyclists.
One third of French elite road cyclists were found to have hyperferritinemia on antidoping control tests performed during the Tour de France in 1998. This study was undertaken to determine whether hyperferritinemia corresponded to elevated body iron stores or not and, affirmatively, what were its mechanism, its clinical consequences, and its spontaneous course. 83 elite road male cyclists presenting with hyperferritinemia, defined as serum ferritin level greater than 300 microg.L-1, were studied with respect to consumption of iron and other drugs, serum iron tests, HFE mutations, and hepatic iron concentration (HIC; N < 35 micromol.g-1 dry weight). All cyclists were asymptomatic and had normal physical and cardiac examination. Their median (range) serum ferritin, serum iron, and transferrin saturation levels were 504 microg.L-1 (306-1671), 20 micromol.L-1 (8.5-36.3), and 39% (20-76), respectively. HIC was increased in 24/27 up to 187 micromol.g-1. Allelic frequency of the H63D mutation was increased in cyclists when compared to controls (P = 0.04). However, iron tests did not differ according to HFE genotypes. Most cyclists (89%) had been supplemented with iron. The median iron supplementation was 25.5 g (range: 1.4-336) and correlated well (P = 0.002) with serum ferritin. Evolution of serum ferritin levels did not differ whether cyclists had been continuing iron supplementation or not. Hyperferritinemia in elite road cyclists accounted for increased body iron stores caused by and persisting after cessation of excessive iron supplementation. Even when mild, iron excess may expose to long-term complications and should be removed, at least at the time when professional cyclists retire. To prevent iatrogenic iron overload, supplementation with iron must be done according to serum ferritin follow-up and not either blindly or on the basis of serum iron determination only.


Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors.
Adoptive T cell transfer (ACT) has achieved clinical success in treating established cancer, particularly in combination with lymphodepleting regimens. Our group previously demonstrated that ACT following whole-body irradiation (WBI) promotes high-level T cell accumulation, regression of established brain tumors, and long-term protection from tumor recurrence in a mouse model of SV40 T antigen-induced choroid plexus tumors. Here we asked whether an approach that can promote strong donor T-cell responses in the absence of WBI might also produce this dramatic and durable tumor elimination following ACT. Agonist anti-CD40 antibody can enhance antigen-specific CD8(+) T-cell responses and has shown clinical efficacy as a monotherapy in the setting of cancer. We show that anti-CD40 conditioning promotes rapid accumulation of tumor-specific donor CD8(+) T cells in the brain and regression of autochthonous T antigen-induced choroid plexus tumors, similar to WBI. Despite a significant increase in the lifespan, tumors eventually recurred in anti-CD40-conditioned mice coincident with loss of T-cell persistence from both the brain and lymphoid organs. Depletion of CD8(+) T cells from the peripheral lymphoid organs of WBI-conditioned recipients failed to promote tumor recurrence, but donor cells persisted in the brains long-term in CD8-depleted mice. These results demonstrate that anti-CD40 conditioning effectively enhances ACT-mediated acute elimination of autochthonous tumors, but suggest that mechanisms associated with WBI conditioning, such as the induction of long-lived T cells, may be critical for protection from tumor recurrence.


Effects of Tourniquet Release on Total Knee Arthroplasty.
This study investigated the clinical outcomes of early and late tourniquet release (tourniquet release after cementing the prosthesis vs tourniquet release after wound closure and pressure dressing) in total knee arthroplasty (TKA). The study was conducted by searching PubMed, Embase, Web of Science, and Cochrane Central databases for articles on randomized controlled trials comparing early and late tourniquet release in primary TKA that were published from 1966 to March 2015. Relevant data were extracted, and the Physiotherapy Evidence Database (PEDro) Scale was used to assess the methodologic quality. Stata software (StatCorp, College Station, Texas) was used to perform a meta-analysis. Sixteen articles were included with a total of 1073 patients and 1097 knees. For blood loss, there were no significant differences between the 2 groups in calculated blood loss, decrease in hemoglobin level, drop in hematocrit level, and measured postoperative blood loss, although total measured blood loss and postoperative blood transfusion rate were significantly higher in the early tourniquet release group than in the late tourniquet release group. No statistical differences were found for operative time and incidence of deep venous thrombosis (DVT) between the 2 groups. Wound complication rate in the early tourniquet release group was significantly lower than in the late tourniquet release group. Primary TKA with early tourniquet release is similar to TKA with late tourniquet release regarding perioperative blood loss, operative time, and incidence of DVT. Early tourniquet release reduced the incidence of wound complications compared with late tourniquet release. [Orthopedics. 2016; 39(4):e642-e650.].


Hypoxia-Responsive Photosensitizer Targeting Dual Organelles for Photodynamic Therapy of Tumors.
Developing safe and precise image-guided photodynamic therapy is a challenge. In this study, the hypoxic properties of solid tumors are exploited to construct a hypoxia-responsive photosensitizer, TPA-Azo. Introducing the azo group into the photosensitizer TPA-BN with aggregation-induced emission quenches its fluorescence. When the nonfluorescent TPA-Azo enters hypoxic tumors, it is reduced by the overexpressed azoreductase to generate a fluorescent photosensitizer TPA-BN with an amino group that exhibits fluorescence-activatable image-guided photodynamic therapy with dual-organelle (lipid droplets and lysosomes) targeting. This design strategy provides a basis for the development of fluorescence-activatable photosensitizers.


Miniaturized laser readout head for application in a double-wedge prism scanner.
Double-wedge prism scanners are typically used for one-dimensional (1D) scanning in imaging systems. This type of scanner operates on the principle of two identical wedge prisms counter-rotating around the optical axis with identical angular velocity in order to move the image formed by the optical system in the plane of detector arrays. However, the relationship between the deviation and rotation angles is not linear. The proposed solution to this problem involves using a metal ring inscribed with line markers. The interval between each of the line markers is unequal, and each line marker corresponds with the unequal angular orientation of the wedge prisms. The line markers are detected by a laser readout head (LRH), which converts the line marker signals to electric clock pulses to correct for the nonlinear distortion of the double-wedge prism scanner. This study presents a miniaturized LRH, electric driver circuit, and photodetector amplifier for this purpose.


A Laparoendoscopic Single-site Surgical Approach to Laparoscopic Salpingectomy.
To demonstrate a laparoendoscopic single-site (LESS) surgical approach to salpingectomy. A technical video showing step-by-step a LESS surgical approach to salpingectomy (Canadian Task Force classification level III). Institutional review board approval was not required for this study. Of all gynecologic cancer types, ovarian cancer has the highest mortality rate and is the fifth leading cause of cancer deaths among women [1,2]. The leading theory of epithelial ovarian carcinogenesis indicates that serous, endometrioid, and clear cell ovarian carcinomas originated from the fallopian tube and endometrium and not directly from the ovary itself [1-10]. This has led to the use of prophylactic salpingectomy as a theoretical form of ovarian cancer risk reduction at the time of hysterectomy or as a means of tubal sterilization. Prophylactic salpingectomy does not appear to increase the risk of complications and appears to be safe [2]. Ovarian function does not seem to be compromised by salpingectomy based on serum markers or response rates with in vitro fertilization [11-16]. A LESS approach may reduce the morbidity associated with the placement of multiple ports and can improve cosmetic outcomes. Prophylactic LESS bilateral salpingo-oohorectomy was shown to be feasible and safe for high-risk patients for ovarian cancer [17]. Laparoscopic salpingectomy at the time of hysterectomy or as a means of tubal sterilization using the LESS technique. This is a simple and reproducible technique for preventing major complications associated with LESS salpingectomy. This approach permits easier specimen retrieval because of the large solitary incision that is made. There is a significant improvement in cosmetic satisfaction when compared with a traditional laparoscopic approach in the setting of prophylactic risk reduction surgery [18].


[Successful lingular segmentectomy using bronchoplasty in a patient with early hilar second primary lung carcinoma].
A 71-year-old man was admitted to our hospital with a small protrusive lesion at the lingular orifice of the left upper bronchus. He had undergone a right lower lobectomy and mediastinal dissection for lung carcinoma (large cell carcinoma, pT1N0M0) 14 months earlier. Early hilar squamous cell carcinoma was diagnosed by chest radiograph, CT and transbronchial biopsy. We performed a lingular segmentectomy with wedge resection of the left upper bronchus and N 1 lymph node dissection. The tumor was histopathologically diagnosed as early hilar second primary lung carcinoma. The patient's postoperative course was uncomplicated. At present, he is alive with good respiratory condition and without any evidence of recurrence. Segmentectomy is appropriate for a patient with contralateral second primary lung carcinoma as well as a patient with early hilar lung carcinoma. Bronchoplasty seems to increase the likelihood that such a patient will be a candidate for segmentectomy.


Role of FBXL5 in redox homeostasis and spindle assembly during oocyte maturation in mice.
As an E3 ubiquitin ligase, F-box and leucine-rich repeat protein 5 (FBXL5) participates in diverse biologic processes. However, the role of Fbxl5 in mouse oocyte meiotic maturation has not yet been fully elucidated. The present study revealed that mouse oocytes depleted of Fbxl5 were unable to complete meiosis, as Fbxl5 silencing led to oocyte meiotic failure with reduced rates of GVBD and polar body extrusion. In addition, Fbxl5 depletion induced aberrant mitochondrial dynamics as we noted the overproduction of reactive oxygen species (ROS) and the accumulation of phosphorylated γH2AX with Fbxl5 knockdown. We also found that Fbxl5-KD led to the abnormal accumulation of CITED2 proteins in mouse oocytes. Our in vitro ubiquitination assay showed that FBXL5 interacted with CITED2 and that it mediated the degradation of CITED2 protein through the ubiquitination-proteasome pathway. Collectively, our data revealed critical functions of FBXL5 in redox hemostasis and spindle assembly during mouse oocyte maturation.


Medication communication during ward rounds on medical wards: Power relations and spatial practices.
Communication plays a crucial role in the management of medications. Ward rounds are sites where health professionals from different disciplines and patients come together to exchange medication information and make treatment decisions. This article examines power relations and spatial practices surrounding medication communication between patients and health professionals including doctors, nurses and pharmacists during ward rounds. Data were collected in two medical wards of a metropolitan teaching hospital in Melbourne, Australia. Data collection methods involved participant observations, field interviews, video-recordings, together with individual and group reflexive interviews. A critical discourse analysis was undertaken to identify the location sites where power relations were reproduced or challenged in ward rounds. Findings demonstrated that traditional medical hierarchies constructed the ways in which doctors communicated about medications during ward rounds. Nurses and pharmacists ventured into the ward round space by using the discourse of preparation and occupying a peripheral physical position. Doctors privileged the discourse of medication rationalization in their ward round discussions, competing with the discourse of inquiry taken up by patients and families. Ward rounds need to be restructured to provide opportunities for nurses and pharmacists to speak at dedicated times and in strategic locations. By critically reflecting upon the complex process of medication communication during ward rounds, greater opportunities exist for enhanced team communication among health professionals.


Construction of All-Solid-State Batteries based on a Sulfur-Graphene Composite and Li9.54 Si1.74 P1.44 S11.7 Cl0.3 Solid Electrolyte.
Herein an effective way for construction of all-solid-state lithium-sulfur batteries (LSBs) with sulfur/reduced graphene oxide (rGO) and Li9.54 Si1.74 P1.44 S11.7 Cl0.3 solid electrolyte is reported. In the composite cathode, the Li9.54 Si1.74 P1.44 S11.7 Cl0.3 powder is homogeneously mixed with the S/rGO composite to enhance the ionic conductivity. Coupled with a metallic Li anode and solid electrolyte, the designed S/rGO-Li9.54 Si1.74 P1.44 S11.7 Cl0.3 composite cathode exhibits a high specific capacity and good cycling stability. A high initial discharge capacity of 969 mAh g-1 is achieved at a current density of 80 mA g-1 at room temperature and the cell retains a reversible capacity of over 827 mAh g-1 after 60 cycles. The enhanced performance is attributed to the intimate contact between the S/rGO and Li9.54 Si1.74 P1.44 S11.7 Cl0.3 electrolyte, and high electrical conductivity of rGO and high ionic conductivity of the solid electrolyte.


Extramedullary Plasmacytoma of the Oral Cavity in a Young Man: a Case Report.
Extramedullary plasmacytomas are rare solitary soft tissue tumors that arise from proliferations of malignant transformed monoclonal plasma cells and can be diagnosed through biopsy and histopathologic examination. These lesions are closely associated with multiple myelomas, which should be ruled out in all these cases by necessary laboratory and radiographic examinations. A 25-year-old man was referred to our clinic with a rapidly-growing painless lesion measuring about 2.5×3×3 cm in the palatal side of the left maxillary second and third molar teeth. A diagnosis of solitary plasmacytoma was made on the basis of clinical, radiographic, and histopathological findings. Early diagnosis of extramedullary plasmacytomas is of great importance. Radiotherapy is the common modality of treatment with or without adjuvant chemotherapy. Progression to multiple myeloma is possible; thus, close follow-up of the patient is essential after completion of the therapeutic procedure.


Topical sevoflurane for chronic venous ulcers infected by multi-drug-resistant organisms.
Several anaesthetic drugs have demonstrated antibacterial properties in vitro. Anaesthetics can primarily affect the cell wall of both susceptible and multi-resistant bacteria. They may also have a synergistic effect with conventional antibiotics through an unknown mechanism. We present three cases of a chronic venous ulcer infected by multi-resistant bacteria refractory to conventional systemic antibiotics, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Treatment with topical sevoflurane was performed for 1 month without systemic antibiotics. Patients with an MRSA infection showed progressive improvement with negative culture at the end of the treatment. Multi-drug-resistant P. aeruginosa infection persisted at the end of treatment with positive culture. The local adverse events were mild and transient, including heat, pruritus and erythema. Topical sevoflurane may have an antibacterial effect on sensitive and multi-resistant strains. It can allow more complete surgical cleaning, leaving a cleaner wound with less fibrin and necrotic tissue. This decreases the bacterial colonisation and therefore the infectious risk, the bad smell and the exudation. The simultaneous use of conventional antibiotics and topical sevoflurane can have a synergistic antimicrobial effect.


Obstetric medicine training: picking up where the licentiate in midwifery left off.
Obstetric medicine is the care of women with medical problems in pregnancy. Medical problems may predate or arise de novo in pregnancy. Some are common and some are dangerous. Both obstetricians and physicians recognise the need for greater numbers of appropriately trained clinicians to care for such women. There is a demand for such training, particularly from trainee obstetricians. The Royal College of Obstetricians and Gynaecologists (RCOG) and the Royal College of Physicians (RCP) agree that there is a need for more formalised training in maternal/obstetric medicine and they are working together to develop special interest training in maternal medicine. The training will be open to both obstetricians and physicians and include theoretical and practical components. The practical training will take place in centres with established medical obstetric clinics and will be tailored (with appropriate modules) to the amount of previous experience in medicine or obstetrics.


Two-Dimensional Plate Theory for the Analysis of Coupling Vibrations in Shear Mode FBARs.
The shear mode film bulk acoustic wave resonators (FBARs) have been developed rapidly in recent years due to the increased interest in biosensors. In this article, the mode coupling effects that are unavoidable in real devices are theoretically analyzed and discussed. Mindlin's approximation method of expanding the displacement fields with power series along the plate thickness direction is employed, and a system of 2-D plate equations is obtained. The accuracy of the plate theory is validated through the comparison of dispersion curves with the results calculated by 3-D exact theory. Free coupling vibrations of the cross-sectional plane of finite-sized shear mode FBAR plates are further studied with the derived 2-D theory. The results in this article show that the presented plate theory is accurate and efficient for the structural analyses of shear mode FBARs. Besides, the selection of aspect ratios can be used to avoid strong mode couplings, which is helpful for device designs.


Successful Rescue Ventilation of an Infant With a Laryngeal Mask Airway After Accidental Extubation in the Prone Position During Open Calvarial Reconstruction of a Craniosynostosis: A Case Report.
In this case report, we present a critical situation during an open calvarial reconstruction involving an 11-month-old infant. The patient experienced accidental extubation, requiring immediate intervention while in the prone position. Approximately two hours post-incision, ventilation became increasingly difficult due to a significant leak detected in the system. On closer inspection, it was observed that both the rubber tourniquet responsible for securing the anesthesia circuit and the tape that held the endotracheal tube in place had become loosened. In response to this emergency, the decision was made to remove the displaced endotracheal tube. We successfully introduced a 1.5 laryngeal mask airway (LMA; Unique™, Teleflex Incorporated, Wayne, PA), which restored ventilation. The patient maintained stable oxygen levels throughout this emergency period, displaying no signs of desaturation. An hour post-intervention, the surgical procedure was completed. The process of removing the LMA was uneventful without any complications. In the setting of emergent airway management, especially for patients in the prone position during surgical procedures, accidental extubation presents a challenge for healthcare providers. This case highlights the importance of prompt decision-making and having alternative airway devices on hand, such as an LMA.


Long-term vocal outcomes of refined nerve-muscle pedicle flap implantation combined with arytenoid adduction.
The objective of this study is to evaluate long-term efficacy of refined nerve-muscle pedicle (NMP) flap implantation combined with arytenoid adduction (AA) for treatment of unilateral vocal fold paralysis (UVFP). The authors retrospectively reviewed 33 patients with UVFP who received refined NMP flap implantation with AA and were followed up over a 1-year period. Evaluation of vocal fold vibration (regularity, amplitude, and glottal gap), aerodynamic analysis (maximum phonation time [MPT] and mean airflow rate [MFR]), and perceptual evaluation (Grade and Breathiness) were performed preoperatively and at five different time points (1, 3, 6, 12, and 24 months) postoperatively. All voice parameters improved significantly postoperatively. All parameters except MFR also continued to improve over the course of 24 months. In the videostroboscopic analysis, the parameter for regularity 24 months after surgery was significantly improved compared with that at 1, 3, and 6 months after surgery. There were also significant improvements in amplitude and the glottal gap 24 months after surgery in comparison with values at 3 and 6 months after surgery and 3 months after surgery, respectively. Significant improvement in aerodynamic and perceptual measurements during the follow-up period together with near-normal vocal fold vibration was achieved by delayed reinnervation with refined NMP flap implantation and AA. The combined surgical technique is effective in the treatment of severe breathy dysphonia due to UVFP. Level of evidence 4.


Identification of common or distinct genes related to antitumor activities of a medicinal herb and its major component by oligonucleotide microarray.
Although the physiological actions of many herbs are gradually being elucidated at the molecular level, it remains unclear how individual components of herbs contribute to their biological activities. In the present study, the antiproliferative activity of Coptidis rhizoma, a medicinal herb, and the major component berberine was investigated in 8 human pancreatic cancer cell lines. Gene expression patterns associated with sensitivities to each agent were analyzed with oligonucleotide arrays that comprised approximately 11,000 genes. We used a tetrazolium dye (MTT) assay to determine ID(50) values after the 8 cell lines were exposed to the 2 agents for 72 hr. The ID(50) value for berberine was correlated positively with that for C. rhizoma (r=0.725, p=0.0401). C. rhizoma killed tumor cells more effectively than purified berberine when normalized to the level of berberine present in the herb. From the oligonucleotide array data, we selected 20 and 13 genes with strong correlations (r(2)>0.81) to ID(50) values for berberine and C. rhizoma, respectively. Among these 33 genes, the levels of expression of 12 were correlated with the ID(50) values of both agents, suggesting that these genes are associated with tumor-killing activity of berberine in C. rhizoma. Expression of the remaining 21 genes was correlated with the ID(50) value of either purified berberine or C. rhizoma. Thus, we identified common and distinct genes responsible for anti-proliferative activities of purified berberine and C. rhizoma. This strategy may improve our understanding of the actions of herbs with antitumor activities.


Thinking ahead about medical treatments in advanced illness: a qualitative study of barriers and enablers in end-of-life care planning with patients and families from ethnically diverse backgrounds.
This study explored whether or not, and how, terminally ill patients from ethnically diverse backgrounds and their family caregivers think ahead about deterioration and dying, and explored their engagement with health-care professionals in end-of-life care planning. The aim was to address the question, what are the barriers to and enablers of ethnically diverse patients, family caregivers and health-care professionals engaging in end-of-life care planning? This was a qualitative study comprising 18 longitudinal patient-centred case studies, interviews with 19 bereaved family caregivers and 50 public and professional stakeholder responses to the findings. The study was set in Nottinghamshire and Leicestershire in the UK. Key barriers - the predominant stance of patients was to live with hope, considering the future only in terms of practical matters (wills and funerals), rather than the business of dying. For some, planning ahead was counter to their faith. Health-care professionals seemed to feature little in people's lives. Some participants indicated a lack of trust and experienced a disjointed system, devoid of due regard for them. However, religious and cultural mores were of great importance to many, and there were anxieties about how the system valued and enabled these. Family duty and community expectations were foregrounded in some accounts and concern about being in the (un)care of strangers was common. Key enablers - effective communication with trusted individuals, which enables patients to feel known and that their faith, family and community life are valued. Health-care professionals getting to 'know' the person is key. Stakeholder responses highlighted the need for development of Health-care professionals' confidence, skills and training, Using stories based on the study findings was seen as an effective way to support this. A number of behavioural change techniques were also identified. It was attempted to include a broad ethnic diversity in the sample, but the authors acknowledge that not all groups could be included. What constitutes good end-of-life care is influenced by the intersectionality of diverse factors, including beliefs and culture. All people desire personalised, compassionate and holistic end-of-life care, and the current frameworks for good palliative care support this. However, health-care professionals need additional skills to navigate complex, sensitive communication and enquire about aspects of people's lives that may be unfamiliar. The challenge for health-care professionals and services is the delivery of holistic care and the range of skills that are required to do this. Priorities for future research: How can health professionals identify if/when a patient is 'ready' for discussions about deterioration and dying? How can discussions about uncertain recovery and the need for decisions about treatment, especially resuscitation, be most effectively conducted in a crisis? How can professionals recognise and respond to the diversity of faith and cultural practices, and the heterogeneity between individuals of beliefs and preferences relating to the end of life? How can conversations be most effectively conducted when translation is required to enhance patient understanding? This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. X. See the NIHR Journals Library website for further project information.


Multi-resolution polymer Brownian dynamics with hydrodynamic interactions.
A polymer model given in terms of beads, interacting through Hookean springs and hydrodynamic forces, is studied. A Brownian dynamics description of this bead-spring polymer model is extended to multiple resolutions. Using this multiscale approach, a modeller can efficiently look at different regions of the polymer in different spatial and temporal resolutions with scalings given for the number of beads, statistical segment length, and bead radius in order to maintain macro-scale properties of the polymer filament. The Boltzmann distribution of a Gaussian chain for differing statistical segment lengths gives a diffusive displacement equation for the multi-resolution model with a mobility tensor for different bead sizes. Using the pre-averaging approximation, the translational diffusion coefficient is obtained as a function of the inverse of a matrix and then in closed form in the long-chain limit. This is then confirmed with numerical experiments.


Transanal Surgery: A History of taTME Ancestry.
Transanal total mesorectal excision (taTME) is the culmination of major developments in rectal cancer management and minimally invasive surgery. This surgical breakthrough holds great promise and excitement for the care of the rectal cancer patient. We would be remiss in discussing taTME to not acknowledge the role of transanal abdominal transanal proctosigmoidectomy, transanal endoluminal microsurgery, laparoscopy, and natural orifice transluminal endoscopic surgery that got us to this modern day explosion of the taTME approach. In this article, we detail and explain the convergence of these disparate experiences, how they culminated in the development of the taTME, and explore future directions in this field.


Preparation, Optimization and Physicochemical Characterization of Aripiprazole Loaded Nano-porous in situ Forming Implant.
Multiple applications of antipsychotic agents are the main obstacle in the treatment of schizophrenia. Due to behavioral abnormalities, low compliance is observed in most of the psychotic patients. Designing of new drug delivery systems to overcome compliance problem seems to be necessary. In situ forming implants are a suitable choice for the delivery of antipsychotic agents due to their easy administration process and sustained release kinetics. In this study, a novel poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) based nanoporous in situ implant system is developed for delivery of aripiprazole. Entrapment efficiency, drug loading, rheological features, morphological characteristics and release profile of nano-porous in situ implant system are analyzed in this study. Entrapment efficiency and drug loading coefficient were modeled and impact of different experimental parameters was analyzed using D-optimal study. Entrapment efficiency and drug loading were optimized at 99.32% and 75.23%, respectively. Rheological analyses demonstrated that the developed formulation is a highly cross-linked gel with possible capability for controlled delivery of aripiprazole. According to the FTIR studies, aripiprazole was intact within polymer networks. SEM and light microscopic analyses proved the acceptable morphological characteristics of in situ gels. Release studies demonstrated a biphasic pattern of release. After initial burst release, a sustained pattern was observed for 18 days. The release data was fitted to Korsmeyer-Peppas model and release pattern was found out to be Fickian. In addition, the release profile was compared with novel pluroniccarrageenan based hydrogel system. PHBV based in situ forming implant seems to be a novel formulation for delivery of Aripiprazole.


Dual ectopic thyroid: a case report with review of literature.
The ectopic thyroid gland is a rare entity which is mostly found along the line of descent of the thyroid gland. Most of the patients present with midline swelling and usually seek medical attention. Dual ectopic thyroid gland is even rarer. The clinical examination and different imaging modalities establish its diagnosis. Radionuclide studies are highly sensitive and specific in demonstrating the functional tissues in patients with ectopic thyroid, thereby guiding further management. The authors reported a case of ectopic thyroid gland in a girl with midline neck swelling initially, subsequently lost to follow-up. She again presented with enlarged swelling after a period of three years with dual ectopic thyroid in the neck region on thyroid scan. Thyroid scintigraphy demonstrated that progression in the size of ectopic glands was due to neglect in treatment.


Religion and spirituality: Pathways to positive body image.
Positive body image is a multidimensional construct referring to love, respect, and acceptance of one's body, including aspects inconsistent with sociocultural ideals. The aim of the present study was to investigate potential pathways leading from religion and spirituality to positive body image. Participants were 345 women who completed questionnaire measures of engagement with formal religion, spirituality, gratitude, self-objectification, and positive body image. Both engagement with formal religion and spirituality were found to be positively associated with positive body image. Further, mediation analyses showed that the relationship between spirituality and positive body image was mediated by gratitude and reduced self-objectification. It was concluded that a broader spiritual consciousness may assist women to develop a loving, appreciative, and respectful relationship with their bodies. In addition, gratitude and a de-emphasis on external appearance provide useful goals and potential intervention points for promoting positive body image.


Evidence for specific RNA/protein interactions in the differential segment of the W sex chromosome in the amphibian Pleurodeles waltl.
Pleurodeles exhibits a ZZ/ZW system of GSD (genotype sex determination). However, the Z and W sex chromosomes appear to be morphologically identical. A short RNA sequence is described that was specifically bound to lampbrush loops in the differential segment of the sexual bivalent IV. The distribution of these labeled loops in experimentally produced ZZ and WW females enabled us to demonstrate that such labeled loops were perfectly correlated with the W chromosome. Therefore, this RNA sequence constitutes an excellent marker for the W differential segment. Furthermore, analysis of the labeled loops under various experimental conditions suggested that their labeling is caused by specific interactions between this RNA sequence and lampbrush loop-associated proteins (RNA/protein interactions). North-western assays revealed that nuclear polypeptide(s) of 65 kDa could be responsible for such binding.


The pathophysiology of peripheral arterial disease: rational targets for drug intervention.
The most common cause of peripheral arterial disease (PAD) is atherosclerosis, which begins with an alteration in endothelial biology due to hypercholesterolemia, diabetes mellitus, hypertension, tobacco use, elevated levels of lipoprotein(a) or homocystinemia. With chronic and severe arterial disease, changes begin to occur in the microcirculation, including obstruction at the microvascular level and tissue injury. Based on insights into the vascular biology of PAD, new therapies have been developed and are at various stages of clinical trials. Future pharmacotherapy for PAD will include agents that have one or more of the following attributes; (1) reduce, or even reverse, the progression of atherosclerosis; (2) inhibit plaque rupture; (3) inhibit thrombosis by a novel mechanism; (4) induce angiogenesis; (5) reverse microvascular derangements; (6) affect blood rheology; and (7) enhance skeletal muscle's ability to use available nutrients.


Cloning of cDNAs and hybridization analysis of lysozymes from two oyster species, Crassostrea gigas and Ostrea edulis.
In bivalve molluscs including oysters, lysozymes play an important role in the host defense mechanisms against invading microbes. However, it remains unclear in which sites/cells the lysozyme genes are expressed and which subsequently produced the enzyme. This study cloned lysozyme cDNAs from the digestive organs of Pacific oyster Crassostrea gigas and European flat oyster Ostrea edulis. Both complete sequences of two oysters' lysozymes were composed of 137 amino acids. Two translated proteins present a high content in cysteine residues. Phylogenetic analyses showed that these oysters' lysozymes clustered with the invertebrate-type lysozymes of other bivalve species. In the Pacific oyster, lysozyme mRNA was expressed in all tissues except for those of the adductor muscle. In situ hybridization analyses revealed that lysozyme mRNA was expressed strongly in basophil cells in the digestive gland tubule of C. gigas, but not in digestive cells. Results indicated that the basophil cells of the oyster digestive gland are the sites of lysozyme synthesis.


Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure.
Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg(-1)·h(-1)) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep (n = 6) and sheep with pacing-induced HF (n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (-8 ± 4 mmHg and -4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF.


Revealing the Origin of Fast Electron Transfer in TiO2-Based Dye-Sensitized Solar Cells.
In dye-sensitized solar cells (DSCs), the electron transfer from photoexcited dye molecules to semiconductor substrates remains a major bottleneck. Replacing TiO2 with ZnO is expected to enhance the efficiency of DSCs, owing to the latter possesses a much larger electron mobility, but similar bandgap and band positions as TiO2 remain. However, the record efficiency of ZnO-based DSCs is only 7% compared with 13% of TiO2-based DSCs due to the even slower electron-transfer rate in ZnO-based DSCs, which becomes a long-standing puzzle. Here, we computationally investigate the electron transfer from the dye molecule into ZnO and TiO2, respectively, by performing the first-principles calculations within the frame of the Marcus theory. The predicted electron-transfer rate in the TiO2-based DSC is about 1.15 × 10(9) s(-1), a factor of 15 faster than that of the ZnO-based DSC, which is in good agreement with experimental data. We find that the much larger density of states of the TiO2 compared with ZnO near the conduction band edge is the dominant factor, which is responsible for the faster electron-transfer rate in TiO2-based DSCs. These denser states provide additional efficient channels for the electron transfer. We also provide design principles to boost the efficiency of DSCs through surface engineering of high mobility photoanode semiconductors.


Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project.
In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals. In order to contribute to filling this gap, one of the project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) aims at developing novel in vitro methods for the detection of endocrine metabolic disruptors. Efforts will comprise projects related to specific signaling pathways, for example, involving mTOR or xenobiotic-sensing nuclear receptors, studies on hepatocytes, adipocytes and pancreatic beta cells covering metabolic and morphological endpoints, as well as metabolism-related zebrafish-based tests as an alternative to classic rodent bioassays. This paper provides an overview of the approaches and methods of these PARC projects and how this will contribute to the improvement of the toxicological toolbox to identify substances with endocrine disrupting properties and to decipher their mechanisms of action.


Cardiovascular effects of thoracic compression in horses subjected to euthanasia.
Six horses scheduled for euthanasia were instrumented for the measurement of blood flow by thermodilution, pulmonary arterial, right atrial and arterial blood pressures and collection of arterial blood for pH and blood gas analysis. The horses were anaesthetised with intravenous (iv) thiamylal sodium (10 mg/kg) and placed in right lateral recumbency. After euthanasia with an overdose of pentobarbitone sodium (100 mg/kg, iv) and loss of the electrocardiogram and arterial pulse pressure, thoracic compression at rates of 40, 60 and 80 compressions/min was instituted. Thoracic compression was accomplished by an investigator who delivered a blow to the chest wall with his knee while dropping from a standing or crouching position. Compression rates of 40, 60 and 80/min produced blood flows of 5.65 +/- 0.5, 6.33 +/- 1.11 and 8.28 +/- 2.16 litres/min, respectively. Compression rates of 80/min produced significantly (P < 0.05) greater blood flows and mean arterial blood pressures than did slower rates. The blood flows produced by 80 thoracic compressions/min were approximately 50% of those reported for deeply anaesthetised horses and while not sufficient to sustain life might be used to prolong life in order to facilitate distribution of resuscitative drugs to vital tissues.


Ventricular and vascular remodelling effects of the angiotensin II receptor blocker telmisartan and/or the angiotensin-converting enzyme inhibitor ramipril in hypertensive patients.
Angiotensin II induces inflammatory activation of vascular smooth muscle cells and can cause left ventricular hypertrophy (LVH). Telmisartan is an angiotensin II receptor blocker with demonstrated beneficial effects on cardiac and vascular structure and function in animal models. The angiotensin-converting enzyme inhibitor ramipril also reduces ventricular and vascular remodelling. The open-label study observed 75 treatment-naive, moderately or severely hypertensive (systolic blood pressure 160-190 mmHg, diastolic blood pressure 90-110 mmHg) patients (age range, 42-58 years) treated with once-daily telmisartan 40 mg force-titrated to 80 mg after 1 month (n=25), once-daily ramipril 2.5 mg force-titrated to 5 mg after 1 month (n=25), or once-daily telmisartan 40 mg plus ramipril 2.5 mg (n=25); the total duration of treatment was 6 months. At baseline, blood pressure, left ventricular mass index (LVMI), carotid intima-media thickness (IMT) and carotid cross-sectional intima-media area (CSA) were measured. Measurements were repeated 1, 3 and 6 months after initiation of treatment. After 6 months, comparable blood pressure reductions were achieved with the three treatments. Reductions in LVMI after 6 months' treatment were 11.4%, 9.9% and 15.6% with telmisartan, ramipril, and telmisartan plus ramipril, respectively. Respective reductions in IMT were 14.6%, 12.0% and 18.2%, and for CSA were 7.8%, 4.3% and 11.5%. In conclusion, treatment with telmisartan or ramipril for 6 months resulted in regression of LVH and vascular remodelling. When a combination of telmisartan and ramipril was administered, additional regression and remodelling occurred.


Effect of widespread agricultural chemical use on butterfly diversity across Turkish provinces.
Although agricultural intensification is thought to pose a significant threat to species, little is known about its role in driving biodiversity loss at regional scales. I assessed the effects of a major component of agricultural intensification, agricultural chemical use, and land-cover and climatic variables on butterfly diversity across 81 provinces in Turkey, where agriculture is practiced extensively but with varying degrees of intensity. I determined butterfly species presence in each province from data on known butterfly distributions and calculated agricultural chemical use as the proportion of agricultural households that use chemical fertilizers and pesticides. I used constrained correspondence analyses and regression-based multimodel inference to determine the effect of environmental variables on species composition and richness, respectively. The variation in butterfly species composition across the provinces was largely explained (78%) by the combination of agricultural chemical use, particularly pesticides, and climatic and land-cover variables. Although overall butterfly richness was primarily explained by climatic and land-cover variables, such as the area of natural vegetation cover, threatened butterfly richness and the relative number of threatened butterfly species decreased substantially as the proportion of agricultural households using pesticides increased. These findings suggest that widespread use of agricultural chemicals, or other components of agricultural intensification that may be collinear with pesticide use, pose an imminent threat to the biodiversity of Turkey. Accordingly, policies that mitigate agricultural intensification and promote low-input farming practices are crucial for protecting threatened species from extinction in rapidly industrializing nations such as Turkey. Efectos del Uso Extensivo de Agroquímicos sobre la Diversidad de Mariposas en Provincias Turcas.


Electrospun polymeric nanofibers: New horizons in drug delivery.
Nanofibers obtained using electrospinning technique are being used since ages especially in fields of textile industry, sensors, filters, protective clothing and tissue engineering. Their use as drug delivery system is an emerging platform in the field of pharmaceuticals and now-a-days formulation scientists are paying great attention to the technology due to several advantages prime being easy modulation of drug release profile depending upon the properties of polymer/polymeric blends/other materials used. Although there are several reports citing the use of antibiotics-loaded nanofibers as wound dressing materials and as antimicrobial therapy in periodontics; still there is a good scope of expanding the horizon for its application in newer ailments. This article reviews various aspects related to loading and release of drug as such or in nano-particulate form to polymeric nanofibers by taking critical process parameters (CPPs) for electrospinning and critical material attributes (CMAs) into account. Commercially available products and electrospinning technologies are described in brief along with some of the patents related to their use as drug delivery systems. The main focus of this review is applicability of drug/drug nanoparticle loaded nanofibers in the management of diseases/disorders related to the brain, eye, ear, cardiovascular system, lungs and oral cavity. Use in diseases with higher mortality rates like diabetes, Acquired immunodeficiency syndrome (AIDS) and cancer is also described in brief.


The epidemiology of diabetes and its complications in New Zealand.
New Zealand is a country in the South Pacific with a high proportion of Polynesians. While the prevalence of diabetes appears the same in New Zealand Europeans as Europeans elsewhere, Maori and Pacific Islands people have a 2 to 4-fold excess prevalence of diabetes. Although Europeans make up the majority of diabetic New Zealanders, the greatest concern lies with the Maori and Pacific Islands patients who experience an earlier age at diagnosis, greater obesity, higher rates of smoking (in Maori), poorer diabetes knowledge, poorer glucose control, and more end stage renal failure and blindness. Efforts are now being made to control the current epidemic.


Diaphorina citri (Hemiptera: Liviidae) Vector Competence for the Citrus Greening Pathogen 'Candidatus Liberibacter Asiaticus'.
Characterizing the vector competence of Diaphorina citri Kuwayama for 'Candidatus Liberibacter asiaticus,' the pathogen causing citrus greening, is essential for understanding the epidemiology of this disease that is threatening the U.S. citrus industry. Vector competence studies have been difficult because of the biology of D. citri, the inability to culture the pathogen, and the available diagnostic methods used to detect the bacteria in plant and insect tissues. The methods employed in many studies of D. citri vector competence may have overestimated amounts of live 'Ca. L. asiaticus' in both plant and insect tissues, and it is possible that the amounts of phloem ingested by psyllids may not contain sufficient detectable pathogen using current diagnostic methods. As a result of the difficulty in characterizing D. citri vector competence, the several daunting challenges for providing D. citri that are unable to inoculate 'Ca. L. asiaticus', as a novel method to control greening are discussed. Suggestions to overcome some of these challenges are provided.


Stable association of processed antigen with antigen-presenting cell membranes.
Th cells recognize a processed form of Ag in association with class II histocompatibility molecules expressed on the surface of APC. The physical nature of the cell surface association of physiologically processed Ag was investigated by using membranes isolated from Ag-pulsed APC. Such membranes were sufficient to directly activate class II-restricted T cell hybridomas without further Ag processing. T cell-stimulating activity remained after treatment of membranes in harsh conditions, including pH 4.0, pH 9.0, high salt, and chaotropic solvents. Activity was lost after exposure to pH 2.0 or protease. The capacity of pH 2.0 (but not protease) treated membranes to present artificially processed, peptide Ag to T cells suggests that exposure to pH 2.0 results in the selective dissociation of processed Ag from membranes. Similar results were obtained in parallel experiments with peptide-pulsed membranes. No qualitative differences were found between physiologically processed Ag and peptide Ag with respect to their remarkably stable association with the APC plasma membrane.


Anti-allergic activities of the beta-adrenoceptor stimulant formoterol (BD 40A).
The effects of formoterol (BD 40A) on the rat and guinea-pig hypersensitivity reactions and on mouse IgE antibody formation was investigated. The inhibitory effect of intravenously (i.v.) and perorally (p.o.) administered formoterol on (mouse) IgE-mediated 24-hr passive cutaneous anaphylaxis (PCA) in rats was 6.3 and 33 times, respectively, more potent than that of salbutamol. This action was antagonized by pretreatment with propranolol. Formoterol at the dose exhibiting considerable PCA inhibition had no effect on histamine- and 5-hydroxytryptamine-induced skin reactions. Formoterol, administered i.v. or p.o., inhibited (guinea-pig) IgE-mediated 8-day PCA in guinea-pigs. In the isolated guinea-pig lung, both formoterol and salbutamol exhibited dose-dependent inhibition of antigen-induced histamine release. However, in the isolated rat mesenterium these two drugs showed only partial inhibition of antigen-induced mast cell degranulation, whereas disodium cromoglycate (DSCG) manifested dose-dependent inhibition. Neither formoterol nor salbutamol affected the hapten-specific IgE antibody response in female BDF1 mice.


Urticaria and mimickers of urticaria.
Urticaria is a common skin condition encountered across various specialties in medicine, especially in dermatology and allergy/immunology practice. It has a heterogeneous presentation hence it is unsurprising that many skin conditions may be confused with urticaria. Urticaria may present as acute or chronic urticaria, the latter can be further categorised into chronic spontaneous and chronic inducible. In this article, we explore, explain, and summarise various skin lesions that are considered mimickers of urticaria, to promote understanding of each of the conditions highlighted, improve recognition, and reduce misdiagnosis.


Ethanol fuel improves arthropod capture in pitfall traps and preserves DNA.
We tested the value of ethanol fuel as a killing solution in terms of sampling efficiency (species richness and accumulated abundance) and DNA preservation of Ensifera ground-dwelling specimens. Sampling efficiency was evaluated comparing abundance and species richness of pitfall sampling using 100% ethanol fuel, with two alternative killing solutions. We evaluated the DNA preservation efficiency of the killing solutions and of alternative storage solutions. Ethanol fuel was the most efficient killing solution, and allowed successful DNA preservation. This solution is cheaper than other preserving liquids, and is easily acquired near field study sites since it is available at every fuel station in Brazil and at an increasing number of fuel stations in the U.S. We recommend the use of ethanol fuel as a killing and storage solution, because it is a cheap and efficient alternative for large-scale arthropod sampling, both logistically and for DNA preservation. For open habitat sampling with high day temperatures, we recommend doubling the solution volume to cope with high evaporation, increasing its efficacy over two days.


Positioning a medical school for modern biomedical research: the department of genome sciences at the University of Washington School of Medicine.
The availability of genome sequences from a multitude of organisms, which began about a decade ago, has had enormous impact throughout the biomedical sciences. These sequence data have changed the way research studies are carried out and have led to the explosive growth of computational biology as an approach to analyze biological processes and evolution. In medicine, the completion of the human genome sequence has illuminated the function of many genes, facilitated the correlation of mutant genes to disease phenotypes, and provided a basis for the study of human variation. At the University of Washington, the two academic departments whose overall programs were most centrally affected by the sequencing revolution were Genetics and Molecular Biotechnology. These departments were fused in 2001 to form the Department of Genome Sciences in order to best exploit these developments and to become a prototype for the basic biomedical science department of the future. The department's goal is to address leading-edge questions in biology and medicine through the application of genetics, genomics, proteomics, and computational approaches to the increasing collection of known genome sequences and their encoded products. The authors review the events that led up to the founding of this department and discuss the initiatives that have been undertaken, which include the recruitment of faculty, the establishment of a new interdisciplinary graduate program, the continued development of an outreach program, and the construction of a building to house the department. Lessons learned in crafting this department are also discussed, as well as how these might apply to other medical schools.


Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier.
Metastasis is the leading cause of colorectal cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering microRNA (miRNA) to vascular endothelial cells, facilitating cancer metastasis. The mechanism by which Epithelial-mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal cancer (CRC) tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT-cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.


Family Members' Experience With Hospice in Nursing Homes.
Research has documented numerous benefits and challenges associated with receipt of hospice care in nursing homes; however, study of this partnership from the perspective of residents' family members has been limited. The purpose of this qualitative investigation was to explore family members' experience with hospice services received in the nursing home setting. Researchers conducted a secondary data analysis of 175 family member interviews using a thematic analytic approach. Findings highlighted the critical role of communication in supporting residents and their family members. Care coordination, support and oversight, and role confusion also impacted family members' experience of hospice care in the nursing home. Efforts directed at enhancing communication and more clearly articulating the roles of members of the health care team are indicated.


The role of a Mediterranean diet and physical activity in decreasing age-related inflammation through modulation of the gut microbiota composition.
Chronic inflammation is known to be a predominant factor in the development of many age-related conditions including CVD, type II diabetes and neurodegenerative diseases. Previous studies have demonstrated that during the ageing process there is an increase in inflammatory biomarkers, which may be partially brought about by detrimental changes in the gut microbiota. The Mediterranean diet (MedDiet) and physical activity (PA) are protective against inflammation and chronic disease, and emerging evidence has shown that these effects may be partially mediated through favourable changes in the gut microbiota. In this review, we have evaluated the published literature on the effect of a MedDiet and PA on the gut microbiota. We also discuss the relationship between the gut microbiota and inflammation with a focus on healthy ageing. While inconsistent study designs make forming definitive conclusions challenging, the current evidence suggests that both a MedDiet and PA are capable of modifying the gut microbiota in a way that is beneficial to host health. For example, the increases in the relative abundance of SCFA producing bacteria that are considered to possess anti-inflammatory properties. Modification of the gut microbiota through a MedDiet and PA presents as a potential method to attenuate age-related increases in inflammation, and additional studies utilising older individuals are needed to fill the knowledge gaps existing in current literature.


The ethics of biobanking: Assessing the right to control problem for broad consent.
The biobank consent debate is one with deeply held convictions on both the 'broad' and 'specific' side with little sign of resolution. Recently, Thomas Ploug and Soren Holm have developed an alternative to both specific and broad consent: a meta-consent framework. The aim here is to consider whether meta-consent provides a 'solution' to the biobank consent debate. We clarify what 'meta-consent' actually is (arguing that the label is a misnomer and 'consent à la carte' is more accurate). We identify problems with Ploug and Holm's arguments, and some challenges for meta-consent. We focus on whether there is any ethical obligation to provide consent à la carte. There may seem to be so, especially if we draw upon an unclear appeal to the ethical significance of 'respect for autonomy'. Similarly, there might seem to be an intuitive inference from the fact that ethically legitimate research requires informed consent to the conclusion that it thereby requires consent à la carte. It is shown that this line of inference is mistaken.


Diversities in presentations of extrapulmonary tuberculosis.
The incidence of extrapulmonary tuberculosis (EPTB) has been increasing worldwide over the last few years. Tuberculous lymphadenitis is the most common form of the disease and is reported to occur in 25-60% of all EPTB cases. It is commonly seen in the cervical lymph nodes, but may also be in the larynx, pharynx, parotid and rarely, in the sinuses and petrous bone. The posterior triangle, supraclavicular and jugular nodes are most frequently affected. They are usually unilateral, although diffuse adenopathy may occur. TB involving cervical lymph nodes represents 50% of extrapulmonary TB. A series of six cases of tuberculous lymphadenitis with varying clinical features is documented here to alert one of its prevalence in developing countries.


Two-week normobaric intermittent-hypoxic exposures stabilize cerebral perfusion during hypocapnia and hypercapnia.
The effect of moderately extended, intermittent-hypoxia (IH) on cerebral perfusion during changes in CO2 was unknown. Thus, we assessed the changes in cerebral vascular conductance (CVC) and cerebral tissue oxygenation (ScO2) during experimental hypocapnia and hypercapnia following 14-day normobaric exposures to IH (10% O2). CVC was estimated from the ratio of mean middle cerebral arterial blood flow velocity (transcranial Doppler sonography) to mean arterial pressure (tonometry), and ScO2 in the prefrontal cortex was monitored by near-infrared spectroscopy. Changes in CVC and ScO2 during changes in partial pressure of end-tidal CO2 (PETCO2, mass spectrometry) induced by 30-s paced-hyperventilation (hypocapnia) and during 6-min CO2 rebreathing (hypercapnia) were compared before and after 14-day IH exposures in eight young nonsmokers. Repetitive IH exposures reduced the ratio of %ΔCVC/ΔPETCO2 during hypocapnia (1.00 ± 0.13 vs 1.94 ± 0.35 vs %/mmHg, P = 0.026) and the slope of ΔCVC/ΔPETCO2 during hypercapnia (1.79 ± 0.37 vs 2.97 ± 0.64 %/mmHg, P = 0.021), but had no significant effect on ΔScO2/ΔPETCO2. The ventilatory response to hypercapnia during CO2 rebreathing was significantly diminished following 14-day IH exposures (0.83 ± 0.07 vs 1.14 ± 0.09 L/min/mmHg, P = 0.009). We conclude that repetitive normobaric IH exposures significantly diminish variations of cerebral perfusion in response to hypercapnia and hypocapnia without compromising cerebral tissue oxygenation. This IH-induced blunting of cerebral vasoreactivity during CO2 variations helps buffer excessive oscillations of cerebral underperfusion and overperfusion while sustaining cerebral O2 homeostasis.


Dietary Alteration of the Gut Microbiome and Its Impact on Weight and Fat Mass: A Systematic Review and Meta-Analysis.
Dietary alteration of the gut microbiome is an important target in the treatment of obesity. Animal and human studies have shown bidirectional weight modulation based on the probiotic formulation used. In this study, we systematically reviewed the literature and performed a meta-analysis to assess the impact of prebiotics, probiotics and synbiotics on body weight, body mass index (BMI) and fat mass in adult human subjects. We searched Medline (PubMed), Embase, the Cochrane Library and the Web of Science to identify 4721 articles, of which 41 were subjected to full-text screening, yielding 21 included studies with 33 study arms. Probiotic use was associated with significant decreases in BMI, weight and fat mass. Studies of subjects consuming prebiotics demonstrated a significant reduction in body weight, whereas synbiotics did not show an effect. Overall, when the utilization of gut microbiome-modulating dietary agents (prebiotic/probiotic/synbiotic) was compared to placebo, there were significant decreases in BMI, weight and fat mass. In summary, dietary agents for the modulation of the gut microbiome are essential tools in the treatment of obesity and can lead to significant decreases in BMI, weight and fat mass. Further studies are needed to identify the ideal dose and duration of supplementation and to assess the durability of this effect.


Quasiperpendicular High Mach Number Shocks.
Shock waves exist throughout the Universe and are fundamental to understanding the nature of collisionless plasmas. Reformation is a process, driven by microphysics, which typically occurs at high Mach number supercritical shocks. While ongoing studies have investigated this process extensively both theoretically and via simulations, their observations remain few and far between. In this Letter we present a study of very high Mach number shocks in a parameter space that has been poorly explored and we identify reformation using in situ magnetic field observations from the Cassini spacecraft at 10 AU. This has given us an insight into quasiperpendicular shocks across 2 orders of magnitude in Alfvén Mach number (M_{A}) which could potentially bridge the gap between modest terrestrial shocks and more exotic astrophysical shocks. For the first time, we show evidence for cyclic reformation controlled by specular ion reflection occurring at the predicted time scale of ~0.3τ_{c}, where τ_{c} is the ion gyroperiod. In addition, we experimentally reveal the relationship between reformation and M_{A} and focus on the magnetic structure of such shocks to further show that for the same M_{A}, a reforming shock exhibits stronger magnetic field amplification than a shock that is not reforming.


Acute Periprosthetic Hip Joint Infection Caused by Multidrug-Resistant Acinetobacter Baumannii: Is Debridement, Antibiotics, Irrigation, and Implant Retention a Viable Treatment Option?
In this study, we aimed to investigate the effectiveness of debridement, antibiotics, irrigation, and implant retention (DAIR) in periprosthetic hip joint infection caused by multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii). From July 2019 to June 2020, we retrospectively reviewed all patients treated for periprosthetic hip joint infections caused by MDR A. baumannii at our institution. The diagnosis of periprosthetic joint infection (PJI) was established based on the Musculoskeletal Infection Society (MSIS) 2018 criteria. The Charlson Comorbidity Index (CCI) was used to estimate the risk of mortality. The patients were followed up for over a year, until their death, or loss to follow-up. Four patients (three females and one male), with a mean age of 68 years, were included in the study. A. baumannii exhibited resistance to fluoroquinolones in all cases. All patients were treated with the DAIR procedure followed by intravenous tigecycline and colistin combination treatment. Prosthesis retention with good functional results was achieved in two patients. One patient required resection arthroplasty and one patient died two months after the initial surgical treatment, yielding a success rate of 50% for the DAIR procedure. Periprosthetic hip joint infection caused by MDR A. baumannii is one of the most demanding and challenging complications in orthopaedic practice. This case series suggests that the outcome of the DAIR is affected by a number of factors that are in a complex interplay. Our results indicate a limited success rate for the DAIR procedure in the treatment of a periprosthetic hip joint infection caused by MDR A. baumannii.


Diversity-oriented construction of highly substituted indolizinones.
Rapid generation of a small library of highly functionalized indolizonones was realized by exploiting three palladium-catalyzed cross-coupling reactions of 2-iodoindolizinones which in turn were readily accessed via sequential iodine-mediated cyclization/1,2-shift reactions of propargylic alcohols.


Canine infection by rickettsiae and ehrlichiae in southern Brazil.
This study evaluated the infection caused by Rickettsia and Ehrlichia agents among dogs in southern Brazil. A total of 389 dogs were tested by the indirect immunofluorescence assay (IFA) for Rickettsia rickettsii, Rickettsia parkeri, Rickettsia amblyommii, Rickettsia rhipicephali, Rickettsia bellii, and Ehrlichia canis. Overall, 42.4% (165/389) of the dogs were seroreactive to at least one Rickettsia species, but only 11 canine sera reacted with another Rickettsia species without reacting with R. parkeri. A total of 100 (25.7%) canine sera showed titers to R. parkeri at least 4-fold higher than those to any of the other rickettsial antigens, allowing us to consider that these dogs were infected by R. parkeri. Dogs that had direct contact with pasture or forest areas were > 2 times more likely to be seroreactive to Rickettsia than dogs with no such direct contact. Only 19 (4.8%) of the 389 dogs were seroreactive to E. canis.


Frequency-tunable terahertz graphene laser enabled by pseudomagnetic fields in strain-engineered graphene.
Graphene-based optoelectronic devices have recently attracted much attention for the next-generation electronic-photonic integrated circuits. However, it remains elusive whether it is feasible to create graphene-based lasers at the chip scale, hindering the realization of such a disruptive technology. In this work, we theoretically propose that Landau-quantized graphene enabled by strain-induced pseudomagnetic field can become an excellent gain medium that supports lasing action without requiring an external magnetic field. Tight-binding theory is employed for calculating electronic states in highly strained graphene while analytical and numerical analyses based on many-particle Hamiltonian allow studying detailed microscopic mechanisms of zero-field graphene Landau level laser dynamics. Our proposed laser presents unique features including a convenient, wide-range tuning of output laser frequency enabled by changing the level of strain in graphene gain media. The chip-scale graphene laser may open new possibilities for graphene-based electronic-photonic integrated circuits.


Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness.
The non-keratinizing undifferentiated subtype of nasopharyngeal carcinoma (NPC) is a malignancy characterized by an intimate relationship between neoplastic cells and a non-neoplastic lymphoid component. Tumor-associated macrophages (TAMs) foster tumor progression through production of soluble mediators that support proliferation, angiogenesis, survival and invasion of malignant cells. However, the role of macrophages in the progression of NPC remains poorly understood. This study aims to investigate the functional and phenotypic changes that occur to macrophages in macrophage-NPC cell co-culture systems, and how these changes influence tumor cells. We found that monocytes, including THP-1 cells and primary human monocytes, co-cultured with C666-1 NPC cells upregulate expression of pro-inflammatory cytokines at the early stages, followed by the induction of metastasis-related genes and interferon-stimulated genes at the later stage of coculture, indicating that TAMs are "educated" by NPC cells for cancer progression. Importantly, the induction of these factors from the TAMs was also found to enhance the migratory capabilities of the NPC cells. We have also identified one of these macrophage-derived factor, phospholipase A2 Group 7 (PLA2G7), to be important in regulating tumor cell migration and a novel tumor-promoting factor in NPC. Further studies to characterize the role of PLA2G7 in tumor metastasis may help determine its potential as a therapeutic target in NPC.


Overcoming Deactivation of Amine-Based Catalysts: Access to Fluoroalkylated γ-Nitroaldehydes.
Organocatalytic conjugate addition reactions of aldehydes to fluoroalkylated nitroolefins with chiral amine catalysts offer a straightforward stereoselective path to fluoroalkylated γ-nitroaldehydes and downstream derivatives. However, amine-based catalysts suffer from deactivation by reaction with electron-poor fluoroalkylated nitroolefin. Here, we show that catalyst deactivation can be overcome by catalysts that bear an intramolecular acid for protonation and release of the alkylated catalyst through ß-elimination of the nitroolefin. NMR spectroscopic, kinetic, and molecular modeling studies provided detailed structural and mechanistic insights into the factors that control reversible catalyst alkylation and facilitate efficient catalysis.


Apoptotic pathways of epothilone BMS 310705.
BMS 310705 is a novel water-soluble analog of epothilone B currently in phase I clinical evaluation in the treatment of malignancies such as ovarian, renal, bladder, and lung carcinoma. Using an early passage cell culture model derived from the ascites of a patient clinically refractory to platinum/paclitaxel therapy, we evaluated the pathway of caspase-mediated apoptosis. Cells were treated for 1 h and subsequently evaluated for apoptosis, survival, and caspase activity. Apoptosis was determined by fluorescent microscopy. Caspase-3, -8, and -9 activities were determined by fluorometry using target tetrapeptide substrates. Mitochondrial release of cytochrome c was determined by immunoblot analysis. After treatment with BMS 310705, apoptosis was confirmed in >25% of cells at 24 h. Survival was significantly lower (P < 0.02) in cells treated with 0.05 micro M BMS 310705 vs paclitaxel. Analysis revealed an increase of caspase-9 and -3 activity; no caspase -8 activity was observed. Release of cytochrome c was detected at 12 h following treatment. SN-38 and topotecan failed to induce apoptosis. BMS 310705 induces significant apoptosis, decreases survival, and utilizes the mitochondrial-mediated pathway for apoptosis in this model.


Patterns of intracellular compartmentalization, trafficking and acidification of 5'-fluorescein labeled phosphodiester and phosphorothioate oligodeoxynucleotides in HL60 cells.
We have examined the intracellular compartmentalization and trafficking of fluorescein labeled (F) phosphodiester (PO) and phosphorothioate (PS) oligodeoxynucleotides (oligos) in HL60 cells. A series of F-oligos (PO and PS) were incubated for 6 hrs. with HL60 cells and the mean intracellular fluorescence determined by flow cytometry. The F signal was normalized by the addition of the ionophore monensin. An increase in signal intensity following addition of monensin indicated that the oligo was resident in an acidic intracellular environment. F-PS, but not F-PO oligos were found to reside in an acidic environment. An exception was a PO homopolymer of 15 cytidine bases (FOdC15) which was acidified. Using two different methods, the average resident intracellular pH of F-PS oligos and F-OdC15 was shown to be approximately 1 pH unit lower than that of F-PO oligos. Acidification of F-PS oligos could be blocked by the antibiotic bafilomycin, indicating that acidification was occurring in endosomes or vacuoles. F-PO and F-PS oligos were effluxed from HL60 cells from two intracellular compartments. However, approximately 60% of internalized F-PO oligo resided in a 'shallow' compartment that was turned over rapidly (t1/2 = 5-10 min.) whereas only 20% of F-PS oligo resided in this compartment. Conversely, approximately 80% of the internalized F-PS oligo but only 40% of F-PO oligo resided in a 'deep' compartment that turned over with t1/2 = 2-5 hrs. This report is the first quantitative demonstration that PO and PS oligos, and PO oligos of different sequences are trafficked differently by HL60 cells.


Cardiac metastasis from thyroid carcinoma.
Cardiac metastasis from epithelial thyroid cancer is a very rare and potentially serious complication. We have identified only 54 reported cases over a 130-year period. Here we review this literature. Cardiac metastases are frequently asymptomatic, but when symptoms develop these tend to be severe and often fatal. The prognosis of cardiac metastases from thyroid cancer is unclear as survival data are often missing or absent in reported cases. However, as many patients died suddenly from cardiac complications, the prognosis seems poor. Of those patients who survived, all underwent surgical intervention. Trans-thoracic echocardiography is the diagnostic modality of choice as it allows dynamic evaluation of intracardiac masses. Metastatic involvement of the heart from thyroid cancer is uncommon. Left untreated this complication seems likely to be fatal. Therefore, in patients with established thyroid malignancy who develop cardiac arrhythmias, new murmurs, or signs of cardiac decompensation, we suggest that cardiac metastases be considered. Echocardiography should be performed in patients with advanced thyroid cancer and cardiac symptoms or signs. If a cardiac metastasis is present, we recommend surgical intervention if possible.


Central exercise action increases the AMPK and mTOR response to leptin.
AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR) are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus.


Adding the missing voice: How self-report of autistic youth self-report on an executive functioning rating scale compares to parent report and that of youth with attention deficit hyperactivity disorder or neurotypical development.
Executive functions are often impaired in autistic people and relate to important outcomes such as mental health, success in school and work, and quality of life. Evaluating executive functions helps autistic people, clinicians, and families identify targets for external supports and skill building. Youth self-report of executive function has not been studied, yet we know that self-report from autistic youth is key to understanding other cognitive/behavioral phenomena in autism such as anxiety, obsessions/compulsions, sensory sensitivities, and repetitive behaviors. We investigated self- and parent-report of executive function problems in 197 autistic youth without intellectual disability (ages 11-18 years), including the magnitude and profiles of executive function problems autistic youth report across subdomains of executive function. We compared autistic self-report with that of 114 youth with attention deficit hyperactivity disorder without intellectual disability and 197 neurotypical youth. We found that autistic youth report significant executive function problems compared to neurotypical youth and a distinctive profile of challenges in comparison to attention deficit hyperactivity disorder youth. Parents and their autistic children diverged regarding the magnitude of the youth's executive function difficulties, but both identify inflexibility as the most impaired executive function subdomain. Autistic youth and their parents were somewhat more concordant in their report of executive function problems than youth with attention deficit hyperactivity disorder and their parents, but only showed moderate concordance at best. These findings elevate the importance of asking autistic youth directly about their executive functioning when engaging them in assessment and intervention, or researching executive functions in autism.


Exposure to Music Alters Cell Viability and Cell Motility of Human Nonauditory Cells in Culture.
Although music is part of virtually all cultures in the world, little is known about how it affects us. Since the beginning of this century several studies suggested that the response to music, and to sound in general, is complex and might not be exclusively due to emotion, given that cell types other than auditory hair cells can also directly react to audible sound. The present study was designed to better understand the direct effects of acoustic vibrations, in the form of music, in human cells in culture. Our results suggest that the mechanisms of cell growth arrest and/or cell death induced by acoustic vibrations are similar for auditory and nonauditory cells.


Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: a randomized controlled trial.
Megestrol acetate (MA) (Bristol-Myers Squibb Co., Princeton, NJ) increases weight gain in AIDS and cancer patients and in age-related cachexia; however, the weight gain is predominately fat. We determined if adding resistance exercise and/or testosterone (T) replacement to MA administration would result in a more favorable body composition change than MA alone. Thirty older men (aged 67.0 +/- 5.8) completed this 12-wk study. All subjects received MA and were randomly assigned to one of the following groups: placebo (P) injections, resistance training (RT) and P (RT + P), weekly injections of T (100 mg/wk) or, RT and T (RT + T). The mean increase in body weight for all groups combined was 3.8 kg (P < 0.0001), but this increase was not different between groups. There was a significant interaction for the change in thigh muscle cross-sectional area (P = 0.0006). Thigh muscle cross-sectional area was significantly reduced from baseline by 5.20 [1.62] cm(2) (P = 0.05) in P which was not prevented in T [-4.44 (1.66) cm(2) from baseline; P = 0.04]. RT prevented this decline [+0.61 (1.41) cm(2) from baseline]. Muscle cross-sectional area increased 4.51 (1.69) cm(2) from baseline in RT + T (P = 0.002 vs. P and P = 0.002 vs. T). Despite significant weight gain, MA appears to have an antianabolic effect on muscle size even when combined with T replacement. Resistance exercise attenuated this reduction in muscle mass and when combined with T had an anabolic effect on muscle mass.


A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability.
The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs) - PLANETRA and PLANETAS - performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies.