Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2.
The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective genes leading to pathogenic expansions of polyglutamine stretches in the encoded proteins. In general, unstable CAG repeats have an uninterrupted CAG repeat, whereas stable CAG repeats are either short or interrupted by CAA codons, which - like CAG codons - code for glutamine. Here we report on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency of paternal germ-line repeat sequence instability of the expanded SCA2 locus.


In situ estrogen metabolism in proliferative endometria from untreated women with polycystic ovarian syndrome with and without endometrial hyperplasia.
The aim of the present investigation was to study whether the endocrinological status of women bearing polycystic ovarian syndrome (PCOS) affects the endometrial in situ steroid metabolism. For this purpose, we evaluated the mRNA levels (RT-PCR), and the activity of steroid metabolic enzymes: P450 aromatase, steroid sulfatase (STS), estrogen sulfotransferase (EST) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in 23 samples of normal endometria (CE), 18 PCOS endometria without treatment (PCOSE), 10 specimens from PCOS women with endometrial hyperplasia (HPCOSE), and 7 endometria from patients with endometrial hyperplasia not associated to PCOS (EH). The data showed lower levels of STS mRNA for PCOSE and HPCOSE (p<0.05, p<0.01, respectively) and of EST for HPCOSE and EH compared to control (p<0.05). However, higher levels for EST mRNA were obtained in PCOSE (p<0.05) versus CE. The mRNA and protein levels for P450 aromatase were undetectable in all analyzed endometria. The relationship between the activities of STS and EST was lower in PCOSE and HPCOSE (p<0.05) versus CE. The ratio between the mRNA from 17beta-HSD type 1/type 2 was higher in PCOSE (p<0.05), whereas, a diminution in the 17beta-HSD type 2 activity was observed in PCOSE (p<0.05). These results indicate that the activity of enzymes related to the steroid metabolism in analyzed PCOSE differ from those found in the CE. Consequently, PCOSE may present an in situ deregulation of the steroid metabolism.


Tolerance induction during ontogeny. II. Distinct unresponsive states in immature mice question the generality of clonal abortion.
Multivalent trinitrophenyl (TNP) conjugates of both human gamma-globulin (HGG) and bovine serum albumin (BSA) are capable of inducing hapten-specific unresponsiveness in neonatal mice, as assessed by challenge with TNP on thymus-dependent carriers. When such mice are challenged with TNP on thymus-independent carriers, however, only TNP-HGG- but not TNP-BSA-treated mice are found to be substantially unresponsive to the hapten. Moreover, unresponsiveness induced by BSA, but not HGG, as a carrier was associated with the presence of antigen-specific suppressor cells. Thus, contrary to predictions made by defendants of the classical clonal abortion hypothesis, functional deletion of hapten-specific B cells appears to depend on the nature of the hapten-carrier complex. This conclusion is supported by B cell-precursor frequency estimates indicating that the number of hapten-specific precursor cells is significantly lower in TNP-HGG-treated mice, but remains unaltered in TNP-BSA-treated mice relative to the precursor frequency in untreated animals. While it remains a formal possibility that the differences in tolerogenicity seen between the two carriers can be interpreted in terms of a difference in serum half-life, we favor the interpretation that the distinction lies in molecular aspects of the carrier, which allow for differences in antigen handling by sets of interacting cells.


Crystal structure of a synthetic cyclodecapeptide for template-assembled synthetic protein design.
The structural prototype of a new generation of regioselectively addressable functionalized templates (RAFTs) for use in protein de novo design has been synthesized and crystallized. The structure of the aromatically substituted cyclodecapeptide was determined by X-ray diffraction; it consists of an antiparallel beta sheet spanned by heterochirally induced type IIprime prime or minute beta turns, similar to that observed in gramicidin S. The three-dimensional structure of the artificial template was also examined by an NMR spectroscopic analysis in solution and shown to be compatible with a beta-sheet plane suitable for accommodating secondary functional peptide fragments for the synthesis of template-assembled synthetic proteins (TASPs).


White Paper: SSAT Commitment to Workforce Diversity and Healthcare Disparities.
The Society for Surgery of the Alimentary Track (SSAT) is committed to diversity and inclusiveness of its membership, promotion of research related to healthcare disparities, cultural competency of practicing gastrointestinal surgeons, and cultivation of leaders with unique perspectives. The SSAT convened a task force to assess the current state of diversity and inclusion and recommend sustainable initiatives to promote these goals. Working through the current committee structure of the Society, and by establishing a permanent Diversity and Inclusion liaison committee, the SSAT will maintain its commitment and strive towards diversity of thought and inclusiveness on every level to improve the well-being and betterment of its membership and the patients they serve.


Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study.
Hyperpolarized (HP) 13C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP 13C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera. Six patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized 13C-pyruvate, where pyruvate-to-lactate conversion rate (kPL) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses. We observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean kPL value of 0.020 ± 0.006 (s-1) and 0.026 ± 0.000 (s-1) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high kPL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of kPL from 0.026 at baseline to 0.015 (s-1) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9). HP 13C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative kPL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP 13C-pyruvate MRI in the setting of advanced prostate cancer.


Antidiuretic factor from the nervous corpora cardiaca of the migratory locust: improvement of an existing in vitro bioassay.
Nervous lobes of the migratory locust corpora cardiaca contain an antidiuretic (AD) factor which increases the fluid reabsorption of isolated recta in a dose-dependent manner. Several extraction procedures were developed and compared. The very satisfactory thermostability of the AD factor was demonstrated. By using a succession of different incubating media on the same preparation, we improved our bioassay. The developed variant is faster and more sensitive than the existing test and saves time and biological material.


The prevalence of chondrocalcinosis (CC) of the acromioclavicular (AC) joint on chest radiographs and correlation with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease.
Digital imaging combined with picture archiving and communication system (PACS) access allows detailed image retrieval and magnification. Calcium pyrophosphate dihydrate (CPPD) crystals preferentially deposit in fibrocartilages, the cartilage of the acromioclavicular (AC) joint being one such structure. We sought to determine if examination of the AC joints on magnified PACS imaging of chest films would be useful in identifying chondrocalcinosis (CC). Retrospective radiographic readings and chart reviews involving 1,920 patients aged 50 or more who had routine outpatient chest radiographs over a 4-month period were performed. Knee radiographs were available for comparison in 489 patients. Medical records were reviewed to abstract demographics, chest film reports, and diagnoses. AC joint CC was identified in 1.1 % (21/1,920) of consecutive chest films. Patients with AC joint CC were 75 years of age versus 65.4 in those without CC (p < 0.0002). Four hundred eighty-nine patients had knee films. Six of these patients had AC joint CC, and of these, five also had knee CC (83 %). Of the 483 without AC joint CC, 62 (12 %) had knee CC (p = 0.002). Patients with AC joint CC were more likely to have a recorded history of CPPD crystal deposition disease than those without AC joint CC (14 versus 1 %, p = 0.0017). The prevalence of AC joint CC increases with age and is associated with knee CC. A finding of AC joint CC should heighten suspicion of pseudogout or secondary osteoarthritis in appropriate clinical settings and, in a young patient, should alert the clinician to the possibility of an associated metabolic condition.


Nurse staffing and life expectancy at birth and at 65 years old: Evidence from 35 OECD countries.
To measure the possible magnitude of the role nurse staffing has on increasing life expectancy at birth and at 65 years old. The statistical technique of panel data analysis was applied to investigate the relationship from the number of practicing nurses' density per 1000 population to life expectancy at birth and at 65 years old. Five control variables were used as the proxies for the levels of medical staffing, health care financial and physical resources, and medical technology. The observations of 35 member countries of Organization for Economic Co-operation and Development (OECD) were collected from OECD Health Statistics over 2000-2016 period. There were meaningful relationships from nurse staffing to life expectancy at birth and at 65 years with the long-run elasticities of 0.02 and 0.08, respectively. Overall, the role of nursing characteristics in increasing life expectancy indicators varied among different health care systems of OECD countries and in average were determined at the highest level in Japan (0.25), followed by Iceland (0.24), Belgium (0.21), Czech Republic (0.21), Slovenia (0.20) and Sweden (0.18). A higher proportion of nursing staff is associated with higher life expectancy in OECD countries and the dependency of life expectancy to nursing staff would increase by aging. Hence, the findings of this study warn health policy makers about ignoring the effects nursing shortages create e.g. increasing the risk of actual age-specific mortality, especially in care of elderly people.


Extended sphere method for complete investigation of the phase-matching properties of sum- and difference-frequency generation.
We demonstrate the feasibility of a complete experimental investigation of the phase-matching properties of sum- and difference-frequency generation in a single crystal cut as a sphere over its entire transparency range. The class of the studied crystal is the only initial data that is required. This feasibility study was carried out with rubidium titanyl arsenate.


Alantolactone induces concurrent apoptosis and GSDME-dependent pyroptosis of anaplastic thyroid cancer through ROS mitochondria-dependent caspase pathway.
Anaplastic thyroid cancer (ATC) is one of the fatal cancers and has not effective treatments. Alantolactone (ATL), a terpenoid extracted from traditional Chinese medicinal herb Inula helenium L., confers significant anti-inflammatory, antibacterial and antitumor activity. However, the activity and mechanisms of ATL in ATC remain unclear. To investigate the potential anti-ATC effects in vitro and in vivo and the mechanisms involved. The anti-proliferative activity of Alantolactone (ATL) against ATC cells was analyzed through CCK-8 and colony formation assays. Flow cytometry assay was performed to assess the cell cycle, cell apoptosis, ROS, and mitochondrial membrane potential (ΔΨm), whereas the cellular localization of cytochrome c and calreticulin were determined using cellular immunofluorescence assays. The lactate dehydrogenase (LDH) enzyme activity in the cell culture medium was measured using a commercial LDH kit, whereas ELISA was conducted to assess the secretory function of IL-1β. Western blot assays were conducted to determine the expression or regulation of proteins associated with apoptosis and pyroptosis. Subcutaneous tumor model of nude mice was established to evaluate the anticancer activity of ATL in vivo. The expression of Ki67, cyclin B1, cleaved-PARP, cleaved-caspase 3, and IL-1β in the animal tumor tissues was profiled using immunohistochemistry analyses. Our data showed that ATL significantly inhibited the proliferation and colony formation activity of ATC cells. ATL induced ATC cell cycle arrest at G2/M phase, and downregulated the expression of cyclin B1 and CDC2. Furthermore, ATL induced concurrent apoptosis and pyroptosis in the ATC cells, and the cleavage of PARP and GSDME. It also significantly increased the release of LDH and IL-1β. Mechanically, ATL-mediated increase in ROS suppressed the Bcl-2/Bax ratio, downregulated the mitochondrial membrane potential and increased the release of cytochrome c, leading to caspase 9 and caspase 3 cleavage. We also found that ATL induced the translocation of an immunogenic cell death marker (calreticulin) to the cell membrane. In addition, it inhibited the growth of the ATC subcutaneous xenograft model, and activated proteins associated with apoptosis and pyroptosis, with a high safety profile. Taken together, these results firstly demonstrated that ATL exerted an anti-ATC activity by inducing concurrent apoptosis and GSDME-dependent pyroptosis through ROS-mediated mitochondria-dependent caspase activation. Meanwhile, these cell deaths exhibited obvious characteristics of immunogenic cell death, which may synergistically increase the potential of cancer immunotherapy in ATC. Further studies are needed to explore deeper mechanisms for the anti- ATC activity of ATL.


[Possibilities and limitations of color duplex guided compression therapy of puncture-induced blood vessel lesions in the groin].
Colour Doppler imaging (CDI) is a useful tool for non-invasive diagnosis and treatment of postcatheterisation lesions of the femoral artery. The aim of the present study was to evaluate success and limitations of the method in unselected patients. A total of 29 patients, including 24 patients with pseudoaneurysms and 5 patients with arteriovenous fistulas, were treated by CDI-guided compression therapy. 17 of 24 (71%) pseudoaneurysms, but only 1 of 5 (20%) arteriovenous fistulas were successfully occluded. Successful treatment of pseudoaneurysms was limited by continuous anticoagulation and local pain during compression. However, arteriovenous fistulas, except one, could not be occluded due to high flow velocities in the shunt. CDI-guided compression therapy is the treatment of choice for postcatheterisation pseudoaneurysms, while arteriovenous fistulas should be repaired surgically. If possible, anticoagulation therapy should be discontinued and analgesic drugs should be prescribed.


Asymmetries of the skull and handedness. Phrenology revisited.
Some of the asymmetries noted in cerebral computerized transaxial tomography (CTT) studies are reflected in the shape of the skull resulting most often in backward protrusion of the occipital bone on the left and a less striking forward protrusion of the right frontal bone. Asymmetries are less marked in left-handed individuals but the opposite features, i.e. forward protrusion of the left frontal bone and posterior protrusion of the right occipital bone, are more frequent in left handers than in right handers.


Declined placental PLAC1 expression is involved in preeclampsia.
This study aimed to clarify the change of the expression of placenta-specific 1 (PLAC1) in the placenta of preeclamptic women and to explore the regulatory effects on thophoblast by PLAC1. Nineteen women with preeclampsia and 19 with normal pregnancies were recruited, and then we determined the expression of PLAC1 by immunohistochemistry (IHC) and Western blotting. To observe the effect of hypoxia on the expression of PLAC1, trophoblasts were cultured at the normoxia or hypoxia condition. Small interference of ribonucleic acid (siRNA) was used to silence PLAC1. The proliferation, migration and invasion of trophoblasts were evaluated with cell counting kit-8 and transwell analysis, and the apoptosis of trophoblast was evaluated by flow cytometry with FITC and PI staining. Placental PLAC1 expression was significantly decreased in severe preeclampsia compared with control (P < .001). The expression of PLAC1 in trophoblasts was significantly decreased after treated with low oxygen concentration (P = .018). PLAC1 siRNA significantly inhibited the proliferation (P < .001), the migration (P < .001) and invasion (P < .001) of trophoblasts, but increased the apoptosis (P = .004 for Swan-71; P = .031 for Jar). The expression of PLAC1 was declined in preeclampsia and this inhibited the function of trophoblast, suggesting PLAC1 may play a role in the development of preeclampsia.


Unusual presentation of localized gingival enlargement associated with a slow-growing odontogenic myxoma.
Unusual presentation of localized gingival enlargement associated with a subjacent tumoural pathology is reported. The patient was a 55-year-old black male, whose chief complaint was a progressive gingival overgrowth for more than ten years, in the buccal area of the anterior left mandible. According to the clinical features and the radiological diagnosis of odontogenic keratocyst, a conservative surgery with enucleation and curettage was performed. Tissue submitted for histopathological analysis rendered the diagnosis of odontogenic myxoma. After 12-month of follow-up, no evidence of recurrence was found. Clinicians should be cautious when facing any gingival enlargement to avoid diagnostic pitfalls and to indicate the appropriate treatment.


Studies on plasmids of multidrug resistant uropathogens isolated from patients with urinary tract infection in a tertiary hospital in Calabar, Nigeria.
Urinary tract Infections caused by multidrug resistant uropathogens have become a significant global public health problem with Nigeria being no exception. This study is aimed at profiling and curing the plasmids of selected multidrug resistant uropathogens isolated from patients with urinary tract infection in a tertiary hospital in Calabar, Nigeria. Isolates were obtained from urine samples of patients using standard microbiological techniques. Multidrug resistant bacterial isolates were then selected for plasmid DNA analysis and curing. The study revealed that E. coli, K. pneumoniae, P. aeruginosa and Proteus mirabilis were resistant to the antibiotics tested. The extracted plasmid DNA showed the presence of TEM, SHV and CTX-M genes in the isolates with sizes of 400-600bp, 300bp and 500-800bp, respectively. All isolates possessed the SHV genes while few had TEM and CTX-M genes. Cells were subjected to curing and plasmid curing was achieved at 200-300µl of ethidium bromide. The reduction in percentage resistance due to plasmid curing observed in this study suggests that the resistance of the isolates to antibiotics were plasmid-mediated. Antibiogram and monitoring of plasmid mediated resistance are necessary for proper management of urinary tract infections.


Simplified capillary isoelectric focusing with chemical mobilization for intact protein analysis.
We report a capillary isoelectric focusing system based on a sequential injection method for simplified chemical mobilization. This system was coupled to an ion trap mass spectrometer with an electrokinetically pumped nanoelectrospray interface. The nanoelectrospray emitter employed an acidic sheath electrolyte. To simplify focusing and mobilization, a plug of ammonium hydroxide was first injected into the capillary, followed by a section of mixed sample and ampholyte. During focusing, the NH3 H2 O section worked as catholyte. As focusing progressed, the NH3 H2 O section was titrated to lower pH by the acidic sheath electrolyte. Chemical mobilization started automatically once the ammonium hydroxide was consumed by the acidic sheath flow electrolyte, which then acted as the mobilization solution. In this report, the lengths of the NH3 H2 O section and sample were optimized. With a 1 m long capillary, a relative short plug of the NH3 H2 O section (3 cm) produced both fast migration and reasonable separation resolution. The simplified capillary isoelectric focusing mass spectrometry system produced base peak intensity relative standard deviation of 8.5% and migration time relative standard deviation ≤0.6% for myoglobin and cytochrome C in triplicate runs.


[BCGitis/BCGosis in children: Diagnosis, classification and exploration].
The Bacille Calmette-Guérin (BCG) vaccine is used extensively worldwide, and more than 100 million children are vaccinated each year. This is a live vaccine that protects against severe tuberculosis in children. However, BCG complications, specific to the BCG vaccine, do occur, although the epidemiology differs from one country to another. Nevertheless, these complications are considered to be rare and range from benign local BCGitis to BCGosis, a potentially lethal disseminated disease. Etiologies of BCGitis/BCGosis can be related to the vaccine itself (technical errors, vaccinal strain) or to the patient. Indeed, it is well established that some immunodeficiencies, primary or acquired, can expose the patient to BCG disease. The diagnosis of a BCG disease lies on clinical examination and laboratory results. Recent advances in molecular biology help to distinguish BCG disease from other mycobacterial infections, especially from tuberculosis. When BCG complications have been confirmed, the underlying defect should be investigated, particularly if other features of immunodeficiency are reported, such as recurrent infection, failure to thrive, etc. Prognosis largely depends on the immune status, but also on the management of the BCG disease. Although the therapeutic protocols are still controversial, there are more and more publications on the diagnosis and management guidelines of the disease.


[Use of a new type of endoprosthesis in internal biliary drainage].
The authors, reporting the present value and importance of the interventional biliary radiology in the therapy of the obstructive inoperable jaundice, describe the features of a "long" endoprosthesis and its advantages in comparison with the common endoprosthesis.


Current management of postoperative complications and benign biliary strictures.
Postoperative complications after surgery of the biliary tract are usually amenable to endoscopic treatment. Such complications are most frequent after laparoscopic cholecystectomy. Bile leaks and bile duct strictures are the two main biliary injuries. Bile leaks are usually detected during the early postoperative period and can be treated by endoscopic drainage of the biliary tree (endoscopic sphincterotomy with or without nasobiliary drain). Postoperative biliary strictures are usually identified months or years after surgery. Endoscopic placement of an increasing number of plastic stents can achieve morphologic disappearance of the stricture and persistent dilation on long-term follow-up in most cases.


The effect of water temperature and velocity on barnacle growth: Quantifying the impact of multiple environmental stressors.
Organisms employ a wide array of physiological and behavioral responses in an effort to endure stressful environmental conditions. For many marine invertebrates, physiological and/or behavioral performance is dependent on physical conditions in the fluid environment. Although factors such as water temperature and velocity can elicit changes in respiration and feeding, the manner in which these processes integrate to shape growth remains unclear. In a growth experiment, juvenile barnacles (Balanus glandula) were raised in dockside, once-through flow chambers at water velocities of 2 versus 19 cm s(-1) and temperatures of 11.5 versus 14 °C. Over 37 days, growth rates (i.e., shell basal area) increased with faster water velocities and higher temperatures. Barnacles at high flows had shorter feeding appendages (i.e., cirri), suggesting that growth patterns are unlikely related to plastic responses in cirral length. A separate experiment in the field confirmed patterns of temperature- and flow-dependent growth over 41 days. Outplanted juvenile barnacles exposed to the faster water velocities (32±1 and 34±1 cm s(-1); mean±SE) and warm temperatures (16.81±0.05 °C) experienced higher growth compared to individuals at low velocities (1±1 cm s(-1)) and temperatures (13.67±0.02 °C). Growth data were consistent with estimates from a simple energy budget model based on previously measured feeding and respiration response curves that predicted peak growth at moderate temperatures (15 °C) and velocities (20-30 cm s(-1)). Low growth is expected at both low and high velocities due to lower encounter rates with suspended food particles and lower capture efficiencies respectively. At high temperatures, growth is likely limited by high metabolic costs, whereas slow growth at low temperatures may be a consequence of low oxygen availability and/or slow cirral beating and low feeding rates. Moreover, these results advocate for approaches that consider the combined effects of multiple stressors and suggest that both increases and decreases in temperature or flow impact barnacle growth, but through different physiological and behavioral mechanisms.


Cost-effectiveness of 20-valent pneumococcal conjugate vaccine compared with 23-valent pneumococcal polysaccharide vaccine among adults in a Norwegian setting.
The morbidity and mortality of adult diseases caused by S. pneumoniae increase with age and presence of underlying chronic diseases. Currently, two vaccine technologies against S. pneumoniae are used: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccines, one of which is the 20-valent pneumococcal conjugate vaccine (PCV20) that has recently been approved for adults. This study was conducted to investigate the cost-effectiveness of implementing PCV20 in a reimbursement scheme for Norwegian adults aged 18-99 years at risk of pneumococcal diseases and those aged 65 years and older at low risk compared to PPV23. An established Markov model was adapted to a Norwegian setting to estimate the economic and clinical consequences of vaccinating the Norwegian population in specific age and risk groups against pneumococcal diseases. Inputs for the model were found in Norwegian or Danish real-world evidence or retrieved from available studies. The costs and clinical outcomes were assessed using a health sector perspective and a lifetime time horizon. The results showed that PCV20 was associated with better health outcomes including fewer disease cases, fewer disease-attributable fatalities, a higher gain of life years and quality-adjusted life years compared to PPV23. In addition, PCV20 had a lower total cost compared to PPV23. Therefore, PCV20 was the dominant vaccination strategy. The base case result was investigated in multiple sensitivity analyses, which showed that the results were robust to changes in input parameters and methodological assumptions, as PCV20 remained the dominant vaccination strategy in almost all scenarios. Results showed that vaccinating the Norwegian adults with PCV20 was cost-effective compared to PPV23. Changes in the hospital cost of pneumonia, the price of PCV 20, the effectiveness of PCV20 against pneumonia, and the pneumonia disease incidence had the highest impact on the ICER, i.e., were the main drivers of the results.


Mirror training device improves dental students' performance on virtual simulation dental training system.
Clinical practice of dentistry entails the use of indirect vision using a dental mirror. The Mirrosistant is a device that helps dental students become proficient with use of indirect vision mirror operation. This study aimed to explore the role of the Mirrosistant on students' performance with the virtual simulation dental training system. A total of 72 dental students were equally assigned to the Control group and the Experimental group. Subsequently, Mirrosistant was used to conduct a series of mirror training exercises in the Experimental group. The training consisted of tracing the edge and filling in the blank of the prescribed shape, as well as preparing the specified figure on raw eggs using indirect vision via Mirrosistant. Next, both groups were examined using the SIMODONT system, a virtual reality dental trainer, for mirror operation. In addition, a five-point Likert scale questionnaire was used to assess student feedback by using Mirrosistant. The mirror operation examination conducted by the SIMODONT system revealed that mirror training using Mirrosistant had statistically improved students' performances (score: 80.42 ± 6.43 vs. 69.89 ± 15.98, P = 0.0005) and shorten their performance time of mirror operation (time of seconds: 243.28 ± 132.83 vs. 328.53 ± 111.89, P = 0.0013). Furthermore, the questionnaire survey indicated that the participants had positive attitudes toward the mirror training using Mirrosistant. Most students believed that the mirror training device could improve their perceptions of direction and distance, as well as their sensations of dental operation and dental fulcrum. Mirror training using Mirrosistant can enhance dental students' mirror perceptual and operational skills on virtual simulation dental training system.


Renal cell carcinoma in a transplanted kidney: MR imaging findings.
We report the MR findings of a 42-year-old man who developed renal cell carcinoma in an allograft kidney, 10 years after transplantation. The lower pole of the transplant kidney showed a solid lesion which was well shown on the post gadolinium fat suppressed images as a heterogeneously enhancing 2 cm mass lesion.


Detection of Cladosporium spinulosum on an engraving by Rembrandt and susceptibility profile to eco-friendly antifungal treatments.
Interdisciplinary studies on cultural heritage artworks provide efficient solutions to control fungal growth and the negative effects of biodeterioration. In this study, we aimed to identify the population of filamentous fungi colonizing an engraving by the Dutch painter Rembrandt, whose conservation status was compromised and showed visible stains of biodeterioration. Microbiological techniques, such as cultivation-dependent approaches and molecular biology, have been used to identify fungal populations. In addition, the anaerobic atmosphere technique and eco-friendly antifungal agents, such as essential oils (EOs) of Curcuma longa, Thymus vulgaris, and Melaleuca alternifolia, were tested against the metabolically active fungal population Cladoposporium spinulosum. Furthermore, in vitro assays revealed that the interaction between the fungal strains and EO was positive, inhibiting the growth of these fungi, and the EOs from T. vulgaris and M. alternifolia showed low minimum inhibitory concentration values. Exposure to anaerobic conditions for 35 days was effective in the total elimination of isolated fungal strains. In conclusion, this study demonstrated the effectiveness of a nondestructive technique for artwork on engraving colonized by fungal strains and using EO as an alternative to toxic antifungals used in conventional treatments in artworks. Thus, this interdisciplinary study involving applied microbiology and botanical and preventive conservation presents a tool to control microbial growth while maintaining artwork integrity.


Clinical everolimus experience in pediatric renal transplant patients.
Everolimus is a potent immunosuppressive agent that has antiproliferative activities. This study sought to share our experience among renal transplanted children who required conversion from calcineurin inhibitors (CNIs) to the mammalian target of rapamycin inhibitor everolimus. Exclusion criteria were multiple organ transplantations, loss of a previous graft due to immunologic reasons, receipt of an organ donated after cardiac death, donor age <5 years or >65 years, panel reactive antibodies >25%, platelets <75,000/mm(3), absolute neutrophil count of <1,500/mm(3), leucocytes <2,500/mm(3), hemoglobin <6 g/dL, severe liver disease, cold ischemia time >40 hours or anti-HLA panel-reactive antibodies >50%. Eighteen renal transplant patients (10 male, 8 female) underwent conversion to everolimus from CNI: 8 from cyclosporine (CsA) and 10 from tacrolimus. The mean age was 12.6 ± 0.9 years and the mean body mass index 21.8 ± 1.7 kg/m(2). The mean 2-hour postdose level of CsA before conversion was 671 ± 142 ng/mL; the patients on tacrolimus showed a mean trough concentration of 4.5 ng/mL. Six (33,3%) were taking mycophenolate mofetil and 12 (66.6%) enteric-coated mycophenolate sodium. No significant changes were observed in either hepatic functions, serum lipids, or hemograms. There was no mortality or graft loss. The mean level of serum creatinine was 1.3 ± 0.7 mg/dL before and 1.09 ± 0.6 mg/dL after conversion. Proteinuria observed in only 1 patient was well controlled with angiotensin-converting enzyme inhibitor therapy. All patients responded to statin therapy. One patient developed unilateral lower extremity edema and 1 a lymphocele. Although there were 3 cases (14%) of biopsy-confirmed acute rejection, there was no mortality or graft loss. Everolimus conversion has become an excellent choice, offering safety and efficacy with good outcomes.


Healthcare and Social Needs Assessment and Response Quality Among Black Men.
To understand Black men's healthcare and social needs and determine if the resources that healthcare systems offer meet expectations. We surveyed men who had previously participated in at least one Minority Men's Health Fair in Cleveland, Ohio. In this descriptive study, we spoke with men up to three times (i.e., phases) between May and October 2020 by email and/or telephone. Phase 1 was a needs assessment survey. Phase 2 involved outreach to those who identified a need to provide a resource. Phase 3 determined whether the resource met individuals' needs. We described the demographic characteristics of the survey respondents, the percentage of men reporting a need and wanting a resource, and whether the resource resolved their need. Of the 768 men contacted, 275 completed the survey (36% response rate). The majority of respondents were 50-69 years old, identified as Black, and had at least a bachelor's degree. Eighty-five percent reported a need, of which wellness, financial, and healthcare access were among the top-reported needs. Among the men identifying a need, 35% were interested in a resource. Resources that were provided for employment, behavioral health, oral health, vision, or wellness needs were deemed insufficient. A few individuals reported that resources for food/personal hygiene, financial support, health care access, annual health screening, and medication met their needs. Among men with healthcare and social needs, only a fraction were interested in a resource, and fewer reported that the resource met their needs. These results warrant a greater understanding of what constitutes a resolution of healthcare and social needs from patients' perspectives.


Possibility of active targeting to tumor by local hyperthermia with temperature-sensitive nanoparticles.
Recently, the concept of drug delivery requires that the release of encapsulated drug be produced only at the diseased site with controllable rates. Given that thermosensitive hydrogels have been widely investigated for controlled delivery based on their phase transition, we speculate that nanoparticles with the novel polymers play a key role in tumor therapy respond to thermal activity. Therefore, we here hypothesize that enhanced delivery of therapeutics might be achieved by conjugation to thermosensitive polymers, in concert with targeted hyperthermia by precisely specifying the phase transition temperature of the thermosensitive polymer. By local hyperthermia at tumor site, a targeted drug delivery system could be obtained, exploiting both the temperature-sensitive and the site-specific behaviors. The proposition may provide a new strategy into the development of a novel drug delivery system for tumor therapy.


Pancreatic insulin content regulation by the estrogen receptor ER alpha.
The function of pancreatic beta-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ER alpha and ER beta, are important molecules involved in glucose metabolism, yet their role in pancreatic beta-cell physiology is still greatly unknown. In this report we show that both ER alpha and ER beta are present in pancreatic beta-cells. Long term exposure to physiological concentrations of 17beta-estradiol (E2) increased beta-cell insulin content, insulin gene expression and insulin release, yet pancreatic beta-cell mass was unaltered. The up-regulation of pancreatic beta-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA). The use of ER alpha and ER beta agonists as well as ER alphaKO and ER betaKO mice suggests that the estrogen receptor involved is ER alpha. The up-regulation of pancreatic insulin content by ER alpha activation involves ERK1/2. These data may be important to explain the actions of E2 and environmental estrogens in endocrine pancreatic function and blood glucose homeostasis.


Barrier spraying to control the malaria vector Anopheles albimanus: laboratory and field evaluation in the Dominican Republic.
To develop a new strategy for control of exophilic/exophagic malaria vectors which rest on peridomestic foliage, Anopheles albimanus was used for laboratory bioassays of mosquito adulticides applied to various vegetation types. Of the three classes of insecticide tested, the pyrethroid (permethrin at 112 g/ha) showed greater foliar persistence than either the carbamate (bendiocarb at 340 g/ha) or the organophosphorus compound (malathion at 277 g/ha). Field evaluation of barrier spraying against An.albimanus was evaluated in rural villages of southwest Dominican Republic during 1989. The pyrethroid deltamethrin was sprayed aerially for ultra-low volume application at treatment rates of 17-19 g a.i./ha in a radius of 500 m around two villages. An.albimanus were monitored by light-traps and human bait collections at both treated villages, compared with two similar untreated villages, up to 9 nights posttreatment. Densities of female An.albimanus were significantly reduced in the sprayed villages for at least 8 or 9 nights. Further evaluation of barrier spraying is recommended to determine optimal pyrethroid formulations and applications rates, their impact on non-target fauna and efficacy against malaria transmission.


Neodymium-YAG laser intranasal photocoagulation in hereditary hemorrhagic telangiectasia: an update report.
Hereditary hemorrhagic telangiectasia is a challenging problem for the otolaryngologist since frequent, often severe epistaxis is the major symptom. Options for therapy in the past have included nasal packing, electrocautery, systemic estrogens, septal dermatoplasty, arterial embolization, and arterial ligation. Although successful treatment has been achieved with some of these methods, particularly septal dermatoplasty, other forms of therapy are needed prompting the use of laser photocoagulation. The neodymium yttrium-aluminum-garnet (Nd-YAG) laser was used to treat a group of 19 patients with hereditary hemorrhagic telangiectasia over a 4-year period without complications. Endonasal laser photocoagulation was effective in decreasing epistaxis in patients not requiring frequent transfusions prior to laser therapy. Three patients with the most severe epistaxis received minimal or no benefit from Nd-YAG laser photocoagulation. In most patients Nd-YAG photocoagulation is successful in treating epistaxis associated with hereditary hemorrhagic telangiectasia and should be a therapeutic option for this chronic disease having no available cure.


Efficacy and safety of zonisamide as the first additional treatment in Chinese patients with focal or secondary bilateral tonic-clonic seizures: An observational ,prospective study.
To evaluate the efficacy and safety of zonisamide (ZNS) as the first additional treatment for focal or secondarily bilateral tonic-clonic seizure (sBTCS). A total of 118 patients between 18 and 75 years of age with focal or sBTCS were recruited from multiple hospitals in Shandong province between May 13, 2021, and February 16, 2022. All received ZNS as the first additional treatment after clinical judgment. Seizure frequency, retention, and adverse events (AEs) were assessed 2 and 5 months after the introduction of ZNS. Overall response rates at 2 and 5 months were 79.5% and 75.5%, respectively, whereas seizure-free rates at the same point were 53.6% and 51%, respectively. The review's retention rates at 2 and 5 months were 95% and 86%, respectively. The most common AEs were anorexia with weight loss (11.8%), dizziness (6.9%), and headache (3.9%). Our real-world study confirmed the efficacy and safety of ZNS as a first-additional treatment for focal or sBTCS in Chinese patients, with a high short-term retention rate.


Preparation and properties of rabbit-muscle glyceraldehyde-phosphate dehydrogenase with equal binding parameters for the third and fourth NAD+ molecules.
1. A method of preparing rabbit-muscle glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 126.96.36.199) is described which yields a preparation differing in important respects from those previously described and resembling the enzyme isolated from sturgeon muscle. 2. Direct binding measurements at 25 degrees C by equilibrium gel filtration fit dissociation constants for the first two molecules that are too low to be measured by this technique and 0.9 micrometer for the third and fourth molecules. The dissociation constant of the fourth molecule is much lower than that previously reported for the rabbit-muscle enzyme. 3. In contrast to previous results with the rabbit-muscle enzyme, the increase in absorbance at 360 nm between three and four molecules of NAD+ bound to the enzyme was, within experimental error, the same as that with each of the first three molecules. 4. Data on the quenching of the protein fluorescence by NAD+ at 15 degrees C at different enzyme concentrations closely fit dissociation constants of 0.028 micrometer for the first two molecules and 0.27 micrometer for the third and fourth molecules.


Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling.
Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various central nervous system diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Herein, we uncovered the function and underlying mechanism of the circRNA UCK2 (circUCK2) in ischemia stroke. The oxygen-glucose deprivation model in HT-22 cells was used to mimic ischemia stroke in vitro. Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Middle cerebral artery occlusion was conducted to evaluate the function of circUCK2 in mice. The levels of circUCK2 were significantly decreased in brain tissues from a mouse model of focal cerebral ischemia and reperfusion. Upregulated circUCK2 levels significantly decreased infarct volumes, attenuated neuronal injury, and improved neurological deficits. circUCK2 reduced oxygen glucose deprivation (OGD)-induced cell apoptosis by regulating transforming growth factor β (TGF-β)/mothers against decapentaplegic homolog 3 (Smad3) signaling. Furthermore, circUCK2 functioned as an endogenous miR-125b-5p sponge to inhibit miR-125b-5p activity, resulting in an increase in growth differentiation factor 11 (GDF11) expression and a subsequent amelioration of neuronal injury. Consequently, these findings showed that the circUCK2/miR-125b-5p/GDF11 axis is an essential signaling pathway during ischemia stroke. Thus, the circRNA circUCK2 may serve as a potential target for novel treatment in patients with ischemic stroke.


Vibrational assignment and structure of dibenzoylmethane. A density functional theoretical study.
Molecular structure and vibrational frequencies of 1,3-diphenyl-1,3-propanedione, known as dibenzoylmethane (DBM), have been investigated by means of density functional theory (DFT) calculations. The results were compared with those of benzoylacetone (BA) and acetylacetone (AA), the parent molecule. IR and Raman spectra of DBM and its deuterated analogue were clearly assigned. The calculated hydrogen bond energy of DBM is 16.15 kcal/mol, calculated at B3LYP/6-311++G** level of theory, which is 0.28 kcal/mol more than that of AA. This result is in agreement with the vibrational and NMR spectroscopy results. The molecular stability and the hydrogen bond strength were investigated by applying the Natural Bond Orbital analysis (NBO) and geometry calculations. The theoretical calculations indicate that the hydrogen bond in DBM is relatively stronger than that in BA and AA.


[A new experimental approach to evaluate the use of thermoplasticized gutta-percha for canal obturation].
The author describes a new method of thermoplasticized gutta-percha and examines the problems of this modern technique; particularly he discusses the problem of apical extension of root canal fillings, describing the results of an experimental study.


Inhibition of extranodal NK/T-cell lymphoma by Chiauranib through an AIF-dependent pathway and its synergy with L-asparaginase.
Extranodal NK/T-cell lymphoma (NKTL) is a rare and aggressive form of extranodal lymphoma with a poor prognosis. Currently, there are very limited treatment options for patients with advanced-stage disease or those with relapsed/recurrent disease. Here we show that Chiauranib, an orally small molecule inhibitor of select serine-threonine kinases (aurora B, VEGFRs, PDGFR, CSF1R, c-Kit), inhibited NKTL cell proliferation, induced cell cycle arrest, as well as suppressed the microvessel density in vitro and in vivo similar as in other types of cancer cells. Surprisingly, Chiauranib unfolded a new effect to induce apoptosis of NKTL cells by triggering AIF-dependent apoptosis other than the traditional cyt-c/caspase mitochondrial apoptosis pathway. The knockdown of AIF in vitro and in vivo dramatically blocked the efficacy of Chiauranib on NKTL. Mechanistically, the release of AIF from mitochondria is due to the upregulation of VDAC1 by the AKT-GSK3β pathway and activation of calcium-dependent m-calpain, which promotes the cleavage of VDAC1 and therefore permits the release of AIF. Notably, the low expression of Bax in both NKTL cells and patient tissues restrained the cyt-c release. It resulted in the inhibition of cyt-c/caspase mitochondrial pathway, suggesting that drugs targeting this traditional pathway may not be effective in NKTL. Furthermore, we found that L-asparaginase triggered CD95 (Fas/Apo-1)-caspase 8-caspase 3 apoptotic pathway in NKTL cells, and combination of Chiauranib and L-asparaginase exhibited a synergistic effect, suggesting a feasibility to combine these two drugs for effective treatment of NKTL. This study demonstrates Chiauranib's positive efficacy toward NKTL through the activation of the AIF-dependent apoptosis pathway for the first time. The novel and multi-targets of Chiauranib and the synergistic effect with L-asparaginase may provide a promising therapy for NKTL patients.


Pituitary adenoma and meningioma in the same patient. Report of three cases.
Three patients are presented in whom both pituitary adenoma and meningioma were found. The pituitary tumour was a prolactinoma in one case and non-secreting adenoma in the other two. In one case the meningioma originated from the planum sphenoidale and was seperate from the pituitary adenoma. Another patient had a parasellar meningioma, which was suspected preoperatively by different enhancement on the CT scan. In the third case, both tumours were mainly infradiaphragmatic and could not be differentiated preoperatively or intraoperatively. This appears to be the first case with both tumours below the diaphragm. The clinical, radiological and histopathological findings are presented.


Functional polymorphism of matrix metalloproteinase-9 (MMP9) gene is not associated with schizophrenia and with its deficit subtype.
The deficit subtype of schizophrenia is hypothesized to constitute a pathophysiologically distinct subgroup of schizophrenia patients suffering from enduring, idiopathic negative symptoms and various neuropsychological deficits. Matrix metalloproteinases (MMPs) are extracellularly acting endopeptidases the substrates of which are matrix and adhesion molecules. Recently, MMP9 has been shown to be involved in various forms of synaptic plasticity, learning and memory consolidation. The primary aim of the present study was to evaluate associations between the functional MMP-9 -1562C/T gene polymorphism and the deficit and non-deficit subtypes of schizophrenia. The study was conducted between 2009 and 2012. Deficit schizophrenia was diagnosed using the SDS. The sample consisted of 468 patients, Caucasians, of Polish descent with ICD 10 diagnosis of schizophrenia: 189 [51% males] were included in a non-deficit subgroup, 279 patients [53% males] were included in a deficit subgroup. The control group consisted of 532 subjects, Caucasians, of Polish descent [51% males]. MMP-9 -1562C/T gene polymorphism was genotyped using the fluorescence resonance energy transfer (FRET) method and the Light Cycler System 2.0. The frequencies of genotypes and alleles did not differ between the schizophrenia patients and control group. The deficit and non-deficit patients did not differ in terms of the genotype and allele frequencies. No differences were found in genotype and allele frequencies between the deficit patients and the controls and between the non-deficit patients and the controls. We found no evidence for the association between the functional MMP-9 -1562C/T gene polymorphism and deficit/non-deficit subtypes of schizophrenia.


A comparison of clinical outcomes and cost of radiofrequency catheter ablation for atrial fibrillation with monitored anesthesia care versus general anesthesia.
Monitored anesthesia care (MAC) or general anesthesia (GA) can be used during catheter ablation (CA) of atrial fibrillation (AF). However, each approach may have advantages and disadvantages with variability in operator preferences. The optimal approach has not been well established. The purpose of this study was to compare procedural efficacy, safety, clinical outcomes, and cost of CA for AF performed with MAC versus GA. The study population consisted of 810 consecutive patients (mean age: 63 ± 10 years, paroxysmal AF: 48%) who underwent a first CA for AF. All patients completed a preprocedural evaluation by the anesthesiologists. Among the 810 patients, MAC was used in 534 (66%) and GA in 276 (34%). Ten patients (1.5%) had to convert to GA during the CA. Although the total anesthesia care was longer with GA particularly in patients with persistent AF, CA was shorter by 5 min with GA than MAC (p < 0.01). Prevalence of perioperative complications was similar between the two groups (4% vs. 4%, p = 0.89). There was no atrioesophageal fistula with either approach. GA was associated with a small, ~7% increase in total charges due to longer anesthesia care. During 43 ± 17 months of follow-up after a single ablation procedure, 271/534 patients (51%) in the MAC and 129/276 (47%) patients in the GA groups were in sinus rhythm without concomitant antiarrhythmic drug therapy (p = 0.28). With the participation of an anesthesiologist, and proper preoperative assessment, CA of AF using GA or MAC has similar efficacy and safety.


[Dialectical Behavior Therapy (DBT)--developments and empirical evidence].
Dialectical Behavior Therapy has been initially designed and evaluated as an outpatient-treatment program for chronic suicidal female patients. Within the last years, several adaptations of DBT for specific comorbidities, other settings or other disorders related to emotion dysregulation have been developed. This report reviews conceptual aspects and the scientific evidence of initially designed Dialectical Behavior Therapy and the adaptations. Systematic literature search and systematic review. Recently, two meta-analyses which are based on randomized controlled trials conclude robust and stabile effects of DBT Evidence from further RCTs and other studies show promise for the properties of many DBT adaptations. The current review of the literature suggests a good effectiveness of DBT, especially on complex disorders with deficits in the field of emotion regulation.


Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth.
Ferroptosis has attracted increasing interest in cancer therapy. Emerging evidences suggest that naturally occurring naphthoquinones exhibit potent anti-glioma effects via various mechanisms. The anti-glioma effects of plumbagin were evaluated by in vitro and in vivo experiments. Anti-glioma mechanism of plumbagin was studied by proteomics, flow cytometry, MDA assay, western blot, and RT-PCR. Gene knockdown/overexpression, molecular docking, PharmMappper database, and coimmunoprecipitation were used to study the targets of plumbagin. Plumbagin showed higher blood-brain barrier penetration ability than that of lapachol and shikonin and elicited significant growth inhibitory effects in vitro and in vivo. Ferroptosis was the main mechanism of plumbagin-induced cell death. Mechanistically, plumbagin significantly downregulated the protein and mRNA levels of xCT and decreased GPX4 protein levels. NAD(P)H quinone dehydrogenase 1 (NQO1) was revealed as a plumbagin predictive target using PharmMappper database and molecular docking. Plumbagin enhanced NQO1 activity and decreased xCT expression, resulting in NQO1-dependent cell death. It also induced GPX4 degradation via the lysosome pathway and caused GPX4-dependent cell death. Plumbagin inhibited in vitro and in vivo glioma growth via targeting NQO1/GPX4-mediated ferroptosis, which might be developed as a novel ferroptosis inducer or anti-glioma candidate.


What Is the Utility of Posters? Qualitative Study of Participants at a Regional Primary Healthcare Conference in Asia.
Posters are used extensively as a mode of presentation at scientific conferences, but little is documented about their value to presenters or viewers. The study aimed to explore conference delegates' views and experiences of poster presentations, and their perceptions of the strengths and weaknesses of posters compared with oral presentations, and also to identify ways to enhance the educational value of posters. This was a qualitative study using brief, semi-structured, face-to-face interviews amongst delegates at a 3-day Asia Pacific regional academic primary care conference in Singapore. Interviews were digitally recorded, transcribed verbatim, and their contents analysed thematically. Eighty-nine interviews were analysed. Respondents were mainly early career researchers (58%), and a third were presenting (poster or oral) at the conference. Many positive attributes of posters were identified. For the viewers, these included the ability to gain a rapid overview of research activity (for "benchmarking", "updating", and "inspiration"); the ability to choose who to engage with and when, in contrast to the tightly scheduled oral sessions; and opportunity to discuss content in a leisurely and detailed fashion with the presenter. Presenters considered posters "less threatening" than oral presentations and valued posters for the networking opportunities they created. However, posters were reported to be more demanding on the skills of précis and their preparation was considered arduous and more expensive than an oral presentation. Posters were also perceived to have lower academic status and dominate the presenter's time at the conference, reducing the opportunities for them to see the work of others. Suggestions for incorporating technologies to enhance the impact of posters included QR codes to access more detailed information, pre-recorded presentations, and online interactive clarification sessions with poster authors. Posters are perceived as a valuable mode of presentation at scientific conferences by presenters and viewers. Their unique strengths challenge the perception that posters are somehow inferior to oral presentations, suggesting a need for their advantages to be promoted by researchers and conference organisers. The incorporation of technology within the traditional display may enhance poster utility. Given the time and money spent on academic conferences there is an urgent need to evaluate the different styles of presentation used at conferences and how they differ in their ability to impact on medical science knowledge and evidence-based clinical practice. The online version contains supplementary material available at 10.1007/s40670-022-01657-z.


Development and prospective validation of a risk score model in guiding individualized concurrent chemoradiotherapy in stage II nasopharyngeal carcinoma in intensity-modulated radiotherapy era.
We aimed to develop and prospectively validate a risk score model to guide individualized concurrent chemoradiotherapy (CCRT) for patients with stage II nasopharyngeal carcinoma (NPC) in intensity-modulated radiotherapy (IMRT) era. In total, 1220 patients who received CCRT or IMRT alone were enrolled in this study, including a training cohort (n = 719), a validation cohort (n = 307), and a prospective test cohort (n = 194). Patients were stratified into different risk groups by a risk score model based on independent prognostic factors, which were developed in the training cohort. Survival rates were compared by the log-rank test. The validation and prospective test cohorts were used for validation. Total tumor volume, Epstein-Barr virus DNA, and lactate dehydrogenase were independent risk factors for failure-free survival (FFS, all p < 0.05). A risk score model based on these three risk factors was developed to classify patients into low-risk group (no risk factor, n = 337) and high-risk group (one or more factors, n = 382) in the training cohort. In the high-risk group, CCRT had better survival rates than IMRT alone (5-year FFS: 82.6% vs. 74.0%, p = 0.028). However, there was no survival difference between CCRT and IMRT alone either in the whole training cohort (p = 0.15) or in the low-risk group (p = 0.15). The results were verified in the validation and prospective test cohorts. A risk score model was developed and prospectively validated to precisely select high-risk stage II NPC patients who can benefit from CCRT, and thus guided individualized treatment in IMRT era.


X-ray scattering study of activated Arp2/3 complex with bound actin-WCA.
Previous structures of Arp2/3 complex, determined in the absence of a nucleation-promoting factor and actin, reveal its inactive conformation. The study of the activated structure has been hampered by uncontrollable polymerization. We have engineered a stable activated complex consisting of Arp2/3 complex, the WCA activator region of N-WASP, and one actin monomer, and studied its structure in solution by small angle X-ray scattering (SAXS). The scattering data support a model in which the first actin subunit binds at the barbed end of Arp2, and disqualify an alternative model that places the first actin subunit at the barbed end of Arp3. This location of the first actin and bound W motif constrains the binding site of the C motif to subunits Arp2 and ARPC1, from where the A motif can reach subunits Arp3 and ARPC3. The results support a model of activation that is consistent with most of the biochemical observations.


Treatment of non-small cell lung cancer with external beam radiotherapy and high dose rate brachytherapy.
Between August 1985 and September 1989, 62 patients with medically inoperable or surgically unresectable, non-small cell lung cancer were treated with both external beam radiotherapy and high dose rate bronchial brachytherapy. Treatment consisted of external beam radiotherapy (5000-6000 cGy in 5-6 1/2 weeks) and weekly high dose rate bronchial brachytherapy (three to five fractions, 500 cGy at 1 cm from the source) delivered either concurrently or sequentially. Median survival for all patients was 13 months (m). Stage I and Stage IIIA-B patients had median survivals of 20 m and 10 m, respectively. Patients without nodal disease (No) had a significantly longer median survival compared to patients with regional node metastases (N1-3), 17 m versus 9 m. A total of 54 patients were evaluable for local tumor control analysis. Local tumor control was achieved in six of eight patients who had a normal pre-treatment radiograph. Patients with measurable tumor on the pre-treatment radiograph and negative regional nodes had local tumor control in eight of twenty-two (36%) cases. In patients with regional lymphadenopathy, loco-regional tumor control was achieved in four of eight cases. Additionally, there were sixteen patients with non-measurable tumor due to associated effusion, atelectasis and/or infiltrate. Four of these (25%) were considered to have local tumor control. Of 60 evaluable patients, there were nine occurrences of fatal hemorrhage, one of whom was disease-free (NED) at autopsy. The remaining eight patients had either clinical or pathological evidence of recurrent or persistent tumor. Patients who had follow up bronchoscopies were found to have varying degrees of concentric narrowing in the treated areas. One such patient had total lung collapse with no evidence of tumor. While this form of treatment may yield high local control rates in earlier stages, this study suggests the potential risk of fatal complication. Additional studies are warranted to further investigate the use of this modality in the treatment of lung cancer.


Effect of 7-year infancy-onset dietary intervention on serum lipoproteins and lipoprotein subclasses in healthy children in the prospective, randomized Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study.
We previously showed that low-saturated-fat dietary intervention from infancy until 5 years of age safely and effectively reduced serum cholesterol concentration. We now report how such intervention influenced serum lipids, LDL particle size, and HDL subfractions in children when they reached the age of 7 years. Healthy 7-month-old infants (n=1062) were randomized to the intervention (n=540) and control (n=522) groups. Each year, two individualized counseling sessions were organized to the intervention families. Serum lipid values were measured annually. The intervention boys had 0.20 to 0.39 mmol/L lower serum cholesterol values than the control boys throughout the follow-up (always P<0.05), but the values of the intervention and control girls did not differ. The LDL particle sizes and HDL subfractions were determined in a random subgroup of 96 intervention and 101 control children at the age of 7 years. The mean particle diameter of major LDL peak was 262.6 A in the intervention boys and 258.5 A in the control boys (P=0.05), and 259.2 A in the intervention girls and 261.3 A in the control girls (P=0.30). HDL2 and HDL3 cholesterol concentrations did not differ between the intervention and control children or between the two genders. The 7-year intervention favorably influenced not only the serum total and LDL cholesterol concentrations but also the LDL particle size in boys. LDL particle size remained unchanged in girls, as did HDL2 and HDL3 concentrations in both genders.


Luekocyte adherence inhibition in response to human orbital and lacrimal extracts in patients with Graves' ophthalmopathy.
Leukocyte adherence inhibition (LAI) may be a test for cell-mediated immunity or cytophilic antibodies. LAI tests were carried out on patients with Graves' ophthalmopathy, using normal human lacrimal gland, orbital fat, and eye muscle extracts as antigens. The results were expressed as % LAI. The percentage leukocyte adherence inhibition in tests from patients and normal subjects were not significantly different for any preparation (Mann-Whitney tests). Taking the upper limit of normal as the mean % LAI + 2SD for normal subjects, tests were positive, to eye muscle extract, in only one patient whilst borderline inhibition, in response to eye muscle and fat extracts respectively, was demonstrated in two patients. All three had active disease. LAI tests may be positive only during the acute stage of Graves' ophthalmopathy. The significance of these findings in respect to the pathogenesis of Graves' ophthalmopathy is discussed.


Cow's milk allergy presenting Hirschsprung's disease-mimicking symptoms.
The authors present a neonatal case of allergic colitis, which manifested the difficulty of spontaneous defecation and irregular narrowing of distal rectum in contrast enema. Rectal suction biopsy showed positive acetylcholinesterase activity. These clinical, radiological and histological findings were indistinguishable from Hirschsprung's disease. Gastrointestinal symptoms were improved by the cessation of cow's milk formula. The present findings may impact on the less recognizable gastrointestinal manifestation of allergic colitis.


COOH-terminal propeptides of the major human procollagens. Structural, functional and genetic comparisons.
The sequences of the carboxy-terminal extensions (COOH-propeptides) of at least one chain of all of the major human procollagens have only recently been deduced, and include those of the interstitial (alpha 1(I), alpha 2(I), alpha 1(II), alpha 1(III)), basement membrane (alpha 1(IV)) and pericellular (alpha 2(V)) procollagens. Comparisons of DNA and protein sequences, corresponding to these COOH-propeptides domains, established the early divergence of the basement membrane alpha 1(IV) COOH-propeptide from the corresponding sequences of the interstitial and pericellular procollagens. The latter are relatively highly conserved and share 58% primary peptide sequence similarities, whereas sequence similarities relative to alpha 1(IV) are limited. Hydropathy profiles and secondary structure potentials further emphasize the clustering of conserved and variable regions among the interstitial and pericellular COOH-propeptides, and provided further evidence for significant structural differences between these sequences and the alpha 1(IV) COOH-propeptide. The most highly conserved sequences of the alpha 1(I), alpha 2(I), alpha 1(II), alpha 1(III) and alpha 2(V) COOH-propeptides include regions surrounding the carbohydrate attachment site, cysteine-containing regions and the COOH-terminal sequences. Cysteinyl, tyrosyl and tryptophanyl residues were found to be highly conserved as were most charged residues. Localization of variable regions, in general, occurs within hydrophilic sequences with high beta-turn potentials that are proximal to intron/exon splice junctions. The most variable sequences are associated with the telopeptides and adjoining NH2-terminal portions of the COOH-propeptides as demonstrated by predictive secondary structure analyses. These results, combined with similar analyses of abnormal alpha 2(I) COOH-propeptide (osteogenesis imperfecta) permitted the identification of subsequences that are likely to be a prerequisite for COOH-propeptide functions, namely procollagen chain recognition and nucleation sites for triple helix formation. These functions are also common to the alpha 1(IV) COOH-propeptide; however, the lack of cleavage of this region and its additional postulated structural role in extracellular matrix interactions likely account for its divergent primary and secondary structure.


Severe Left Atrial Spontaneous Echo Contrast in Nonvalvular Atrial Fibrillation: Clinical Characteristics and Impact on Ischemic Risk Postablation.
Spontaneous echo contrast (SEC) is an important precursor for intracardiac thrombus and stroke. There are very limited data on characteristics of severe SEC and its impact on ischemic risk of nonvalvular atrial fibrillation (NVAF) patients after radiofrequency catheter ablation. Transesophageal echocardiography files were reviewed between March 2009 and March 2021 in this monocentric retrospective study. SEC was classified into four levels. The primary endpoint was thromboembolic event (stroke, myocardial infarction, systemic embolism, and ensuing death), and the secondary endpoint included nonischemic mortality and recurrent atrial arrhythmia. Six hundred SEC cases were enrolled and classified into mild SEC group (Grade 1-2, n = 515) and severe SEC group (Grade 3-4, n = 85). Independent risk factors for severe SEC included higher brain natriuretic peptide (BNP), erythrocyte sedimentation rate (ESR), and LAd/∆LVED (LAd = left atrial diameter; ∆LVED = left ventricular end-diastolic diameter - left ventricular end-systolic diameter). The severe SEC group had a higher peri-procedural ischemic event occurrence (7.1 vs. 1.9%, p = 0.007). At a median follow-up of 55 months, the severe SEC group had a lower freedom rate from ischemic events (90.1 vs. 75.3%, p < 0.001); older age and severe SEC were independent risk factors for ischemic events. In patients undergoing redo-procedure (n = 100), a remarkably reduced ESR (17.8 ± 12.0 vs. 28.2 ± 19.0 mm/h, p < 0.001) was observed in patients whose SEC disappeared. Higher BNP, ESR, and LAd/∆LVED were the independent predictors for severe SEC. Severe SEC was associated with higher peri-procedural and long-term ischemic risks. ESR and LAd/∆LVED, as indicators of hematological and hemodynamic change, seemed helpful in identifying NVAF patients prone to developing severe SEC.


Bioethics for Neonatal Cardiac Care.
Clinicians caring for neonates with congenital heart disease encounter challenges with ethical implications in daily practice and must have some basic fluency in ethical principles and practical applications. Good ethical practice begins with a thorough understanding of the details and narrative of each individual case, examination via classic principles of bioethics, and further framing of that translation into practice. We explore some of these issues and expand awareness through the lens of a case presentation beginning with fetal considerations through end-of-life discussions. We include specific sections that bring attention to shared decision-making, research ethics, and outcomes reporting. We review empirical evidence and highlight recommendations.


Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord.
The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we demonstrate that a group of ipsilateral interneurons, V2a interneurons, plays an essential role in the control of left-right alternation. In the absence of V2a interneurons, the spinal cord fails to exhibit consistent left-right alternation. Locomotor burst activity shows increased variability, but flexor-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways.


Comparative genomic analysis of eutherian connexin genes.
The eutherian connexins were characterized as protein constituents of gap junctions implicated in cell-cell communications between adjoining cells in multiple cell types, regulation of major physiological processes and disease pathogeneses. However, conventional connexin gene and protein classifications could be regarded as unsuitable in descriptions of comprehensive eutherian connexin gene data sets, due to ambiguities and inconsistencies in connexin gene and protein nomenclatures. Using eutherian comparative genomic analysis protocol and 35 public eutherian reference genomic sequence data sets, the present analysis attempted to update and revise comprehensive eutherian connexin gene data sets, and address and resolve major discrepancies in their descriptions. Among 631 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated, in aggregate, 349 connexin complete coding sequences. The most comprehensive curated eutherian connexin gene data set described 21 major gene clusters, 4 of which included evidence of differential gene expansions. For example, the present gene annotations initially described human CXNK1 gene and annotated 22 human connexin genes. Phylogenetic tree calculations and calculations of pairwise nucleotide sequence identity patterns proposed revised and updated phylogenetic classification of eutherian connexin genes. Therefore, the present study integrating gene annotations, phylogenetic analysis and protein molecular evolution analysis proposed new nomenclature of eutherian connexin genes and proteins.


Responsibility and cancer disclosure in Japan.
In Japan, as in many countries around the world, cancer patients are often not told the truth about their illness. Despite polls showing a majority of those surveyed wish to be told, surveys of physicians indicate only a small percentage will tell, especially when the cancer is advanced or terminal. We interviewed physicians from various specialties with experience managing advanced or terminal cancer patients to investigate their approaches to cancer disclosure. Our analysis reveals physicians divide into two groups: those who usually do not tell (non-tellers) such patients and those who usually do tell (tellers). Non-tellers reported the shock of disclosure inhibits telling patients, families' wishes for non-disclosure cannot be ignored, and most patients themselves do not wish to be told. Tellers asserted disclosure is unavoidable and patients want to be told, few problems result when they tell, and telling has many advantages such as not having to lie to the patient. Despite the experience of non-tellers, most physicians continue to follow the traditional approach, for advanced or terminal cancers. Physicians, as well as families and patients, display an aversion to taking responsibility for the potential risks of disclosure, and this may perpetuate the status quo.


Patterns of white matter diffusivity abnormalities in Leber's hereditary optic neuropathy: a tract-based spatial statistics study.
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by retinal ganglion cell degeneration and optic nerve atrophy, leading to a loss of central vision. The aim of this study was to explore the topographical pattern of damage to the brain white matter (WM) tracts from patients with chronic LHON using diffusion tensor (DT) MRI and tract-based spatial statistics (TBSS). Brain dual-echo and DT MRI scans were acquired from 13 patients with chronic LHON and 25 matched controls using a 3.0 T scanner. TBSS analysis was performed using the FMRIB's Diffusion Toolbox. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary retinal nerve fiber layer thickness (PRNFL) measurements, was obtained in all patients. Mean average and temporal PRNFL thicknesses were decreased significantly in LHON patients. Compared to controls, TBSS analysis revealed significant diffusivity abnormalities in these patients, which were characterized by a decreased fractional anisotropy (FA) and an increased mean diffusivity and radial diffusivity, affecting exclusively the optic tracts and optic radiations (OR). In patients, a significant correlation was found between optic tract average FA and mean visual acuity (r = 0.57, p = 0.04). In LHON patients, DT MRI reveals a microstructural alteration of the WM along the entire visual pathways, with a sparing of the other main WM tracts of the brain. Damage to the OR may be secondary either to trans-synaptic degeneration, which in turn is due to neuroaxonal loss in the retina and optic nerve, or to local mitochondrial dysfunction.


Retrospective evaluation of venous thromboembolism: Are all transient provoking events the same?
Venous thromboembolism (VTE) provoked by transient risk factors has traditionally been classified as a single entity with lower risk of recurrence. We evaluated the association between different categories of transient provoking factors and the relative risk of recurrence. Retrospective evaluation of VTE events in non-cancer patients from July 2011 to December 2012 at two tertiary institutions in Australia with a minimum follow-up of 24 months. A total of 747 VTE cases were identified, and following exclusion of cases with mortality within 30 days of presentation (n=26), unprovoked cases (40.2%) had a higher risk of recurrence (4.6 vs 2.3/100 event-years, P=.01). Provoking factors included surgery (40.4%), injury (16.7%), medical-related factors including non-surgical hospitalisation or active infection (22.0%), travel (13.2%) and oestrogen related (6.5%). Air travel had the highest recurrence rate of 5.9/100 event-years, comparable to unprovoked VTE. VTE provoked by surgery showed lower recurrence rate at 1.8/100 event-years (P=.03). 62.5% of patients with provoked VTE recurred with an unprovoked event. Transient provoking factors for VTE are heterogeneous with varying potency and should not be considered a single entity. The high recurrence rate after travel-provoked VTE suggests that it is a "minor," if not negligible provoking factor with higher thrombotic predisposition.


Inhibition of gastric acid secretion by a standardized aqueous extract of Cecropia glaziovii Sneth and underlying mechanism.
Cecropia glazioui Sneth (Cecropiaceae) is used in folk medicine in tropical and subtropical Latin America as cardiotonic, diuretic, hypotensive, anti-inflammatory and anti-asthmatic. The hypotensive/antihypertensive activity of the plant aqueous extract (AE) and isolated butanolic fraction (BuF) has been confirmed and putatively related to calcium channels blockade in vascular smooth musculature [Lapa, A.J., Lima-Landman, M.T.R., Cysneiros, R.M, Borges, A.C.R., Souccar, C., Barreta, I.P., Lima, T.C.M., 1999. The Brazilian folk medicine program to validate medicinal plants - a topic in new antihypertensive drug research. In: Hostettman, K., Gupta, M.P., Marston, A. (Eds.), Proceedings Volume, IOCD/CYTED Symposium, Panamá City, Panamá, 23-26 February 1997. Chemistry, Biological and Pharmacological Properties of Medicinal Plants from the Americas. Harwood Academic Publishers, Amsterdam, pp. 185-196; Lima-Landman, M.T., Borges, A.C., Cysneiros, R.M., De Lima, T.C., Souccar, C., Lapa, A.J., 2007. Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii Sneth in rats: an in vivo approach to the hypotensive mechanism. Phytomedicine 14, 314-320]. Bronchodilation and antidepressant-like activities of both AE and BuF have been also shown [Delarcina, S., Lima-Landman, M.T., Souccar, C., Cysneiros, R.M., Tanae, M.M., Lapa, A.J., 2007. Inhibition of histamine-induced bronchospasm in guinea pigs treated with Cecropia glaziovi Sneth and correlation with the in vitro activity in tracheal muscles. Phytomedicine 14, 328-332; Rocha, F.F., Lima-Landman, M.T., Souccar, C., Tanae, M.M., De Lima, T.C., Lapa, A.J., 2007. Antidepressant-like effect of Cecropia glazioui Sneth and its constituents -in vivo and in vitro characterization of the underlying mechanism. Phytomedicine 14, 396-402]. This study reports the antiulcer and antisecretory gastric acid activities of the plant AE, its BuF and isolated compounds with the possible mechanism involved. Both AE and BuF were assayed on gastric acid secretion of pylorus-ligated mice, on acute models of gastric mucosal lesions, and on rabbit gastric H(+), K(+)-ATPase preparations. Intraduodenal injection of AE or BuF (0.5-2.0g/kg, i.d) produced a dose-related decrease of the basal gastric acid secretion in 4-h pylorus-ligated mice. At 1.0g/kg, BuF decreased the volume (28%) and total acidity (33%) of the basal acid secretion, and reversed the histamine (2.5mg/kg, s.c.)- or bethanecol (1.0mg/kg, s.c.)-induced acid secretion to basal values, indicating inhibition of the gastric proton pump. Pretreatment of mice with the BuF (0.05-0.5g/kg, p.o.) protected against gastric mucosal lesions induced by 75% ethanol, indomethacin (30mg/kg, s.c.) or restraint at 4 degrees C. BuF also decreased the gastric H(+), K(+)-ATPase activity in vitro proportionately to the concentration (IC(50)=58.8microg/ml). The compounds isolated from BuF, consisting mainly of cathechins, procyanidins and flavonoids [Tanae, M.M., Lima-Landman, M.T.R., De Lima, T.C.M., Souccar, C., Lapa, A.J., 2007. Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antacid secretion and antidepressant-like activities. Phytomedicine 14, 309-313], inhibited the in vitro gastric H(+), K(+)-ATPase activity at equieffective concentrations to that of BuF. The results indicate that C. glazioui constituents inhibit the gastric proton pump; this effect may account for the effective antisecretory and antiulcer activities of the standardized plant extract.


Myocardial function may improve equally in diabetic patients following both multivessel percutaneous coronary intervention and coronary artery bypass grafting: results from a CARDia trial substudy.
The CARDia (Coronary Artery Revascularization in Diabetes) trial compared coronary artery bypass grafting (CABG) and optimal percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary disease. Patients enrolled had symptoms of myocardial ischaemia. As symptom assessment is flawed in diabetic patients, a substudy was undertaken to compare the extent to which these revascularization strategies alter reversible ischaemia. Seventy-one patients underwent stress echo at baseline and at 6 months. A 17-segment echocardiographic wall motion score index (WMSI) was assigned at baseline [WMSI(pre)] and at 6 months [WMSI(post)]. An overall score defined the difference: WMSI(∂) = WMSI(pre)--WMSI(post). Of 71 patients recruited, 42 underwent PCI and 29 CABG. Mean WMSI(pre) in the PCI group was 1.63 and mean WMSI(post) was 1.32. Mean WMSI(pre) in the CABG group was 1.69 and mean WMSI(post) was 1.46. The PCI WMSI(∂) was 0.31 and CABG WMSI(∂) was 0.23 (P = 0.8). Of 42 PCI patients, 39 demonstrated ischaemia at baseline. At 6 months 31 had improvements in ischaemia (79%), 5 showed no improvement, and 3 ischaemia worsened. Of 29 CABG patients, 23 demonstrated ischaemia at baseline. At 6 months, 20 had improvements in ischaemia (87%), 2 had no improvement, and in 1 ischaemia worsened. No difference was seen in the number of patients with improvements in reversible ischaemia between PCI and CABG [79 vs. 87%, (P = 0.9)]. Optimal revascularization in diabetic patients with multivessel disease remains controversial. This subset analysis of the CARDia trial suggests both PCI and CABG achieve similar improvement in reversible ischaemia.


In situ mechanical behavior of posterior spinal ligaments in the lumbar region. An in vitro study.
The posterior ligaments: ligamentum flavum, articular, interspinous and supraspinous ligaments of twenty five fresh cadaveric intervertebral segments, from T11-T12 to L4-L5, extracted from fourteen spines were tested in tension. A progressive dissection method was used, that is, each segment was tested after first resecting the disk with the ligaments intact and a force-elongation curve obtained. Then one ligament was cut and the test repeated, and so on. The most restrictive ligament was found to be the ligamentum flavum followed by the articular, interspinous, and supraspinous ligaments.


Inflammasomes and the IL-1 Family in Bone Homeostasis and Disease.
Inflammasomes are multimeric protein structures with crucial roles in host responses against infections and injuries. The importance of inflammasome activation goes beyond host defense as a dysregulated inflammasome and subsequent secretion of IL-1 family members is believed to be involved in the pathogenesis of various diseases, some of which also produce skeletal manifestations. The purpose of this review is to summarize recent developments in the understanding of inflammasome regulation and IL-1 family members in bone physiology and pathology and current therapeutics will be discussed. Small animal models have been vital to help understand how the inflammasome regulates bone dynamics. Animal models with gain or loss of function in various inflammasome components or IL-1 family signaling have illustrated how these systems can impact numerous bone pathologies and have been utilized to test new inflammasome therapeutics. It is increasingly clear that a tightly regulated inflammasome is required not only for host defense but for skeletal homeostasis, as a dysregulated inflammasome is linked to diseases of pathological bone accrual and loss. Given the complexities of inflammasome activation and redundancies in IL-1 activation and secretion, targeting these pathways is at times challenging. Ongoing research into inflammasome-mediated mechanisms will allow the development of new therapeutics for inflammasome/IL-1 diseases.


WITHDRAWN: Auditory hallucination and agitation due to memantine in a patient with Alzheimer's disease: a case report.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Nanoparticles: Emerging carriers for drug delivery.
The core objective of nanoparticles is to control and manipulate biomacromolecular constructs and supramolecular assemblies that are critical to living cells in order to improve the quality of human health. By definition, these constructs and assemblies are nanoscale and include entities such as drugs, proteins, DNA/RNA, viruses, cellular lipid bilayers, cellular receptor sites and antibody variable regions critical for immunology and are involved in events of nanoscale proportions. The emergence of such nanotherapeutics/diagnostics will allow a deeper understanding of human longevity and human ills that include cancer, cardiovascular disease and genetic disorders. A technology platform that provides a wide range of synthetic nanostructures that may be controlled as a function of size, shape and surface chemistry and scale to these nanotechnical dimensions will be a critical first step in developing appropriate tools and a scientific basis for understanding nanoparticles.


The state of emergency medical technician education in Ghana.
The National Ambulance Service (NAS) provides emergency medical services throughout Ghana and trains emergency medical technicians (EMTs) at the NAS Prehospital Emergency Care Training School (PECTS). Currently the majority of EMT training occurs primarily in a traditional didactic format. Students and faculty were interviewed to better understand their views of the current curriculum. Additionally, any barriers to integration of simulation-based learning were assessed. Following the interviews, the faculty was trained to conduct obstetric and neonatal simulations. The faculty was then observed introducing the simulations to the EMT students. A standardized list of questions developed in consultation with an education expert was used to elicit student and faculty expression of opinion. Interviews were conducted in-person in small group settings. Training sessions were conducted in-person in large group settings. Students and faculty alike expressed pride in their work and 14/25 groups felt that teaching efforts were high. However, students verbalized concern involving their lack of rest (12/18) and the high volume of lectures per day (11/18). Both students and faculty felt limited by the lack of simulation tools (17/25), library resources (14/25), internet access (17/25), and infrastructure (20/25). All groups felt favorably towards the integration of simulation-based learning (25/25). The faculty and students of PECTS support the transition from a curriculum based on traditional didactic learning to one based on simulation learning.


Effect of glutaraldehyde and lead on the activity of hepatic glucose-6-phosphatase. A biochemical and cytochemical study.
The sensitivity of mouse liver glucose-6-phosphatase activity towards glutaraldehyde fixation has been analysed by biochemical and cytochemical means. The degree of enzymatic inhibition and various enzymatic properties have been studied. Several differences have been observed in the Km determination, the sensitivity to pH 5 and the activity related to pH between fixed and unfixed enzymes. The role of Pb++ ions in the cytochemical media has also been estimated. It is concluded that several enzymatic differences appear between fixed and unfixed enzymes and that the inhibition by Pb ions is dependent on the buffer and on the amount of substrate used.


The impact of the Orphan Drug Act on the development and advancement of neurological products for rare diseases: a descriptive review.
Many neurological diseases or conditions are rare disorders. The Orphan Drug Act (ODA) of 1983 was promulgated to promote the development of products for such conditions. In this Opinion piece, we discuss how the ODA has affected neurological diseases, note how current and future sponsors (any person(s) or entity (i.e., academic, corporate body, individual, manufacturer) that applies for an official regulatory action) of products for rare neurological diseases can take advantage of ODA incentives, identify areas of success and continuing needs, and review data that can help drive the future development of products for rare neurological conditions.


The Self Care Assessment Schedule (SCAS)--II. Reliability and validity.
Evaluation of the SCAS in three groups of patients demonstrates high levels of test-retest reliability and satisfactory internal consistency. Multiple investigations of validity support the use of the SCAS as a measure of self care deficit which is related to social disability. The potential uses of the SCAS in clinical work and research are discussed.


Functional consequences of treating turkey liver fructose-1,6-bisphosphatase with penicillin G.
Treatment of turkey liver fructose-1,6--bisphosphatase with penicillin G progressively inactivated the enzyme and desensitized the enzyme toward high substrate inhibition. The treatment also led to reduced sensitivity to AMP inhibition and the loss of cooperative interaction among AMP-binding sites. These altered properties were not reversed by dialysis, but were prevented when treatment with penicillin G was perfomed in the presence of substrate.


Effect of Cervical Stenosis and Rate of Impact on Risk of Spinal Cord Injury During Whiplash Injury.
Finite Element Study. To determine the risk of spinal cord injury with pre-existing cervical stenosis during a whiplash injury. Patients with cervical spinal stenosis are often cautioned on the potential increased risk of spinal cord injury (SCI) from minor trauma such as rear impact whiplash injuries. However, there is no consensus on the degree of canal stenosis or the rate of impact that predisposes cervical SCI from minor trauma. A previously validated three-dimensional finite element model of the human head-neck complex with the spinal cord and activated cervical musculature was used. Rear impact acceleration was applied at 1.8 m/s and 2.6 m/s. Progressive spinal stenosis was simulated at the C5 to C6 segment, from 14 mm to 6 mm, at 2 mm intervals of ventral disk protrusion. Spinal cord von Mises stress and maximum principal strain were extracted and normalized with respect to the 14 mm spine at each cervical spine level from C2 to C7. The mean segmental range of motion was 7.3 degrees at 1.8 m/s and 9.3 degrees at 2.6 m/s. Spinal cord stress above the threshold for SCI was noted at C5 to C6 for 6 mm stenosis at 1.8 m/s and 2.6 m/s. The segment (C6-C7) inferior to the level of maximum stenosis also showed increasing stress and strain with a higher rate of impact. For 8 mm stenosis, spinal cord stress exceeded SCI thresholds only at 2.6 m/s. Spinal cord strain above SCI thresholds were only noted in the 6 mm stenosis model at 2.6 m/s. Increased spinal stenosis and rate of impact are associated with greater magnitude and spatial distribution of spinal cord stress and strain during a whiplash injury. Spinal canal stenosis of 6 mm was associated with consistent elevation of spinal cord stress and strain above SCI thresholds at 2.6 m/s.


The release of zearalenone-induced heterophil extracellular traps in chickens is associated with autophagy, glycolysis, PAD enzyme, and P2X1 receptor.
Zearalenone (ZEA) is produced mainly by fungi belonging to genus Fusarium in foods and feeds. Heterophil extracellular traps (HETs) are a novel defense mechanism of chicken innate immunity involving activated heterophils. However, the conditions and requirements for ZEA-triggered HET release remain unknown. In this study, immunostaining analysis demonstrated that ZEA-triggered extracellular fibers were composed of histone and elastase assembled on DNA skeleton, showing that ZEA can induce the formation of HETs. Further experiments indicated that ZEA-induced HET release was concentration-dependent (ranging from 20 to 80 μM ZEA) and time-dependent (ranging from 30 to 180 min). Moreover, in 80 μM ZEA-exposed chicken heterophils, reactive oxygen species (ROS) level, catalase (CAT), superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione (GSH) content were increased. Simultaneously, ZEA at 80 μM activated ERK and p38 MAPK signaling pathways by increasing the phosphorylation level of ERK and p38 proteins. Pharmacological inhibition assays revealed that blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, ERK, and p38 mitogen-activated protein kinase (MAPK) reduced ZEA-induced ROS levels but had no impact on HET formation. Furthermore, immunostaining analysis indicated that the heterophil underwent the formation of autophagosome based on being stained with LC3B. The pharmacological inhibition assays demonstrated that rapamycin-, wortmannin-, and 3-methyladenine (3-MA)-treatments modulated ZEA-triggered HET formation, indicating that heterophil autophagy played a key role in ZEA-induced HET formation. Further studies on energy metabolism showed that inhibition of lactate/glucose transport, hexokinase-2 (HK-2), fructose-2,6-biphosphatase 3 (PFKFB3) in glycolysis abated ZEA-induced HETs, implying that glycolysis was one of the factors influencing the ZEA-induced HET formation. Besides, inhibition of the peptidylarginine deiminase (PAD) enzyme and P2X1 significantly reduced the ZEA-induced HET formation. In conclusion, we demonstrated that ZEA-triggered HET formation, which was associated with glycolysis, autophagy, PAD enzyme, and P2X1 receptor activation, providing valuable insight into the negative effect of ZEA on chicken innate immunity.


Maternal transplantation medications during breastfeeding.
Previously transplanted women have maintained successful pregnancies yet have been discouraged from breastfeeding. The American Academy of Pediatrics cautions against breastfeeding due to documented presence of cyclosporine in breast milk and unknown long-term effects on nursing infants. Transplant centers, however, report mothers breastfeeding with no measurable cyclosporine serum concentrations or untoward effects in their infants. Few data are available with regard to levels of other transplant medications in breast milk. Given the small number of published reports involving lactating women and relatively short follow-up of their infants, routine medication levels should be part of any screening regimen for such breastfed infants until further studies are available.