Hypertensive retinopathy in a child caused by pheochromocytoma: identification after a failed school vision screening.
A 7-year-old girl was referred for ophthalmological examination after the result of a routine school vision screening identified unilateral vision loss. Fundus examination showed bilateral but markedly asymmetric macular exudates and optic disk edema. After the results of two blood pressure measurements were within normal limits, a third markedly elevated measurement revealed malignant hypertension and led to a diagnosis of pheochromocytoma, a rare catecholamine-secreting tumor. The tumor was resected, and 6 months later the patient's blood pressure had normalized; however, although visual acuity had improved to 20/20 in the right eye, it remained 20/200 in the left eye, with decreased disk edema but the persistence of the macular exudates. The identification of an abdominal malignancy through a school vision screening may have saved this child's life. The need for repeated blood pressure measurement is also highlighted.


Nocardia asteroides cerebral abscess in immunocompetent hosts: report of three cases and review of surgical recommendations.
Nocardia asteroides cerebral abscesses are rare intracranial lesions. They account for only 2% of brain abscesses. Existing literature takes the form of anecdotal reports, small case series, and retrospective studies. An optimal treatment approach has not been established. However, there is evidence that the size of the lesion and clinical and immune status of the patient are relevant to surgical decision making. Three recent cases are presented and the existing literature is reviewed. The outcome in all three cases was satisfactory. Although the currently recommended neurosurgical management protocols were followed, one patient had a prolonged course, which may have been shortened had an earlier biopsy of the cerebral lesion been performed. The surgical approach to suspected Nocardia spp. cerebral abscesses has recently become less aggressive. A more aggressive approach than that currently preferred for suspected Nocardia spp. cerebral abscesses may be appropriate. Earlier biopsy of lesions to achieve specific identification and anti-microbial sensitivity profiles is suggested even in cases where an extracranial focus of infection is found. Delays in obtaining a biopsy may lead to non-specific or unhelpful results that may prolong the course in hospital and jeopardize the outcome.


The epidemiology of traumatic musculoskeletal injuries in Kuwait: Prevalence and associated risk factors.
Epidemiological explorations of traumatic injuries are essential to provide benchmarks for future planning to address multidimensional challenges. The study aimed to describe the epidemiology of traumatic musculoskeletal injuries in Kuwait, including their prevalence and associated risk factors. The Orthopedic Admission Database of a level II trauma center in Kuwait was retrospectively reviewed from January 2018 to February 2020. Traumatic fractures of the spine and upper and lower limbs were explored. The study included 564 patients with 788 traumatic injuries who were 33.0 (23.0) years of age (median and interquartile range): 78.0% were male, and 43% were Kuwaitis. Spinal fractures were the most prevalent injury, at 21.7%, followed by tibial fractures, at 11.3%, and ankle fractures, at 10.2%. Road traffic accidents were the leading mechanism of injury, at 37.9%, followed by falling over and falling from height, at 29.3% and 16.8%, respectively. Risk factors included injury mechanism, nationality, and age (p < 0.05). Road traffic accidents were at risk for sustaining spinal, scapular, clavicle, humeral, pelvic, hip, tibial, and fibular fractures; those for falling over were radial, ulnar, femoral, and patellar fractures; and those for falling from height were foot and ankle fractures. Kuwaitis were found to be at risk of spinal, humeral, pelvic and femoral fractures, whereas non-Kuwaitis were found to be at risk of scapular, shoulder, elbow, ulnar, radial, hip, patellar, tibial, fibular, foot, and ankle fractures. The age range of 19-49 years was associated with the highest risk for all fracture sites. Epidemiological characteristics of traumatic injuries in Kuwait have been determined to guide preventive strategies and healthcare planning.


Proliferating Trichilemmal Tumor of the Auricula: A Very Rare Locus.
Proliferating trichilemmal tumor (PTT) is a rare but morphologically characteristic tumor, derived from the external root sheath. They are commonly localized as a solitary lesion on the scalp. They rarely occur in other regions. PTTs generally behave in a benign fashion, up to 20% of the lesions may undergo malignant transformation into squamous carcinoma. We present an elderly woman with a cystic swelling on the crus of auricular helix diagnosed as PTT. To our knowledge, this is the first case in the English literature, of PTT of the auricula.


Sudden asphyxia caused by retropharyngeal hematoma after blunt thyrocervical artery injury.
Retropharyngeal hematomas are often associated with blunt cervical spine injury. Generally, they improve with conservative treatment; however, rarely, airway obstruction occurs due to delayed swelling of retropharyngeal hematoma. To report a case of sudden asphyxia due to retropharyngeal hematoma caused by blunt thyrocervical artery injury. A 30-year-old woman was admitted to the Emergency Department of Tokai University Hospital 4h after injury in a motor vehicle collision. On arrival, she had severe dyspnea and neck swelling; thereafter, a 26-mm-thick retropharyngeal swelling was visualized on lateral cervical plain X-ray study, extending from C1 anterior vertebrae to mediastinum. Emergency intubation was performed for the asphyxia. Because extravasation of contrast agent was observed in the hematoma on emergency contrast-enhanced computed tomography (CT) scan, emergency angiography was performed, from which we diagnosed a hemorrhage from the right thyrocervical artery. If a patient with a non-displaced cervical spine injury suffers airway obstruction due to retropharyngeal hematoma, vigorous hemorrhage from a thyrocervical artery injury should be considered as the cause, and emergency contrast-enhanced CT scan of the neck should be performed after emergent tracheal intubation.


The effect of aminopyridines on the activity recorded in the dorsal roots of an isolated hamster spinal cord preparation.
1. The aminopyridines (AP) increase the activity recorded on the dorsal roots of an isolated hamster spinal cord preparation. 2. The threshold for 4-AP was 4 X 10(-6) M and the maximum effect was 3 X 10(-5) M. The threshold for 2AP and 3AP was 3 X 10(-5) M and the maximum effect was at 10(-3) M. 3. It took longer for the preparation to recover on washing from treatment with 4-AP than from 2-AP or 3-AP. Washing often showed a transient increase in activity. 4. Treatment with AP changed the pattern of firing so that the activity after treatment and prolonged washing showed a bursting pattern. 5. The activity recorded in the dorsal roots is generated within the spinal cord and may be related to activity of central pattern generators.


Effects of adjunct treatment with intravenous immunoglobulins on the course of severe COVID-19: results from a retrospective cohort study.
To evaluate the effect of adjunct treatment with Octagam, an intravenous immunoglobulin (IVIG) product, on clinical outcomes and biomarkers in critically ill COVID-19 patients. Data from a single center was analyzed retrospectively. Patients had received preliminary standard intensive care (SIC) according to a local treatment algorithm, either alone or along with IVIG 5% at 30 g/day for 5 days. The two groups were compared regarding baseline characteristics, survival and changes in inflammation markers. Imbalance in baseline APACHE II scores was addressed by propensity score matching. Otherwise, Kaplan-Meier and multiple logistic regression models were used. Out of 93 patients, 51 had received IVIG and 42 had not. About 75% of patients were male and both groups had comparable body mass index and AB0 blood type distribution. IVIG-treated patients were younger (mean 65 ± 15 versus 71 ± 15 years, p = .066) and had slightly lower baseline disease scores (APACHE II: 20.6 versus 22.4, p = .281; SOFA: 5.0 versus 7.0, p = .006). Overall survival was 61% in the SIC + IVIG and 38% in the SIC only group (odds ratio: 2.2, 95% confidence interval: 0.9-5.4, p = .091 after controlling for baseline imbalances). IVIG significantly prolonged median survival time (68 versus 18 days, p = .014) and significantly reduced plasma levels of C-reactive protein (median change from baseline -71.5 versus -0.3 mg/L, p = .049). Clinically relevant benefits through adjunct IVIG treatment in COVID-19 need to be confirmed in a randomized, controlled trial.


Habitat transitions by a large coastal sciaenid across life history stages, resolved using otolith chemistry.
Many coastal species move between estuarine and coastal environments throughout their life. Migration patterns develop as a result of ecology and evolution and must be understood to effectively manage harvested stocks. This study examined movements across estuarine and coastal marine habitats in adult Mulloway (Argyrosomus japonicus); a commercially, indigenous and recreationally harvested sciaenid of south-eastern Australia. Chemical profiles across the otolith (ear bone) were used to examine transitions between estuary and marine habitats over life history. Patterns in otolith Ba:Ca concentrations indicated that the majority of fish migrated between estuary and marine habitats, but a small proportion of fish appeared to remain in either the estuary or the marine habitat. Such movements may potentially be driven by a range of biological and environmental factors. This approach allows questions about the life history and habitat use of Mulloway to be addressed, which will aid management and provide a platform for future research on Mulloway, other sciaenid's and coastal migratory species.


Relationship of within-patient semen variability to outcome of intrauterine insemination.
To define the subpopulation of infertility patients who would benefit from intrauterine insemination (IUI) with swim-up homologous sperm, the relationship of within-patient semen variability to outcome of IUI was studied. The 61 women in the study had negative workups. Men had at least one semen sample with greater than or equal to 20 x 10(6) sperm/ml. The 6-month cumulative pregnancy rate for all patients was 31.8%. Patients with original sperm motilities consistently greater than or equal to 30% had a higher cumulative pregnancy rate (62.9%) than patients with one or more motility less than 30% (22.0%, P = 0.0015, log-rank test). Patients with post-swim-up motilities consistently greater than or equal to 70% had a cumulative pregnancy rate (51.2%) significantly greater than patients inconsistent for this parameter (15.6%, P = 0.0116). Consistency of sperm motility is a useful parameter for defining the subpopulation of patients who would benefit from IUI.


An antimicrobial prophylaxis protocol using rectal swab cultures for transrectal prostate biopsy.
To evaluate the benefit of an antimicrobial prophylaxis protocol using rectal swab cultures in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy in our Veterans Affairs population. Between June 1, 2013, and June 1, 2014, we implemented an antimicrobial prophylaxis protocol using rectal swab cultures on selective media containing ciprofloxacin for all men scheduled for TRUS-guided prostate biopsy. Data from 2759 patients from Jan 1, 2006 to May 31, 2013, before protocol implementation served as historical controls. Patients with fluoroquinolone (FQ)-susceptible organisms received FQ monotherapy, while those with FQ-resistant organisms received targeted prophylaxis. Our objective was to compare the rate of infectious complications 30 days after prostate biopsy before and after implementation of our antimicrobial protocol. One hundred and sixty-seven patients received rectal swab cultures using our protocol. Seventeen (14 %) patients had FQ-resistant positive cultures. Patients with positive FQ-resistant culture results were more likely to have had a history of previous prostate biopsy and a positive urine culture in the last 12 months (p = 0.032, p = 0.018, respectively). The average annual infectious complication rate within 30 days of biopsy was reduced from 2.8 to 0.6 % before and after implementation of our antimicrobial prophylaxis protocol using rectal swab cultures, although this difference was not statistically significant (p = 0.13). An antimicrobial prophylaxis protocol using rectal culture swabs is a viable option for prevention of TRUS-guided prostate biopsy infectious complications. After implementation of an antimicrobial prophylaxis protocol, we observed a nonsignificant decrease in the rate of post-biopsy infectious complications when compared to historical controls.


Transcription factors from oviduct and HeLa cells are similar.
Total HeLa cell extract was separated into multiple components using first DEAE-Sephadex and then phosphocellulose column chromatography. Four major fractions, DE175, DE500, P100, and P1000, from HeLa cells are found to be essential for accurate and efficient transcription of cloned ovalbumin DNA fragments in the reconstituted system. DE175 serves as the source for RNA polymerase II and DE500 minimizes the synthesis of small molecular size RNA. P100 enhances the levels of specific transcription, while P1000 is absolutely required for correct initiation. Chick oviduct crude extract was also fractionated into multiple components according to the same procedure. Similar efficiency of specific initiation could be obtained when an individual fraction (DE175, DE500, P100, or P1000) from oviduct cells was exchanged for a fraction from HeLa cells. These results indicate that chick oviduct tissue also contains general transcription factors like that of HeLa cells and these factors can be fractionated according to the same procedure. In this fractionation scheme, we were able to separate the bulk of RNase activity into the P350 fraction which was not required for initiation of ovalbumin RNA transcription. Thus, this reconstituted system is suitable for studying in vitro transcription in a homologous system derived from tissue extracts, even though a substantial amount of cellular ribonuclease may be associated with it.


A quantitative evaluation of radiolabelled lectin retention on oral mucosa in vitro and in vivo.
Previous work has identified lectins that bind to the cells present on the oral mucosa for their potential use as a means of retaining a drug delivery system on the mucosal surfaces of the mouth. In this study, a radiolabelling technique was developed to allow the quantification of lectin binding to human buccal cells in vitro, and the retention of the lectins in the oral cavity of a rat model in vivo. Lectins were labelled with 99mTc using a cyclic diethylene triamine pentaacetic acid conjugation technique. In the in vitro study, human buccal cells were obtained by scraping the inner surface of the cheek. The suspended cells were exposed to the labelled lectin solution for 30 min and after washing with buffer the activity associated with the cells determined. In the in vivo study, male Wistar rats were briefly anaesthetized during which 10 microl of a solution containing labelled lectin was applied into the buccal pouch. At set times the rats were killed and the lower buccal cavity mucosal tissue and tongue dissected out and monitored for bound lectin. The in vitro study indicated that the lectins from Arachis Hypogaea, Canavalia ensiformis and Triticum vulgaris bound to oral mucosal cells. The T. vulgaris lectin showed the greatest binding, calculated to be 6.77 x 10(9) molecules per cell. The in vivo retention of C. ensiformis and T. vulgaris lectins on rat oral mucosal tissue was also evident. The T. vulgaris lectin showed significantly higher levels of retained lectin after 30 min (29.54 +/- 4.20 microg SD) on the oral mucosal tissue and 28.37 microg (+/-2.13 SD) on the tongue and was still detected at similar levels after 2 h. These studies indicate that significant lectin binding to human buccal cells occurs in vitro and retention in an animal model occurs for over 2 h in vivo. The T. vulgaris lectin showed most promise for further work.


Long-term follow-up of a case of posterior microphthalmos (PRSS56) with hyperautofluorescent retinal pigment epithelial deposits.
To report a case of posterior microphthalomos (PM) related to PRSS56 gene mutation with long term follow up with multimodal imaging findings. Single retrospective case report. A 43-year old male patient presented in 2009 with bilateral reduced vision. Clinical examination and multimodal imaging showed features consistent with posterior microphthalmos with prominent bilateral horizontal papillomacular retinal folds. Posterior pole hyperautofluorescent RPE deposits were present. Gradual worsening of visual acuity and rod and cone photoreceptor function more so on the left was demonstrated during the 8 years of follow up. Hyperautofluorescent RPE deposits may occur in patients with posterior microphthalmos and such patient's may experience only gradual disease progression over long term follow up.


Prominent transverse (Bowdler) bone spurs as a diagnostic clue in a case of neonatal hypophosphatasia without metaphyseal irregularity.
Transverse midshaft spurs allowed a diagnosis of hypophosphatasia in a newborn infant without metaphyseal irregularity.


The rate of adaptive molecular evolution in wild and domesticated Saccharomyces cerevisiae populations.
Through its fermentative capacities, Saccharomyces cerevisiae was central in the development of civilisation during the Neolithic period, and the yeast remains of importance in industry and biotechnology, giving rise to bona fide domesticated populations. Here, we conduct a population genomic study of domesticated and wild populations of S. cerevisiae. Using coalescent analyses, we report that the effective population size of yeast populations decreased since the divergence with S. paradoxus. We fitted models of distributions of fitness effects to infer the rate of adaptive ( ω a $$ {\omega}_a $$ ) and non-adaptive ( ω na $$ {\omega}_{na} $$ ) non-synonymous substitutions in protein-coding genes. We report an overall limited contribution of positive selection to S. cerevisiae protein evolution, albeit with higher rates of adaptive evolution in wild compared to domesticated populations. Our analyses revealed the signature of background selection and possibly Hill-Robertson interference, as recombination was found to be negatively correlated with ω na $$ {\omega}_{na} $$ and positively correlated with ω a $$ {\omega}_a $$ . However, the effect of recombination on ω a $$ {\omega}_a $$ was found to be labile, as it is only apparent after removing the impact of codon usage bias on the synonymous site frequency spectrum and disappears if we control for the correlation with ω na $$ {\omega}_{na} $$ , suggesting that it could be an artefact of the decreasing population size. Furthermore, the rate of adaptive non-synonymous substitutions is significantly correlated with the residue solvent exposure, a relation that cannot be explained by the population's demography. Together, our results provide a detailed characterisation of adaptive mutations in protein-coding genes across S. cerevisiae populations.


Biological and anthropogenic predictors of metal concentration in the Eurasian otter, a sentinel of freshwater ecosystems.
Toxic metals have been linked to a range of adverse health effects in freshwater organisms. However, for higher vertebrates, there is little understanding of the large-scale drivers of exposure. We quantified toxic metal/semi-metal concentrations in a sentinel freshwater top predator, the Eurasian otter (Lutra lutra), across England and Wales, and determined how this varied with key natural and anthropogenic factors. We related liver concentrations in 278 otters that died between 2006 and 2017 to habitat biogeochemistry, proximity to point source contamination and to biological characteristics (length, sex, condition). Evidence for any positive association with putative anthropogenic sources (mining, human population, known discharges) was weak or lacking in nearly all cases, with the exception of a positive association between lead and human population density. Despite concerns that burgeoning use of nanosilver in consumer products might increase silver concentrations in waste waters, there was no increase over time. Spatial variation in soil/sediment pH, precipitation, and soil calcium oxide are indicated as significant predictors of metal concentrations in otters (higher cadmium and silver in areas with lower pH and higher rainfall, and higher chromium and lead in areas of lower calcium oxide). Liver chromium and nickel concentrations declined significantly over time (Cr 0.030 ± 1.2 to 0.015 ± 1.3 μg/g dry weight, Ni 0.0038 ± 1.2 to 0.00068 ± 1.5 μg/g, between 2006-2009 and 2014-2017), but other metals showed no temporal change. Biotic associations were important, with age related accumulation indicated for mercury and cadmium (as well as interactions with body condition). Our results suggest that larger-scale geochemical and hydrological processes are important in determining metal exposure in otters, and we provide an indication of risk factors that may be of relevance for freshwater vertebrates in other countries with well-developed water pollution management.


A novel dammarane triterpenoid alleviates atherosclerosis by activating the LXRα pathway.
We have previously demonstrated that ginsenoside compound K can attenuate the formation of atherosclerotic lesions. Therefore, ginsenoside compound K has potential for atherosclerosis therapy. How to improve the druggability and enhance the antiatherosclerotic activity of ginsenoside compound K are the core problems in the prevention and treatment of atherosclerosis. CKN is a ginsenoside compound K derivative that was previously reported to have excellent antiatherosclerotic activity in vitro, and we have applied for international patents for it. Male C57BL/6 ApoE-/- mice were fed a high-fat and high-choline diet to induce atherosclerosis and were subjected to in vivo studies. In vitro, the CCK-8 method was applied to evaluate cytotoxicity in macrophages. Foam cells were utilized, and cellular lipid determination was performed for in vitro studies. The area of atherosclerotic plaque and fatty infiltration of the liver were measured by image analysis. Serum lipid and liver function were determined by a seralyzer. Immunofluorescence and western blot analysis were conducted to explore the alterations in the expression levels of lipid efflux-related proteins. Molecular docking, reporter gene experiments and cellular thermal shift assays were used to verify the interaction between CKN and LXRα. After confirming the therapeutic effects of CKN, molecular docking, reporter gene experiments and cellular thermal shift assays were used to predict and investigate the antiatherosclerotic mechanisms of CKN. CKN exhibited the greatest potency, with a 60.9% and 48.1% reduction in en face atherosclerotic lesions on the thoracic aorta and brachiocephalic trunk, reduced plasma lipid levels and decreased foam cell levels in the vascular plaque content in HHD-fed ApoE-/- mice. Moreover, CKN in the present study may exert its antiatherosclerotic effects through activated ABCA1 by promoting LXRα nuclear translocation and reducing the adverse effects of LXRα activation. Our results revealed that CKN prevented the formation of atherosclerosis in ApoE-/- mice by activating the LXRα pathway.


Surgical management of the facial nerve in craniofacial trauma and long-standing facial paralysis: cadaver study and clinical presentations.
Examination of the extratemporal branches of the facial nerve reveals several branching patterns of the facial nerve, indicating the variability in the course of the nerve. Due to such variance, injury to this nerve often accompanies facial trauma and surgical dissection for the repair of facial bone injuries, and it may result in high morbidity. A study of 12 fresh cadavers was performed to 1) review the variability in location of the extratemporal branches of the facial nerve, 2) identify the soft tissue injuries in which the facial nerve is at risk, and 3) discuss surgical options for repair. The authors identified the zygomatic and buccal and the extratemporal branches of the facial nerve. Among the five extratemporal branches, there is a significant crossover between all, except the temporal and the mandibular branches. This indicates that dissection should proceed with great caution, since injury to the temporal and marginal mandibular branches is unlikely to resolve spontaneously. The management of injuries within one year and those of longer duration is discussed. Two of the 5 major branches of the extratemporal facial nerve have a high morbidity following injury. Repair should be performed within the first 72 hours. Graft, if required, should be placed in 9 to 12 months.


Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota.
Mounting evidence has linked changes in human gut microbiota to proton pump inhibitor (PPI) use. Accordingly, multiple studies have analyzed the gut microbiomes of PPI users, but PPI-microbe interactions are still understudied. Here, we performed a meta-analysis of four studies with available 16S rRNA gene amplicon sequencing data to uncover the potential changes in human gut microbes among PPI users. Despite some differences, we found common features of the PPI-specific microbiota, including a decrease in the Shannon diversity index and the depletion of bacteria from the Ruminococcaceae and Lachnospiraceae families, which are crucial short-chain fatty acid-producers. Through training based on multiple studies, using a random forest classification model, we further verified the representativeness of the six screened gut microbial genera and 20 functional genes as PPI-related biomarkers, with AUC values of 0.748 and 0.879, respectively. Functional analysis of the PPI-associated 16S rRNA microbiome revealed enriched carbohydrate- and energy-associated genes, mostly encoding fructose-1,6-bisphosphatase and pyruvate dehydrogenase, among others. In this study, we have demonstrated alterations in bacterial abundance and functional metabolic potential related to PPI use, as a basis for future studies on PPI-induced adverse effects.


Subarctic-scale transport of 134Cs to ocean surface off northeastern Japan in 2020.
We studied the spatiotemporal variations in 134Cs, 137Cs, and 228Ra concentrations at the sea surface off southeastern Hokkaido, Japan (off-Doto region) from 2018 to 2022 using low-background γ-spectrometry. The 134Cs concentrations in the off-Doto region, decay-corrected to the date of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, exhibited wide lateral variation each year (e.g., 0.7-1.1 mBq/L in 2020). By studying the 228Ra concentrations and salinity, this variation was explained based on the current mixing patterns. Furthermore, the 134Cs concentrations in the waters highly affected by the Oyashio Current (OYC) gradually increased from 2018 to 2020, and subsequently decreased in 2022. This implies that the water mass maximally contaminated with 134Cs was transported back to the side of the Japanese islands 10 years after the FDNPP accident along with counter-clockwise currents (e.g., the OYC) in the northern North Pacific Ocean. The 134Cs concentrations in the OYC-affected waters in the off-Doto region in 2020 were ~ 1/6 times those in the 134Cs-enriched core of waters off the western American Coast in 2015, which can be ascribed to dilution via spatial dispersion during subarctic current circulation. Overall, we elucidated the ocean-scale subarctic current systems in the northwestern North Pacific Ocean, including water circulation timespans.


A Comparison of Microwave Ablation and Cryoablation for the Treatment of Renal Cell Carcinoma: A Systematic Literature Review and Meta-analysis.
To conduct a systematic review and meta-analysis comparing microwave ablation (MWA) and cryoablation for renal cell carcinoma (RCC). The systematic search was performed in MEDLINE, Embase, and Cochrane databases. Studies published in English from January 2006 to February 2022 that assessed adults with primary RCC who received MWA or cryoablation were included. Study arms from RCTs, comparative observational, and single-arm studies were eligible. The outcomes included local tumor recurrence (LTR), overall survival, disease-free survival, overall/major complications, procedure/ablation time, 1- to 3-month primary technique efficacy, and technical success. Single-arm meta-analyses were performed using the random effects model. Sensitivity analyses excluding low-quality studies assessed using the MINORs scale were performed. Univariable and multivariable examined the effects of prognostic factors. Baseline characteristics were similar between groups and mean tumor size for MWA and cryoablation were 2.74 and 2.69 cm. Single-arm meta-analyses were similar for LTR and secondary outcomes between cryoablation and MWA. Ablation time was significantly shorter with MWA than with cryoablation (meta-regression weighted mean difference 24.55 minutes, 95% confidence interval -31.71, -17.38, P < .0001). One-year LTR was significantly lower with MWA than cryoablation (odds ratio 0.33, 95% confidence interval 0.10-0.93, P = .04). There were no significant differences for other outcomes. MWA provides significantly improved 1-year LTR and ablation time compared with cryoablation for patients with RCC. Other outcomes appeared similar or favorable for MWA; however, results were not statistically significant. MWA of primary RCC is as safe and effective as cryoablation, which should be confirmed with future comparative studies.


Primary umbilical endometriosis coexisiting with multiple uterine fibroids: A case report.
Uterine fibroids and endometriosis are independent causes of infertility/subfertility in women of reproductive age. Primary umbilical endometriosis is rare. Here, we report a case of primary umbilical endometriosis coexisting with multiple uterine fibroids in a 35 year old nulliparous woman who presented with abdominal swelling as well as cyclical pain and swelling of the umbilicus without any previous surgery. She had abdominal myomectomy and excision of the umbilical lesion with histological confirmation of uterine fibroids and umbilical and peri-umbilical endometriosis. Primary umbilical endometriosis should be considered as a possible differential diagnosis in cases of umbilical disorders even if the patient has no typical symptoms of pelvic endometriosis. The clinical features include an umbilical swelling (90%), often associated with cyclical pain (81.5%) and bleeding or discharge (49.2%); while some patients may be asymptomatic. The diagnosis of umbilical endometriosis could be made based on clinical findings but histological confirmation is the gold standard for diagnosis. The definitive treatment for umbilical endometriosis is surgical excision. Although rare, primary umbilical endometriosis may coexist with uterine fibroids and should be suspected in women of reproductive age who complain of cyclical umbilical disorders in addition to abdominal swelling or other symptoms of uterine fibroids.


A computerized version of the Chou and Fasman method for predicting the secondary structure of proteins.
A novel computerized program has been developed for predicting the secondary structure of proteins from their amino acid sequences. The scheme of the Chou and Fasman method (1978, Adv. Enzymol. Relat. Subj. Biochem. 47, 45-148) is closely followed. Some of their qualitative rules have been converted to numeric scales to obtain unambiguous predictions. This program has been tested on 21 proteins with known three-dimensional structures constituting a 4457 amino acids data base. The percentage of correctly predicted amino acids is between 41 and 66% for a three-state (helix, sheet, and coil) description of protein secondary structure.


The Physiotherapy Evidence Database (PEDro) has better free full-text access than PubMed: An observational study.
Access to full-text articles is an essential element of evidence-based practice. Estimate the percentage of articles in the Physiotherapy Evidence Database (PEDro) that have free full-text access and compare free access between PEDro and PubMed. Secondary objectives for access via PEDro: determine if publication year and geographic location impact on free access; determine if adding a link to a portable document format (PDF) locator website would improve free access; and evaluate the association between article characteristics and free access. This observational study used a random sample of 200 articles published in 2000-2019 and indexed in PEDro. Data collectors in Australia, Brazil, Nepal, and Spain attempted to access free full text for each article via PEDro. One data collector attempted to access free full text via PubMed. One data collector attempted to access full text via a PDF locator (http://www.pdfsearchengine.net/). The percentage (95% confidence interval [CI]) of articles with free full-text access from PEDro, PubMed, and the PDF locator website were calculated. Logistic regression was used to evaluate the association between free full-text access and article characteristics. Free full text could be accessed via PEDro for 51% of the articles (95% CI: 44, 58). PEDro had 4% higher free access than PubMed (95% CI: 1, 7). Access via PEDro did not vary systematically with time, geographic location, or article characteristics. Access improved by 9% (95% CI: 6, 14) by adding a PDF locator website. PEDro is a good source of free full-text articles for physical therapists and other rehabilitation professionals. Evidence resources, professional organisations, employers, researchers, and research agencies could all help to increase access to free full text.


In vitro protection of amphibian gastric mucosa by nutrient HCO3- against aspirin injury.
The effects of luminal aspirin [acetylsalicylic acid (ASA)] at luminal pH 4.5 and pH 3.0 on Ussing chambered amphibian gastric fundic and antral mucosae were investigated using different concentrations of HCO3- ([HCO3-]) in the nutrient solution in histamine-stimulated or metiamide-treated tissues. The severe surface cell and oxyntic gland injury seen in histamine-stimulated tissues after a 3-h exposure to 20 mM ASA at luminal pH 4.5 in HCO3- -free nutrient solution (HEPES) was prevented by including 18 mM or 48 mM HCO3- in the nutrient solution. At luminal pH 3.0, 48 mM HCO3- in the nutrient solution delayed the histologic damage to the surface epithelium and oxyntic glands caused by a 30-min exposure to 20 mM luminal ASA, but it afforded no protection to a 60-min exposure. This protection of the gastric epithelium by a high nutrient [HCO3-] did not occur in metiamide-treated tissues at luminal pH 3.0. Although the injury to antral epithelial cells exposed to 20 mM luminal ASA at luminal pH 3.0 or 4.5 was less severe than that in fundic mucosae, 48 mM HCO3- in the nutrient solution also afforded clear protection in this tissue. A high nutrient [HCO3-] prevented the sharp fall in the potential difference observed in fundus exposed to ASA at luminal pH 4.5 and delayed the fall in potential difference observed in fundic and antral mucosae exposed to ASA at luminal pH 3.0. The high nutrient [HCO3-] did not prevent the increase in resistance observed in tissues during ASA exposure at luminal pH 4.5 and 3.0. The electrical data reflect not only the damaged surface and oxyntic cells caused by ASA, but also the complex effects of ASA on active and passive ion transport. We conclude the following: (a) The mucosal injury to the fundus and antrum caused by luminal ASA is prevented by 48 mM HCO3- in the nutrient solution when luminal pH is 3.0 and by 18 mM HCO3- when luminal pH is 4.5. Absence of nutrient HCO3- accentuates the injury caused by luminal ASA. (b) The luminal pH, concentration, and time of exposure influence the depth and severity of ASA injury to the fundic and antral mucosa. (c) The electrophysiologic and morphologic changes after ASA exposure are not interrelated, due to the complex effects of ASA on the ion transport and morphology of the gastric epithelium.


Erratum: Nitrogen Supply Affects Yield and Grain Filling of Maize by Regulating Starch Metabolizing Enzyme Activities and Endogenous Hormone Contents.
[This corrects the article DOI: 10.3389/fpls.2021.798119.].


Combination of ultrasound treatment and starter culture for improving the quality of beef jerky.
The effects of treatment by ultrasound (US), inoculation of Pediococcus acidilactici BP2 strain (BP), and their combination (US-BP) on the quality characteristics of beef jerky were investigated during fermentation for 6 days. Moisture contents and water activity were highest after the US and US-BP treatments (P < 0.05). These effects were attributed to the decreased moisture mobility in beef jerky during ultrasonication. Meanwhile, samples treated with US and US-BP displayed more broken muscle fibers and larger gaps and cavities between the adjacent muscle bundles, resulting in lower shear force values compared to the other samples (P < 0.05), which indicated that the US and US-BP treatments improved the tenderness of beef jerky. Moreover, treatment with BP promoted the flavor development of beef jerky. The US-BP treatment improved the sensory attributes of beef jerky. In conclusion, US-BP is a promising strategy to improve the quality of beef jerky.


Of Mice and Men and Plethysmography Systems: Does LKB1 Determine the Set Point of Carotid Body Chemosensitivity and the Hypoxic Ventilatory Response?
Our recent studies suggest that the level of liver kinase B1 (LKB1) expression in some way determines carotid body afferent discharge during hypoxia and to a lesser extent during hypercapnia. In short, phosphorylation by LKB1 of an as yet unidentified target(s) determines a set point for carotid body chemosensitivity. LKB1 is the principal kinase that activates the AMP-activated protein kinase (AMPK) during metabolic stresses, but conditional deletion of AMPK in catecholaminergic cells, including therein carotid body type I cells, has little or no effect on carotid body responses to hypoxia or hypercapnia. With AMPK excluded, the most likely target of LKB1 is one or other of the 12 AMPK-related kinases, which are constitutively phosphorylated by LKB1 and, in general, regulate gene expression. By contrast, the hypoxic ventilatory response is attenuated by either LKB1 or AMPK deletion in catecholaminergic cells, precipitating hypoventilation and apnea during hypoxia rather than hyperventilation. Moreover, LKB1, but not AMPK, deficiency causes Cheyne-Stokes-like breathing. This chapter will explore further the possible mechanisms that determine these outcomes.


Water absorption characteristics of dental composites incorporating hydroxyapatite filler.
Water uptake characteristics of BisGMA-based composites incorporating untreated and surface-treated hydroxyapatite (HA) with a silane coupling agent have been investigated. The water absorption and desorption behaviour of these composites obeyed the classical diffusion theory. The diffusion coefficients of the composites during first absorption were very similar to that for the base resin, suggesting that the water uptake process occur mainly in the resin matrix. The incorporation of HA reduced the water uptake of the base resin and lower uptake was found for those formulated with surface-treated HA. It was also observed that the equilibrium uptake decreased with increasing filler loading. However, the filled specimens had a higher water absorption than which would be expected on the basis of the resin content. This increase in the water uptake was largely due to the presence of porosity and filler particle aggregates in the microstructure of composites, although the adsorption of some water onto the filler surface has not been ruled out. The experimental composites showed higher solubilities than that obtained for the base resin.


Fecal indicator bacteria are abundant in wet sand at freshwater beaches.
Potential fecal contamination of sand in the wave-washed zone of public bathing beaches is overlooked in beach monitoring programs. Activity in this zone can bring pathogens to the sand surface or into the water, presenting a health risk to sensitive populations. On a unit weight basis (colony forming units per 100g), the mean summer abundance of the fecal indicator bacteria enterococci and Escherichia coli was 3-38 times higher in the top 20 cm of wet-sand cores than in the water column at six freshwater bathing beaches. E. coli were 4 times more abundant than enterococci in water but counts were similar in the sand. A correlation (r=0.60) existed between E. coli counts in the water and in the top 5 cm of sand only, whereas no relationship existed between enterococci abundance in water and sand. In general, enterococci were most numerous in the 5-10 cm sand stratum and E. coli in the 0-5 cm stratum. These preliminary data show that wet freshwater beach sand is a reservoir of fecal indicator bacteria. Enteric pathogens may also be present in beach sand.


Decoding working memory-related information from repeated psychophysiological EEG experiments using convolutional and contrastive neural networks.
Objective.Extracting reliable information from electroencephalogram (EEG) is difficult because the low signal-to-noise ratio and significant intersubject variability seriously hinder statistical analyses. However, recent advances in explainable machine learning open a new strategy to address this problem.Approach.The current study evaluates this approach using results from the classification and decoding of electrical brain activity associated with information retention. We designed four neural network models differing in architecture, training strategies, and input representation to classify single experimental trials of a working memory task.Main results.Our best models achieved an accuracy (ACC) of 65.29 ± 0.76 and Matthews correlation coefficient of 0.288 ± 0.018, outperforming the reference model trained on the same data. The highest correlation between classification score and behavioral performance was 0.36 (p= 0.0007). Using analysis of input perturbation, we estimated the importance of EEG channels and frequency bands in the task at hand. The set of essential features identified for each network varies. We identified a subset of features common to all models that identified brain regions and frequency bands consistent with current neurophysiological knowledge of the processes critical to attention and working memory. Finally, we proposed sanity checks to examine further the robustness of each model's set of features.Significance.Our results indicate that explainable deep learning is a powerful tool for decoding information from EEG signals. It is crucial to train and analyze a range of models to identify stable and reliable features. Our results highlight the need for explainable modeling as the model with the highest ACC appeared to use residual artifactual activity.


Transplantation of fetal brain tissue into the site of intracerebral hemorrhage in rats.
The purpose of this study was to evaluate whether transplantation of fetal forebrain tissue into the hematoma site of rats with intrastriatal hemorrhage could improve the final neurological outcome. Nine to twelve days after collagenase-induced intracerebral hemorrhage, day 14 fetal forebrain fragments were transplanted into hematoma site. Quantitative measures of behavioral function were repeatedly evaluated until the rats were killed 10 weeks after grafting. Histology was used to assess the survival of the grafts and overall brain morphology. Surviving grafts were located in the residual cavity at the hematoma site. However, comparison of rats with live transplants to control rats with no transplant, sham transplant, or dead tissue transplant revealed no statistically significant differences in any of the motor tests.


An inexpensive, rapid and precise affinity chromatography method for the measurement of glycosylated haemoglobins.
We have assessed an affinity chromatography technique, using commercially available materials, for the estimation of total glycosylated haemoglobin in the routine clinical chemistry laboratory. The method gives good discrimination between normals (7.31 +/- 0.92%) and diabetics (12.70 +/- 2.88%) and has excellent precision (CV 1.5-2.0%). Labile glycosylated haemoglobin is normally removed as it is so variable. There is no significant correlation between labile glycosylated haemoglobin and blood glucose. Immediate analysis of incubated haemolysates is preferable to storage of haemolysates or erythrocytes. The affinity gel can be reused about 16 times, but oxidation must be reduced by keeping the gel at 4 degrees C in the dark when not in use. The cost of the gel is about 7p a test and 60 samples can be analysed in a working day. The method is not affected by the presence of up to 20% met-haemoglobin and should also give correct values for samples containing genetic variants of haemoglobin.


Structure and proposed activity of a member of the VapBC family of toxin-antitoxin systems. VapBC-5 from Mycobacterium tuberculosis.
In prokaryotes, cognate toxin-antitoxin pairs have long been known, but no three-dimensional structure has been available for any given complex from Mycobacterium tuberculosis. Here we report the crystal structure and activity of a member of the VapBC family of complexes from M. tuberculosis. The toxin VapC-5 is a compact, 150 residues, two domain alpha/beta protein. Bent around the toxin is the VapB-5 antitoxin, a 33-residue alpha-helix. Assays suggest that the toxin is an Mg-enabled endoribonuclease, inhibited by the antitoxin. The lack of DNase activity is consistent with earlier suggestions that the complex represses its own operon. Furthermore, analysis of the interactions in the binding of the antitoxin to the toxin suggest that exquisite control is required to protect the bacteria cell from toxic VapC-5.


Novel cationic polyelectrolyte coatings for capillary electrophoresis.
The use of bare fused silica capillary in CE can sometimes be inconvenient due to undesirable effects including adsorption of sample or instability of the EOF. This can often be avoided by coating the inner surface of the capillary. In this work, we present and characterize two novel polyelectrolyte coatings (PECs) poly(2-(methacryloyloxy)ethyl trimethylammonium iodide) (PMOTAI) and poly(3-methyl-1-(4-vinylbenzyl)-imidazolium chloride) (PIL-1) for CE. The coated capillaries were studied using a series of aqueous buffers of varying pH, ionic strength, and composition. Our results show that the investigated polyelectrolytes are usable as semi-permanent (physically adsorbed) coatings with at least five runs stability before a short coating regeneration is necessary. Both PECs showed a considerably decreased stability at pH 11.0. The EOF was higher using Good's buffers than with sodium phosphate buffer at the same pH and ionic strength. The thickness of the PEC layers studied by quartz crystal microbalance was 0.83 and 0.52 nm for PMOTAI and PIL-1, respectively. The hydrophobicity of the PEC layers was determined by analysis of a homologous series of alkyl benzoates and expressed as the distribution constants. Our result demonstrates that both PECs had comparable hydrophobicity, which enabled separation of compounds with log Po/w > 2. The ability to separate cationic drugs was shown with β-blockers, compounds often misused in doping. Both coatings were also able to separate hydrolysis products of the ionic liquid 1,5-diazabicyclo[4.3.0]non-5-ene acetate at highly acidic conditions, where bare fused silica capillaries failed to accomplish the separation.


Prenatal exposure to silver is associated with an elevated risk for neural tube defects: a case-control study.
Exposure to copper, silver, and titanium has been reported to be associated with a variety of adverse effects on humans, but it is little focused on the fetus. We investigated the associations between prenatal exposure to the three metals (copper, silver, and titanium) and risk for fetal neural tube defects (NTDs). Placental samples from 408 women with pregnancies affected by NTDs and 593 women with normal pregnancies were collected from 2003 to 2016 in Pingding, Xiyang, Shouyang, Taigu, and Zezhou counties of China. Multilevel mixed-effects logistic regression and Bayesian kernel machine regression (BKMR) were used to evaluate the single and joint effects of the metals on NTDs. Silver was associated with an increased risk for NTDs in a dose-response fashion in single-metal logistic regression, with adjusted odds ratios (95% confidence intervals) of 1.78 (1.04-3.06) and 1.92 (1.11-3.32) in the second and third tertiles, respectively, compared to the lowest tertile. BKMR revealed toxic effects of silver on NTDs and the association appeared to be linear. No interaction of silver with any of the other two metals was observed. Besides, silver concentration was positively correlated with maternal certain dietary intakes. Placental high silver concentrations are associated with an elevated risk for NTDs. Maternal diet may be a source of silver exposure.


Prevalence of moderate and severe renal insufficiency in older persons with hypertension, diabetes mellitus, coronary artery disease, peripheral arterial disease, ischemic stroke, or congestive heart failure in an academic nursing home.
To determine the prevalence of moderate and severe renal insufficiency in older persons in an academic nursing home. The prevalence of an estimated glomerular filtration rate (GFR) determined by the Modification of Diet in Renal Disease equation less than 60 mL/min/1.73 m(2) was investigated in older persons in an academic nursing home with either hypertension, diabetes mellitus, coronary artery disease (CAD), peripheral arterial disease (PAD), ischemic stroke, or congestive heart failure (CHF). An academic nursing home. Two hundred and two persons (104 women and 98 men), mean age 73 years (range 50 to 98 years) residing in an academic nursing home. Prevalence of a GFR less than 60 mL/min/1.73 m(2). A GFR less than 60 mL/min/1.73 m(2) was present in 60 (42%) of 143 persons with hypertension, in 30 (48%) of 62 persons with diabetes mellitus, in 28 (52%) of 52 persons with CAD, in 13 (50%) of 26 persons with PAD, in 10 (44%) of 23 persons with ischemic stroke, and in 15 (63%) of 24 persons with CHF. Older persons with hypertension, diabetes mellitus, CAD, PAD, ischemic stroke, or CHF have a high prevalence of moderate or severe renal insufficiency and should be treated optimally to reduce the increased risk of cardiovascular events and mortality in this high-risk population.


Role of TGF-beta in proliferative vitreoretinal diseases and ROCK as a therapeutic target.
Cicatricial contraction of preretinal fibrous membrane is a cause of severe vision loss in proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). TGF-beta is overexpressed in the vitreous of patients with proliferative vitreoretinal diseases and is also detectable in the contractile membranes. Therefore, TGF-beta is presumed to contribute to the cicatricial contraction of the membranes, however, the underlying mechanisms and TGF-beta's importance among various other factors remain to be elucidated. Vitreous samples from PDR or PVR patients caused significantly larger contraction of hyalocyte-containing collagen gels, compared with nonproliferative controls. The contractile effect was strongly correlated with the vitreal concentration of activated TGF-beta2 (r = 0.82, P < 0.0001). PDR or PVR vitreous promoted expression of alpha-smooth muscle actin (alpha-SMA) and phosphorylation of myosin light chain (MLC), a downstream mediator of Rho-kinase (ROCK), both of which were dramatically but incompletely suppressed by TGF-beta blockade. In contrast, fasudil, a potent and selective ROCK inhibitor, almost completely blocked the vitreous-induced MLC phosphorylation and collagen gel contraction. Fasudil disrupted alpha-SMA organization, but it did not affect its vitreal expression. In vivo, fasudil significantly inhibited the progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells by electroretinographic and histological analyses. These results elucidate the critical role of TGF-beta in mediating cicatricial contraction in proliferative vitreoretinal diseases. ROCK, a key downstream mediator of TGF-beta and other factors might become a unique therapeutic target in the treatment of proliferative vitreoretinal diseases.


Genistein attenuates oxidative damage in preeclamptic placental trophoblast.
To evaluate the effect of genistein supplementation on the oxidative/nitrative stress and antioxidant capacity of normotensive and preeclamptic placental trophoblast. The stress status of placental trophoblast was assessed by measuring their respective markers before and after incubation with genistein. A significant increase in stress along with decrease in antioxidant status was observed in preeclamptic placental trophoblast, whereas genistein incubation significantly alters oxidant-antioxidant status. The study revealed that genistein may play a significant role in controlling oxidative/nitrative stress during preeclampsia. Hence, genistein can be used as an effective dietary supplement for the treatment and management of preeclampsia.


Quantification of plasticity of plant traits in response to light intensity: comparing phenotypes at a common weight.
Plasticity of plant traits is commonly quantified by comparing different phenotypes at the same age. In this paper, we present a method in which the effect of resource conditions on plant weight is used as a basis for quantifying the plasticity of individual plant traits. Abutilon theophrasti individuals were grown in, and some transferred between, high and low intensity light conditions, resulting in four phenotypes. Plant traits were found to exhibit different degrees of plasticity, decreasing in this order: height; specific leaf area; allocation to branch roots; allocation to leaf area; number of nodes; allocation to tap roots; allocation to stem; allocation to leaf weight. Under these conditions, individuals of the four phenotypes had very similar heights when compared at the same age, but very different heights when compared at the same plant weight. The latter comparison indicates that light intensity influences height independently of its influence on plant weight. Individuals that were transferred from high to low light had greater allocation that had not been transferred, but individuals of all phenotypes had nearly the same leaf weight allocation when compared at the same plant weight. The latter comparison indicates that light intensity influeces leaf weight allocation mostly by influencing plant weight. In the phenotype resulting from the transfer of plants from low to high light, reproduction was stimulated much less than plant weight and axillary leaf growth, and reproductive allocation was delayed relative to the other three phenotypes. We conclude that when plasticity is measured by comparing phenotypes at the same plant weight, the effects of resources on plant size can be excluded from the quantification.


Advancing the scholarship and practice of stakeholder engagement in working landscapes: a co-produced research agenda.
Participatory approaches to science and decision making, including stakeholder engagement, are increasingly common for managing complex socio-ecological challenges in working landscapes. However, critical questions about stakeholder engagement in this space remain. These include normative, political, and ethical questions concerning who participates, who benefits and loses, what good can be accomplished, and for what, whom, and by who. First, opportunities for addressing justice, equity, diversity, and inclusion interests through engagement, while implied in key conceptual frameworks, remain underexplored in scholarly work and collaborative practice alike. A second line of inquiry relates to research-practice gaps. While both the practice of doing engagement work and scholarly research on the efficacy of engagement is on the rise, there is little concerted interplay among 'on-the-ground' practitioners and scholarly researchers. This means scientific research often misses or ignores insight grounded in practical and experiential knowledge, while practitioners are disconnected from potentially useful scientific research on stakeholder engagement. A third set of questions concerns gaps in empirical understanding of the efficacy of engagement processes and includes inquiry into how different engagement contexts and process features affect a range of behavioral, cognitive, and decision-making outcomes. Because of these gaps, a cohesive and actionable research agenda for stakeholder engagement research and practice in working landscapes remains elusive. In this review article, we present a co-produced research agenda for stakeholder engagement in working landscapes. The co-production process involved professionally facilitated and iterative dialogue among a diverse and international group of over 160 scholars and practitioners through a yearlong virtual workshop series. The resulting research agenda is organized under six cross-cutting themes: (1) Justice, Equity, Diversity, and Inclusion; (2) Ethics; (3) Research and Practice; (4) Context; (5) Process; and (6) Outcomes and Measurement. This research agenda identifies critical research needs and opportunities relevant for researchers, practitioners, and policymakers alike. We argue that addressing these research opportunities is necessary to advance knowledge and practice of stakeholder engagement and to support more just and effective engagement processes in working landscapes. The online version contains supplementary material available at 10.1007/s42532-022-00132-8.


Recombinant human bone morphogenetic protein 2 outcomes for maxillary sinus floor augmentation: a systematic review and meta-analysis.
To study the effect of the recombinant human bone morphogenetic protein 2 (rhBMP-2) on sinus volumetric and histometric changes after sinus floor augmentation compared to a conventional approach of non-biologic bone grafting materials. An electronic search of 4 databases (January 1990-February 2015), including PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Central, and a hand search of peer-reviewed journals for relevant articles were performed. Human clinical trials with data on comparison of sinus volumetric and/or histometric outcomes with and without the use of rhBMP-2 in sinus grafting procedures, with ≥10 augmentation sites in each study group, and with a follow-up period of at least 6 months, were included. Random-effects meta-analyses were performed to analyze weighted mean difference (WMD) and confidence interval (CI) for the recorded variables according to PRISMA guidelines. Six randomized controlled trials (RCTs) were included. The results of the meta-analyses showed that the WMD of vertical bone height gain was -0.14 mm (95% CI = -1.91 to 1.62 mm, P = 0.87), the WMD of bone density was -142.42 mg/cm3 (95% CI = -310.62-25.78 mg/cm3 , P = 0.10), the WMD of the percentage of vital bone was -4.59% (95% CI = -11.73-2.56%, P = 0.21), and the WMD of the percentage of residual bone grafting materials was -9.90% (95% CI = -26.38-6.58%, P = 0.21). The comparison of implant survival rate presented an overall risk ratio of 1.00 (95% CI = 0.94-1.07). The two approaches (conventional bone grafting compared to BMPs) demonstrated comparable effectiveness for both clinical and histomorphometric measures. This systematic review revealed that the use of rhBMP-2 in maxillary sinus floor augmentation achieved similar clinical and histometric outcomes when compared to conventional sinus grafting procedures after a healing period of 6-9 months. However, previous studies showed the morbidity and other patient-reported outcomes were improved in rhBMP-2 approaches as compared to bone autograft procedures (both intraoral and extraoral bone harvesting because no donor site is required). Long-term studies are required to determine the cost-benefit of sinus floor augmentation procedures for patients requiring implant reconstruction.


Agreement between Self- and Physician‑Sampling for Detection of High‑Risk Human Papillomavirus Infections in Women Attending Cervical Screening at National Cancer Institute, Thailand.
We determined testing of self-sampling vagina swabs for Human Papilloma Virus (HPV) can be used to screen for cervical disease in outpatient clinics. In this study, women attending cervical cancer screening clinic and gynecology clinic of the National Cancer Institute were invited to take a vaginal self-sampling and physician-collected cervical sampling. Of 268 participants, 20 (7.5%) were HPV-positive on the physician-collected samples. Among these screen-positive women, only two (0.7%) had HPV 18 and/or 45 and none had HPV 16 infections. For the self-collected samples, 4 participants had invalid HPV test results. Of the remaining 264 women with valid test results on self-collected samples, 29 (11.0 %) were HPV-positive, of whom, two (0.8%) were infected with HPV 16 and one (0.4%) with HPV 18 and/or 45 infections. The agreement between self-sampling and physician-sampling HPV test results (when two HPV results categories were considered) was 92. 8% with a moderate Kappa value of 0.57. Overall, self-sampling seems to be a reliable alternative to health-provider collection. However, instructions on proper procedures for sample collection to the women are important step before general roll out.


Results of sequential swallowing assessments in patients undergoing upfront surgery for oral tongue squamous cell carcinoma.
The swallowing outcomes in patients undergoing glossectomy have been inconsistently reported in the literature owing to variable follow up times, different tools for assessment and lack of single institution large scale studies. The aim of our study was to assess the patterns of swallowing outcomes over time and identify factors affecting nasogastric tube dependency at 1-year post-surgery. This was a retrospective study of treatment naïve patients with oral tongue carcinoma who underwent surgery and attended the speech and swallow clinic between January 2016 and December 2019 at our institute were included in the study. The findings of swallowing assessment by a speech language pathologist at three time points were recorded. A total of 606 patients were found eligible for the study. The median age of the patients was 50 years with the 211 (34.8%) patients having T3/T4 disease. The swallowing outcomes in terms of tube dependence and the spectrum of diet tolerance seem to improve over time with an increasing number of patients switching over to a solid diet by 1 year. A higher defect class (HR = 24.43 [3.48-171.27]) and presence of co-morbidities (HR = 4.17 [1.59-10.92]) were associated with sustained feeding tube dependency status at 1 year. A nomogram was developed based on these findings. The swallowing outcomes in terms of tube dependence and the spectrum of diet tolerance seem to improve over time. A higher defect class and presence of co-morbidities were associated with NGT dependency at 1 year.


Illustrated guide to surgical technique for vasectomy of the common marmoset.
The surgical technique for vasectomy of the common marmoset (Callithrix jacchus) is described and illustrated.


The relative incidence of fractures at the base of the proximal phalanx of the thumb in children.
There is disagreement in the literature about the most common fracture type at the base of the proximal phalanx of the thumb in children below the age of adolescence. In this prospective study, 58 consecutive children aged 10 years or less with isolated fractures of the base of the proximal phalanx of the thumb were included and their radiographs were reviewed. The study included 38 boys and 20 girls with a mean age of 8 (range 1-10) years. After excluding one patient, in whom the type of fracture could not be determined, the most common fracture in the remaining 57 cases was the Salter-Harris type II fracture (72%), followed by the juxta-epiphyseal type II fracture (18%).


Beyond performance: the role of task demand, effort, and individual differences in ab initio pilots.
Aviation safety depends on the skill and expertise of pilots to meet the task demands of flying an aircraft in an effective and efficient manner. During flight training, students may respond differently to imposed task demands based on individual differences in capacity, physiological arousal, and effort. To ensure that pilots achieve a common desired level of expertise, training programs should account for individual differences to optimize pilot performance. This study investigates the relationship between task performance and physiological correlates of effort in ab initio pilots. Twenty-four participants conducted a flight simulator task with three difficulty levels and were asked to rate their perceived demand and effort using the NASA TLX. We recorded heart rate, EEG brain activity, and pupil size to assess changes in the participants' mental and physiological states across different task demands. We found that, despite group-level correlations between performance error and physiological responses, individual differences in physiological responses to task demands reflected different levels of participant effort and task efficiency. These findings suggest that physiological monitoring of student pilots might provide beneficial insights to flight instructors to optimize pilot training at the individual level.


Therapy of obese patients with cardiovascular disease.
Obesity has reached epidemic proportions and is a significant public health concern. Obesity is associated with increased diabetes, cardiovascular and kidney disease, and associated morbidity and mortality. Despite the increasing public health problem of obesity, there is a dearth of effective treatment options. Following the FDA mandated withdrawal of sibutramine, the treatment options for obesity were limited to orlistat as the only pharmacological treatment option for long-term management of obesity. Recently two new medications (Belviq and Qsymia) were approved by FDA for long-term management of obesity. Many other antiobesity drugs are under development. Bariatric surgery has been shown to be effective in the treatment of obesity and its comorbidities. The available data suggest that even modest weight loss improves diabetes and cardiovascular disease (CVD) risk factors. We summarize the treatment options for obesity and the efficacy of these options in ameliorating cardiovascular risk factors. We also focus on the recently approved antiobesity drugs.


Imipridones affect tumor bioenergetics and promote cell lineage differentiation in diffuse midline gliomas.
Pediatric diffuse midline gliomas (DMGs) are incurable childhood cancers. The imipridone ONC201 has shown early clinical efficacy in a subset of DMGs. However, the anticancer mechanisms of ONC201 and its derivative ONC206 have not been fully described in DMGs. DMG models including primary human in vitro (n = 18) and in vivo (murine and zebrafish) models, and patient (n = 20) frozen and FFPE specimens were used. Drug-target engagement was evaluated using in silico ChemPLP and in vitro thermal shift assay. Drug toxicity and neurotoxicity were assessed in zebrafish models. Seahorse XF Cell Mito Stress Test, MitoSOX and TMRM assays, and electron microscopy imaging were used to assess metabolic signatures. Cell lineage differentiation and drug-altered pathways were defined using bulk and single-cell RNA-seq. ONC201 and ONC206 reduce viability of DMG cells in nM concentrations and extend survival of DMG PDX models (ONC201: 117 days, P = .01; ONC206: 113 days, P = .001). ONC206 is 10X more potent than ONC201 in vitro and combination treatment was the most efficacious at prolonging survival in vivo (125 days, P = .02). Thermal shift assay confirmed that both drugs bind to ClpP, with ONC206 exhibiting a higher binding affinity as assessed by in silico ChemPLP. ClpP activation by both drugs results in impaired tumor cell metabolism, mitochondrial damage, ROS production, activation of integrative stress response (ISR), and apoptosis in vitro and in vivo. Strikingly, imipridone treatment triggered a lineage shift from a proliferative, oligodendrocyte precursor-like state to a mature, astrocyte-like state. Targeting mitochondrial metabolism and ISR activation effectively impairs DMG tumorigenicity. These results supported the initiation of two pediatric clinical trials (NCT05009992, NCT04732065).


Metabolic clearance rate of plasma deoxycorticosterone sulfate in men and women.
In the present investigation, we determined the metabolic clearance rate of plasma deoxycorticosterone sulfate in adult men and nonpregnant women and in one women pregnant at 42 weeks gestation with an anencephalic fetus. The values obtained varied from 618 to 10701/24 h. The metabolic clearance rate of deoxycorticosterone sulfate, expressed as a function of body surface area, was 495 +/- 31.71/24 h/m2 (mean +/- SEM) and was not significantly different among men and nonpregnant women. In a woman pregnant with an anencephalic fetus at 42 weeks gestation, the metabolic clearance rate of deoxycorticosterone sulfate was 6441/24 h/m2. We suggest that the high clearance rate of this steroid 21-sulfate, compared with those of other steroid sulfates, is due to rapid excretion of deoxycorticosterone sulfate into bile and irreversible metabolism in intestine by bacterial enzymes.


Finding risk in all the right places.
In this issue of Neuron, Cruchaga et al. (2013) identify genetic variability linked to altered levels of tau protein in cerebrospinal fluid. They show that the same genetic variants can also confer risk for Alzheimer's disease.


Using the past to predict the future.
This research addressed three issues. First, we examined whether retrospective confidence judgments (RCJs) and judgments of learning (JOLs) assess memory differently. Second, we examined the relative accuracy of JOLs and RCJs at predicting future recall performance. Third, we examined whether making JOLs improves subsequent recall better than making RCJs or making no metacognitive judgment. Results suggest that RCJs and JOLs are both based on retrievability, but that participants use their memory differently when making JOLs. RCJs were more accurate than JOLs at predicting future recall for some subsets of items, but the reverse was true for other subsets of items. Finally, eventual recall performance was facilitated when participants made JOLs but not when they made RCJs, suggesting that the JOL task helps to improve people's learning of the items.


Vasa previa: clinical presentations, outcomes, and implications for management.
To review experience with diagnosis, clinical associations, and outcomes of vasa previa in a single institution. This was a retrospective review of all identified vasa previa cases from January 1 1990, to June 30, 2010. Sixty cases of vasa previa were identified (53 singletons, seven twins); 56 cases were diagnosed before delivery. An abnormal cord insertion or abnormal placental location was present in 55 cases. Missed diagnoses were attributed to technical and observer factors. Preterm bleeding was encountered in 25 (42%) case group participants. Seven case group participants required an emergent delivery, with significant neonatal morbidity and mortality. Twin pregnancies had a significantly earlier median age at delivery of 32 weeks of gestation compared with 35 weeks of gestations in singletons (P=.01). The seven twin pregnancies had a 28.6% emergent preterm delivery rate, whereas singletons had a 4.1% rate (P=.07). In 14 case group participants, the membranous fetal vessel was located in the lower uterus and not directly over the cervix. The vessel location was not related to the risk of emergent delivery. Transvaginal ultrasound scans of at-risk patients can identify most cases of vasa previa. Preterm bleeding does not usually require immediate delivery. The rate of emergent preterm delivery was low in singleton pregnancies. Twins were delivered, on average, 3 weeks earlier than singletons. III.


Extrapulmonary Pleuropulmonary Blastoma in a 3-Year-Old Child: A Case Report and Review of Literature.
Pleuropulmonary blastomas (PPBs) are very rare, highly aggressive, dysembryonic neoplasms of thoracopulmonary mesenchyme. These have been reported in the pediatric population and account for only 0.5%-1% of all primary malignant lung cancers. They normally arise from lung tissue, however rarely the parietal pleura may be the tissue of origin (extra pulmonary PPB) which are extremely rare. Common age of presentation is three to 4 years. The prognosis is poor with distant metastasis to central nervous system and bone with survival rate of approximately 42.9% at 5 years. They are managed by aggressive multimodal therapies including surgery and chemotherapy. We report a case of a 3-year-old male child with Type 2 PPB of the left hemithorax, managed by surgical excision of the mass and adjuvant chemotherapy.


Rabbit lung after inhalation of soluble nickel. II. Effects on lung tissue and phospholipids.
Rabbits were exposed to soluble nickel chloride, about 0.3 mg/m3 as nickel, for about 1 month (5 days/week, 6 hr/day). The upper lobe in the left lung was examined with light microscopy and samples from the left lower lobe with electron microscopy. Nodular accumulation of macrophages and laminated structures occurred in alveoli of all exposed rabbits, but otherwise no inflammatory reactions. Volume density of the alveolar epithelial type II cells was doubled due to increased cell number as well as cell volume. The tissue content of phospholipids, determined in the lower lobe of the left lung, had increased by about 40%, mainly due to elevated disaturated phosphatidylcholines. The effect pattern was almost identical to that seen earlier in inhalation experiments with metallic nickel dust, strongly indicating that nickel ions are responsible also for the changes seen after exposure to metallic nickel. This suggests that all nickel compounds may produce the pathological condition, which is similar to that seen in the disease pulmonary alveolar proteinosis.


Imaging of developmental dysplasia of the hip: ultrasound, radiography and magnetic resonance imaging.
Developmental dysplasia of the hip (DDH) describes a broad spectrum of developmental abnormalities of the hip joint that are traditionally diagnosed during infancy. Because the development of the hip joint is a dynamic process, optimal treatment depends not only on the severity of the dysplasia, but also on the age of the child. Various imaging modalities are routinely used to confirm suspected diagnosis, to assess severity, and to monitor treatment response. For infants younger than 4 months, screening hip ultrasound (US) is recommended only for those with risk factors, equivocal or positive exam findings, whereas for infants older than 4-6 months, pelvis radiography is preferred. Following surgical hip reduction, magnetic resonance (MR) imaging is preferred over computed tomography (CT) because MR can not only confirm concentric hip joint reduction, but also identify the presence of soft-tissue barriers to reduction and any unexpected postoperative complications. The routine use of contrast-enhanced MR remains controversial because of the relative paucity of well-powered and validated literature. The main objectives of this article are to review the normal and abnormal developmental anatomy of the hip joint, to discuss the rationale behind the current recommendations on the most appropriate selection of imaging modalities for screening and diagnosis, and to review routine and uncommon findings that can be identified on post-reduction MR, using an evidence-based approach. A basic understanding of the physiology and the pathophysiology can help ensure the selection of optimal imaging modality and reduce equivocal diagnoses that can lead to unnecessary treatment.


Spectral analysis identifies sites of high-frequency activity maintaining atrial fibrillation in humans.
The identification of sites of dominant activation frequency during atrial fibrillation (AF) in humans and the effect of ablation at these sites have not been reported. Thirty-two patients undergoing AF ablation (19 paroxysmal, 13 permanent) during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126+/-13 points per patient throughout both atria and coronary sinus. At each point, 5-second electrograms were obtained to determine the highest-amplitude frequency on spectral analysis and to construct 3D dominant frequency (DF) maps. The temporal stability of the recording interval was confirmed in a subset. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at sites with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient > or =20%) was evaluated by determining the change in AF cycle length (AFCL) and the termination and inducibility of AF. The spatial distribution of the DF sites was different in patients with paroxysmal and permanent AF; paroxysmal AF patients were more likely to harbor the DF site within the pulmonary vein, whereas in permanent AF, atrial DF sites were more prevalent. Ablation at a DF site resulted in significant prolongation of the AFCL (180+/-30 to 198+/-40 ms; P<0.0001; kappa=0.77), whereas in the absence of a DF site, there was no change in AFCL (169+/-22 to 170+/-22 ms; P=0.4). AF terminated during ablation in 17 of 19 patients with paroxysmal and 0 of 13 with permanent AF (P<0.0001). When 2 patients with nonsustained AF during mapping were excluded, 13 of 15 (87%) had AF termination at DF sites (54% at the initially ablated DF site): 11 pulmonary veins and 2 atrial. In addition, AF could no longer be induced in 69% with termination of AF at a DF site. There were no significant differences in the number or percentage of DF sites detected (5.4+/-1.6 versus 4.9+/-2.1; P=0.3) and ablated (1.9+/-1.0 versus 2.4+/-1.0; P=0.3) in those with and without AF termination. The duration of radiofrequency ablation to achieve termination was significantly shorter than that delivered in those with persisting AF (34.8+/-24.0 versus 73.5+/-22.9 minutes; P=0.0002). All patients with persisting AF had additional DF sites outside the ablated zones. Spectral analysis and frequency mapping identify localized sites of high-frequency activity during AF in humans with different distributions in paroxysmal and permanent AF. Ablation at these sites results in prolongation of the AFCL and termination of paroxysmal AF, indicating their role in the maintenance of AF.


A case of pre-leukaemia masquerading as haemolytic anaemia due to multi-enzymopathy of the red cell.
A 19 year old woman presented as a case of haemolytic anaemia due to multi-enzyme deficiency of the erythrocyte. After a transient improvement with folic acid therapy, she developed acute myeloblastic leukaemia. This is the second reported case of a myelodysplastic syndrome presenting with a haemolytic picture and subsequently developing an acute myeloblastic leukaemia.


Knowledge and attitudes towards rotavirus diarrhea and the vaccine amongst healthcare providers in Yogyakarta Indonesia.
Rotavirus has been identified as the most common pathogen associated with severe diarrhoea. Two effective vaccines against the pathogen have been licensed. However, many countries including Indonesia have yet to introduce the vaccine into their national immunisation programs. This study aimed to examine the attitudes of healthcare providers (HCPs) and other health stakeholders towards the pathogen and the vaccine. Semi-structured in-depth interviews were undertaken in two districts of Yogyakarta Province, Indonesia with nurses, midwives, primary care providers, pediatricians and other health stakeholders. Thematic analysis was undertaken. Fourteen interviews were conducted between August and October 2013. We identified that while participants do not consider diarrhea to be an important problem in Indonesia, they do acknowledge that it can be serious if not properly treated. While the majority had some level of knowledge about rotavirus, not all participants knew that a vaccine was available. There were mixed feelings towards the need for the vaccine. Some felt that the vaccine is not ranked as a priority as it is not listed on the national program. However, others agreed there is a rationale for its use in Indonesia. The cost of the vaccine (when sold in the private sector) was perceived to be the primary barrier impacting on its use. The high cost and the low priority given to this vaccine by the public health authorities are the biggest obstacles impacting on the acceptance of this vaccine in Indonesia. HCPs need to be reminded of the burden of disease associated with rotavirus. In addition, reminding providers about the costs associated with treating severe cases versus the costs associated with prevention may assist with improving the acceptance of HCPs towards the vaccine. Promotion campaigns need to target the range of HCPs involved in the provision of care to infants and pregnant women.


A diastereoselective Mannich-type reaction of α-fluorinated carboxylate esters: synthesis of β-amino acids containing α-quaternary fluorinated carbon centers.
We report a diastereoselective Mannich-type reaction of α-alkyl, α-aryl, and α-vinyl fluoroacetates with N-tert-butylsulfinyl imines. This method provides a powerful means to access a broad range of highly functionalized β-amino acids containing α-fluorinated quaternary stereogenic carbon centers. We also show that the stereochemical outcome of the present reaction is highly dependent on the steric and electronic properties of the fluorocarbon nucleophiles. This protocol uses readily available starting materials, tolerates a variety of functional groups, and is operationally simple.


Postoperative cardiac damage after standardized carotid endarterectomy procedures in low- and high-risk patients.
We conducted a comparison of postoperative cardiac damage, defined as cardiac troponin I (cTn-I) elevation, after carotid endarterectomy in low- and high-risk patients. The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) criteria for stratifying patients considered for carotid endarterectomy into low and high surgical risk groups were used prospectively. All patients had preoperative full cardiologic evaluations and cTn-I value assessments that were repeated on postoperative days 1, 3, and 7. Postoperative cTn-I values ranging from 0.05 to 0.5 ng/mL were classified as myocardial ischemia; values >0.5 ng/mL were classified as myocardial infarction. Mortality was 1.2%, the stroke rate was null, and symptomatic myocardial infarction was null. Among the 56 high-risk patients, 8 had cTn-I values>0.5 ng/mL. Among the 106 low-risk patients, 10 patients had cTn-I value >0.5 ng/mL and 4 patients had cTn-I values that were >0.05 ng/mL and ≤0.5 ng/mL. All patients with increased cTn-I levels were asymptomatic. Concerning all patients, the mean preoperative cTn-I value was 0.007 ng/mL, which increased to 0.438 ng/mL on postoperative day 1 (P=0.017), 0.168 ng/mL on postoperative day 3 (P=0.06), and 0.019 ng/mL on postoperative day 7 (P=0.02). In the high-risk group, the mean preoperative cTn-I value was 0.008 ng/mL, which increased to 0.829 ng/mL on postoperative day 1, 0.270 ng/mL on postoperative day 3, and 0.030 ng/mL on postoperative day 7. In the low-risk group, the mean preoperative cTn-I value was 0.007 ng/mL, which increased to 0.198 ng/mL on postoperative day 1, 0.119 ng/mL on postoperative day 3, and 0.013 ng/mL on postoperative day 7. Patients without cardiac damage showed analogous tendencies in their troponin values. Comparison of troponin values between high- and low-risk patients on each day showed no statistical difference. Electrocardiogram alterations were seen in 20 of the 22 patients with asymptomatic troponin elevation but in none without troponin elevation. Carotid endarterectomy is followed by an increase in cTn-I value>0.5 ng/mL in 14% of all cases, although symptomatic cardiac ischemia is very low. However, high-risk patients as defined by the SAPPHIRE criteria do not show an increased risk of cardiac damage compared to low-risk patients. Larger studies using cTn-I as a marker of postoperative cardiac damage, after carotid endarterectomy or stenting, are needed.


Influence of Paleobacteria on the Proliferative Activity of Human Lymphocytes In Vitro.
When testing the proliferative activity of 14 strains of permafrost microorganisms in the reaction of blast transformation of human lymphocytes in vitro, a strain (Alcaligenes sp.) with mitogen properties was isolated (20-fold increase in the rate of lymphocyte proliferation in comparison with the control). Four strains activated lymphocyte proliferation by 3-9 times in comparison with the control. Three strains produced substances with cytostatic properties and reduced proliferation activity by 33-43% and one strain (Bacillus sp.) almost completely suppressed phytohemagglutinin-induced lymphocyte proliferation. These data indicate that strains with a unique immunobiological potential are concentrated in the population of permafrost microorganisms that have undergone rigorous evolutionary selection.


Predicting factors for emergency peripartum hysterectomy in women with placenta previa.
The aim of the study was to identify predictive factors for peripartum hysterectomy in women with placenta previa. We retrospectively reviewed all singleton pregnancies with a diagnosis of placenta previa, with the distance between the lower placenta edge and the internal cervical os is ≤2 cm, during the period June 2006-May 2010. Antepartum characteristics of women who did and did not undergo peripartum hysterectomy were compared: they include demographical data, obstetrics history, clinical course of the index pregnancy and sonographic findings. Two-hundred and forty-seven women were selected. peripartum hysterectomy was required in 12 cases (4.9%). A statistically significant increased risk emerged for a history of cesarean section (p < 0.001), major placenta previa (p < 0.001), sonographic suspect of placenta accreta (p < 0.001) and gestational age at delivery <34 weeks' gestation (p < 0.001). These four variables were entered into an unconditioned logistic regression model. The resulting adjusted ORs were 23.1 (95% CI 2.3-235.3, p = 0.008), 14.6 (95% CI 0.6-346.5, p = 0.097), 42.4 (95% CI 5.1-354.5, p = 0.001) and 9.3 (95% CI 1.1-76.9, p = 0.037), respectively. This study confirms that placenta previa is a condition at substantial risk of peripartum hysterectomy. A history of cesarean section, the sonographic suspect of placenta accreta and gestational age at delivery were found to be independently associated with this risk. Antepartum ultrasonography in particular plays a crucial role in predicting hysterectomy in these cases.


Histochemical analysis and immunohistochemical profile of mucoepidermoid carcinoma of the conjunctiva.
To elucidate the distinct histochemical and immunohistochemical profile of mucoepidermoid carcinoma of the conjunctiva (MECC) and to determine which combination of stains is most useful in diagnosing MECC and differentiating it from squamous cell carcinoma of the conjunctiva (SCC) in cases where the clinical or cytological findings are not definitive. Eight specimen of MECC from 4 patients and 4 specimens of SCC from 4 patients were examined using a variety of special stains and immunohistochemical markers. The results were then analyzed for usefulness in diagnosing MECC. The most useful markers in diagnosing MECC and differentiating it from SCC are mucicarmine, colloidal iron, and alcian blue all with sensitivities of 88%, and a specificity of 100%; CEA with a sensitivity of 83% and a specificity of 75%; and, mucin-1 with a sensitivity of 100% and a specificity of 25%, but which showed a distinct pattern of staining of MECC when compared to SCC. In our series, the sensitivity of the CK7+/CK20- combination for MECC was only 38%. The most useful stains in ruling out SCC in a suspected case of MECC were shown to be mucicarmine and the glycosaminoglycan (GAG) stains. However, in cases where mucicarmine and the GAG stains are negative or difficult to interpret and there is suspicion of a diagnosis of MECC, CEA and mucin-1 may be helpful for this diagnosis. The findings of CK7+/CK20- also may be of assistance, but are not as sensitive when compared to analogous salivary gland lesions, when differentiating MECC from SCC.


Cluster analysis of Minnesota Multiphasic Personality Inventory (MMPI) profiles in a chronic headache population.
Minnesota Multiphasic Personality Inventory (MMPI) profiles from 123 chronic headache sufferers (48 migraine, 47 muscle contraction, 28 mixed) were cluster analyzed in order to replicate results from other pain populations and to examine differences among the clusters along headache parameters and demographic variables. Four homogeneous subgroups were obtained and a multiple discriminant analysis was successful in correctly classifying 97.56% of the headache subjects. Obtained clusters closely resembled those evidenced in previous pain research. Results indicated that diagnostic category was unrelated to cluster membership; however, frequency of headache occurrence was a differentiating factor. Implications for headache treatment and future research are discussed.


High rate of recanalization of middle cerebral artery occlusion during 2-MHz transcranial color-coded Doppler continuous monitoring without thrombolytic drug.
Experimental evidence indicates that ultrasound can accelerate thrombolysis. We report our findings on early recanalization during transcranial color-coded Doppler (TCCD) continuous monitoring in acute stroke patients with middle cerebral artery (MCA) main stem occlusion. We performed continuous TCCD monitorings in 6 consecutive patients with acute MCA main stem occlusion using a 2-MHz transducer. Patients were not treated with recombinant tissue plasminogen activator. Partial recanalization, defined as blunted waveforms, occurred during monitoring in 5 patients (83%). The mean time to beginning of recanalization was 17.2+/-9.6 minutes. Complete recanalization at 24 hours occurred in only 1 patient. The mean National Institutes of Health Stroke Scale score in the patients who recanalized during monitoring was 21.2+/-4.1 at baseline, 19.2+/-5 at 2 hours, and 15.6+/-3.4 at 24 hours (P=0.1). In this short series of patients with acute MCA main stem occlusion, not treated with recombinant tissue plasminogen activator, we found a high rate of early partial recanalization during continuous exposure to 2-MHz ultrasound.


CRYSTALLINE RETINOPATHY IN A 6-YEAR-OLD BOY WITH HISTORY OF HIGH-DOSE TAMOXIFEN USE.
To report a case of crystalline retinopathy following high-dose tamoxifen use in a pediatric patient. Observational case report. A 6-year-old boy with history of more than 80-g cumulative tamoxifen use over 25 months for the treatment of atypical teratoid/rhabdoid tumor of the posterior fossa presented with a 4-month history of blurred vision. Fundus examination demonstrated multiple superficial foveal refractile opacities in each eye, and spectral optical coherence tomography revealed numerous punctate hyperreflective deposits located within the inner retina. These findings were suggestive of tamoxifen retinopathy. To our knowledge, this is the first report of multimodal retinal imaging of tamoxifen retinopathy in a pediatric patient. Given the risk of permanent vision loss, ophthalmic baseline screening and monitoring should be considered for children receiving tamoxifen.


Accumulation of 152+154Eu(III) by Aspergillus sydowii and Trichoderma harzianum.
Radionuclides-resistant filamentous fungi were isolated from radionuclides' contaminated soils. Effects of contact time, mycelia dosage, pH, ionic strength and thiol compounds on 152+154Eu(III) accumulation on two kinds of filamentous fungi (Aspergillus sydowii and Trichoderma harzianum, denoted as A. sydowii and T. harzianum, respectively) were investigated by batch techniques. The maximum tolerance to Eu(III) concentration of A. sydowii and T. harzianum reached 3000 mg/L and 3500 mg/L, and the Eu(III) accumulation on A. sydowii and T. harzianum can be fitted better with the pseudo-second-order kinetic model, respectively. Filamentous fungi were characterized by FT-IR and acid base titrations, and morphological structures of mycelia changed obviously under Eu(III) stress by SEM and TEM analysis. The results suggested that filamentous fungi could play an important role in the migration and transformation of radionuclides in the environment.


Spiral ganglion cell density in young and old gerbils.
The Mongolian gerbil, like other mammalian species, has a decreased number of spiral ganglion cells as a function of age. This loss of cells was first seen in 24- to 30-month old animals in the basal end of the ganglion. In the oldest individuals the apical end of the ganglion was also affected. There were approximately 15-25% fewer cells in the affected areas in the 36- to 42-month old animals. In the oldest animals degeneration of the stria vascularis was seen in the apical turn and some degenerative changes in the organ of Corti were seen throughout the length of the cochlear duct. The aging pattern in the gerbil cochlea, is similar to that described for other species. Vacuoles, previously described in the gerbil cochlear nucleus, were also seen in the auditory nerve within the modiolus, but central to the Schwann-glial border in all animals. Vacuoles were not present within the spiral ganglion or the peripheral processes of the ganglion cells. Because the ganglion cell axons should be similar on either side of the Schwann-glial border, but the vacuoles were confined to the central nervous system, it is concluded that the degenerative process affects glial cells as opposed to neurons.


An Approach to the Identification and Phylogenetic Analysis of Emerging and Hemorrhagic Fever Viruses.
An important aspect of virological surveillance is the identification of the detected viruses. Broad surveillance, that typically employs deep sequencing of collected tissue samples, provides the investigator with many sequence files constructed from overlapping stretches of DNA sequences. Directed surveillance for viruses of a specific taxonomic group provides the investigator with sequence files from cDNA amplified using specific primers to conserved viral regions. Here we will describe general approaches to identify hemorrhagic viral agents through phylogenetic analysis of cDNA sequences obtained during surveillance activities.


A rare case of Niemann-Pick disease type C without neurological involvement in a 66-year-old patient.
The case of a 66 year-old female - the oldest known living patient with Niemann-Pick disease type C (NP-C) who remains free of any neurological or psychiatric manifestations 18 years after presentation - is presented. An incidental finding of massive splenomegaly was detected during a routine pelvic ultrasound. The pathology report after splenectomy showed the presence of lipid-laden macrophages. Fibroblasts cultured in LDL-enriched medium revealed abnormal filipin staining consistent with cholesterol-filled vesicles and the rate of cholesterol esterification in response to stimulation of LDL-cholesterol uptake was significantly depressed at 6% of that seen in cells from normal controls, but at a level similar to that observed in an NP-C positive control. Molecular genetic testing later revealed a compound heterozygous mutant NP-C genotype comprising two previously described disease-causing mutations in the NPC1 gene, one in exon 8 (c.1133T>C [V378A]) and one in exon 13 (c.1990G>A [V664M]). These findings confirmed the diagnosis of NP-C. Only three patients with this disorder aged > 53 years have previously been reported, all of whom presented with neurological or neuropsychiatric manifestations. Our patient is the first reported NP-C patient, now in her seventh decade of life, who has to date only manifested splenomegaly. This case highlights the extreme clinical variability of NP-C, and the need to consider this disease in the differential diagnosis of organomegaly, even in the absence of neurological, psychiatric and related clinical signs. An elderly female patient with confirmed NP-C and isolated splenomegaly has remained asymptomatic for neurological, cognitive, psychiatric or ophthalmologic abnormailities into her seventh decade of life.


The early results of the Brunelli procedure for trapeziometacarpal instability.
We report the results of Brunelli's abductor pollicis longus transfer for symptomatic instability of the trapeziometacarpal joint in 15 hands (14 patients) at a mean follow-up of 21 months. Patients were assessed subjectively, and objectively by an independent observer. All but one of the patients were very satisfied with the result of the operation, including the six patients who had significant degeneration of the carpometacarpal joint surface preoperatively. Four patients said they had no pain and the mean pain score overall on a visual analogue scale was 1.2 (out of a maximum of 10). Overall the outcome was rated good or excellent in 11 of the 15 thumbs.