Focal nodular hyperplasia of the liver: a clinicopathologic study and review of the literature.
We received the clinical records and pathologic material of 20 patients with biopsy proven hepatic focal nodular hyperplasia. The majority of the patients were females of child bearing age, five of whom had a history of oral use of contraceptives. In every instance focal nodular hyperplasia was an incidental finding; liver function tests were always normal. Focal nodular hyperplasia is a distinct histopathologic entity, distinguishable from liver cell adenoma. Specifically it consists of nodular aggregates of cytologically normal hepatocytes with foci of intranodular bile duct proliferation. Focal nodular hyperplasia appears to be a benign entity, even in patients in whom the lesion was not excised. The association between focal nodular hyperplasia and oral use of contraceptives may be coincidental, although hormonally related vascular changes may be responsible for rupture of the lesion.


How to Write an Urban History of STM on the "Periphery".
Within the STEP research agenda there has never been an explicit focus on the city as a central place for knowledge production. Scholars of the urban history of science tend to concentrate on the metropolis and have not looked in any systematic way at the scientific culture in "peripheral" urban contexts. To fill this gap, this essay proposes to focus on: (1) the role of science, technology and medicine in everyday life and the experiences of the citizens; (2) the plurality of the often conflicting notions of urban modernity; (3) the complex networks of interurban connections between the "peripheries."


Publisher Correction: Discovery and engineering of colchicine alkaloid biosynthesis.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Subtalar Joint Arthrodesis for Elective and Posttraumatic Foot and Ankle Deformities.
Subtalar joint arthrodesis is a procedure used in posttraumatic arthritis, osteoarthritis, tarsal coalition management, posterior tibial tendon dysfunction, and inflammatory arthropathies, and can be used in deformity correction. The goals of the procedure are to eliminate pain, improve function, restore stability, and realign the hind foot. The procedure has high patient satisfaction with low complications while preserving motion in adjacent tarsal joints. Joint preparation is important and time should be spent preparing the joint for successful arthrodesis and the fixation construct needs to be done well and effectively to provide a solid Arbeitsgemeinschaft für Osteosynthesefragen (AO) construct for good results.


Deformability of ascending thoracic aorta aneurysms assessed using ultrafast ultrasound and a principal strain estimator: In vitro evaluation and in vivo feasibility.
Noninvasive vascular strain imaging under conventional line-by-line scanning has a low frame rate and lateral resolution and depends on the coordinate system. It is thus affected by high deformations due to image decorrelation between frames. To develop an ultrafast time-ensemble regularized tissue-Doppler optical-flow principal strain estimator for aorta deformability assessment in a long-axis view. This approach alleviated the impact of lateral resolution using image compounding and that of the coordinate system dependency using principal strain. Accuracy and feasibility were evaluated in two aorta-mimicking phantoms first, and then in four age-matched individuals with either a normal aorta or a pathological ascending thoracic aorta aneurysm (TAA). Instantaneous aortic maximum and minimum principal strain maps and regional accumulated strains during each cardiac cycle were estimated at systolic and diastolic phases to characterize the normal aorta and TAA. In vitro, principal strain results matched sonomicrometry measurements. In vivo, a significant decrease in maximum and minimum principal strains was observed in TAA cases, whose range was respectively 7.9 ± 6.4% and 8.2 ± 2.6% smaller than in normal aortas. The proposed principal strain estimator showed an ability to potentially assess TAA deformability, which may provide an individualized and reliable evaluation method for TAA rupture risk assessment.


Liquid chromatography method for quantifying D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (D-threo-PPMP) in mouse plasma and liver.
A high-performance liquid chromatography (HPLC) method was developed to measure levels of d-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (d-threo-PPMP) in mouse plasma and liver. d-threo-PPMP was measured by HPLC with a Luna Pheny-Hexyl column (5 microm, 250 mm x 4.6 mm) employing UV detection at 210 nm using a mobile phase of potassium phosphate buffer (20mM, pH 3.0)-acetonitrile in a 45:55 (v/v) ratio. d-threo-1-phenyl-2-pentadecanoylamino-3-morpholino-1-propanol (PC15MP) was employed as an internal standard (IS). The lower limit of quantitation (LLOQ) was 0.3 microg/ml. The assay was linear over a concentration range of 0.3-10 microg/ml, with acceptable precision and accuracy. Assayed in plasma, the intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. The method was applied to samples from athymic (nu/nu) mice treated with d-threo-PPMP by intraperitoneal injection. d-threo-PPMP levels of approximately 10-20 microg/ml ( approximately 20-40 microM) in plasma and approximately 45 microg/g in liver were obtained. The present method can be used to quantify d-threo-PPMP in mice for bioavailability and dose-response studies.


Sperm bauplan and function and underlying processes of sperm formation and selection.
The spermatozoon is a highly differentiated and polarized cell, with two main structures: the head, containing a haploid nucleus and the acrosomal exocytotic granule, and the flagellum, which generates energy and propels the cell; both structures are connected by the neck. The sperm's main aim is to participate in fertilization, thus activating development. Despite this common bauplan and function, there is an enormous diversity in structure and performance of sperm cells. For example, mammalian spermatozoa may exhibit several head patterns and overall sperm lengths ranging from ∼30 to 350 µm. Mechanisms of transport in the female tract, preparation for fertilization, and recognition of and interaction with the oocyte also show considerable variation. There has been much interest in understanding the origin of this diversity, both in evolutionary terms and in relation to mechanisms underlying sperm differentiation in the testis. Here, relationships between sperm bauplan and function are examined at two levels: first, by analyzing the selective forces that drive changes in sperm structure and physiology to understand the adaptive values of this variation and impact on male reproductive success and second, by examining cellular and molecular mechanisms of sperm formation in the testis that may explain how differentiation can give rise to such a wide array of sperm forms and functions.


Pain paths among post-COVID-19 condition subjects: A prospective cross-sectional study with in-person evaluation.
New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features. A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria. The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension. Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications. COVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.


Lentinan extends lifespan and increases oxidative stress resistance through DAF-16 and SKN-1 pathways in Caenorhabditis elegans.
Lentinan, extracted from Lentinus edodes, exhibits bioactive properties in vitro; however, little is known about the antioxidant potential in vivo. In this study, the effects of lentinan at 0.05, 0.25 and 1.25 mg/mL on the lifespan, locomotion, reproductive capacity, and oxidative stress resistance in Caenorhabditis elegans were determined. Compared to the untreated control, lentinan at 0.05, 0.25 and 1.25 mg/mL significantly prolonged the lifespan by 17.6%, 35.3% and 25.3% (p < 0.001), respectively, and improved the brood size, locomotion and stress resistance of the nematodes. Furthermore, lentinan at 0.25 mg/mL significantly reduced accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) by 38.1% (p = 0.013) and 49.7% (p = 0.028), respectively. In addition, lentinan at all tested concentrations significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT). The expression of skn-1 and daf-16 in the treatments with lentinan at 0.25 and 1.25 mg/mL was significantly (p < 0.005) up-regulated compared with the untreated control, whereas that of the daf-2 gene was significantly down-regulated. Further evidence revealed that ROS production in lentinan-treated daf-16 and skn-1 mutant strains was similar to the untreated control. Consistent with the aforementioned results, lentinan enhanced the nuclear translocation of DAF-16 and SKN-1. Our results demonstrated that lentinan could increase lifespan and protect the nematodes from oxidative stress through DAF-16 and SKN-1.


Multiple arterial coronary bypass grafting is associated with better survival compared with second-generation drug-eluting stents in patients with stable multivessel coronary artery disease.
We sought to compare the long-term outcomes of multiarterial graft (MAG) coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) to treat stable multivessel coronary artery disease. This study was a multicenter population-based retrospective analysis of all residents of Ontario, Canada, from January 1, 2011, to December 31, 2019. We identified 3600 cases of elective primary isolated CABG with MAG and 2187 cases of PCI with second-generation DES. After the application of propensity score-weighting using overlap weights, MAG was associated with better survival over 5 years compared with DES (96.8% vs 94.5%; hazard ratio [HR], 0.56; 95% CI, 0.37-0.85). MAG was also associated with better secondary outcomes including a composite of death, myocardial infarction, and stroke (94.3% vs 88.5%; HR, 0.49; 95% CI, 0.36-0.65). The rate of death, stroke, myocardial infarction, and repeat revascularization (91.2% vs 70.7%; HR, 0.24; 95% CI, 0.20-0.30), and the individual end points of myocardial infarction (1.4% vs 6.9%; HR, 0.22; 95% CI, 0.13-0.35), and repeat revascularization (4.1% vs 24.2%; HR, 0.14; 95% CI, 0.10-0.18) were lower with MAG. PCI with second-generation DES was associated with a lower rate of stroke up to 5 years (0.6% vs 1.8%; HR, 3.97; 95% CI, 1.45-10.88). CABG with MAG was associated with better survival and fewer major cardiac adverse events compared with second-generation DES and might be considered the treatment of choice for patients with stable multivessel coronary artery disease. Further randomized controlled trials are needed to confirm this hypothesis.


Characterisation of an inflammation-related epigenetic score and its association with cognitive ability.
Chronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-wide association study identified DNA methylation correlates of C-reactive protein (CRP)-a widely used acute-phase inflammatory biomarker. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. We utilise a DNA methylation-based score for CRP and investigate its trajectories with age, and associations with cognitive ability in comparison with serum CRP and a genetic CRP score in a longitudinal study of older adults (n = 889) and a large, cross-sectional cohort (n = 7028). We identified no homogeneous trajectories of serum CRP with age across the cohorts, whereas the epigenetic CRP score was consistently found to increase with age (standardised β = 0.07 and 0.01) and to do so more rapidly in males compared to females. Additionally, the epigenetic CRP score had higher test-retest reliability compared to serum CRP, indicating its enhanced temporal stability. Higher serum CRP was not found to be associated with poorer cognitive ability (standardised β = - 0.08 and - 0.05); however, a consistent negative association was identified between cognitive ability and the epigenetic CRP score in both cohorts (standardised β = - 0.15 and - 0.08). An epigenetic proxy of CRP may provide a more reliable signature of chronic inflammation, allowing for more accurate stratification of individuals, and thus clearer inference of associations with incident health outcomes.


Local axon guidance in cerebral cortex and thalamus: are we there yet?
Normal brain function requires the development of precise connections between thalamus and cerebral cortex. In this issue of Neuron, Cang et al. and Tori and Levitt argue that EphA/ephrin-A signaling in the target tissue guides sensory thalamic axons to the correct cortical area, and sensory cortical axons to precise thalamic targets. Although EphA/ephrin-A signaling organizes sensory maps within areas, and thalamocortical axons in the internal capsule, both papers argue that each developmental event is dissociable from the others.


Interaction of ArmZ with the DNA-binding domain of MexZ induces expression of mexXY multidrug efflux pump genes and antimicrobial resistance in Pseudomonas aeruginosa.
Multidrug efflux pumps play an important role in antibiotic resistance in bacteria. In Pseudomonas aeruginosa, MexXY pump provides intrinsic resistance to many antimicrobials, including aminoglycosides. The expression of mexXY operon is negatively regulated by MexZ repressor. The repression is alleviated in response to the antibiotic-induced ribosome stress, which results in increased synthesis of anti-repressor ArmZ, interacting with MexZ. The molecular mechanism of MexZ inactivation by ArmZ is not known. Here, we showed that the N-terminal part of MexZ, encompassing the DNA-binding domain, is required for interaction with ArmZ. Using the bacterial two hybrid system based mutant screening and pull-down analyses we identified substitutions in MexZ that diminished (R3S, K6E, R13H) or completely impaired (K53E) the interaction with ArmZ without blocking MexZ activity as a transcriptional repressor. Introduction of corresponding mexZ missense mutations into P aeruginosa PAO1161 chromosome impaired (mexZ K6E, mexZ R13H) or blocked (mexZ K53E) tetracycline mediated induction of mexY expression. Concomitantly, PAO1161 mexZ K53E strain was more susceptible to aminoglycosides. The identified residues are highly conserved in MexZ-like transcriptional regulators found in bacterial genomes encoding both MexX/MexY/MexZ and ArmZ/PA5470 orthologs, suggesting that a similar mechanism may contribute to induction of efflux mediated resistance in other bacterial species. Overall, our data shed light on the molecular mechanism of ArmZ mediated induction of intrinsic antimicrobial resistance in P. aeruginosa.


Strain and strain rate echocardiography for evaluation of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension.
Optimizing the non-invasive imaging of right ventricular (RV) function is of increasing interest for therapy monitoring and risk stratification in patients with idiopathic pulmonary hypertension (IPAH). Therefore, this study evaluated strain and strain rate echocardiography as a tool for comprehensive assessment of RV function and disease severity in IPAH patients. In 30 IPAH patients [WHO functional classes II-IV; mean pulmonary artery pressure (mPAP) 48.8 +/- 12.5 mmHg; pulmonary vascular resistance (PVR) 7.9 +/- 5.3 Wood units] and in 10 matched healthy control subjects' two-dimensional echocardiography, 6-MWD and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were obtained. In IPAH patients when compared with controls, RV systolic strain (-18.8 +/- 4.3 vs. -34.5 +/- 3.8%, p = 0.0016) and strain rate (-1.6 +/- 0.6 vs. -2.7 +/- 0.5 s(-1), p = 0.018) were significantly altered and correlated significantly with elevated NT-proBNP levels (r = 0.73 and r = 0.62; p < 0.001, respectively) and reduced 6-MWD (r = -0.76 and r = -0.81; p < 0.001). In IPAH patients, reduced strain correlated with both mPAP (r = 0.61, p = 0.01 for strain; and r = 0.55, p = 0.04 for strain rate, respectively), and PVR (r = 0.84, p < 0.001 for strain; and r = 0.67, p < 0.001 for strain rate, respectively). This study gives first comprehensive evidence that strain echocardiography allows accurate non-invasive assessment of RV function and disease severity in patients with IPAH.


The burden and epidemiology of hepatitis B and hepatitis D in Georgia: findings from the national seroprevalence survey.
The burden of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections is unknown in Georgia. This analysis describes the prevalence of hepatitis B and coinfection with HDV and the demographic characteristics and risk factors for persons with HBV infection in Georgia. This is a cross-sectional seroprevalence study. A cross-sectional, nationwide survey to assess hepatitis B prevalence among the general adult Georgian population (age ≥18 years) was conducted in 2015. Demographic and risk behavior data were collected. Blood specimens were screened for anti-hepatitis B core total antibody (anti-HBc). Anti-HBc-positive specimens were tested for hepatitis B surface antigen (HBsAg). HBsAg-positive specimens were tested for HBV and HDV nucleic acid. Nationally weighted prevalence estimates and adjusted odds ratios (aORs) for potential risk factors were determined for anti-HBc and HBsAg positivity. The national prevalence of anti-HBc and HBsAg positivity among adults were 25.9% and 2.9%, respectively. Persons aged ≥70 years had the highest anti-HBc positivity (32.7%), but the lowest HBsAg positivity prevalence (1.3%). Anti-HBc positivity was associated with injection drug use (aOR = 2.34; 95% confidence interval [CI] = 1.46-3.74), receipt of a blood transfusion (aOR = 1.68; 95% CI = 1.32-2.15), and sex with a commercial sex worker (aOR = 1.46; 95% CI = 1.06-2.01). HBsAg positivity was associated with receipt of a blood transfusion (aOR = 2.72; 95% CI = 1.54-4.80) and past incarceration (aOR = 2.72; 95% CI = 1.25-5.93). Among HBsAg-positive persons, 0.9% (95% CI = 0.0-2.0) were HDV coinfected. Georgia has an intermediate to high burden of hepatitis B, and the prevalence of HDV coinfection among HBV-infected persons is low. Existing infrastructure for hepatitis C elimination could be leveraged to promote hepatitis B elimination.


A Case Report of an Intestinal Helminth Infection of Human Hymenolepiasis in Rural Gambia.
Hymenolepis nana, also called dwarf tapeworm infection, is an intestinal helminth not previously reported in The Gambia and only very rarely reported in West Africa. We report a case of H. nana infection in a 29-month-old child living in a rural community of the north bank of the Upper River Region (URR) in The Gambia. The child presented with mild iron deficiency anaemia and granulocytosis but was otherwise mostly asymptomatic despite the moderate-intensity of infection. We support treatment of H. nana infection even in largely asymptomatic children to prevent autoinfection and spread of this intestinal helminth in The Gambia and in other West African countries. GCP: Good Clinical Practice; HAZ: Height-for-age z-score; IHAT-GUT: Acronym for the Iron Hydroxide Adipate Tartrate Supplementation Study; ICH: International Conference on Harmonisation; SD: Standard Deviation; URR: Upper River Region; WAZ: Weight-for-age z-score; WHO: World Health Organization; WHZ: Weight-for-height z-score.


Incidence of free colorectal cancer cells on the peritoneal surface.
The etiology and significance of port site recurrence occurring after laparoscopic-assisted resection for colorectal cancers will not be determined until controlled clinical trials determine if it is a predictor of outcome. Indirect evidence in support of transcoelomic spread of viable cancer cells to port sites during resection can be postulated by the presence of free cells on the fresh surface of colorectal specimens during primary resection. The study contained herein was undertaken to determine the incidence of free surface colorectal cancer cells by cytology during elective open resection and to correlate their presence with clinicopathologic variables. Fresh clamped and ligated consecutive colorectal cancer specimens were assessed in the operating room during primary resection for the presence of free colorectal cancer cells during an 18 month period at one institution. Clinicopathologic variables were assessed prospectively and blinded to cytology results. Interobserver reliability of cytologists was excellent (unweighted kappa, 0.93). Overall, 15 of 103 (14.6 percent) colorectal cancers had positive cytology for cancer cells on the peritoneal or perirectal surface of the bowel. T3 and T4 tumors, the size or site of the tumor, lymph node status, mucinous characteristic, degree of differentiation, and the presence of vascular or neural invasion did not reach statistical significance as predictors of positive cytology in this study sample. The operative procedure performed was a statistically significant predictor of positive cytology. More than 50 percent of lymph nodes involved (28 percent), poorly differentiated tumors (28 percent), and the presence of liver metastases (22 percent) demonstrated a higher incidence of positive cytology, but this did not reach significant levels because of the limited power of the study sample for subgroup analysis. The presence of free surface colorectal cancer cells gives only indirect support to the transcoelomic route to port site recurrence. The significance and true incidence will only be determined by prospective database analysis and randomized, controlled trials.


Heterotopic pancreas as a rare cause of gastrointestinal hemorrhage in the newborn: report of a case.
We report herein a female infant in whom a heterotopic pancreas in the stomach caused gastrointestinal hemorrhage during the newborn period. Endoscopy was essential for ruling out other causes of hemorrhage and to follow the patient until the time of elective surgery at 6 months of age. Heterotopic pancreas should be borne in mind as a rare cause of gastrointestinal hemorrhage in the newborn when an unexplained gastrointestinal hemorrhage continues, and the lesion was discussed in relation to our experience of upper gastrointestinal endoscopies and a review of the literature.


Correlation of Inflow Velocity Ratio Detected by Phase Contrast Magnetic Resonance Angiography with the Bleb Color of Unruptured Intracranial Aneurysms.
Intraoperative rupture is the most fatal and catastrophic complication of surgery for unruptured intracranial aneurysms (UIAs); thus, it is extremely useful to predict reddish and thin-walled regions of the UIA before surgery. Although several studies have reported a relationship between the hemodynamic characteristics and intracranial aneurysm wall thickness, a consistent opinion is lacking. We aimed to investigate the relationship between objectively and quantitatively evaluated bleb wall color and hemodynamic characteristics using phase-contrast magnetic resonance angiography (PC-MRA). Ten patients diagnosed with UIA who underwent surgical clipping and preoperative magnetic resonance imaging along with PC-MRA were included in this study. Bleb wall color was evaluated from an intraoperative video. Based on the Red (R), Green, and Blue values, bleb wall redness (modified R value; mR) was calculated and compared with the hemodynamic characteristics obtained from PC-MRA. The wall redness distribution of 18 blebs in 11 UIAs in 10 patients was analyzed. Bleb/neck inflow velocity ratio (Vb/Va: r = 0.66, P = 0.003) strongly correlated with mR, whereas bleb/neck inflow rate ratio (r = 0.58, P = 0.012) correlated moderately. Multivariate regression analysis revealed that only Vb/Va (P = 0.017) significantly correlated with mR. There was no correlation between wall shear stress and mR. The bleb redness of UIAs and Vb/Va, calculated using PC-MRA, showed a significantly greater correlation. Thus, it is possible to predict bleb thickness noninvasively before surgery. This will facilitate more detailed pre- and intraoperative strategies for clipping and coiling for safe surgery.


Does primary trauma lead to developmental defects in permanent teeth?
Introduction A systematic review of existing evidence to determine if trauma in the primary dentition causes alteration in the development of the underlying permanent dentition.Data sources Six electronic databases (PubMed, Medline, MEDES, Scopus, Lilacs and Embase) were used to search a range of dental terms relating to dental trauma to locate studies between 1972-2020.Study selection Study selection was carried out by two authors by reviewing title, abstract and then full articles. A third author was consulted if consensus for inclusion was needed. Eligibility criteria included all scientific articles concerning sequalae to the human permanent dentition following trauma to the primary dentition. Only English, German and Spanish languages were included. For evaluation, the studies must have satisfied the following: a) minimum sample of 50 children to be representative; b) radiographic examination; and c) appropriate follow-up period up to permanent successor eruption.From 537 studies, 18 studies were identified for consideration in the review, comprising of 13 cross-sectional studies, two cohort studies and three case control studies.Data extraction and synthesis The Newcastle-Ottawa Scale was used to extract data and determine study quality. Only studies determined as high quality were included in the review. Four cross-sectional studies and three case control studies, totalling seven studies, were used. Data from these high-quality studies was summarised into table format.Results Large variation in study sample size existed from 138-753 traumatised teeth and 78-879 children. Both sexes were included in all studies and the children were aged between 0-17 years.Some studies found there was no difference in rate of trauma between girls and boys, while others found there was a higher incidence of trauma in boys than girls. The most frequently traumatised teeth were the upper primary central incisors. Whilst most studies covered all types of primary trauma, two only studied intrusion and one specified the type of primary trauma as luxation or fracture injuries.Whilst some of the studies concluded a higher frequency of defects to permanent teeth following primary intrusion trauma aged four and under, others showed no significant differences between the age of intrusion and the effect to the successor incisor.Enamel defects of the permanent teeth were the most common sequalae with a wide prevalence reported between 4.5-68.8%. Enamel defects were classified as hypoplasia and hypocalcification. Ectopic or altered eruption, crown or root dilacerations and odontoma development were observed less often, with the latter very rarely.Conclusions Primary tooth intrusion trauma causes the highest proportion of sequalae presenting as enamel defects. Younger patients experiencing primary trauma are more likely to obtain damage to the succeeding dentition. The existing quality of evidence is limited due to the observational nature of the studies available.


Outcomes of Articulating Spacers With Autoclaved Femoral Components in Total Knee Arthroplasty Infection.
In 2-stage revision of total knee arthroplasty (TKA) infection, articulating antibiotic spacers show similar eradication rates and superior range of motion compared with static spacers. This study evaluated infection control and other outcomes in articulating spacers with an autoclaved index femoral component. We reviewed 59 patients who underwent 2-stage treatment of TKA infection using articulating antibiotic spacers with an autoclaved femoral component with at least 2-year follow-up (mean: 5.0 years) from spacer placement. Reinfection was defined as any subsequent infection; recurrence was defined as reinfection with the same organism, need for chronic antibiotics, or conversion directly to amputation/arthrodesis. Nine patients (15%) experienced a recurrence and 22 patients (37%) experienced a reinfection. Incidence of diabetes mellitus was significantly higher in patients who became reinfected. Other comorbidities, revision history, prior spacer, or presence of virulent organisms did not predict infection recurrence. Forty-seven spacers underwent reimplantation, 6 (13%) of these went on to above-knee amputation, 6 (13%) received another 2-stage procedure, and 3 (6%) underwent subsequent irrigation and debridement. Three patients (5%) proceeded directly from spacer to above-knee amputation (2) or arthrodesis (1). Nine spacers (15%) in 7 patients were retained indefinitely (mean: 3.4 years), with overall good motion and function. Accounting for methodology, articulating spacers with autoclaved femoral components provide similar infection control to previous reports. Most patients with reinfection grew different organisms compared with initial infection, suggesting that some subsequent infections may be host related. Some patients retained spacers definitively with overall good patient satisfaction.


Comparison of oral Midazolam and Midazolam-Ketamine as sedative agents in paediatric dentistry.
We compared the efficacy of sedation with oral Midazolam and a combination of oral Midazolam and Ketamine, used as alternatives to general anaesthesia during tooth extraction. Retrospective study. A total of 30 patients aged between 3 and 9 years, who had elective tooth extraction were included in the study. Subjects in Group A (n. 15) were given 0.75 mg/kg Midazolam orally while those in Group B (n. 15) were given 0.75 mg/kg Midazolam orally+5 mg/kg ketamine. Acceptance of orally administered drugs, sedation and anxiety scores and reactions to local anaesthetic injection and tooth extraction were assessed. Sedation and anxiety scores in Group B were better than in Group A (p<0.05). Reactions to local anaesthetic injection and tooth extraction were very significantly less common in Group B (p<0.0001). Requirement for an additional medication was more common in Group A (p<0.05). Side effects were not observed in either group. Patient demographics and time to discharge were analysed by Mann-Whitney U test, whereas Chi-square test was used to analyse compliance to sedation, anxiety and sedation scores, reaction to tooth extraction, side effects and additional drug requirement. Compared to oral Midazolam only, a combination of oral Midazolam+Ketamine resulted in better sedation and surgical comfort in children during a painful procedure such as tooth extraction.


Corynebacterium group D2 ("Corynebacterium urealyticum") constitutes a new genomic species.
Twenty-one Corynebacterium group D2 ("C. urealyticum") strains were found to constitute a tight DNA hybridization group distinct from named Corynebacterium species. The strains of Corynebacterium group D2 had cell wall component type IV, short chain mycolic acids and G+C content of DNA of 65-66 mol %. Corynebacterium group D2 constitutes a genomic species which can be identified by phenotypic tests.


Lenke 1C, King type II curves: surgical recommendations.
The objectives of this article are twofold. The first is to discuss the surgical experience in patients who have Lenke 1C (King type II) curves, including the experience with newer instrumentation. These patients present a significant challenge to the deformity surgeon because they have structural thoracic deformities and significant, but nonstructural, lumbar curves. Over the years, selective instrumentation and fusion of the thoracic curve have been the primary approach to preserve motion of the lumbar segments, and thus, improve the long-term outlook. This strategy has been undertaken with the expectation that the uninstrumented lumbar curve will allow for a well-balanced spinal column postoperatively. The second objective of this article is to present basic strategies that may be helpful when planning for surgery in these patients.


Acute superior vena caval syndrome with airway obstruction following elective mediastinoscopy.
A 47-year-old female patient had a subclinical superior vena caval syndrome which developed into the 'full blown' acute condition when she was placed into the left lateral position after mediastinoscopy. She developed airway obstruction requiring urgent re-intubation and subsequent admission to the intensive care unit. This subclinical condition might have been suspected pre-operatively if closer attention had been paid to the history, physical examination and review of the computerised axial tomography scan: she had a history of intermittent dysponea, wheeze and cough which was worse on waking and improved as the day progressed, she had a positive Pemberton's sign and the computerised axial tomography scan showed that the lesion was encroaching on the superior vena cava.


Extreme Learning Machine Design for Dealing with Unrepresentative Features.
Extreme Learning Machines (ELMs) have become a popular tool for the classification of electroencephalography (EEG) signals for Brain Computer Interfaces. This is so mainly due to their very high training speed and generalization capabilities. Another important advantage is that they have only one hyperparameter that must be calibrated: the number of hidden nodes. While most traditional approaches dictate that this parameter should be chosen smaller than the number of available training examples, in this article we argue that, in the case of problems in which the data contain unrepresentative features, such as in EEG classification problems, it is beneficial to choose a much larger number of hidden nodes. We characterize this phenomenon, explain why this happens and exhibit several concrete examples to illustrate how ELMs behave. Furthermore, as searching for the optimal number of hidden nodes could be time consuming in enlarged ELMs, we propose a new training scheme, including a novel pruning method. This scheme provides an efficient way of finding the optimal number of nodes, making ELMs more suitable for dealing with real time EEG classification problems. Experimental results using synthetic data and real EEG data show a major improvement in the training time with respect to most traditional and state of the art ELM approaches, without jeopardising classification performance and resulting in more compact networks.


Recovery of a temporally based visual discrimination after visual cortex lesion in the rat.
In Expt. 1, rats were conditioned to emit a shock avoidance response when the pulse rate of a light was increased. Then, after bilateral visual cortex lesions, the rats were given 10, 20, or 40 days recovery before relearning the discrimination. While all rats were able to relearn the discrimination response, lesion rats had a performance deficit after all recovery periods. Expt. 2 compared the effects of postoperative visual pulse rate training to those of auditory pulse rate training on relearning of the photic pulse-rate discrimination 10 days after visual decortication. Recovery of discrimination responding was better after auditory pulse rate training than after visual training. These data suggest that visual cortex lesions in the rat disrupt perceptual or associational functions involving the temporal features of a visual stimulus. In addition, generalization of relational properties during cross-modal training through multimodal CNS structures appears to enhance recovery of behavior after brain insult.


Acute central nervous system vasculitis as a manifestation of neurosarcoidosis: A case report and literature review.
Neurosarcoidosis (NS) affects various sites of the central nervous system, including the cranial nerve, meninges, brain parenchyma, hypothalamus, and pituitary gland. NS rarely causes intracerebral vasculitis and subsequent strokes, or cerebral infarction and hemorrhage, which are associated with high mortality. Herein, we report a 71-year-old woman's case of stroke associated with NS, which showed aggressive cerebral vasculitis with brain herniation; it was resolved with corticosteroid therapy after accurate histopathological diagnosis. This case highlights the necessity of expecting NS to sometimes follow an aggressive course, presenting with vasculitis. Most patients with NS satisfactorily respond to corticosteroids, but this is not always the case. In cases of unfamiliar ischemic or hemorrhagic lesions, the possibility of NS must be considered.


Bismuth molybdate incorporated functionalized carbon nanofiber as an electrocatalytic tool for the pinpoint detection of organic pollutant in life samples.
Herein, we fabricated a feasible and accurate sensing platform for the quantification of toxic organic pollutant 2-nitroaniline (2-NA) in water samples through electrocatalyst made up of bismuth molybdate (Bi2MoO6, BMO) functionalized carbon nanofiber (f-CNF) modified electrode. The preparation of BMO/f-CNF composite is of two methods, such as co-precipitation (C-BMO/f-CNF) and ultrasonication method (U-BMO/f-CNF). The physicochemical properties of the composites were characterized by XRD, FTIR, Raman, BET, FE-SEM, and HR-TEM techniques. At U-BMO/f-CNF, the charge transfer resistance was low (Rct = 12.47 Ω) compared to C-BMO/f-CNF because nanosized U-BMO particles correctly aim at the defective sites of the f-CNF surface wall. Further, the electrocatalytic activity of C&U-BMO/f-CNF composites was examined by cyclic voltammetry (CV) and differential pulse voltammetry techniques (DPV) for the electrochemical detection of 2-nitroaniline (2-NA). The U-BMO/f-CNF/GCE shows a higher cathodic current, wide dynamic linear range of 0.01-168.01 µM, and superior electrocatalytic activity with a low detection limit (0.0437 µM) and good sensitivity (0.6857 μA μM-1 cm-2). The excellent selectivity nature of U-BMO/f-CNF/GCE was observed in the presence of various organic pollutants and a few toxic metal cations. The practical applicability such as stability, repeatability towards 2-NA outcomes with accepted results. Besides, the practical viability of as proposed U-BMO/f-CNF sensor was investigated in soil and lake water samples delivers good recovery results. Hence from these analyses, we conclude that U-BMO/f-CNF/GCE potential for the determination of hazardous environmental pollutant 2-NA.


Acquired factor VII deficiency in hematopoietic stem cell transplant recipients.
Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8-35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined.


Percutaneous treatments for trigeminal neuralgia.
Trigeminal neuralgia (TN) is a neurologic disorder, defined by paroxysmal electric shocklike painful attacks in 1 or more trigeminal nerve branches. Treatment of TN is diverse and includes minimally invasive percutaneous techniques, which consist of balloon compression, glycerol rhizotomy, and radiofrequency thermocoagulation. Although all 3 techniques are generally safe, efficient, and effective, a clear consensus has not been reached regarding their specific indications and degree of efficacy. The aim of this article is to describe the percutaneous treatments available for TN and outline their characteristics, technique, indications and efficacy.


A new immunofluorostaining method using red fluorescence of PerCP on formalin-fixed paraffin-embedded tissues.
Immunofluorostaining, a versatile tissue staining method, is used in biomedical research because of its clear contrast and precise quantification of positive signals. However, its application in clinical diagnosis has been limited. A major obstacle is high fluorescent background of formalin-fixed, paraffin-embedded tissue sections (paraffin sections). On paraffin sections, strong and broad fluorescence of the section overlapping that of conventional fluorescent dyes such as fluorescein isothiocyanate (FITC) prevents detection of target immunofluorescence. To circumvent the background, we selected an albuminous dye, peridinin chlorophyll a protein (PerCP), for immunostaining of human tumor sections with tumor-reactive monoclonal antibodies. Red fluorescence of PerCP clearly distinguished the tumor region within the yellow-green autofluorescence of the section. Furthermore, it was possible to observe tissue morphology simultaneously without any counterstaining; autofluorescence served as counterstaining in this method. Digital quantification of PerCP-stained image intensity correlated (r2>0.99) well with extracted PerCP amount, indicating the usefulness of image quantification. We conclude that this new and simple immunofluorostaining method can be applied to pathological diagnosis of a wide range of conditions, including cancer.


Influenza economics. Providers and suppliers who usually reap big profits during flu season might find that a pandemic could backfire on their bottom lines.
Health and Human Services Secretary Mike Leavitt, right, spoke about avian influenza at the National Press Club in Washington last week. President Bush's plan involves asking Congress to invest billions of dollars in development, production and stockpiling of antiviral drugs and vaccines in case the flu strain becomes a pandemic. HHS hopes to stockpile enough of vaccine to inoculate 20 million Americans.


Oral physostigmine in Alzheimer's disease: effects on norepinephrine and vasopressin in cerebrospinal fluid and plasma.
Physostigmine is a cholinesterase inhibitor which enhances central and peripheral cholinergic activity. In this study, we explored in persons with Alzheimer's disease (AD) the effects of an acute dose of physostigmine in patients receiving chronic physostigmine treatment on the activity of the cholinergically regulated noradrenergic and arginine vasopressin (AVP) systems. Specifically, we estimated the effects of sustained release oral physostigmine on central and peripheral noradrenergic and AVP systems by measuring norepinephrine (NE) and AVP in cerebrospinal fluid (CSF) and plasma. Lumbar punctures were performed in both physostigmine and no drug treatment conditions. In some subjects the effects of physostigmine on the plasma AVP response to the osmolar stimulus of a hypertonic saline infusion also were measured. NE concentrations in both CSF and plasma were significantly lower in the physostigmine than in the no drug condition. AVP concentrations did not differ between conditions in either compartment, nor did physostigmine affect the AVP response to hypertonic saline. Physostigmine appears to decrease both central and peripheral noradrenergic activity in AD.


Special Issue: Emerging Approaches for the Performance Assessment and Prediction of Cement-Based Materials.
The current Special Issue, entitled "Emerging Approaches for Performance Assessment and Prediction of Cement-Based Materials", aims to showcase cutting-edge research into the technologies, smart sensing systems, and tools for assessing and predicting the performance of cement-based materials [...].


2,6-Bis(2-chloro-phen-yl)-4-oxo-3,5-diphenyl-heptane-1,1,7,7-tetra-carbo-nitrile.
In the title compound, C(35)H(24)Cl(2)N(4)O, the phenyl rings are oriented almost parallel to each other, making a dihedral angle of 0.6 (2)°, whereas the chloro-phenyl rings are oriented at a dihedral angle of 28.3 (1)°. The crystal structure is stabilized through an extensive series of C-H⋯N, C-H⋯O and C-H⋯Cl inter-actions. One of the C-H⋯N inter-actions generates an R(2) (2)(12) ring motif around a crystallographic inversion centre. C(5), C(10) and C(12) chain motifs are observed in the unit cell through C-H⋯N and C-H⋯Cl inter-actions. During the structure analysis, it was observed that the unit cell contains large accessible voids, which host disordered solvent mol-ecules. This affects the diffraction pattern, mostly at low scattering angles and was corrected with the SQUEEZE program [Spek, A. L. (2009 ▶). Acta Cryst. D65, 148-155].


[Clinical Value of White Light Image, Endoscopic Ultrasonography and Magnifying Endoscopy with Narrow Band Imaging in Evaluation of Indications for Endoscopic Treatment of Early Gastric Cancer].
To explore the application value of white light image (WLI), endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) in the endoscopic treatment of early gastric cancer (EGC), and to provide basis for decision-making in clinical diagnosis and treatment. The clinicopathological data of EGC patients who underwent endoscopic submucosal dissection (ESD) at West China Hospital, Sichuan University between December 2013 and October 2020 were included. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EGC invasive depth were compared between WLI and EUS. The role of ME-NBI in predicting the differentiation types of EGC was analyzed. A total of 280 patients (291 lesions) were enrolled in the study. Among them, 199 patients (207 lesions) received EUS and 160 patients (168 lesions) received ME-NBI. The overall accuracy of WLI in diagnosing the invasive depth of EGC was 87.0%, significantly higher than that of EUS (46.4%, P<0.001). When WLI was combined with EUS, the diagnostic accuracy (87.4%) was not significantly improved. The overall accuracy of determining the differentiation degree of EGC with ME-NBI was 92.3% (155/168), and the accuracy of determining undifferentiated EGC with ME-NBI was significantly lower than that of differentiated EGC (41.2% vs. 98.0%, P<0.001). In the evaluation of indications for endoscopic treatment of EGC, WLI showed better performance in predicting the invasive depth of EGC, while EUS demonstrated limited value. ME-NBI showed better accuracy for predicting the differentiation degree of most EGC, especially for differentiated EGC.


Staging of porcine embryos: Comparison of Standard Event System-based statistical clusters with a Carnegie-based staging system.
Methods to compare events defined as newly occurring characters in development has advanced vertebrate developmental research but events are not easily extrapolated into traditional staging systems used in biomedical research. First, we scored 95 porcine embryos in the age range of 15 to 33 days post conception by stereomicroscopy using to a slightly modified version of the Standard Event System (SES). Subsequent statistical clustering allowed the embryos to be grouped into 15 clusters. Staging of the same embryos in a way that generally follow the description of external features of human embryos in the Carnegie stages 10 to 23 allowed us to describe 14 stages of porcine embryonic development that correlate to the Carnegie stages of human development with minor species differences. When arranged by average age, the statistic clusters had a distribution that correlated well with the stages produced by the Carnegie-based staging system. Statistical analysis of developmental events allow grouping of porcine embryos into clusters that can be extrapolated into a Carnegie-based staging system, thus serving the dual purpose of facilitating the use of the pig as a biomedical model animal and providing data for integrating porcine developmental events into a phylogenetic context.


Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma.
Retinoblastoma is a cancer of the infant retina primarily driven by loss of the Rb tumor suppressor gene, which is undruggable. Here, we report an autocrine signaling, mediated by secreted frizzled-related protein 2 (SFRP2), which suppresses nitric oxide and enables retinoblastoma growth. We show that coxsackievirus and adenovirus receptor (CXADR) is the cell-surface receptor for SFRP2 in retinoblastoma cells; that CXADR functions as a "dependence receptor," transmitting a growth-inhibitory signal in the absence of SFRP2; and that the balance between SFRP2 and CXADR determines nitric oxide production. Accordingly, high SFRP2 RNA expression correlates with high-risk histopathologic features in retinoblastoma. Targeting SFRP2 signaling by SFRP2-binding peptides or by a pharmacological inhibitor rapidly induces nitric oxide and profoundly inhibits retinoblastoma growth in orthotopic xenograft models. These results reveal a cytokine signaling pathway that regulates nitric oxide production and retinoblastoma cell proliferation and is amenable to therapeutic intervention.


Similarities in resorption patterns of maxillary and mandibular ridges.
The differences in the posterior arch widths between opposing maxillae and mandibles were studied in 100 edentulous denture-wearing patients. Panoramic radiographs of 67 of these patients were used to assess the percentage of mandibular height reduction from that considered present before extractions. Comparisons between posterior maxillary and mandibular arch widths, reductions in mandibular height, and edentulous age accompanied by denture wearing were made. The following conclusions emerged: 1. The mandible does not progressively widen as its opposing maxillae becomes narrower, nor does a progressive incremental increase occur in posterior maxillomandibular width relations with increased resorption or resorptive age. 2. The arch width of the mandible exceeds the arch width of the maxillae in the molar region by an average of 6 to 7 mm after sufficient resorption establisheds a definitive alveolar crest. This difference remains the same regardless of the amount of resorption or resorptive age. 3. The progressive and irreversible mandibular alveolar resorption rate is greatest in the earlier stages of edentulism and slows with loss of bone, longevity of edentulism, and attendant wearing of dentures.


Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.
The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa.


Changes in cell membrane Na,K-ATPase activity associated with induction of dietary obesity in the rat.
The effect of diet-induced obesity on tissue Na, K-ATPase activity ("sodium pump") has been determined in the intact rat exposed to a cafeteria diet. Mature female Charles River rats showed significant increases in carcass lipid on this regimen (P less than 0.01), whereas male rats exposed to cafeteria diet and control male and female animals on laboratory chow showed no increase in carcass lipid over the 54 to 103 days that the animals were studied. In the female cafeteria-diet group, red blood cell membrane Na, K-ATPase activity and carcass lipid were highly correlated (r = 0.847, P less than 0.001). Significant trends in Na, K-ATPase activity as a function of carcass lipid did not occur in either kidney or liver crude membrane preparations from cafeteria-diet females. No correlation was seen in red cell, liver, or kidney membrane Na, K-ATPase with carcass lipid in male cafeteria-diet animals or in the control males and females. In this animal model of nongenetic obesity, changes in tissue Na, K-ATPase activity can be induced by dietary manipulation and are sex-specific and organ-specific.


Phenotyping spontaneous locomotor activity in inbred and outbred mouse strains by using Digital Ventilated Cages.
Mouse strains differ markedly in all behaviors, independently of their genetic background. We undertook this study to disentangle the diurnal activity and feature key aspects of three non-genetically altered mouse strains widely used in research, C57BL/6NCrl (inbred), BALB/cAnNCrl (inbred) and CRL:CD1(ICR) (outbred). With this aim, we conducted a longitudinal analysis of the spontaneous locomotor activity of the mice during a 24-h period for 2 months, in two different periods of the year to reduce the seasonality effect. Mice (males and females) were group-housed in Digital Ventilated Cages (Tecniplast), mimicking standard housing conditions in research settings and avoiding the potential bias provided in terms of locomotor activity by single housing. The recorded locomotor activity was analyzed by relying on different and commonly used circadian metrics (i.e., day and night activity, diurnal activity, responses to lights-on and lights-off phases, acrophase and activity onset and regularity disruption index) to capture key behavioral responses for each strain. Our results clearly demonstrate significant differences in the circadian activity of the three selected strains, when comparing inbred versus outbred as well as inbred strains (C57BL/6NCrl versus BALB/cAnNCrl). Conversely, males and females of the same strain displayed similar motor phenotypes; significant differences were recorded only for C57BL/6NCrl and CRL:CD1(ICR) females, which displayed higher average locomotor activity from prepuberty to adulthood. All strain-specific differences were further confirmed by an unsupervised machine learning approach. Altogether, our data corroborate the concept that each strain behaves under characteristic patterns, which needs to be taken into consideration in the study design to ensure experimental reproducibility and comply with essential animal welfare principles.


Antisperm antibodies in infertile and homosexual men: relationship to serologic and clinical findings.
The incidence and significance of antisperm antibodies in different groups of men were evaluated by a modified enzyme-linked immunosorbent assay. In serum, 4.0% of dermatologic patients (n = 223), 9.6% of andrologic patients (n = 178), and 28.6% of homosexual men (n = 42) were positive for IgG and/or IgM antibodies. In seminal fluids, 7.3% of the andrologic patients had IgA (and IgG) antibodies to spermatozoa. Only 1 of 29 positive men had antibodies both in serum and in seminal fluid. No correlation between antisperm antibodies and IgG/IgM concentrations was found in serum, whereas in seminal plasma men with antisperm antibodies showed higher IgG/IgA concentrations than men without (IgA, 3.2 versus 1.7 mg/dl; IgG, 9.8 versus 6.3 mg/dl). It is concluded that there is a high incidence of antisperm antibodies among homosexual men, probably because of contact of spermatozoa with the immune system by passive anal intercourse. There is little correlation between antisperm antibodies in serum and seminal plasma of infertile men because of a lack of relevant antibody transfer from the serum and the formation of local antibodies in seminal plasma. Antisperm antibodies in seminal fluid are associated with elevated local IgG and IgA concentrations.


Prescreening tools for diabetes and obesity-associated dyslipidaemia: comparing BMI, waist and waist hip ratio. The D.E.S.I.R. Study.
To compare the sensitivities of BMI, waist circumference and waist hip ratio (WHR) in identifying subjects who should be screened for diabetes and/or for obesity-associated dyslipidaemia. Cross-sectional study. Central-western France. More than 3000 men and women, aged 40-64 years, from the French study: data from an epidemiological study on the insulin resistance syndrome (D.E.S.I.R.). Sensitivity and specificity for screened diabetes (fasting plasma glucose>or=7.0 mmol/l) and screened dyslipidaemia (triglycerides>or=2.3 mmol/l and/or HDL-cholesterol <0.9/1.1 mmol/l (men/women)) according to BMI, waist circumference and WHR. Sensitivities increased as more corpulent subjects were screened, but they increased slowly after screening the top 30%: body mass index (BMI)>or=27/26 kg/m(2) (men/women) or waist >or=96/83 cm or WHR>or=0.96/0.83. These values were chosen as thresholds. In men, BMI had a nonsignificantly higher sensitivity than waist or WHR for both diabetes and dyslipidaemia (77 vs 74 and 66% P<0.3, 0.09; 56 vs 54 and 49% P<0.5, 0.16). For women, waist had a slightly higher sensitivity than BMI or WHR (82 vs 77 and 77% P<0.8, 0.7) for diabetes; for dyslipidaemia, waist and WHR had similar sensitivities, higher than for BMI (65 and 67 vs 54% P<0.16, 0.13). We propose that for screening in a French population 40-64 years of age, the more obese 30% of the population, identified either by BMI, waist or WHR be screened for diabetes and obesity-associated dyslipidaemia.


A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients.
People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load. We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity. This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies. Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks. ClinicalTrials.gov Identifier NCT04589897 (retrospectively registered).


[Remote ischemic conditioning: short-term effects on rat liver ischemic-reperfusion injury].
Several techniques have been developed to reduce ischemic-reperfusion injury. A novel method is the remote ischemic perconditioning, applied parallel with target organ ischemia. The aim of the study was to determine the extent of liver ischemic-reperfusion injury via the application of this novel method. Male Wistar rats (n = 30, 10/group) were subjected to 60-minute partial liver ischemia and 60-minute reperfusion. Rats in the perconditioned group received conditioning treatment during the last 40 minutes of liver ischemia by infrarenal aortic clamping. Hepatic and lower limb microcirculation was monitored by laser Doppler flowmeter during reperfusion. After reperfusion, liver samples were taken for routine histological examination and redox-state assessment. Serum transaminase activities and liver tissue heat-shock protein-72 expression were measured. Parameters of microcirculation showed significant (p<0.05) improvement in the perconditioned group in comparison with the control. Besides the significant improvement observed in the serum alanine amino-transferase activities, significantly milder tissue injury was detected histologically in the liver sections of the perconditioned group. Moreover, significant improvement was found in the redox-state parameters. Perconditioning may be a reasonable possibility to reduce liver ischemic-reperfusion injury.


Sensitivity to the prototype in children with high-functioning autism spectrum disorder: An example of Bayesian cognitive psychometrics.
We present a case study of hierarchical Bayesian explanatory cognitive psychometrics, examining information processing characteristics of individuals with high-functioning autism spectrum disorder (HFASD). On the basis of previously published data, we compare the classification behavior of a group of children with HFASD with that of typically developing (TD) controls using a computational model of categorization. The parameters in the model reflect characteristics of information processing that are theoretically related to HFASD. Because we expect individual differences in the model's parameters, as well as differences between HFASD and TD children, we use a hierarchical explanatory approach. A first analysis suggests that children with HFASD are less sensitive to the prototype. A second analysis, involving a mixture component, reveals that the computational model is not appropriate for a subgroup of participants, which implies parameter estimates are not informative for these children. Focusing only on the children for whom the prototype model is appropriate, no clear difference in sensitivity between HFASD and TD children is inferred.


Local Management of Anogenital Warts in Non-immunocompromised Adults: A Systematic Review and Meta-analyses of Randomized Controlled Trials.
Several therapeutic options are available to manage anogenital warts (AGWs). However, no hierarchy of treatments is provided in the latest European and American recommendations. This study aimed to determine the efficacy and safety of local treatments for the management of AGWs. A search was conducted through 12 databases from inception to August 2018. All randomized controlled trials (RCTs) in which at least one parallel treatment group composed of immunocompetent adults with AGWs received at least one provider-administered or patient-administered treatment were included. Risk of bias assessment and meta-analyses of aggregated study data were performed on the basis of the Cochrane Handbook, and quality of evidence evaluation followed the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Primary endpoints were complete clearance and recurrence at 3 months. Seventy RCTs (9931 patients) were included. All but four RCTs had a high risk of bias. CO2 laser was slightly more efficacious than cryotherapy [risk ratio (RR) 2.05; 95% confidence interval (CI) 1.61-2.62], with fewer recurrences at 3 months (RR 0.28; 95% CI 0.09-0.89). Electrosurgery was slightly more efficacious than cryotherapy. No differences in efficacy or side effects were found between cryotherapy and imiquimod or trichloroacetic acid. Podophyllotoxin gel was slightly more efficacious than podophyllotoxin cream. 5-Fluorouracil (5-FU) was slightly more efficacious and caused less erosion than CO2 laser (RR 1.37; 95% CI 1.11-1.70). The vast majority of included RCTs had a low level of evidence, thereby preventing the establishment of a hierarchy of treatments. Nevertheless, our results provide an overview of the main AGW treatments available for general practitioners and specialists. While provider-administered treatments are superior, patient-administered treatments (e.g., imiquimod, podophyllotoxin) are useful solutions for compliant patients. PROSPERO-CRD42015025827.


Adenine phosphoribosyl transferase polymorphism in baboons.
Two allelic isozymes of adenine phosphoribosyl transferase (APRT) were detected by starch gel electrophoresis of baboon hemolysates. Extensive family data verified autosomal codominant inheritance. The gene frequencies of five subspecies of baboons differed significantly. The activity of erythrocyte APRT is sufficiently high to enable the use of this enzyme as a sensitive marker for assessing chimerism in research involving bone marrow transplantation.


[Antioxidant activity of blood plasma of south Altai's indigenous population of low and medium height altitude areas].
Due to the fact that age change theories are still under discussion a study has been conducted on the estimation of antioxidant and antiradical activity of blood plasma. For the experiment was taken a homogeneous group of people which separate populations differ in geographical and climatic parameters of their living conditions. As a result there has been discovered a dependence of Altaians' antioxidant system upon geographical and climatic conditions, and age.


Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia.
Auditory event-related potentials (ERPs) associated with selective attention were recorded in 21 children at high-risk for schizophrenia and in 21 matched controls. The subjects performed a selective listening task. For behavioral evaluation, target counts on the selective listening task and on cognitive performance were assessed. Group-specific differences of ERP components could be demonstrated, as reflected by significant amplitude reductions of the frontally located negative difference wave (Nd) and of the P3 component, following selectively attended stimuli, in the high-risk children. P3 latencies tended to be prolonged in the high-risk group. Reduced Nd was found in 14 and reduced P3 in 16 high-risk children among the 21 matched pairs. Significant correlations between the ERP reductions and psychometric deficit (counting accuracy) were observed. Mismatch negativity (MMN), an ERP component associated with automatic processing of physically deviant stimuli, did not differentiate significantly between groups, but was distinctly reduced in the high-risk group. The Nd and P3 reductions suggest deficits of selective attention in a considerable number of the subjects genetically at risk for schizophrenia. The present findings are discussed with respect to their relevance as indicators of a predisposition to schizophrenia.


Postburn contracture of the neck--our experience with a new dynamic extension splint.
Twenty-eight examples of postburn contracture of the neck managed during the last 5 years gave us a better understanding of the problems of anaesthesia, contracture release, skin grafting, splintage and maintenance of the fully release state. The severe contracture should be incised before intubation under a local anaesthetic agent. The release should include the adjoining contractures of mandibular and pectoral regions lest the skin graft is pulled by the existing contracture. Haemostasis should be meticulously secured to avoid graft loss. Splintage should be a static splint for 4-6 weeks followed by a dynamic splint until the applied graft becomes soft, supple and wrinkle free. Ideally, however, contractures should be prevented by nursing the patient with a neck extension in the acute phase and wearing a cervical collar during the subacute phase of wound healing.


A comparison of glycopyrrolate and atropine during reversal of nondepolarizing neuromuscular block with neostigmine.
Glycopyrrolate and atropine were compared as to their effects on heart rate, arrhythmias, blood pressure, and volume of oropharyngeal secretions. Glycopyrrolate protects against neostigmine-induced bradycardia, produces less initial tachycardia, causes a lower incidence of cardiac arrhythmias, and is a superior oropharyngeal drying agent. Use of this drug instead of atropine should be considered during reversal of nondepolarizing neuromuscular block.


Full-Length 16S rRNA Gene Analysis Using Long-Read Nanopore Sequencing for Rapid Identification of Bacteria from Clinical Specimens.
Amplicon sequencing of the 16S ribosomal RNA (rRNA) gene is a practical and reliable measure for taxonomic profiling of bacterial communities. This chapter describes the detailed workflow for full-length 16S rRNA gene amplicon analysis using nanopore sequencing and bioinformatics pipelines to analyze nanopore sequencing data for taxonomic assignment. This approach offers a higher taxonomic resolution for bacterial identification from clinical specimens with a markedly reduced timeframe and improved versatility.


Point-of-Care Ultrasound Assists Diagnosis of Spontaneously Passed Common Bile Duct Stone.
Choledocholithiasis complicates approximately 10% of gallstone disease. Spontaneous stone migration out of the common bile duct (CBD) may occur in as many as 20% of choledocholithiasis cases. A decrease in CBD caliber occurs in the setting of spontaneous stone passage, but to our knowledge, this finding has not been appreciated using point-of-care ultrasound (POCUS) in the emergency medicine setting. A 49-year-old woman presented to our Emergency Department (ED) with a complaint of epigastric pain radiating to the left shoulder. On examination she was found to have epigastric tenderness to palpation, but no guarding or rebound. POCUS demonstrated a dilated common bile duct, and her liver function tests were abnormally high. She was admitted to Medicine with concern for choledocholithiasis and plan for endoscopic retrograde cholangiopancreatography (ERCP), but her pain had resolved shortly after ED arrival. A repeat ultrasound examination demonstrated a normal-caliber common bile duct approximately 3 h after the initial scan. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Choledocholithiasis often requires admission and invasive testing. Using POCUS in conjunction with liver function tests and patient assessments may obviate a need for ERCP.


Nucleotide sequence of a pregnancy-specific beta 1 glycoprotein gene family member. Identification of a functional promoter region and several putative regulatory sequences.
The pregnancy-specific beta 1 glycoprotein (PSG) genes encode a group of heterogeneous proteins produced in large amounts by the human syncytiotrophoblast. Their expression seems to be regulated at the transcriptional level during normal pregnancy. In the present work, we isolated from a human placental library a 17 kb genomic fragment corresponding to a member of the PSG multigene family. DNA sequence analysis of 1190 nucleotides upstream of the translational start and of the first intron, revealed the presence of several putative regulatory sequences. In a transient chloramphenicol acetyltransferase expression assay, 5' flanking sequences within 123 nucleotides upstream to the first major transcription initiation site, functioned as a strong promoter in COS-7 cells. Meanwhile, sequences 5' further upstream had the ability to abolish this promoter activity. The sequence analyzed did not contain any obvious TATA-like boxes or G+C-rich regions, suggesting the existence of unique promoter elements implicated in transcription initiation and regulation of this PSG gene family member.


[Pulmonary metastasectomy in renal cell carcinoma].
In patients with isolated meta- or synchronous pulmonary metastases from renal cell cancer, lung metastasectomy could be an appropriate treatment option after successful treatment of primary cancer. Presentation of lung metastasectomy as a treatment option in patients with pulmonary metastatic renal cell cancer and the postoperative outcome. Description of alternative treatment modalities focusing on "targeted therapies". Systematical literature research and qualitative analysis of studies on patients undergoing lung metastasectomy after primary nephrectomy published since 01 January 2000. We assessed operative findings, survival data, and prognostic factors. Pulmonary metastasectomy results in a median postmetastasectomy survival of 26-94 months. The 5‑year survival rates vary between 33 and 58%. The patients' prognosis depends on a prolonged disease-free interval and complete resection of all suspected metastases. In particular, number and location of lung metastases should play a minor role for the indication for lung metastasectomy. Pulmonary metastasectomy should be considered the treatment of choice in selected patients with successfully resected primary cancer showing no evidence of extrapulmonary metastases and having guaranteed operability and complete resection.


Multiple novel transcription initiation sites for NRG1.
The large neuregulin 1 gene (NRG1) has been mapped to a 1.125 Mb region on chromosome 8p11-21. Three major forms of NRG1 (types I-III), all with distinct amino-termini encoded by unique 5'-exons, have been described. We report here the discovery of nine novel NRG1 exons, including six alternative 5'-exons, increasing the number of potential promoters in NRG1 from three to nine. The novel transcripts of NRG1 described here use the novel 5'-exons which are either coding or non-coding. The functional relevance of the predicted proteins they encode has not been evaluated. Three of the novel 5'-exons are well conserved in syntenic rat and mouse sequences; they encode proteins with novel amino-termini, here termed types IV-VI. NRG1 plays a central role in neural development and is most likely involved in regulation of synaptic plasticity, or how the brain responds or adapts to the environment. The unusually complex gene structure may facilitate spatial and temporal regulation of NRG1 expression, fine-tune NRG1 protein function at different stages during development of the nervous system, and adapt responses to the environment in the adult brain.


Ferulic acid, an efficient inhibitor of type B trichothecene biosynthesis and Tri gene expression in Fusarium liquid cultures.
The effect of ferulic acid, the most abundant phenolic acid in wheat bran, was studied in vitro on type B trichothecene biosynthesis by Fusarium. It was demonstrated that ferulic acid is an efficient inhibitor of mycotoxin production by all strains of Fusarium tested, including different chemotypes and species. To analyse the mechanism of toxin biosynthesis inhibition by ferulic acid, expression of representative Tri genes, involved in the trichothecene biosynthesis pathway, was monitored by real-time RT-PCR. A decrease in the level of Tri gene expression was measured, suggesting that inhibition of toxin synthesis by ferulic acid could be regulated at the transcriptional level. Moreover, toxin production was shown to be reduced proportionally to the initial amount of ferulic acid added in the culture medium. Addition of ferulic acid either at the spore germination step or to a mycelial culture resulted in the same final inhibitory effect on mycotoxin accumulation. A cumulative inhibitory effect on trichothecene biosynthesis was even observed with successive supplementation of ferulic acid. Ferulic acid, which content varies among wheat varieties, could then play an important role in modulating trichothecene biosynthesis by Fusarium in some wheat varieties.


DNA mismatch repair-deficient non-neoplastic endometrial glands are common in Lynch syndrome patients and are present at a higher density than in the colon.
The hallmark of Lynch syndrome (LS) is DNA mismatch repair protein (MMR) deficiency. Recently, MMR deficiency in non-neoplastic colonic crypts has been identified as a novel indicator of LS. We aimed to determine whether MMR-deficient non-neoplastic endometrial glands can distinguish patients with and without LS, and to compare the level of MMR deficiency in the normal endometrium and colon in LS patients. We evaluated the immunohistochemical expression of MMR proteins in the normal endometrial mucosa from 64 patients, including 34 patients with confirmed LS (17 with endometrial cancer and 17 without cancer), 30 patients with endometrial cancer without LS (10 with tumours with MLH1 promoter hypermethylation and 20 with MMR-proficient tumours), and in the normal colonic mucosa from 30 LS patients. MMR-deficient non-neoplastic endometrial glands were identified in 47% of LS patients and in no patients without LS (P < 0.001). MMR-deficient non-neoplastic glands were more often identified in LS patients with endometrial cancer (65%) than in those without endometrial cancer (29%) (P = 0.04). In contrast to what was seen in the normal colon, MMR-deficient glands in the normal endometrium were seen as large, contiguous groups, ranging in number from two to 101 (87% versus 45%, P = 0.02). MMR-deficient glands were identified at a higher density in the endometrium than in the colon in LS patients (median number of MMR-deficient glands, 22 versus two, P = 0.02). Our findings indicate that MMR-deficient non-neoplastic endometrial glands constitute an indicator of LS, and that MMR-deficient glands in the endometrium are present in a pattern of contiguous large groups.


Measurement of 224Ra uptake in a fern actively accumulating radium.
A method is proposed for determining the level of 224Ra in plant samples by measuring its descendant nuclide 212Pb at 239 keV by gamma-ray spectrometry. Variations of 224Ra and 212Pb over time during sample preparation and counting were delineated prior to gamma-ray measurement. The 224Ra concentrations in plant samples were measured by their direct uptake from soil, which could be determined and distinguished from that resulting from decay of 228Th inside the plants. We propose that a field-growing Dicranopteris linearis, which actively accumulates radium, can be used as an indicator of the nutritional transportation and metabolic rate of radium and other alkaline earth elements. We investigated the influence of rainfall on 224Ra concentrations in fronds of D. linearis and the corresponding uptake rates. 224Ra could serve as a natural tracer of growth in plants over a several days. Its presence and content in plants implies a temporal mineral metabolic rate, which can provide useful information for plant physiological and environmental investigations.


Workflow for automated quantification of cerebromicrovascular gelatinase activity.
The gelatinase enzymes, matrix metalloproteinases -2 and -9, are central mediators of blood-brain barrier disruption, actively studied in experimental models of neurological disease. Staining with in situ zymography (ISZ) allows visualization of gelatinase activity directly in brain tissue sections. However, quantifying microvascular gelatinase activity from ISZ-images is challenging and time consuming, as surrounding cell types often show significant confounding activity. We describe validation and performance of a workflow for automated image analysis of cerebromicrovascular gelatinase activity, now released for open-access use. In comparison to manual analysis, the automated workflow showed superior accuracy, was faster to execute and allows for more detailed analysis of heterogeneity in the microvasculature. We further suggest recommendations for quantifying and reporting this type of activity in experimental studies, focusing on ischemic stroke.


Detection of SARS-CoV-2 RNA in the corneal epithelium of a patient after recovery from COVID-19.
To report a case of a patient presenting with unilateral keratouveitis associated with ocular hypertension six weeks after being discharged from the hospital for COVID-19. Ocular specimens were obtained for testing. A 69-year-old African American woman developed poor vision while hospitalized for COVID-19 in April but did not seek ophthalmic care until end of May. She had an edematous cornea, stromal keratitis, and highly elevated intraocular pressure by June. After lack of response to oral valacyclovir, aqueous fluid and swabs of her conjunctiva and limbal epithelium with corneal epithelium anterior to the limbus were sent for real-time polymerase chain reaction (PCR) for herpes simplex virus, herpes zoster virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epithelium from the cornea and limbus was positive for SARS-CoV-2 by PCR; specimens from the other two ocular sites were negative. All specimens were negative for herpes simplex virus and varicella zoster virus. The patient refused further treatment despite intraocular pressure above 50 mm Hg at last follow-up. Although SARS-CoV-2 and severe acute respiratory syndrome coronavirus (SARS-CoV) have been detected by PCR in the conjunctiva and tears of patients with acute respiratory infection, presence in corneal tissue has not been described. In addition, no one has studied whether ocular tissues in convalesced patients can harbor viral RNA. Here we describe unilateral keratouveitis in a convalesced patient whose corneal epithelium/limbal tissue was positive for SARS-CoV-2 by PCR. Further investigation is required to determine whether active viral replication or viral remnants account for this result.


Potential for optimizing the perioperative care in robotic prostatectomy patients by adoption of enhanced recovery after surgery principles.
Several benefits have been reported after applying the principles of enhanced recovery after surgery (ERAS) into the perioperative care of patients undergoing robot-assisted radical prostatectomy (RARP). Nevertheless, there are still barriers. We aimed to identify the key areas by systematically surveying urology departments in Germany and Austria. A 27-question survey on the adoption of ERAS principles for the perioperative care of RARP patients was designed, in compliance with the guidelines on good practice in conducting and reporting of survey research. After positive testing for face and content validity, the survey was distributed via postal mail to 82 departments performing RARP. In total, 39 departments responded to our survey (response rate 48%). The ERAS adoption rates ranged from 21 to 97%, with nine ERAS principles being widely adopted (72-92% of the departments). The lowest adoption rates and, subsequently, the largest potential for optimization were detected for the preoperative nutrition counselling (21%), preoperative pelvic floor physiotherapy (54%), postoperative early initiation of nutrition (44%) and postoperative patient audit for further quality improvement (36%). High-volume centers performed more frequently a perioperative nutrition counselling (8/27; 30%) than low-volume centers (0/12; 0%; p = 0.036). The implementation of the ERAS principles into the perioperative care algorithm were medium-to-high, yet not optimal. Our real-world data assessment revealed four key areas showing low adoption rates (nutrition counselling, preoperative pelvic floor physiotherapy, early initiation of nutrition and patient audit), implying a great potential for further optimization.


Analysis of 24 cases of epithelioid glioblastoma: Experience from a tertiary centre of North India.
Epithelioid glioblastoma (eGB) is a recently recognized and a rare variant of glioblastoma. This study aimed to describe the clinical, histological and immunohistochemical spectrum and outcome of eGB from a tertiary care hospital in north India. Twenty four cases of eGB diagnosed over past 10 years were reviewed with detailed morphological and immunohistochemical analysis (GFAP, EMA, Vimentin, Myogenin, INI-1, Cytokeratin, Synaptophysin, CD99, S100, MelanA, IDH1, ATRX, p16, EZH2, Ki-67, and BRAF V600E mutant antibody). The mean age was 29.9 years (3-54 years), with equal male and female patients. All had supratentorial tumor. All cases showed epithelioid cells in sheets; however, focal spindling (7 cases, 29.2%), grouping/nesting (6 cases, 25%) and papillary configuration (5 cases, 20.8%) were also noted. All showed microvascular proliferation (MVP) and all except one demonstrated areas of necrosis. INI1 was retained in all cases, while 2 showed patchy loss. EZH2 overexpression (>25%) was observed in 4 cases, while 5 cases showed loss of p16 expression. BRAF V600E mutant protein expression was seen in 12/23 (52.2%) cases. Outcome was available in 8 cases, out of which 6 (75%) experienced recurrence. The median survival was 25.5 months. Cases with tumor infiltrating lymphocytes had a better outcome. eGB is a distinct variant of glioblastoma which has predilection towards younger age group. It shows high percentage of BRAF V600E mutation and a subset of it shows longer survival. Cases with presence of tumor infiltrating lymphocytes are associated with better outcome.


Enlarged and prominent nucleoli may be indicative of MYCN amplification: a study of neuroblastoma (Schwannian stroma-poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index.
According to the International Neuroblastoma Pathology Classification, neuroblastomas exhibiting MYCN amplification (A-MYCN) have unique histologic features-namely, undifferentiated/poorly differentiated subtype with a high mitosis-karyorrhexis index (U/PD-H). Nonetheless, certain tumors possessing these histologic characteristics contain a nonamplified MYCN gene (NA-MYCN). The clinical characteristics of patients from the Children's Cancer Group (CCG) 3881 and 3891 studies who had neuroblastoma, U/PD-H, exhibiting A-MYCN (n=68) or NA-MYCN (n=33) were investigated. The histologic and cytologic features of tumors (A-MYCN, n=62; NA-MYCN, n=28) filed at the Pathology Reference Laboratory, Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, were reviewed, and nucleolar areas in undifferentiated neuroblastic cells were evaluated using image analysis methods. All 68 patients whose tumors exhibited A-MYCN had disease that was in an advanced clinical stage (Stage III or IV); 89.7% of these patients were diagnosed between ages 0.5 and 3.5 years, and 67 of the 68 had been treated with the high-risk protocol in the CCG-3891 study. Children whose tumors exhibited NA-MYCN were evenly distributed across all age groups; 30 of these 33 children had advanced-stage disease, and 26 had been treated with a high-risk protocol. The prognosis associated with A-MYCN (event free survival [EFS], 15.7%; overall survival [OS], 22.2%) was significantly poorer than the prognosis associated with NA-MYCN (EFS, 56.1%; OS, 69.3%). The lone histologic/cytologic difference between tumors exhibiting A-MYCN and tumors exhibiting NA-MYCN involved nucleolar appearance. Neuroblastic cells in tumors exhibiting A-MYCN were characterized by the presence of 1 or more large, prominent nucleoli, and the mean nucleolar area was significantly greater in the 18 tumors exhibiting A-MYCN that were assessed (7.63 microm2) than in the 16 tumors exhibiting NA-MYCN that were assessed (5.53 microm2; P=0.004). Neuroblastomas, U/PD-H, were found to vary in terms of molecular background and clinical behavior. The results of the current study indicate that nucleolar enlargement in neuroblastic cells may be a sign of MYCN amplification.


Information = equity? How increased access to information can enhance equity and improve health outcomes for pregnant women in Peru.
The Peruvian health system provides care through numerous, disconnected health establishments and information systems. Our objective was to explore information use and needs of pregnant women to improve quality of care. We carried out a mixed methods study in the Lima capital metropolitan area in 15 health centers. This included four focus groups with 34 pregnant women and surveys with 403 pregnant women. Pregnant women's information needs depend on their age, number of pregnancies and environment. Women relied on their social networks for pregnancy-related advice and valued high-quality, timely and targeted information from the health system. Participants' information needs include access to reliable information and responses to their questions in a warm, caring and safe environment. These needs can be met during prenatal check-ups and in group settings through informational talks and visual displays in waiting areas, as well as through appropriate digital technologies such as SMS messages and electronic health records. Pregnant women need individualized health information in an understandable, secure and friendly manner to maximize their understanding of their pregnancy, follow recommendations and optimize health outcomes. Customizing e-Health programs that reach many pregnant women has greater potential for more equitable health outcomes. electronic health records, health information systems, healthcare disparities, maternal health services, pregnant women, text messaging.


Immunomodulation and TNF-α inhibition for tubulointerstitial nephritis and uveitis syndrome: a case series.
Tubulointerstitial nephritis and uveitis (TINU) syndrome combines acute inflammatory nephritis (AIN) and uveitis. Uveitis in TINU often requires systemic immunomodulatory therapy (IMT), including steroid-sparing agents. Although common for other noninfectious uveitides, the use of tumor necrosis factor-α inhibitors (TNFi) in TINU has seldom been described. This retrospective case series included patients <18 years of age with TINU followed at our tertiary care pediatric hospital. Disease characteristics at time of diagnosis and subsequent ophthalmological and rheumatologic evaluations were extracted from the record. AIN was defined as the presence of abnormal renal function and urinalysis or renal biopsy findings consistent with TINU. Uveitis grading, site of inflammation, inactivity, and flare were defined according to Standardization of Uveitis Nomenclature. A total of 10 patients (median age, 12.3 years; 6 females) were included. AIN preceded uveitis onset in 6 patients. Uveitis was bilateral at onset in 7 patients. Uveitis inactivity was achieved with systemic corticosteroids (CS) in 2 and with mycophenolate mofetil (MMF) in 3 patients. Because of persistent ocular inflammation, despite CS and IMT, 4 patients were treated with TNFi. All rapidly achieved uveitis quiescence and maintained prolonged inactivity under combined treatment with TNFi and MMF. Most patients in our study cohort required a steroid-sparing immunomodulator to achieve and maintain uveitis control. In the 50% of the cohort in whom conventional IMTs were inadequate, TNFi were able to maintain quiescence. TNF inhibition might be a useful treatment in IMT-refractory uveitis in TINU patients.


Dorsal silicone rods in the primary care of war injuries.
During armed combat serious hand injuries are often neglected only to receive the attention they deserve far too late. The authors have employed a vigorous approach to the primary care of severe war injuries to dorsum of the hand introducing silicone rods where extensor tendons have been destroyed and where skin closure is obtained using inguinal skin flaps.


PeptideBERT: A Language Model Based on Transformers for Peptide Property Prediction.
Recent advances in language models have enabled the protein modeling community with a powerful tool that uses transformers to represent protein sequences as text. This breakthrough enables a sequence-to-property prediction for peptides without relying on explicit structural data. Inspired by the recent progress in the field of large language models, we present PeptideBERT, a protein language model specifically tailored for predicting essential peptide properties such as hemolysis, solubility, and nonfouling. The PeptideBERT utilizes the ProtBERT pretrained transformer model with 12 attention heads and 12 hidden layers. Through fine-tuning the pretrained model for the three downstream tasks, our model is state of the art (SOTA) in predicting hemolysis, which is crucial for determining a peptide's potential to induce red blood cells as well as nonfouling properties. Leveraging primarily shorter sequences and a data set with negative samples predominantly associated with insoluble peptides, our model showcases remarkable performance.


On the histochemistry of neuronal and glial TPPase.
Thiamine pyrophosphatase (TPPase) activity in the neuronal Golgi apparatus and in glia cells was investigated using different tissue preparation techniques such as fresh frozen and fixed frozen sections, the effect of ATP as an activator and the fine structural localization of the enzyme activity in glia cell processes and the glio-vascular contact point was observed under the electron microscope. TPPase was demonstrated in the glia cell using only a fixed frozen tissue preparation, activated by ATP with the concentration as low as 0.1 mM. On the contrary, enzyme activity was detected in the Golgi apparatus of the neuron regardless of tissue preparation, fresh or fixed frozen, or by the addition of ATP to the incubation medium. The identity of the glia cell type showing a positive reaction for TPPase is thought to be part astrocyte and part microglia. The fine structural observation of TPPase localization at the glia cell process ending, particularly at the glio-vascular and glio-fibral (medullated fiber) contact point suggests a functional role of this enzyme for transport of metabolites through glia cell processes to neurons and/or the blood capillary, and also may play a role in regulation of co-carboxylase.


Two new lignans and anti-HBV constituents from Illicium henryi.
Two new lignans, dihydrodehydrodiconiferyl alcohol 9-O-β-D-(3″-O-acetyl)-xylopyranoside (1) and threo-4,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan 7-O-α-rhamnopyranoside (2) were isolated from Illicium henryi, together with ten known compounds, 3-12. Their structures were elucidated by extensive spectroscopic analyses. The anti-hepatitis B virus (anti-HBV) activity of compounds 1-12 inhibiting HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion on Hep G2.2.15 cell line was evaluated. (-)-Dihydrodehydrodiconiferyl alcohol (4) showed moderate inhibitory activity on both HBsAg and HBeAg secretion with IC(50) values of 0.06 and 0.53 mM, respectively.


Single-cell analysis of early B-lymphocyte development suggests independent regulation of lineage specification and commitment in vivo.
To better understand the process of B-lymphocyte lineage restriction, we have investigated molecular and functional properties in early B-lineage cells from Pax-5-deficient animals crossed to a B-lineage-restricted reporter mouse, allowing us to identify B-lineage-specified progenitors independently of conventional surface markers. Pax-5 deficiency resulted in a dramatic increase in the frequency of specified progenitor B-cells marked by expression of a λ5 (Igll1) promoter-controlled reporter gene. Gene expression analysis of ex vivo isolated progenitor cells revealed that Pax-5 deficiency has a minor impact on B-cell specification. However, single-cell in vitro differentiation analysis of ex vivo isolated cells revealed that specified B-lineage progenitors still displayed a high degree of plasticity for development into NK or T lineage cells. In contrast, we were unable to detect any major changes in myeloid lineage potential in specified Pax-5-deficient cells. By comparison of gene expression patterns in ex vivo isolated Pax-5- and Ebf-1-deficient progenitors, it was possible to identify a set of B-cell-restricted genes dependent on Ebf-1 but not Pax-5, supporting the idea that B-cell specification and commitment is controlled by distinct regulatory networks.