Isolation of two genomic sequences encoding the Mr = 14,000 subunit of rat prostatein.
Complementary DNAs to rat ventral prostate poly(A) RNA were cloned into pBR322 by the "dG-dC tailing" procedure. Clones containing cDNAs to the mRNAs coding for each of the three subunits of a major secretory protein (prostatein) were identified by hybrid-arrested translation. A 457-nucleotide base pair cDNA (E45) and a portion of a 365-base pair cDNA (E85) were analyzed to determine the composite complete DNA coding sequence for the Mr = 14,000 (C3) subunit of prostatein. A sequence of 12-nucleotide bases (TTTGCTGCTATG) in the signal peptide of C3 was noted to be homologous to signal peptide nucleotide sequences reported in cDNAs coding for the other two prostatein subunits, Mr = 6,000 (C1) and 10,000 (C2). Complementary DNA coding for the C3 subunit was used as a hybridization probe to screen an EcoRI rat genomic DNA library. Two unique 12-kilobase genomic clones, each containing mRNA coding sequences within 2.5-3-kilobase fragments, were identified by restriction enzyme mapping and Southern blot analysis. Restriction enzyme sites within the coding regions of both genes were analogous to the cDNA. Differences in restriction enzyme sites in regions of intervening sequences and flanking DNA established the uniqueness of the two genes. It is suggested that both genes may be transcribed in vivo.


Hemifacial atrophy: a case report of fat transplantation.
A case of hemifacial atrophy affecting a young female is presented and the manifestations of this uncommon disorder are reviewed. The various methods employed in correcting the facial deformity including the relatively new technique of fat injection are described.


TBX22 and tongue-tie.
To resolve if TBX22 mutations cause isolated tongue-tie in the Finnish population. Mutation analysis of the coding region of the TBX22 gene in 50 Finnish isolated tongue-tie patients and 61 control samples. One putative sequence variation was identified from two male patients, but whether this represents a polymorphism or causative mutation remains unknown. Mutations in the coding region of the TBX22 gene are not a major cause of ankyloglossia in the Finnish population and do not explain the sex difference or inheritance of tongue-tie.


CRISPR/Cas13a-assisted AMP generation for SARS-CoV-2 RNA detection using a personal glucose meter.
Herein, we described a washing- and label-free clustered regularly interspaced short palindromic repeats (CRISPR)/LwaCas13a-based RNA detection method utilizing a personal glucose meter (PGM), which relies on the trans-cleavage activity of CRISPR/Cas13a and kinase reactions. In principle, the presence of target RNA activates the trans-cleavage of CRISPR/Cas13a, generating 2',3'-cyclic phosphate adenosine, which is converted to adenosine monophosphate (AMP) by the T4 polynucleotide kinase. Subsequently, the AMP is converted to adenosine diphosphate (ADP) through phosphorylation by a myokinase; ADP is then used as a substrate in the cascade enzymatic reaction promoted by pyruvate kinase and hexokinase. The overall reaction leads to the continuous conversion of glucose to glucose-6-phosphate, resulting in a reduction of glucose concentration proportional to the level of target RNA, which can therefore be indirectly measured with a PGM. By employing this novel strategy, severe acute respiratory syndrome coronavirus-2 RNA can be successfully detected with excellent specificity. In addition, we were able to overcome non-specific responses of CRISPR/Cas13a and distinguish single nucleotide polymorphisms by introducing a single-base mismatch in the complementary RNA. Our study provides an alternative coronavirus disease 2019 detection technology that is affordable, accessible, and portable with a fast turnaround time and excellent selectivity.


Effectiveness of corneal abrasion prevention interventions for adults undergoing general anesthesia for more than one hour: a systematic review protocol.
The question of this review is: what is the effectiveness of eye lubrication, tape and/or a combination of these interventions in preventing corneal abrasions in adult patients aged 18 and over undergoing general anesthesia for more than one hour?


The influence of adrenergic blockade in rats with apical periodontitis under chronic stress conditions.
To investigate the influence of chronic stress and adrenergic blockade in a rat model of apical periodontitis. Thirty-two Wistar rats were submitted to an animal model of periapical lesion and randomly divided into 4 groups (n = 8): no stress (NS); stress + saline solution (SS); stress + β-adrenergic blocker (Sβ); stress + α-adrenergic blocker (Sα). The SS, Sβ and Sα groups were submitted to an animal model of chronic stress for 28 days and received daily injections of saline solution, propranolol (β adrenergic blocker) and phentolamine (α adrenergic blocker), respectively. After 28 days the animals were euthanized and the following analyses were carried out: a) serum corticosterone levels through Radioimmunoassay; b) measurement of serum levels of IL-1B, IL-6, IL-10 and IL-17 by enzyme-linked immunosorbent assay (ELISA); c) volume of periapical bone resorption by micro-computed tomography; d) histomorphometric analysis by staining with hematoxylin and eosin; e) expression of β-AR, α-AR, receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) by immunohistochemistry; f) tartrate-resistant acid phosphatase (TRAP) staining; g) ex-vivo cytokine release followed by the stimulation with LPS in superfusion system, by ELISA. SS group displayed significantly higher corticosterone levels than NS group (non-stressed). Higher IL-1β serum level was observed in the NS group (p < .05); compared to all stressed groups. Other cytokines were present in similar amounts in the serum of all groups. All groups presented similar periapical lesions. All groups presented moderate inflammatory infiltrate, without statistically significant differences between them. No differences were observed regarding β-AR, α-AR, Rank-L and OPG expression. The number of TRAP-positive cells was significantly decreased in the groups that received daily injections of adrenergic blockers. The IL-1β release followed LPS stimulation was significantly suppressed when the superfusion media contained propranolol (p < .05). Perfusion containing phentolamine induced a greater release of IL-10. TGF-β was significantly suppressed by phentolamine perfusion in the NS group (p < .05). Chronic stress can significantly change the inflammatory cytokines release. Rank-L/OPG system and periapical lesion volume were not affected following the current method applied. The administration of adrenergic blockers was not able to modulate the inflammatory response but presented effectivity in reducing the number of osteoclasts in the periapical region.


Structure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration.
ABCA4 is a member of the superfamily of ATP-binding cassette (ABC) transporters that is preferentially localized along the rim region of rod and cone photoreceptor outer segment disc membranes. It uses the energy from ATP binding and hydrolysis to transport N-retinylidene-phosphatidylethanolamine (N-Ret-PE), the Schiff base adduct of retinal and phosphatidylethanolamine, from the lumen to the cytoplasmic leaflet of disc membranes. This ensures that all-trans-retinal and excess 11-cis-retinal are efficiently cleared from photoreceptor cells thereby preventing the accumulation of toxic retinoid compounds. Loss-of-function mutations in the gene encoding ABCA4 cause autosomal recessive Stargardt macular degeneration, also known as Stargardt disease (STGD1), and related autosomal recessive retinopathies characterized by impaired central vision and an accumulation of lipofuscin and bis-retinoid compounds. High resolution structures of ABCA4 in its substrate and nucleotide free state and containing bound N-Ret-PE or ATP have been determined by cryo-electron microscopy providing insight into the molecular architecture of ABCA4 and mechanisms underlying substrate recognition and conformational changes induced by ATP binding. The expression and functional characterization of a large number of disease-causing missense ABCA4 variants have been determined. These studies have shed light into the molecular mechanisms underlying Stargardt disease and a classification that reliably predicts the effect of a specific missense mutation on the severity of the disease. They also provide a framework for developing rational therapeutic treatments for ABCA4-associated diseases.


Effect of γ-irradiation on the growth of ZnO nanorod films for photocatalytic disinfection of contaminated water.
The growth of ZnO nanorods on a flat substrate containing γ-irradiated seeds and their ability to photocatalytically eliminate bacteria in water were studied. The seed layer was obtained, by the spray pyrolysis technique, from zinc acetate solutions γ-irradiated within the range from 0 to 100 kGy. Subsequently, to grow the rods, the seeds were immersed in a basic solution of zinc nitrate maintained at 90 °C. The rate of crystal growth on the seed layer during the thermal bath treatment was kept constant. The resulting materials were characterized morphologically by scanning electron and atomic force microscopies; X-ray diffraction was used to study their morphology and structure and ultraviolet-visible spectroscopy to determine their absorbance. The obtained seed films were morphologically dependent on the radiation dose and this was correlated with the ZnO nanorod films which presented a texture in the (002) direction perpendicular to the substrate. The rods have a hexagonal mean cross section between 20 and 140 nm. Using these rods, the photocatalytic degradation of Escherichia coli bacteria in water was studied; a positive influence of the crystalline texture on the degradation rate was observed.


Combining transcriptomics and network pharmacology to reveal the mechanism of Zuojin capsule improving spasmolytic polypeptide-expressing metaplasia.
Spasmolytic polypeptide-expressing metaplasia (SPEM) is a gastric precancerous lesion (GPL). Zuojin capsule (ZJC), consisting of Coptis chinensis Franch. (Ranunculaceae, recorded in the Chinese Pharmacopoeia as Rhizoma Coptidis) and Tetradium ruticarpum (A.Juss.) T.G.Hartley (Rutaceae, recorded in the Chinese Pharmacopoeia as Fructus Evodiae), has long been used for various gastrointestinal diseases. However, the effect and mechanism of ZJC on SPEM remain unclear. To clarify the role of ZJC in improving SPEM and study its mechanism. The study utilized SPEM mice induced by 250 mg/kg body weight of tamoxifen (TAM) to assess the effects of ZJC and investigate its possible mechanisms. A strategy of transcriptomics combined with network pharmacology was conducted to explore the targets and mechanisms of ZJC in improving SPEM. The "ingredients-target-pathway" network was constructed, and the possible connections were verified by RT-qPCR and Western blot assays. ZJC significantly attenuated the abnormal serological indices, destruction of the gastric mucosal structure, hyperplasia of gastric pits, increased gastric mucus, massive secretion of CD44 and TFF2, oxyntic atrophy and massive proliferation of stem/progenitor cells in TAM-induced SPEM mice. Combined transcriptomics and network pharmacology analysis, 50 core targets of ZJC related to SPEM improvement were obtained. KEGG results showed that the core targets were significantly enriched in the cell cycle, and PI3K-AKT signaling pathway. The top-ranked targets according to PPI network analysis were CDK1, CCNB1, and CCNA2, which are also associated with cell cycle. Combined experiments demonstrated that ZJC can induce G2/M phase cycle arrest and inhibit TAM-induced malignant proliferation by regulating abnormal activation of cell cycle-related proteins such as CDK1, CCNB1, CCNA2 and PI3K-AKT signaling pathways. ZJC may improve TAM-induced SPEM by inhibiting abnormal activation of cell cycle-related proteins (CDK1, CCNB1, CCNA2) and PI3K-AKT signaling pathway. This finding supports the use of ZJC, a famous traditional Chinese medicine compound, as a potential treatment for gastric precancerous lesions.


Relationships of changes in craniofacial morphology, head posture, and nasopharyngeal airway size following mandibular osteotomy.
The aim of the present study was to illustrate a possible relationship between changes in craniofacial morphology after mandibular osteotomy and changes in head posture and nasopharyngeal airway size. The material comprised standardized profile cephalograms of 52 patients with mandibular prognathism, all of whom underwent orthodontic adjustment before mandibular osteotomy. Mean age of the patients was 24.3 years; 12 men and 40 women participated in the study. The first profile radiograph of each patient was taken 1 day before surgical treatment in the natural head (mirror) position. All patients underwent mandibular surgery with a bilateral vertical ramus osteotomy. The cephalometric investigation was repeated approximately 1 year after the surgical procedure (means = 1.12 years). Craniofacial morphology was evaluated by 12 parameters describing sagittal and vertical jaw relationship. Head posture was evaluated by the craniocervical angulation and airway as nasopharyngeal airway size. Pearson's correlation analysis was used to evaluate the relationship between morphology, posture, and airway size before surgery and changes in these parameters after surgery. Before surgical treatment statistically significant correlations were found between posture and many morphologic variables, mostly mandibular. Small correlations were observed between posture and airway size, and airway size and morphology. After the surgical procedure, changes in posture were still related to changes in mandibular morphology, while other correlations between posture and morphology had been eliminated. Changes in nasopharyngeal airway size were not correlated to any changes in morphology, apart from maxillary prognathism, nor to changes in posture. The results indicated that mandibular morphology and function play a significant role in determining head posture.


Multicenter cross-sectional study of nontuberculous mycobacterial infections among cystic fibrosis patients, Israel.
This 2-year cross-sectional evaluation of nontuberculous mycobacterial (NTM) infections involved all Israeli medical centers that treat cystic fibrosis patients. The study comprised 186 patients whose sputum was analyzed for NTM. The prevalence of NTM isolates was 22.6%, and 6.5% and 10.8% of the patients fulfilled the 1997 and 2007 American Thoracic Society criteria for NTM lung disease, respectively. Mycobacterium simiae (40.5%), M. abscessus (31.0%), and M. avium complex (14.3%) were the most prevalent. Presence of Aspergillus spp. in sputum and the number of sputum specimens processed for mycobacteria were the most significant predictors for isolation of NTM (odds ratio [OR] = 5.14, 95% confidence interval [CI] 1.87-14.11 and OR = 1.47, 95% CI 1.17-1.85, respectively). The incidence of NTM pulmonary infections is increasing among cystic fibrosis patients, reflecting the increase in longevity of such patients as well as environmental exposure to various species of mycobacteria.


Oxysterols in cancer cell proliferation and death.
Oxysterols have been shown to interfere with proliferation and cause the death of many cancer cell types, such as leukaemia, glioblastoma, colon, breast and prostate cancer cells, while they have little or no effect on senescent cells. The mechanisms by which oxysterols may influence proliferation are manifold: they control the transcription and the turnover of the key enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase, by binding to Insig-1, Insig-2 and liver X receptors. Oxysterols are thought to be generated in proportion to the rate of cholesterol synthesis. Although there is no consensus about the mechanism by which these oxysterols are generated in vivo, it clearly has to be ubiquitous. The 25- and the 27-cholesterol hydroxylases, present in almost all tissues, are possible candidates. Cholesterol uptake from lipoproteins, intracellular vesicle transport and lipid transfer are also modified by oxysterols. Oxysterols interfere with ERK, hedgehog and wnt pathways of proliferation and differentiation. When administered in vitro to cancer cell lines, oxysterols invariably both slow down proliferation and provoke cell death. Perhaps is it sufficient to stop proliferation of a cancer to provoke its eradication. Therefore, the two facets of oxysterol action that seem important for cancer treatment, cytostaticity and cytotoxicity, will be discussed.


Age effects on the neural processing of object-context associations in briefly flashed natural scenes.
In daily life, fast visual recognition of surrounding objects is facilitated through context-based expectations. However the ability to rapidly and accurately recognize unexpected stimuli in a given environment is also crucial and this ability is impaired with age. The present fMRI study aimed at comparing in young and older adults the neural correlates of fast object processing. Patterns of cerebral activity were investigated in response to briefly-presented (100 ms) congruent and incongruent natural scenes. Participants were slower and less accurate when categorizing objects in incongruent relative to congruent contexts. This behavioral cost was notably more pronounced in the older group. Height and multivariate patterns of fMRI activity in context-selective regions were equivalent in both age groups, suggesting preserved processing of coarse scene features in older participants. Incongruent scenes elicited additional activity in the parahippocampal gyrus that possibly reflected simultaneous activation of rarely co-occurring neural representations. Contextual effects were observed in object-selective cortex for the young group only, and may be driven by detection of mismatch between actually perceived and previously-experienced associations. In the older group exclusively, increased bilateral prefrontal and left fusiform activity in response to incongruent scenes was observed. However this supplemental activity was not found to efficiently contribute to improve task performance in difficult visual conditions. Altogether these results suggest age-related changes in the interaction between object- and context-processing pathways, that may subserve impairment in fast identification of unexpected objects in natural scenes.


Proton density fat fraction (PDFF) maps aid fat metaplasia evaluation in the sacroiliac joints in additional to T1WI: Improved diagnostic accuracy in axial spondyloarthritis.
To evaluate the added value of qualitative and quantitative fat metaplasia analysis using proton-density fat fraction (PDFF) map in additional to T1-weighted imaging (T1WI) of the sacroiliac joints (SIJ) for diagnosis of axial spondyloarthritis (axSpA). Patients aged 18-45 years with axSpA were enrolled. Non-SpA patients and healthy volunteers were included as controls. All participants underwent 3.0T MRI of the SIJs including semi-coronal T1WI and semi-coronal chemical-shift encoded MRI sequence for generating PDFF map. Each joint was divided into four quadrants for analysis. Two independent readers scored fat metaplasia on T1WI alone or with additional PDFF map and measured PDFF values in different reading sessions. Using clinical diagnosis as the reference, diagnostic accuracy of visual scores and PDFF measurements was evaluated by area under the receiver operating characteristic curve (AUC). Inter-reader agreement was evaluated by the intra-class correlation coefficient (ICC). Forty-nine patients with axSpA and thirty-six controls were included. Qualitative fat metaplasia scores using additional PDFF map performed better than using T1WI alone (AUC: Reader 1, 0.847 vs 0.795, p = 0.082; Reader 2, 0.785 vs 0.719, p = 0.048). AUCs of quantitative analysis using number of quadrants with PDFF value ≥75 % were higher than qualitative analysis using T1WI alone (Reader 1, 0.863 vs 0.795, p = 0.046; Reader 2, 0.823 vs 0.785, p = 0.011). ICCs were 0.854 to 0.922 for qualitative analysis and 0.935 for quantitative analysis. Additional PDFF map can increase the diagnostic accuracy for axSpA by qualitative and quantitative fat metaplasia analysis, in comparison to using T1WI alone.


Cancer incidence in a cohort of infertile women who underwent in vitro fertilization.
To assess whether ovarian hyperstimulation and IVF increase the risk for cancer. Historical cohort analysis. SETTING; IVF units of two medical centers in Israel. Five thousand twenty-six women who underwent IVF between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined through linkage to the National Cancer Registry and were compared with expected rates with respect to age, sex, and place of birth. Development of cancer. Twenty-seven cases of cancer were observed, and 35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]). Eleven cases of breast cancer were observed, whereas 15.86 were expected (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73 cases expected, respectively. The type of infertility, number of IVF cycles, and treatment outcome did not significantly affect risk for cancer. In a cohort of women treated with IVF, no excess risk for cancer was noted.


Intention to Vaccinate against COVID-19 in Adolescents: A Systematic Review.
Multiple COVID-19 vaccines have been approved for use in adolescents; these vaccines play a critical role in limiting the transmission and impact of COVID-19. This systematic review aims to summarize the willingness of adolescents aged 10 to 19 years to receive the COVID-19 vaccination and the factors influencing their decision. A search of literature published between January 2018 and August 2022 was performed in Medline©, EMBASE©. and CINAHL© electronic databases. Studies published in English that assessed adolescents' intentions to receive the COVID-19 vaccine were included. Qualitative studies and those unrelated to the COVID-19 vaccine were excluded. The study was conducted based on the PRISMA guidelines. Of the 1074 articles retrieved, 13 were included in the final review. Most studies were conducted in the US (n = 3) and China (n = 3). The pooled prevalence of COVID-19 vaccine acceptance among adolescents was 63% (95% CI: 52-73%). Factors influencing intent to vaccinate were divided into five categories: "Socio-demographic determinants"; "Communication about COVID-19 pandemic and vaccination"; "COVID-19 vaccine and related issues"; "COVID-19 infection and related issues" and "Other determinants". The enablers were sociodemographic factors including older age, higher education level, good health perception, and parental norms in terms of parental vaccination acceptance; perceived vaccine effectiveness and safety; a desire to protect themselves and others; recent vaccination; and anxiety. The barriers were concerns over vaccine effectiveness, safety, and long-term side effects; low perceived necessity and risk of infection; and needle phobia. This review highlighted that adolescents' intent to vaccinate is driven by a desire to protect themselves and others. However, concerns over vaccine effectiveness, safety, and long-term side effects hinder COVID-19 vaccine uptake. To improve vaccination acceptance, policymakers should address adolescents' concerns via more targeted public health messaging, while schools should leverage peer norms to positively influence vaccination intent.


Analysis of empty responses from electronic resources in infobutton managers.
Infobuttons provide context-aware educational materials to both providers and patients and are becoming an important element in modern electronic health records (EHR) and patient health records (PHR). However, the content from different electronic resources (e-resource) as responses from infobutton manager has not been fully analyzed and evaluated. In this paper, we propose a method for automatically analyzing responses from infobutton manager. A tool is implemented to retrieve and analyze responses from infobutton manager. To test the tool, we extracted and sampled common and uncommon concepts from EHR usage data in Intermountain Healthcare's enterprise data warehouse. From the output of the tool, we evaluate infobutton performance by multiple categories, including against the most and less common used concepts, grouped by different modules in patient portal, by different e-resources, and by type of access (standardized Health Level Seven (HL7) vs not). Based on the results of our evaluation, we provide suggestions for further enhancements of infobuttons to the current implementation, including suggesting accessing priorities of e-resources and encouraging the use of the HL7 standard.


Ultrastructural localization of Thermoplasma acidophilum surface carbohydrate by using concanavalin A.
Surface carbohydrate, presumably the lipopolysaccharide, of Thermoplasma acidophilum was visualized by means of the concanavalin A, horseradish peroxidase, and diaminobenzidine cytochemical staining procedure.


The evaluation of a culturally appropriate, community-based lifestyle intervention program for elderly Chinese immigrants with chronic diseases: a pilot study.
The 'Healthy Habits Program' is a 6-month community-based program, which offers exercise facilities, training and weekly health education group to underserved elderly Chinese Americans with chronic medical diseases in their native languages. This pilot study evaluates the acceptability and the health effects of the 'Healthy Habits Program'. Ninety-nine subjects participated in the 'Healthy Habits Program' in 2011. Before and after the program, the participants were assessed in their physical and mental health using various fitness tests as well as measures of disability and psychological functioning. Participants provided overwhelmingly positive feedback on the program, which was associated with significant improvements in physical and mental health including a significant decrease in body mass index (BMI), blood pressure and increase in stamina. The participants reported lower mean scores on the Patient Health Questionnaire-9 item Scale (PHQ-9), indicating improved psychological well-being. These promising pilot study results from this lifestyle intervention program for elderly Chinese American immigrants with chronic diseases inform the design of a more definitive trial using a randomized design and larger sample size.


Preliminary report on the effects of hyperoxia on cochlear potential in chinchilla.
Anesthestized chinchilla with round window electrodes were placed in a Plexiglas chamber. When they inhaled 100% oxygen at 1 atm, two types of neural effects were observed: 1. fast and reversible AP depression in response to brief exposure to 100% O2; and 2. a slowly developed chronic depression of AP and latency shift due to multiple hyperoxic exposures. The severity of the latter is a function of the dosage of the O2 inhaled, i.e., the concentration of oxygen and the length of time of exposure. For the type-1 effect, carbon dioxide deprivation is felt to be the immediate cause while the type-2 effect is mainly due to O2 toxicity developed at the intracellular level by high O2 concentration. The possible role of superoxide in the auditory O2 toxicity was discussed.


Characterization of new D-beta-aspartate-containing proteins in a lens-derived cell line.
Although proteins are generally composed of l-alpha-amino acids, biologically uncommon D-beta-aspartic acid (Asp)-containing proteins have been reported in various tissues from elderly individuals. Our previous study indicated that the N/N1003A cell line, derived from rabbit lens, includes D-beta-Asp-containing proteins of approximately 50 kDa by Western blot analysis of a 2D-gel using a polyclonal antibody that is highly specific for D-beta-Asp-containing proteins. In this study, we identified the D-beta-Asp-containing proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the Mascot online database searching algorithm. The results indicate that one of these 50 kDa proteins is an enolase showing homology with tau-crystallin. Other D-beta-Asp-containing proteins, which we have recently discovered include lamin A/C, cytoplasmic NADP+-dependent isocitrate dehydrogenase, fructose-bisphosphate aldolase A, aldose reductase, L-lactate dehydrogenase A or calponin H2, phosphoglycerate mutase 1, phosphatidylethanolamine-binding protein, alpha-B-crystallin, and peptidyl-prolyl cis-trans isomerase A (PPlase).


A rare case of fibrosarcoma of the jaws in a 4-year-old male.
A case of fibrosarcoma in a 4-year-old male child is reported. Primary fibrosarcomas of bone in the head and neck region are rare. The histological appearance of the tumour is related to its grade of differentiation. It could present a high level of cellularity and the amount of collagen is variable. The accepted treatment is radical surgery; however, metastases could occur in the lungs. This article is presented to highlight the rarity of fibrosarcomas in the jaws of children.


Age-related differences in the blood alcohol levels of Wistar rats.
Knowledge of blood alcohol levels (BALs) that are achieved following ethanol administration is critical for contemporary efforts to develop animal models of alcoholism. Adolescent and adult male Wistar rats were administered varying doses of ethanol (0.75, 1.5 and 3.0 g/kg) via gavage or intraperitoneal injection and BALs were measured over a two hour period. The results showed that adolescent animals had lower BALs across all time points in comparison to adults following administration of 0.75 g/kg ethanol and that 1 h after administration of 1.5 g/kg ethanol, adolescent animals showed an enhanced rate of elimination. The highest dose of ethanol (3.0 g/kg) produced comparable BALs for both adolescents and adults during the two-hour sampling period; however, the BALs for both ages were lower following administration of ethanol by gavage at this dose. Furthermore, an order effects analysis highlights that depending on the route of administration, initial dose size can influence the BALs produced by lower doses of ethanol. The current data identify the importance of measuring the level of alcohol in the blood to confirm that target BALs are achieved for adolescents and equivalent BALs are being reached for both adolescent and adult animals when such comparisons are made.


Classification of serous ovarian carcinoma based on immunogenomic profiling.
Treatment of serous ovarian cancer (SOC) remains a clinical challenge. Classification of SOC based on immunogenomic profiling is important for establishing immunotherapy strategies. We extracted RNA-seq data of SOC from TCGA-OV. The samples were ultimately classified into high immune (Immunity_H) group and low immune (Immunity_L) group based on the immunogenomic profiling of 29 immune signatures by using unsupervised machine learning methods and modified by multifaceted characterization of immune response. High immune group showed the lower tumor purity and higher anti-tumor immune activity, and the higher expressions of PDCD1, CD274 and CTLA4. Furthermore, the overall survival time and the progression-free interval were significantly longer in high-immun group. The differentially expressed genes were mainly enriched in some immune response related functional terms and PI3K-AKT signaling pathway. According to ImmuCellAI, the abundance of various T cell subtypes in high immune group were significantly higher than those in low immune group. This novel immunotyping shows promise for prognostic and immunotherapeutic stratification in SOC patients.


Preclinical activity of the novel B-cell-specific Moloney murine leukemia virus integration site 1 inhibitor PTC-209 in acute myeloid leukemia: Implications for leukemia therapy.
Curing patients with acute myeloid leukemia (AML) remains a therapeutic challenge. The polycomb complex protein B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of leukemia stem cells. We investigated the prognostic significance of BMI-1 in AML and the effects of a novel small molecule selective inhibitor of BMI-1, PTC-209. BMI-1 protein expression was determined in 511 newly diagnosed AML patients together with 207 other proteins using reverse-phase protein array technology. Patients with unfavorable cytogenetics according to Southwest Oncology Group criteria had higher levels of BMI-1 compared to those with favorable (P = 0.0006) or intermediate cytogenetics (P = 0.0061), and patients with higher levels of BMI-1 had worse overall survival (55.3 weeks vs. 42.8 weeks, P = 0.046). Treatment with PTC-209 reduced protein level of BMI-1 and its downstream target mono-ubiquitinated histone H2A and triggered several molecular events consistent with the induction of apoptosis, this is, loss of mitochondrial membrane potential, caspase-3 cleavage, BAX activation, and phosphatidylserine externalization. PTC-209 induced apoptosis in patient-derived CD34(+)CD38(low/-) AML cells and, less prominently, in CD34(-) differentiated AML cells. BMI-1 reduction by PTC-209 directly correlated with apoptosis induction in CD34(+) primary AML cells (r = 0.71, P = 0.022). However, basal BMI-1 expression was not a determinant of AML sensitivity. BMI-1 inhibition, which targets a primitive AML cell population, might offer a novel therapeutic strategy for AML.


Towards identifying a learning curve for robotic abdominal wall reconstruction: a cumulative sum analysis.
Over the past decade, an increase has been seen in robotics used for hernia repair, specifically robotic abdominal wall reconstruction (rAWR). However, the learning curve for rAWR can be steep and presently, little is understood regarding the optimal case volume required to achieve proficiency. The aim of our study was to review skill acquisition and describe the learning curve for rAWR. A retrospective, single-surgeon case series of consecutive patients who underwent rAWR from 2018 to 2022. The primary outcome was operative time, obtained from console time identified through the MyIntutive application. A one-sided cumulative sum analysis (CUSUM) curve for the total operative time was derived based on the mean operative time of chronological procedures (207 min). 185 patients underwent rAWR between 2018 and 2022. These patients were more likely to be female, Caucasian, and have undergone two previous hernia repairs. ASA complexity increased over time with ASA 3 being predominant from 2020 onwards. The median hernia length was 15.0 cm and the median width was 7 cm. Average operative time was 207.8 min and decreased over time. The CUSUM analysis identified four phases of skill acquisition with the following case volumes: Initial Learning Curve (0-20), Stabilization Phase (21-55), Second Learning Curve (56-70), 4) Skill Proficiency (> 70). In the early learning curve of rAWR, operative time decreased consistently after 70 cases, with an initial inflection after 20 cases. We identified varying stages of skill acquisition that are likely typical of a surgeon as they would progress through the learning curve of advanced robotic surgery. Future studies are needed to confirm the optimal case volume for determining the skill level for the performance of rAWR.


Gold nanoparticles paper as a SERS bio-diagnostic platform.
Bioactive papers are usually challenged by four major limitations: sensitivity, selectivity, simplicity and strength (4S). Gold nanoparticles (AuNPs) treated paper has previously been demonstrated as a Surface Enhanced Raman Scattering (SERS) active substrate, capable of addressing the 4S issues. In this study, AuNPs on paper substrate were functionalized by a series of biomolecules to develop a generic SERS platform for antibody-antigen detection. The functionalization steps were performed by taking advantage of the high affinity association between Streptomyces avidinii-derived protein, streptavidin, and biotin. Streptavidin was firstly bound onto the AuNPs treated paper using biotinylated-thiol. Subsequently, desired biotinylated-antibody was bound onto the streptavidin. SERS spectra of each functionalization step were obtained to ensure specific adsorption of the bio-molecules. The binding interaction of the antibody with its specific antigen was detected using SERS. Shifts of Raman band associated with α-helix and β-sheet structures indicated structural modification of the antibody upon interaction with its antigen. Predominant tryptophan and tyrosine residue bands were also detected, confirming the presence of antigen. Reproducible spectral features were quantified as AuNP papers were subjected to different concentrations of antigen; the spectra intensity increased as a function of the antigen concentration. The retention of AuNPs on paper remained constant after all the consecutive washing and functionalization steps. The feasibility of AuNPs paper as a low-cost and generic SERS platform for bio-diagnostic applications was demonstrated.


Recent advances in imidazoline receptor research: ligands--localization and isolation--signaling--functional and clinical studies.
In this article we outline the highlights of this special issue of the journal containing a series of articles covering many aspects of current interest in the field of imidazoline receptor research. This volume is the result of an international symposium held in September 1997 in Melbourne as an official satellite of the inaugural meeting of the International Society of Autonomic Neurosciences held in Cairns, Australia. A wide range of topics relating to imidazoline receptors were canvassed, including endogenous and synthetic ligands, identification and localisation of binding sites, putative transduction mechanisms and experimental and clinical functional studies.


Altered matrix metalloproteinases and tissue inhibitors of metalloproteinases in embryos from diabetic rats during early organogenesis.
Maternal diabetes increases the risks for embryo malformations. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are two relevant MMPs for embryo development. Here, we addressed whether changes in these MMPs and in tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 are altered in embryos and decidua from type 1 diabetic rats during early organogenesis. Our results demonstrate MMP-2 and MMP-9 overactivities and overexpression, together with increases in lipid peroxidation and nitric oxide production in embryos and decidua from diabetic animals. There is a concomitant increase in the inhibitory activity of TIMP-1 and TIMP-2 in embryos and decidua, and an increase in protein expression of embryonic TIMP-1 and TIMP-2. In situ zymography demonstrated MMPs overactivities despite increased TIMPs in embryos and decidua in maternal diabetes during early organogenesis. This study reveals that maternal diabetes leads to profound alterations in MMPs/TIMPs balance during embryo organogenesis, the gestational period during which most malformations are induced.


Predicting the Sustained Implementation of an Evidence-Based Parenting Program: A Structural Equation Modelling Approach.
Sustained implementation is required for evidence-based parenting programs to promote children and their families' wellbeing at the societal level. Previous literature has examined the role of a range of different factors in enhancing sustainability. However, the inter-relationship between, and the relative importance of different factors remain largely unknown. The overall aim of this study is to identify predictors of sustained program use, the relative importance of factors, and potential mediation pathways. We surveyed 1202 practitioners who were trained in at least one variant of the Triple P-Positive Parenting Program, at least one and half years before data collection. The present data were linked with data collected during professional training. We first examined the independent effect of each factor on sustained program use, then, developed and evaluated a structural equation model of sustained program use. The structural equation model explained a considerable amount of variance in sustained program use, with seven positive predictors and one negative predictor identified. Organisational support was identified as a key facilitator, which was not only positively linked with other facilitators but also had an independent positive effect. Perceived usefulness of the program was the most important practitioner-level facilitator, which might be contributed by both research-based evidence and practice-based evidence. Practitioners' self-regulation in program delivery impacted sustained use by influencing other factors such as perceived usefulness of the program. The findings provided insight into factors influencing the sustainability of evidence-based parenting programs which could be used to inform future implementation practice.


Influence of mistletoe ( Viscum album) extracts on phagocytosis/burst activity of human phagocytes.
The aim of the present study was to examine the in vitro effects of various mistletoe extracts on human phagocytes. Phagocytosis, oxidative burst, and intracellular killing were analyzed by flow cytometry. None of the mistletoe preparations investigated exhibited significant phagocytosis-enhancing properties. Different mistletoe lectin concentrations ranging from 0.025 to 20 ng/ml showed only marginal influence on phagocyte activity. Contrary to the opinion of numerous practitioners of complementary medicine, the mistletoe preparations tested do not enhance phagocytic function.


Preliminary development of a clinical prediction rule for determining which patients with low back pain will respond to a stabilization exercise program.
To develop a clinical prediction rule to predict treatment response to a stabilization exercise program for patients with low back pain (LBP). A prospective, cohort study of patients with nonradicular LBP referred to physical therapy (PT). Outpatient PT clinics. Fifty-four patients with nonradicular LBP. A standardized stabilization exercise program. Treatment response (success or failure) was categorized based on changes in the Oswestry Disability Questionnaire scores after 8 weeks. Eighteen subjects were categorized as treatment successes, 15 as treatment failures, and 21 as somewhat improved. After using regression analyses to determine the association between standardized examination variables and treatment response status, preliminary clinical prediction rules were developed for predicting success (positive likelihood ratio [LR], 4.0) and failure (negative LR, .18). The most important variables were age, straight-leg raise, prone instability test, aberrant motions, lumbar hypermobility, and fear-avoidance beliefs. It appears that the response to a stabilization exercise program in patients with LBP can be predicted from variables collected from the clinical examination. The prediction rules could be used to determine whether patients with LBP are likely to benefit from stabilization exercises.


Replicating vectors for gene therapy of cancer: risks, limitations and prospects.
There are good theoretical arguments for exploring the use of replicating gene-transfer vectors for human cancer therapy. Such vectors should be derived from weakly pathogenic human viruses with initially broad tissue tropism. Coat protein engineering and promoter engineering might be used successfully to narrow the tropism of the vector, enhancing its ability to target tumour cells. Killing of uninfected 'bystander' tumour cells could be achieved through prodrug activation by a vector-encoded enzyme. Rapid elimination of infused vector particles by circulating antiviral antibody would limit access to tumour deposits after repeated administration, but might be circumvented by the use of infectious nucleic acid which is poorly imunogenic [64]. This putative therapeutic strategy is illustrated in Figure 1.


Treatment of Esthetic Complications with Peri-implant Soft Tissue: A Description of the "Apical Approach" Surgical Technique and Presentation of Two Clinical Cases
Peri-implant soft tissue deformities are an increasingly common phenomenon in the esthetic zone. While the most widely studied esthetic complications are peri-implant soft tissue dehiscences, there are other esthetic concerns in routine clinical practice that require investigation and treatment. Thus, this report on two clinical cases describes a surgical approach using the apical access technique to treat peri-implant soft tissue discoloration and fenestration. In both clinical scenarios, the defect was accessed via a single horizontal apical incision without removing the cement-retained crowns. A bilaminar technique using apical access with a simultaneous connective tissue graft seems to offer promising results for the treatment of peri-implant soft tissue deformities. At the 12-month reevaluation, an increase in peri-implant soft tissue thickness was observed, resolving the pathologies presented.


The clinical safety, biodistribution and internal radiation dosimetry of [¹⁸F]fluciclovine in healthy adult volunteers.
We report on the biodistribution and internal radiation dosimetry in humans of [(18)F]fluciclovine, a synthetic L-leucine analogue being investigated as a potential diagnostic biomarker for neoplasia. Whole-body positron emission tomography (PET) scans of 6 healthy volunteers were acquired at up to 16 time points up to about 5 h after a bolus administration of [(18)F]fluciclovine (153.8 ± 2.2 MBq). Venous blood samples were taken up to about 4 h post-injection from which (18)F activity concentrations in whole blood and plasma were measured. Urine was collected as voided up to 4 h post-injection, from which the excreted (18)F activity was measured. Absolute values of the (18)F activity contained in up to 11 source regions (brain, salivary glands, lung, heart, pancreas, spleen, liver, red bone marrow, kidneys, uterus and urinary bladder contents) were determined directly from quantitative analysis of the images. For each source region, the (18)F activity decay-corrected and normalised to that injected, as a function of time, was fit by an analytical function which was subsequently integrated to yield the cumulated activity normalised to the injected activity. These normalised cumulated activities were then used as input to the Organ Level INternal Dose Assessment/EXponential Modelling (OLINDA/EXM) package to calculate the internal radiation dosimetry of each subject following the Medical Internal Radiation Dose (MIRD) schema. An effective dose was then estimated for each subject. [(18)F]Fluciclovine was clinically well tolerated in this study. Very little (18)F was excreted with only a mean value of 3.3% present in the urine at about 4 h post-injection; no activity within the intestinal contents was noted. The highest mean initial uptakes were measured in the liver (13.8%), red bone marrow (11.1%) and lung (7.1%). The highest mean radiation absorbed doses per unit administered activity were received by the pancreas (102.2 μGy/MBq), the cardiac wall (51.7 μGy/MBq) and the uterine wall (44.6 μGy/MBq). The mean effective dose per unit administered activity was 22.1 μSv/MBq. The internal radiation dosimetry of [(18)F]fluciclovine appears acceptable for PET imaging.


Combined lensectomy, vitrectomy, and primary intraocular lens implantation in patients with traumatic eye injury.
To analyse the postoperative anatomic and functional outcomes in addition to complications after combined lensectomy, vitrectomy, and primary intraocular lens (IOL) implantation in patients with traumatic eye injury. Retrospective review of patients with traumatic cataract and posterior segment injury who underwent combined lensectomy, vitrectomy, and primary IOL implantation with a minimum follow up (FU) of 3 months. Thirteen consecutive patients (all male) with a mean age of 42.8 years (range 17-82 years) underwent combined lensectomy, vitrectomy, and primary IOL implantation from February 2000 to January 2006. Postoperative FU ranged from 3 to 54 months (mean 17.6 months). Best corrected visual acuity (BCVA) at presentation ranged from 20/30 to hand movement and was worse than 20/200 in eight patients (61%). Four patients (31%) had blunt trauma with no globe rupture. Of the nine patients (69%) with a penetrating eye injury (PEI), eight had an intraocular foreign body (IOFB) with one retinal detachment at presentation. Four patients had primary closure at the time of the vitrectomy. All eight IOFBs were removed. Seven patients had additional scleral buckling and four intravitreal gas injection. BCVA at last FU ranged from 20/20 to 20/300 and was 20/40 or better in eight eyes (62%). All patients had an attached retina at last FU. One eye had further surgery for epiretinal membrane proliferation and ptosis. These results suggest that combined vitrectomy, lensectomy and primary intraocular implantation can offer good visual rehabilitation in patients with traumatic cataract and posterior segment injury.


Integrative modeling of protein-protein interactions with pyDock for the new docking challenges.
The seventh CAPRI edition imposed new challenges to the modeling of protein-protein complexes, such as multimeric oligomerization, protein-peptide, and protein-oligosaccharide interactions. Many of the proposed targets needed the efficient integration of rigid-body docking, template-based modeling, flexible optimization, multiparametric scoring, and experimental restraints. This was especially relevant for the multimolecular assemblies proposed in the CASP12-CAPRI37 and CASP13-CAPRI46 joint rounds, which were described and evaluated elsewhere. Focusing on the purely CAPRI targets of this edition (rounds 38-45), we have participated in all 17 assessed targets (considering heteromeric and homomeric interfaces in T125 as two separate targets) both as predictors and as scorers, by using integrative modeling based on our docking and scoring approaches: pyDock, IRaPPA, and LightDock. In the protein-protein and protein-peptide targets, we have also participated with our webserver (pyDockWeb). On these 17 CAPRI targets, we submitted acceptable models (or better) within our top 10 models for 10 targets as predictors, 13 targets as scorers, and 4 targets as servers. In summary, our participation in this CAPRI edition confirmed the capabilities of pyDock for the scoring of docking models, increasingly used within the context of integrative modeling of protein interactions and multimeric assemblies.


Strategies for selection of subjects for sequencing after detection of a linkage peak.
Linkage analysis has the potential to localize disease genes of interest, but the choice of which subjects to select for follow-up sequencing after identifying a linkage peak might influence the ability to find a disease gene. We compare nine different strategies for selection of subjects for follow-up sequencing using sequence data from the Genetic Analysis Workshop 17. We found that our more selective strategies, which included methods to identify case subjects more likely to be affected by genetic causes, out-performed sequencing all case and control subjects in linked pedigrees and required sequencing fewer individuals. We found that using genotype data from population control subjects had a higher benefit-cost ratio than sequencing control subjects selected as being the opposite extreme of the case subjects. We conclude that choosing case subjects for sequencing based on more selective strategies can be reliable and cost-effective.


A new magnetic resonance imaging tumour response grading scheme for locally advanced rectal cancer.
The potential of using magnetic resonance image tumour-regression grading (MRI-TRG) system to predict pathological TRG is debatable for locally advanced rectal cancer treated by neoadjuvant radiochemotherapy. Referring to the American Joint Committee on Cancer/College of American Pathologists (AJCC/CAP) TRG classification scheme, a new four-category MRI-TRG system based on the volumetric analysis of the residual tumour and radiochemotherapy induced anorectal fibrosis was established. The agreement between them was evaluated by Kendall's tau-b test, while Kaplan-Meier analysis was used to calculate survival outcomes. In total, 1033 patients were included. Good agreement between MRI-TRG and AJCC/CAP TRG classifications was observed (k = 0.671). Particularly, as compared with other pairs, MRI-TRG 0 displayed the highest sensitivity [90.1% (95% CI: 84.3-93.9)] and specificity [92.8% (95% CI: 90.4-94.7)] in identifying AJCC/CAP TRG 0 category patients. Except for the survival ratios that were comparable between the MRI-TRG 0 and MRI-TRG 1 categories, any two of the four categories had distinguished 3-year prognosis (all P < 0.05). Cox regression analysis further proved that the MRI-TRG system was an independent prognostic factor (all P < 0.05). The new MRI-TRG system might be a surrogate for AJCC/CAP TRG classification scheme. Importantly, the system is a reliable and non-invasive way to identify patients with complete pathological responses.


Immunohistochemical detection of HIF-1alpha and CAIX in advanced head-and-neck cancer. Prognostic role and correlation with tumor markers and tumor oxygenation parameters.
Tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant Levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Tumortissue sections of 34 patients with advanced head-and-neck cancertreated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1alpha and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Bivariate analysis showed a significant correlation of HIF-1alpha expression with high P53 and high OPN expression, high serum VEGF Levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1alpha and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1alpha or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1alpha or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Expression of HIF-1alpha and CAIX was correlated with different tumor parameters. Only combined HIF-1alpha and CAIX expression was significantly predictive of patients' overall survival.


Bridging the gap in knowledge and use of antibiotics among pediatric caregivers: comparing two educational interventions.
The inappropriate use of antibiotics in pediatrics contributes to antimicrobial resistance. Behavior change intervention involving education to improve the use of antibiotics is a strategy included in antimicrobial stewardship. This study aims to evaluate and compare the impact of two educational interventions on knowledge of antibiotic and its use among pediatric home caregivers. This was a cross-sectional study conducted in the pediatric out-patient department of a healthcare facility. A structured questionnaire was administered to sixty pediatric caregivers. Pediatric caregivers were grouped in two of 30. Caregivers in a group filled the questionnaire, and refilled the same questionnaire after a one-on-one education. The second arm refilled the questionnaire after a group education. Ethical clearance was obtained and participants gave consent. Data analysis was done using SPSS version 22 and Graph pad Instat, p values < 0.05 were considered significant. Fouty-nine (81.7%) participants believe that antibiotics can treat malaria infection [8(13.3%) after education)], 43(71.7%) of respondents agreed that antibiotics can be used to treat all kinds of diarrhea, while 45(65%) of them thought that antibiotics in powder form can be reconstituted with hot or warm water before use [7(11.7%) after education]. Mean score among the sixty participants before and after education on knowledge and use of antibiotics were 36.1 ± 6.467 versus 46.7 ± 4.027 (p≤0.0001) and 29.82 ± 4.949 versus 36.92 ± 3.997 (p≤ 0.0001), respectively. Mean score on knowledge and use of antibiotics for one-on-one versus group education were 46.7 ± 4.027 versus 43.3 ± 6.249 (p = 0.022) and 37.9 ± 3.044 versus 35.93 ± 4.608 (p = 0.039), respectively. Many pediatric caregivers had poor knowledge on antibiotics and use which improved significantly after education. One-on-one education has more impact than group education. Pharmacists and other healthcare professionals can use counseling opportunity to inform caregivers on appropriate knowledge and use of antibiotics consistently to change behavior.


Cardiac function in congenital adrenal hyperplasia: a pattern of reversible cardiomyopathy.
To evaluate cardiac function in infants with congenital adrenal hyperplasia (CAH) before and after corticosteroid replacement therapy. This prospective, case-control study included 9 infants with CAH. Cardiac function was assessed by echocardiography at presentation and after corticosteroid replacement therapy. Six term infants underwent 2 echocardiograms each and served as the control group. Data on fractional shortening (FS), rate-corrected velocity of circumferential fiber shortening (Vcf), wall stress, tissue Doppler indices, myocardial performance index, left ventricular mass, and Vcf/wall stress were obtained. The infants with CAH exhibited myocardial dysfunction at baseline and lower systolic blood pressure (SBP) compared with the control group. FS, a measure of systolic contractility, differed significantly from before to after corticosteroid treatment (mean, 32.3%±4.7% pretreatment, 39.9%±5.0% posttreatment). Vcf, a preload-independent measure of cardiac contractility, also differed significantly before and after treatment (mean, 1.23±0.16 circumferences/second pretreatment, 1.45±0.22 circumferences/second posttreatment). SBP was also lower (mean, 84±9.3 mmHg) and improved with treatment (mean, 95±4.8 mmHg). The control group demonstrated no statistically significant changes in FS, Vcf, or SBP. There was a change in left ventricular mass in the control group between the 2 studies. Newborns with CAH have evidence for cardiac dysfunction at baseline that reverses with corticosteroid replacement therapy. These data suggest that corticosteroids play a direct role in modulating cardiac function in the newborn.


Ten-year mortality among older male recreational endurance athletes in the Birkebeiner Aging Study in comparison with older men from the Tromsø Study.
Physical activity (PA) is associated with reduced mortality. However, whether there is an added benefit of long-term endurance training is unclear. Thus, we aimed to examine 10-year mortality in older male endurance athletes compared with an older male general population. Male athletes (n = 503) participating in an annual long-distance ski race (median years of participation: 14, range: 1-53) from the Norwegian Birkebeiner Aging study (BiAS), and non-athletic men (n = 1867) attending the sixth Tromsø Study (Tromsø6) aged ≥65 years were included. Associations with endurance sport practice and joint exposures of endurance sport practice and self-reported leisure-time PA with all-cause mortality were examined. We analyzed the data with Cox proportional hazard models and regression standardization. After 10 years (median: 10.4, range: 0.5-11.1) the mortality rate was lower in athletes (hazard ratio (HR) 0.34, 95% confidence interval (CI): 0.24-0.49) compared with non-athletes, corresponding to a 15% (95% CI: 12-19%) absolute risk reduction associated with endurance sport practice. In joint analyses categorized according to PA and endurance sport practice, we observed an inverse dose-response relationship with mortality (p < 0.001). Compared to inactive non-athletes, PA was associated with lower mortality in both active non-athletes and athletes. However, the observed benefit among participants reporting moderate-to-vigorous PA was larger in athletes (HR: 0.21, 95% CI: 0.14-0.32) than non-athletes (HR: 0.43, 95% CI: 0.31-0.59) (p < 0.01). Endurance sport practice was associated with reduced 10-year mortality, beyond the effect of PA in older men. This study suggests that long-term endurance sport practice maintained into older adulthood promotes longevity.


Fast and efficient removal of mercury from water samples using magnetic iron oxide nanoparticles modified with 2-mercaptobenzothiazole.
Mercury in the lowest levels of concentrations is dangerous for human health due to its bioaccumulation in body and toxicity. This investigation shows the effective removal of mercury (II) ions from contaminated surface waters by modified magnetic iron oxide nanoparticles (M-MIONPs) with 2-mercaptobenzothiazole as an efficient adsorbent. The proposed method is fast, simple, cheap, effective and safe for treatment of mercury polluted waters. Preparation of adsorbent is easy and removal time is short. Non-modified magnetic iron oxide nanoparticles (MIONPs) can adsorb up to 43.47% of 50 ngmL(-1) of Hg (II) ions from polluted water, but modified magnetic ironoxide nanoparticles (M-MIONPs) improved the efficiency up to 98.6% for the same concentration. The required time for complete removal of mercury ions was 4 min. Variation of pH and high electrolyte concentration (NaCl) of the solution do not have considerable effect on the mercury removal efficiency. Loading capacity of adsorbent for Hg ions is obtained to be 590 μgg(-1).


Simple method for the selection of the appropriate food simulant for the evaluation of a specific food/packaging interaction.
Knowledge of the extent of food/packaging interactions is essential to provide assurance of food quality and shelf life, especially in migration and sorption processes that commonly reach equilibrium during the lifetime of a commercial packaged foodstuff. The limits of sorption and migration must be measured in the presence of the specific food or an appropriate food simulant. The partition equilibrium of food aroma compounds between plastic films and foods or food simulants (K(A,P/L) has been characterized. Two polymers (LLDPE and PET), three organic compounds (ethyl caproate, hexanal and 2-phenylethanol), four food products with varying fat content (milk cream, mayonnaise, margarine and oil) and three simulants (ethanol 95%, n-heptane and isooctane) were selectedfor study. The results show the effect of the aroma compound volatility, and polarity, as well as its compatibility with the polymer and the food or food simulant. Equilibrium constants for the organic compound between the polymers and a gaseous phase (K(A,P/V)) as well as between the food (or food simulant) and a gaseous phase (K(A,L/V)) were also determined. An approach is presented to estimate K(A,P/V) from the binary equilibrium constants K(A,P/V) and K(A,L/V). Calculated results were shown to describe experimental data very well and indicated that compatibility between the aroma and the food or food simulant is the main contributing factor to the partition equilibrium describing the extent of food/packaging interactions. Therefore, the measurement of liquid/vapour equilibrium can be regarded as a powerful tool to compare the effectiveness of food simulants as substitutes of a particular food product and can be used as a guide for the selection of the appropriate simulant.


Factors affecting aboriginal nutrition.
A description of the past and present mode of living of Aboriginals in the Northern Territory is followed by information on sources of food. Other factors which have affected the nutritional situation are described. The article concludes with a discussion on the philosophical and socioeconomic aspects of improving Aboriginal nutrition.


Panmedullary edema with inferior olivary hypertrophy in bilateral medial medullary infarction.
Bilateral medial medullary infarction (MMI) is a rare type of stroke with poor outcomes. Inferior olivary nucleus hypertrophy results from a pathologic lesion in the Guillain-Mollaret triangle. The relationship between inferior olivary nucleus hypertrophy and the medullary lesion is obscure. To the best of our knowledge, only 1 autopsy case with unilateral medial medullary infarction that was associated with ipsilateral inferior olivary nucleus hypertrophy has been reported. We describe a rare case with acute infarction in the bilateral medial medulla oblongata accompanied by subacute bilateral inferior olivary nucleus hypertrophy and panmedullary edema. The hypertrophy appeared to have been caused by local ischemic damage to the termination of the central tegmental tract at the bilateral inferior olivary nucleus.


Phenomenological features of dreams: Results from dream log studies using the Subjective Experiences Rating Scale (SERS).
Self-ratings of dream experiences were obtained from 144 college women for 788 dreams, using the Subjective Experiences Rating Scale (SERS). Consistent with past studies, dreams were characterized by a greater prevalence of vision, audition, and movement than smell, touch, or taste, by both positive and negative emotion, and by a range of cognitive processes. A Principal Components Analysis of SERS ratings revealed ten subscales: four sensory, three affective, one cognitive, and two structural (events/actions, locations). Correlations (Pearson r) among subscale means showed a stronger relationship among the process-oriented features (sensory, cognitive, affective) than between the process-oriented and content-centered (structural) features--a pattern predicted from past research (e.g., Bulkeley & Kahan, 2008). Notably, cognition and positive emotion were associated with a greater number of other phenomenal features than was negative emotion; these findings are consistent with studies of the qualitative features of waking autobiographical memory (e.g., Fredrickson, 2001).


The artificial heart: infection-related morbidity and its effect on transplantation.
Between October, 1985, and September, 1987, a total of 195 patients received cardiac allografts and 15 candidates required mechanical support with the Jarvik-7 total artificial heart. Seven of the 15 died within 60 days of total artificial heart implant. There have been no late deaths, and survivors are unrestricted. Six of 7 deaths were related to infection (mediastinitis, 5; pneumonia and sepsis, 1), and the remaining 1 was due to failure of the transplanted heart. Respiratory tract infection occurred in each of the recipients who died with infection, and the same organisms appeared to be related to subsequent mediastinitis in 3 patients (Serratia marcescens, 2; Pseudomonas, 1) and caused fatal sepsis in another (Enterobacter aerogenes, Candida albicans). One patient died with pneumonia and sepsis prior to transplantation, and another succumbed with mediastinal infection known to be present before transplantation.


Highly sensitive sensing device based on highly luminescent lanthanide nanocluster for biomarker in human urine and serum.
The level of L-kynurenine (L-kyn) can reflect the health state of human body, and the determination of L-kyn can be used for the medical diagnosis of several cancers and neurological diseases. In this work, a series of air-, water-, and thermo-stable dinuclear lanthanide nanoclusters [Ln2(2,5-DFBA)6(phen)2] (Tb 1, Eu 2, Gd 3, 2,5-DFBA = 2,5-difluorobenzoic acid, phen = 1,10-phenanthroline) are obtained by a facial method. 1 and 2 show very high luminescence quantum yields (QYs) of 71.7% and 81.8%, respectively. Interestingly, investigation reveals that 1 is a quick, highly sensitive and selective sensor for L-kyn in real samples of urine and serum. Furthermore, transmission electron microscope (TEM) results reveal that nanocluster 1 is stable in solution and can be uniform distributed on the base, suggesting it can be deposited on various supports to fabricate sensing devices. Thus, 1 is fabricated into a sensitive test paper for the eye-readable detection of L-kyn in real samples of human urine and serum. The limit of detection (LOD) as low as 0.3 μM, which is enough to rapidly determine L-kyn in human body liquor (usually 5 μM in healthy human body).


Investigating the transparency of reporting in two-sample summary data Mendelian randomization studies using the MR-Base platform.
Two-sample Mendelian randomization (2SMR) is an increasingly popular epidemiological method that uses genetic variants as instruments for making causal inferences. Clear reporting of methods employed in such studies is important for evaluating their underlying quality. However, the quality of methodological reporting of 2SMR studies is currently unclear. We aimed to assess the reporting quality of studies that used MR-Base, one of the most popular platforms for implementing 2SMR analysis. We created a bespoke reporting checklist to evaluate reporting quality of 2SMR studies. We then searched Web of Science Core Collection, PsycInfo, MEDLINE, EMBASE and Google Scholar citations of the MR-Base descriptor paper to identify published MR studies that used MR-Base for any component of the MR analysis. Study screening and data extraction were performed by at least two independent reviewers. In the primary analysis, 87 studies were included. Reporting quality was generally poor across studies, with a mean of 53% (SD = 14%) of items reported in each study. Many items required for evaluating the validity of key assumptions made in MR were poorly reported: only 44% of studies provided sufficient details for assessing if the genetic variant associates with the exposure ('relevance' assumption), 31% for assessing if there are any variant-outcome confounders ('independence' assumption), 89% for the assessing if the variant causes the outcome independently of the exposure ('exclusion restriction' assumption) and 32% for assumptions of falsification tests. We did not find evidence of a change in reporting quality over time or a difference in reporting quality between studies that used MR-Base and a random sample of MR studies that did not use this platform. The quality of reporting of two-sample Mendelian randomization studies in our sample was generally poor. Journals and researchers should consider using the STROBE-MR guidelines to improve reporting quality.


Omission of axillary dissection after a positive sentinel lymph-node: Implications in the multidisciplinary treatment of operable breast cancer.
Omission of axillary dissection in women with breast cancer and one or two positive sentinel-node biopsy is a major advancement in the management of this disease. Supported by a sound rationale and confirmed by prospective, randomized trials, omission of axillary dissection is now recommended in women who have undergone breast conserving surgery and who are candidate to adjuvant radiotherapy. Because breast cancer is best managed in the context of a multidisciplinary team, this surgical shift in the paradigm is expected to have implications that extend also to the other specialties involved in the team. In fact, the full evaluation of the axillary tumor burden has been historically considered an essential part of tumor staging and the absolute number of involved node critical information to tailor post-surgical treatments. Lack of this information in a patient with axillary involvement documented by a positive sentinel lymph-node biopsy may represent a challenge when deciding on further, post-surgical treatments. This review will address the critical aspects and the potential implications of omission of axillary dissection in the context of the multidisciplinary breast team.


Changes in terpene production following nitrogen fertilization of grand fir (Abies grandis (Dougl.) Lindl.) seedlings.
Of ten terpenes that comprise most of the volatiles of grand fir foliage only four were affected by addition of nitrogen. Levels of beta-phellandrene, camphene and bornyl acetate and terpinolene were significantly reduced with nitrogen added to the equivalent amount of 44.8 g/m2. A quantity of 22.4 g/m2 did not affect terpene production. Several populations were examined and these did not respond consistently on a regional basis, yet a significant interaction effect was apparent between treatment and local population response. Overall, total yield of terpenes as a function of fertilization was not altered.


[The role of Versajet in the surgical treatment of rhinophyma. Case report].
Rhinophyma is an hypertrophy of the nose occurring primarily in men, from the age of 40, secondary to hyperplasia and fibrosis of sebaceous glands. This pathology is particularly unsightly and sometimes responsible of nasal obstruction. The treatment of this pathology is primarily surgical and the purpose of all techniques is to carry out a decortication. The authors describe one case of surgical treatment of rhinophyma by hydro-dissection using Versajet. After having presented the other possibilities of surgical technics for the treatment of this pathology, the authors compare the advantages and drawbacks of this new technique compared to those described in the international literature.


Panax ginseng polysaccharide suppresses metastasis via modulating Twist expression in gastric cancer.
It was previously reported that an antitumor polysaccharide (PGPW1) was isolated from the root of Panax ginseng. To extend our study, we investigated here the anti-invasive and metastatic effects of PGPW1 on human gastric cancer cell line HGC-27 and tried to determine its possible mechanism of action. Both scratch wound-healing and Transwell assay identified that PGPW1 dose-dependently inhibited migration and invasiveness of HGC-27 cells. Furthermore, results of western blot showed that protein levels of Twist and AKR1C2 were inhibited by PGPW1, whereas an increase of NF1 was observed. Moreover, down-regulation of Twist expression by PGPW1 blocked epithelial-mesenchymal transition (EMT), characterized by a gain of epithelial cell markers, E-cadherin, and loss of the mesenchymal markers, vimentin and N-cadherin, at protein levels. Collectively, we confirmed that PGPW1 decreased migration and invasion of HGC-27 cells by regulation of Twist, AKR1C2, NF1, E-cadherin, vimentin and N-cadherin expression. In conclusion, PGPW1 may serve as a powerful chemopreventive agent against gastric cancer metastasis.


Methodological and statistical approaches to criteria development in rheumatic diseases.
We have discussed methodological and statistical considerations in developing disease classification and assessment criteria. In choosing cases with disease and nondisease controls, classification criteria should be developed with an eye toward face, content and construct validity, and toward their ultimate applicability. The validity of disease criteria should be tested in a patient sample different from the one used to develop the criteria. Several analytic approaches are available to reduce the candidate diagnostic elements to those that will define the presence of disease. Methodological issues in the assessment of disease severity, activity or damage are similar to those faced in criteria development studies, although the analytic concerns are different and the options more varied.


Morphological comparison of internal auditory canal diverticula in the presence and absence of otospongiosis on computed tomography and their impact on patterns of hearing loss.
The association of internal auditory canal (IAC) fundal diverticula with otospongiosis (OS) and their clinical significance remain unclear. We explored whether isolated IAC diverticula were morphologically different from those with additional CT features of OS, and whether IAC diverticula morphology influenced patterns of hearing loss. Consecutive temporal bone CT studies with (n = 978) and without (n = 306) features of OS were retrospectively assessed. Two independent observers evaluated the presence of IAC diverticula morphological features (depth, neck:depth ratio, definition of contour and angulation of shape), and these were correlated with the presence of fenestral and pericochlear OS. Audiometric profiles were analysed for the isolated IAC diverticula and those with fenestral OS alone. Continuous data was compared using Wilcoxon rank sum tests and categorical data with chi-squared and Fisher's exact tests. Ninety-five isolated IAC diverticula were demonstrated in 54/978 patients (5.5%) without CT evidence of OS (31M, 23F, mean age 46), and 119 IAC diverticula were demonstrated in 71/306 patients (23%) with CT evidence of OS (23M, 48F, mean age 55). Reduced neck:depth ratio, ill definition and angulation were all significantly associated with the presence of pericochlear OS (p < 0.001), whilst only ill definition was associated with the presence of fenestral OS alone (p < 0.05). No morphological feature was associated with conductive hearing loss in isolated diverticula or with sensorineural hearing loss in diverticula with fenestral OS alone. IAC diverticula associated with pericochlear OS demonstrate different morphological features from isolated IAC diverticula. There are no clear audiometric implications of these morphological features.


Pharyngogastrostomy for treatment of severe caustic stricture of the pharynx and esophagus.
Four cases of combined pharyngeal and esophageal stricture were managed by pharyngogastrostomy 4 months to 42 years after injury. The stomach was brought up to the neck via the posterior mediastinum after the esophagectomy. A thoracotomy was not used. The results were suprisingly good in 3 patients followed to 3 years. A fourth patient died 6 months after the operation. In those patients benefiting from the operation, regurgitation was minimal when a few precautions were observed. The patients have normal hunger pains and appetite. They are able to eat a full-sized meal. The advantages of stomach compared to colon replacement of the esophagus are discussed.


Dynamic functional connectivity: causative or epiphenomenal?
Dynamic coupling of neural signals is a hallmark of brain networks, but its potential relevance is still debated. Does coupling play a causal role for network functions, or is it just a by-product of structural connectivity or other physiological processes? With intervention techniques that have become available, experiments seem within reach that may provide answers to this long-standing question.


Atherogenic inflammatory and oxidative stress markers in relation to overweight values in male former athletes.
To evaluate inflammation- and oxidative stress-related (OxS) background in former athletes in relation to overweight and abdominal obesity status. Cross-sectional data from ongoing follow-up study. A total of 60 middle-aged former athletes (46.6+/-7.5 years; 181.1+/-7.2 cm; 88.1 +/- 12.9 kg) and 54 age-matched controls (48.1+/-7.3 years; 181.4 +/- 6.2 cm; 89.7 +/- 14.4 kg). Anthropometric characteristics, serum lipoproteins (CHOL, HDL-C, LDL-C, TG), oxidized LDL (oxLDL), diene conjugates (DC) and high-sensitive C-reactive protein (hsCRP). Information about the physical activity and other lifestyle variables were collected by the questionnaire. Ex-athletes were characterized by significantly higher physical activity characteristics and lower CHOL and oxLDL in comparison with controls. Correlation analysis among ex-athletes revealed negative associations between all measured overweight data (body mass index, fat percentage, waist to hip circumferences and waist circumference (WC)), and current physical activity. Current physical activity was significantly related to OxS and inflammatory characteristics (oxLDL, DC and hsCRP) among the ex-athletes, but not among the control group. The most expressed positive correlations were found between WC, hsCRP, triglycerides (TG), DC and oxLDL in both study groups. Our study results suggest that there exists an independent (adjusted for potential confounders) association between overweight, abdominal obesity, and atherogenic inflammatory and oxidative stress markers in ex-athletes as well as in age-matched controls. Major findings of our study show that WC is the best correlate of hsCRP, oxLDL, DC and TG levels.


A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis.
Screening newborns for cystic fibrosis (CF) is considered to be an ethical undertaking in regions with a significant incidence of the condition. Current screening protocols result in recognition of infants with an equivocal diagnosis. A survey of European practice suggested inconsistencies in the evaluation and management of these infants. We have undertaken a consensus process using a modified Delphi method. This has enabled input of CF specialists from a wide geographical area to a rigorous process that has provided a clear pathway to a consensus statement. A core group produced 21 statements, which were modified over a series of three rounds (including a meeting arranged at the European CF Conference). A final document of 19 statements was produced, all of which achieved a satisfactory level of consensus. The statements cover four themes; sweat testing, further assessments and investigations, review arrangements and database. This consensus document will provide guidance to CF specialists with established screening programmes and those who are in the process of implementing newborn screening in their region.


MR imaging of a carcinoid tumor metastatic to the orbit.
This is a report of the magnetic resonance study in a case of orbital metastasis from a carcinoid tumor. A rather unusual feature of this lesion was its relatively short T2 as compared with other metastatic orbital lesions.


Pharmacological Modulation of Vagal Nerve Activity in Cardiovascular Diseases.
Cardiovascular diseases are life-threatening illnesses with high morbidity and mortality. Suppressed vagal (parasympathetic) activity and increased sympathetic activity are involved in these diseases. Currently, pharmacological interventions primarily aim to inhibit over-excitation of sympathetic nerves, while vagal modulation has been largely neglected. Many studies have demonstrated that increased vagal activity reduces cardiovascular risk factors in both animal models and human patients. Therefore, the improvement of vagal activity may be an alternate approach for the treatment of cardiovascular diseases. However, drugs used for vagus nerve activation in cardiovascular diseases are limited in the clinic. In this review, we provide an overview of the potential drug targets for modulating vagal nerve activation, including muscarinic, and β-adrenergic receptors. In addition, vagomimetic drugs (such as choline, acetylcholine, and pyridostigmine) and the mechanism underlying their cardiovascular protective effects are also discussed.


Correlation artifacts in speed of sound estimation in scattering media.
A recently described method for speed of sound estimation in tissues in pulse-echo mode involves reception of echoes generated by an ultrasonic pulse by means of a linearly tracking transducer. When the peaks of echo amplitudes are used as markers of arrival time, stairstep-like artifacts appear in the echo arrival time vs. transducer position plots. We postulate that these artifacts are a consequence of the speckle phenomenon commonly encountered in ultrasonic imaging. To test this hypothesis, we report computer simulations and water tank experiments which demonstrate similarities between the behavior of the stairsteps and the properties of ultrasonic speckle. Additionally, equations describing the precision of the speed of sound estimation in terms of the second order statistical properties of the stairstep artifact are derived.


Synthesis of a novel Cu/DPA-MOF/OP/CS hydrogel with high capability in antimicrobial studies.
Today, with the indiscriminate use of antibiotics, we face the resistance of some bacterial strains against some antibiotics. Therefore, it is essential to report and synthesize new compounds with antimicrobial properties. A novel copper/dipicolinic acid-metal-organic framework cross-linked oxidized pectin and chitosan (Cu/DPA-MOF/OP/CS) hydrogel polymer was synthesized under environmental conditions with the controllable process, which uses biodegradable polymer compounds such as pectin and chitosan in its structure. The efficient physicochemical features of the synthesized Cu/DPA-MOF/OP/CS hydrogel using SEM, FT-IR, TGA, BET, XRD, and EDS/mapping were identified and confirmed. The newly synthesized Cu/DPA-MOF/OP/CS hydrogel showed activity against Gram-positive and Gram-negative bacterial strains and fungal species, and significant antibacterial and antifungal properties were observed. In antibacterial activity, the MIC against Gram-positive species was in the range of 16-128 mg/mL, the MIC against Gram-negative species was in the range of 64-256 mg/mL, and the MIC against fungal species was in the range of 128-512 mg/mL. In antimicrobial evaluations, in addition to the MIC test, the MBC test, the MFC test, and the IZD test were performed, and the results were reported. The results were compared with commercial antibiotics in the market. Development of novel nanostructures based on hydrogel polymers with distinctive functionality can affect the performance of these nanostructures in different areas.


The evaluation of palatal bone thickness for implant insertion with cone beam computed tomography.
The palate is an alternative anchoring site for orthodontic implants and screws. The use of osseointegrated implants in the intermaxillary suture has recently been described as a fast, effective, and low-cost technique for patients with atrophy of the maxillae. The aim of this study was to use cone beam computed tomography (CBCT) to evaluate the thickness of the bone surrounding the intermaxillary suture in relation to the insertion of osseointegrated implants. CBCT images of 144 patients (72 males, 72 females) aged 35-86 years were evaluated. The vertical bone height of the intermaxillary suture was measured using coronal and sagittal Images 5, 10, 15, 20, and 25 mm posterior to the incisive foramen. The mean bone thicknesses from the anterior to the posterior region were 5.59, 4.38, 3.91, 3.95, and 3.94 mm, respectively. Bone thickness was significantly different among the five anteroposterior areas of the suture, but there were no significant differences between males and females, or among age groups. The highest part of the intermaxillary suture was in the anterior region. Three-dimensional imaging is recommended to accurately identify palate bone thickness for implant placement.


Artificial intelligence for histological subtype classification of breast cancer: combining multi-scale feature maps and the recurrent attention model.
The aim of this study was to apply a two-stage deep model combining multi-scale feature maps and the recurrent attention model (RAM) to assist with the pathological diagnosis of breast cancer histological subtypes by the use of whole slide images (WSIs). In this article, we propose an integrated framework combining multi-scale feature maps from Inception V3 and the recurrent attention model to classify the six histological subtypes of breast cancer. This model was trained with 194 WSIs, and on 63 validation WSIs the model achieved accuracies of 0.9030 for patch-level classification and 0.8889 for WSI-level classification. In the testing stage, a total of 65 WSIs were used to achieve an accuracy of 0.8462 without any form of data curation. The t-distributed stochastic neighbour embedding showed that features extracted by the feature network of the RAM from WSIs of the same category can cluster together after training, and the visualization of decision steps showed that the decision-making glimpses are focused on the middle tumour area of an example from test WSIs. Finally, the false classification patches indicated that the morphological similarities between tumour tissues of different subtypes or non-tumour tissues and tumour tissues in patches might contribute to misclassification. This model can imitate the diagnostic process of pathologists, pay attention to a series of local features on the pathology image, and summarize related information, in order to accurately classify breast cancer into its histological subtypes, which is important for treatment and prognosis.


Long term bone marrow culture in metastatic neuroblastoma.
We have developed a long term marrow culture assay for the study of advanced bone marrow metastatic neuroblastoma. In this in vitro system the hemopoietic growth (GM-CFU) is not affected by the presence of tumor cells. The neuroblastoma cells grow and differentiate partially when in contact with the stromal layer, arresting the culture. We present culture and histological data suggesting that the solid tumors interact specifically with the stromal layer of marrow origin.


Timeline: Mitochondria.
Mitochondria perform diverse yet interconnected cellular functions and are dynamically regulated by complex signaling pathways. Interest in this fascinating organelle has recently undergone a renaissance due to a series of discoveries revealing that mitochondrial function goes beyond the generation of molecular fuel. This Timeline highlights some of the groundbreaking events over the last 30 years in our understanding of how mitochondria are made and turned over, and how they integrate and signal within the cell and organism. To view this Timeline, open or download the PDF.


CEST2022 - mapping multi-pool CEST signal changes in an animal model of brain tumor with quasi-steady-state reconstruction-empowered CEST quantification.
Chemical exchange saturated transfer (CEST) MRI has biomarker potential to assess tissue microenvironment in brain tumors. Multi-pool Lorentzian or spinlock models provides useful insights into the CEST contrast mechanism. However, T1 contribution to the complex overlapping effects of brain tumors is difficult under the non-equilibrium state. Therefore, this study evaluated T1 contributions on multi-pool parameters with quasi-steady-state (QUASS) algorithm reconstructed equilibrium data. MRI scans were performed in rat brain tumor models, including relaxation, diffusion, and CEST imaging. A pixel-wise seven-pool spinlock-model was employed to fit QUASS reconstructed CEST Z-spectra and evaluated the magnetization transfer (MT), amide, amine, guanidyl, and nuclear-overhauled effect (NOE) signals in tumor and normal tissues. In addition, T1 was estimated from the spinlock-model fitting and compared with measured T1. We observed tumor had a statistically significant increase in the amide signal (p < 0.001) and decreases in the MT and NOE signals (p < 0.001). On the other hand, the differences in amine and guanidyl between the tumor and contralateral normal regions were not statistically significant. The differences between measured and estimated T1 values were 8% in the normal tissue and 4% in the tumor. Furthermore, the isolated MT signal strongly correlated with R1 (r = 0.96, P < 0.001). In summary, we successfully unraveled multi-factorial effects in the CEST signal using spinlock-model fitting and QUASS method and demonstrated the effect of T1 relaxation on MT and NOE.


Real-Time PCR and Droplet Digital PCR Are Accurate and Reliable Methods To Quantify Pseudomonas syringae pv. actinidiae Biovar 3 in Kiwifruit Infected Plantlets.
Pseudomonas syringae pv. actinidiae is the etiological agent of kiwifruit canker disease, causing severe economic losses in kiwifruit production areas around the world. Rapid diagnosis, understanding of bacterial virulence, and rate of infection in kiwifruit cultivars are important in applying effective measures of disease control. P. syringae pv. actinidiae load in kiwifruit is currently determined by a labor-intense colony counting method with no high-throughput and specific quantification method being validated. In this work, we used three alternative P. syringae pv. actinidiae quantification methods in two infected kiwifruit cultivars: start of growth time, quantitative PCR (qPCR), and droplet digital PCR (ddPCR). Method performance in each case was compared with the colony counting method. Methods were validated using calibration curves obtained with serial dilutions of P. syringae pv. actinidiae biovar 3 (Psa3) inoculum and standard growth curves obtained from kiwifruit samples infected with Psa3 inoculum. All three alternative methods showed high correlation (r > 0.85) with the colony counting method. qPCR and ddPCR were very specific, sensitive (5 × 102 CFU/cm2), highly correlated to each other (r = 0.955), and flexible, allowing for sample storage. The inclusion of a kiwifruit biomass marker increased the methods' accuracy. The qPCR method was efficient and allowed for high-throughput processing, and the ddPCR method showed highly accurate results but was more expensive and time consuming. While not ideal for high-throughput processing, ddPCR was useful in developing accurate standard curves for the qPCR method. The combination of the two methods is high-throughput, specific for Psa3 quantification, and useful for research studies (e.g., disease phenotyping and host-pathogen interactions).


The Relationship Between the Thickness of cpRNFL in Segments and Intraocular Pressure.
The aim of this study was to investigate whether the retinal nerve fibre layer (RNFL) in some segments of the optic nerve disc in pathological intraocular pressure is more damaged in eyes without antiglaucoma treatment. The cohort consisted of 69 subjects (122 eyes), 32 males (6x one, 26x both eyes) aged 21 to 76 years and 37 females (4x one and 30x both eyes) aged 22 to 75 years, who were measured to have IOP greater than 21 mmHg (21-36) in routine ambulatory care. Measurements were performed using the Ocular Response Analyser, taking into account corneal hysteresis. RNFL thickness was measured using the Avanti RTVue XR and was assessed in 8 segments (1-IT, 2-TI, 3-TS, 4-ST, 5-SN, 6-NS, 7-NI, 8-IN). The visual field was examined with a fast threshold glaucoma program using the Medmont M700. The overall defect (OD) was evaluated. Pearson's correlation coefficient r was used to assess the dependence between the selected parameters. The largest peripapillary changes in RNFL were observed in segments 1, 4, 5 and 8. It should be emphasized that segments 1 and 4 have been temporarily shifted. Segments 5 and 8 then corresponded to the upper (at no. 12) and lower (at no. 6) sectors. The most important result of this study is the finding that the greatest changes in the RNFL layer were observed in pathological IOP at segment 5 (r=-0.3) and 8 (r=-0.28), at the point where the fibres of the magnocellular retinal ganglion cells enter the retina.


[Anatomical study of the temporalis tendon. Value in temporalis lengthening myoplasty].
The lengthening temporalis myoplasty is indicated in long standing and congenital facial paralysis. Its principle is the transfer of the coronoid tendinous insertions onto the lip and the nasolabial fold. The knowledge of the anatomy of this strong and wide tendon is necessary to use successfully their anatomical advantages. A study of ten cadavers (20 temporalis muscles) confirmed the surgical anatomy found during lengthening temporalis myoplasty procedure: the strong tendon, when liberated from the coronoid process, is from 4 to 6 cm long.


Murine leukemia virus in organs of senescence-prone and -resistant mouse strains.
A series of inbred strains of mice have been developed that are either prone (SAMP) or resistant (SAMR) to accelerated senescence. All of these strains originated from an inadvertent cross or crosses between the AKR/J mouse strain and an unknown strain(s). The characteristics of the nine senescence-prone lines differ, with all strains showing generalized aspects of accelerated aging but with each line having a specific aging-related change that is emphasized, e.g. learning and memory deficits, osteoporosis and senile amyloidosis. The senescence-resistant strains have normal patterns of aging and do not show the specific aging-related changes seen in SAMP strains. The fact that AKR mice have high levels of endogenous, ecotropic murine leukemia virus (MuLV) prompted an examination of the expression levels of MuLV in SAM strains. Analysis of brain, spleen and thymus samples revealed that seven of nine SAMP strains had high levels of MuLV and contained the Emv11 provirus (previously termed Akv1) that encodes the predominant MuLV found in AKR mice. In contrast, none of the SAMR strains had Emv11 or significant amounts of virus. The current findings represent an initial step in determining the role of MuLV in the accelerated senescence seen in SAMP strains.