Expression and hypomethylation of alpha-fetoprotein gene in unicentric and multicentric human hepatocellular carcinomas.
The messenger RNA and DNA methylation of the alpha-fetoprotein gene were studied in 101 resected primary hepatocellular carcinomas, of which 93 were unicentric and 8 were multicentric. Fifty-five were 5 cm or less in diameter (small) and 46 were more than 5 cm in diameter (large). In 48.5% of the cases, we detected alpha-fetoprotein messenger RNA in hepatocellular carcinomas, more frequently in large (60.9%) than in small (38.2%; p < 0.00001) but not in any of the nontumorous livers. The alpha-fetoprotein messenger RNA was detected in 83%, 70% and 6.8% of patients with serum alpha-fetoprotein levels of 320 ng/ml or more, 100 to 319 ng/ml and less than 100 ng/ml, respectively. This finding suggests that alpha-fetoprotein gene expression in hepatocellular carcinoma contributes to the serum alpha-fetoprotein elevation in patients with hepatocellular carcinoma. alpha-Fetoprotein messenger RNA appeared as a major band of 2.4 kb, with two minor species of about 6.5 and 3.6 kb in the hepatocellular carcinoma and the fetal liver. Hypomethylation of the 5' end of the alpha-fetoprotein gene was detected in 78.3% of hepatocellular carcinomas expressing alpha-fetoprotein messenger RNA but infrequently (16.7%) in hepatocellular carcinomas with no detectable alpha-fetoprotein messenger RNA (p < 0.0003). This finding suggests that hypomethylation at the 5' region of the gene is associated with alpha-fetoprotein gene reexpression in hepatocellular carcinoma. The alpha-fetoprotein gene expression helped to differentiate unicentric from multicentric hepatocellular carcinomas and to identify other hidden alpha-fetoprotein-secreting hepatocellular carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)


Phyletic aspects of the distribution of 3-hydroxyretinal in the class Insecta.
The distribution of 3-hydroxyretinal (R3), a recently discovered retinoid used as the visual pigment chromophore in some insects, was investigated in the class Insecta using HPLC technology. We studied 138 species in 24 orders, sampling from a wide range of taxonomic groups as well as varied habitats. In addition to groups already known to have R3, we find this retinoid in Hemiptera (suborder Heteroptera), Plecoptera, Megaloptera, and Hymenoptera. We also find retinal (R1) in Hemiptera (suborder Homoptera), Mecoptera, and Trichoptera, groups previously thought to have only R3. The pattern of R3 occurrence indicates that this retinoid cannot be considered a phylogenetic marker, having a scattered distribution in the class Insecta as well as within some orders of insects. Several environmental factors that might influence the selection of chromophore have been considered, but none correlates with its distribution. The evolutionary reasons for the pattern of occurrence of R3 therefore remain unknown.


The Impact of the Covid-19-Related Transition to Telehealth on Visit Adherence in Mental Health Care: An Interrupted Time Series Study.
Covid-19 has led to an unprecedented shift to telemental health (TMH) in mental healthcare. This study examines the impact of this transition on visit adherence for mental health services in an integrated behavioral health department. Monthly visit data for 12,245 patients from January, 2019 to January, 2021 was extracted from the electronic medical record. Interrupted time series (ITS) analysis examined the impact of the Covid-19 transition to TMH on immediate level and trend changes in the percentage of cancelled visits and no shows in the 10 months following the transition. ITS also compared changes across the three largest services types: adult, pediatric, and substance use. Following the TMH-transition, completed visits increased by 10% amounting to an additional 3644 visits. In April, 2020, immediately following the TMH-transition, no shows increased by 1.4%, (95% CI 0.1, 2.7, p < 0.05) and cancellations fell by 13.5% (95% CI - 17.9, - 9.0, p < 0.001). Across the 10-month post-TMH period, 18.2% of visits were cancelled, compared to 28.3% across the 14-month pre-TMH period. The proportion of no-shows remained the same. The pattern was similar for pediatric and adult sub-clinics, but no significant changes in cancellations or no shows were observed in the substance use sub-clinic. TMH during the Covid-19 pandemic is associated with improved visit adherence over time and may be a promising model for improving the efficiency of mental health care delivery once it is safe to resume in person care.


Conformational alteration of bradykinin in presence of GM1 micelle.
We report here the interaction of bradykinin with ganglioside GM1 by circular dichroism, steady-state fluorescence, and one-dimensional 1H NMR spectroscopy. Circular dichroism spectroscopy is indicative of a turn formation of bradykinin backbone in the presence of GM1 micelle. The fluorescence quenching efficiencies of iodide and acrylamide are substantially reduced, indicating a shielding of phenylalanine residue of bradykinin from aqueous environment. Significant line broadening of NMR resonances of bradykinin, suggestive of motional restriction, is observed.


The diagnosis and treatment of malaria in Australia.
The number of reported malaria cases is increasing each year with several deaths reported recently. This article reviews the types of malarias, including their incidence, prevention, presentation and the standard treatment protocols.


Psychosomatic disease and acupuncture.
The medical philosophy implied by a "mind-body unity" hypothesis is outlined and the type of therapy appropriate to the stage of development of disease is discussed; special reference is made to the place of acupuncture within a modern medical program. Starting from the premise that mind is the primary causal force determining neural states, it is concluded that the highest level medical art would be "psychosomatic psychoanalysis." The next highest form of therapy would deal directly with nerve impulses (acupuncture, etc.), followed by drug therapies directed at intra- and extracellular fluid composition, hormone macromolecule manipulation, and finally minor and major surgery.


Preventive effect of vinpocetine on calcifications: atherosclerosis in experimental rabbits.
The action of vinpocetine (14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14, 15 eburnamine) on calcifications in liver, kidney, and CNS tissues from cholesterol-induced atherosclerosis in 16 experimental rabbits was studied. Three of 4 groups (4 rabbits each group) feeding on a cholesterol-rich diet developed atherosclerosis after 3 months. Two of the 4 groups were also fed vinpocetine supplements and analysis by neutron activation method showed a decrease in calcium content in CNS tissues and in liver and kidney. Results suggest that vinpocetine acts to decalcify cholesterol-induced atherosclerotic lesions in these tissues.


Roxatidine inhibits fibrosis by inhibiting NF‑κB and MAPK signaling in macrophages sensing breast implant surface materials.
Capsular contracture is an important complication after silicone mammary implant surgery. Fibroblasts and macrophages play critical roles in the pathogenesis of capsular contracture, making these two cell types therapeutic targets. It has been reported that inhibiting histamine receptors results attenuates fibrosis, but the role of roxatidine (a histamine receptor 2 inhibitor) in preventing fibrosis caused by breast implant materials remains unknown. The aim of the present study was to assess the hypothesis that roxatidine might have a prophylactic effect in capsular contracture induced by implant material. Inflammation induced by breast implant materials was mimicked by co‑culturing macrophages or fibroblasts with these materials in vitro. Capsular contracture was modeled in mice by planting breast implant materials in a subcutaneous pocket. Roxatidine was added in the culture medium or administered to mice bearing breast implant materials. By co‑culturing macrophages or fibroblasts with common breast implant materials (micro‑textured or smooth breast implants), the present study demonstrated that macrophages respond to these materials by producing pro‑inflammatory cytokines, a process that was abolished by addition of roxatidine to the culture medium. Although fibroblasts did not respond to implant surface materials in the same way as macrophages, the conditioned media of macrophages induced proliferation of fibroblasts. Mechanistically, administration of roxatidine inhibited activation of NF‑κB and p38/mitogen‑activated protein kinase (MAPK) signaling in macrophages. Furthermore, treatment with roxatidine in implant‑bearing mice reduced serum concentrations of transforming growth factor‑β and the abundance of fibroblasts around the implant. The present study concluded that roxatidine plays an important role in preventing fibrosis by inhibiting activation of NF‑κB and p38/MAPK signaling in macrophages.


On a new species of Neoechinorhynchus Hamann, 1892 (Acanthocephala: Neoechinorhynchoidea Southwell et Macfie, 1925) from Indian threadfin fish, Leptomelanosoma indicum Shaw, 1804 from Visakhapatnam coast, Andhra Pradesh, India.
A new acanthocephalan of the genus Neoechinorhynchus Hamman, 1892 (Acanthocephala: Neoaechinorhynchoidea Southwell et Macfie, 1925) parasitic on threadfin fish, Leptomelanosoma indicum Shaw, 1804 from Visakhapatnam coast, Andhra Pradesh, India is described. Neoechinorhynchus indicus sp. nov is characterized by an enormous body size, structural characteristics of the hooks on proboscis, presence of body annulations, two guard cells, unequal lemnisci, sub-terminal genital pore and the host. N. indicus sp.nov is included in the genus by the presence of three rows of six hooks each on the proboscis and a single layered proboscis receptacle.


Carotid Sheath Dissection and Histopathology During Neck Dissection in Head and Neck Carcinomas.
To investigate the carotid sheath in neck dissection (ND) specimens histopathologically in patients with head and neck carcinomas who had no evidence of previous neck surgery or direct involvement of the carotid sheath in their pre- or intra-operative evaluations. In this study, carotid sheath (CS) specimens of 40 patients with head and neck carcinomas (HNCA) who, depending on the condition of the primary tumor, required unilateral or bilateral elective or therapeutic selective neck dissection were histopathologically investigated by an expert head and neck pathologist to find any lymphoid or thyroid like tissue or tumor cells infiltration. A total of 50 carotid sheath (CS) specimens were investigated. None of the samples showed any evidence of tumor infiltration or accumulation of lymphatic tissue. We conclude that in patients with no histopathologic involvement of the carotid sheath in pre-operative or intra-operative tumor invasion, it is not necessary to remove CS in routine neck dissection.


Co-variation between graphic pattern stability and attentional cost: a clue for the difficulty to produce handwritten traces.
Attentional cost incurred for generating handwritten graphic patterns was investigated using a classic dual-task procedure, in which a concurrent reaction time (RT) task was used as an index of the attentional cost incurred by the primary graphic task. Eight right-handed adults had to trace graphic patterns, characterized by a 0°, 45°, 90°, 135° or 180° relative phase and corresponding to shapes ranging from lines to ellipses to circles, while responding by a key press as fast as possible to an auditory signal. The results evidenced a strong and significant correlation between the stability of the produced pattern and the associated attentional cost. The amplitude of the minor and major axes of the produced ellipsoids decreased with the increase of movement frequency, as expected by nonlinear models of oscillatory pattern generation. These findings pave the way to the study for the (coordinative) processes for letter (mal)formation in cursive handwriting.


Indications, techniques, and graft survival of mini and corneo-scleral tectonic keratoplasties: A retrospective single-center case series.
Tectonic keratoplasties (TK) are used to treat corneal and scleral perforations and to prevent the loss of the eye. In this study, we retrospectively analyzed indications, surgical procedures, and outcomes of eccentric mini and corneo-scleral tectonic keratoplasties with respect to anatomical survival and clear graft survival rates to identify risk factors for graft failure. This retrospective study includes 33 eccentric mini (graft diameter <6 mm) and/or corneo-scleral TK of 32 consecutive patients of a total of 41 TK carried out between 2005 and 2020 in the Eye Center, University of Freiburg, Germany, making up 0.7% of all keratoplasties performed during this period (n = 5557). Patient and graft specific data were extracted from medical files. Anatomical survival-defined as achieving integrity of the globe without further surgical interventions-and clear graft survival-defined as persisting graft clarity-were estimated using the Kaplan-Meier method. We also fitted Cox proportional hazard models to account for factors influencing anatomical and clear graft survival. Median duration of anatomical success was 72.5 months (95% confidence interval (CI) 18.1-infinite (inf.)) and median duration of clear graft survival was 29.6 months (95% CI 12.5-Inf.). The 1-year survival rate for anatomical survival was 67.6% (95% CI 52.2% - 87.6%) and for clear graft survival 66.4% (95% CI 50.5%- 87.1%). No enucleation was necessary during this time-period. Non-inflammatory primary causes (n = 14) presented a trend towards better anatomical survival rates (median remained above 0.75 during follow-up) compared to inflammatory primary causes (n = 19, median 18.1 months (95% CI 2.8 - inf.)) and longer clear graft survival (median 29.6 months (95% CI 12.5 - inf.) versus 13.1 months (95% CI 3.2 - inf.)). Corneo-scleral grafts (n = 18) compared to corneal grafts (n = 15) showed a trend towards better anatomical survival (more than 50% of eyes did not fail during follow-up period (95% CI 21.9-Inf. months) versus 18.1 months (95% CI 2.4-Inf.)) and clear graft survival (median 29.6 months (95% CI 12.6-Inf.) versus 6.2 months (95% CI 2.8-Inf.)). Old age (n = 11, 75.2 - 90.1 years) compared to young age (n = 11, 6.2 - 60.2 years) was the only hazard ratio (hazard ratio 0.04 (95% CI 0.002-0.8)) that reached the level of significance (p = 0.03). Eccentric TK is helpful in the successful treatment of a variety of severe eye diseases. Patients at young age, with pre-existing inflammatory conditions or corneal TK are at higher risk for anatomical failure as well as clear graft failure and therefore need to be monitored closely.


Accuracy of the doses computed by the Eclipse treatment planning system near and inside metal elements.
Metal artefacts degrade clinical image quality which decreases the confidence of using computed tomography (CT) for the delineation of key structures for treatment planning and leads to dose errors in affected areas. In this work, we investigated accuracy of doses computed by the Eclipse treatment planning system near and inside metallic elements for two different computation algorithms. An impact of CT metal artefact reduction methods on the resulting calculated doses has also been assessed. A water phantom including Gafchromic film and metal inserts was irradiated (max dose 5 Gy) using a 6 MV photon beam. Three materials were tested: titanium, alloy 600, and tungsten. The phantom CT images were obtained with the pseudo-monoenergetic reconstruction (PMR) and the iterative metal artefact reduction (iMAR). Image sets were used for dose calculation using an Eclipse treatment planning station (TPS). Monte Carlo (MC) simulations were used to predict the true dose distribution in the phantom allowing for comparison with doses measured by film and calculated by TPS. Measured and simulated percentage depth doses (PDDs) were not statistically different (p > 0.618). Regional differences were observed at edges of metallic objects (max 8% difference). However, PDDs simulated with and without film were statistically different (p < 0.002). PDDs calculated by the Acuros XB algorithm based on the dose-to-medium approach best matched the MC reference regardless of the CT reconstruction methods and inserts used (p > 0.078). PDDs obtained using other algorithms significantly differ from the MC values (p < 0.011). The Acuros XB algorithm with a dose-to-medium approach provides reliable dose calculation in all metal regions when using the Varian system. The inability of the AAA algorithm to model backscatter dose significantly limits its clinical application in the presence of metal. No significant impact on the dose calculation was found for a range of metal artefact reduction strategies.


Separation of human brain angiotensin-converting enzyme from enkephalin-degrading activity.
Angiotensin-converting enzyme and enkephalin-degrading enzyme activities were solubilized and purified from a particulate fraction of human diencephalon. Converting enzyme activity and enkephalin-degrading activity elute in different fractions following ion exchange chromatography on DEAE-cellulose, suggesting that they are different enzymes. Both enzymes were purified further by ion exchange chromatography on hydroxylapatite and by gel filtration on Sephadex G-200. The purified enzymes had markedly different sensitivities to known inhibitors of angiotensin-converting enzyme. The data do not support the hypothesis that angiotensin-converting enzyme and enkephalin degrading-enzyme are identical.


Ultrastructural and immunocytochemical changes of prolactin cells of grafted pituitary after the injection of dopamine in the albino rat.
Anterior pituitary glands were homografted into the anterior chamber of the eye in female rats. The pituitary grafts survived and were well vascularized three weeks after the transplantation. The prolactin cells were morphologically active as shown by their well-developed Golgi complexes and granular endoplasmic reticulum and the exocytosis of secretory granules. The injection of dopamine into the common carotid artery of the graft-bearing rat rapidly suppressed the granule extrusion and then gradually induced a remarkable morphological atrophy in the prolactin cells.


Conformational restrictions of the sheep testicular receptor discriminates pituitary lutropin and placental gonadotropins.
A membrane preparation from the testis of maturing Dorset-Leicester-Suffolk sheep, capable of discriminating pituitary LH (lutropin) from placental gonadotropins human choriogonadotropin (hCG) and equine choriogonadotropin is described. Maximum binding of 125I-oLH (ovine lutropin) to the testicular receptors occurred at 4 degrees C in a rapid manner, attaining equilibrium in 12-16 h. Under such optimal conditions, only unlabeled ovine LH or the structurally identical bovine LH effectively competed for receptor occupation. Other highly purified pituitary LH preparations from rat and human pituitaries were weakly (4-10%) active in displacement assays. Purified hCG or equine choriogonadotropin, which were highly potent in rat testicular LH receptor assays, could not compete with 125I-oLH for binding to the sheep LH receptor at 4 degrees C. Thus, the sheep testicular LH receptor was highly specific in recognizing pituitary LH conformation. The presence of an ovine/bovine LH alpha- or beta-subunit in recombinants with hCG subunit counterparts was required to generate an effective conformation capable of receptor recognition. Chemically deglycosylated hCG, containing 75% less carbohydrate and which showed greater binding to other LH receptors, failed to recognize sheep LH receptor, suggesting that excess carbohydrate in hCG was not a factor in hindering binding of the native placental hormone. Scatchard analysis using 125I-hCG/125I-oLH revealed that there were separate sites with similar affinities but vastly different capacities. The hCG binding sites, which could also be effectively occupied by oLH, were less than 10% of oLH binding sites. Thus, the Dorset-Leicester-Suffolk sheep testicular receptor provides an important and unique in vitro test system to distinguish pituitary LH from placental LH-like hormones. We infer that temperature-dependent conformational restrictions of the sheep testicular LH receptor are involved in recognizing differences in these highly similar and structurally homologous hormones.


8. Steroids and differentiation. The role of estrogen in the differentiation of prolactin producing cells.
The capacity to synthesize PRL and GH was studied in normal mice and in Snell and Ames dwarfs. In normal mice GH synthesis turned on dramatically between day 16-17 of gestation whereas PRL was not detectable throughout gestation or the first week of life, was barely detectable in 8-day-old mice and was clearly demonstrable by 12 days of age. However, transplantation of pituitaries from newborn mice into adult female hosts resulted in substantial PRL synthesis. Treatment of mice with DES at various ages showed that neonates failed to respond to the hormone; in older pups, an age-dependent increase in the magnitude of PRL synthesis was observed. There was a direct correlation between nuclear estrogen receptor levels and PRL cell function. Snell and Ames dwarf mice failed to synthesize PRL or GH at any stage of development, nor could we detect immunoreactive peptides which might represent mutant forms of the hormones. Our findings suggest that: (1) GH gene expression precedes that of PRL by about 2 weeks; (2) the development of PRL cell function is dependent on estrogen; (3) the capacity to respond to estrogen is present before the endogenous initiation of PRL synthesis and is limited by the availability of estrogen receptor; and (4) in Snell and Ames mutants, both types of alleles result in failure of the pituitary to initiate PRL and GH synthesis.


Cardiorespiratory fitness and TV viewing in relation to metabolic risk factors in Portuguese adolescents.
The purpose of this study was to examine whether adolescents who have high levels of cardiorespiratory fitness (CRF) co-existing with low levels of television (TV) viewing present a better metabolic risk profile compared to their low fit and high TV viewing counterparts. A total of 372 students (aged 12-15 years old) comprised the sample of this study. Anthropometric data (body mass index and waist circumference) was collected. CRF was calculated based upon the 20 metres shuttle run test. A questionnaire was used to estimate weekly TV viewing. Information about biological maturity and parental education was collected. Participants were then categorized into one of four category profiles according to the scores they achieved: low TV-Fit; high TV-Fit; low TV-Unfit and high TV-Unfit. Metabolic risk score (MRS) was calculated based on the sum of the Z-scores of all the metabolic variables analysed. Logistic regression analyses indicated that the high TV-Unfit group was almost 3-times more likely to be assigned to the high MRS group (OR = 2.85, 95% CI = 1.08-7.50) compared to their low TV-Fit group counterparts. The data showed that the high TV-Unfit group was associated with an increased metabolic risk in adolescents after adjustment for gender, age, biological maturity and parental education.


Transition of epithelial toward mesenchymal differentiation during ovarian carcinosarcoma tumorigenesis.
It was the purpose of this study to test the monoclonal theory in ovarian carcinosarcoma. Twenty-six women with a diagnosis of ovarian carcinosarcoma were subjected to a clinicopathologic analysis. Biopsies from metastatic lesions obtained at primary surgery and surgery for recurrent disease were reviewed. Special attention was paid to the composition of metastatic lesions and to florid desmoplastic reaction as a potential pitfall for the detection of sarcomatous areas. Biopsies derived from metastatic disease at primary surgery (n = 107) consisted of carcinoma cells only (n = 71, 66%), >50% carcinoma cells (n = 21, 20%), >50% sarcoma cells (n = 13, 12%), or sarcoma cells only (n = 2, 2%). The microscopic analysis demonstrated a preponderance of epithelial cells in the primary setting and suggested the epithelial component to drive the tumor, a finding consistent with the monoclonal theory. Biopsies derived from surgery for recurrent disease (n = 8) consisted of carcinoma cells only (0%), >50% carcinoma cells (n = 1, 13%), >50% sarcoma cells (n = 4, 50%), or sarcoma cells only (37%). Since sarcomatous cells dominated the tumorigenic cell population in the recurrent setting, this analysis revealed a change of the composition of metastatic lesions in time when compared to the data in the primary setting. This change was supported by the observation of a threefold higher incidence of sarcoma-dominated metastatic lesions at interval debulking when compared to primary debulking (24 vs 8%, respectively). The potential of a phenotypic change during ovarian cancer progression was further highlighted by the detection of two cases of carcinosarcoma that presented as a recurrence of epithelial ovarian carcinoma. Our results are consistent with the monoclonal theory of ovarian carcinosarcoma histogenesis, but suggest that there is a tendency toward a sarcomatous differentiation during disease progression. These data are important to understand the tumor biology and might have implications for a tailored treatment of ovarian carcinosarcoma.


Biophysical scenario of giant gel formation in the northern Adriatic sea.
The macroscopic gel phase (mucilage) appears episodically in the northern Adriatic Sea covering tens of square kilometers of sea surface. Current views leave no doubt on phytoplankton production as a proximal source of polymers constituting the gel network, but the mechanism leading to its rapid production remains unknown. We introduced electrochemical sensing of marine microparticles and atomic force microscopy to image supramolecular organization of marine gel network. Our biophysical scenario of mucilage event features self-organization of biopolymers into microparticles ("marine vesicles") that under specific conditions transform to giant gel by a fast vesicle-to-gel transition.


Management of supraglottic stenosis using a novel stent design.
To present a novel design for a stent for management of a traumatic supraglottic web. Case report and literature review (PubMed 1964-2013). A 48-year-old man was presented after penetrating laryngeal trauma. He had severe dysphonia and was tracheotomy dependent. He had been treated previously with open reduction and fixation of laryngeal fracture. On examination, we identified an avulsed left vocal fold and a supraglottic web. He initially underwent reapproximation of the avulsed left vocal fold, and subsequently, the supraglottic web was treated using a stent designed by the senior author (R.T.S.). In addition, he underwent later resection of scar tissue to improve dysphonia and then he was decanulated. There are a few techniques presented in the literature and mostly are adaptations of subglottic stenosis management techniques. Individualized treatment is needed for these difficult cases. We present our experience with supraglottic web treatment to expand the literature on this uncommon disorder.


The therapeutic potential of tacrine.
Tacrine, a non-competitive inhibitor of acetylcholine esterase, has been approved for the treatment of patients with mild to moderate Alzheimer's disease in 1995. The available evidence suggests that in a substantial proportion of patients tacrine has the potential to improve cognitive functions, to ameliorate behavioural problems, and to delay the time to significant clinical endpoints. Thus, tacrine meets realistic expectations from symptomatic treatment. The major safety concern about tacrine is the probability of liver enzyme elevations and the high frequency of adverse events, particularly gastrointestinal. Findings are presented from an open-label multicentre study showing that tacrine is a safe and manageable compound in private practice.


The death of a pet. How it can affect owners.
The death of a family pet can be a difficult and upsetting experience. In this article, human reactions after pet death are described as a normal bereavement sequence and a case study is used to describe and explain major issues associated with a pet's death.


[Operating models and organizational structures: opportunities and challenges for human milk banking in Germany].
Donor human milk is the recommended alternative for feeding preterm infants if mother's own milk is unavailable. Human milk banks collect, screen, store and distribute donated human milk according to pre-specified standard operating procedures to premature infants without mothers own milk. Herein we characterize current operating models and the structural organisation of German milk bank institutions. The analysis of current and future opportunities and challenges may support the development of a comprehensive donor milk service within Germany. Summary of the panel discussion entitled "Operating models and organizational structures: opportunities and risks for donor human milk bank in Germany" during the 3rd Scientific Symposium of the German Human Milk Bank Initiative (FMBI), November 25th to 26th 2022, in Nuremberg, Germany. Differing operator models may facilitate the use of donor human milk by incorporating unique site-specific factors, pre-existing infrastructure, and individual needs. In addition to the establishment of milk banks serving single neonatal units, high-capacity milk banks should be enabled to provide donor human milk using several hub-and-spoke systems. This may create a nationwide network for a sustainable human milk supply for preterm infants that is based on qualified breastfeeding and lactation support.


Ethidium bromide inhibits rat brain acetylcholinesterase activity in vitro.
Ethidium bromide (EtBr), a fluorescent dark red compound and stain for double-stranded DNA and RNA was used to study acetylcholinesterase (AChE) activity in vitro together with kinetic parameters of this enzyme in the striatum (ST), hippocampus (HP), cerebral cortex (CC) and cerebellum (CB) of adult rats. AChE activity in vitro in the ST, HP, CC and CB was significantly reduced (p<0.05) in the presence of EtBr at concentrations of 0.00625, 0.0125, 0.025, 0.05 and 0.1 mM. For the analysis of the kinetic three concentrations of EtBr were tested (0.00625, 0.025 and 0.1 mM). An uncompetitive inhibition type was observed in the ST, HP and CC, whereas in the CB the inhibition type was mixed. These data indicate that EtBr should be considered a strong inhibitor of AChE activity demonstrating that there is an interaction between this compound and the cholinergic system.


Deletion analysis of the internal signal-anchor domain of the human asialoglycoprotein receptor H1.
The human asialoglycoprotein receptor H1 is a single-spanning membrane protein with the amino terminus facing the cytoplasm and the carboxy terminus exposed on the exoplasmic side of the plasma membrane. It has been shown earlier that the transmembrane segment, residues 38-65, functions as an internal signal directing protein synthesis to the endoplasmic reticulum and initiating membrane insertion. This process is co-translational and mediated by signal recognition particle (SRP). To identify subsegments within this region containing the signal information, we prepared deletion mutants at the level of the cDNA and analysed them in a wheat germ in vitro translation system with microsomes as the target membrane. Insertion and membrane anchoring were judged by the glycosylation of the protein, its resistance to exogenous protease and the extent to which it can be extracted from the microsomes by alkaline treatment. It was found that very small deletions already reduce the stability of membrane anchoring. However, nearly half of the transmembrane domain can be deleted, both from the amino-terminal and from the carboxy-terminal side, without completely abolishing membrane insertion. Several mutants, although not inserted, still interact with SRP. The results support the notion that the main feature of a signal sequence is a hydrophobic stretch of sufficient length (10-12 residues in our sequence), and indicate that recognition by SRP is not sufficient for membrane insertion.


Long noncoding RNA LINC00982 upregulates CTSF expression to inhibit gastric cancer progression via the transcription factor HEY1.
Upregulating the expression of long noncoding RNA LINC00982 controlled cell proliferation in gastric cancer, but the regulatory molecular mechanisms are yet to be expounded. We here aimed to elaborate how LINC00982 regulated the malignancy of gastric cancer cells. RT-qPCR and Western blot analysis were used to detect the expression of LINC00982 and cathepsin F (CTSF) in gastric cancer tissues and cells. Modulatory effect of LINC00982 on gastric cancer cells was assessed by CCK-8, colony formation, Transwell migration, and invasion assays. The relationship between LINC00982, YRPW motif 1 (HEY1), and CTSF was examined by RNA-binding protein immunoprecipitation, luciferase assay, and chromatin immunoprecipitation, and their interaction in the regulation of gastric cancer cellular functions was analyzed by performing gain-of-function and rescue assays. The nude mouse model of tumor formation was developed to examine the effects of LINC00982 on tumorigenesis. LINC00982 was lowly expressed in gastric cancer tissues, whereas its overexpression impaired the proliferative, migratory, and invasive properties of gastric cancer cells. Furthermore, LINC00982 could bind to transcription factor HEY1 and inhibited its expression. Through blocking the binding of HEY1 to CTSF promoter, LINC00982 promoted the expression of CTSF. Overexpression of HEY1 or inhibition of CTSF could reverse the antitumor effects of LINC00982 on gastric cancer, which were further demonstrated in vivo. All these taken together, LINC00982 acted as a tumor suppressor in gastric cancer, which is therefore suggested to be a potential antitumor target for gastric cancer.NEW & NOTEWORTHY We identified LINC00982 as a promising antitumor target for the treatment of patients with gastric cancer. We also determined a regulatory network involved in the pathophysiology of gastric cancer wherein LINC00982 could bind to HEY1 to impair its binding to cathepsin F (CTSF) promoter and hence promote CTSF expression, which aids in better understanding of molecular mechanisms related to gastric tumorigenesis.


Artificial Intelligence Literacy: Developing a Multi-institutional Infrastructure for AI Education.
To evaluate the effectiveness of an artificial intelligence (AI) in radiology literacy course on participants from nine radiology residency programs in the Southeast and Mid-Atlantic United States. A week-long AI in radiology course was developed and included participants from nine radiology residency programs in the Southeast and Mid-Atlantic United States. Ten 30 minutes lectures utilizing a remote learning format covered basic AI terms and methods, clinical applications of AI in radiology by four different subspecialties, and special topics lectures on the economics of AI, ethics of AI, algorithm bias, and medicolegal implications of AI in medicine. A proctored hands-on clinical AI session allowed participants to directly use an FDA cleared AI-assisted viewer and reporting system for advanced cancer. Pre- and post-course electronic surveys were distributed to assess participants' knowledge of AI terminology and applications and interest in AI education. There were an average of 75 participants each day of the course (range: 50-120). Nearly all participants reported a lack of sufficient exposure to AI in their radiology training (96.7%, 90/93). Mean participant score on the pre-course AI knowledge evaluation was 8.3/15, with a statistically significant increase to 10.1/15 on the post-course evaluation (p= 0.04). A majority of participants reported an interest in continued AI in radiology education in the future (78.6%, 22/28). A multi-institutional AI in radiology literacy course successfully improved AI education of participants, with the majority of participants reporting a continued interest in AI in radiology education in the future.


Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease.
To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT). Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed by quantitative polymerase chain reaction, immunofluorescence microscopy, and Western blotting. Immunohistochemical staining revealed cells expressing the EC-specific marker CD31 in the subendothelial, perivascular, and parenchymal regions of the lungs from all SSc patients. Confocal microscopy identified cells displaying simultaneous expression of von Willebrand factor and α-smooth muscle actin in small and medium-sized arterioles in the SSc lung tissue but not in normal control lungs. CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell-specific genes (type I collagen, type III collagen, and fibronectin), EC-specific genes (type IV collagen and VE-cadherin), profibrotic genes (transforming growth factor β1 and connective tissue growth factor), and genes encoding EndoMT-related transcription factors (TWIST1 and SNAI2). Cells coexpressing EC- and mesenchymal cell-specific molecules are present in the lungs of patients with SSc-associated ILD. CD31+CD102+ ECs isolated from SSc lungs simultaneously expressed mesenchymal cell- and EC-specific transcripts and proteins. Collectively, these observations demonstrate the occurrence of EndoMT in the lungs of patients with SSc-associated ILD.


The growth performance, body composition and nonspecific immunity of white shrimps (Litopenaeus vannamei) affected by dietary Astragalus membranaceus polysaccharide.
The aim of this study was to investigate the effects of Astragalus membranaceus polysaccharide (AMP) on the growth performance, body composition and non-specific immune index of white shrimps (Litopenaeus vannamei). AMP was used to replace 0 (control), 10, 30, and 50 g kg-1 of the cellulose in the basic diet to formulate four kinds of test feeds. Sixplicate groups of shrimps with an average weight of 0.51 ± 0.03 g were fed with one of diets four times daily. Dietary 50 and 30 g kg-1 of AMP increased body weight gain, feed efficiency, body protein, superoxide dismutase activity, catalase activity, acid phosphatase activity, lysozyme, disease resistance ability against Vibrio alginolyticus and decreased body lipid level of shrimps compared with those of the control group. However, a high level of AMP (50 g kg-1) did not improve the efficiency of AMP on the growth performance, body composition and non-specific immune index of shrimps further compared to moderate level of AMP (30 g kg-1). The results demonstrated that AMP with appropriate dose could promote the growth of shrimps and improve their disease resistance.


Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.
Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.


Transcript profiling in Arabidopsis with genome tiling microarrays.
Microarray technology is at present a standardized workflow for genome-wide expression analysis. Whole-genome tiling microarrays have emerged as an important platform for flexible and comprehensive expression profiling. In this chapter we describe a detailed standardized workflow for experiments assessing the transcriptome of Arabidopsis using tiling arrays and provide useful hints for critical steps from experimental design to data analysis. Although the protocol is optimized for AGRONOMICS1 arrays, it can readily be adapted to other tiling arrays. AGRONOMICS1 is the first platform that enables strand-specific expression analysis of the Arabidopsis genome with a single array. Moreover, it includes all perfect match probes from the original ATH1 array, allowing readily integration with the large existing ATH1 knowledge base. This workflow is designed for the analysis of raw data for any number of samples and it does not pose any particular hardware requirements.


Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo.
The formation of intersegmental blood vessels (ISVs) in the zebrafish embryo serves as a paradigm to study angiogenesis in vivo. ISV formation is thought to occur in discrete steps. First, endothelial cells of the dorsal aorta migrate out and align along the dorsoventral axis. The dorsal-most cell, also called tip cell, then joins with its anterior and posterior neighbours, thus establishing a simple vascular network. The vascular lumen is then established via formation of vacuoles, which eventually fuse with those of adjacent endothelial cells to generate a seamless tube with an intracellular lumen. To investigate the cellular architecture and the development of ISVs in detail, we have analysed the arrangement of endothelial cell junctions and have performed single cell live imaging. In contrast to previous reports, we find that endothelial cells are not arranged in a linear head-to-tail configuration but overlap extensively and form a multicellular tube, which contains an extracellular lumen. Our studies demonstrate that a number of cellular behaviours, such as cell divisions, cell rearrangements and dynamic alterations in cell-cell contacts, have to be considered when studying the morphological and molecular processes involved in ISV and endothelial lumen formation in vivo.


Absence of the spleen(s) in conjoined twins: a diagnostic clue of laterality defects? Radiological study of historical specimens.
Laterality defects are quite common in thoracoileopagus and parapagus dicephalus but rare in other types of conjoined twins. To present the presumed laterality defects in cephalothoracoileopagus and prosopothoracoileopagus conjoined twins, based on the unilateral or bilateral absence or duplication of the spleen. Three human anatomical specimens of craniothoracoileopagus (CTIP) twins and one of prosopothoracoileopagus (PTIP) twins were investigated. The specimens were part of the Museum Vrolik collection of the Department of Anatomy and Embryology of the Academic Medical Centre, University of Amsterdam, The Netherlands. The specimens were taken out of their jars and scanned with multidetector CT and volumetric T2-weighted MRI at 1.5 T. The internal anatomy of the specimens was largely in accordance with previous reports. However, there was no recognisable spleen in the right twin in one CTIP specimen, in the left twin in one other CTIP specimen, and in both twins in the third CTIP specimen and in the PTIP specimen. Asplenia and polysplenia are considered reliable indicators of right and left isomerism, respectively. However, three of our four specimens had laterality patterns that did not correspond with those previously reported. Since no other parameters of laterality defects could be verified in these specimens, we concluded that asplenia was unlikely to be caused by laterality defects.


A structural connectivity atlas of limbic brainstem nuclei.
Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of important monoaminergic ascending fibers including the noradrenergic locus coeruleus, serotonergic dorsal raphe nucleus, and dopaminergic ventral tegmental area. However, due to practical challenges to their study, there is limited data regarding their in vivo anatomic connectivity in humans. To evaluate the structural connectivity of the following brainstem nuclei with limbic cortical areas: locus coeruleus, ventral tegmental area, periaqueductal grey, dorsal raphe nucleus, and nucleus tractus solitarius. Additionally, to develop a group average atlas of these limbic brainstem structures to facilitate future analyses. Each nucleus was manually masked from 197 Human Connectome Project (HCP) structural MRI images using FSL software. Probabilistic tractography was performed using FSL's FMRIB Diffusion Toolbox. Connectivity with limbic cortical regions was calculated and compared between brainstem nuclei. Results were aggregated to produce a freely available MNI structural atlas of limbic brainstem structures. A general trend was observed for a high probability of connectivity to the amygdala, hippocampus and DLPFC with relatively lower connectivity to the orbitofrontal cortex, NAc, hippocampus and insula. The locus coeruleus and nucleus tractus solitarius demonstrated significantly greater connectivity to the DLPFC than amygdala while the periaqueductal grey, dorsal raphe nucleus, and ventral tegmental area did not demonstrate a significant difference between these two structures. Monoaminergic and other modulatory nuclei in the brainstem project widely to cortical limbic regions. We describe the structural connectivity across the several key brainstem nuclei theorized to influence emotion, reward, and cognitive functions. An increased understanding of the anatomic basis of the brainstem's role in emotion and other reward-related processing will support targeted neuromodulatary therapies aimed at alleviating the symptoms of neuropsychiatric disorders.


Religiosity is associated with greater size, kin density, and geographic dispersal of women's social networks in Bangladesh.
Human social relationships, often grounded in kinship, are being fundamentally altered by globalization as integration into geographically distant markets disrupts traditional kin based social networks. Religion plays a significant role in regulating social networks and may both stabilize extant networks as well as create new ones in ways that are under-recognized during the process of market integration. Here we use a detailed survey assessing the social networks of women in rural Bangladesh to examine whether religiosity preserves bonds among kin or broadens social networks to include fellow practitioners, thereby replacing genetic kin with unrelated co-religionists. Results show that the social networks of more religious women are larger and contain more kin but not more non-kin. More religious women's networks are also more geographically diffuse and differ from those of less religious women by providing more emotional support, but not helping more with childcare or offering more financial assistance. Overall, these results suggest that in some areas experiencing rapid social, economic, and demographic change, religion, in certain contexts, may not serve to broaden social networks to include non-kin, but may rather help to strengthen ties between relatives and promote family cohesion.


Black Turmeric and Aloe Vera in the Management of Oral Submucous Fibrosis: A Prospective Clinical Study.
To determine the therapeutic efficacy of Kali haldi in the management of Oral submucous Fibrosis (OSMF) v/s steroid therapy. A clinical prospective study was conducted on 42 patients of oral submucous fibrosis were equally divided into 2 groups. Group A patients were treated with a mixture of powdered Kali Haldi and aloe vera gel in equal ratio 3 times a day for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with oral antioxidant supplements for 3 months. Burning sensation, cheek flexibility, mouth opening, and tongue protrusion were evaluated before, during, and after treatment at an interval of 15 days, 1 month, 2, month and 3 months. Statistically significant results were obtained at the end of 3 months duration for both the groups (P < 0.001). The Symptomatic correction was more evident in the case of Group A patients than Group B. Response of the ayurvedic regimen was potentially better as compared to the regular steroid therapy. The study concludes that Combination therapy works wonders in the case of OSMF in stages I, II, III and can be a good option, comparatively safe and with negligible side effects, but potent and equally effective management of oral submucous fibrosis. Henceforth, it will be better to do such kinds of studies on a vast scale including larger samples and longer duration to check the efficacy and durability of this ancient ayurvedic regimen.


Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK-3β in 3xTg-AD mice.
Moderate dietary restriction can ameliorate age-related chronic diseases such as Alzheimer's disease (AD) by increasing the expression of neurotrophic factors and promoting neurogenesis in the brain. Glycogen synthase kinase-3β (GSK-3β) signaling is essential for the coordination of progenitor cell proliferation and differentiation during brain development. The mechanisms by which GSK-3β is involved in dietary restriction-induced neurogenesis and cognitive improvement remain unclear. Six-month-old male 3xTg-AD and wild-type mice were fed on alternate days (intermittent fasting, IF) or ad libitum (AL) for 3 months. GSK-3β activity was regulated by bilaterally infusing lentiviral vectors carrying siRNA targeting GSK-3β into the dentate gyrus region of the hippocampus. Intermittent fasting promoted neuronal differentiation and maturation in the dentate gyrus and ameliorated recognized dysfunction in 3xTg-AD mice. These effects were reversed by siRNA targeting GSK-3β. After intermittent fasting, the insulin and protein kinase A signaling pathways were inhibited, while the adenosine monophosphate-activated protein kinase and brain-derived neurotrophic factor pathways were activated. These findings suggest that intermittent fasting can promote neuronal differentiation and maturation in the hippocampus by activating GSK-3β, thus improving learning and memory.


Acrosome reaction of human sperm used for in vitro fertilization.
The acrosomal reaction of human spermatozoa was assessed, according to a triple-stain technique, at the end of a 17-hour capacitation period in the search for a predictive test of sperm efficiency in an in vitro fertilization program. A 400% increase in the acrosomal reaction rate of the living spermatozoa was observed (4.2% +/- 3.2% before incubation versus 16% +/- 11% after incubation). No correlation could be evidenced between the abilities for spermatozoa to react and to fertilize mature human oocytes in vitro, whatever the initial semen quality. The acrosome reaction rate was not enhanced by the presence of the cumulus oocyte complex, by the selection of motile spermatozoa, or by the increase in albumin concentration of the culture medium.


Radiation therapy for prostate cancer.
Radiation therapy is an effective treatment for newly diagnosed prostate cancer, salvage treatment, or for palliation of advanced disease. Herein we briefly discuss the indications, results, and complications associated with brachytherapy and external beam radiotherapy, when used as monotherapy and in combination with each other or androgen deprivation.


Epoxidation of linear, branched and cyclic alkenes catalyzed by unspecific peroxygenase.
Unspecific peroxygenases (EC 18.104.22.168) represent a group of secreted heme-thiolate proteins that are capable of catalyzing the mono-oxygenation of diverse organic compounds, using only H2O2 as a co-substrate. Here we show that the peroxygenase secreted by the fungus Agrocybe aegerita catalyzed the oxidation of 20 different alkenes. Five branched alkenes, among them 2,3-dimethyl-2-butene and cis-2-butene, as well as propene and butadiene were epoxidized with complete regioselectivity. Longer linear alkenes with a terminal double bond (e.g. 1-octene) and cyclic alkenes (e.g. cyclohexene) were converted into the corresponding epoxides and allylic hydroxylation products; oxidation of the cyclic monoterpene limonene yielded three oxygenation products (two epoxides and an alcohol). In the case of 1-alkenes, the conversion occurred with moderate stereoselectivity, in which the preponderance for the (S)-enantiomer reached up to 72% ee for the epoxide product. The apparent Michaelis-Menten constant (Km) for the epoxidation of the model substrate 2-methyl-2-butene was 5mM, the turnover number (kcat) 1.3×10(3)s(-1) and the calculated catalytic efficiency, kcat/Km, was 2.5×10(5)M(-1)s(-1). As epoxides represent chemical building blocks of high relevance, new enzymatic epoxidation pathways are of interest to complement existing chemical and biotechnological approaches. Stable and versatile peroxygenases as that of A. aegerita may form a promising biocatalytic platform for the development of such enzyme-based syntheses.


Optimal conditions for the fusion of lymphoid cell lines.
A series of hydrolytic enzymes were compared with lysolecithin, glycerol monooleate, and inactivated Sendai virus for their ability to bring about the fusion of several human and mouse lymphoid cell lines. The agents were tried alone and in various combinations, and a variety of incubation conditions were tested to determine those optimal for fusion. Sendai virus was found to produce the best results with the mouse lymphoid cells; lysolecithin plus glycerol monooleate was slightly superior with the human lymphoid cells. A mixture of hyaluronidase plus collagenase produced low (2 to 6%), but significant, fusion of the human lymphoid cells; both the human and mouse lymphoid cell lines were found to contain relatively high amounts of prolyl hydroxylase, the enzyme which forms collagen from protocollagen. The maximum fusion obtained with the human cells was 16%; with a mouse plasmacytoma line, the maximum was 7.5%; and with a mouse leukemic line derived from L5178Y, the maximum was 60%.


Dynamics and composition of serum lipids in hyperlipoproteinemias.
The microviscosity of serum lipids in patients with hyperlipoproteinemia and normal donors was determined by monitoring the degree of fluorescence polarization of the fluorescent probe 1,6-diphenyl-1,3,5-hexatrine (DPH). Determination of serum lipids--serum total cholesterol, serum triglycerides, and serum phospholipids--revealed that an increase in the ratio of cholesterol/triglyceride + phospholipid is accompanied by an increase in the degree of fluorescence polarization and an increase in the microviscosity values. Similar results were obtained with sonicated liposomes prepared from serum lipids extracts. This correlation between dynamics and composition of serum lipids was further supported by results obtained with an artificial model system of sonicated lipids dispersions. The results have shown that high microviscosity values are characteristic in patients with high levels of serum cholesterol, and that low microviscosity values are characteristic in patients with high levels of serum triglycerides. It is suggested therefore that this technique may serve as a basis for a rapid screening test for hyperlipoproteinemias.


Pancreaticogastrostomy: the preferred operation for pain relief in chronic pancreatitis.
We present the results of surgery in 53 patients with intractable pain due to chronic pancreatitis associated with pancreatic duct dilatation. Using a limited mucosal to mucosal anastomosis over a silastic T tube the main pancreatic duct was drained in 33 patients into a Roux-en-Y jejunal loop (pancreaticojejunostomy, PJ) and in 20 patients into the stomach (pancreaticogastrostomy, PG). There was one postoperative death in the PJ group and none in the PG group. All patients were followed up for a minimum of four years. There was significantly greater pain relief in the PG group both at 1 (P less than 0.01) and 4 years (P less than 0.05) after surgery. We argue that PG is the operation of choice to relieve intractable pain in most patients with chronic pancreatitis associated with duct dilatation.


Designing teacher professional development programs to support a rapid shift to digital.
From a design perspective, this paper offers a response to the impact, value, and application of a manuscript published by Philipsen et al. (Improving teacher professional development for online and blended learning: A systematic meta-aggregative review. Educational Technology and Research Development, 67, 1145-1174. 10.1007/s11423-019-09645-8, 2019). Philipsen et al. (2019) reviewed what constitutes an effective teacher professional development program (TPD) for online and blended learning (OBL), with our response focusing on its value and application in light of an emergency shift to digital to address a global pandemic. This paper also proceeds to examine limitations in previous research into the subject and future research opportunities to investigate important components that inform the design of a resilient and scalable TPD for OBL.


Descending thoracic aortic aneurysm repair: 12-year experience using distal aortic perfusion and cerebrospinal fluid drainage.
The benefit of distal aortic perfusion and cerebrospinal fluid drainage over the "clamp and sew" technique during repairs of the descending thoracic aorta is still being debated. The purpose of this report is to analyze our experience with regard to neurologic deficit (paraplegia and paraparesis) and mortality using the adjuncts of distal aortic perfusion and cerebrospinal fluid drainage. Between February 1991 and September 2004, we repaired 355 descending thoracic aortic aneurysms. Excluded from analysis were 29 patients who required profound hypothermic circulatory arrest as a result of transverse arch involvement and 26 patients with aortic rupture, leaving a group of 300 patients for which outcomes were analyzed. Mean patient age was 67 years, and 102 (34%) of the patients were women. The adjunct group of distal aortic perfusion and cerebrospinal fluid drainage used in 238 (79.3%) patients was compared with a group of 62 patients who underwent simple cross-clamp with or without the addition of a single adjunct. Multivariable data were analyzed by Cox regression. The incidence of neurologic deficit after all repairs was 2.3% (7 of 300 patients). The incidence of neurologic deficit (immediate and delayed) in the adjunct group was 1.3% (3 of 238 patients), and in the nonadjunct group was 6.5% (4 of 62 patients; p < 0.02). One case of delayed paraplegia occurred in each group. All neurologic deficits occurred in patients with aneurysmal involvement of the entire descending thoracic aorta (extent C; p < 0.02). Statistically significant predictors for neurologic deficit were the use of the adjunct (odds ratio [OR], 0.19; p = 0.02), previous repaired abdominal aortic aneurysm (OR, 7.0; p = 0.005), type C aneurysm (OR, 13.73; p = 0.02), and cerebrovascular disease history (OR, 4.7; p < 0.03). Thirty-day mortality was 8% (24 of 300 patients). Significant multivariate predictors of 30-day mortality were preoperative renal dysfunction (OR, 4.6; p < 0.01) and female sex (OR, 2.9; p < 0.03). Repairs of the descending thoracic aorta using the adjunct of distal aortic perfusion and cerebrospinal fluid drainage can be performed with a low incidence of neurologic deficit and an acceptable mortality. The use of the adjuncts should be considered during elective repairs of the descending thoracic aorta.


Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria.
Plasmodium sp. are obligate intracellular parasites that derive most of their nutrients from their host meaning the metabolic circuitry of both are intricately linked. We employed untargeted, global mass spectrometry to identify metabolites present in the culture supernatants of P. falciparum-infected red blood cells synchronized at ring, trophozoite and schizont developmental stages. This revealed a temporal regulation in release of a distinct set of metabolites compared with supernatants of non-infected red blood cells. Of the distinct metabolites we identified pipecolic acid to be abundantly present in parasite lysate, infected red blood cells and infected culture supernatant. Further, we performed targeted metabolomics to quantify pipecolic acid concentrations in both the supernatants of red blood cells infected with P. falciparum, as well as in the plasma and infected RBCs of P. berghei-infected mice. Measurable and significant hyperpipecolatemia suggest that pipecolic acid has the potential to be a diagnostic marker for malaria.


Effects of a pre-visit online information tool about genetic counselling for ovarian cancer patients, a randomized controlled trial.
In the Netherlands, patients with ovarian cancer are offered genetic testing. Pre-test preparation may help counseling patients. The aim of this study was to determine if use of a web-based intervention, leads to more effective genetic counseling of ovarian cancer patients. Between 2016 and 2018, 127 ovarian cancer patients referred for genetic counseling in our hospital participated in this trial. 104 Patients were analyzed. All patients filled out questionnaires pre- and post-counseling. The intervention group also completed a questionnaire after visiting an online tool. Length of consultation, patients' satisfaction, knowledge, anxiety, depression and distress were compared before and after counselling. The intervention group had the same level of knowledge compared to the counseling group, but at an earlier point in time. They were satisfied with the intervention (86%) and better prepared for counseling (66%). The intervention did not lead to shorter consultations. No differences in levels of anxiety, depression, distress and satisfaction were observed. Although consultation length was unaffected, the improvements in knowledge after online education and patients satisfaction indicates that this tool can be an effective addition to genetic counseling. Use of an educational tool may lead to a more effective, personalized way of genetic counselling and enables shared decision making.


Research on the Top-Down Parsing Method for Context-Sensitive Graph Grammars.
The parsing problem is one of the key problems of graph grammars. The typical parsing algorithm uses the bottom-up method. The time-complexity of this method is high, and it is difficult to apply. In order to reduce the time-complexity, this paper uses the top-down method for parsing. This method avoids the subgraph isomorphism judgment and selects the productions specifically, so that the time-complexity is greatly reduced.


Involvement of growth hormone-insulin-like growth factor I system in cranial remodeling during halibut metamorphosis as indicated by tissue- and stage-specific receptor gene expression and the presence of growth hormone receptor protein.
The role of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the tissue remodeling associated with the transition of a symmetrical larva to an asymmetrical juvenile during flatfish metamorphosis is unknown. In order to investigate the potential role of these hormones in the remodeling of cranial bone and soft tissue that accompanies eye migration during metamorphosis of Atlantic halibut (Hippoglossus hippoglossus) larvae, tissue-specific gene expression was monitored by in situ hybridization for Atlantic halibut type I growth hormone receptor (hhGHR), type II hhGHR, and insulin-like growth factor-I receptor (hhIGF-IR). Polyclonal antibody generated against the extracellular domain of type I hhGHR was used for the immunohistochemical localization of type I GHR protein. Type I hhGHR, type II hhGHR, and hhIGF-IR mRNA were expressed in fibroblasts, frontal bone osteocytes, and dorsal chondrocytes at the onset of metamorphosis (stage 8), during metamorphic climax (stage 9), and in fully metamorphosed juveniles (stage 10). Type I GHR protein showed similar expression patterns to those of type I hhGHR mRNA, except in chondrocytes in which little GHR protein was detected. The localization of GHR and IGF-IR transcripts and GHR protein in cranial structures that undergo remodeling is intriguing and suggests that, in addition to thyroid hormones, the GH-IGF-I system is involved in morphological transformations during metamorphosis in Atlantic halibut.


Laparoscopic simple enucleation and coagulation on tumor bed using argon beam coagulator for treating small renal cell carcinomas: an animal study followed by clinical application.
The animal experiments of coagulation therapy on the wound tissue bed during partial nephrectomy with an argon beam coagulator were performed on 16 rabbits, which were randomly divided into 4 groups. Groups A and B had renal artery occlusion; the treatment time of coagulation was 4 seconds and 6 seconds, respectively. Groups C and D did not have renal artery occlusion; the treatment time of coagulation was 2 seconds and 4 seconds, respectively. Then 30 clinical operations of laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator were performed. All 16 rabbits successfully underwent the operation. By the histological examination, the scab depth of the wound tissue bed in groups A, B, C, and D were 2.76 ± 0.17 mm, 3.15 ± 0.15 mm, 2.28 ± 0.16 mm and 2.75 ± 0.06 mm, respectively. Group A differed significantly from groups B and C (P=0.012, 0.007), and group D differed significantly from groups B and C (P=0.002, 0.002). In the clinical study, all 30 patients successfully underwent the operation. The mean operative time was 182 minutes, and the mean blood loss was 280 ml. With a median follow-up time of 37 months, neither local recurrence nor distant metastasis was found by computerized tomography scan. Laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator can be considered for treating small renal cell carcinomas. However, the indication of this procedure should be highly selected.


Short-term effects of angiotensin II receptor blockade in patients with primary glomerulonephritis: pilot study.
There is evidence that angiotensin II, the main effector of renin-angiotensin system, plays a crucial role in the pathogenesis of chronic renal injury. Angiotensin II type 1 (AT-1) receptor blockers reduce renin-angiotensin system activity by blocking the receptor, the activation of which is responsible for the majority of deleterious angiotensin II effects. The aim of the present study was to investigate renal and metabolic effects of specific AT-1 receptor blocker-losartan in patients with primary glomerulonephritis. Pilot clinical study. Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland. Fifteen patients aged 43.3 +/- 11.3 years with primary glomerulonephritis confirmed by renal biopsy were studied. Creatinine clearance, urinary excretion of protein and uric acid, urinary activity of N-acetyl-beta-D-glucosaminidase, and serum concentrations of lipids, protein, and uric acid were evaluated before and after 3 months of losartan (Cozaar; Merck Sharp & Dohme, Harlow, Essex, United Kingdom) treatment at a dose of 25 mg daily. We found a significant reduction of urinary excretion of protein (P <.008; average, 32%). Results also revealed a decrease of serum uric acid level (P <.01), probably as a consequence of elevated uric acid urinary excretion (P <.09). No significant changes in creatinine clearance, N-acetyl-beta-D-glucosaminidase activity, protein, or lipid levels were observed. We concluded that losartan treatment at a small dose of 25 mg daily produces antiproteinuric effect without adverse effects, notably with no decrease of glomerular filtration, and simultaneously induces beneficial changes in purine metabolism.


Improved fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study.
The aim of this study was to investigate the effects of lifestyle intervention on the levels of plasminogen activator inhibitor (PAI-1) and fibrinogen in subjects participating in the Finnish Diabetes Prevention Study (DPS). In five DPS centres, 321 subjects with impaired glucose tolerance (intervention group, n=163; control group, n=158) had their PAI-1 and fibrinogen levels measured at baseline and at the 1-year follow-up. Additional 3-year follow-up assessments were carried out in a sample of 97 subjects in one of the DPS centres (Turku). The intervention programme included an intensive lifestyle intervention aiming at weight reduction, healthy diet and increased physical activity. During the first intervention year, PAI-1 decreased by 31% in the intervention group but showed no change in the control group (p<0.0001). In the Turku subgroup, the decrease in PAI-1 persisted throughout the 3-year follow-up. Changes in PAI-1 were associated with the number of lifestyle changes made during the first year (p=0.008). Weight reduction was the most important factor explaining the decrease in PAI-1. Changes in fibrinogen levels did not differ between the groups. In addition to the previously reported reduction in the risk of type 2 diabetes in DPS participants with impaired glucose tolerance, the intensive dietary and exercise intervention had beneficial long-term effects on fibrinolysis as indicated by the reduced levels of PAI-1. These results suggest that elevated PAI-1 levels in obese subjects with impaired glucose tolerance are mostly reversible by lifestyle changes, especially those geared to weight reduction.


The use of covert sensitization and social skills training in the treatment of an obscene telephone caller.
This case study examines the use of covert sensitization and social skills training to treat an obscene telephone caller on a behaviorally-oriented inpatient psychiatric unit. Rapid decreases in penile tumescence associated with obscene telephone calling were obtained after covert sensitization treatment and were maintained at one year follow-up. Social skills training led to a decrease in social anxiety and increase in social behavior. Results support the combined clinical effectiveness of covert sensitization and social skills training for the treatment of obscene telephone calling.


Magnetic stimulation of the brain: starting or stopping.
A very brief magnetic pulse is able to stimulate cortical neurons through the intact scalp. It can elicit movement of a limb by activation of pyramidal cells either directly or via interneurons. When making a voluntary movement, a corresponding program of the task is thought to be compiled beforehand. In patients with ideomotor apraxia who can not perform a task, a lesion of the left hemisphere is frequently found. A magnetic cortical stimulus given directly before a movement is executed is known to delay the onset without altering the pattern. When it will become feasible to deliver a localized stimulus to one hemisphere, this will induce a temporary pause in that area and thus simulating a lesion in intact brain. In this way information can be gathered on the localization of voluntary action in intact brains.


Lack of robust protective effect of quercetin in two types of 6-hydroxydopamine-induced parkinsonian models in rats and dopaminergic cell cultures.
In the present study, we examined the ability of a flavonoid quercetin to prevent 6-hydroxydopamine (6-OHDA)-induced oxygen radical formation and cytotoxicity in vitro and neurotoxicity in vivo. Quercetin (10-100 microM) had an acute significant antioxidant effect against the 6-OHDA-induced (30 microM) oxygen radical formation in catecholaminergic SH-SY5Y neuroblastoma cells. Moreover, in these cells, quercetin at 10-50 microM had a significant protective effect against 6-OHDA though at 100 microM it was itself harmful to the cells. The possible effect of quercetin in preventing neurotoxicity in unilateral medial forebrain bundle (full nigral lesion) or striatal (partial lesion) 6-OHDA rat lesion models of Parkinson's disease was studied in three treatment schedules: a 7-day pre- or post-treatment or their combination. Rotational responses to apomorphine (0.1 mg/kg, subcutaneously) and d-amphetamine (2.5 mg/kg, intraperitoneally) were assessed at weeks 1 and 2 post-lesion. Quercetin had no consistent neuroprotective effect in either model at 50-200 mg/kg once a day or 100 mg/kg twice a day. Furthermore, no protection was observed in tyrosine hydroxylase positive nigral cell numbers, striatal fiber density or in striatal levels of dopamine. These in vitro and in vivo results cast doubt on the theory that quercetin exerts reliable neuroprotective effects against 6-OHDA-induced toxicity. In vitro, quercetin seems to be protective at low doses but damaging at high doses.


Involvement of L3T4+, LYT2.2+ T cell subsets and non-T cells in the resistance of mice against Trypanosoma cruzi infection.
Cellular populations involved in resistance against T. cruzi infection were characterized from mice chronically infected with the parasite. Mice transfused with spleen cells (SC), nylon-wool-non-adherent spleen cells (NWNA) or sera from mice chronically infected with T. cruzi, showed an enhanced resistance against challenge with the parasite. The protective activity of NWNA but not of SC was completely abrogated by treatment with anti-Thy1.2 monoclonal antibodies (mAb) and complement (C). Pretreatment of NWNA cells from chronically infected mice with either anti-L3T4 or anti-Lyt 2.2 mAb partially reduced the transfer of resistance. When both L3T4+ and Lyt2.2+ cells were depleted from NWNA populations, transfer of resistance was abolished. These results appear to indicate that L3T4+, Lyt2.2+ T cell subsets and non-T cells are involved in the immunity to T. cruzi.


Contribution of positively charged flanking residues to the insertion of transmembrane helices into the endoplasmic reticulum.
Positively charged residues located near the cytoplasmic end of hydrophobic segments in membrane proteins promote membrane insertion and formation of transmembrane alpha-helices. A quantitative understanding of this effect has been lacking, however. Here, using an in vitro transcription-translation system to study the insertion of model hydrophobic segments into dog pancreatic rough microsomes, we show that a single Lys or Arg residue typically contributes approximately -0.5 kcal/mol to the apparent free energy of membrane insertion (DeltaG(app)) when placed near the cytoplasmic end of a hydrophobic segment and that stretches of 3-6 Lys residues can contribute significantly to DeltaG(app) from a distance of up to approximately 13 residues away.


Diagnostic and therapeutic impact of PET/CT with 18F-DCFPyL versus 18F-Fluorocholine in initial staging of intermediate-/high-risk prostate cancer: a pilot study.
To assess the diagnostic and therapeutic impact of PET/CT with 18F-DCFPyL with respect to 18F-Fluorocholine in initial staging of intermediate-/high-risk prostate cancer (PCa). Patients with recent diagnosis of intermediate-/high-risk PCa without androgen deprivation therapy and previous 18F-Fluorocholine-PET/CT (negative for extraprostatic disease or with oligometastatic disease) were referred to 18F-DCFPyL-PET/CT. Patients' disease characteristic as grade group, D'Amico risk category (intermediate/high), prostate-specific antigen (PSA) closest to PET/CTs and its kinetics were obtained. The overall detection rate (DR) and molecular imaging TNM (miTNM) stage according to the prostate cancer molecular imaging standardized evaluation (PROMISE) criteria were assessed for both radiotracers, and their concordance (Kappa coefficient) was analyzed. The diagnostic and therapeutic impact of 18F-DCFPyL with respect to 18F-Fluorocholine was evaluated. Fifty-eight patients were analyzed (84.5% high-risk). 18F-Fluorocholine showed a higher DR than 18F-DCFPyL of prostate gland involvement (100% versus 93.1%) and pelvic node disease (37.9% versus 31%; k = 0.436, p = 0.001). On the other hand, 18F-DCFPyL-PET/CT showed a higher DR of metastatic disease than 18F-Fluorocholine-PET/CT, 9/58 patients (15.5%): 3 M1a, 5 M1b and 1 M1c) versus 5/58 (8.6%) patients: 1 M1a and 4 M1b), k = 0.426; p = 0.001. No significant association was found between clinical characteristics (grade group, risk category, PSA level and kinetic) and 18F-Fluorocholine or 18F-DCFPyL results. The results of 18F-DCFPyL-PET/CT modified the previously planned treatment compared to 18F-Fluorocholine-PET/CT in 13 patients (22.4%). 18F-Fluorocholine and 18F-DCFPyL PET/CT showed a similar DR of prostate gland and lymph node involvement, although with moderate concordance for the latter. 18F-DCFPyL was superior to 18F-Fluorocholine in detecting regional and distant metastasis with a therapeutic impact in one of every five patients.


The effect of semaphorin 3A on fracture healing in osteoporotic rats.
Semaphorin 3A (Sema3A) was demonstrated to exert an osteoprotective effect by both inhibiting osteoclastic bone resorption and promoting osteoblastic bone formation. The effect of Sema3A on fracture healing of osteoporotic rats was investigated in this study. Twelve weeks after bilateral ovariectomy, all animals underwent unilateral transverse osteotomy on the proximal tibiae, and were then randomly divided into two groups. Rats received vehicle (control) or weekly local injection of Sema3A (500 μg/kg) into the injury site (group Sema3A) after fracture surgery until sacrifice at 4 and 8 weeks. Specimens were harvested and examined by radiography, iDXA, histology, micro-CT, and three-point bending test. Compared to control, Sema3A treatment significantly increased bone mineral density, percent bone volume and biomechanical strength of the callus at 4 and 8 weeks post-fracture. At 8 weeks after fracture, the bone volume of callus showed no difference between groups, while the average cross-sectional area of callus in the control group was 43.8 % higher than that of Sema3A group. Histological images showed increased callus formation at 4 weeks post-fracture and better callus ossification in the Sema3A group, while callus remodeling in the control group seemed to be delayed and not well bridged. Results in this study indicated that Sema3A treatment increased callus volume and density at 4 weeks post-fracture, and induced promoted callus ossification and remodeling at 8 weeks post-fracture compared to control.


Chemotherapy of mammary carcinomas arising in ras transgenic mice.
Transgenic female mice carrying the V-Ha-ras transgene linked to the MMTV promoter, which developed mammary carcinomas, were treated with selected cancer chemotherapy drugs. Agents were administered i.p. on a daily x 9 schedule when mice developed tumors that were 50-100 mg in size. Drugs which are clinically effective against breast cancer were quite efficacious in the transgenic model at their maximum tolerated dose. Doxorubicin produced excellent responses in tumor-bearing transgenic mice, with several mammary carcinomas undergoing tumor shrinkage. Two anthrapyrazoles, DuP 937 and DuP 941, novel anticancer drugs with phase 2 activity against breast cancer, were as effective as doxorubicin in the oncomice. Mitoxantrone, a synthetic agent with some properties similar to the anthracyclines, also had antitumor activity, but not as pronounced as obtained with doxorubicin or the anthrapyrazoles. Cisplatin, a drug with limited use in human breast cancer, only caused modest antitumor responses. A computerized data analysis method based on the area under the tumor growth curve was developed to better quantitate the data and provide statistical information. This quantitative analysis confirmed the high statistical significance of the activity of doxorubicin or the anthrapyrazoles in the ras transgenic model, and defined an excellent dose response relationship for each drug tested. Our results suggest that the ras transgenic model may be useful for identifying drugs that have efficacy for breast cancer in women.


Quantitation of photochemically induced focal cerebral ischemia in the rat.
This study was carried out with a recently developed model of focal cerebral ischemia in the rat based on the photochemical induction of thrombotic stroke using the dye Rose Bengal. We examined the change in the volume of the lesion and brain water content, in separate groups of rats, at different times (1, 4, 24, 72, and 168 h) after the induction of the ischemic lesion. The volume of ischemic damage increased rapidly between 1 and 24 h after the ischemic insult and decreased between 24 and 168 h. The lesion at 168 h was significantly larger than that following 1 h of ischemia and similar to that obtained at 4 h, suggesting that the maximum extent of tissue damage (without the involvement of significant edema) was reached within the first 4 h in this model. The enlargement of the lesion after 4 h correlated closely with changes in brain water content.


Trials of treating myocarditis in mice infected with coxsackie B3 viruses.
On the assumption of an immunologic background of chronic myocarditis after infection with Coxsackie B3 viruses, mice were treated with prednisolone or cyclophosphamide, starting 18 days after infection, for periods of three months. The favorable therapeutic effect indicates that chronic myocarditis is an immunologic disease.


[Robotic sacrocolpopexy - two case reports and literature overview].
To describe first two cases of robotic sacrocolpopexy in the Czech Republic. Two case reports with literature overview. Department of Obstetrics and Gynaecology, Faculty of Medicine and Dentistry, Palacky University in Olomouc. Robotic sacrocolpopexy was performed in two patients of the age 36 and 59 at the department of obstetrics and gynecology in Olomouc in 2009. We describe vaginal prolapse treatment in one case, and supracervical hysterectomy with cervicosacropexy in the other. These two cases are compared with literature overview, including long-term follow-up. Robotic sacrocolpopexy encompasses all advantages of minimally invasive surgery. Our results, as well as published data show very good long term results of vaginal prolapse treatment using this approach.


Health effects related to releases of hazardous substances on the Superfund priority list.
The Agency for Toxic Substances and Disease Registry maintains an active, state-based surveillance system to record the public health consequences of hazardous substance releases. During 1992, the 9 participating states reported 1,876 events; 80% of the events occurred at fixed facilities, and 20% were transportation related. The most frequently released substances were volatile organic compounds, acids, herbicides, and ammonia. In 263 events, 600 people were injured and 4 died. Employees were injured more frequently (71%) than first responders or the general public. The most frequently reported injuries were respiratory and eye irritation. Evacuations occurred in 13% of the events. These results provide information for preparedness planning and training of first responders and employees.


Emergency burn education: Evaluating a surgical simulation-based intervention.
Medical simulation has provided favorable outcomes in the improvement of clinical competence at both the undergraduate and postgraduate levels. The recall of information demonstrably increases when it has been taught in environments similar to the workplace. This study aimed to evaluate the role of a one-day burn simulation session in improving students' knowledge of burn management and interest in plastic surgery as a specialty. A one-day course was designed to deliver multiple lectures covering surgical topics such as the classification and management of burns, followed by a series of practical workshops. Participants were instructed to undergo a pre-course knowledge assessment and a survey focusing on interest in plastic surgery. Students were subsequently instructed to complete a post-course assessment and a survey of knowledge and confidence in managing burns as well as interest in plastic surgery both immediately and 6 weeks post-course. The students' knowledge demonstrated a 54.2% increase in the post-course assessment (p < 0.01). 27% of participants (n = 14) participated in a 6-week post-course quiz. The knowledge assessment of these participants at 6 weeks post-course also demonstrated a sustained increase of 61.0% (p < 0.01). Interest in plastic surgery was increased by 31.4% post-course (p < 0.01). At 6 weeks post-course, a sustained increase of 14.7% was demonstrated in comparison to pre-course data (p = 0.03). Simulation teaching provides good outcomes in both information retention and interest in plastic surgery as a specialty. Therefore, medical school curriculums may benefit from including burn simulations.


The basic property of biomembranes: an explanation for the geometric progression of vesicles.
In order to explain the experimentally obtained results with biomembranes it has been assumed, that the diameter of all vesicles, defined by a lipid bilayer, form a perfect crystal. Later on it appeared that biomembranes are liquid crystals. Nevertheless already with biomembranes as crystals it was possible to calculate the diameters of all existing vesicles. As shown in the present paper, the results with liquid crystals were identical to those with a perfect crystal-model. Here I demonstrate that the geometric progression of the diameters of vesicles of biomembranes is based on the entropy of the lipids and it is shown that the diameters of biomembranes fit four geometric series. The surface areas of these series of biomembranes can be approximated by the two geometric series published previously.


Urticaria and Allergy-Mediated Conditions.
Urticaria is a common condition that involves pruritic, raised skin wheals. Although urticaria is a benign, self-limiting condition, it may cause frustration for patients, often because of its chronicity and its tendency to recur. It can also be a life-threatening allergic reaction. Diagnosis is made clinically. It affects 20% of the general population. The first-line treatment for nonremitting cases includes H-1anti-histamines. However, other therapies may be employed. Other allergy-mediated skin conditions include angioedema, contact dermatitis, and atopic dermatitis. Diagnosis is clinical, and management focuses on prevention, avoiding triggers, and treating the itching and inflammation that accompany these conditions.


General morphology and axonal ultrastructure of the olfactory nerve of the pike, Esox lucius.
The olfactory nerve of the European pike (Esox lucius) contains 5.1 X 10(6) axons with an average diameter of 0.20+/-0,04 micron and a length of 5.5 cm in 1 meter long pike. Each axon contains an average of 4 microtubules as well as neurofilaments, smooth endoplasmic reticulum and about 500 mitochondria per centimeter. The number of neurofilaments ranges from zero in 15% of the cross sections to over 10 in 6%. Neurofilaments generally occur in clusters located opposite to microtubule regions. Smooth ER can not be identified in 14% of the cross sections suggesting that this structure may not be continuous. Microtubules often display annular regions (halos) of low electron density ranging in size from 800 to 1300 A. Halos from adjacent tubules usually merge into regional halos. The ratio of axoplasm to glial cytoplasm is 4.4:1, while the ratio of axonal plasma membrane to glial plasma membrane exceeds 7:1. A 4 cm nerve contains 1280 cm2 of axolemma. This nerve represents an extreme in high density axonal packing and is therefore exceptionally well suited for biochemical, biophysical and physiological investigations.


Estimated or Measured GFR in Living Kidney Donors Work-up?
The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web-based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD-EPI) and on MDRD-eGFR. GFR was measured using 51 Cr- ethylene-diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web-based tool was used to predict those with mGFR < 80 mL/min/1.73 m2 . Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web-based probability of mGFR <90 mL/min/1.73 m2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m2 . The positive predictive value was 0.19. A CKD-EPI-eGFR threshold of 104 mL/min/1.73 m2 and an MDRD-eGFR threshold of 100 mL/min/1.73 m2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m2 . We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web-based application to identify potential donors who should benefit from GFR measurement.


Isozyme variation and heterozygosity in Pinus halepensis L.
The genetic polymorphism of a population of Pinus halepensis was studied using 12 electrophoretically detectable enzyme systems encoded by 7 monomorphic and 10 polymorphic loci. An estimation of population parameters revealed a relatively high average heterozygosity (H = 0.179). The total variation present in the population was partitioned into a high amount of genetic variation within groups, with only 1.3-4.4% of the total variation resulting from genic differences among groups.


Sub-hourly measurement datasets from 6 real buildings: Energy use and indoor climate.
The data presented here were collected independently for 6 real buildings by researchers of different institutions and gathered in the context of the IEA EBC Annex 81 Data-driven Smart Buildings, as a joint effort to compile a diverse range of datasets suitable for advanced control applications of indoor climate and energy use in buildings. The data were acquired by energy meters, both consumption and PV generation, and sensors of technical installation and indoor climate variables, such as temperature, flow rate, relative humidity, CO2 level, illuminance. Weather variables were either acquired by local sensors or obtained from a close by meteorological station. The data were collected either during normal operation of the building, with observation periods between 2 weeks and 2 months, or during experiments designed to excite the thermal mass of the building, with observation periods of approximately one week. The data have a time resolution varying between 1 min and 15 min; in some case the highest resolution data are also averaged at larger intervals, up to 30 min.


A Chip-Scale Oscillation-Mode Optomechanical Inertial Sensor Near the Thermodynamical Limits.
Modern navigation systems integrate the global positioning system (GPS) with an inertial navigation system (INS), which complement each other for correct attitude and velocity determination. The core of the INS integrates accelerometers and gyroscopes used to measure forces and angular rate in the vehicular inertial reference frame. With the help of gyroscopes and by integrating the acceleration to compute velocity and distance, precision and compact accelerometers with sufficient accuracy can provide small-error location determination. Solid-state implementations, through coherent readout, can provide a platform for high performance acceleration detection. In contrast to prior accelerometers using piezoelectric or capacitive readout techniques, optical readout provides narrow-linewidth high-sensitivity laser detection along with low-noise resonant optomechanical transduction near the thermodynamical limits. Here an optomechanical inertial sensor with an 8.2 μg Hz-1/2 velocity random walk (VRW) at an acquisition rate of 100 Hz and 50.9 μg bias instability is demonstrated, suitable for applications, such as, inertial navigation, inclination sensing, platform stabilization, and/or wearable device motion detection. Driven into optomechanical sustained-oscillation, the slot photonic crystal cavity provides radio-frequency readout of the optically-driven transduction with an enhanced 625 μg Hz-1 sensitivity. Measuring the optomechanically-stiffened oscillation shift, instead of the optical transmission shift, provides a 220× VRW enhancement over pre-oscillation mode detection.


Time from first clinical contact to abortion in Texas and California.
To assess whether having an abortion in Texas, a U.S. state with many restrictive abortion laws, is associated with increased time between contacting an abortion provider and receiving an abortion, compared to having an abortion in California, a less restrictive U.S. state. This is a multisite, cross-sectional survey of 434 patients in 12 abortion facilities (ambulatory surgical centers and clinics) in Texas (n = 291) and three abortion clinics in California (n = 143) from 2018 to 2019. At 11 facilities in Texas the response rate was 76%. The response rate was not collected at other sites. We compare the clinical-contact-to-abortion time interval between the facilities in these two states using mixed-effects multivariable logistic regression, adjusting for age, race, education, household income, parity, marital status, and insurance status. We also compare barriers to scheduling and traveling to abortion appointments. Median clinical-contact-to-abortion time is similar among respondents in Texas and California [(9 vs 8 days, p = 0.86). The odds of having a clinical-contact-to-abortion time ≥7 days is similar among respondents in Texas compared to California (adjusted odds ratio 1.0 (95% confidence interval, 0.4-2.6, p = 0.98). Respondents in Texas travel farther for their abortion (mean 22.1 vs 13.5 miles, p < 0.01), are more likely to sell something of value or delay paying another expense to pay for their abortion (49.7% vs 11.4%, p < 0.01), and to miss work to attend their abortion (73.9% vs 61.3%, p = 0.03). In this study, we found no difference in clinical-contact-to-abortion time between respondents in Texas and those in California. Respondents in Texas, however, face other significant barriers in obtaining abortion care, which result in life disruptions and financial hardship. Patients face greater financial barriers when seeking abortion in Texas compared to California. Though we found no significant difference in clinical-contact-to-abortion time in this sample between the two states, clinical-contact-to-abortion time may be a useful measure of facility congestion and the obstacles patients face obtaining abortion care.


Racial and ethnic differences in human papillomavirus positivity and risk factors among low-income women in Federally Qualified Health Centers in the United States.
Reasons for racial/ethnic disparities in HPV infection are unclear. This study assessed racial/ethnic differences in and risk factors for HPV positivity among low-income women. Data were collected from 984 low-income women visiting Federally Qualified Health Centers across Illinois (2009-2011). Pearson chi square and Logistic regression analyses were used to examine associations with HPV positivity. Our results showed Mexican-born Hispanics had the lowest HPV positivity (16%), followed by non-Hispanic whites (29%), US-born Hispanics (35%), and non-Hispanic blacks (39%). Mexican-born Hispanics reported fewer risk behaviors for HPV positivity, including first sexual intercourse before age 16 years (9% versus 27%), multiple sexual partners in lifetime (48% versus 90%), and current cigarette smoking status (10% versus 35%) when compared to non-Hispanic whites (p<0.001). In multivariate-adjusted logistic regression, being non-Hispanic black, first sexual intercourse before age 16 years, increasing numbers of recent or lifetime sexual partners and current cigarette smoking status were associated with a higher likelihood of HPV positivity. Our findings highlight racial/ethnic differences in HPV positivity and risk factors in a population of women with similar socioeconomic characteristics. When measuring HPV risk factors within the Hispanic population, foreign-born status and other mediating factors, such as social norms and cultural characteristics, may be relevant to assess the intragroup heterogeneity.