Measuring inter-rater reliability of the sequenced performance inventory and reflective assessment of learning (SPIRAL).
To measure the inter-rater reliability of the Sequenced Performance Inventory and Reflective Assessment of Learning (SPIRAL), a twenty-three item scoring rubric designed to assess first and second-year students' competencies such as "acquisition of knowledge," "peer teaching and communication skills," and "professional behavior" in a problem-based learning (PBL) curriculum at the University of North Dakota School of Medicine and Health Sciences. In 2001, the authors constructed a 69-item multiple-choice questionnaire consisting of descriptions of "prototypical" (representing real students) PBL student performances. For each of the 23 SPIRAL items, the authors chose competency descriptions of an "emerging," a "developing," and an "advanced" student (69 prototypical students). These descriptions were obtained from narrative comments by PBL facilitators of real students in their classes in 2000-2001. Seventeen experienced facilitators (PBL tutors) were subsequently asked to rank the 69 prototypical students based on SPIRAL anchor points in the three competency levels. Kendall's coefficient of concordance was used to test inter-rater reliability. Modes were also determined to illustrate the extent to which the ratings of the 17 facilitators aligned with the ratings anticipated by the authors. Overall, inter-rater scoring for all items combined was considered to be reliable (Kendall's coefficient of concordance W =.75). Inter-rater scoring was also determined for each of the 23 SPIRAL items, with Ws ranging from.97 to.53. Facilitators rated students according to 55 of the 69 SPIRAL descriptors as the researchers anticipated. The scoring rubric is reliable. Further criterion-related validation study is warranted.


Methotrexate in acute persistent humoral rejection: an option for graft rescue.
Humoral response emerges as an important component in acute graft rejection and a new challenge to clinicians in posttransplant care. Management of recurrent episodes and persistent activation of the humoral component of the immune system, despite the usual therapeutic approach to rejection, remains unknown. This article describes the successful use of methotrexate as an option for rescuing a graft in this worrisome situation.


Carbonic anhydrase inhibition and cerebral cortical oxygenation in the rat.
We report here the results of our study of the carbonic anhydrase inhibitor acetazolamide on cerebral vascular and metabolic function, correlated with the effects of this agent on systemic arterial blood gases and pH. We found that the effects of acetazolamide were to increase PaO2, decrease bicarbonate ion concentration and decrease pH. While these effects were maintained for many hours after both high and low dose acetazolamide, the cerebral metabolic and vascular effects of the drug were transient. The central effects of carbonic anhydrase inhibition were consistent with increased oxygen delivery and increased tissue oxygenation. Hypoxia such as encountered at altitude, represents a challenge to the mechanisms which control blood flow in the brain. The decreased arterial oxygen content at altitude is a ventilatory drive which has the effect of 1) increasing somewhat the PaO2; 2) decreasing the PaCO2; 3) alkalinizing the blood. The decreased PaCO2 then leads to decreased CBF compounding the problem of hypoxemia. In this situation, increasing CBF helps to relieve the tissue hypoxia. This has been done by either increased inhalation of CO2 (Harvey et al., 1988) or by acetazolamide (Cain and Dunn, 1966; Forwand et al., 1968). A common feature in both treatments might be increased tissue CO2 retention (Kjällquist et al., 1969; Meyer et al., 1961) and tissue acidification (Heuser et al., 1975). The two treatments are not identical since acetazolamide seems to have additional effects on cerebral metabolism that elevated CO2 does not. Thus, we can deduce that the primary pathologic effects of acute hypoxia are due to the decreased cerebral blood flow produced by hyperventilation-induced hypocapnia.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of spontaneous diabetes mellitus on fatty acid oxidation, beta-hydroxybutyrate dehydrogenase activity and respiratory coupling of hepatic mitochondria in the guinea-pig (Cavia porcellus).
1. The purpose of this study was to determine whether hepatic mitochondria of guinea-pigs with spontaneous diabetes mellitus differ from those of non-diabetic guinea-pigs in the oxidation of fatty acids, the activity of beta-hydroxybutyrate dehydrogenase, or respiration-linked oxidative phosphorylation. During the course of the study, a third group of animals (referred to as the unclassified group) was discovered which, on the basis of the clinical chemistry and histological changes in the pancreas, appeared to be in a pre-diabetic or post-diabetic state. 2. No differences in the respiratory control ratios were found between any of the three groups. Fatty-acid oxidation in hepatic mitochondria was greater in both the unclassified and diabetic groups than in the non-diabetic group. Beta-Hydroxybutyrate dehydrogenase activity, however, was increased only in the diabetic group. These findings suggest that increased fatty acid oxidation is probably an intermediate change in the development of or the recovery from diabetes mellitus, whereas the activity of beta-hydroxybutyrate dehydrogenase is affected only in more advanced stages.


Primary tubercular psoas abscess: a rare presentation.
Primary tubercular psoas abscess is a rare clinical entity and has seldom been reported in an otherwise healthy person. Here we report an interesting case of primary tubercular psoas abscess in an immunocompetent male with no other traceable source.


Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population.
Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource. We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue. By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis.


Effect of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension.
Acute sublingual administration of nifedipine 10--20 mg to 13 hypertensive patients caused a rapid decrease in blood pressure (BP) and a concomitant increase in heart rate (HR), plasma noradrenaline (NA) and plasma renin activity (PRA); there was no significant change in plasma adrenaline (A) or aldosterone (ALDO). Basal PRA was the major determinant of the rise in PRA, as a close correlation was present between the basal value and the increase caused by nifedipine (r = 0.92), p less than 0.001). The rise in PRA was also correlated with the plasma concentration of nifedipine after 60 min (r = 0.80, p less than 0.01), but it was not correlated with the decrease in BP, the rise in HR or the increase in NA. Nifedipine 30--60 mg daily for 6 weeks caused a reduction in mean BP from 133 to 113 mmHg (p less than 0.001). Body weight and serum potassium decreased but no consistent change was noted in NA, PRA, ALDO or 24 h-excretion of catecholamines. A significant correlation was present between the change in NA and that in PRA (r = 0.74, p less than 0.01). The alterations in the various parameters in the acute and chronic studies were not correlated. The findings indicate that different regulatory mechanisms are activated during acute and chronic administration of nifedipine. It is suggested that an initial rise in sympathetic activity gradually decreases during prolonged therapy, but it still remains a determinant of PRA.


The use of corticosteroids in patients with COPD or asthma does not decrease lung squamous cell carcinoma.
Asthma and COPD (chronic obstructive pulmonary disease) lead to persistent airway inflammation and are associated with lung cancer. The objective of the study was to assess the relationship between inhaled (ICS) and oral corticosteroid (OCS) use, and risk of lung squamous cell carcinoma (SqCC). This study was a nested case-control study. Patients with newly diagnosed asthma or COPD between 2003 and 2010 were identified from the National Health Insurance Database. Cases were defined as patients diagnosed with SqCC after enrollment. For each case, four control individuals who were randomly matched for sex and age and date diagnosis of asthma or COPD were selected. From the 1,672,455 eligible participants, 793 patients with SqCC were matched with 3,172 controls. The odds ratios (ORs) of SqCC in men who received high and low-dose ICS were 2.18 (95 %CI, 1.56-3.04) and 1.77 (1.22-2.57), respectively. Similarly, the ORs were 1.46 (95 %CI, 1.16-1.84) and 1.55 (95 %CI, 1.22-1.98) for men who were placed on low and high dose OCS. However, there was no significant association between cumulative ICS and/or OCS and risk of SqCC in women. Recent dose increase in corticosteroid was significantly associated with risk of SqCC. Specifically, among men, the ORs for SqCC were 8.08 (95 %CI, 3.22-20.30) for high-dose ICS + OCS, 4.49 (95 % CI, 2.05-9.85) for high-dose ICS, and 3.54 (95 % CI, 2.50-5.01) for high-dose OCS treatments, respectively. The OR for SqCC in women who received high-dose OCS was 6.72 (95 %CI, 2.69-16.81). Corticosteroid use did not decrease SqCC in patients with asthma or COPD. Recent dose increase in corticosteroids was associated with SqCC.


Glucose-sensitive adenylate cyclase in toluene-treated cells of Escherichia coli B.
Toluene treatment of Escherichia coli B makes it possible to measure adenylate cyclase activity directly using [alpha-32-P]-ATP as substrate. In contrast to French press extracts, the activity of adenylate cyclase in toluene-treated cells shows many of the characteristics of the enzyme seen in the intact cell. In both toluene-treated and intact cells the activity of adenylate cyclase is inhibited at least 85% by glucose, while in French press extracts the enzyme activity is much lower and is not sensitive to inhibition by glucose. In toluene-treated cells, glucose inhibits at 10 muM, and the effect is rapid in onset and readily reversible. The activity is not inhibited by glucose 6-phosphate suggesting that glucose is responsible for the inhibition. The measurement of the activity and sensitivity to glucose of adenylate cyclase in toluene-treated cells requires the presence of potassium phosphate in the assay medium. Since it does not increase the activity or sensitivity of the enzyme in the French press extract, it is suggested that potassium phosphate is required for the maintenance of cellular integrity necessary for the activity and sensitivity of adenylate cyclase.


Morphology of the ovary of Caiman crocodilus (Crocodylia: Alligatoridae).
We describe the ovarian histology and characterize the folliculogenesis of adult females of Caiman crocodilus in order to compare them with other species of Reptilia. The gonad has a thin irregular cortex and a well-developed reticular stroma, composed of vascularized chordae, drained by large lymphatic vessels and separated by extensive lacunae. Simple cuboidal to squamous epithelium, dense connective tissue with numerous elastin fibers, and smooth muscle constitute the ovarian wall. This morphology is similar to that of other Crocodylia, Aves and Testudines. Germinal nests are distributed in the ovarian cortex, some of them with oogonia. Oocytes leave the germinal nests with a single layered cuboidal granulosa, remaining simple during vitellogenesis, as in other Archosauria and Testudines and different from Squamata. As the oocyte grows, the theca is formed by numerous fibroblasts, collagen fibers, and smooth muscle fibers, becoming very thick, highly vascularized and developing muscle bands at advanced vitellogenesis. Folliculogenesis shares morphological features with other species of Reptilia. The corpus luteum is similar to that described for Archosauria; during luteolysis, the theca shrinks and the amount of luteinic cells decreases. The relationship of the corpus luteum to vitellogenesis and egg maintenance is unclear in Crocodylia. Follicular regression in Caiman crocodilus corresponds to an invasive atresia type. Histological features seen in the ovary of Caiman crocodilus are similar to those described in Alligator mississippiensis indicating that these features could be shared among Crocodylia. Also several of these morphological characteristics are observed in Aves suggesting a similar reproductive functional morphology in Archosauria.


Mitochondrial calcium release as induced by Hg2+.
Addition of Hg2+ to mitochondria of rat kidney induces efflux of intramitochondrial Ca2+. This reaction is accompanied by a diminution of the NAD(P)H/NAD(P) ratio and a decrease of the internal negative membrane potential. These effects were enhanced by dithiothreitol. The binding of mercuric ions to mitochondria saturates with a maximal binding of 9 nmol min-1 mg-1. The stoichiometry between Ca2+ released and Hg2+ bound showed that in the presence of dithiothreitol, the binding of approximately 1 nmol of Hg2+/mg of protein suffices to induce the release of the accumulated Ca2+. In the electrophoretic analysis of Hg-labeled mitochondrial proteins it was found that 203Hg2+ bound mainly to proteins that have molecular masses of 20 and 30 kDa. It is proposed that Hg2+-induced Ca2+ release is due to modification of--SH groups of these latter proteins.


Surface modification on polyethylene terephthalate films with 2-methacryloyloxyethyl phosphorylcholine.
In this study, the surface of polyethylene terephthalate (PET) was modified to improve the protein and cell adhesion behavior with low temperature ammonia plasma treatment followed by 2-methacryloyloxyethyl phosphorylcholine (MPC) grafting. The x-ray photoelectron spectroscopy (XPS) results showed that the -COO(-), -N-C=O and -P-O-H groups were successfully incorporated onto the sample surface after MPC grafting. Furthermore, formation of new bonds, -N= and N-H on the sample surface grafted with MPC was recorded by Fourier transform infrared spectroscopy (FTIR). A large number of spherical particles at submicron to nanometer scale were also observed on the surface by atomic force microscopy (AFM). The cell adhesion experiments on PET film surfaces were evaluated and the highly hydrophilic surfaces could not promote cell adhesion and spreading. All results achieved in this study have clearly indicated that the method combining low temperature ammonia plasma treatment and MPC grafting is an effective way of producing a suitably hydrophilic PET surface with the capability of weakening the protein adsorption greatly.


Impaired antioxidant defense in hemoglobin E-containing erythrocytes: a mechanism protective against malaria?
Red blood cell (RBC) antioxidant defense was investigated in eight individuals with hemoglobin E (Six EE and two E-B(+) thalassemia) and compared to that in six individuals with thalassemia and ten normal subjects. Individuals with hemoglobin E had increased incubated Heinz body formation (68% +/- 18%; p less than 0.001) compared to normal and thalassemic RBC (10% +/- 2% and 11% +/- 5%, respectively). Stimulated pentose phosphate shunt activity was increased in the thalassemic and decreased in the hemoglobin E RBC as compared to normal. The 2,3-diphosphoglycerate (DPG) content of the EE RBC was increased to 5.59 +/- 0.69 mumol/ml RBC as compared to normal (4.51 +/- 0.77; p less than 0.001). In the EE RBC, there was a direct correlation between Heinz body formation and DPG content (r = 0.73). Ascorbic and dehydroascorbic acid (0.1 and 1.0 mM) were able to decrease the degree of Heinz body formation in the hemoglobin E RBC. Ascorbic acid (0.1 mM) prolonged the response of the pentose shunt. Thus impaired antioxidant defense may account for the persistence of the hemoglobin E gene in areas where malaria is endemic. Oxidant medications should be used with caution in individuals of Southeast Asian origin.


Acute post-streptococcal polymyalgia: two new cases with a review of the literature.
Two patients with acute post-streptococcal polymyalgia are described with a review of the seven cases previously reported cases. The common features are sudden onset of muscular pain with fever usually after an acute upper respiratory tract infection. Antistreptolysin O titre and inflammatory indexes are increased and muscle enzymes are normal. Acute post-streptococcal polymyalgia should be considered as a possible diagnosis in every child complaining acute polymyalgia.


Reporting neural activity with genetically encoded calcium indicators.
Genetically encoded calcium indicators (GECIs), based on recombinant fluorescent proteins, have been engineered to observe calcium transients in living cells and organisms. Through observation of calcium, these indicators also report neural activity. We review progress in GECI construction and application, particularly toward in vivo monitoring of sparse action potentials (APs). We summarize the extrinsic and intrinsic factors that influence GECI performance. A simple model of GECI response to AP firing demonstrates the relative significance of these factors. We recommend a standardized protocol for evaluating GECIs in a physiologically relevant context. A potential method of simultaneous optical control and recording of neuronal circuits is presented.


Mechanism of induction of hypercalcemia and hyperphosphatemia by lead acetate in the rat.
The present study is an investigation of the mechanism of hypercalcemia and hyperphosphatemia induced by the intravenous injection of lead acetate (Pb-Ac). A total of 118 male rats were injected with 30 mg/kg of Pb-Ac, or with 16.5 mg/kg of sodium acetate as the control. The levels of serum calcium, phosphorus and lead were then determined at various time periods after the injections. Serum calcium and phosphorus levels increased with time after Pb-Ac injection and the maximum values of calcium (17 mg%) were found after 1 h and of phosphorus (13.5 mg%) after 30 min. Both calcium and phosphorus levels reverted to the normal range after 12 h. The maximum net rates of increase of calcium and phosphorus were found immediately after Pb-Ac injection. At that time, deposition of lead at the calcifying sites of bone and incisor dentin was demonstrated by a histochemical examination. In other experiments the changes in the calcium and phosphorus contents in the medium after shaking bone powder in serum with Pb-Ac in an in vitro system were studied. It was confirmed that the calcium and phosphorus were displaced from the bone mineral, the extent of the displacement being correlated with the concentration of the Pb-Ac added to the medium, and that these displacements were very rapid reactions. These results suggest that hypercalcemia and hyperphosphatemia following Pb-Ac injection results from a direct action of lead on the bone mineral.


Modulation of attention in discrimination learning: the roles of stimulus relevance and stimulus-outcome correlation.
The advantage in learning after an intradimensional shift rather than an extradimensional shift has been widely used as a behavioural marker of attentional changes during discrimination learning in different fields of neuroscientific study. However, some of the factors assumed to guide these attentional changes have not been completely disentangled by previous research. In two predictive-learning experiments, we investigated the importance of stimulus relevance and of stimulus-outcome correlation for the modulation of attention. In each experiment, participants were trained on two discrimination problems given in successive order. Each problem required participants to differentiate stimuli varying on two dimensions. We found that acquisition of the second discrimination was influenced by whether its relevant dimension (Exp. 1) or its irrelevant dimension (Exp. 2) had previously been trained as relevant and uncorrelated or as irrelevant and uncorrelated. We also observed that acquisition of the second discrimination was independent of whether its relevant dimension (Exp. 1) or its irrelevant dimension (Exp. 2) had previously been trained as relevant and uncorrelated or as relevant and correlated. Our results indicated that the modulation of attention is guided by stimulus relevance and not by stimulus-outcome correlation.


Principles of Molecular Utility for CMS Classification in Colorectal Cancer Management.
Colorectal cancer (CRC) is the second cause of cancer-related deaths in both sexes globally and presents different clinical outcomes that are described by a range of genomic and epigenomic alterations. Despite the advancements in CRC screening plans and treatment strategies, the prognosis of CRC is dismal. In the last two decades, molecular biomarkers predictive of prognosis have been identified in CRC, although biomarkers predictive of treatment response are only available for specific biological drugs used in stage IV CRC. Translational clinical trials mainly based on "omic" strategies allowed a better understanding of the biological heterogeneity of CRCs. These studies were able to classify CRCs into subtypes mainly related to prognosis, recurrence risk, and, to some extent, also to treatment response. Accordingly, the comprehensive molecular characterizations of CRCs, including The Cancer Genome Atlas (TCGA) and consensus molecular subtype (CMS) classifications, were presented to improve the comprehension of the genomic and epigenomic landscapes of CRCs for a better patient management. The CMS classification obtained by the CRC subtyping consortium categorizes CRC into four consensus molecular subtypes (CMS1-4) characterized by different prognoses. In this review, we discussed the CMS classification in different settings with a focus on its relationships with precursor lesions, tumor immunophenotype, and gut microbiota, as well as on its role in predicting prognosis and/or response to pharmacological treatments, as a crucial step towards precision medicine.


Sensorimotor and cognitive slowing in schizophrenia as measured by the Symbol Digit Substitution Test.
A vast amount of studies demonstrates the presence of psychomotor slowing in schizophrenia. The objective of the present study was to investigate whether this overall psychomotor slowing can be divided into distinct processes that differentially affect cognitive functioning in schizophrenia. The pen-tip movements of 30 schizophrenic inpatients and 30 matched controls were digitally recorded during performance of the Symbol Digit Substitution Test (SDST) and analysed to differentiate matching time and writing time, representing the cognitive and sensorimotor component of slowing, respectively. In addition, the results were compared to each other and to the scores of traditional neuropsychological tests that assess domains such as memory and attention. Both matching time and writing time were longer in the schizophrenic patients relative to the controls but did not correlate. Only matching time correlated significantly with the conventional neuropsychological test results. Although schizophrenic patients display both sensorimotor and cognitive slowing, the two processes are unrelated. Furthermore, only the cognitive component was associated with most of the cognitive deficits as measured by traditional neuropsychological tests.


Determination of sex steroid receptor in human basal cell carcinoma.
The role of estrogens in the development of skin cancer is controversial. Sex steroids have a profound effect on the epidermis and epidermal appendages. Estradiol in pharmacologic doses has been reported to stimulate basal cell carcinoma in an animal model. Sex hormones act by means of a specific protein receptor. In this study we used a specific, highly sensitive monoclonal antibody to evaluate sex steroid receptors in human basal cell carcinoma. No estrogen or progesterone receptor protein was detected in the basal cell tumor, despite clear positive control tissues. We conclude that these sex steroid receptors are not present in significant amounts to mediate a direct effect in basal carcinoma.


Grazing resistance in nutrient-stressed phytoplankton.
Grazing experiments were performed with the zooplankters Daphnia pulex and Daphnia magna, feeding on phosphorus-saturated and phosphorus-limited cells of two green algae (Scenedesmus subspicatus and Selenastrum capricornutum). P-limited algal cells passed largely intact through the gut and were thus spared from heavy grazing pressure. P-saturated algal cells, in contrast, were efficiently assimilated. Structural and morphological changes in the P-limited cells most probably reduced their digestibility. This phenomenon may be an important factor in zooplankton production and competition, and may serve as an example of a highly efficient strategy of P-limited algae to resist heavy grazing pressure.


Phalloplasty using the free radial forearm flap.
Our experience of phalloplasty using the radial forearm flap in five transsexual cases is reported. The results are disappointing due to the high incidence of complications. We had partial success in two cases, both complicated by a fistula, and complete failure in three cases due to vascular thrombosis.


Effectiveness of the self-fatigue assessment in guiding early postoperative ambulation in gynaecological oncology patients: study protocol for a randomised controlled trial.
Enhanced recovery after surgery (ERAS) guidelines strongly recommends that patients be in early postoperative ambulation within 24 hours. This study aims to assess the effectiveness and safety of the self-fatigue assessment method to guide patients' early postoperative ambulation. This is a single-centre, randomised, open, parallel-controlled trial. Five hundred and fifty-two patients who meet the inclusion criteria for gynaecological oncology surgery are randomly assigned in a 1:1 ratio to either a self-fatigue assessment group (study group) or a fixed activity distance assessment group (control group). The fixed activity distance group adopts a fixed early postoperative ambulation distance to guide the patient's activity, while the self-fatigue assessment group uses the Borg Exercise Scale to assess the patient's fatigue and stops activity when the fatigue level reaches 5-6. The primary outcome measure is the time to first postoperative flatus. Secondary outcome measures are the time to first bowel movement, the incidence of moderate to severe bloating, the incidence of bowel obstruction or venous thromboembolism, the incidence of adverse events (nausea, vomiting, dizziness), patient satisfaction, sleep quality scores, patient compliance with activities, hospital costs and days in hospital. This study was approved by the Independent Ethics Committee of Xiangyang Central Hospital affiliated with Hubei University of Arts and Sciences and registered with the China Clinical Trials Registry in May 2021. The results of the trial will be disseminated through open access peer-reviewed journals and abstracts will be submitted to relevant national and international conferences. CTR2100046035.


Microbial spoilage and formation of biogenic amines in fresh and thawed modified atmosphere-packed salmon (Salmo salar) at 2 degrees C.
To evaluate the microbial spoilage, formation of biogenic amines and shelf life of chilled fresh and frozen/thawed salmon packed in a modified atmosphere and stored at 2 degrees C. The dominating microflora, formation of biogenic amines and shelf life were studied in two series of storage trials with naturally contaminated fresh and thawed modified atmosphere-packed (MAP) salmon at 2 degrees C. Photobacterium phosphoreum dominated the spoilage microflora of fresh MAP salmon at more than 10(6) cfu g(-1) and the activity of this specific spoilage organism (SSO) limited the shelf life of the product to ca 14 and 21 d in the two experiments. Despite the high levels of P. phosphoreum, less than 20 mg kg(-1) histamine was observed in fresh MAP salmon prior to sensory spoilage. Freezing eliminated P. phosphoreum and extended the shelf life of MAP salmon at 2 degrees C by 1-2 weeks. Carnobacterium piscicola dominated the spoilage microflora of thawed MAP salmon and probably produced the ca 40 mg kg(-1) tyramine detected in this product at the end of its shelf life. Photobacterium phosphoreum dominated the spoilage microflora of fresh MAP salmon but produced only small amounts of biogenic amines in this product. The elimination of P. phosphoreum by freezing allowed this bacteria to be identified as the SSO in fresh MAP salmon. The identification of P. phosphoreum as the SSO in fresh MAP salmon facilitates the development of methods to determine and predict the shelf life of this product, as previously shown with fresh MAP cod.


YTHDF2 Gene rs3738067 A>G Polymorphism Decreases Neuroblastoma Risk in Chinese Children: Evidence From an Eight-Center Case-Control Study.
Neuroblastoma is a primary malignancy mainly occurring in children. We have reported that polymorphisms of several N6-methyladenosine (m6A) RNA modification-related genes contributed to neuroblastoma risk in previous studies. YTHDF2, a "reader" of RNA m6A modification, is involved in cancer progression. Here, we estimated the association between a YTHDF2 gene rs3738067 A>G polymorphism and neuroblastoma susceptibility in 898 neuroblastoma patients and 1,734 healthy individuals from China. We found that the rs3738067 A>G could decrease neuroblastoma risk [AG vs. AA: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.64-0.90, P = 0.002; AG/GG vs. AA: adjusted OR = 0.81, 95% CI = 0.69-0.95, P = 0.011). Besides, the rs3738067 AG/GG genotype was related to reduced neuroblastoma risk in the following subgroups: children aged 18 months and under, boys, patients with tumors originating from retroperitoneal, patients at clinical stage IV, and cases at clinical stages III plus IV. Importantly, false-positive report probability analysis proved our significant results worthy of close attention of. The expression quantitative trait locus analysis results revealed that the rs3738067 was associated with the expression of YTHDF2.


'Fast-track' colonic surgery in Austria and Germany--results from the survey on patterns in current perioperative practice.
'Fast-track' rehabilitation has been shown to accelerate recovery, reduce general morbidity and decrease hospital stay after elective colonic surgery. Despite this evidence, there is no information on the acceptance and utilization of these concepts among the entirety of Austrian and German surgeons. In 2006, a questionnaire concerning perioperative routines in elective, open colonic resection was sent to the chief surgeons of 1270 German and 120 Austrian surgical centres. The response rate was 63% in Austria (76 centres) and 30% in Germany (385 centres). Mechanical bowel preparation is used by the majority (Austria, 91%; Germany, 94%); the vertical incision is the standard method of approach to the abdomen in Austria (79%) and Germany (83%), nasogastric decompression tubes are rarely used, one-third of the questioned surgeons in both countries use intra-abdominal drains. Half of the surgical centres allow the intake of clear fluids on the day of surgery and one-fifth offer solid food on that day. Epidural analgesia is used in three-fourths of the institutions. Although there is an evident benefit of fast-track management, the survey shows that they are not yet widely used as a routine in Austria and Germany.


Lyme borreliosis in pregnancy and associations with parent and offspring health outcomes: An international cross-sectional survey.
Lyme disease (LD) is a complex tick-borne pathology caused by Borrelia burgdorferi sensu lato bacteria. Currently, there are limited data regarding the health outcomes of people infected during pregnancy, the potential for perinatal transmission to their fetus, and the long-term effects on these children. Therefore, the primary objective of this survey study was to investigate the impact of LD in pregnancy on both the parent and their offspring. A seven-section survey was developed and administered in REDCap. Although recruitment was primarily through LD-focused organizations, participation was open to anyone over the age of 18 who had been pregnant. Participant health/symptoms were compared across those with "Diagnosed LD," "Suspected LD," or "No LD" at any time in their lives. The timing of LD events in the participants' histories (tick bite, diagnosis, treatment start, etc.) were then utilized to classify the participants' pregnancies into one of five groups: "Probable Treated LD," "Probable Untreated LD," "Possible Untreated LD," "No Evidence of LD," and "Unclear." A total of 691 eligible people participated in the survey, of whom 65% had Diagnosed LD, 6% had Suspected LD, and 29% had No LD ever. Both the Diagnosed LD and Suspected LD groups indicated a high symptom burden (p < 0.01). Unfortunately, direct testing of fetal/newborn tissues for Borrelia burgdorferi only occurred following 3% of pregnancies at risk of transmission; positive/equivocal results were obtained in 14% of these cases. Pregnancies with No Evidence of LD experienced the fewest complications (p < 0.01) and were most likely to result in a live birth (p = 0.01) and limited short- and long-term offspring pathologies (p < 0.01). Within the LD-affected pregnancy groups, obtaining treatment did not decrease complications for the parent themselves but did ameliorate neonatal health status, with reduced rates of rashes, hypotonia, and respiratory distress (all p < 0.01). The impact of parent LD treatment on longer-term child outcomes was less clear. Overall, this pioneering survey represents significant progress toward understanding the effects of LD on pregnancy and child health. A large prospective study of pregnant people with LD, combining consistent diagnostic testing, exhaustive assessment of fetal/newborn samples, and long-term offspring follow-up, is warranted.


Nursing students' learning strategies for e-learning during the Covid-19 pandemic in Iran: a qualitative study.
In response to the emergency brought about by the Covid-19 pandemic, many universities around the world had to change their teaching methods from in-person classes to e-learning. The purpose of this study was to identify the learning strategies of nursing students in e-learning during the pandemic. This study had a qualitative design and used content analysis approach to collect and analyze the data. Sixteen semi-structured interviews were conducted with 12 Iranian undergraduate nursing students who were selected using purposive sampling method. Most nursing students in this study generally used two different strategies for e-learning, namely self-centered learning strategies and collaborative learning strategies. Some students, on the other hand, adopted a passive approach in which they did not take any effective action to contribute to their learning. In e-learning during the pandemic, students adopted different learning strategies. Therefore, designing teaching strategies tailored to the students' strategies can promote their learning and academic achievement. Also, knowledge of these strategies helps policy makers and nursing educators to take necessary measures in order to optimize and facilitate student learning in an e-learning environment.


Responding to Cardiac Arrest in the Community in the Digital Age.
Sudden cardiac arrest (SCA) is a common event, affecting almost 400,000 individuals annually in North America. Initiation of cardiopulmonary resuscitation (CPR) and early defibrillation using an automated external defibrillator (AED) are critical for survival, yet many bystanders are reluctant to intervene. Digital technologies, including mobile devices, social media, and crowdsourcing might help play a role to improve survival from SCA. In this article we review the current digital tools and strategies available to increase rates of bystander recognition of SCA, prompt immediate activation of emergency medical services (EMS), initiate high-quality CPR, and to locate, retrieve, and operate AEDs. Smartphones can help to educate and connect bystanders with EMS dispatchers, through text messaging or video calling, to encourage the initiation of CPR and retrieval of the closest AED. Wearable devices and household smart speakers could play a future role in continuous vital signs monitoring in individuals at risk of lethal arrhythmias and send an alert to either chosen contacts or EMS. Machine learning algorithms and mathematical modelling might aid EMS dispatchers with better recognition of SCA as well as policymakers with where to best place AEDs for optimal accessibility. There are challenges with the use of digital tech, including the need for government regulation and issues with data ownership, accessibility, and interoperability. Future research will include smart cities, e-linkages, new technologies, and using social media for mass education. Together or in combination, these emerging digital technologies might represent the next leap forward in SCA survival.


Homemade laparoscopic surgical simulator: a cost-effective solution to the challenge of acquiring laparoscopic skills?
Laparoscopic surgery is well known to have a long and variable learning curve and there is a potential benefit from earlier integration of laparoscopic skills in medical education. The aim of this study was to assess the challenges facing surgical trainees regarding the acquisition of laparoscopic skills and second to assess their opinion regarding the use of a homemade laparoscopic surgical simulator. A homemade laparoscopic surgical simulator (HLSS) was constructed. An online survey using Survey Monkey® of surgical trainees at a tertiary referral university teaching hospital was conducted assessing their experience with laparoscopic surgery. Surgical trainees were voluntarily enrolled to assess the self-designed laparoscopic trainer. Each trainee was asked to perform simple exercises without supervision. All trainees (n = 34) responded to the survey. No trainee had full-time access to a laparoscopic box trainer. The mean time spent per week using the simulator was 0.38 h (range 0-3 h), with 61.8 % (n = 21) reporting not using the simulator at all. 94.1 % (n = 32) enrolled in our study. 90.6 % (n = 29) found the HLSS easy to use compared to 93.8 % (n = 30) with the CLS (p = 1.00). 96.9 % (n = 31) reported an overall satisfaction with the HLSS. There was no difference with regard to the completing the tasks: peg transfer (78.1 vs 78.1 %, p = 1.00), cutting patterns (65.6 vs 71.9 %, p = 0.788) or knot tying (12.5 vs 18.8 %, p = 0.732) whether using HLSS and the CLS. Homemade laparoscopic surgical simulators are easy to construct, affordable, usable and of interest to trainees.


Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa (SIS) to a stomach defect in rats.
Small intestinal submucosa (SIS) represents a novel bio-scaffolding material that may be used to repair hollow-organ defects. However, it is unclear whether neurophysiologic responses return to SIS-grafted areas in the gut. We evaluated the functional recovery of a stomach defect grafted with the porcine-derived SIS. Twelve rats had a full-thickness defect created in the stomach. SIS was secured to the gastric wall. After 6 months, muscle strips were harvested from within the grafted area to perform both a histologic and a functional study. Additional full-thickness muscle strips were harvested from the posterior in the same stomach as controls. A dose response curve was obtained with carbachol (CCH) or sodium nitroprusside (SNP). Activation of intrinsic nerves was achieved by electrical field stimulation (EFS). The response to CCH and amplitude in EFS showed tonic contraction in both controls and SIS strips in a concentration-dependent and frequency-dependent manner. The magnitude after each stimulation was significantly lower in SIS strips compared with controls (P < .01). However, the contraction ratio of EFS to ED(50) of CCH was not significantly different between the groups. Additionally, SNP produced relaxation in both strips in a concentration-dependent manner. Histologic findings revealed that an insufficient amount of smooth-muscle cells existed in the muscularis propria, whereas compensated growth was observed in the submucosa with nerve regeneration. This study demonstrates that SIS provides a template for nerve migration to the graft in the rodent stomach. Innervations showed a similar distribution to that observed in the controls. The clinical implications of such findings warrant additional investigation.


Luminescent material based on the [Eu(TTA)3(H2O)2] complex incorporated into modified silica particles for biological applications.
Amino-functionalized luminescent silica particles were investigated for use in immunoassays. The particles were prepared by the Stöber method where the [Eu(TTA)3(H2O)2] complex (TTA: 3-thenoyltrifluoroacetonate) was incorporated into silica particles during the hydrolysis and condensation of TEOS: tetraethylorthosilicate. Then, the amino groups were introduced in the particle surface using APTS: 3-aminopropyltriethoxisilane. The resulting particles were characterized by scanning electron microscopy (SEM), X ray diffraction (XRD) and photoluminescence spectroscopy. In order to demonstrate the viability of the use of luminescent particles as optical markers, an enzyme-substrate reaction was performed using HRP: horseradish peroxidase. It was possible to verify the binding of HRP-oxidized LDL (low density lipoprotein) and anti-oxLDL antibody-luminescent silica particles through the evaluation of the presence of HRP. The bioassay data open a broad field for the development of protein-tagged luminescent particles for use in biomedical sciences.


Downregulation of the vitamin D receptor expression during acute gastrointestinal graft versus host disease is associated with poor outcome after allogeneic stem cell transplantation.
The vitamin D receptor (VDR) is critical in regulating intestinal homeostasis and emerging evidence demonstrates that VDR deficiency is a critical factor in inflammatory bowel disease pathology. However, no clinical data exist regarding the intestinal expression of VDR in patients after allogeneic haematopoietic stem cell transplantation (HSCT). Analyzing intestinal biopsies from 90 patients undergoing HSCT with mortality follow-up, we demonstrated that patients with severe acute gastrointestinal graft versus host disease (GI-GvHD) showed significant downregulation of VDR gene expression compared to mild or no acute GI-GvHD patients (p = 0.007). Reduced VDR expression was already detectable at acute GI-GvHD onset compared to GvHD-free patients (p = 0.01). These results were confirmed by immunohistochemistry (IHC) where patients with severe acute GI-GvHD showed fewer VDR+ cells (p = 0.03) and a reduced VDR staining score (p = 0.02) as compared to mild or no acute GI-GvHD patients. Accordingly, low VDR gene expression was associated with a higher cumulative incidence of treatment-related mortality (TRM) (p = 1.6x10-6) but not with relapse-related mortality (RRM). A multivariate Cox regression analysis identified low VDR as an independent risk factor for TRM (p = 0.001, hazard ratio 4.14, 95% CI 1.78-9.63). Furthermore, VDR gene expression significantly correlated with anti-microbial peptides (AMPs) gene expression (DEFA5: r = 0.637, p = 7x10-5, DEFA6: r 0 0.546, p = 0.001). In conclusion, our findings suggest an essential role of the VDR in the pathogenesis of gut GvHD and the prognosis of patients undergoing HSCT.


The phosphorus budget of the Thame catchment, Oxfordshire: 2. Modelling.
The phosphorus budget of the River Thame was modelled at a daily time scale, using estimates of diffuse and point source contributions of discharge. The model simulated suspended sediment (SS), soluble unreactive phosphorus (SUP), soluble reactive phosphorus (SRP) and particulate phosphorus (PP) concentrations within the main river and major tributaries. Diffuse source estimates of phosphorus loads were based on characteristic losses from identified main landscape classes, with hydrology described by a simple conceptual storage model. In-stream flow was modelled using a kinematic wave equation. Transfer of suspended sediment and phosphorus components was approximated by advection. In-stream sources and sinks included uptake and release of soluble reactive phosphorus by bed sediment, instant equilibration between SRP and the PP concentration on suspended sediment, and flow-related entrainment and deposition of suspended sediment. Simulations at sites within the catchment were compared with measurements made in 1998-1999. Results showed the P budget is dominated by mixing of diffuse and point source water, but some within-river processes have been shown to be capable of significantly influencing SRP concentrations. The development of a sediment entrainment and deposition component of the model has proved particularly valuable in emulating the hysteretic relationship between discharge and suspended sediment concentration in the river. It also provides a measure of available bed sediment.


Increased susceptibility to complicated pneumonia among egyptian children with FokI (rs2228570), not TaqI (rs731236), vitamin D receptor gene polymorphism in association with vitamin D deficiency: a case-control study.
Determining a genetic contribution to the development of complicated community-acquired pneumonia in children may help understand underlying pathogenesis. We aimed to investigate the association between two vitamin D receptor (VDR) gene polymorphisms, FokI and TaqI, and susceptibility to complicated pneumonia in Egyptian children compared to uncomplicated pneumonia. Associations with 25 hydroxy-vitamin D serum level were studied. This was a case-control study that included 320 participants divided into 2 groups: patients and controls. The patients' group included 100 children hospitalized with complicated pneumonia and 100 with uncomplicated pneumonia. 120 age and sex-matched apparently healthy children served as controls. The VDR FokI and TaqI polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 25 hydroxy-vitamin D level was estimated in serum using ELISA. Regarding FokI, homozygous CC genotype was more common in complicated (52%) than uncomplicated pneumonia (28%) and controls (10%) (OR = 65; 95%CI (5.13-822.63), p < 0.001) and (OR = 4.3; 95%CI (0.7-27.16), p = 0.003), respectively. Children carrying C allele possessed 3 higher odds for complicated than uncomplicated pneumonia (OR = 3.08; 95%CI (1.33-7.14), p < 0.001). Heterozygous CT genotype increased susceptibility to complicated pneumonia (OR = 13.7; 95%CI (4.6-40.1), p < 0.001), not uncomplicated pneumonia (OR = 1.56; 95%CI (0.86-2.85), p = 0.145). Among complicated pneumonia, vitamin D level was lower in CC (6.92 ± 2.6ng/ml) than CT (9.55 ± 3.2 ng/ml) and TT genotype carriers (13.13 ± 3.6ng/ml) (p < 0.001). There was no significant difference between patients and controls as regards TaqI genotypes and alleles. In association with vitamin D deficiency, VDR gene FokI polymorphism, not TaqI, is a genetic risk factor for complicated pneumonia in Egyptian children.


Comparative study of extraction methods of silver species from faeces of animals fed with silver-based nanomaterials.
Extractions methods based on ultrapure water, tetramethylammonium hydroxide (TMAH), and tetrasodium pyrophosphate (TSPP) were applied to faeces collected from two in vivo experiments of pigs and chickens fed with a silver-based nanomaterial to study the fate and speciation of silver. For TMAH extraction, cysteine and CaCl2 were used to evaluate their stabilization effect on the silver forms. The analytical techniques single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS), hydrodynamic chromatography hyphenated to ICP-MS (HDC-ICP-MS) and asymmetric flow field flow fractionation coupled to ICP-MS (AF4-ICP-MS) were applied to the simultaneous detection of particulate and dissolved silver. Results have shown that water extraction was a suitable option to assess the environmental release of silver, with percentages of 3 and 9% for faeces of pigs and chickens, respectively. The use of TMAH extraction combined with SP-ICP-MS analysis was useful to characterize Ag-containing particles (less than 1%). Both stabilizers, cysteine and CaCl2, have a similar effect on silver nanoparticle preservation for chicken faeces, whereas cysteine-Triton was better for pig samples. In any case, silver extraction efficiency with TMAH was low (39-42%) for both types of faeces due to a matrix effect. TSPP followed by ICP-MS enabled the fractionation of the silver in the faeces, with silver sulphide (41%) and ionic silver (62%) being the most abundant fractions.


The estrous cycle surpasses sex differences in regulating the transcriptome in the rat medial prefrontal cortex and reveals an underlying role of early growth response 1.
Males and females differ in cognitive functions and emotional processing, which in part have been associated with baseline sex differences in gene expression in the medial prefrontal cortex. Nevertheless, a growing body of evidence suggests that sex differences in medial prefrontal cortex-dependent cognitive functions are attenuated by hormonal fluctuations within the menstrual cycle. Despite known genomic effects of ovarian hormones, the interaction of the estrous cycle with sex differences in gene expression in the medial prefrontal cortex remains unclear and warrants further investigations. We undertake a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult medial prefrontal cortex transcriptome and report that females with high and low ovarian hormone levels exhibited a partly opposed sexually biased transcriptome. The extent of regulation within females vastly exceeds sex differences, and supports a multi-level reorganization of synaptic function across the estrous cycle. Genome-wide analysis of the transcription factor early growth response 1 binding highlights its role in controlling the synapse-related genes varying within females. We uncover a critical influence of the estrous cycle on the adult rat medial prefrontal cortex transcriptome resulting in partly opposite sex differences in proestrus when compared to diestrus females, and we discovered a direct role for Early Growth Response 1 in this opposite regulation. In addition to illustrating the importance of accounting for the estrous cycle in females, our data set the ground for a better understanding of the female specificities in cognition and emotional processing.


Identification and expression analysis of ten novel small non-coding RNAs (sncRNAs) in cancer cells using a high-throughput sequencing approach.
Non-coding RNAs are characterized as RNA molecules, which lack the capacity to encode protein structures and appear to include a level of internal signals. Moreover, they control various stages of gene expression, thus controlling the cell physiology and development. In this study, we implemented a high-throughput sequencing approach based on the primary semi-conductor technology and computational tools, in order to identity novel small non-coding RNAs. Fourteen human cancer cell lines were cultured, and RNA samples were enriched for small RNAs following semi-conductor next generation sequencing (NGS). Bioinformatics analysis of NGS data revealed the existence of several classes of ncRNAs using the miRDeep* and CPSS 2.0 software. To investigate the existence of the predicted non-coding RNA sequences in cDNA pools of cell lines, a developed qPCR-based assay was implemented. The structure of each novel small ncRNA was visualized, using the RNAfold algorithm. Our results support the existence of twenty (20) putative new small ncRNAs, ten (10) of which have had their expression experimentally validated and presented differential profiles in cancerous and normal cells. A deeper comprehension of the ncRNAs interactive network and its role in cancer can therefore be translated into a wide range of clinical applications. Despite this progress, further scientific research from different perspectives and in different fields is needed, so that the riddle of the human transcriptome can be solved.


Amplitude-integrated electroencephalography for neonatal seizure detection. An electrophysiological point of view.
Seizures in the newborn are associated with high morbidity and mortality, making their detection and treatment critical. Seizure activity in neonates is often clinically obscured, such that detection of seizures is particularly challenging. Amplitude-integrated EEG is a technique for simplified EEG monitoring that has found an increasing clinical application in neonatal intensive care. Its main value lies in the relative simplicity of interpretation, allowing nonspecialist members of the care team to engage in real-time detection of electrographic seizures. Nevertheless, to avoiding misdiagnosing rhythmic artifacts as seizures, it is necessary to recognize the electrophysiological ictal pattern in the conventional EEG trace available in current devices. The aim of this paper is to discuss the electrophysiological basis of the differentiation of epileptic seizures and extracranial artifacts to avoid misdiagnosis with amplitude-integrated EEG devices.


Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.
In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.


[Antiinflammatory potential of seven plant extracts in the ultraviolet erythema test. A randomized, placebo-controlled study].
Phytotherapeutics are widely used in medicine. The aim of this study was the evaluation of the antiinflammatory potential of seven medical plant extracts using the ultraviolet- (UV)-erythema test. Randomized, placebo-controlled study on 40 healthy subjects. Test areas on the upper back were irradiated with the 1.5 fold UV-B minimal erythema dose (MED). Formulations of Aloe vera, Chamomilla recutita, Hamamelis virginiana, Melissa officinalis, Mentha arvensis, Melaleuca alternifolia, Coriandrum sativum as well as 1% hydrocortisone acetate and 0.1% betamethasone valerate as positive controls and unguentum leniens as vehicle control were applied under occlusion on the irradiated areas and on non-irradiated area on the contralateral side. Photometric assessment of the erythema was performed before the application of the substances (t0), at 24 h (t1) and at 48 h (t2). Aloe vera, Chamomilla recutita, Melissa officinalis, Melaleuca alternifolia and Coriandrum sativum showed an antiinflammatory effect compared to UV-control and unguentum leniens. However, the results were only statistically significant for Aloe vera. All tested plant extracts were well tolerated. Aloe vera possesses an antiinflammatory effect on UV-induced erythemas.


Antibody stimulation of benzo(a)pyrene carcinogenesis.
Benzo(a)pyrene (BP) was conjugated to horse serum albumin (HSA) and then attached to aldehyde fixed human erythrocytes. These cells were used in a passive hemagglutination test to measure BP antibody. BP antibodies were found to be induced in Swiss mice injected with tumorigenic doses of BP. Of the mice treated with BP, those which developed tumors soonest had the highest levels of BP antibody. This observation suggested that the antibody to BP may stimulate tumor development. When rabbit antibody to BP was injected with BP a significantly increased tumor formation occurred. Active immunization using BP conjugated to a foreign protein also significantly increased tumor formation when the mice were treated with BP. Our findings suggest that the immune response to carcinogens is an important component of the carcinogenic process.


The role of calcium and cyclic AMP in the contractile action of angiotensin II upon rat descending colon.
The effect of procedures which affect calcium availability and tissue levels of cyclic AMP were investigated upon the contractions of rat colon to angiotensin II, PGE2 and KCl. Calcium free Tyrode containing EDTA (25 microM) reduced the response to angiotensin more than to PGE2 and KCl. An increase in calcium concentration to 3.6 mM potentiated responses to angiotensin and KCl. A further increase to either 7.2 mM or 10.8 mM still potentiated responses to angiotensin but those to KCl wre reduced. SKF 525A (2.6 x 10(-5) M) and verapamil (3.5 x 10(-6) M) inhibited the responses to KCl but the responses to PGE2 and angiotensin were less affected. Isoprenaline, Theophylline and dibutyryl cyclic AMP preferentially reduced the responses to angiotensin and PGE2. It is suggested that part of the response to angiotensin involves an influx of calcium, independent of depolarisation.


A Tubing-Free Microfluidic Wound Healing Assay Enabling the Quantification of Vascular Smooth Muscle Cell Migration.
This paper presents a tubing-free microfluidic wound healing assay to quantify the migration of vascular smooth muscle cells (VSMCs), where gravity was used to generate a laminar flow within microfluidic channels, enabling cell seeding, culture, and wound generation. As the first systemic study to quantify the migration of VSMCs within microfluidic environments, the effects of channel geometries, surface modifications and chemokines on cellular migration were investigated, revealing that 1) height of the micro channels had a significant impact on cell migration; 2) the surface coating of collagen induced more migration of VSMCs than fibronectin coated surfaces and 3) platelet derived growth factor resulted in maximal cell migration compared to tumor necrosis factor alpha and fetal bovine serum. Furthermore, migrations of five types of VSMCs (e.g., the human vascular smooth muscle cell line, two types of primary vascular smooth cells, and VSMCs isolated from two human samples) were quantified, finding that VSMCs from the cell line and human samples demonstrated comparable migration distances, which were significantly lower than the migration distances of two primary cell types. As a platform technology, this wound healing assay may function as a new model to study migration of VSMCs within microfluidic environments.


Penile prosthesis implantation surgery: a statewide population based analysis of 2354 patients.
Minimally invasive therapy for erectile dysfunction (ED) has changed the frequency of penile prosthesis surgery. The purpose of this study is to describe the changes in frequency, hospital stay, hospital charges and penile prosthesis type in North Carolina. The data source was a statewide hospital discharge database which includes data on hospitalized patients for all 151 hospitals in North Carolina. From 1988-1993, 2354 patients underwent implantation of penile prostheses. The total number of penile prostheses implanted has declined over this six year period. Similarly, hospital stay has declined from an average of 4.03-2.96 d with a 46.6% decrease in total hospital days. Despite this change in hospital stay, hospital charges rose significantly from an average of $7252.48 to $12,842.18 driving total charges from $2973,516.80 to $3,826,969.60 (1993) representing a 28.7% increase. Minimally invasive therapy and changes in reimbursement have had a major impact on the number of patients undergoing penile prosthesis implantation for ED. This downward trend may continue as more treatment options develop from the marked increase in research in this field. However, this may result in an increase of patients seeking treatment overall.


Fatal Disseminated Strongyloidiasis in an Immunosuppressed Patient During COVID-19 Pandemic.
This report presents a fatal case of disseminated strongyloidiasis in a patient with myasthenia gravis and diabetes mellitus who had received corticosteroid therapy. The patient was a 67-year-old woman living in a rural area endemic for Strongyloides stercoralis in northern Iran. Disseminated strongyloidiasis was diagnosed in the advanced stage of the disease, with enormous numbers of larvae demonstrated in direct smears prepared from stool samples and stomach biopsy. Despite treatment with ivermectin and antibiotics, the patient succumbed to the severity of the infection. Clinicians working in endemic areas should be mindful of the possibility of gastric involvement in strongyloidiasis, even if symptoms are nonspecific. We recommend that high-risk individuals be screened for S. stercoralis prior to immunosuppressive therapy in endemic regions to raise awareness and prevent similar cases.


Sense the moment: A highly sensitive antimicrobial activity predictor based on hydrophobic moment.
Computer-aided identification and design tools are indispensable for developing antimicrobial agents for controlling antibiotic-resistant bacteria. Antimicrobial peptides (AMPs) have aroused intense interest, since they have a broad spectrum of activity, and therefore, several systems for predicting antimicrobial peptides have been developed, using scalar physicochemical properties; however, regardless of the machine learning algorithm, these systems often fail in discriminating AMPs from their shuffled versions, leading to the need for new training methods to overcome this bias. Aiming to solve this bias, here we present "Sense the Moment", a prediction system capable of discriminating AMPs and shuffled versions. The system was trained using 776 entries: 388 from known AMPs and another 388 based on shuffled versions of known AMPs. Each entry contained the geometric average of three hydrophobic moments measured with different scales. The model showed good accuracy (>80%) and excellent sensitivity (>90%) for AMP prediction, exceeding deep-learning-based methods. Our results demonstrate the system's applicability, aiding in identifying and discarding non-AMPs, since the number of false negatives is lower than false positives. The application of this model in virtual screening protocols for identifying and/or creating antimicrobial agents could aid in the identification of potential drugs to control pathogenic microorganisms and in solving the antibiotic resistance crisis. The system was implemented as a web application, available at <http://portoreports.com/stm/>.


Efficacy of cooling therapy and α-lipoic acid derivative against chemotherapy-induced alopecia in an animal model.
Chemotherapy-induced alopecia is frequently induced by various regimens of chemotherapy and has a significant impact on mental health and quality of life. However, the effect of available current treatment for chemotherapy-induced alopecia is not sufficient. This study aimed to clarify the therapeutic effects and mechanism of skin cooling and the antioxidant α-lipoic acid derivative on chemotherapy-induced alopecia. We developed a chemotherapy-induced alopecia model of cyclophosphamide (120 μg/g) using Institute of Cancer Research mice. We used cooling therapy and α-lipoic acid derivative application as the treatments. We compared the alopecia score, hair bulb diameter, insulin-like growth factor-1 level, vascular permeability, and apoptosis between the control and treatment groups. The alopecia score significantly improved in each treatment group compared with that in the cyclophosphamide group. Hair bulb diameter significantly improved in the cyclophosphamide + cooling group compared with that in the cyclophosphamide group. The insulin-like growth factor-1 level and vascular permeability level was significantly retained and suppressed, respectively, in each treatment group compared with that in the cyclophosphamide group. The number of apoptotic cells in the vascular endothelium significantly decreased in the cyclophosphamide + α-lipoic acid derivative group compared with that in the cyclophosphamide group. In conclusion, cooling therapy and α-lipoic acid derivative facilitated recovery from chemotherapy-induced alopecia caused by cyclophosphamide through decreasing vascular permeability.


Amphiphilic activities of anionic sodium cholate (NaC), zwitterionic 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and their mixtures: a comparative study.
Anionic biological surfactant sodium cholate (NaC) and the zwitterionic nontoxic surfactant CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) having common steroidal skeleton have not been studied in a comparative level to explore their amphiphilic behaviors separately and in mixed states. Their adsorption at the interface in relation to self-association in solution has been examined in both pure and mixed states with reference to detailed thermodynamic analysis of their surface chemical and solution behaviors. Their head group differences are responsible for the differences in their properties viz. critical micelle concentration (CMC), aggregation number (N), hydrodynamic diameter, Gibbs surface excess (Γmax), minimum head group area (Amin), mixed micelle composition and their mixing ideality/nonideality. Although the CMC values found from tensiometry and isothermal titration calorimetry (ITC) are in good agreement, the standard enthalpy of micellization (ΔHm(0)) found from ITC at different temperatures are different from that evaluated by the van't Hoff method. This is because van't Hoff rationale is a differential method which estimates the enthalpy of the monomer ↔ micelle equilibrium process whereas calorimetry is an integral process that evaluates all probable/possible processes in addition to monomer to micelle conversion. Results are analyzed, compared and discussed in the light of physicochemical parameters of pure NaC and CHAPS and their mixtures. These fundamental findings are considered prospective in pharmaceutical, biochemical and biomedical applications of the studied bio-friendly amphiphiles.


Self-assessments and determinants of HRQoL in a German MS population.
The importance of health-related quality of life (HRQoL) in multiple sclerosis (MS) is widely acknowledged. In 2015, a multicenter study was launched to assess the HRQoL and coping styles of chronically ill persons in Germany. The aims of this paper were (i) to describe how persons affected by MS assess their HRQoL and (ii) find out sociodemographic and disease-specific determinants of HRQoL. A quantitative survey (optionally per paper-pencil or online) was conducted between March and October 2015 in Germany. Recruitment ways were as follows: Associations of the German Multiple Sclerosis Society (DMSG), medical practices specialized in neurology/MS, hospitals, public events, social networks, and self-help clearinghouses. To measure HRQoL, the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire and the short form of the Fear of Progression Questionnaire (FoP-Q) were used. A total of 1220 individuals with MS participated in the study. Frequent problems reported were related to activities of daily living as well as sentimental and sexual life. Multiple regression analyses identified disease severity and comorbidity-in different directions (positive and negative)-as the strongest factors in predicting activities of daily living, symptoms, sentimental and sexual life, and reject. The demographic variables sex, age, education, and employment status also have different impact on the HRQoL. Using HRQoL measures can be feasible outcomes in addition to clinical assessments of MS and other chronic diseases and can help better managing the care. Some challenges have to be taken into account involving patients and the limitations of our empirical study.


Cilia on bovine mammary epithelium: ultrastructural observations.
Ultrastructural examination of bovine mammary tissues revealed the presence of 9+0 or primary cilia protruding from surfaces of alveolar epithelial and myoepithelial cells. Cilia of epithelial cells protruded approximately 1200 nm into lumina of alveoli and arose from a basal body centriole, the associated centriole of the diplosome, and an accessory rootlet system. Cilia on epithelial cells were more frequently observed than cilia on myoepithelial cells. Occasional cilia made contact with macrophages in the alveolar lumen. The structures were more commonly found in tissues from nonlactating cows, and most were observed in the ventral portion of the mammary gland.


Late Complications of Allogenic Stem Cells Transplantation in Leukaemia.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure leukaemia. However, long term complications of post transplantation interfere with the patients' full recovery. The objective of this review was to identify the various long term complications and to assess their individual prevalences. Electronic databases including PubMed, Google Scholar and Cochrane were searched for years 2004-2017. The keywords used were leukaemia, allogenic stem cell transplantation, prevalence, side effects, long term, delayed, adverse effects, complications and outcome. A total of ten articles were included for analysis. There were 5 prospective studies, 3 retrospective studies and 2 cross sectional studies. A total of 40,069 patients, (20,189 males and 17,191 females) participated in these 10 studies. The gender of 2689 patients were not disclosed. Most common late complications and prevalence were chronic graft versus host disease (43% at 5 years post HSCT), secondary tumor (21% at 20 years post HSCT), hypothyroidism (11% at 15 years), bronchiolitis obliterans (9.7% at 122 days), cardiovascular disease (7.5% at 15 years) and avascular necrosis (5.4% at 10 years). The prevalence of azoospermia was 71.1% and depression, 18%. For the latter two conditions no time limit was available. Follow up duration ranged from 2 years till 30 years post HSCT. While allogenic stem cell transplantation is an effective cure for leukaemia, the procedure is associated with complications that can have their onset many years after the procedure.


Cranial and spinal dural arteriovenous malformations and fistulas: an update.
Awareness of a potential arteriovenous fistula is critical for diagnosis of cranial as well as spinal fistulas. The natural history of cranial and spinal dural arteriovenous fistulas has been clarified during the last decade and interdisciplinary therapies have experienced a substantial development recently. The classification of Cognard & Merland is now the most widely accepted one for cranial dural AVF. It is based on the degree of flow reversal in the sinuses and cortical veins and reflects well the natural history of the different lesions and serves as basis for therapeutic indications. Several studies have defined the annual bleeding risk of cranial dural fistulas between 1.8 and 15%, depending on the pattern of venous drainage and initial symptomatology. Surgical, endovascular and radiosurgical methods must be selectively chosen for the treatment. The risk associated with surgical or endovascular treatment of benign fistulas is higher than the risk of eliminating fistulas that have already led to cortical venous reflux. Transvenous endovascular occlusion or surgical disconnection of draining veins is the treatment of first choice for cranial and spinal dAVF with venous flow reversal. Benign cranial dural arteriovenous fistulas are a developing indication for radiosurgery.


Assessment of Trace Metals Concentration in Tree Barks as Indicator of Atmospheric Pollution within Ibadan City, South-West, Nigeria.
Tree bark species were randomly collected from 65 sites having different anthropogenic activities, such as industrial, high traffic commercial, residential high and residential low traffic volume areas of Ibadan City, Nigeria. Levels of Cd, Cu, Pb, Zn, Co, and Cr of the dry-ashed bark samples were determined by AAS. The mean metal concentrations (mg kg(-1)) in samples from industrial zone were found as Pb: 3.67 ± 1.97, Cd: 0.10 ± 0.07, Zn: 30.96 ± 32.05, Cu: 7.29 ± 5.17, Co: 0.91 ± 0.58, and Cr: 2.61 ± 1.84. The trend of mean trace metal concentrations at high traffic commercial zone follows the order: Zn > Pb > Cu > Cr > Co > Cd. Residential high traffic and low traffic zones revealed the same trend as Cd < Co < Cr < Pb < Cu < Zn. Relatively strong positive correlation between the heavy metals at ρ < 0.05, such as Zn versus Cu (r = 0.79) and Co versus Cu (r = 0.77), was observed. The results of the study suggest that tree bark samples could potentially serve as bioindicators for Cu, Pb, Zn, Cr, and possibly Co and Cd. Furthermore, interspecies variation of heavy metal concentrations in plants barks is recommended.


Toxicity of the herbicides 2,4-D, DEF, propanil and trifluralin to the Dungeness crab, Cancer magister.
Lethal and sublethal responses to the herbicides 2,4-D, DEF, propanil, and trifluralin of various life history stages of the Dungeness crab, Cancer magister, were examined to estimate maximum acceptable toxicant concentrations (MATC) of each compound for this species. Zoeae were found, in long term tests, to be the most sensitive stage. Based on the experiments with this stage, MATCs were concluded to be greater than 0.95, less than 6.9 microgram/L for DEF, greater than or equal to 26, less than 220 microgram/L for trifluralin, greater than or equal to 1,700 microgram/L for propanil, and less than 1,000 microgram/L for the free acid form of 2,4-D.


Self-reported symptoms after COVID-19 vaccination. Distinct sex, age, and geographical outcomes in Lebanese and Italian cohorts.
Following the COVID-19 discovery in December 2019, different vaccines were authorized in 2021 in Italy and Lebanon, but side effects and the impact of sex and age remained partly explored. We designed a web-based "Google Form" questionnaire to record self-reported systemic and local side effects up to 7 days after 1st and 2nd dose of the vaccine in two distinct Italian and Lebanese cohorts. Twenty-one questions in Italian and Arabic languages explored the prevalence and severity of 13 symptoms. Results were compared with respect to living country, timing, sex, and age classes. A total of 1,975 Italian subjects (age 42.9 ± SD16.8 years; 64.5% females) and 822 Lebanese subjects (age 32.5 ± SD15.9 years; 48.8% females) joined the study. The most common symptoms in both groups were injection site pain, weakness, and headache after the 1st and 2nd doses. The rate of post-vaccinal symptoms and the severity score were significantly higher in females than in males and progressively decreased with increasing age following both doses. We find that among two populations from the Mediterranean basin, the anti-COVID-19 vaccine generates mild age and sex-dependent adverse effects, with ethnic differences and prevalent symptoms rate and severity in females.


Plant microRNAs: biogenesis, gene silencing, web-based analysis tools and their use as molecular markers.
MicroRNAs (miRNAs) are tiny (20-24 nt bp) regulatory non-protein-coding RNA molecules that have been extensively characterized and found important for many physiological and developmental processes. The miss-expression of miRNAs leads to various defects in plants. MicroRNAs repress gene expression by directing mRNA degradation or translational arrest. Several proteins such as PP43A, HYL1, DCL, HST are indispensable role players in promoting miRNA biogenesis in plants. During miRNA biogenesis, lariat RNAs are produced as by-products of pre-mRNA splicing which have a negative role in regulation of miRNA homeostasis. By acting as a decoy and by sequestering to the dicing complex, lariat RNA can prevent the processing of miRNAs. A number of bioinformatic tools with different methodologies are available to identify and validate miRNAs and their targets. Many miRNAs have been reported in different crops for different traits; however, no reports are available on their use in plant breeding. Recently, researchers have developed trait specific miRNA-based molecular markers (miRNA-SSRs/SNP) for many quantitative traits in different plant species. In the future, these molecular markers can be used for plant breeding programs. In this review, a comprehensive up-to-date information is provided on the bioinformatic tools used for analysis of plant miRNAs and their targets, the number of miRNAs, their biogenesis, gene silencing mechanism and miRNA-based molecular markers.


A corpus-based study of modal verbs in Chinese-English governmental press conference interpreting.
This study investigates the use of modal verbs in Chinese-English government press conference (GPC) interpretation. Modal verbs mark the speaker's opinion of or attitude toward the event described in a sentence. Interpreters also use modal verbs to indicate the stances of the source language speakers. The use of modal verbs has been examined in such contexts as research papers, textbooks, and second language learners' output; however, studies that compare differences in modal verbs between source and target languages in the context of interpreting are sparse. The investigation being reported is based on a comparable corpus-an original Chinese GPC and its English-translated version-and a parallel corpus-a translated English GPC and the original English version from the US. The results of the comparable corpus analysis indicate that the frequency of modal verbs in translated English is significantly higher than in original Chinese, in which only 40% of the modal verbs in translated English are consistent with their Chinese counterparts, while others are employed through amplification and value variation. The results of the parallel corpus analysis suggest that the increase of modal verbs in the target texts may help to achieve certain types of pragmatic functions in English.


Resting energy expenditure and body composition following cerebro-vascular accident.
The aim of this study was to measure resting energy expenditure (REE) in patients routinely admitted to hospital following a cerebro-vascular accident (CVA). The REE of 15 patients (8 female; 7 male) was measured using indirect calorimetry 24-72 hours after the CVA; 11 patients (7 female; 4 male) were measured again 10-14 days later. Body composition was assessed using skin-fold thickness, near infra-red interactance and bioelectrical impedance techniques. Initial REE in females was 1133 kcal/day (+/-67) and in males 1526 kcal/day (+/-111). There was little or no difference in REE or body composition between the first and second measurements. REE was between 95%-107% of the values predicted by 10 reference tables and equations and up to 118% of that predicted by another. We conclude that the total energy requirements of patients following a stroke are not high, probably because of decreased physical activity and changes in muscular tone subsequent to CVA.


Clinical significance of fetal choroid plexus cysts.
Choroid plexus (CP) cysts are commonly detected on routine mid-trimester ultrasound scan. When associated anomalies are detected, the risk is sufficient to justify an invasive diagnostic test such as amniocentesis. However, the risk when no associated anomalies are detected is much less well defined. This information is required to determine the appropriate management in cases of apparently isolated CP cysts. We thought the only way to resolve the difficulties in counselling prospective parents was to conduct a prospective study in a large unselected population. A registry of fetal CP cysts detected over 3 years in the Yorkshire Region was compiled and we identified 524 CP cysts. These cases were then amalgamated and analysed with 1361 cases from prospective studies reported in the world English literature and a further 71 unpublished cases identified from a 2 year prospective series from Ninewells Hospital, Dundee. The risk of chromosomal abnormalities was 1 in 150 (95% CI 1 in 85, 1 in 261) when no fetal anatomic abnormalities, apart from the CP cysts themselves, were detected antenatally. The risk increased to approximately 1 in 3 if any other associated ultrasound abnormalities were detected antenatally. The risk did not appear to be related to whether or not cyst size diminished as gestation progresses, whether they were unilateral or bilateral, and whether they were small or large in size (60-80% < 10 mm). 76% of aneuploidic cases were trisomy 18 and 17% were trisomy 21. The risk of Down's syndrome in fetuses with CP cysts but no other anomalies detected antenatally is 1 in 880. The probability of a chromosomal abnormality is high when CP cysts are associated with any other antenatally detected anomaly, indicating a clear need to offering amniocentesis. The predictive value is much lower when no other anomalies are detected. In such cases, it is probably advisable to regard CP cysts as an indication for detailed ultrasound assessment, rather than invasive testing.


Utility of Follow-Up Echocardiograms in Uncomplicated Surgical Secundum Atrial Septal Defect Closures: Preliminary Analysis.
Though less common in the current era, surgical closure of secundum atrial septal defects (ASD2) is still performed in certain clinical situations. Guidelines currently recommend lifelong follow-up with transthoracic echocardiograms (TTE) for patients who have undergone a surgical ASD2 closure. The goal of this study was to determine the utility of follow-up TTE in patients who underwent an uncomplicated ASD2 closure. Chart review was performed on patients who had a surgical ASD2 closure between April 1, 1996, and August 30, 2021. Patients were excluded if they had other congenital heart disease, had a diagnosis of a residual ASD2, atrial/ventricular arrhythmias, pulmonary hypertension, heart failure, or did not have a follow-up TTE > 6 months after the procedure. The most recent TTEs and clinic notes were evaluated. A total of 30 patients met the criteria. The median age at ASD2 surgery was 4.0 years (IQ; 1.9-10.5). ASD2 was closed via patch repair in 16 patients and primarily closed in 14 patients. The most recent TTE was performed a median of 9.5 years (IQ; 4.0, 14.7) after ASD2 closure. Two patients had mild right atrial and ventricular dilation, one patient had mild right atrial dilation, and one patient had mild right ventricular dilation. All other patients had qualitatively normal right-sided chamber sizes. All patients had normal biventricular function (left ventricular fractional shortening (median 36% (IQ; 33, 42)), no evidence of residual atrial shunts, and no evidence of pulmonary hypertension. No patient was on any cardiac medications at last clinic visit. Four patients were discharged from cardiology clinic and 10 patients were lost to follow-up. There were no deaths. Twenty-four patients had 46 repeat echocardiograms > 1 year after ASD2 with no change in clinical management. In patients who underwent an uncomplicated ASD2 closure, there were no significant abnormalities noted on follow-up TTEs. The need for repeat lifetime TTEs and their frequency, in this uncomplicated population, should be reassessed if larger studies with longer follow-up confirm these initial findings.


Theoretical rates of increase of gregarious and solitarious populations of the Desert Locust.
Leslie matrices are used to compare theoretical populations of gregarious and solitarious Desert Locusts, Schistocerca gregaria (Forsk.). Despite their lower fecundity, the synchrony and faster maturation of gregarious populations permit them to have much faster rates of increase than solitarious populations. When realistic mortality estimates are assumed the differences can be very pronounced even when the rates of mortality are the same for both phases; this suggests that the longer period during which solitarious locusts are susceptible to predation is critical. The conclusions are briefly discussed with respect to the genesis and maintenance of locust plagues and the evolutionary significance of gregarisation.


3D In Vitro Model (R)evolution: Unveiling Tumor-Stroma Interactions.
The complex microenvironment in which malignant tumor cells grow is crucial for cancer progression. The physical and biochemical characteristics of this niche are involved in controlling cancer cell differentiation, proliferation, invasion, and metastasis. It is therefore essential to understand how cancer cells interact and communicate with their surrounding tissue - the so-called tumor stroma - and how this interplay regulates disease progression. To mimic the tumor microenvironment (TME), 3D in vitro models are widely used because they can incorporate different patient-derived tissues/cells and allow longitudinal readouts, thus permitting deeper understanding of cell interactions. These models are therefore excellent tools to bridge the gap between oversimplified 2D systems and unrepresentative animal models. We present an overview of state-of-the-art 3D models for studying tumor-stroma interactions, with a focus on understanding why the TME is a key target in cancer therapy.


Induction of hepatic drug-metabolizing enzymes in rats treated with 1-nitropyrene.
The inducing effects of 1-nitropyrene (1-NP) on the microsomal cytochrome P-450 system were studied in rats. Intraperitoneal administration of 1-NP led to increases in cytochrome P-450 content and aryl hydrocarbon hydroxylase, ethoxycoumarin, and ethoxyresorufin-O-deethylase activities. These increases were dose dependent. Cytochrome b5 content and aminopyrine and p-nitroanisole demethylase activities were not affected by treatment of rats with 1-NP. Substrate specificity, sensitivity to mixed-function oxidase inhibitors, and electrophoretic pattern of 1-NP-induced cytochrome(s) P-450 were compared to the major forms of cytochrome P-450 induced by phenobarbital and methylcholanthrene. Furthermore microsomes from 1-NP-induced rats showed greater ability to metabolize the chemical as compared with those from control animals; this result indicates that 1-NP induces a form(s) of cytochrome P-450 especially effective in the metabolism of the substance itself.


Cerebellar hemangioblastoma simulating arachnoid cyst on imaging and surgery.
A case of posterior fossa hemangioblastoma simulating arachnoid cyst on imaging and peroperatively is presented. In vivo proton MR spectroscopy showed evidence of large lactate and resonance at 2.37 ppm not observed earlier in the cystic lesions, including arachnoid cyst. The demonstration of this resonance may help in characterization of these lesions that may be confused with arachnoid cysts on imaging and during surgery.


Lumbar puncture position in infants-a systematic review and meta-analysis.
To analyze the optimal lumbar puncture position in infants. A systematic review and meta-analysis. Infants (age < 1 year). December 2022 in PubMed, Scopus, and Web of Science. Randomized controlled trials focusing on lumbar puncture positions were included. Other lumbar puncture position than standard lateral decubitus position. First puncture success and overall success rate. Secondary outcome was desaturation during puncture and procedure-related harms. Risk of bias 2.0 assessment was performed. Outcomes are reported as risk ratios (RR) with 95% confidence intervals (CI). We screened 225 abstracts, and six studies were included. Four studies compared sitting position, one study head elevated lateral position, and one study prone position to lateral position. Risk of bias was high in two studies. First puncture success rate in sitting position (RR 1.00, CI: 0.78-1.18; 2 studies) and overall success rate in sitting position were similar to lateral position (RR 0.97, CI: 0.87-1.17; 3 studies). First attempt success rate was higher in elevated lateral position (RR 1.48, CI: 1.14-1.92; 1 study) and in prone position (RR 1.09, CI: 1.00-1.17; 1 study). Conclusion: Sitting position seems to be equally effective in terms of first attempt and overall success in lumbar puncture than standard lateral position. Elevated lateral position and prone positions had better first attempt success than standard lateral position, but these were assessed only in one study each and thus further studies in these positions are needed. Trial registration: This review was registered in PROSPERO. ID: CRD42022382953. What is Known: • Success rate in lumbar puncture has been poor and first attempt success rate has varied between 50 to 80% in literature. • Optimal lumbar puncture positions for infants have been debated between sitting and lateral decubitus position mostly. What is New: • This is the first meta-analysis focused on lumbar puncture positions in infants, and it found that sitting position was equal to standard lateral position. • Prone position and head elevated lateral positions had higher first puncture success rates, but these were assessed both only in one study, which creates uncertainty to the finding.


Rubratoxin B mycotoxicosis in the Syrian hamster: ultrastructural alterations.
Rubratoxin B was given to Syrian hamsters as a single intraperitoneal dose of 0.4 mg/kg. Hamsters were killed at 1, 2, 4, and 6 hr after dosing, and the kidneys and liver were fixed by intravascular perfusion. Renal ultrastructural alterations were evident at 1 hr after treatment and were limited to the straight portion of the proximal tubule. The most prominent alterations were brush border disruption, dilation of smooth endoplasmic reticulum, mitochondrial swelling, cytoplasmic rarefaction, myelin figure formation, and swelling of basal interdigitating processes. Renal alterations were suggestive of damage to membrane structure and/or transport functions and interference with cellular bioenergetics. Hepatic alterations were not seen in the rubratoxin B-treated hamsters of this study.


Impact of the SARS-CoV-2 pandemic on routine immunisation services: evidence of disruption and recovery from 170 countries and territories.
The SARS-CoV-2 pandemic has revealed the vulnerability of immunisation systems worldwide, although the scale of these disruptions has not been described at a global level. This study aims to assess the impact of COVID-19 on routine immunisation using triangulated data from global, country-based, and individual-reported sources obtained during the pandemic period. This report synthesised data from 170 countries and territories. Data sources included administered vaccine-dose data from January to December, 2019, and January to December, 2020, WHO regional office reports, and a WHO-led pulse survey administered in April, 2020, and June, 2020. Results were expressed as frequencies and proportions of respondents or reporting countries. Data on vaccine doses administered were weighted by the population of surviving infants per country. A decline in the number of administered doses of diphtheria-pertussis-tetanus-containing vaccine (DTP3) and first dose of measles-containing vaccine (MCV1) in the first half of 2020 was noted. The lowest number of vaccine doses administered was observed in April, 2020, when 33% fewer DTP3 doses were administered globally, ranging from 9% in the WHO African region to 57% in the South-East Asia region. Recovery of vaccinations began by June, 2020, and continued into late 2020. WHO regional offices reported substantial disruption to routine vaccination sessions in April, 2020, related to interrupted vaccination demand and supply, including reduced availability of the health workforce. Pulse survey analysis revealed that 45 (69%) of 65 countries showed disruption in outreach services compared with 27 (44%) of 62 countries with disrupted fixed-post immunisation services. The marked magnitude and global scale of immunisation disruption evokes the dangers of vaccine-preventable disease outbreaks in the future. Trends indicating partial resumption of services highlight the urgent need for ongoing assessment of recovery, catch-up vaccination strategy implementation for vulnerable populations, and ensuring vaccine coverage equity and health system resilience. US Agency for International Development.


Delayed discovery of Hsp60 and subsequent characterization of moonlighting functions of multiple Hsp60 genes in Drosophila: a personal historical perspective.
The pioneering studies carried out on heat shock-induced synthesis of specific proteins in the early 1970s did not identify any Hsp60 family protein in Drosophila. By the early 1980s, although the members of Hsp60 family of heat shock proteins (Hsp) were identified in a wide range of eukaryotes as homologs of the bacterial GroEL, none was known in Drosophila. The existence of the Hsp60 family protein was serendipitously revealed in Drosophila in my laboratory in 1989. Contrary to the earlier reports that all tissues in flies display the canonical heat shock response, the larval Malpighian tubules (MT) did not show induction of any of the major Hsps but synthesis of a putative Hsp60 family protein was found to be the most abundant in this tissue. A few years later, we identified this MTspecific heat shock-induced protein to indeed be a member of the Hsp60/chaperonin family. The Drosophila genome sequence projects subsequently revealed four putative Hsp60 gene sequences in the D. melanogaster genome. The present historical perspective chronicles contributions from my and other laboratories that unraveled several aspects of intriguing biology of the multiple Hsp60 genes in D. melanogaster, and highlights challenging questions awaiting future studies.


Applications of gas-liquid chromatography in protein chemistry. II. Determination of amide residues in nanomolar amounts of proteins.
A method for the quantitative determination of amide residues in nanomolar amounts of proteins is described, based on dilute acid hydrolysis at 100 degrees, followed by isothermal gas-liquid chromatography of the ammonia released by on-column neutralisation of the hydrolysate and quantitation by means of a conductometric detector. Amide contents are given for twenty well characterised proteins, as well as for asparagine and glutamine.