Strategy of the EORTC-MCG trial programme for adjuvant treatment of moderate-risk and high-risk melanoma.
Trials in high-risk melanoma patients evaluating the role of postoperative adjuvant treatment with interferons or other cytokines, ganglioside-based vaccines, or vaccines based on melanoma cells are ongoing or planned internationally. In Europe, the two largest randomised trials are carried out by the European Organization for Research and Treatment of Cancer-Melanoma Cooperative Group (EORTC-MCG). In stage IIA patients (T3N0M0) with a moderate risk of micrometastatic disease (35-40%), Trial 18,961 compares observation with ganglioside GM2 vaccination. This trial will be activated during the spring of 1998 and is expected to enrol 1000 patients. In stage IIB-IIIB (T4N0M0-TxN12M0) patients with a high risk of micrometastatic disease (approximately 80%), trial 18,952 compares observation with adjuvant therapy using two intermediate dosage regimens of interferon alfa-2b (IFN-alpha 2b). These trials and the philosophy of the EORTC-MCG programme allow more toxic treatment regimens to be investigated in patients with high-risk disease and only treatments with minimal toxicity to be evaluated in patients with moderate- to low-risk disease. Recently completed and other ongoing trials also are discussed. Overall, if clinical efficacy is demonstrated, the toxicity, impact on quality of life and treatment costs determine the acceptance and applicability of a treatment.


Diagnostic accuracy of b800 and b1500 DWI-MRI of the pelvis to detect residual rectal adenocarcinoma: a multi-reader study.
To compare the sensitivity, specificity and intra-observer and inter-observer agreement of pelvic magnetic resonance imaging (MRI) b800 and b1500 s/mm2 sequences in the detection of residual adenocarcinoma after neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer (LARC). Detection of residual adenocarcinoma after neoadjuvant CRT for LARC has become increasingly important and relies on both MRI and endoscopic surveillance. Optimal MRI diffusion b values have yet to be established for this clinical purpose. From our MRI database between 2018 and 2019, we identified a cohort of 28 patients after exclusions who underwent MRI of the rectum before and after neoadjuvant chemoradiation with a protocol that included both b800 and b1500 s/mm2 diffusion sequences. Four radiologists experienced in rectal MRI interpreted the post-CRT MRI studies with either b800 DWI or b1500 DWI, and a minimum of 2 weeks later re-interpreted the same studies using the other b value sequence. Surgical pathology or endoscopic follow-up for 1 year without tumor re-growth was used as the reference standard. Descriptive statistics compared accuracy for each reader and for all readers combined between b values. Inter-observer agreement was assessed using kappa statistics. A p value of 0.05 or less was considered significant. Within the cohort, 19/28 (67.9%) had residual tumor, while 9/28 (32.1%) had a complete response. Among four readers, one reader had increased sensitivity for detection of residual tumor at b1500 s/mm2 (0.737 vs. 0.526, p = 0.046). There was no significant difference between detection of residual tumor at b800 and at b1500 for the rest of the readers. With all readers combined, the pooled sensitivity was 0.724 at b1500 versus 0.605 at b800, but this was not significant (p = 0.119). There was no difference in agreement between readers at the two b value settings (67.8% at b800 vs. 72.0% at b1500), or for any combination of individual readers. Aside from one reader demonstrating increased sensitivity, no significant difference in accuracy parameters or inter-observer agreement was found between MR using b800 and b1500 for the detection of residual tumor after neoadjuvant CRT for LARC. However, there was a suggestion of a trend towards increased sensitivity with b1500, and further studies using larger cohorts may be needed to further investigate this topic.


Downregulation of SHMT2 promotes the prostate cancer proliferation and metastasis by inducing epithelial-mesenchymal transition.
Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme that regulates serine/glycine transition; however, its specific function and molecular mechanisms in tumors remain controversial. In this study, we aimed to enhance the understanding in this regard. Through in vitro and in vivo experiments, as well as data analyses using public databases, we investigated the effect of SHMT2 in prostate cancer. Our results indicated that SHMT2 acts as a prostate cancer tumor proliferation suppressor and negatively regulates the aggressive behavior of prostate cancer through activation of epithelial-mesenchymal transition. Additionally, downregulated SHMT2 expression was observed in more advanced prostate cancer phenotypes, and further analysis showed that its depletion promoted proliferation and migration in prostate cancer cell lines. Taken together, our results revealed the function of SHMT2 in prostate cancer and may potentially play a role in the exploration of new therapeutic strategies.


Stress, coping and silver linings: How depressed perinatal women experienced the COVID-19 pandemic.
Research on perinatal mental health during the COVID-19 pandemic has largely focused on data from community samples. This study sought to understand the experiences of pregnant and postpartum women with histories of clinically elevated symptoms of depression. Participants included 60 perinatal women who participated in wellness intervention trials for women with antenatal depression. We used a mixed methods approach, assessing depression, anxiety, stressors and coping behaviors, along with narrative responses to questions regarding COVID-specific effects on mental health. Over three-fourths of the sample indicated a worsening of mental health during the pandemic, with 31.7% of women endorsing clinically elevated depression symptoms and 36.7% screening positive for anxiety. Women reported negative impacts on their emotional wellbeing, especially a resurgence of mental health symptoms. Participants also articulated positive experiences during the pandemic, including an appreciation for increased time with family, especially infants. Women detailed numerous, mostly adaptive, coping strategies they had used to mitigate stress; self-isolation and spending time outdoors were associated with having depression above or below the clinical cut off, respectively. The study had a small sample, and the generalizability of findings may be limited, given that participants were clinical trial completers. Although the pandemic upended many aspects of life for perinatal women and raised mental health concerns, many also reported adaptive means of coping and positive experiences or 'silver linings' related to pandemic restrictions. Some coping strategies that were utilized, including wellness-based behaviors, may have helped to mitigate the impact of COVID-19 related stress.


Production and characterization of polyclonal and monoclonal antibodies against Aflatoxin B1 oxime-BSA in an enzyme-linked immunosorbent assay.
From a single aflatoxin B1 oxime - bovine serum albumin conjugate, polyclonal and monoclonal antibody preparations were produced. The four rabbit polyclonal antisera were specific for aflatoxin Bi in a microtitration plate enzyme - linked immunosorbent assay. The monoclonal antibodies showed a wide range of differing specificities, recognizing, for example, aflatoxins B1, B2, G1 and G2; B1 and B2; B1 and G1; and G1 alone. No antibody preparations reacted with aflatoxin M1. The significance of these results to the strategy of anti-aflatoxin antibody production for use in quantitative enzyme immunoassays is discussed.


SAPHO syndrome and pustulotic arthro-osteitis.
Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10-30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements.


The passage of spermatozoa through the vitelline membrane in the domestic fowl, Gallus gallus.
The developing outer layer of the vitelline membrane of the ovum in the posterior part of the infundibulum of the domestic fowl contains many spermatozoa in nearly parallel orientation with its inner layer. When the acrosomal region of a spermatozoon approaches or contacts the inner layer, promptly undergoes the acrosome reaction. The outer acrosomal membrane and overlying plasma membrane fuse together and the apical region of the acrosome opens, so that the acrosomal contents are released. Meanwhile the spermatozoon remains a time in contact with the surface of the inner layer, and the network of the inner layer just under the tip of the sperm head begins to be dissolved. This dissolution extends downward forming a tunnel, approximately 9 micrometer in diameter. The spermatozoon then passes through the inner layer obliquely via the central region of the tunnel and arrives at the perivitelline space.


'Debulking' surgery is unnecessary in advanced abdominal Burkitt lymphoma in Iraq.
In a previous study (Burkitt lymphoma study I, BL I) between 1982 and 1984, we used a multidrug rotating chemotherapy schedule, now known as 'GRAB', to treat 24 Iraqi children with non-localised BL (Murphy stages II, III and IV). At the time of reporting, actuarial survival was 50% (current actual survival 42%) and the major morbidity and mortality was not from resistant or relapsed lymphoma, but from complications of the tumour lysis syndrome, sepsis and early abdominal surgery. The study (BL II) reported here was carried out between 1984 and 1986; we used GRAB to treat 24 newly and consecutively diagnosed children with advanced Burkitt lymphoma but discouraged early 'debulking' surgery and paid special attention to supportive care during the first two weeks of treatment. As in BL I, no radiotherapy was used. Twenty patients (83.8%) attained complete remission: 17 (71%), including three of the seven stage IV patients, survive continuously disease-free at a median of 26 months (range 18-36 months) from diagnosis. We have previously pointed out that GRAB, without radiotherapy, may be especially suited for use in some developing countries. From this study we conclude that, with appropriate supportive care and minimal surgery, survival rates over 50% may be achieved. Our next studies are aimed at defining a 'good risk' group of patients, who may be curable without alkylating agents and a 'poor risk' group, who need more intensive therapy.


Pulmonary atherosclerosis associated with an atrial septal defect in old age: case report of an elderly autopsied patient.
In the literature, there are few studies on atherosclerosis in the pulmonary artery in human beings, especially in aging. The aim of the study was to report the anatomic pathological aspects of an old patient who had severe pulmonary atherosclerosis associated with an atrial septal defect (ASD). The patient had marked atherosclerosis in the pulmonary trunk and its branches, probably caused by a series of hemodynamic and endothelial changes, subsequent to the ASD. The left to right shunt could have caused an increase in the blood flow and pulmonary hypertension, intensified by the vascular alterations in the region. This hypertension probably became intense to the point of reversing the direction of the shunt, from the right to the left, characterizing a probable Eisenmenger syndrome, responsible for the patient's dyspnea and cyanosis. Our study demonstrates a condition that is especially infrequent because of the patient's age of 64 years and, thus, adds to the literature.


Variations in the composition of arterial wall isomeric chondroitin sulfate proteoglycans among different animal species.
1. Isomeric chondroitin sulfate proteoglycans were extracted from human, bovine, swine and rabbit aortas by 4 M guanidine-HCl and were fractionated and purified by CsCl isopycnic centrifugation, Sepharose CL-4B gel filtration, DEAE-Sepharose ion-exchange chromatography and octyl-Sepharose hydrophobic interaction chromatography. 2. The molecular size and the composition of isomeric chondroitin sulfate proteoglycans varied among species. Variations were also noted in the composition and molecular weight of constituent glycosaminoglycan chains. 3. Observations made on chondroitinase ABC and chondroitinase AC digests of proteoglycans indicate that dermatan sulfate is linked to the core proteins through chondroitin sulfates.


No abortion-inducing effect of the ulcer-healing dose of the synthetic prostaglandin E2 analogue enprostil in first trimester.
Milligram-range doses of E2 prostaglandins have long been used to induce labor or abortion in the second and third trimesters of pregnancy. Enprostil, a synthetic dehydroprostaglandin E2 structural analogue, is administered in microgram doses for the treatment of acute duodenal ulcer and acute gastric ulcer. This study examined the effect of the ulcer-healing dose and twice the ulcer-healing dose upon women in the first trimester of pregnancy. Two hundred and seven women who had requested legal abortion in the first trimester participated in two randomized, double-blind, placebo-controlled, parallel studies. They received two doses of enprostil 35 micrograms (the recommended dose for the treatment of duodenal and gastric ulcer) (n = 51), 70 micrograms (twice the recommended dose) (n = 53), or placebo (n = 103) 12 h apart. No drug-induced abortions occurred in any of the first-trimester pregnancies. Vaginal bleeding occurred in 4% of volunteers receiving the lower dose and 4% receiving the higher dose of enprostil. Vaginal bleeding occurred in up to 2% of volunteers on placebo. Although not recommended for pregnant women, if enprostil is given inadvertently to pregnant women with ulcers, it is unlikely to endanger the pregnancy during the first trimester.


Two paleopathological cases suggestive of paralabral cysts of the shoulder.
To undertake differential diagnosis of scapular bone defects found in two medieval skeletons buried in different necropoles of Friuli Venezia Giulia (Italy) and to evaluate the clinical significance of paralabral cysts in the context of shoulder pathology. Individual JoT36 is an adult male exhumed from a necropolis belonging to a rural agricultural settlement dated to the 10th to 11th century A.D. Individual CIVT58 is an adult male from a Langobard necropolis dated to 630-670 A.D. Macroscopic examination of the skeletons was performed using standard osteological methods and review of pertinent clinical literature to assist differential diagnosis. Between the glenoid cavity and the spinoglenoid notch of the right scapula of JoT36 there is a multilocular circular defect adjacent to the glenoid rim. On the neck of the left scapula of CIVT58, immediately above the spinoglenoid notch, there is a unilocular circular depression. In both cases, the cortical bone appears smooth without any evidence of erosion or sclerosis. Skeletal findings and historical/archaeological contexts of both cases are compatible with the diagnosis of paralabral cysts. Paralabral cysts are relatively frequently observed in clinical settings but very few examples have been documented in paleopathological literature. This study seeks to improve recognition and interpretation of this pathology in historical/archaeological contexts. Findings from a case report can neither generate epidemiological information nor be generalized. Identification of new cases may add valuable information about lifestyles and related shoulder pathologies in ancient times.


Can monocyte to HDL cholesterol ratio and monocyte to lymphocyte ratio be markers for inflammation and oxidative stress in patients with vitiligo? A preliminary study.
Both systemic inflammation and oxidative stress play crucial roles in the pathogenesis of vitiligo. In recent studies, monocyte to high-density lipoprotein cholesterol ratio (MHR), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV) and plateletcrit (PCT) have been shown to reflect inflammation and oxidative stress in chronic inflammatory and autoimmune diseases. In this study, we aimed to investigate the hematological and inflammatory parameters in patients with vitiligo and to evaluate their possible relationship with disease severity. The parameters including MHR, MLR, NLR, PLR, MPV, and PCT were retrospectively investigated in patients with vitiligo and healthy controls. Disease severity was evaluated using the vitiligo extent tensity index (VETI) score. A total of 180 patients with vitiligo, and age-gender-matched 180 healthy controls were enrolled in the study. MHR, MLR, PLR, PCT values were found to be significantly higher in patients with vitiligo (p < 0.05). MPV and NLR values showed no statistically significant difference between the two groups. A positive correlation was also detected between MHR and MLR values, disease duration, and VETI score (p < 0.05). We suggest that MHR and MLR can be used as markers of inflammation and oxidative stress in patients with vitiligo. Both markers may also reflect disease severity.


Contrasting effects on ganciclovir susceptibility and replicative capacity of two mutations at codon 466 of the human cytomegalovirus UL97 gene.
Human cytomegalovirus (HCMV) infections cause significant morbidity in immunocompromised hosts. Resistance to ganciclovir is predominantly associated with alterations in the HCMV UL97 kinase and, more occasionally, with mutations in the HCMV DNA polymerase gene. The aim of this study was to investigate the impact of two different mutations found at the same UL97 codon on drug susceptibility and viral replicative capacity. Mutation V466G was observed in a solid organ transplant recipient whereas mutation V466M was observed in a patient with AIDS. Two HCMV UL97 mutations, V466M and V466G, were transferred to recombinant viruses using a bacterial artificial chromosome system. Susceptibility testing of the recombinant wild-type and mutant viruses was performed using a standard plaque reduction assay. Replication kinetics of recombinant viruses was investigated using a yield assay. Mutant V466G was resistant to ganciclovir and had significant replicative defect whereas mutant V466M was drug susceptible and had unaltered replication kinetics. Furthermore, mutant V466G formed small viral plaques with intracellular inclusions. To our knowledge, this is the first report of such contrasting phenotypes for drug susceptibility and replicative capacity for HCMV mutations found at the same codon of the UL97 gene.


Synergistic use of higher-protein diets or nutritional supplements with resistance training to counter sarcopenia.
Resistance exercise training helps older people treat sarcopenia. The consumption of diets that include sources of high-quality protein and total protein intakes that are moderately above the recommended dietary allowance of 0.8 g x kg(-1) x d(-1) while regularly performing resistance exercises can help older people retain or increase whole-body fat-free mass and muscle mass. Limited research suggests that protein-enriched nutritional supplements do not influence training-induced improvements when adequate dietary protein is consumed.


Garlic (Allium sativum) attenuate glomerular glycation in streptozotocin-induced diabetic rats: A possible role of insulin.
This study investigated the effect of fresh garlic aqueous extract on glomerular glycation in streptozotocin-induced diabetic rats. Serum insulin and glucose, in addition to renal corpuscles and erythrocyte hemoglobin glycation were determined in normal saline-treated normal rats (NS-NR), normal saline-treated diabetic rats (NS-DR) and garlic-treated diabetic rats (G-DR). Compared to NS-NR, NS-DR showed significant decrease in serum insulin and increase in serum glucose and hemoglobin glycation. NS-DR also showed intense, diffused glomerular periodic acid Schiff activity. Compared to NS-DR, G-DR showed significant increase in serum insulin and decrease in serum glucose and hemoglobin glycation. Furthermore, the G-DR glomerular periodic acid Schiff activity and distribution was almost restored to that observed in NS-NR. Garlic may attenuate glomerular glycation in streptozotocin-induced diabetic rats. This effect could be partially mediated via euglycemia induced by revitalization of endogenous insulin.


Problems and pitfalls of compression fixation of long bone fractures: a review of results and complications.
The complications encountered in the compression fixation of 70 cortical long bone fractures are reviewed. The results represent the initial experience with the AO fixation equipment following its introduction to a centre with staff relatively untrained in the technique. Infection was the most serious complication, with a deep sepsis rate of 10.5 per cent, but fixation failure, delayed union and refracture also occurred. The various problems are discussed in detail and suggestions are made as to how they can be avoided.


Two different pathways of interferon mediated suppression of antibody secretion.
Interferon suppresses a variety of in vitro immune responses by a mechanism which has not been well defined. Both direct suppression and activation of suppressor T cells have been suggested as possible mechanisms of interferon action. In an attempt to examine this question interferon-alpha (IFN alpha)-mediated suppression of a plaque forming cell response to a T cell independent antigen by spleen cells or by B cells was examined. Somewhat greater quantities of IFN alpha were required to suppress plaque forming cell responses by B cells than by spleen cells to the antigen fluoresceinated-Brucella abortus (FITC-BA). However, suppression of spleen cell responses could be blocked by addition of either 2-mercaptoethanol, levamisole or monoclonal antibodies against the lymphokine, soluble immune response suppressor (SIRS), whereas suppression of B cell responses by interferon-alpha was unaffected by these agents. Each of these agents interferes with SIRS mediated suppression of immune responses. Addition of T cells to B cell cultures stimulated with FITC-BA did not affect the total plaque forming cell response nor the extent of suppression by IFN alpha, but it did restore 2-mercaptoethanol sensitivity to IFN alpha-mediated suppression. As few as 1 X 10(5) T cells were effective and it was necessary to add T cells within 3 h of addition of IFN alpha to confer 2-mercaptoethanol sensitivity to IFN alpha mediated suppression. These data suggest that IFN alpha can suppress immune responses by two different pathways and that in the presence of T cells, activation of suppressor T cells is the dominant pathway. The presence of T cells must also prevent direct suppression of B cells by IFN alpha.


Long-acting contraception in adolescents and young women with type 1 and type 2 diabetes.
Adolescent pregnancy is a major public health problem worldwide. Adolescents living with diabetes are not aware of the risks of unplanned pregnancy and the high rate of fetal and maternal complications when gestation occurs in women with significant hyperglycemia. These data highlight the significance of pregnancy prevention in young women with diabetes. Long-acting reversible contraceptives (LARCs), which include subdermal progestin implants and hormonal and nonhormonal intrauterine devices (IUDs), have been recommended by the American College of Obstetricians Gynecologists and the American Academy of Pediatrics as a first-line contraceptive option for adolescents and young women. This article reviews LARC options for adolescents and young women with type 1 (T1D) and type 2 (T2D) diabetes as well as the possible complications and side effects.


Comparative molecular dynamics simulations of the antimicrobial peptide CM15 in model lipid bilayers.
We report altogether 3-μs molecular dynamics (MD) simulations of the antimicrobial peptide CM15 to systematically investigate its interaction with two model lipid bilayers, pure POPC and mixed POPG:POPC (1:2). Starting with either an α-helical or a random-coil conformation, CM15 is found to insert into both bilayers. Peptide-lipid interaction is stronger with the anionic POPG:POPC than the zwitterionic POPC, which is largely attributed to the electrostatic attraction between CM15 and the negatively charged POPG. Simulations initiated with CM15 as a random coil allowed us to study peptide folding at the lipid-water interface. Interestingly, CM15 folding appears to be faster in POPC than POPG:POPC, which may be explained by a lower activation energy barrier of structural rearrangement in the former system. Our data also suggest that compared with the random-coil conformation, CM15 in a pre-folded α-helix has significantly reduced interactions with the lipids, indicating that peptide initial structures may bias the simulation results considerably on the 100-ns timescale. The implications of this result should be considered when preparing and interpreting future AMP simulations.


Comparison of the predictive validity of three fall risk assessment tools and analysis of fall-risk factors at a tertiary teaching hospital.
The main purpose of this study was to identify the best fall-risk assessment tool, among the Morse Fall Scale, the Johns Hopkins fall-risk Assessment Tool and the Hendrich II fall-risk Model, for a tertiary teaching hospital. The study also analysed fall-risk factors in the hospital, focusing on the items of each fall assessment tool. Data on falls were obtained from the patient safety reports and electronic nursing records of a tertiary teaching hospital. A retrospective study was conducted to compare the sensitivity, specificity, area under the curve, positive predictive value, negative predictive value, Youden index and accuracy of the Morse Fall Scale, the Johns Hopkins fall-risk Assessment Tool and the Hendrich II fall-risk Model. This study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology guideline for reporting case-control studies. By analysing the association between falls and the items included in the three tools, we identified significant fall-risk factors such as gait, dizziness or vertigo, changes in mental status, impulsivity, history of falling, elimination disorder, drugs affecting falls, and depression. The Hendrich II fall-risk Model had the best predictive performance for falls of the three tools, considering the highest in the area under the curve and the Youden index that comprehensively analysed sensitivity and specificity, while the Johns Hopkins fall-risk Assessment Tool had the highest accuracy. The most significant fall-risk predictors are gait, dizziness or vertigo, change in mental state, and history of falling. To improve the fall assessment performance of the Morse Fall Scale at the study hospital, we propose that it be supplemented with four most significant fall-risk predictors identified in this study.


A novel MRI-based deep learning networks combined with attention mechanism for predicting CDKN2A/B homozygous deletion status in IDH-mutant astrocytoma.
To develop a high-accuracy MRI-based deep learning method for predicting cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion status in isocitrate dehydrogenase (IDH)-mutant astrocytoma. Multiparametric brain MRI data and corresponding genomic information of 234 subjects (111 positives for CDKN2A/B homozygous deletion and 123 negatives for CDKN2A/B homozygous deletion) were obtained from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) respectively. Two independent multi-sequence networks (ResFN-Net and FN-Net) are built on the basis of ResNet and ConvNeXt network combined with attention mechanism to classify CDKN2A/B homozygous deletion status using MR images including contrast-enhanced T1-weighted imaging (CE-T1WI) and T2-weighted imaging (T2WI). The performance of the network is summarized by three-way cross-validation; ROC analysis is also performed. The average cross-validation accuracy (ACC) of ResFN-Net is 0.813. The average cross-validation area under curve (AUC) of ResFN-Net is 0.8804. The average cross-validation ACC and AUC of FN-Net is 0.9236 and 0.9704, respectively. Comparing all sequence combinations of the two networks (ResFN-Net and FN-Net), the sequence combination of CE-T1WI and T2WI performed the best, and the ACC and AUC were 0.8244, 0.8975 and 0.8971, 0.9574, respectively. The FN-Net deep learning networks based on ConvNeXt network achieved promising performance for predicting CDKN2A/B homozygous deletion status of IDH-mutant astrocytoma. A novel deep learning network (FN-Net) based on preoperative MRI was developed to predict the CDKN2A/B homozygous deletion status. This network has the potential to be a practical tool for the noninvasive characterization of CDKN2A/B in glioma to support personalized classification and treatment planning. • CDKN2A/B homozygous deletion status is an important marker for glioma grading and prognosis. • An MRI-based deep learning approach was developed to predict CDKN2A/B homozygous deletion status. • The predictive performance based on ConvNeXt network was better than that of ResNet network.


Bioenvironmental Trace Elements in Warm Climatic Plant, Pigeon Pea (Cajanus cajan).
Bioenvironmental trace elements play a vital role in plant, animal, and man metabolism. This study aims to determine trace element concentration in different parts (pods, pericarp, seeds, cotyledon, and taste) of the warm climate plant pigeon pea (Cajanus cajan L. Millsp.). The pigeon pea pods were collected from the farms on the shore of the High Dam Lake, Egypt. Elements (Ag, Au, Co, Cr, Sr, Fe, Cu, Ni, Mn, and Zn) in the pods and its different parts were determined by an atomic absorption spectrophotometer. Statistical analysis (cluster, Pearson correlation coefficient, and factor analysis) was applied to trace elements in different parts of pigeon pea. The results reveal that seeds exhibited the highest concentrations of Cu, Ni, Cr, and Zn, while Ag, Co, Pb, and Fe in the pods. Factor and cluster analyses explain a good relationship among the trace elements in pigeon pea. Also, transfer factor of the elements between plant and soil shows that the high transfer factor of most elements was observed for pods and pericarp. The studied elements in the pods and its different parts were in the safety baseline levels for both man and animal uses.


Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study.
This phase II trial assessed the activity and tolerability of a daily oral dose of 500 mg gefitinib (ZD1839, Iressa) in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma, and explored the clinical value of determining the status of the epidermal growth factor receptor (EGFR). Primary measure of efficacy was progression-free survival at 6 months. Mutations in exons 18 to 21 of EGFR and/or immunohistochemical expression of EGFR were evaluated in tumor specimens from patients enrolled in this trial as well as from patients not treated with gefitinib. Twenty-seven of 30 (90%) patients were eligible and evaluable for analysis of gefitinib efficacy and toxicity. Of these, four survived progression-free >6 months with one objective response (4%). The most commonly observed grade 3 toxicities were dermatologic (15%, 4 of 27) and diarrhea (30%, 8 of 27). Specimens from 26 of 26 or 25 of 26 patients were evaluable for immunohistochemical or mutation analysis, respectively. The response rate for patients with EGFR-positive tumors was 9% (1 of 11). EGFR expression was associated with longer progression-free survival (P = 0.008) and possibly longer survival (P = 0.082). The patient with the only objective response had a mutation in the catalytic domain of the tumor's EGFR (P = 0.04). Among 32 invasive tumors from patients not treated with gefitinib, one exhibited a catalytic domain mutation. Gefitinib was well tolerated but had minimal activity in unscreened patients with recurrent ovarian or primary peritoneal carcinoma. Prescreening patients for activating mutations in EGFR may improve response rate to gefitinib. This report is the first to document activating mutations in catalytic domain of EGFR in 3.5% (2 of 57) of ovarian cancers.


Quality and Safety in Health Care, Part XIV: The External Environment and Research for Diagnostic Processes.
The work system in which diagnosis takes place is affected by the external environment, which includes requirements such as certification, accreditation, and regulations. How errors are reported, malpractice, and the system for payment are some other aspects of the external environment. Improving the external environment is expected to decrease errors in diagnosis. More research on improving the diagnostic process is needed.


Closure of the uterine incision with one or two layers after caesarean section: a randomized controlled study in sheep.
To compare the quality of the uterine scar with one or two layer closure after caesarean section by studying biomechanical and pathological properties of the scar. A randomized controlled trial performed on eight term pregnant ewes assigned into two groups during caesarean according to type of uterine closure: single-layer or double-layer. Hysterectomy was performed 8 months after caesarean delivery. Tensile strength of all scars and of unscarred myometrium was measured. Pathological properties of the scars were analyzed histologically. The force required to reach the yield point was similar between scarred and unscarred myometrium (p=0.96), and between the scars in single-layer and double-layer closure groups (p=0.65). There was a significant increase in fibrosis width on the superficial part of the uterus in the double-layer closure group compared to the single-layer group (p=0.02). Double-layer uterine closure modified wound healing without significant change in biomechanical properties.


Molecular detection of Rickettsia felis in common fleas in Greece and comparative evaluation of genotypic methods.
Rickettsia felis is the causative agent of flea-borne spotted fever (FBSF), an emerging zoonosis. Although there is evidence of FBSF in Greece, fleas, the classic vectors of R. felis, have not been adequately studied. Thus, the aim of this study was to detect and characterize bacteria of genus Rickettsia and especially R. felis from common fleas parasitizing domestic cats and dogs in Greece and evaluate the efficiency of established molecular techniques. DNA of flea-pools (samples) by animal-host was investigated by quantitative real-time PCRs (qPCR), and 16S metagenomics (16S). Determination of Rickettsia spp., Rickettsia felis-like organisms (RFLOs), and R. felis was based on a combination of qPCRs targeting gltA and ompB genes, 16S automated metagenomics and manual comparison of 16S sequences for >99% similarity with the publicly available 16S R. felis GenBank sequences using the Basic Local Alignment Search Tool (BLAST>99). Information for the animal-hosts was available and statistically analyzed. Among 100 flea-pools, R. felis was detected in 14 samples with a combination of six, five and three assays in 10, two and two samples, respectively. The sensitivity of the assays for Rickettsia genus (16S, and genus specific qPCRs) ranged from 62.5% to 93.8% and the specificity from 65.0% to 100%. R. felis-targeting qPCRs for gltA and ompB demonstrated sensitivity and specificity of 92.9% and 100%, and 100.0% and 87.5%, respectively. 16S metagenomics using the assay software was not able to identify R. felis positive specimens, although manual BLAST>99 did identify the species, but demonstrated sensitivity of 92.9% and specificity of 65.0%. No association of the detection rate of Rickettsia genus or R. felis, with the epidemiological data collected, was identified. These observations suggest the occurrence of R. felis in fleas from pets in Attica, Greece, but PCR and sequencing assays varied considerably in sensitivity and specificity and a consensus methodology for assigning the positivity status is required to be established.


[West's syndrome after Reye's syndrome (author's transl)].
A four month old boy with typical clinical, biochemical and pathological picture of Reye's syndrome is reported. He was treated with peritoneal dialysis and survived. He presented flexor-spasms with hipsarrythmic E.E.G. one month after the beginning of the clinical picture. Some coments are made on the relation of both conditions and prognostic data on the Reve's syndrome.


Analysis of signal transduction pathways regulating cytokine-mediated Fc receptor activation on human eosinophils.
Igs can be potent stimulants of eosinophil activation since interaction with IgA or IgG-coated particles can lead to eosinophil degranulation. We have investigated the comparative roles of mitogen-activated protein (MAP) kinases (MAPKs; ERK1/2 and p38) and phosphatidylinositol-3 kinase (PI3K) in the priming and regulation of Fc receptor functioning on human eosinophils utilizing a MAPK kinase (MEK) inhibitor (PD98059), a p38 inhibitor SB203580, and the widely used PI3K inhibitors wortmannin and LY294002. We demonstrate that priming of human eosinophils with Th2-derived cytokines, IL-4 and IL-5, differentially activate phosphotyrosine-associated PI3K and ERK and p38 MAP kinases. This activation can be inhibited by pre-incubation with wortmannin or LY294002, PD98059, and SB203580, respectively. Analysis of the effects of the inhibitors on rosette formation between human eosinophils and IgA- or IgG-coated beads revealed that activation of MEK was not required for IgA binding after priming with IL-4 or IL-5. However, inhibition of MEK did inhibit IL-5-primed binding of IgG-beads. The rosette formation of primed eosinophils with IgA-beads could be completely inhibited by wortmannin and LY294002 treatment, demonstrating a critical role for PI3K. Interestingly, inhibition of the p38 pathway also resulted in a complete blockade of IgA rosette formation. This work demonstrates regulatory control by inside-out signaling of Fc receptors by various cytokines on human eosinophils. Thus in vivo the local production of Th2-derived cytokines will regulate the effector functions of Fc receptors.


Mussel-inspired proteins functionalize catheter with antifouling and antibacterial properties.
Bacterial adhesion and subsequent biofilm formation on catheter can cause inevitably infection. The development of multifunctional antibacterial coating is a promising strategy to resist the bacteria adhesion and biofilm formation. Herein, a mussel-inspired chimeric protein MZAgP is prepared and employed to modify a variety of polymeric catheters. The MZAgP is composed of mussel-adhesive peptide, zwitterionic peptide, and silver-binding peptide, which can endow catheters with antifouling, bactericidal and biocompatibility performances. Expectedly, negligible biofilm is observed on the MZAgP coated catheters after incubating with bacteria for 120 h. And ignorable hemolysis and cytotoxicity are obtained on coated catheters. In addition, the modified catheters also display persistent antifouling and bacteriostatic properties throughout 168 h under hydrodynamic conditions. Moreover, the coated catheters can still remain excellent antifouling and antibacterial properties even after 2 months of storage. This multifunctional coating may be promising as antibacterial and antibiofilm biomaterial, and the coated catheters are potential in clinical application.


[Heat shock proteins: functions and role in adaptation to hyperthermia].
The results are generalized of many-year studies into the adaptive role of heat shock proteins in different animals, including the representatives of cold- and warm-blooded species that inhabit regions with different thermal conditions. Adaptive evolution of the response to hyperthermia can lead to different results depending on the species. The thermal threshold of induction of the heat shock proteins in desert thermophylic species is, as a rule, higher than in the moderate climate species. In addition, thermoresistant species are often characterized by a certain level of heat shock proteins in cells even at a physiologically normal temperature. Although adaptation to hyperthermia is achieved in most cases without changes in the number of heat shock genes, they can be amplified in some cases in termophylic species. The role of mobile elements in evolution of the heat shock genes was shown and approach was developed for directional introduction of mutations in the promoter regions of these genes.


Bcl-2 family proteins and cancer.
BCL-2 was the first anti-death gene discovered, a milestone with far reaching implications for tumor biology. Multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including six antiapoptotic, three structurally similar proapoptotic proteins and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. These proteins, in turn, are regulated through myriad post-translational modifications and interactions with other proteins. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis and autophagy, thus operating as nodal points at the convergence of multiple pathways with broad relevance to oncology. Experimental therapies targeting Bcl-2-family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may soon be available.


Recent developments in myofibroblast biology: paradigms for connective tissue remodeling.
The discovery of the myofibroblast has opened new perspectives for the comprehension of the biological mechanisms involved in wound healing and fibrotic diseases. In recent years, many advances have been made in understanding important aspects of myofibroblast basic biological characteristics. This review summarizes such advances in several fields, such as the following: i) force production by the myofibroblast and mechanisms of connective tissue remodeling; ii) factors controlling the expression of α-smooth muscle actin, the most used marker of myofibroblastic phenotype and, more important, involved in force generation by the myofibroblast; and iii) factors affecting genesis of the myofibroblast and its differentiation from precursor cells, in particular epigenetic factors, such as DNA methylation, microRNAs, and histone modification. We also review the origin and the specific features of the myofibroblast in diverse fibrotic lesions, such as systemic sclerosis; kidney, liver, and lung fibrosis; and the stromal reaction to certain epithelial tumors. Finally, we summarize the emerging strategies for influencing myofibroblast behavior in vitro and in vivo, with the ultimate goal of an effective therapeutic approach for myofibroblast-dependent diseases.


The role of endoscopic retrograde cholangiography in the diagnosis and management of patients with primary sclerosing cholangitis.
The clinical and radiological findings in four patients with primary sclerosing cholangitis one of whom had coexistent cholangiocarcinoma, are reported. The need for surgical exploration to make the diagnosis was averted by the use of endoscopic retrograde cholangiography in one patient who was managed initially with medical treatment alone. Endoscopic cholangiography may be used to monitor the progress of the sclerosing lesions; but failure to fill the intrahepatic ducts is associated with a poor prognosis due either to the severity of the sclerosing process or the presence of coexistent cholangiocarcinoma.


Endodermal cyst of septum pellucidum and pregnancy: a case report.
Endodermal or Neurenteric cysts are commonly found in spine. Their intracranial occurrence is rare and such a cyst in the septum pellucidum is exceptional. We report a woman, with 33 week pregnancy, presenting in a semiconscious state due to raised intracranial pressure (ICP) due to hydrocephalus caused by a large lesion in the septum pellucidum. Computed tomography (CT) revealed the lesion which was better characterised by the Magnetic Resonance Imaging (MRI). First baby was delivered by LSCS and bilateral ventriculo-peritoneal shunts were inserted; and later on the cyst was excised. There was full neurological recovery following the insertion of VP shunt. After excision of cyst cerebrospinal fluid (CSF) pathway was established and shunts could be removed. Post-operative period was complicated by septic ventriculitis. Eventually patient was discharged home in excellent condition. Endodermal cyst of septum pellucidum is an uncommon condition. Such lesions may be large when revealed, good outcome is expected after surgical excision.


[Inhibition of rat liver delta 4-3-ketosteroid-5 alpha-reductase by steroids in vitro].
The inhibition of the hydrogenation of testerone to 5alpha-dihydrotestosterone in microsomes of female rat liver has been studied by progesterone-, testosterone- and estradiol derivatives. In the pregnane series, progesterone, 17alpha-OH-progesterone and its acetate were the strongest inhibitors. In the estradiol series, 3-hydroxy-compounds with a CH2X-substituent at 17alpha-position were stronger inhibitors than the respective 3-methoxy derivatives. The most potent inhibitor till now is an estradiol derivative with a SeCN group in 16alpha-position.


Matrix metalloproteinase-9 is elevated in serum of alcohol abusers.
Moderate alcohol consumption has been shown to protect against coronary heart disease. However, excessive alcohol use has been suggested to have detrimental effects on the cardiovascular system. We examined whether there is an association between alcohol abuse and circulating levels of matrix metalloproteinase-9 (MMP-9), which has been linked to unstable coronary heart disease and arterial inflammation. Serum MMP-9 concentrations were compared between 40 male alcoholics (mean age 42 years) with ethanol consumption > 1000 g week(-1) and 40 social drinker males with an ethanol consumption of < 200 g week(-1) (mean age 45 years). The mean serum MMP-9 concentration was significantly higher in sera of alcoholics compared to control subjects (70.9 +/- 47.7 g L(-1) and 43.1 +/- 19.2 g L(-1), respectively; P = 0.001). Within the alcoholic group, MMP-9 concentration did not correlate with age, gamma glutamyl transferase, carbohydrate-deficient transferrin, aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase. Our finding of elevated MMP-9 concentrations in sera of chronic alcohol abusers helps understand the mechanisms of cardiovascular risk among these subjects.


Characteristics of single atmospheric particles in a heavily polluted urban area of China: size distributions and mixing states.
To investigate the chemical composition, size distribution, and mixing state of aerosol particles on heavy pollution days, single-particle aerosol mass spectrometry was conducted during 9-26 October 2015 in Xi'an, China. The measured particles were classified into six major categories: biomass burning (BB) particles, K-secondary particles, elemental carbon (EC)-related particles, metal-containing particles, dust, and organic carbon (OC) particles. BB and EC-related particles were the dominant types during the study period and mainly originated from biomass burning, vehicle emissions, and coal combustion. According to the ambient air quality index, two typical episodes were defined: clean days (CDs) and polluted days (PDs). Accumulation of BB particles and EC-related particles was the main reason for the pollution in Xi'an. Most types of particle size were larger on PDs than CDs. Each particle type was mixed with secondary species to different degrees on CDs and PDs, indicating that atmospheric aging occurred. The mixing state results demonstrated that the primary tracers were oxidized or vanished and that the amount of secondary species was increased on PDs. This study provides valuable information and a dataset to help control air pollution in the urban areas of Xi'an. Graphical abstract.


Differences in short-term clinical and radiological outcomes depending on timing of balloon kyphoplasty for painful osteoporotic vertebral fracture.
Balloon kyphoplasty or vertebroplasty is widely performed as a surgical intervention for osteoporotic vertebral fracture (OVF) and the effects have been investigated in many previous studies. However, the influence of the timing of the procedure on patient outcomes has not been studied formally. The purpose of this study was to investigate differences in the surgical outcomes of OVFs according to the timing of balloon kyphoplasty. This was a multicenter cohort study. Participants comprised 72 consecutive patients who underwent balloon kyphoplasty between January 2012 and January 2016. Patients were analyzed in two groups according to the timing of kyphoplasty after onset (Early group: ≤2 months; Late group: >2 months). Follow-up continued for more than 6 months. A total of 72 patients were effectively analyzed. Of these, 27 (38%) patients underwent kyphoplasty within 2 months after symptom onset. The Late group showed greater angular motion of fractured vertebrae (p = 0.005) and compression of anterior vertebral height (p = 0.001) before surgery. Final outcomes adjusted for age and preoperative outcome showed lower visual analog scale (VAS) scores for low back pain in the Early group than in the Late group (19.9 vs. 30.4, p = 0.049). Final relative anterior vertebral height and kyphotic angle were more preserved in the Early group than in the Late group (p = 0.002 and p = 0.020, respectively), although absolute differences were not significant. Vertebral height and kyphotic angle before and after balloon kyphoplasty were greater in patients who underwent kyphoplasty within 2 months after onset, and the VAS score for low back pain at final follow-up was better. Our results support kyphoplasty within 2 months.


A metagenomic study of the rumen virome in domestic caprids.
This project sought to investigate the domestic caprid rumen virome by developing a robust viral DNA isolation and enrichment protocol (utilizing membrane filtration, ultra-centrifugation, overnight PEG treatment and nuclease treatment) and using RSD-PCR and high throughput sequencing (HTS) techniques. 3.53% of the reads obtained were analogous to those of viruses denoting Siphoviridae, Myoviridae, Podoviridae, Mimiviridae, Microviridae, Poxviridae, Tectiviridae and Marseillevirus. Most of the sequenced reads from the rumen were similar to those of phages, which are critical in maintaining the rumen microbial populations under its carrying capacity. Though identified in the rumen, most of these viruses have been reported in other environments as well. Improvements in the viral DNA enrichment and isolation protocol are required to obtain data that are more representative of the rumen virome. The 102,130 unknown reads (92.31%) for the goat and 36,241 unknown reads (93.86%) for the sheep obtained may represent novel genomes that need further study.


Management of harmful benthic dinoflagellates requires targeted sampling methods and alarm thresholds.
Concern regarding Benthic Harmful Algal Blooms (BHABs) is increasing since some harmful benthic species have been identified in new areas. In the Mediterranean basin, the most common harmful benthic microalgae are Ostreopsis cf. ovata and Prorocentrum lima, which produce palytoxin-like compounds and okadaic acid respectively, and the need to implement monitoring activities has increased. However, a general agreement on appropriate strategies (e.g. sampling season, definition of alarm thresholds, etc.) is still lagging behind, especially for P. lima, whose proliferation dynamics are still poorly known.


Magnetic resonance imaging of brain tumors: application of gadolinium-DTPA and comparison to computed tomography.
In general, CT examinations still seem to be necessary for preoperative classification of brain masses. With increasing experience it should become clear whether sensitivity and specifity of MRI in the diagnosis of brain tumors can be further improved. Although much more work will be necessary in order to establish the optimal dose, timing, and pulse sequences when using Gd-DTPA, this study demonstrates that contrast changes due to Gd-DTPA can have clinical value.


Toluene gas phase biofiltration by Paecilomyces lilacinus and isolation and identification of a hydrophobin protein produced thereof.
Paecilomyces lilacinus consumed toluene as the sole carbon source in a gas-phase biofilter packed with perlite obtaining an average elimination capacity of 50 g m(-3) h(-1), a removal efficiency of 53%, and a final biomass of 31.6 mg biomass g dry support(-1). Hydrophobin proteins from the mycelium produced in the biofilter were purified by formic acid extraction and precipitated by electrobubbling, and the molecular weight was found to be 10.6 +/- 0.3 kDa. The peptide mass fingerprinting analysis of the purified hydrophobin by matrix-assisted laser desorption/ionization time-of-flight resulted in the identification of two peptides that presented high homology with sequences of class I hydrophobin proteins from other ascomycetous fungi when compared against the National Center for Biotechnology Information database. The yield of hydrophobin (PLHYD) from P. lilacinus was 1.1 mg PLHYD g biomass(-1). These proteins modified the hydrophobicity of Teflon by lowering the contact angle from 130.1 (+/-2) degrees to 57.0 (+/-5) degrees supporting hot sodium dodecyl sulfate washing. This work is the first report about biodegradation of toluene by the nematophagous fungus P. lilacinus in a gas-phase biofilter and the identification of its hydrophobin protein.


Non-coding RNA identification with pseudo RNA sequences and feature representation learning.
Distinguishing non-coding RNAs (ncRNAs) from coding RNAs is very important in bioinformatics. Although many methods have been proposed for solving this task, it remains highly challenging to further improve the accuracy of ncRNA identification. In this paper, we propose a coding potential predictor using feature representation learning based on pseudo RNA sequences named CPPFLPS. In this method, we use the pseudo RNA sequences generated by simulating RNA sequence mutations as new samples for data augmentation, and six string operations simulating RNA sequence mutations are considered: base replacement, base insertion, base deletion, subsequence reversion, subsequence repetition and subsequence deletion. In the feature representation learning framework, different types of pseudo RNA sequences are added to the training set to form new training sets that can be used to train baseline classifiers, thus obtaining baseline models. The resulting labels of these baseline models are used as feature vectors to represent RNA sequences, and the resulting feature vectors acquired after feature selection are used to train a predictive model for distinguishing ncRNAs from coding RNAs. Our method achieves better performance compared with that of existing state-of-the-art methods. The implementation of the proposed method is available at https://github.com/chenxgscuec/CPPFLPS.


Short-wavelength automated perimetry and frequency-doubling technology perimetry in glaucoma.
Standard automated perimetry (SAP) is today still the clinical standard for the management of glaucoma and its progression, though it has been shown that it may detect the disease only after the death of a high number of retinal ganglion cells (RGCs). A number of "unconventional" perimetries have recently been evaluated by several clinical studies which showed their ability to identify the earliest glaucoma changes; the most promising of these techniques are short-wavelength automated perimetry (SWAP) and frequency-doubling technology perimetry (FDT). The applicability of these techniques is still limited by a number of factors: the limited economic resources allocated to perimetry; the paucity of well-conducted, prospective longitudinal studies showing the superiority of SWAP and FDT over SAP; and the lack of a consensus on the criteria to define test abnormality with these techniques. The aim of this article is to review the rationale, the limits, and the potentiality of SWAP and FDT for glaucoma management and to summarize the tasks required to improve the clinical usefulness of these two instruments in the future.


Auditory evoked responses and their modifications during conditioning paradigm in autistic children.
Auditory evoked responses (AERs) were recorded from 16 autistic children (ages 2-10 years) and age-matched normal and retarded controls. In order to test the ability to form auditory-visual cross-modal associations, often impaired in autism, the effects on AERs of coupling sound and light were studied with a paradigm that did not require the cooperation of the subject. Several differences between groups were found concerning the frequency and the amplitudes of present AERs. The pattern characterizing the effects on AERs of coupling sound and light (conditioning phenomenon) was observed for both autistic and normal controls, and not for retarded children. Results suggest that autistic children may have a real but slow learning ability.


Considerations on the mechanism of photosynthetic water oxidation - dual role of oxo-bridges between Mn ions in (i) redox-potential maintenance and (ii) proton abstraction from substrate water.
Two mechanistic problems of photosynthetic water oxidation at the Mn complex of Photosystem II (PS II) are considered. (I) In the four Mn-oxidizing transitions, any pure Mn oxidation is predicted to cause an increase in redox potential that renders subsequent oxidation steps impossible (redox-potential problem). Formation of unprotonated oxo-bridges may counteract the potential increase. (II) The O-O formation step without any high-pK bases acting as proton acceptors is energetically unfavorable (acceptor-base problem). The pK of oxides in a bridging position between Mn ions may increase drastically upon reduction of Mn in the water-oxidation step (>10 units), thus rendering them favorable proton acceptors. It is proposed that in PS II, in the course of the four oxidizing transitions at least two unprotonated oxo-bridges are formed. Thereby (i) a redox potential increase is prevented and (ii) proton acceptors are prepared for the O-O formation step. Water oxidation in the O-O bond formation step is facilitated by simultaneous Mn reduction and proton transfer to bridging oxides amounting to hydrogen atom or hydride transfer from substrate water to the Mn-oxo core of the Mn complex of PS II.


TGF-beta 1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors.
Fibroblasts have a major role in the synthesis and reorganization of extracellular matrix that occur during wound repair. An impaired biosynthetic or functional response of these cells to stimulation by growth factors might contribute to the delayed wound healing noted in aging. We, therefore, compared the responses of dermal fibroblasts from young and elderly individuals (26, 29, 65, 89, 90, and 92 years of age) to transforming growth factor-beta 1 (TGF-beta 1) with respect to: (1) the synthesis of type I collagen and SPARC (two extracellular matrix proteins that are highly expressed by dermal fibroblasts during the remodeling phase of wound repair) and (2) the contraction of collagen gels, and in vitro assay of wound contraction. With the exception of one young donor, all cultures exposed for 44 hours to 10 ng/ml TGF-beta 1 exhibited a 1.6- to 5.5-fold increase in the levels of secreted type I collagen and SPARC, relative to untreated cultures, and exhibited a 2.0- to 6.2-fold increase in the amounts of the corresponding mRNAs. Moreover, the dose-response to TGF-beta 1 (0.1-10 ng/ml), as determined by synthesis of type I collagen and SPARC mRNA, was as vigorous in cells from aged donors as in cells from a young donor. In assays of collagen gel contraction, fibroblasts from all donors were stimulated to a similar degree by 10 ng/ml TGF-beta 1. In conclusion, cells from both young and aged donors exhibited similar biosynthetic and contractile properties with exposure to TGF-beta 1. It therefore appears that the impaired wound healing noted in the aged does not result from a failure of their dermal fibroblasts to respond to this cytokine.


Controlled flight of a microrobot powered by soft artificial muscles.
Flying insects capable of navigating in highly cluttered natural environments can withstand in-flight collisions because of the combination of their low inertia1 and the resilience of their wings2, exoskeletons1 and muscles. Current insect-scale (less than ten centimetres long and weighing less than five grams) aerial robots3-6 use rigid microscale actuators, which are typically fragile under external impact. Biomimetic artificial muscles7-10 that are capable of large deformation offer a promising alternative for actuation because they can endure the stresses caused by such impacts. However, existing soft actuators11-13 have not yet demonstrated sufficient power density to achieve lift-off, and their actuation nonlinearity and limited bandwidth create further challenges for achieving closed-loop (driven by an input control signal that is adjusted based on sensory feedback) flight control. Here we develop heavier-than-air aerial robots powered by soft artificial muscles that demonstrate open-loop (driven by a predetermined signal without feedback), passively stable (upright during flight) ascending flight as well as closed-loop, hovering flight. The robots are driven by multi-layered dielectric elastomer actuators that weigh 100 milligrams each and have a resonance frequency of 500 hertz and power density of 600 watts per kilogram. To increase the mechanical power output of the actuator and to demonstrate flight control, we present ways to overcome challenges unique to soft actuators, such as nonlinear transduction and dynamic buckling. These robots can sense and withstand collisions with surrounding obstacles and can recover from in-flight collisions by exploiting material robustness and vehicle passive stability. We also fly two micro-aerial vehicles simultaneously in a cluttered environment. They collide with the wall and each other without suffering damage. These robots rely on offboard amplifiers and an external motion-capture system to provide power to the dielectric elastomer actuators and to control their flight. Our work demonstrates how soft actuators can achieve sufficient power density and bandwidth to enable controlled flight, illustrating the potential of developing next-generation agile soft robots.


Interactions between earthworm hemolysins and sheep red blood cell membranes.
The hemolytic activity exhibited by the coelomic fluid of the Annelid Eisenia fetida andrei is mediated by two lipoproteins of mass 40 and 45 kDa, each of them capable of hemolysis. Such an activity is not inhibited by zymosan, inulin or lipopolysaccharide (LPS), nor by hydrazine or methylamine, suggesting that earthworm hemolysins are not related to C3 or C3b complement components. Among the membrane lipids tested (phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingomyelin and cholesterol) only sphingomyelin inhibited hemolysis. The analysis of E.f. andrei proteins bound to sphingomyelin microvesicles, as well as to sheep red blood cell (SRBC) membranes, revealed a polymerization of E.f. andrei 40 kDa and/or 45 kDa hemolysins. Consequently, sphingomyelin appears a likely candidate for hemolytic complex receptor. Electron microscopy observations suggested that the polymerization causes an open channel through the lipid bilayer. As demonstrated using metal ions, heparin, chondroitin sulfate, poly(L-lysine) and protamine chloride, the mode of action of earthworm hemolytic complex is not analogous to that of C9 or perforine.


The influence of pretreatment with PPI on Helicobacter pylori eradication: A systematic review and meta-analysis.
In this meta-analysis, we aimed to comprehensively investigate the impact of pretreatment with proton pump inhibitor (PPI) on Helicobacter pylori (H. pylori) eradication and provide novel inspiration to clinical practice. Relevant studies were selected through PubMed, Embase, and Cochrane Library from inception to March 2021. Two reviewers performed the selection independently. The primary outcome of the meta-analysis was the eradication rate. A modified Jadad scale was used to evaluate literature quality quantitatively. Ten studies were included in this research. The results showed no significant difference between PPI pretreatment and standard treatment on eradication of H. pylori [relative risk (RR): 1.17, 95% confidence interval (95% CI): 0.0.73-1.88]. There was no significant difference between the PPI pretreatment group and the standard therapy group for conventional triple therapy, PPI and amoxicillin and clarithromycin (RR: 1.29, 95% CI: 0.60-2.77). Similar results were obtained in the therapy strategy of PPI and amoxicillin and metronidazole (RR: 3.01, 95% CI: 0.62-14.74). Interestingly, for the therapy regimen of PPI and clarithromycin and metronidazole, PPI pretreatment indicated superiority on H. pylori eradication rate (RR: 0.48, 95% CI: 0.23-0.97, P < .05). PPI pretreatment did not affect the H. pylori eradication rates, regardless of the various types of bacteriostatic antibiotic, except the therapy regimen of PPI and clarithromycin and metronidazole.


Cell-intrinsic differences between human airway epithelial cells from children and adults.
The airway epithelium is a protective barrier that is maintained by the self-renewal and differentiation of basal stem cells. Increasing age is a principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in the airway epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites from pediatric and adult donors and compared their cellular composition and gene expression profile (in laser capture-microdissected whole epithelium, fluorescence-activated cell-sorted basal cells, and basal cells in cell culture). Histologically, pediatric and adult tracheobronchial epithelium was similar in composition. We observed age-associated changes in RNA sequencing studies, including higher interferon-associated gene expression in pediatric epithelium. In cell culture, pediatric cells had higher colony formation ability, sustained in vitro growth, and outcompeted adult cells in a direct competitive proliferation assay. Our results demonstrate cell-intrinsic differences between airway epithelial cells from children and adults in both homeostatic and proliferative states.


Correlates of high grade and low grade Haemophilus influenzae bacteremia.
Routine use of the Isolator 1.5 Microbial Tube lysis direct plating blood culture system at our institution since November, 1983, provided a unique opportunity to study bacteremia in children from a quantitative perspective. In a 3-year period, 90 episodes of Haemophilus influenzae bacteremia occurred in immunocompetent outpatients; 83 of these met the criteria for study. Patients with high grade bacteremia (greater than 100 colony-forming units/ml) were more likely to have meningitis than those with low grade bacteremia (less than or equal to 100 colony-forming units/ml); conversely low grade bacteremia patients were more likely to have cellulitis or arthritis. Of 38 meningitis patients those with high grade bacteremia (n = 25) had a significantly shorter duration of illness before presentation than those with low grade bacteremia (median, 1 vs. 3 days; P less than or equal to 0.006). In addition high grade bacteremia patients had significantly lower white blood cell counts (median, 11.4 vs. 17.3 X 10(3)/mm3; P less than or equal to 0.007) and absolute neutrophil counts (5.5 vs. 11.1 X 10(3)/mm3; P less than or equal to 0.01). Only 1 of 8 meningitis patients who were pretreated with appropriate antibiotics had high colony counts compared to 7 of 8 matched controls (P = 0.04).


Combining donor derived cell free DNA and gene expression profiling for non-invasive surveillance after heart transplantation.
Donor-derived cell free DNA (dd-cfDNA) and gene expression profiling (GEP) offer noninvasive alternatives to rejection surveillance after heart transplantation; however, there is little evidence on the paired use of GEP and dd-cfDNA for rejection surveillance. A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd-cfDNA and GEP. The primary outcomes were survival and rejection-free survival at 1 year post-transplant. In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), P < .01. At 1-year, there were no differences between the paired testing and GEP groups in survival (98.4% vs. 94.7%, P = .23) or rejection-free survival (81.3% vs. 73.7% P = .28). Compared to post-transplant rejection surveillance with GEP alone, pairing dd-cfDNA and GEP testing was associated with similar survival and rejection-free survival at 1 year while requiring significantly fewer biopsies.


Diagnosis of acoustic neuroma with computed tomography.
Sixty-one acoustic neuromas were examined with computed tomography (CT). For differential diagnosis the tumors were thoroughly analyzed for manner of growth, shape, volume, calcification, attenuation pattern, constrast enhancement, presence of peripheral edema, and cisternal deformation.


Effect of systematic dental shape modification in bitemarks.
Studies on human cadaver models have reported significant levels of distortion of bitemarks in skin, indicating that tooth characteristics are not reliably transferred and recorded in the bitten subject. Moreover, matches among the anterior biting dentition in open population studies have been found. This prompts the question as to what degree of difference in shape will distinguish one dentition from another as reflected in a bitemark. In order to understand how these variables appear on skin, 10 dental casts with systematic variations in tooth positions were produced. The height of the lateral incisors was systematically altered in 1mm increments up to 3mm and lateral incisor/canines were altered in facial/lingual displacement in 1mm increments up to 5mm. Each of the models was used to produce a series of 10 repeated bites, distributed over arms and legs of un-embalmed cadavers. Landmark-based geometric morphometrics were used for analysis of digital images of the bitemarks. Results indicate that alterations of height and displacement of particular teeth affected the position of impressions created by the adjacent teeth. Displacement of one lateral incisor/canine led to a relative shift in impressions of the central incisors and unaltered canines, while height alteration of the lateral incisors led to a shift in relative position of central incisors as recorded in the bitemark. The prominence of displacements was more pronounced in the bitemarks than in images of the dentition used to make the bites, thus the bitemarks tended to exaggerate the differences. It was found that a displacement of 5mm between teeth allowed for reliable distinction between bitemarks. No such threshold of distinction could be established for differences in height of teeth under these experimental conditions. The effect of distortion was more significant in the mandibular than maxillary arch, suggesting that the mandible exhibits higher variation than the maxilla, as impressed in skin. Numerous bitemarks also exhibited arch flattening, consistent with recent studies showing arch width as the principal variable in a bitemark.


[Evaluation of the influence of the bacterial vaccines Pneumo-23 and Act-HIB on the course of the chronic inflammatory process of the respiratory organs in children].
The effectiveness and safety of vaccination of children having chronic inflammatory lung diseses with Pneumo-23 and Act-HIB were evaluated. The group under study included 38 children having chronic pneumonia, congenital defects of lung development, Kartagener's syndrome, mucoviscidosis; of these children, 25 were vaccinated with Pneumo-23 and 13--with Act-HIB. For comparison a group of 40 children with the same pathology, but not vaccinated, was used. A favorable course of the postvaccinal period was noted. Prior to vaccination Streptococcus pneumoniae in association with Haemophilus influenzae were isolated from all patients; in a year after vaccination with Pneumo-23 these microorganisms were isolated only in monoculture: S. pneumoniae in 3 out of 25 cases (88% elimination) and H. influenzae in 10 out of 25 cases (60% elimination).


Trends in health care resource use and expenditures in patients with newly diagnosed paroxysmal supraventricular tachycardia in the United States.
Few data are available on the temporal patterns of health resource utilization (HRU) and expenditures around paroxysmal supraventricular tachycardia (PSVT) diagnosis. This study assessed the longitudinal trends in HRU and expenditures in the 3 years preceding and subsequent to PSVT diagnosis. Adult patients (age 18-65 years) with newly diagnosed PSVT were identified using administrative claims from the IBM MarketScan Research Database between January 1, 2008 and December 31, 2016 and propensity-score matched (1:1) with non-PSVT controls. Among the 12,305 PSVT patients compared with matched controls, PSVT was associated with statistically significant higher annual rates of emergency department visits, physician office visits, inpatient hospitalizations, and diagnostic testing. HRU increased in the years preceding PSVT diagnosis, reaching its peak in the year following PSVT diagnosis. Over the 6-year follow-up period, PSVT was associated with higher mean annual per patient expenditures ($12,665) compared to matched controls ($6,004; P < .001). Upon diagnosis of PSVT, the mean expenditures per PSVT patient doubled from $11,714 in the year immediately preceding index diagnosis to $23,335 in the first postdiagnosis year. Inpatient services, diagnostic testing, and ablation procedures were the principle drivers of higher mean expenditures in the first year post-PSVT diagnosis versus the year prior to PSVT diagnosis. PSVT presents a substantial economic burden to health care systems. The annual expenditure per PSVT patient is within the range previously reported for atrial fibrillation. The increased HRU and expenditures in the year following diagnosis, which do not return to baseline, suggest a potential gap in non-interventional, long-term PSVT management.


Cardiac Autonomic Modulation is a Key Factor for High Blood Pressure in Adolescentes.
The interest regarding hypertension among children and adolescents has increased since the blood pressure rating system was updated to be compared with the adult rating system, changing the terminology from "normal high" to "prehypertension". This study aimed to analyze the association between cardiac autonomic modulation and pressure levels of adolescents. 203 adolescents were grouped according to systolic blood pressure (SBP) and diastolic blood pressure (DBP). One group was characterized as prehypertension, and the other as normotensive. Anthropometric, cardiovascular and sleep quality characteristics were collected. Initially, the data were submitted to the Kolmogorov-Smirnov normality test. Continuous quantitative variables were analyzed using the unpaired Student t-test. For the analysis of categorical variables, a chi-square test was used. A logistic regression model was performed. The level of significance was set at p<0.05. The data were expressed as mean ± standard deviation and confidence interval. The R software was used for data analysis. The effect size was calculated using the Cohen's formula. The prehypertension group showed an increase in Shannon entropy and a decrease in total variance. Also, in the logistic regression model, adolescents in this group were 1.03 times more likely to have Shannon entropy's affected when SBP was adjusted for gender, sexual maturation, school time, age, waist circumference, and sleep quality. Our data show that autonomic modulation may play an important role in the development of elevated blood pressure in adolescents, when controlling for other factors, such as school time and sleep quality.


A leucine-supplemented diet restores the defective postprandial inhibition of proteasome-dependent proteolysis in aged rat skeletal muscle.
We tested the hypothesis that skeletal muscle ubiquitin-proteasome-dependent proteolysis is dysregulated in ageing in response to feeding. In Experiment 1 we measured rates of proteasome-dependent proteolysis in incubated muscles from 8- and 22-month-old rats, proteasome activities, and rates of ubiquitination, in the postprandial and postabsorptive states. Peptidase activities of the proteasome decreased in the postabsorptive state in 22-month-old rats compared with 8-month-old animals, while the rate of ubiquitination was not altered. Furthermore, the down-regulation of in vitro proteasome-dependent proteolysis that prevailed in the postprandial state in 8-month-old rats was defective in 22-month-old rats. Next, we tested the hypothesis that the ingestion of a 5% leucine-supplemented diet may correct this defect. Leucine supplementation restored the postprandial inhibition of in vitro proteasome-dependent proteolysis in 22-month-old animals, by down-regulating both rates of ubiquitination and proteasome activities. In Experiment 2, we verified that dietary leucine supplementation had long-lasting effects by comparing 8- and 22-month-old rats that were fed either a leucine-supplemented diet or an alanine-supplemented diet for 10 days. The inhibited in vitro proteolysis was maintained in the postprandial state in the 22-month-old rats fed the leucine-supplemented diet. Moreover, elevated mRNA levels for ubiquitin, 14-kDa ubiquitin-conjugating enzyme E2, and C2 and X subunits of the 20S proteasome that were characteristic of aged muscle were totally suppressed in 22-month-old animals chronically fed the leucine-supplemented diet, demonstrating an in vivo effect. Thus the defective postprandial down-regulation of in vitro proteasome-dependent proteolysis in 22-month-old rats was restored in animals chronically fed a leucine-supplemented diet.


[Adenosine deaminase activity in peripheral lymphocytes during acute viral hepatitis (preliminary data)].
Adenosine deaminase (ADA) activity was determined in peripheral lymphocytes of 6 patients with HBsAg positive acute viral hepatitis (AVH), 8 patients with HBsAg negative AVH and 12 normal controls. The average of ADA activity in these three groups was 25, 25 and 21 nmoles/min/mg prot. respectively without significance for statistical analysis. However high ADA values (40, 32 and 39) were observed in the peripheral lymphocytes of three patients with AVH.


Direct measurement of denitrification in a Prosopis (Mesquite) dominated Sonoran Desert ecosystem.
Denitrification was directly measured using the acetylene inhibition technique in a Sonoran Desert ecosystem dominated by Prosopis glandulosa. Soil under Prosopis and from the unvegetated area between Prosopis was wetted with 50 mm of water and denitrification measured for 48 hours. The mean denitrification rate under Prosopis was 11.6 g N ha-1h-1 compared to only 0.2 g N ha-1h-1 away from Prosopis. The denitrification response to wetting was rapid and rates peaked about 24 h after water application.The much higher denitrification under Prosopis probably results from high available organic C under Prosopis, but other soil chemical and physical changes effected by Prosopis may influence denitrification rates. About 0.5 kg N ha-1 of Prosopis cover may be lost from this ecosystem by denitrification after infrequent major rainfalls.


Models of hostplant location by butterflies: the effect of search images and search efficiency.
An earlier model of hostplant exploitation by insects (Courtney 1982b) fails to take account of differences between strategists in search efficiencies. Modifications which accommodate such differences are presented which increase the explanatory power of the model. Some novel deductions for insect-host coevolution arise. Hostplants may be under selection for chemical crypsis when the insect identifies the host by a positive chemical stimulus; by crypsis, a hostplant may increase the 'handling time' of females searching for oviposition sites. Contrary to earlier predictions, the evolution of a monophagous relationship is possible even when alternative hosts are present.


[Constrictive pericarditis and post-radiotherapy myocarditis with mitral incompetence (author's transl)].
The cardiac complications of radiotherapy of the thorax (e.g. for Hodgkin's disease and carcinoma of the breast) are various: 1) Pleural effusions, occurring a few months to two years after radiotherapy, spontaneously curable but may give signs of tamponnade or lead to constriction. 2) Constrictive pericarditis often several years after irradiation, with a poor prognosis in spite of attempts at pericardectomy which is indicated at the stage of hemodynamic constriction. 3) Myocardial involvement with advanced fibrosis and with various clinical presentations. The failure of pericardectomy and mitral incompetence were evidence of myocarditis in the case reported here.


Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response.
Hepatitis B virus (HBV) causes hepatic diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. These diseases are closely associated with persistent HBV infection. To prevent the progression of hepatic diseases, it is thus important to suppress persistent HBV infection. Daunorubicin (DNR), a topoisomerase II (Top II) poison, is a clinically used anticancer agent with a wide spectrum of activity against malignancies. DNR was recently reported to cause DNA damage-dependent interferon (IFN)-β induction through exogenous cyclic GMP-AMP synthetase (cGAS) and subsequently to suppress Ebola virus replication. In the present study, we demonstrated that DNR caused the inhibition of cell proliferation, but not cell death, through the DNA damage response in immortalized human hepatocyte NKNT-3/NTCP cells. Interestingly, DNR triggered the endogenous cGAS-dependent innate immune response and subsequently suppressed viral production of HBV in NKNT-3/NTCP cells. Top II poisons may be anti-HBV drug candidates.


Effects of inter-electrode spacing on complex fractionated atrial electrograms and dominant frequency detection.
The influence of inter-electrode spacing (IES) on complex fractionated atrial electrograms (CFAEs) and dominant frequency (DF) detection was assessed. Bipolar electrograms were recorded via an octapolar catheter (2-mm electrode spacing) from left atrial CFAEs sites in 17 atrial fibrillation patients. The CFE-mean was calculated at IES of the electrode pairs 1-2, 1-3, 1-4, 1-5, and 1-6. The DF, regularity index (RI), and organization index (OI) were simultaneously analyzed. The CFE-mean decreased as the IES increased (from 71 ± 15 ms of IES 1-2 to 61 ± 8 ms of IES 1-3, 57 ± 6 ms of IES 1-4, 57 ± 8 ms of IES 1-5, and 58 ± 9 ms of IES 1-6, respectively; IES 1-2 vs. 1-3 to 1-6, P < 0.01). The DF was unchanged (6.6 ± 1.6 Hz for all; P > 0.99). However, the RI decreased as the IES increased (from 0.30 ± 0.11 to 0.26 ± 0.11, 0.23 ± 0.11, 0.22 ± 0.12, and 0.20 ± 0.12; IES 1-2 vs. 1-3 to 1-6, P < 0.01), as did the OI (from 0.39 ± 0.14 to 0.34 ± 0.12, 0.32 ± 0.13, 0.29 ± 0.13, and 0.28 ± 0.13; IES 1-2 vs. 1-3 to 1-6, P < 0.01). A wider IES might detect dyssynchronous activations, leading to a reduced CFE-mean and RI and OI. Therefore, bipolar signals recorded with a narrower IES might be preferable to more precisely localizing CFAEs and DF sites.


Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy.
Intravesical instillation of Bacillus Calmette-Guérin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guérin therapy. In an attempt to investigate the feasibility of using insect baculovirus-based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the survival rate of mice bearing established orthotopic bladder tumors. When baculoviral vectors were used to co-deliver the mouse CD40 ligand and IL-15 genes through intravesical instillation, the immunogene therapy triggered significantly increased bladder infiltrations of inflammatory monocytes, CD4(+), CD8(+) and γδ T lymphocytes. All treated animals survived beyond 12 months whereas control animals died around 2 months after tumor inoculation. We conclude that direct intravesical instillation of baculoviral gene transfer vectors holds the potential to be a novel therapeutic modality for NMIBC.


Performance correlates of resting metabolic rate in garden skinks Lampropholis delicata.
Resting metabolic rates can vary greatly between individuals of the same species. These differences are generally repeatable and show moderate-to-high heritability, suggesting that they could be a target for natural selection. The present study therefore aimed to determine if inter-individual differences in resting metabolic rates (RMR) in garden skinks Lampropholis delicata were associated with inter-individual differences in a suite of physiological and behavioural variables: aerobic capacity, burst sprinting speed and thermal preference. Whole-animal measures of aerobic capacity and RMR were significantly positively correlated, but mass-independent measures were not. Burst sprinting speed and thermal preference were also not correlated with RMR.


Home-based self-sampling vs clinician sampling for anal precancer screening: The Prevent Anal Cancer Self-Swab Study.
Sexual minority men are at increased risk for anal squamous cell carcinoma. Our objective was to compare screening engagement among individuals randomized to self-collect an anal canal specimen at home or to attend a clinic appointment. Specimen adequacy was then assessed for human papillomavirus (HPV) DNA genotyping. A randomized trial recruited cisgendered sexual minority men and transgender people in the community and assigned them to use a home-based self-collection swabbing kit or attend a clinic-based swabbing. Swabs were sent for HPV genotyping. The proportions of participants completing screening in each study arm and the adequacy of their specimens for HPV genotyping were assessed. Relative risks were estimated for factors associated with screening. A total of 240 individuals were randomized. Age (median, 46 years) and HIV status (27.1% living with HIV) did not differ by study arm. A total of 89.2% and 74.2% of home-arm and clinic-arm individuals returned the swab, respectively (P = .003), difference between groups, 15.0% (95% CI 5.4%-24.6%). Among black individuals, 96.2% and 63.2% in the home and clinic arms screened (P = .006). Among individuals with HIV, 89.5% and 51.9% in the home and clinic arms screened (P < .001). Self-collected swabs and clinician-collected swabs were comparable in adequacy for HPV genotyping (96.3% and 93.3%, respectively). People at highest risk for anal cancer may be more likely to screen if they are able to self-collect swabs at home rather than attend a clinic.


Primary nursing: opinions of nursing staff before and during implementation.
The aim of this investigation was to consider the opinions of the nursing staff concerning the effects of primary nursing before and after the transition to this mode. Data were collected using a self-administered questionnaire which was answered by 62 registered nurses and practical nurses before the introduction of primary nursing and 58 such nurses five months after its introduction. The nursing staff reported both more favourable and detrimental effects during primary nursing than beforehand, the former including the improved opportunities for nurses to get to know their patients and to provide individual care, and the latter the increase in paperwork. The role of the primary nurse was mainly felt to be positive, but sometimes difficult and laborious.


Catheter ablation therapy for atrial fibrillation.
The past several years have witnessed a significant growth in the number of institutions offering catheter ablation for atrial fibrillation (AF). This growth has been a result of a better understanding of pathophysiology of AF and use of instruments and approaches that made catheter ablation of AF a safe and an effective alternative to the drug therapy. The procedure increasingly is becoming a therapy of choice for a select group of symptomatic, drug-refractory patients without structural heart disease, and it is being offered to a rapidly widening patient pool. This article reviews the procedural aspects and clinical evidence supporting this wider use of AF ablation. In addition, new techniques and technologies for AF ablation and new avenues of research in this area are explored.


Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review.
Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.


Primary non-Hodgkin lymphoma of the breast: The Mayo Clinic Experience.
To retrospectively evaluate the characteristics, natural history, results of treatment, and prognostic factors for patients diagnosed with primary breast lymphoma. Between 1973 and 1998, 25 women and 1 man with the diagnosis of primary breast non-Hodgkin lymphoma (PNHLB) were seen at Mayo Clinic Rochester and Mayo Clinic Scottsdale. Patient characteristics, treatment methods, and outcome were analyzed. The median follow-up for surviving patients was 6.6 years (range: 1.8-22.1 years). There were 11 low-grade NHL, 13 intermediate-grade NHL, and 2 high-grade NHL. Three patients underwent mastectomy while 23 had local excision. The Ann Arbor stage of disease included: Stage I-21 patients, Stage II-5 patients. Sixteen patients received radiation after surgery (15 after biopsy, 1 after mastectomy). Chemotherapy was given to 10 patients as part of the initial treatment. Four patients with low-grade disease were treated with excision only. The 5-year overall survival rate was 70% and relapse-free survival rate 42%, while local control rate was 75% and distant control rate 51%. Five-year survival and relapse-free survival rates for patients with low-grade disease were 91 and 61%, respectively. Three of four patients with low-grade disease treated with excision alone were free of local recurrence. For intermediate- and high-grade PNHLB, 5-year survival rate was 61% for those treated with chemotherapy, compared to 31% for those without chemotherapy (P = 0.35), and the 5-year relapse-free survival rates were 49%, compared to 0%, respectively (P = 0.0017). Three patients with intermediate- or high-grade disease developed central nervous system (CNS) dissemination. On univariate analysis, Ann Arbor stage was the only significant prognostic factor for survival (P = 0.0021). The management of PNHLB should be based on histologic grade. Patients with low-grade disease may be managed with local therapy alone. The role of chemotherapy in this group is unclear. Patients with intermediate- or high-grade disease have better outcome if chemotherapy is included. An unusual site of distant dissemination for these patients is the CNS. The only significant prognostic factor for survival is Ann Arbor stage.


Varicella zoster infection and pulmonary complications.
A 34-year-old immunocompetent man with varicella zoster (VZ) infection developed deep vein thrombosis and pulmonary embolism after suffering severe pneumonitis. He recovered after treatment with acyclovir, high-dose steroids, and ventilatory support. The endothelial damage could be a direct link between VZ pneumonitis and pulmonary emboli.


[Length of hospital stay and immobilization of patients with retinal detachment].
Referring to the modern operation techniques (buckling procedures) a reduction of bed rest for patients with retinal detachment is recommended.


Localisation of carcinoembryonic antigen in embryonic and fetal human tissues.
Carcinoembryonic antigen (CEA) was localized in various embryonic and fetal human tissues between 8 and 16 weeks of gestation as well as in the colorectal mucosa of older fetuses, newborns and adults. Among the embryonic tissues, CEA was always present in the esophagus, the gastric antrum, the duodenum and the rectum. CEA positive staining of bile canaliculi of the liver was inconstant. All other embryonic tissues were CEA negative. During early fetal development, CEA positive staining of the esophagus, antrum and duodenum was inconstant. However, the whole colon became intensively stained. An inconstant CEA specific staining was found in parts of the midgut and in the bile canaliculi of the liver. The other organs remained CEA negative. Between the 17th week of gestation and birth, CEA staining pattern of the colorectal mucosa did not change. The staining intensity of late fetal colonic mucosa was similar to that of adult colonic mucosa.


Clinical cases of fusarium-toxicoses in Austrian domestic animals in connection with fusariumtoxinrcontaminated feedstuffs.
A surveillance study of the most important fusarium-toxins in Austrian feed samples, the estrogenic mycotoxin zearalenone (F-2 toxin) as well as the refusal of feed causing deoxynivalenol (vomitoxin), of the last 8 years is given. The author describes predominantly the biologic effects in swine, cattle and poultry from the practical point of view and the correlation between clinical symptoms of the incriminated animals and the mycotoxin-levels found in the suspicious feed samples. Some field cases, the clinical symptoms and the fusariumtoxin-concentrations found are presented in one table.