Transverse myelitis following COVID-19: Insights from a multi-center study and systematic literature review.
We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.


Synthesis of chiral tertiary trifluoromethyl alcohols by asymmetric nitroaldol reaction with a Cu(II)-bisoxazolidine catalyst.
A highly enantioselective and diastereoselective copper(II)-bisoxazolidine catalyzed nitroaldol reaction with aliphatic and aromatic trifluoromethyl ketones is described.


Retinal vessel diameter, obesity and metabolic risk factors in school children (JuvenTUM 3).
The prevalence of childhood obesity is high and its association with future cardiovascular disease in adulthood is well established. The cross-sectional data presented analyze the prevalence of obesity and the association between metabolic risk factors, physical inactivity and retinal vessel diameter in young school children. The examination included 578 school children aged 11.1±0.6 years from secondary schools in the District of Munich, Germany. Anthropometric measurements and blood sampling were conducted using standard protocols for children. Physical activity was evaluated by use of a questionnaire. Retinal microvascular diameters and the arteriolar to venular ratio (AVR) were assessed with a non-mydriatic vessel analyser (SVA-T) using a computer-based program. In our population, 128 (22.2%) children were overweight (ow) or obese (ob). The mean retinal arteriolar and venular calibres were 208.0±15.6 μm and 236.2±16.2 μm, respectively, with a mean AVR of 0.88±0.01. Girls had significantly wider arteriolar and venular diameters compared to boys (p<0.001). ow and ob children had a lower AVR compared to normal weight (nw) children (mean(95% CI); nw: 0.89(0.88-0.89); ow: 0.87(0.86-0.88); ob: 0.85(0.83-0.87); p≤0.05). Wider venular diameters were independently associated with higher BMI and higher hsCRP. Blood pressure was associated with retinal vessel constriction. Higher physical inactivity and BMI were independently associated with a reduced AVR (p=0.032 and p<0.001, respectively). Cardiometabolic risk factors and physical inactivity are associated with retinal microvascular alterations in young children, comparable to associations in adults. Retinal vessel imaging seems to be a feasible assessment for the detection of microvascular impairments in children at risk of developing cardiovascular disease in adulthood.


Adjuvant interferon-alpha for melanoma revisited: news from old and new studies.
Currently the data from 12 randomised phase III trials investigating the role of interferon-alpha (IFNalpha) in patients with stage II-III high-risk melanoma are available. The most prominent differences between these trials concern the dose of IFNalpha, the duration of IFNalpha administration, and the stage of disease. Some of these trials have not yet reached maturity, but despite this the positive results from some immature trials have attracted considerable attention. When only data from mature trials is considered, one may conclude that the use of high-dose IFNalpha does prolong disease-free survival (DFS) but not overall survival (OS). Combined data from low-dose IFNalpha trials does not suggest a benefit in either DFS or OS. A trial with intermediate-dose IFNalpha is still immature. Therefore currently the routine use of IFNalpha cannot be recommended outside the scope of clinical trials.


Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance.
Temozolomide (TMZ) is a newly approved alkylating agent for the treatment of malignant gliomas. To investigate resistance mechanisms in a multidrug therapeutic approach, a TMZ-resistant human glioma cell line, SF188/TR, was established by stepwise exposure of human SF188 parental cells to TMZ for approximately 6 months. SF188/TR showed 6-fold resistance to TMZ and cross-resistance to a broad spectrum of other anticancer agents that included 3-5-fold resistance to melphalan (MEL), gemcitabine (GEM), paclitaxel (PAC), methotrexate (MTX), and doxorubicin (DOX), and 1.6-2-fold resistance to cisplatin (CDDP) and topotecan (TPT). Alkylguanine alkyltransferase (AGT) activity was increased significantly in the resistant cell line compared with the parental cell line (P<0.05), whereas no significant differences occurred in the cellular uptake of TMZ and PAC between resistant and parental cells. Depletion of AGT by O(6)-benzylguanine significantly increased the cytotoxicity of TMZ in both the sensitive and resistant cell lines, but did not influence the cytotoxicity of the other drugs tested. Treatment with TMZ caused SF188 cells to accumulate in S phase, whereas SF188/TR cells were unaffected. Expression of Bcl-2 family members in SF188/TR cells compared with SF188 cells indicated that the pro-apoptotic proteins (i.e. Bad, Bax, Bcl-X(S)) were reduced 2-4-fold in the resistant cell line, whereas the anti-apoptotic proteins Bcl-2 and Bcl-X(L) were expressed at similar levels in both cell lines. In conclusion, the mechanism of resistance of SF188/TR cells to TMZ involved increased activity of AGT, a primary resistance mechanism, whereas the broad cross-resistance pattern to other anticancer drugs was due to a common secondary resistance mechanism related to alterations in the relative expression of the pro-apoptotic and anti-apoptotic proteins.


Lack of value of radioimmunoassay for prostatic acid phosphatase as a screening test for prostatic cancer in patients with obstructive prostatic hyperplasia.
We examined the incidence of prostatic cancer in patients with an elevated radioimmunoassay for prostatic acid phosphatase and clinical benign prostatic hyperplasia on digital rectal examination. Of 295 patients screened with prostatic acid phosphatase tests 17 fulfilled the criteria of having an elevated prostatic acid phosphatase, clinically benign prostate and histological examination of the prostatectomy specimen. None of the 17 patients had histological evidence of prostatic cancer. The results confirm the predictions of mathematical models that prostatic acid phosphatase is of no practical value as a screening test for prostatic cancer in patients with clinical benign prostatic hyperplasia.


Brain Arteriovenous Malformation Recurrence After Apparent Microsurgical Cure: Increased Risk in Children Who Present With Arteriovenous Malformation Rupture.
Do children have an increased risk for brain arteriovenous malformation (AVM) recurrence compared with adults and does this risk vary depending on initial presentation with AVM rupture? We retrospectively studied 115 patients initially presenting with brain AVM under age 25 years who underwent complete surgical resection of the AVM as documented by digital subtraction angiography (DSA) and had delayed follow-up DSA to evaluate for AVM recurrence after apparent initial cure. The mean time from baseline DSA to follow-up DSA was 2.3 years, ranging from 0 to 15 years. Twelve patients (10.4% of the 115 patient cohort and 16.7% of 72 patients with hemorrhage at initial presentation) demonstrated AVM recurrence on follow-up DSA. All patients with recurrence initially presented with intracranial hemorrhage, and intracranial hemorrhage was a significant predictor of recurrence (log rank P=0.037). Among patients with initial hemorrhage, the 5-year recurrence rate was 17.8% (95% CI, 8.3%-35.7%). All recurrences occurred in patients who were children at the time of their initial presentation; the oldest was 15 years of age at the time of initial AVM surgery. The 5-year recurrence rate for children (0-18 years of age) with an initial presentation of hemorrhage was 21.4% (95% CI, 10.1%-41.9%). Using Cox regression, we found the risk of AVM recurrence decreased by 14% per each year increase in age at the time of initial surgical resection (hazard ratio=0.86 [95% CI, 0.75-0.99]; P=0.031). There is a high rate of recurrence of apparently cured brain AVMs in children who initially present with AVM rupture. Imaging follow-up is warranted to prevent re-rupture.


Potential Epigenetic Effects of Human Milk on Infants' Neurodevelopment.
The advantages of human milk feeding, especially in preterm babies, are well recognized. Infants' feeding with breast milk lowers the likelihood of developing a diverse range of non-communicable diseases later in life and it is also associated with improved neurodevelopmental outcomes. Although the precise mechanisms through which human milk feeding is linked with infants' neurodevelopment are still unknown, potential epigenetic effects of breast milk through its bioactive components, including non-coding RNAs, stem cells and microbiome, could at least partly explain this association. Micro- and long-non-coding RNAs, enclosed in milk exosomes, as well as breast milk stem cells, survive digestion, reach the circulation and can cross the blood-brain barrier. Certain non-coding RNAs potentially regulate genes implicated in brain development and function, whereas nestin-positive stem cells can possibly differentiate into neural cells or/and act as epigenetic regulators in the brain. Furthermore, breast milk microbiota contributes to the establishment of infant's gut microbiome, which is implicated in brain development via epigenetic modifications and key molecules' regulation. This narrative review provides an updated analysis of the relationship between breast milk feeding and infants' neurodevelopment via epigenetics, pointing out how breast milk's bioactive components could have an impact on the neurodevelopment of both full-term and preterm babies.


Cyclo-oxygenase-1/cyclo-oxygenase-2 non selective non-steroidal anti-inflammatory drugs: epidemiology of gastrointestinal events.
Non-steroidal anti-inflammatory drug use is associated with gastrointestinal side-effects including complications such as bleeding and perforation, which occur in 1-2% of patients after 6-12 months of therapy. A high level of non-prescription non-steroidal anti-inflammatory drug use is observed among those presenting complications. More common side-effects are symptomatic gastro-duodenal ulcers (annual incidence of 4-8%) and dyspepsia (25-50%). Low-dose aspirin use is also associated with an increased risk of upper gastrointestinal bleeding, but the increase is about 3 times lower than that found with common non-steroidal anti-inflammatory drugs. Recent studies suggest that the risk of bleeding in patients taking preferential cyclooxygenase-II inhibitors (e.g. nimesulide) is similar to that in patients taking non-selective non-steroidal anti-inflammatory drugs. Epidemiological studies have also shown that nitric oxide donors and antisecretory drugs reduce the risk of upper gastrointestinal bleeding both in non-steroidal anti-inflammatory drug and low-dose aspirin users.


The adjuvant role of two cycles of MOPP and low-dose lung irradiation in stage IA through IIB Hodgkin's disease: preliminary results.
Fifty-eight laparotomy-staged I and II patients with upper torso presentations of Hodgkin's disease and 8 patients with lymphangiogram-staged lower torso disease were treated with radiotherapy alone or with 2 cycles of MOPP and radiotherapy. Patients with upper torso disease with either no mediastinal or only small mediastinal disease without hilar involvement and with no "B" symptoms were treated with mantle radiotherapy alone. Patients with large mediastinal masses or hilar disease were treated with 2 cycles of MOPP followed by definitive mantle irradiation and low dose lung irradiation. Those for whom "B" symptoms were the only adverse prognostic feature received 2 cycles of MOPP and mantle radiotherapy. Patients with lower torso disease were treated with radiotherapy alone if the disease was limited to the pelvis. Those with more extensive disease received 2 cycles of MOPP prior to radiotherapy. The 4-year survival for all 66 patients was 97%. The corresponding disease-free and freedom from second relapse figures were 77% and 92%. Survival for the patients with unfavorable presentations who received 2 cycles of MOPP and radiotherapy was 100%. It was 92% for the group with favorable presentations who were treated with radiotherapy only.


[Functional Knee Stability in Handball: An Indispensable Criterion For Safe Sport].
Various studies in recent years have shown that, within ball sports, handball players have a high risk of accidents and injuries. The knee joint is the most frequently injured body region, and ruptures of the anterior cruciate ligament the most common injury to the knee. To prevent consequential damage or recurrent knee injury, good functional stability of the knee is of high importance. Stability not only prevents injuries, but is also crucial for optimising handball-specific movements. Although there are numerous studies on injuries in handball - mostly performed on professional athletes - the field of research focusing on functional knee stability is deficient. This article provides an overview of the current state of research and discusses existing prevention approaches.


Effects of standing cycling and the use of toe stirrups on maximal oxygen uptake.
Twenty-eight subjects (6 normal men, 14 distance runners, and 8 rowers) were tested for maximal oxygen uptake (VO2max) and associated physiological measures during bicycle ergometer exercise with toe stirrups while standing (BEts) and during treadmill exercise (TM). Correlation between BEts VO2max and TM VO2max was high (r = 0.901, p less than 0.05). No significant difference existed between the two VO2max values (60.3 +/- 8.9 vs. 60.5 +/- 9.7 ml.kg-1.min-1; n = 28). No differences were found even when three different subgroups were separately compared. It is concluded that the higher VO2max elicited during BEts as compared with normal sitting cycling may be attributed to the increased muscle blood flow and/or involvement of a larger muscle mass, the latter being partly evidenced by the observation of greater electromyographic activity during BEts.


Teaching research ethics: can web-based instruction satisfy appropriate pedagogical objectives?
Ethical tasks faced by researchers in science and engineering as they engage in research include recognition of moral problems in their practice, finding solutions to those moral problems, judging moral actions and engaging in preventive ethics. Given these issues, appropriate pedagogical objectives for research ethics education include (1) teaching researchers to recognize moral issues in their research, (2) teaching researchers to solve practical moral problems in their research from the perspective of the moral agent, (3) teaching researchers how to make moral judgments about actions, and (4) learning to engage in preventive ethics. If web-based research ethics education is intended to be adequate and sufficient for research ethics education, then it must meet those objectives. However there are reasons to be skeptical that it can.


Isolation and genotyping of Toxoplasma gondii in the Midwestern Brazil revealed high genetic diversity and new genotypes.
We aimed to describe the genetic diversity of Toxoplasma gondii strains isolated from domestic animals, wildlife and humans in the Midwestern Brazil. For this purpose, fragments of tissue samples (heart, brain and lung) from 35 dogs, four cats, 105 wildlife, and amniotic fluids from eight pregnant women were collected and submitted to mouse bioassay test. In a total, 22 isolates from nine dogs, one cat, ten wild animals and two women were obtained. The DNA was extracted from T. gondii isolates (lungs and brains of infected mice) and from "primary samples" (aliquots of tissue homogenate from wild animals and amniotic fluids from pregnant women) in order to screen using a Polymerase Chain Reaction (PCR) targeting a repeated 529-base pairs fragment of the T. gondii genome. All positive PCR samples were genotyped using restriction fragment length polymorphism (RFLP) analysis. To the best of our knowledge, this was the first study to report isolates of T. gondii from Leopardus pardalis, Crax fasciolata, and Dasyprocta azarae. Moreover, multilocus PCR-RFLP revealed 11 T. gondii RFLP genotypes, comprising nine previously described, including the archetypal lineage #2 type III (n = 1); two clonal Brazilian lineages, #6 type BrI (n = 1) and #8 type BrIII (n = 5); #14 (n = 2), #41 (n = 1), #108 (n = 1), #140 (n = 2), #166 (n = 4), #190 (n = 1), one potentially mixed, and two new described genotypes in two isolates. Our results confirmed the high diversity of T. gondii strains in Brazil, including identical genotypes circulating among humans, domestic dogs and wildlife.


Port site metastasis after laparoscopy for uterine cervical carcinoma.
Aim of this study was to review cases reported of port-site recurrence (PSR) after laparoscopy for uterine cervical carcinoma. A Medline computer database search from January 1980 to September 2002. We reported 13 cases published of PSR after laparoscopy for cervical carcinoma. The majority of them were squamous carcinoma (9/13 at least, 69%) and initial staging of disease was Ib (7/13 (54%)). Median of interval between laparoscopy and diagnostic of PSR was 7 months (min 1.5 month, max 48 months). Of 10 cases of laparoscopy with lymphadenectomy, in three cases (30%) nodes were not involved. PSR developed at the port through which tissues was extracted in four cases (30.1%) or another port in five cases (38.5%). At the time of PSR, five patients (38.5%) were free of disease. PSR were reported after laparoscopy for lymphadenenectomy with or without hysterectomy and with or without node involvement. In some cases, umbilical metastases should not be systematically diagnosed as PSR and a diagnosis of Sister Mary Joseph's nodule may be discussed.


The regeneration niche of desert ants: effects of established colonies.
We marked the sites chosen by 338 foundress queens of two desert ant species (Veromessor pergandei and Myrmecocystus flaviceps) and monitored changes in the spacing of both species and the foraging activity at V. pergandei young nests. Although the long established colonies of both species tend intraspecifically toward regular dispersion, queens of both species were intraspecifically clumped. After 3 months, when the first workers emerged, the young colonies (reduced to a total of 42 colonies) were randomly spaced intraspecifically. We also followed the spatial patter of queens with respect to established colonies of both species. Queens founded nests away from the nests of all established colonies on the site. After three months, the young colonies were dispersed away from conspecifics only. During June through August 1986, we censused the number of foragers at the surviving V. pergandei nests. Young colonies that were more active also tended to be far from established conspecifics in July and August. There was no correlation of forating activity with distance to heterospecific established colonies in any month. These results indicate that established conspecifics may reduce the survivorship of young ant colonies.


Flurbiprofen inhibits heterotopic bone formation in total hip arthroplasty.
A double-blind prospective parallel group study comparing slow-release flurbiprofen with placebo in the control of ectopic bone formation was carried out in 68 patients undergoing total hip arthroplasty. Eight weeks after surgery there was evidence, significant at the 1% level, that the incidence and extent of periarticular calcification was lower in the flurbiprofen group. At an early phase, serum calcium level decreased and after 8 weeks serum alkaline phosphatase level increased more in the placebo group than in the flurbiprofen group, indicating an effect of flurbiprofen on bone mineral metabolism. Six patients were withdrawn in each treatment group, four due to side effects in the flurbiprofen group and three due to side effects in the placebo group. Overall, five patients in each group reported side effects, the nature and severity of the side effects being very similar in each group. We conclude that flurbiprofen is an efficient and safe drug in limiting ectopic bone formation following total hip arthroplasty. Heterotopic bone formation is a frequent complication after total hip replacement. Heterotopic bone reduces the extent of hip motion, reduction being more evident in cases with extensive ectopic bone formation around the hip joint. Various treatment regimens have been proposed for discouraging heterotopic bone formation. Anti-inflammatory agents such as indomethacin and ibuprofen have turned out effective. Local irradiation also prevents ectopic bone formation, but diphosphonates seem not be effective in this respect. The aim of the present study was to assess the efficacy of flurbiprofen, a new anti-inflammatory agent, in limiting heterotopic bone formation, and to note the frequency and severity of any side effects of the treatment.


Antioxidant and hepatoprotective potentials of active fractions of Lannea barteri Oliv. (Anarcadiaceae) in rats.
Lannea barteri is used in the folkloric treatment of many disease states ranging from epilepsy, diarrhoea, oedema and ulcers, etc. This study investigated the antioxidant and hepatoprotective potentials of methanol (MFLB), n-hexane (nHFLB) and ethyl acetate (EFLB) leaf fractions of L. barteri and identified the active metabolites. The in vitro models used were 1, 1-diphenyl-1-picrylhydrazyl (DPPH), reducing power and thiobarbituric acid assays while in the in vivo model, carbon tetrachloride-induced oxidative liver damage in albino rats was used, and the biomarkers assayed were aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), serum total protein, serum direct and total bilirubin. Also, histopathological examination of the liver, high performance liquid chromatography (HPLC) profiling and liquid chromatography-mass spectroscopy-electrospray ionization (LC-MS-ESI) analysis of the fractions were done. In the in vitro assays, the decreasing order of DPPH free radical scavenging activity of the ascorbic acid and fractions at 400 μg/ml is as follows: ascorbic acid (86.6%), MFLB (52.8%), EFLB (36.6%), and nHFLB (28.1%). The percentage scavenging activity of the samples at 400 μg/ml in the TBA followed this pattern: ascorbic acid (117.1%), MFLB (82.2%), nHFLB (80.0%), and EFLB (46.9%). The ascorbic acid elicited highest reducing power (42.6%), followed by MFLB (22.5%), nHFLB (13.7%), and EFLB (-0.93%). The in vivo study showed significant (p < 0.0001) reduction in serum AST, ALT, and direct bilirubin with a non-significant reduction in ALP, total bilirubin and MDA, and mild elevation in total protein. Histopathological studies revealed a restorative effect on liver architecture. The phytochemical analyses revealed the presence of resins, terpenoids, flavonoids, carbohydrates, alkaloids, reducing sugar, saponins, tannins and proteins. HPLC-ESI-MS analysis revealed the presence of potentially bioactive compounds in L. barteri fractions. The fractions from L. barteri leaf possessed in vitro antioxidant and hepatoprotective potentials against CCl4-hepatic oxidative damage; therefore, proper isolation and characterization of these identified bioactive compounds responsible for the observed effects are ongoing.


PD98059 inhibits expression of pERK1 protein and collagen alpha1(I) mRNA in rat pancreatic stellate cells activated by platelet-derived growth factor.
Pancreatic stellate cells (PSC) are considered as the principal effector cells in pancreatic fibrosis. We studied the role of platelet-derived growth factor (PDGF) in the activation of PSC. Cultured rat PSC were co-incubated with PDGF-BB (25 ng/mL) and different doses (0-40 ng/mL) of PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK). Expressions of p ERK1 protein and of collagen a1(I) mRNA were measured. Expression of p ERK1 protein was up-regulated by PDGF-BB, and was down-regulated in a dose-dependent manner by PD98059. Expression of collagen a1(I) mRNA also showed an increase with PDGF-BB and non-dose-dependent inhibition by PD98059. Our findings suggest that PSC activation is mediated by PDGF signal pathway, and ERK1 protein plays an important role in this activation.


Characterization of an allosteric inhibitor of fungal-specific C-24 sterol methyltransferase to treat Candida albicans infections.
Filamentation is an important virulence factor of the pathogenic fungus Candida albicans. The abolition of Candida albicans hyphal formation by disrupting sterol synthesis is an important concept for the development of antifungal drugs with high safety. Here, we conduct a high-throughput screen using a C. albicans strain expressing green fluorescent protein-labeled Dpp3 to identify anti-hypha agents by interfering with ergosterol synthesis. The antipyrine derivative H55 is characterized to have minimal cytotoxicity and potent inhibition of C. albicans hyphal formation in multiple cultural conditions. H55 monotherapy exhibits therapeutic efficacy in mouse models of azole-resistant candidiasis. H55 treatment increases the accumulation of zymosterol, the substrate of C-24 sterol methyltransferase (Erg6). The results of enzyme assays, photoaffinity labeling, molecular simulation, mutagenesis, and cellular thermal shift assays support H55 as an allosteric inhibitor of Erg6. Collectively, H55, an inhibitor of the fungal-specific enzyme Erg6, holds potential to treat C. albicans infections.


Fenton-based technologies as efficient advanced oxidation processes for microcystin-LR degradation.
In recent years, the safety and ecology threat of cyanobacterial burst has drawn wide concern, especially the release of toxic microcystin-LR (MC-LR). To break through the bottleneck of uncomplete MC-LR degradation by conventional physical-chemistry methods, Fenton-based advanced oxidation processes (AOPs) developed rapidly due to striking degradation efficiency through the potent hydroxyl radicals (HO·) oxidation. Herein, a comprehensive overview is presented on the recent achievements of the various Fenton-based technologies (including conventional Fenton, photo-Fenton, electro-Fenton, ozone-Fenton and sono-Fenton) for MC-LR degradation. In particular, the comparisons between various Fenton-based technologies about advantages and drawbacks are discussed. Based on analyzing the degradation intermediates and pathways, the destruction of Adda chain via hydroxylation was confirmed to be essential for detoxification of MC-LR. Roles of influencing factors such as MC-LR initial concentration, dosages of the catalyst and oxidant, environment alkalinity, natural organic matters (NOMs) as well as other inorganic ions are specifically summarized. This Review also gave special emphasis on technique optimization trends for Fenton application of MC-LR degradation, as well as key challenges and future opportunities in this fast developing field.


Turnip mosaic virus in oilseed rape activates networks of sRNA-mediated interactions between viral and host genomes.
Virus-induced plant diseases in cultivated plants cause important damages in yield. Although the mechanisms of virus infection are intensely studied at the cell biology level, only little is known about the molecular dialog between the invading virus and the host genome. Here we describe a combinatorial genome-wide approach to identify networks of sRNAs-guided post-transcriptional regulation within local Turnip mosaic virus (TuMV) infection sites in Brassica napus leaves. We show that the induction of host-encoded, virus-activated small interfering RNAs (vasiRNAs) observed in virus-infected tissues is accompanied by site-specific cleavage events on both viral and host RNAs that recalls the activity of small RNA-induced silencing complexes (RISC). Cleavage events also involve virus-derived siRNA (vsiRNA)-directed cleavage of target host transcripts as well as cleavage of viral RNA by both host vasiRNAs and vsiRNAs. Furthermore, certain coding genes act as virus-activated regulatory hubs to produce vasiRNAs for the targeting of other host genes. The observations draw an advanced model of plant-virus interactions and provide insights into the complex regulatory networking at the plant-virus interface within cells undergoing early stages of infection.


Causes of Death in the Seriously Injured -Why do Severely Injured Patients Die Today?
Trauma ist die häufigste Todesursache bei unter 45-Jährigen und trotzdem gibt es nur wenig Daten zu den genauen Todesursachen Schwerverletzter nach Klinikeinlieferung in Deutschland aus den letzten 10 Jahren. Ziel der Arbeit ist 1. eine Auswertung der Daten der verstorbenen Schwerverletzten eines überregionalen TraumaZentrums aus den letzten 10 Jahren. Erforscht werden sollen Verlässlichkeit der Daten, Häufigkeit der Todesursachen und Zusammenhänge mit dem Unfallmechanismus und 2. die Nachvollziehbarkeit der Daten im TraumaRegister DGU. Es erfolgte die Auswertung der Daten von 203 verstorbenen schwerverletzten Patienten aus dem Universitätsklinikum Jena, die von 2007 bis 2017 verunfallt sind. Eine eindeutige Festlegung der Todesursache ist anhand von Klinikdaten in ca. 85% der Fälle möglich. Häufigste Todesursache von Schwerverletzten nach Klinikeinlieferung ist mit 59,6% das Schädel-Hirn-Trauma, gefolgt von 17% Organversagen, 14% Hämorrhagie und 9,4% sonstigen Todesursachen. Die Verifizierung anhand von Daten aus dem TraumaRegister DGU ist möglich. Es besteht ein klarer Zusammenhang zwischen Unfallmechanismus und Todesursache. Welche Todesursache angegeben wird, unterliegt immer auch einer subjektiven Einschätzung. Insbesondere bestehen Schwierigkeiten bei Patienten, die vor weiterer Diagnostik im Schockraum versterben. Häufigste Todesursache ist heute das Schädel-Hirn-Trauma. Es ist sinnvoll, die Todesursache im TraumaRegister DGU extra zu erfassen, da diese anhand von anderen Registerdaten nur teilweise abgeleitet werden kann. Die Zusammenhänge zwischen Unfallmechanismus und Todesursache könnten ggf. für Präventionsmaßnahmen genutzt werden. The leading cause of death among people under 45 years of age is trauma. However, there is little information from the last 10 years on the exact causes of death of seriously injured people after hospital admission in Germany. The aim of the study is to evaluate the data of a level I trauma centre from the last 10 years. The reliability of the data, frequency of the causes of death and correlations with the mechanism of injury as well as the confirmability of the data in the TraumaRegister DGU are to be investigated. The University Hospital Jena data were analysed for 203 deceased trauma patients from accidental death between 2007 and 2017. A clear determination of the cause of death is possible in about 85% of cases on the basis of hospital data. The most frequent cause of death of severely injured patients after admission to the hospital is traumatic brain injury (59.6%), followed by organ failure (17%), haemorrhage (14%) and other causes of death (9.4%). Verification using data from the TraumaRegister DGU is possible. There is a clear correlation between mechanism of injury and cause of death. The cause of death is very often a subjective assessment of the recording doctor. In particular, there are difficulties with patients who die in the resuscitation room before further diagnosis. The most frequent cause of death today is traumatic brain injury. For future evaluations, the new information in the TraumaRegister DGU is helpful because the cause of death can only be partially derived from other registry data. The correlation between the type of accident and the cause of death could be used for preventive measures.


Optimization of uncatalyzed steam explosion pretreatment of rapeseed straw for biofuel production.
Rapeseed straw constitutes an agricultural residue with great potential as feedstock for ethanol production. In this work, uncatalyzed steam explosion was carried out as a pretreatment to increase the enzymatic digestibility of rapeseed straw. Experimental statistical design and response surface methodology were used to evaluate the influence of the temperature (185-215°C) and the process time (2.5-7.5min). According to the rotatable central composite design applied, 215°C and 7.5min were confirmed to be the optimal conditions, considering the maximization of enzymatic hydrolysis yield as optimization criterion. These conditions led to a maximum yield of 72.3%, equivalent to 81% of potential glucose in pretreated solid. Different configurations for bioethanol production from steam exploded rapeseed straw were investigated using the pretreated solid obtained under optimal conditions as a substrate. As a relevant result, concentrations of ethanol as high as 43.6g/L (5.5% by volume) were obtained as a consequence of using 20% (w/v) solid loading, equivalent to 12.4g ethanol/100g biomass.


IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor.
IL-15 induces proliferation, inhibits apoptosis and increases IL-4 production in murine mast cells. There is evidence that these activities are mediated via the uncharacterised receptor, IL-15R-X, rather than the classical three-chain IL-15 receptor. Effects of IL-15 on important aspects of mast cell biology, such as migration and degranulation, are unknown. We report that IL-15 induces migration of murine and human mast cells in a dose-dependent and biphasic manner, with peaks of migration occurring at approximately 10(-15) and approximately 10(-9) M. The potency of the response was similar to that induced by other well-established mast cell chemoattractants. Competition assays performed with murine and human mast cells indicate that both peaks of migration are due to chemotaxis. Pre-treatment of cells with pertussis toxin (PTX), a guanine nucleotide-binding regulatory protein (G-protein) inhibitor, resulted in complete inhibition of murine mast cell migration at approximately 10(-15) M IL-15, and human mast cell migration at approximately 10(-15) and approximately 10(-9) M. This demonstrates that murine and human mast cells express a PTX-sensitive receptor, activated in response to IL-15. Additionally, IL-15 did not induce degranulation in murine mast cells. Locally-produced IL-15 may contribute to mast cell recruitment during inflammatory responses, thereby acting as a linking cytokine between innate and adaptive arms of the immune system.


A tetrapeptide within a receptor-binding region of human follicle-stimulating hormone beta-subunit, hFSH-beta-(34-37), regulates sodium-calcium exchange in Sertoli cells.
In a previous study, we showed that binding of FSH by cultured rat Sertoli cells significantly inhibited basal levels of Na+/Ca2+ exchange. Similar inhibition was observed when proteoliposomes enriched with bovine calf testis follicle-stimulating hormone (FSH) receptors were stimulated with FSH. In the present study, we screened a series of overlapping synthetic peptide amides, representing the entire primary structure of the beta-subunit of hFSH, for their effects on sodium-dependent calcium uptake (as 45Ca2+) by monolayer cultures of Sertoli cells from immature rats. hFSH-beta-(33-53), previously identified as a receptor binding region of hFSH-beta-subunit, significantly (P < 0.05) inhibited Na+/Ca2+ exchange. A tetrapeptide [TRDL, hFSH-beta-(34-37)] contained within this sequence, was observed to be equally as active as hFSH-beta-(33-53) at 200 microM, suggesting that the regulatory effect of hFSH-beta-(33-53) on sodium-dependent 45Ca2+ influx was due to residues 34-37. hFSH-beta-(81-95) also inhibited Na(+)-dependent calcium influx, although to a lesser extent than hFSH-beta-(33-53) or hFSH-beta-(34-37). Sodium-dependent 45Ca2+ entry into Sertoli cells was enhanced in a concentration-related manner when extracellular sodium was replaced by equimolar concentrations (up to 135 mM) of choline chloride. hFSH-beta-(34-37) significantly reduced basal uptake of 45Ca2+ in choline-containing buffer, but was without effect in buffer containing 135 mM NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathological fracture of right tibia, an unusual presentation of endometrial carcinoma: a case report.
A case of bony metastasis from carcinoma of the body of uterus is presented, hitherto unreported. Diagnosis was difficult in this very unusual presentation, but the importance of post-menopausal bleeding must be emphasized.


Exercise training induces insulin-sensitizing PAHSAs in adipose tissue of elderly women.
Adverse effects of aging can be delayed with life-style interventions. We examined how exercise training (ET) alone or combined with omega-3 polyunsaturated fatty acid (PUFA) affects serum and adipose tissue (AT) lipidome in older women. Fifty-five sedentary older women were included in the physical activity program and given either sunflower (Placebo) or wax esters-rich (Calanus) oil capsules for 4 months. Serum and subcutaneous abdominal AT samples were acquired while maximum rates of oxygen consumption (VO2 max), insulin sensitivity (hyperinsulinemic-euglycemic clamps) and comprehensive lipidome profiles were determined before and after the study. ET increased VO2 max in both groups. Lipidomics profiling revealed unusual serum triacylglycerols and phospholipids with ether-bound alkyls in the Calanus group, while ET generally induced shorter-chain triacylglycerols in AT, suggesting increased de novo lipogenesis. The latter was positively associated with whole-body insulin sensitivity. Unexpectedly, insulin-sensitizing lipokines from the family of branched palmitic acid esters of hydroxy stearic acid (PAHSAs) were elevated in both serum and AT after ET, while PAHSAs-containing triacylglycerols were detected in AT. ET stimulated beneficial changes in AT, including PAHSAs synthesis. Although the added value of omega-3 PUFA supplementation was not proven, our discovery can help understand the nature of the metabolic benefits of exercise.


Potassium Postdeposition Treatment-Induced Band Gap Widening at Cu(In,Ga)Se₂ Surfaces--Reason for Performance Leap?
Direct and inverse photoemission were used to study the impact of alkali fluoride postdeposition treatments on the chemical and electronic surface structure of Cu(In,Ga)Se2 (CIGSe) thin films used for high-efficiency flexible solar cells. We find a large surface band gap (E(g)(Surf), up to 2.52 eV) for a NaF/KF-postdeposition treated (PDT) absorber significantly increases compared to the CIGSe bulk band gap and to the Eg(Surf) of 1.61 eV found for an absorber treated with NaF only. Both the valence band maximum (VBM) and the conduction band minimum shift away from the Fermi level. Depth-dependent photoemission measurements reveal that the VBM decreases with increasing surface sensitivity for both samples; this effect is more pronounced for the NaF/KF-PDT CIGSe sample. The observed electronic structure changes can be linked to the recent breakthroughs in CIGSe device efficiencies.


Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-CT Analysis.
Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density-defined osteoporosis. Poor bone quality--defined here as the presence of either osteoporosis or fragile bone strength--is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51-70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm³) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm³ or lower) and fragile bone strength (vertebral strength of 4500 N or lower). Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14-0.97 for BMD; 0.13-0.51 for strength). Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. 3.


Validation and Feasibility of the Postnatal Growth and Retinopathy of Prematurity Retinal Screening Criteria at a Level IV Tertiary Care Neonatal Intensive Care Unit.
Retinopathy of prematurity (ROP) is detected in preterm infants by standardized screening programs, but in general, they have poor sensitivity. The Postnatal Growth and Retinopathy of Prematurity (G-ROP) algorithm uses weight gain to predict ROP superior reported sensitivity. Our objectives are to (1) independently validate the sensitivity of G-ROP criteria for the detection of ROP in infants born at >28 weeks' gestation in a tertiary care unit in the United States and (2) to calculate the cost savings associated with a potential reduction in examinations. This is a retrospective analysis of retinal screening examination data, with post-hoc application of G-ROP criteria to determine whether G-ROP criteria had acceptable sensitivity and specificity in diagnosing Type 1 and Type 2 ROP. All infants born at >28 weeks who were screened by current American Academy of Pediatric Ophthalmologists/American Academy of Pediatrics guidelines at Oklahoma Children's Hospital at the University of Oklahoma Health Sciences Center, between 2014 and 2019, were included. Subset analysis of infants screened by second tier criteria was also performed. Potential cost savings were estimated by analyzing frequency of billing codes. And by calculating the number of infants who could have potentially been spared examination. The G-ROP criteria had 100% sensitivity in detecting type 1 and 87.6% sensitivity in detecting type 2 ROP, which would have reduced infants screened by 50%. All infants in the second tier who would require treatment were detected. A cost saving of 49% was projected. The G-ROP criteria are easy to apply in real-world setting, thus establishing feasibility. The algorithm identified all cases of type 1 ROP; however, some cases of type 2 ROP were not detected. The annual savings in hospital examination cost by using these criteria would be 50%. Therefore, G-ROP criteria can safely be used to screen for ROP and may reduce the number of unnecessary examinations. · The G-ROP screening criteria are safe and predict 100% of treatment warranted ROP.. · Adoption of G-ROP criteria is feasible for level IV NICUs.. · Adoption of G-ROP screening guidelines will result in significant cost savings..


Pre-anaesthetic assessment and the prevention of post-ECT morbidity.
The introduction of anaesthesia and muscle relaxation has made ECT relatively safe. In a retrospective study of the case notes of 367 consecutive patients receiving ECT over a two year period, chest X-ray and full blood count added no significant information and were ineffective in predicting morbidity, in contrast to physical examination alone.


Tyrosine triple mutated AAV2-BDNF gene therapy in an inner retinal injury model induced by intravitreal injection of N-methyl-D-aspartate (NMDA).
Glaucoma is a group of chronic optic neuropathies characterized by the degeneration of retinal ganglion cells (RGCs) and their axons, and they ultimately cause blindness. Because neuroprotection using neurotrophic factors against RGC loss has been proven a beneficial strategy, extensive attempts have been made to perform gene transfer of neurotrophic proteins. This study used the inner retinal injury mouse model to evaluate the neuroprotective effect of tyrosine triple mutated and self-complementary adeno-associated virus (AAV) encoding brain-derived neurotrophic factor (BDNF; tm-scAAV2-BDNF). C57BL/6J mice were intravitreally injected with 1 μl of tm-scAAV2-BDNF and its control AAV at a titer of 6.6 E+13 genome copies/ml. Three weeks later, 1 μl of 2 mM N-methyl-D-aspartate (NMDA) was administered in the same way as the viral injection. Six days after the NMDA injection, we assessed the dark-adapted electroretinography (ERG). Mice were sacrificed at one week after the NMDA injection, followed by RNA quantification, protein detection, and histopathological analysis. The RNA expression of BDNF in retinas treated with tm-scAAV2-BDNF was about 300-fold higher than that of its control AAV. Meanwhile, the expression of recombinant BDNF protein increased in retinas treated with tm-scAAV2-BDNF. In addition, histological analysis revealed that tm-scAAV2-BDNF prevented thinning of the inner retina. Furthermore, b-wave amplitudes of the tm-scAAV2-BDNF group were significantly higher than those of the control vector group. Histopathological and electrophysiological evaluations showed that tm-scAAV2-BDNF treatment offered significant protection against NMDA toxicity. Results showed that tm-scAAV2-BDNF-treated retinas were resistant to NMDA injury, while retinas treated with the control AAV exhibited histopathological and functional changes after the administration of NMDA. These results suggest that tm-scAAV2-BDNF is potentially effective against inner retinal injury, including normal tension glaucoma.


Intravenous xenotransplantation of human placental mesenchymal stem cells to rats: comparative analysis of homing in rat brain in two models of experimental ischemic stroke.
Mesenchymal stem cells from human placenta obtained after term natural delivery were cultured and labeled with vital dye Dil of magnetic fluorescing microparticles. The labeled cells were transplanted intravenously to rats with occlusion of the median cerebral artery. Penetration of cells through the brain-blood barrier and their distribution in the brain of experimental animals were studied on serial cryostat sections. Two models of cerebral artery occlusion associated with different traumatic consequences were used. The efficiency of crossing the blood-brain barrier by transplanted cells, the number of mesenchymal cells attaining the ischemic focus and neurogenic zones, and the time of death of transplanted cells largely depended on the degree and nature of injury to the central nervous system, which should be taken into account when planning the experiments for evaluation of the effects of cell therapy on the models of neurological diseases and in clinical studies in the field of regenerative neurology.


pH-Sensitive polymer blends used as coating materials to control drug release from spherical beads: elucidation of the underlying mass transport mechanisms.
To elucidate the drug release mechanisms from pellets coated with pH-sensitive polymer blends. Verapamil hydrochloride-loaded beads were coated with various blends of a water-insoluble and an enteric polymer, ethylcellulose:Eudragit L and Eudragit NE:Eudragit L, respectively. Both experimental and theoretical techniques were used to characterize the systems before and upon exposure to 0.1 M HCl and phosphate buffer (pH 7.4). Using analytical solutions of Fick's second law of diffusion, optical and scanning electron microscopy, and mechanical and gravimetric analysis, new insight into the underlying drug release mechanisms could be gained. More importantly, the latter can be effectively altered by varying the type of polymer blend and blend ratio. For example, at low pH drug release is primarily controlled by diffusion through the intact film coatings in Eudragit NE:Eudragit L blends, whereas crack formation is of major importance in ethylcellulose:Eudragit L-coated systems. At high pH, the (partial) leaching of the enteric polymer out of the coatings plays an important role. In all cases, the observed drug release profiles could be explained based on the occurring mass transport processes. The obtained new knowledge can be used to effectively adjust desired drug release mechanisms and, thus, release patterns.


The remodeling of alveolar bone supporting the mandibular first molar with different levels of periodontal attachment.
The objective of this study was to investigate alveolar bone remodeling of the mandibular first molar with differing levels of periodontal attachment under mastication loading. Three-dimensional finite element models of the mandibular first molar with differing levels of periodontal attachment were established. The stress distributions and bone density changes were analyzed under mastication loading to simulate the remodeling process of mandibular bone based on the theory of strain energy density. The results showed that the alveolar buccal, lingual ridges and root apex areas experienced higher stresses. The stresses and densities of the alveolar bone increased proportionally to increased mastication loading. Decrease in alveolar bone density under extreme loading indicated bone resorption. The remodeling rate was continual with gradual loading. Periodontal ligament support marginally decreased with an increased remodeling rate under extreme loading. Changes in alveolar bone density can reflect the remodeling process of periodontal tissue under mastication loading. The relationship between the change in density and mastication loading during remodeling can provide useful indicators into clinical treatment and diagnosis of the periodontal disease.


Diagnosis and treatment of posterior interosseous nerve syndrome using soft tissue manipulation therapy: a case study.
Peripheral nerve entrapments of the upper and lower extremity are commonly seen in practice. Chronically repetitive movement patterns lead to constriction of the nerve due to the development of local fibrosis within the soft tissues surrounding the nerve which also affects nerve traction, mobility, and function. A case is presented of a patient with motor weakness in the wrist and hand in order to illustrate the diagnosis and treatment of posterior interosseous nerve (PIN) syndrome. Using Active Release Techniques Soft Tissue Management and Peripheral Nerve Release Systems) the patient's symptomatology was resolved. Soft tissue-based management in conjunction with neural gliding may be beneficial in the conservative management of PIN syndrome. Further research into the pathophysiology of nerve entrapments will have immediate impact on the management of neuropathies and likely result in emphasizing conservative management and rehabilitation rather than surgical intervention particularly in cases not involving denervation or paralysis.


Local climate zones datasets from five Southern European cities: Copernicus based classification maps of Athens, Barcelona, Lisbon, Marseille and Naples.
Here, we provide Local Climate Zones (LCZ) map datasets from five Southern European Mediterranean cities: Athens (Greece), Barcelona (Spain), Lisbon (Portugal), Marseille (France) and Naples (Italy). The maps were produced according to a geographic information system (GIS)-based classification method, using freely available Copernicus Land Monitoring Service (CLMS) input data. Several maps are provided: (i) five LCZv1 maps (one per city) depicting urban LCZ's aggregated by density (no building height information); (ii) five LCZv1_leaf maps (one per city), identical to the previously mentioned ones, with tree cover LCZ classes A and B reclassification according to the Dominant Leaf Type (DLT) (deciduous or coniferous); (iii) two LCZv1_BH maps (Athens and Lisbon) distinguishing urban LCZ classes 123 and 456 according to the dominant building height (BH); and (iv) two LCZv1_leaf_BH maps (Athens and Lisbon) identical to the previous ones with added DLT-based land cover classification. The LCZ classification maps are available in both ArcGIS .lyr layer and GeoTIFF raster formats (Appendix 1 and 2), with a spatial resolution of 50×50m pixels, and are suitable to urban climate-related studies, particularly at the metropolitan and city scales of analysis. The data here provided is related to the article entitled «Local Climate Zones in five Southern European cities: an improved GIS-based classification method based on free data from the Copernicus Land Monitoring Service» [1], and the corresponding method/ArcGIS based custom Toolbox is freely available in «Local Climate Zones classification from Copernicus Land Monitoring Service datasets: an ArcGIS-based Toolbox» [2].


Sequential events of apoptosis induced by zearalenone in cultured hepatocarcinoma cells.
Zearalenone (ZEA) is a fungal metabolite that can contaminate feed and foodstuffs and can cause serious health problems for animals as well as for humans. The present investigation was conducted to determine the chronological succession of the main events that characterise ZEA-induced toxicity in human hepatocarcinoma cells. To this aim, we have monitored the effects of ZEA on (1) cell viability, (2) heat-shock protein expression, (3) oxidative damage, (4) DNA fragmentation, (5) the cell cycle and (6) the cell-death-signalling pathway. Our results demonstrated that ZEA reduced cell viability in a time- and dose-dependent manner. When we exposed HepG2 cells to 100 µM ZEA (80% of cells are viable) for different treatment times (2, 4, 8, 24, 30, 48 and 60 h), we demonstrated an induction of Hsp70 protein, an increase in reactive oxygen species (ROS) generation, DNA fragmentation and cell-cycle arrest. These events begin after only 2 h of mycotoxin exposure and are earlier than those implicated in the execution of apoptosis. However, significant apoptotic cell death was observed after at least 30 h of ZEA exposure as a consequence of increased Bax expression, decreased Bcl-2 expression and mitochondrial membrane potential (Δψm)-released cytochrome c and activated caspase-3 and caspase-9.


Peer review through clinical rounds. A collaborative critical thinking strategy.
Facilitating the development of critical thinking in beginning nursing students is challenging and exciting. Peer review through student-led clinical rounds can be an effective way to promote students' critical thinking in communicating assessment data and identifying client strengths and problems. Nineteen beginning baccalaureate nursing students participated in a peer review clinical round experience and were then asked to describe their critical thinking. Strengths of using the peer-led rounds include promotion of active student learning and encouragement of collaboration among peers.


Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.
Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.


Beta-lactams resistance and presence of class 1 integron in Pseudomonas spp. isolated from untreated hospital effluents in Brazil.
The aim of the present study was to investigate the resistance profile, to detect the presence of beta-lactam resistance genes, phenotypic expression of efflux pump systems and class 1 integrons in Pseudomonas spp. strains obtained from untreated hospital effluents. Effluent samples were collected from four hospitals in Porto Alegre, RS, Brazil. Pseudomonas were isolated on MacConkey agar plates and the identification was confirmed by 16S rRNA PCR and biochemical tests. Susceptibility testing was determined by disk-diffusion method using 11 different beta-lactams and MIC assays were performed on isolates resistant to imipenem and ceftazidime. The beta-lactamase genes bla (IMP), bla (VIM), bla (SPM-1), bla (OXA-23-like), bla (OXA-24-like), bla (OXA-51-like) and the intl1 gene from class 1 integron were analysed by PCR. One hundred and twenty-four isolates were recovered and the most common species was Pseudomonas pseudoalcaligenes. The resistance found among the isolates was considered high, 62 (50%) isolates were multiresistant. No isolate carrying the beta-lactamase genes tested was found among the strains. Seven isolates showed reduction of MIC for imipenem and ceftazidime in the presence of cyanide m-chlorophenylhydrazone, indicating the hyper expression of efflux pumps. From the 124 isolates, 52 (41.9%) were identified as carrying the class 1 integron gene, intI1. Untreated hospital effluents could be a source of environmental contamination due to discharge of antimicrobial resistant bacteria which can carry integron class 1 and act as a reservoir of resistance genes and have efflux pump systems.


Combined p53 and Bcl2 Immunophenotypes in Prognosis of Vietnamese Invasive Breast Carcinoma: A Single Institutional Retrospective Analysis.
Aberrant of p53 and Bcl2 genes cause changes in the quantity and quality of their proteins and contribute to the pathogenesis of some cancer types including breast cancer. Expression of p53 and Bcl2 were associated to adverse clinical outcomes in breast cancer. To predict the survival outcomes of invasive breast cancer in Vietnam, using immunohistochemical expression of p53, Bcl2 proteins. The current study was conducted on 526 breast cancer patients who had surgical operations, but had not received neo-adjuvant chemotherapy, from 2011 to 2014. The clinicopathological characteristics were recorded. Immunohistochemical staining was performed on p53, Bcl2 markers. Expression of p53 and Bcl2 were paired into different immunophenotypes for analysis with clinicopathological characteristics and survival. All breast cancer patients' survival were analyzed by using Kaplan-Meier and Log-Rank models. The presence of p53 protein was detected in 44.1%. Positive p53, and p53+Bcl2- immunophenotype were significantly associated with poorer prognostic features. In contrast, the positive Bcl2 protein accounted on 57.6%, and combination of p53-Bcl2+ were strong correlated with better clinicopathological parameters. Bcl2 positivity was observed in higher than the negative Bcl2 in the five-year OS (Overall survival) proportion (91.2 vs 79.4%, respectively) (p < 0.05). Multivariate analysis revealed that the expression of p53, Bcl2 or combinations of these 2 proteins was no longer remained as an independent prognostic variable. The Bcl2 positivity had a distinct OS and DFS (Disease free survival). The expression of p53 and Bcl2 are inversely correlated to clinical outcomes in breast cancer.


Stimulatory role of transforming growth factors in multistage skin carcinogenesis: possible explanation for the tumor-inducing effect of wounding in initiated NMRI mouse skin.
Mechanical wounding provides a convertogenic ("stage I tumor-promoting") stimulus in initiated NMRI mouse skin, indicating that this stage of carcinogenesis can be entirely controlled by endogenous factors. A search for such factors led to the finding that both platelet-derived Epstein-Barr-virus-inducing factor (EIF), alias human TGF beta 1 and porcine TGF beta, exhibited--upon intracutaneous injection--convertogenic efficacy in initiated NMRI-mouse skin in vivo provided that their injection was combined with a single topical application of the non-convertogenic tumor promoter 12-O-retinolyphorbol-13-acetate (RPA). Since TGF beta inhibits epidermal cell proliferation, the RPA treatment is thought to provide a mitogenic stimulus required for conversion. The RPA treatment can be replaced by intracutaneous injection of transforming growth factor alpha (TGF alpha). These results indicate that the stage of conversion consists of two components, one of which is related to mitogenesis (RPA or TGF alpha), the other to a still unknown activity exhibited by TGF beta-like factors. Thus, endogenous factors with the quality of "wound hormones" may be involved in multistage skin carcinogenesis. This finding could explain the convertogenic effect of skin wounding.


In Silico molecular docking and dynamic analysis of natural compounds against major non-structural proteins of SARS-COV-2.
COVID-19 has infected millions and significantly affected the global economy and healthcare systems. Despite continuous lockdowns, symptomatic management with currently available medications, and numerous vaccination drives, it is still far more difficult to control. Against COVID-19 infection, the pressure to develop vaccines and drugs has led to using some currently available medications like remdesivir, azithromycin, hydroxychloroquine and ritonavir. Understanding the importance and potential of harmless molecules to tackle SARS-COV-2, we designed the present study to identify potential natural phytocompounds. In the present study, we docked natural compounds and standard drugs against SARS-COV-2 proteins: papain-like protease, main protease and helicase. ADME/T and ProTox-II analyses were used to determine the toxicity of phytocompounds and drugs. The docking analysis revealed that podophyllotoxin gave the highest binding affinity scores of -8.1, -7.1 and -7.4 kcal/mol against PLpro, Mpro and helicase, respectively. Among the control drugs, doxycycline hydrochloride showed the highest binding affinity of -10.5, -8.4 and -8.8 kcal/mol against PLpro, Mpro and helicase. The results of this study revealed that podophyllotoxin and doxycycline hydrochloride could be promising inhibitors against SARS-Cov-2. Molecular dynamic simulations were executed for the best docked (PLpro-podophyllotoxin) complex, and the results displayed stable conformation and convergence. Energy plot results predicted a global minima average energy of -95 kcal/mol and indicated podophyllotoxin's role in stabilizing protein and making it compact and complex. FarPPI server used MM/GBSA approach to determine free binding affinity, and helicase-gallic acid complex showed the highest affinity, respectively. Therefore, it can be concluded that there is still a need for in vitro and in vivo studies to support further and validate these findings and validate these findings.Communicated by Ramaswamy H. Sarma.


Effects of ischemic preconditioning in the late phase on homing of endothelial progenitor cells in renal ischemia/reperfusion injury.
The aim of this study was to determine whether the mobilization and recruitment of endothelial progenitor cells (EPCs) contribute to the protection of kidneys from ischemia/reperfusion (I/R) injury after ischemic preconditioning (IPC) during the late phase. Seventy-five male Sprague-Dawley rats were divided into the following groups: sham-operated (group A; n = 25), ischemia/reperfusion hosts that underwent 45 minutes of left renal artery ischemia (group B; n = 25), and ischemic preconditioning-treated group (group C; n = 25). Group C underwent 3 cycles of 5 minutes of occlusion and 5 minutes of reperfusion followed by 24 hours of reperfusion before the following 45 minutes of occlusion. Serum samples were collected and renal tissues harvested for histological examination terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemical staining, and Western blot analysis to determine the expression levels of CD34, VEGFR-2 (Vascular Endothelial Growth Factor Receptor 2)/flk-1, vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1α (SDF-1α). Compared with group B, the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and acute tubulointerstitial injury at 24 hours after operation were significantly reduced in group C. At 72 hours, tubular epithelial cell apoptosis was also decreased (17.6 ± 4.45 vs 63.8 ± 6.10; P < .01). CD34+ and flk-1+ cells that mostly accumulated in the medullopapillary parenchyma were significantly increased at 72 hours (P < .05). Expression levels of VEGF and SDF-1α were also significantly higher in group C (P < .05). The present work suggested that IPC protected kidneys from IR injury in the later phase through enhanced mobilization and recruitment of EPCs. VEGF and SDF-1α may play important roles in this protective effect.


[Children death rates in a rural village of Ivory Coast (author's transl)].
A 10 years statistical study with a global death rate of 63 per 1.0000 and its changes according to the age groups.


Petite deletion map of the mitochondrial oxi3 region in Saccharomyces cerevisiae.
Fifty eight mitochondrial mutants (p + mit- mutants), all deficient in cytochrome oxidase activity and previously assigned to the genetic region oxi3 on the mitochondrial DNA, were mapped by the method of "petite deletion mapping". This procedure resulted in the identification of at least twenty one different classes of oxi3 mutants, which could be arranged in a linear order. Moreover, it provided a set of twenty three p- petite mutants, each containing a differentially deleted mit DNA segment included in the oxi3 region. The two sets of mutants, p+ oxi3- and p- oxi3+, will be of interest for a further genetic and physical analysis of this mitochondrial DNA segment which spans over about ten thousand base pairs and controls the subunit I of cytochrome oxidase.


Linguistic Relativity in Cross-Cultural Context: Converging Evidence From Neuroanthropology.
Kemmerer's discussion of links between semantic typology and embodied cognition is welcome, especially his survey of available evidence. Focusing on mechanisms of embodied enculturation, however, we must understand that language is just one part of developmental assemblies that shape cognition, alongside other cultural elements such as sensory learning, behavior patterns, social interactions, and emotional experience. We believe that a source of this problem is an obsolete definition of "culture" as shared mental information that is inconsistent with models of embodied cognition and yet pervasive in human and cognitive sciences. We point to microethnographies of cognitive ecologies as a tractable remedy.


Multidecadal increase in North Atlantic coccolithophores and the potential role of rising CO₂.
As anthropogenic carbon dioxide (CO2) emissions acidify the oceans, calcifiers generally are expected to be negatively affected. However, using data from the Continuous Plankton Recorder, we show that coccolithophore occurrence in the North Atlantic increased from ~2 to more than 20% from 1965 through 2010. We used random forest models to examine more than 20 possible environmental drivers of this change, finding that CO2 and the Atlantic Multidecadal Oscillation were the best predictors, leading us to hypothesize that higher CO2 levels might be encouraging growth. A compilation of 41 independent laboratory studies supports our hypothesis. Our study shows a long-term basin-scale increase in coccolithophores and suggests that increasing CO2 and temperature have accelerated the growth of a phytoplankton group that is important for carbon cycling.


Structure-based discovery of potent inhibitors of Axl: design, synthesis, and biological evaluation.
Commonly overexpressed in many cancers and associated with tumor growth, metastasis, drug resistance, and poor overall survival, Axl has emerged as a promising target for cancer therapy. However, the availability of new chemical forms for Axl inhibition is limited. Herein, we present the development and characterization of novel Axl inhibitors, including the design, synthesis, and structure-activity relationships (SARs) of a series of diphenylpyrimidine-diamine derivatives. Most of these compounds exhibited remarkable activity against the Axl kinase. In particular, the promising compound m16 showed the highest enzymatic inhibitory potency (IC50 = 5 nM) and blocked multiple tumor cells' proliferation potencies (the CC50 of 4 out of 42 cancer cell lines <100 nM). Furthermore, compound m16 also possessed preferable pharmacokinetic profiles and liver microsome stability. All these favorable results make m16 a good leading therapeutic candidate for further development.


DNA signatures for detecting genetic engineering in bacteria.
Using newly designed computational tools we show that, despite substantial shared sequences between natural plasmids and artificial vector sequences, a robust set of DNA oligomers can be identified that can differentiate artificial vector sequences from all available background viral and bacterial genomes and natural plasmids. We predict that these tools can achieve very high sensitivity and specificity rates for detecting new unsequenced vectors in microarray-based bioassays. Such DNA signatures could be important in detecting genetically engineered bacteria in environmental samples.


Carrion fly (Diptera: Calliphoridae) larval colonization of sunlit and shaded pig carcasses in West Virginia, USA.
Two pig (Sus scrofta L.) carcasses were placed in sunlit and shaded plots in September 2003, and again in May 2004. Mean ambient temperatures between sunlit and shaded plots were not significantly different in either September or May, but mean ambient temperatures at sunlit and shaded plots in 2004 were significantly higher than corresponding means for sunlit and shaded plots in 2003. Mean maggot mass temperatures were significantly higher than ambient plot temperatures for all four experimental plots (i.e., sunlit and shaded carcasses in both 2003 and 2004). In addition, maggot mass temperatures on sunlit carcasses were positively, and significantly, correlated with ambient temperatures, whereas there was no significant correlation between maggot mass and ambient temperatures at shaded plots. Carcass decomposition proceeded more rapidly in 2004 in the presence of higher ambient temperatures, and sunlit carcasses decomposed faster than shaded ones in both 2003 and 2004 experiments. Phaenecia coeruleiviridis (Macquart) and Phormia regina (Meigen) third instars dominated collections on all four carcasses, but there was little temporal overlap between these species with third instars of the former dominating collections in the early portion (approximately 40%) of each experimental period (with the exception of the shaded carcass in 2004 where both species were co-dominant), and the latter assuming dominance in the latter portion (approximately 60%). Lower accumulated degree hour values were calculated for instar development on 2004 carcasses subjected to higher ambient temperatures.


Thirteen-week abdominal pregnancy after hysterectomy.
A case of a 42-year-old woman who presented 11 weeks after a vaginal hysterectomy with a 13-week abdominal pregnancy is presented. The patient had operative intervention, which was complicated by bleeding and a pulmonary embolus. A brief review of the literature relating to post-hysterectomy pregnancy follows. Physicians are urged to consider this diagnosis in women who have had hysterectomies, even if the hysterectomy was performed years earlier.


Swimming of pregnant rats at different water temperatures.
We studied the chronic effect of exercise during water immersion, associated with thermal stress (water temperature at 22, 35 and 40 degrees C) at an intensity of 80% of maximal work load supported in pregnant rats (P) and non-pregnant female rats (NP). P and NP were subdivided into three subgroups according to water temperature during exercise (P22 and NP22; P35 and NP35; P40 and NP40). The animals were submitted to daily swimming sessions of 10-15 min, for 19 days of pregnancy (P) or experimental conditions (NP). Plasma concentration of triglycerides, cholesterol, glucose, total protein, albumin and corticosterone were determined 24 h after the last exercise session. Weight gain and rectal temperature pre- and post-swimming session were also determined. The offspring were examined just after caesarian section on the 20th day of pregnancy to check weight, length and litter size. Pregnant rats showed an increase of triglycerides, reduction of glycemia, total protein and albumin and cholesterol (at 35 degrees C) when compared to non-pregnant animals. Such effects probably lead to an adequate delivery of substrate to the fetus and prepare the mother for lactation. Daily thermal stress did not modify metabolic responses to exercise in pregnant rats. Results also show a deleterious effect on offspring when the mother is exposed daily to extreme temperatures during swimming. These results suggest that water temperature (cold and hot) in swimming have to be considered to avoid damage in fetal development.


Knockdown of USP28 enhances the radiosensitivity of esophageal cancer cells via the c-Myc/hypoxia-inducible factor-1 alpha pathway.
Acquired radioresistance is a major clinical obstacle in the treatment of esophageal cancer (EC). Ubiquitin-specific protease 28 (USP28) has been implicated in tumor growth in various cancer types. However, the role of USP28 and its underlying mechanisms of radioresistance in EC remain unknown. In the current study, we found that USP28 and c-Myc levels were upregulated in EC tissues and EC cell lines. The mRNA expression levels of USP28 and c-Myc were increased in the radioresistant human EC cell line (ECA109R) compared with those in ECA109 cells. In addition, the expression levels of USP28 and c-Myc were increased with increase in culture time after irradiation. Meanwhile, overexpression of USP28 decreased the radiosensitivity of ECA109 cells. In contrast, USP28 knockdown enhanced the radiosensitivity of ECA109R cells. Moreover, USP28 positively regulated the protein level of c-Myc, and c-Myc negatively regulated the radiosensitivity of ECA109 and ECA109R cells. Furthermore, c-Myc reversed the inhibitory effect of USP28 on the radiosensitivity of EC cells. Additionally, c-Myc enhanced the accumulation of hypoxia-inducible factor-1 alpha (HIF-1α) at the posttranscriptional level, and the reinforcing effect of c-Myc silencing on the radiosensitivity of EC cells could be reversed by HIF-1α overexpression. Besides, knockdown of USP28 blocked the effect of c-Myc on activation of ataxia telangiectasia-mutated/ataxia telangiectasia and Rad3-related DNA damage checkpoint after irradiation. In conclusion, knockdown of USP28 enhanced the radiosensitivity of EC cells by destabilizing c-Myc and enhancing the accumulation of HIF-1α. Therefore, USP28 may serve as a novel therapeutic target to overcome EC radioresistance.


Defining covert recording: A qualitative study exploring the experiences of clinicians when a patient records a hospital clinical encounter using a smartphone without consent.
Patients use their smartphones to covertly record their clinical encounters in hospital. However, this issue is poorly understood. Insight into the clinician perspective will help inform policies and practices that deliver safe environments for patients and clinicians. This study aimed to gain a deep understanding of clinician attitudes and behaviours when a patient covertly records a hospital clinical encounter using a smartphone. Semi-structured interviews were undertaken with 20 hospital clinicians. Participants were recruited via purposive and snowball sampling. Interviews were conducted in person or via Microsoft Teams. Interviews were digitally audio recorded and transcribed. Data was analysed using thematic analysis. Most of the 20 participants reported they had either suspected or experienced a patient covertly recording a clinical encounter. Covert recordings occurred across a broad range of clinical disciplines and contexts. Themes were identified from participant perspectives, including discernment of patient intention, likeliness to consent to the recording if asked, anticipated risks and potential benefits associated with the covert recording. These themes have led to the categorisation of three forms of covert recording: (1) Intentional Covert Recording (2) Inadvertently - Covert Recording, and (3) Beneficial Covert Recording. Clinicians have varied experiences and responses when a patient covertly records a clinical encounter. Findings indicate that nuanced strategies may be required to support clinicians to manage covert recording, whilst balancing the needs of patients.


Synthesis of optically active β- or γ-alkyl-substituted alcohols through copper-catalyzed asymmetric allylic alkylation with organolithium reagents.
An efficient one-pot synthesis of optically active β-alkyl-substituted alcohols through a tandem copper-catalyzed asymmetric allylic alkylation (AAA) with organolithium reagents and reductive ozonolysis is presented. Furthermore, hydroboration-oxidation following the Cu-catalyzed AAA leads to the corresponding homochiral γ-alkyl-substituted alcohols.


Sex-dependent programming of glucose and fatty acid metabolism in mouse offspring by maternal protein restriction.
Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome. We aimed to establish a mouse model of metabolic programming focusing on the sex-specific effects of a maternal low-protein diet during gestation on glucose and lipid metabolism in the adult offspring. Pregnant C57BL/6 mice received a control or a low-protein diet (18% vs 9% casein) throughout gestation. Male and female offspring received a low-fat or a high-fat diet from 6 to 22 weeks of age. Maternal low-protein diet during gestation led to deteriorated insulin sensitivity on high-fat feeding in female offspring, as determined by biochemical and microarray analyses. Female offspring of control diet-fed dams were relatively resistant to high-fat diet-induced metabolic dysregulation. In contrast, maternal low-protein diet did not specifically affect the metabolic parameters addressed in male offspring. In males, the high-fat diet led to insulin insensitivity regardless of the diet of the dam. Our findings show that fetal malnutrition has a limited impact on male mouse offspring, yet it does influence the metabolic response to a high-fat diet in females. These findings may have implications for future early diagnostics in metabolic syndrome and for the development of sex-specific treatment regimens.


Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses.
Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted. One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions. Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1-microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-microg group among the three calcitriol groups. Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.


Evaluation of experimental, analytical, and computational methods to determine long-bone bending stiffness.
Methods used to evaluate bone mechanical properties vary widely depending on the motivation and environment of individual researchers, clinicians, and industries. Further, the innate complexity of bone makes validation of each method difficult. Thus, the purpose of the present research was to quantify methodological error of the most common methods used to predict long-bone bending stiffness, more specifically, flexural rigidity (EI). Functional testing of a bi-material porcine bone surrogate, developed in a previous study, was conducted under four-point bending test conditions. The bone surrogate was imaged using computed tomography (CT) with an isotropic voxel resolution of 0.625 mm. Digital image correlation (DIC) of the bone surrogate was used to quantify the methodological error between experimental, analytical, and computational methods used to calculate EI. These methods include the application of Euler Bernoulli beam theory to mechanical testing and DIC data; the product of the bone surrogate composite bending modulus and second area moment of inertia; and finite element analysis (FEA) using computer-aided design (CAD) and CT-based geometric models. The methodological errors of each method were then compared. The results of this study determined that CAD-based FEA was the most accurate determinant of bone EI, with less than five percent difference in EI to that of the DIC and consistent reproducibility of the measured displacements for each load increment. CT-based FEA was most accurate for axial strains. Analytical calculations overestimated EI and mechanical testing was the least accurate, grossly underestimating flexural rigidity of long-bones.


Mechanics of the subtalar joint and its function during walking.
Knowledge of the location of the subtalar joint axis in individual patients would permit clinical assessment of the forces and moments that produce frontal-plane foot and ankle deformities. Biomechanical analysis of the subtalar joint is hindered, however, by the inaccessibility of the talus, which makes locating the joint axis difficult, and by the high degree of intersubject anatomic variation. This article discusses work done with cadaver specimens and using invasive methods in vivo that has enhanced our understanding of the mechanics of the subtalar joint and its function during gait. Also reviewed are investigations of the actions of muscles that cross the subtalar joint.


Randomized controlled expressive writing pilot in individuals with Parkinson's disease and their caregivers.
Individuals with Parkinson's disease (PD) and their caregivers are at risk for emotional distress and hypercortisolism. Expressive writing is an effective complementary intervention to ameliorate the psychological and physiological effects of chronic illness. This pilot study aimed to evaluate feasibility and preliminary effectiveness of an expressive writing intervention for individuals with PD and their caregivers. Individuals with PD (N = 27) and their caregivers (N = 14) were randomly assigned to expressive (N = 15 patients, eight caregivers) or neutral (N = 12 patients, six caregivers) writing conditions. Cortisol awakening response (CAR), non-motor functioning, quality of life, and performance on tests of cognitive functioning were assessed at baseline, immediate post, 4-month, and 10-month post intervention. Attrition was a challenge as eight patients (29.62 %) and four caregivers (28.57 %) chose to discontinue before beginning the intervention or were lost to follow up prior to completing the intervention or the first follow up visit. Significant reduction in anxiety, marginally significant improvement in depression and caregiver burden, and significant improvements in performance on tests of learning and memory were observed, but these changes did not differ by writing condition. CAR significantly differed over time between patients and caregivers and writing conditions. Some evidence for the feasibility and effectiveness of writing to alleviate hypercortisolism was demonstrated in a small sample of PD patients; however, relatively high attrition rates and the lack of difference between expressive and neutral writing conditions on emotional and neurocognitive outcomes suggests expressive writing procedure modifications may be needed to obtain optimal results for this population. ClinicalTrials.gov, NCT02217735 , Study Start Date: August 30, 2011.


[Analysis of thalassemia-related mutations in Pingxiang area of Jiangxi].
To study the distribution of α- and β -thalassemia-related mutations in Pingxiang area of Jiangxi Province, China. PCR and reverse dot blotting (PCR-RDB) were carried out to detect common mutations of α and β globin genes among 2558 individuals with positive results of primary screening. The PCR-RDB assay has identified 1222 carriers of thalassemia-related mutations, which yielded a detection rate of 47.8%. Among these, 645 individuals (including homozygous patients) have carried α globin gene mutations, with the common types including -αSEA/αα, -α3.7/αα and -α4.2/αα. 539 individuals have carried β globin gene mutations, with the common types including IVS-Ⅱ-654, CD41-42, CD17, CD28, CD27-28, βE, and CD71-72. Thirty eight individuals (1.5%) have carried α and β globin gene mutations simultaneously. The carrier rate for α and β globin gene mutations in Jiangxi is high. Attention should be paid to newborn screening as part of the birth defect prevention and control program in order to reduce the birth rate of thalassemia in this region.


Destructive arthritis of the hip in a patient with Crohn's disease.
Isolated destructive peripheral arthropathy is a rare complication of Crohn's disease. We describe the clinical course and radiographic findings of such a case. A 28-yr-old male presented to our chiropractic clinic with chronic left hip pain. The patient was known to have Crohn's disease. Five years earlier the gastrointestinal symptoms resolved with a brief course of prednisone. However, the left hip pain continued. A radiograph of the left hip was read as normal. Repeat radiograph, 2 yr later, revealed destructive changes of the left hip and, in retrospect, early destructive changes could be seen on the initial radiograph. The diagnosis, in this case, was destructive arthritis of the left hip secondary to Crohn's disease. The treatment selected in this case was observation and nonsteroidal anti-inflammatory drug use. This diagnosis, a relatively rare complication of Crohn's disease, should be considered in a young adult patient with Crohn's disease and persistent peripheral joint pain.


Comparison between RGD-peptide-modified titanium and borosilicate surfaces.
The use of synthetic peptides containing adhesive sequences, such as the Arg-Gly-Asp (RGD) motif, represents a promising strategy to control biological interactions at the cell-material interface. These peptides are known to improve the tissue-material contact owing to highly specific binding to cellular membrane receptors known as integrins, thereby promoting the adhesion, migration and proliferation of cells. The peptides were coupled to borosilicate glass and titanium surfaces using silanisation chemistry. A tryptophan residue was incorporated into the amino acid sequences of selected peptides to facilitate the detection of the covalently bound peptides. Successful peptide immobilisation was proven by fluorimetric measurements. The confocal imaging analysis suggests a homogeneous distribution of the immobilised peptide across the biomaterial surface. In vitro cell proliferation assays were employed to compare the adhesion potentials of the well-known RGD-containing peptides GRGDSP, GRADSP and RGDS to the three peptides designed by our group. The results demonstrate that the RGD sequence is not necessarily required to enhance the adhesion of cells to non-biological surfaces. Moreover, it is shown that the number of adhering cells can be increased by changes in the peptide hydrophobicity. Changes in the cytoskeleton are observed depending on the type of RGD-peptide modification.


Prevention and treatment of COVID-19 infection by earthing.
Earthing is a body contact with earth without insulator. In previous studies, grounding revealed anti-inflammatory effect, immunity enhancement, anticoagulation, and rising blood oxygenation. To investigate the role of earthing in treatment and prevention of COVID-19 infection. An observational and interventional study included 71 cases with COVID-19 infection. Earthing was applied as preventive and treatment measures. All participants conducted earthing through direct contact with the earth or connecting apparatus for about 15 min to 6 h/day. Sixty-nine patients were fully improved within 2 h-11 days after commencement of earthing (mean: 2.9 days, SD ± 2, median: 2 days), while the mean illness duration was 8.9 days (SD ± 4.6) and the median was 9 days. Two patients with many risk factors died where earthing was carried out insufficiently and too late. Nine people contracted mild or short-lived illness (mean: 6.3 days, SD ± 5.5) as a consequence of performing prophylactic earthing. There was a spectacular response in a critically ill patient who was unable to speak due to severe dyspnea with blood oxygen level 38% on continuous oxygen supply. On the second day, after two sessions of 3 h daily earthing, his oxygen level raised to 95% with oxygen supply and 77% without oxygen supply. The following symptoms were improved after implementing earthing: fever, dyspnea, cough, weakness, headache, chest pain, taste and smell sensation loss, anorexia, and body pain. Earthing revealed significant curing and preventive effects with a shorter illness duration.


Precluding coccidiosis with an anti-coprophagia drug.
Floor-pen studies were conducted to ascertain whether coccidiosis could be prevented by using a drug added to the litter to preclude coprophagia and ingestion of infective oocysts. An experimental drug (1-pyrrolidinebutyramide, 2-methyl-alpha,alpha-diphenyl) was added to litter contaminated with sporulated Eimeria tenella oocysts. Thereafter 7-day-old broiler chicks were reared on the litter for a nine-day period. Mortality, lesion scores and dropping scores were the criteria selected to determine efficacy. Treatment of the litter at the lowest level (2.3 g kg-1) did not reduce the incidence or severity of the disease, whereas treatment at two higher levels (11.5 and 23.0 g kg-1) significantly reduced both (incidence and severity). The highest level was the most efficacious; however, drug toxicity was also encountered at this level.


Early identification with ultrasonic integrated backscatter of viable but stunned myocardium in dogs.
It has been shown that canine and human hearts exhibit a cardiac cycle-dependent variation of integrated backscatter (cyclic variation) that reflects intrinsic regional contractile performance. To determine whether ultrasound tissue characterization can identify viable though stunned myocardium before recovery of regional wall thickening, transient ischemic injury was produced in eight open chest dogs for 15 min followed by reperfusion for 2 h. Cyclic variation and wall thickening were measured before ischemia, at 15 min after the onset of ischemia and at selected intervals after the onset of reperfusion from multiple sites within the ischemic zone with a novel combined two-dimensional and M-mode acquisition system. Cyclic variation and wall thickening were computed from digitized M-mode integrated backscatter images with an algorithm developed and validated for this purpose. Magnitude and "delay" of cyclic variation and wall thickening were compared. Delay represents the degree of synchrony of regional cyclic variation or wall thickening with global ventricular mechanical systole. Baseline cyclic variation and wall thickening magnitudes were 3.8 +/- 0.2 dB and 37 +/- 1.4%, respectively. With ischemia, cyclic variation and wall thickening decreased to 1.7 +/- 0.2 dB and 17 +/- 2%, respectively (p less than 0.05, compared with baseline). Cyclic variation recovered to baseline levels within 20 min after reperfusion (3.3 +/- 0.4 dB, p = NS). Wall thickening remained depressed for 2 h after the onset of reperfusion (23 +/- 2%, p less than 0.05 compared with baseline). Delay of cyclic variation in a unitless ratio expressed as delay (in milliseconds) divided by the QT interval (in milliseconds) increased from 0.87 +/- 0.03 at baseline to 1.10 +/- 0.12 with ischemia, a change consistent with mild asynchrony, and returned to baseline (0.95 +/- 0.07, p = NS compared with baseline) within 20 min after reperfusion. Delay of wall thickening was 0.88 +/- 0.02 at baseline, increased to 1.23 +/- 0.09 with ischemia and remained significantly increased 2 h after reperfusion (1.07 +/- 0.05, p less than 0.05 compared with baseline). Recovery time constants for cyclic variation and wall thickening with reperfusion reflected earlier restoration of cyclic variation (8.1 min) than of wall thickening (420.5 min). Thus, cyclic variation recovers before wall thickening with reperfusion. Its analysis appears to provide a useful index of the presence of viable and potentially salvageable tissue in regions of stunned myocardium that is independent of wall thickening.


GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans.
Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively, into eight volunteers to study pharmacokinetics and effects on pentagastrin-stimulated gastric acid secretion (plateau stimulation with pentagastrin at D50: 100 ng/kg/hr). The concentration of GLP-1 in plasma increased from 64 +/- 12 to 189 +/- 23 and 631 +/- 76 pmol/liter, respectively. The concentration of truncated GLP increased from approximately 7 pmol/liter to 28 +/- 3 pmol/liter during the high rate of infusion. A similar increase was seen in response to a mixed meal in eight normal volunteers. The metabolic clearance rate (MCR) of GLP-1 was 2.2 +/- 0.3 and 2.6 +/- 0.3 ml/kg/min, respectively, and the half-life in plasma was 17 +/- 2 min. The MCR of truncated GLP-1 was 13 +/- 2.8 ml/kg/min and the half-life 11.4 +/- 2.1 min. GLP-1 reduced the pentagastrin-stimulated acid secretion 16 +/- 9% during the low-rate infusion and 23 +/- 12% during the high rate (P less than 0.05). Truncated GLP-1 caused a 36 +/- 3% inhibition during the high infusion rate. Thus truncated GLP-1, a naturally occurring peptide, is a potent inhibitor of acid secretion in man and more so than GLP-1.


Minimal stochastic complexity snake-based technique adapted to an unknown noise model.
We propose a polygonal snake segmentation technique adapted to objects that can be composed of several regions with gray-level fluctuations described by a priori unknown probability laws. This approach is based on a histogram equalization and on the minimization of a criterion without parameter to be tuned by the user. We demonstrate the efficiency of this approach, which has low computational cost, on synthetic and real images perturbed by different types of optical noise.