bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-existence of virulence factors and antibiotic resistance in new Klebsiella pneumoniae clones emerging in south of Italy
Authors: Fasciana Teresa , Gentile Bernardina , Aquilina Maria , Ciammaruconi Andrea , Mascarella Chiara , Anselmo Anna , Fortunato Antonella , Fillo Silvia , Petralito Giancarlo , Lista Florigio , Giammanco Anna
Published: November 2019

Background

Endemic presence of Klebsiella pneumoniae resistant to carbapenem in Italy has been due principally to the clonal expansion of CC258 isolates; however, recent studies suggest an ongoing epidemiological change in this geographical area.

Methods

50 K. pneumoniae strains, 25 carbapenem-resistant (CR-Kp) and 25 susceptible (CS-Kp), collected from march 2014 to march 2016 at the Laboratory of Bacteriology of the Paolo Giaccone Polyclinic University hospital of Palermo, Italy, were characterized for antibiotic susceptibility and fully sequenced by next generation sequencing (NGS) for the in silico analysis of resistome, virulome, multi-locus sequence typing (MLST) and core single nucleotide polymorphism (SNP) genotypes

Results

MLST in silico analysis of CR-Kp showed that 52% of isolates belonged to CC258, followed by ST395 (12%), ST307 (12%), ST392 (8%), ST348 (8%), ST405 (4%) and ST101 (4%). In the CS-Kp group, the most represented isolate was ST405 (20%), followed by ST392 and ST15 (12%), ST395, ST307 and ST1727 (8%). The in silico β-lactamase analysis of the CR-Kp group showed that the most detected gene was blaSHV (100%), followed by blaTEM (92%), blaKPC (88%), blaOXA (88%) and blaCTX-M (32%). The virulome analysis detected mrk operon in all studied isolates, and wzi-2 was found in three CR-Kp isolates (12%). Furthermore, the distribution of virulence genes encoding for the yersiniabactin system, its receptor fyuA and the aerobactin system did not show significant distribution differences between CR-Kp and CS-Kp, whereas the Klebsiella ferrous iron uptake system (kfuA, kfuB and kfuC genes), the two-component system kvgAS and the microcin E495 were significantly (p < 0.05) prevalent in the CS-Kp group compared to the CR-Kp group.

Core SNP genotyping, correlating with the MLST data, allowed greater strain tracking and discrimination than MLST analysis.

Conclusions

Our data support the idea that an epidemiological change is ongoing in the Palermo area (Sicily, Italy). In addition, our analysis revealed the co-existence of antibiotic resistance and virulence factors in CR-Kp isolates; this characteristic should be considered for future genomic surveillance studies.
Peripheral T cell lymphoma after chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report
Authors: Liu Xiao-hang , Jin Fan , Zhang Meng , Liu Mei-xi , Wang Tao , Pan Bo-ju , Zhang Lu
Published: November 2019

Background

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important.

Case presentation

A 31-year-old woman was admitted with 3 months’ history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy.

Conclusion

We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.
The items in the Chinese version of the Montreal cognitive assessment basic discriminate among different severities of Alzheimer’s disease
Authors: Zhang Yan-Rong , Ding Yun-Long , Chen Ke-liang , Liu Yan , Wei Can , Zhai Ting-ting , Wang Wen-Juan , Dong Wan-Li
Published: November 2019

Background

To determine whether items of the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) could discriminate among cognitively normal controls (NC), and those with mild cognitive impairment (MCI), mild Alzheimer’s disease (AD), and moderate-severe (AD), as well as their sensitivity and specificity.

Methods

MCI (n = 456), mild AD (n = 502) and moderate-severe AD (n = 102) patients were recruited from the memory clinic, Huashan Hospital, Shanghai, China. NC (n = 329) were recruited from health checkup outpatients. Five MoCA-BC item scores were collected in interviews.

Results

The MoCA-BC orientation test had high sensitivity and specificity for discrimination among MCI, mild AD and moderate-severe AD. The delayed recall memory test had high sensitivity and specificity for MCI screening. The verbal fluency test was efficient for detecting MCI and differentiating AD severity.

Conclusions

Various items of the MoCA-BC can identify MCI patients early and identify the severity of dementia.
A feasibility study of activity tracking devices in pregnancy
Authors: Kominiarek Michelle A. , Balmert Lauren C. , Tolo Hallie , Grobman William , Simon Melissa
Published: November 2019

Background

We aimed to evaluate the feasibility of using an activity-tracking device (ATD) during pregnancy and compare self-reported to ATD-calculated energy expenditure in a 2-phase study.

Methods

(Phase 1) Twenty-five pregnant women were asked about exercise, computer use, smartphone ownership, and ATD attitudes. Descriptive statistics were reported. (Phase 2) Women ≥18 years, smartphone owners, < 16-weeks gestation, and without exercise restrictions were approached to participate in 2016–2017. Women received instructions to wear and sync the ATD daily. We assessed protocol adherence and satisfaction via surveys at 36-weeks and used mixed models to assess the relationship between gestational age and ATD data. Energy expenditure from the Pregnancy Physical Activity Questionnaire (PPAQ) was compared to ATD-calculated energy expenditure.

Results

(Phase 1) Walking was the most common exercise; 8% did not perform any activity during pregnancy. All women had internet access and owned a smartphone. Women stated they would wear the ATD all the time during a pregnancy (88%), with the intent to improve their health (80%). (Phase 2) The characteristics of the 48 women were: pre-pregnancy BMI 28, 62% non-Hispanic black, 62% multiparas. Of the 18 women who completed the 36-week survey, only 56% wore the ATD daily, 33% had a lost or broken ATD, and 17% had technical problems; however, 94% enjoyed wearing it, 94% would recommend it to a pregnant friend, and 78% thought it helped them reach activity goals. According to ATD data, the median number of active days was 41 (IQR 20–73) and the median proportion of active days out of potential days was 22% (IQR 11–40). As gestational age increased, mean log steps decreased, active minutes decreased, and sedentary hours increased in unadjusted and adjusted models (P < 0.05 all comparisons). There were no differences in mean energy expenditure (MET-h/week) estimated by PPAQ or ATD data at 28 weeks gestation [212 (22–992 range) vs. 234 (200–281 range), P = 0.66] and at 36 weeks [233 (86–907 range) vs. 218 (151–273 range), P = 0.68]).

Conclusions

Women reported high motivation to wear an ATD and high satisfaction with actually using an ATD during pregnancy; however adherence to the study protocol was lower than expected and ATD technical problems were frequent.
Stratified analysis of the correlation between gestational weight gain and birth weight for gestational age: a retrospective single-center cohort study in Japan
Authors: SATO Noriko , MIYASAKA Naoyuki
Published: November 2019

Background

Japan has an exceptionally high proportion of low-weight births and underweight women. It has been suggested that an appropriate increase in gestational weight gain (GWG) for underweight women will help to prevent low birth weight. The current strategy aims to raise the desired value of GWG equally for all pregnant women within the underweight category. However, it remains elusive whether or not the relationship between GWG and birth weight for gestational age (BW/GA) are uniformly equivalent for all the women.

Methods

We performed a retrospective cohort analysis of women who delivered their newborns at Tokyo Medical and Dental University Hospital from 2013 to 2017. First, in order to examine the direct effect of an increase or decrease in GWG on BW/GA, we analyzed the correlation between inter-pregnancy differences in GWG and BW/GA using a sub-cohort of women who experienced two deliveries during the study period (n = 75). Second, we dichotomized the main cohort (n = 1114) according to BW/GA to verify our hypothesis that the correlation between GWG and BW/GA differs depending on the size of the newborn.

Results

The inter-pregnancy difference in BW/GA was not correlated with that of GWG. However, the correlation between BW/GA of siblings was high (r = 0.63,p = 1.9 × 10− 9). The correlation between GWG and BW/GA in women who delivered larger-sized newborns was higher (r = 0.17,p = 4.1 × 10− 5) than that in women who delivered smaller-sized newborns (r = 0.099,p = 1.9 × 10− 2). This disparity did not change after adjustment for pre-pregnancy BMI. The mean birth weight in the dichotomized groups corresponded to percentile 52.0 and 13.4 of the international newborn size assessed by INTERGROWTH-21st standards.

Conclusions

In our study, GWG was positively correlated with BW/GA for heavier neonates whose birth weights were similar to the average neonatal weight according to world standards. However, caution might be required for low-birth-weight neonates because increased GWG does not always result in increased birth weight.
Prescription of pain medication among older cancer patients with and without an intellectual disability: a national register study
Authors: Segerlantz Mikael , Axmon Anna , Gagnemo Persson Rebecca , Brun Eva , Ahlström Gerd
Published: November 2019

Background

The longevity for people with intellectual disability (ID) has significantly increased in developed countries during the past decades. Consequently, the incidence of cancer is expected to increase in this group. The aim of the present study was to investigate the prescription of pain medication in older cancer patients with intellectual disability (ID) compared to older patients in the general population, surviving or living with a cancer diagnosis.

Methods

This Swedish national registry-based study, included people with ID aged 55 years or older in 2012, and alive at the end of that year (ID cohort, n = 7936). For comparisons, we used a referent cohort, one-to-one matched with the general population by year of birth and sex (gPop cohort, n = 7936). People with at least one diagnosis of cancer during 2002–2012 were identified using the Swedish National Patient Register, resulting in 555 cancer patients with ID and 877 cancer patients from the general population. These two cohorts of cancer patients were compared with respect to prescription of pain medication for the period 2006–2012. Outcome data were aggregated so that each patient was categorized as either having or not having at least one prescription of each investigated drug group during the study period, and relative risks (RRs) for prescription were estimated for prescription in the ID cohort vs the gPop cohort.

Results

Cancer patients with ID were less likely than cancer patients in the gPop cohort to have at least one prescription of COX inhibitors (RR 0.61) and weak opioids (RR 0.63). They were, however, more likely to be prescribed paracetamol (RR 1.16), antidepressants (RR 2.09), anxiolytics (RR 2.84), and “other hypnotics, sedatives, and neuroleptics” (RR 1.39). No statistically significant differences between the two cohorts were found for strong opioids, antiepileptics, tricyclic antidepressants, or hypnotics and sedatives.

Conclusion

In the studied cohort of older people surviving or living with cancer, prescriptions for pain-treatment was less common in patients with ID compared to the general population. These results may suggest that pain is not sufficiently treated among cancer patients with ID, a situation that most likely would compromise the quality of life in this group.
Effect of multi-component school-based program on body mass index, cardiovascular and diabetes risks in a multi-ethnic study
Authors: Costa-Urrutia Paula , Álvarez-Fariña Rafael , Abud Carolina , Franco-Trecu Valentina , Esparza-Romero Julián , López-Morales Cruz Mónica , Rodríguez-Arellano Martha Eunice , Valle Leal Jaime , Colistro Valentina , Granados Julio
Published: November 2019

Background

Mexico occupies one of the first places worldwide in childhood obesity. Its Mestizo and Indigenous communities present different levels of westernization which have triggered different epidemiological diseases. We assessed the effects of a multi-component school-based intervention program on obesity, cardiovascular and diabetes risk factors.

Methods

A physical activity, health education and parent involvement (PAHEPI) program was developed and applied in six urban (Mestizo ethnic group) and indigenous (Seri and Yaqui ethnic groups) primary schools for 12 weeks. A total of 320 children aged 4–12 years participated in intervention program; 203 under Treatment 1 (PAHEPI program) and 117, only from Mestizo groups, under Treatment 2 (PAHEPI+ school meals). For Body Mass Index (BMI), cardiovascular and diabetes factors, pairwise comparisons of values at baseline and after treatments were done using Wilcoxon signed rank test. Generalized linear models were applied to assess the intervention effect by age, sex and nutritional status in relation to ethnicity and treatment.

Results

We observed improvements on BMI in children with overweight-obesity and in triglycerides in the three ethnic groups. The Mestizo ethnic group showed the largest improvements under Treatment 2. While Seris showed improvements only in cardiovascular risk factors, Yaquis also showed improvements in diabetes risk factors, though not in BMI.

Conclusions

This study showed that the same intervention may have positive but different effects in different ethnic groups depending on their lifestyle and their emerging epidemiological disease. Including this type of intervention as part of the school curriculum would allow to adapt to ethnic group in order to contribute more efficiently to child welfare.

Trial registration

This study was retrospectively registered under the identifierNCT03768245.
Intravenous versus intravenous/oral antibiotics for perforated appendicitis in pediatric patients: a systematic review and meta-analysis
Authors: Wang Chuan , Li Yanan , Ji Yi
Published: November 2019

Background

The use of oral (PO) antibiotics following a course of certain intravenous (IV) antibiotics is proposed in order to avoid the complications of IV medications and to decrease the cost. However, the efficacy and safety of sequential IV/PO antibiotics is unclear and requires further study.

Methods

The databases, including PubMed, EMBASE and Cochrane Library, were searched. Studies comparing outcomes in patients with perforated appendicitis receiving sequential IV/PO and PO antibiotics therapy were screened. The Newcastle-Ottawa Scale (NOS) and the Jadad score were used to evaluate the quality of the cohort and the randomized controlled portions of the trial, respectively. Statistical heterogeneity was assessed using theI2value. A fixed or random-effect model was applied according to theI2value.

Results

Five controlled studies including a total of 580 patients were evaluated. The pooled estimates revealed that sequential IV/PO antibiotic therapy did not increase the risk of complications, with a risk ratio (RR) of 0.97 (95% CI 0.51–1.83,P = 0.93) for postoperative abscess, 1.04 (95% CI 0.25–4.36,P = 0.96) for wound infection and 0.62 (95% CI 0.33–1.16,P = 0.13) for readmission.

Conclusions

Our study demonstrates that sequential IV/PO antibiotic therapy is noninferior to IV antibiotic therapy regarding postoperative abscess, wound infection and readmission.
Changes of inflammatory mediators and oxidative stress indicators in children with Henoch-Schönlein purpura and clinical effects of hemoperfusion in the treatment of severe Henoch-Schönlein purpura with gastrointestinal involvement in children
Authors: Zhu Ying , Dong Yang , Wu Lin , Deng Fang
Published: November 2019

Background

To explore the changes of inflammatory and oxidative stress responses in Henoch-Schönlein purpura (HSP) children, and further analyzed the therapeutic effects and mechanisms of hemoperfusion (HP) on HSP with severe gastrointestinal (GI) involvement.

Methods

There were 200 children with HSP were divided into three groups according to their clinical manifestations: 60 in HSP without GI and renal involvement group, 60 in HSP with GI involvement group, and 80 in HSPN group. The HSP with GI involvement group was subdivided into conventional treatment (n = 30) and HP (n = 30) groups. Thirty children who visited the department of children healthcare for healthy physical examinations from January to December 2017 were set as healthy control group. The IL-6 and TNF-α levels were detected by chemoluminescence method. The MDA, SOD and T-AOC levels were determined by thiobarbituric acid colorimetric method, hydroxylamine method and chemical colorimetry.

Results

Compared with healthy group, IL-6, TNF-α and MDA levels in HSP were increased in each group, while SOD and T-AOC were decreased (P = 0.000). IL-6, TNF-α and MDA levels in the HSPN group were the highest, SOD and T-AOC levels were the lowest (P = 0.000). Compared with those before treatment, IL-6, TNF-α and MDA levels in the conventional and HP groups were decreased and SOD and T-AOC levels were increased (P = 0.000). The changes in HP group were more significant than those in conventional group (P < 0.047). Compared with conventional group, glucocorticoid dosage and the occurrence rate of hematuria and/or proteinuria within 3 months were lower in HP group. (P = 0.000, 0.004).

Conclusions

Inflammatory and oxidative stress may be involved in the acute phase of HSP children. The intensity of inflammatory and oxidative stress responses were related to the degree of renal involvement. HP can reduce glucocorticoid dosage and the rate of renal involvement in children with severe HSP with GI involvement. The mechanism may be related to the fact that HP can effectively remove IL-6, TNF-α, MDA in HSP children.
Utilization of key preventive measures for pregnancy complications and malaria among women in Jimma Zone, Ethiopia
Authors: Ouedraogo Mariame , Kurji Jaameeta , Abebe Lakew , Labonté Ronald , Morankar Sudhakar , Bedru Kunuz Haji , Bulcha Gebeyehu , Abera Muluemebet , Potter Beth K. , Roy-Gagnon Marie-Hélène , Kulkarni Manisha A.
Published: November 2019

Background

In Ethiopia, malaria infections and other complications during pregnancy contribute to the high burden of maternal morbidity and mortality. Preventive measures are available, however little is known about the factors influencing the uptake of maternal health services and interventions by pregnant women in Ethiopia.

Methods

We analyzed data from a community-based cross-sectional survey conducted in 2016 in three rural districts of Jimma Zone, Ethiopia, with 3784 women who had a pregnancy outcome in the year preceding the survey. We used multivariable logistic regression models accounting for clustering to identify the determinants of antenatal care (ANC) attendance and insecticide-treated net (ITN) ownership and use, and the prevalence and predictors of malaria infection among pregnant women.

Results

Eighty-four percent of interviewed women reported receiving at least one ANC visit during their last pregnancy, while 47% reported attending four or more ANC visits. Common reasons for not attending ANC included women’s lack of awareness of its importance (48%), distance to health facility (23%) and unavailability of transportation (14%). Important determinants of ANC attendance included higher education level and wealth status, woman’s ability to make healthcare decisions, and pregnancy intendedness. An estimated 48% of women reported owning an ITN during their last pregnancy. Of these, 55% reported to have always slept under it during their last pregnancy. Analysis revealed that the odds of owning and using ITNs were respectively 2.07 (95% CI: 1.62–2.63) and 1.73 (95% CI: 1.32–2.27) times higher among women who attended at least one ANC visit. The self-reported prevalence of malaria infection during pregnancy was low (1.4%) across the three districts. We found that young, uneducated, and unemployed women presented higher odds of malaria infection during their last pregnancy.

Conclusion

ANC and ITN uptake during pregnancy in Jimma Zone fall below the respective targets of 95 and 90% set in the Ethiopian Health Sector Transformation Plan for 2020, suggesting that more intensive programmatic efforts still need to be directed towards improving access to these health services. Reaching ANC non-users and ITN ownership and use as part of ANC services could be emphasized to address these gaps.
Effects of pollution, low temperature and influenza syndrome on the excess mortality risk in winter 2016–2017
Authors: Murtas Rossella , Russo Antonio Giampiero
Published: November 2019

Background

In the winter of 2016–2017, the number of deaths recorded in the north-west Europe was significantly higher than that in previous years. This spike in mortality was attributed principally to an influenza epidemic, but the contribution of air pollution and cold temperature has not been investigated. Information on the combined effect of low temperatures, influenza epidemic, and air pollution on mortality is inadequate. The objective of this study was to estimate the excess mortality in the winter of 2016–2017 in the metropolitan area of Milan, and to evaluate the independent short-term effect of 3 risk factors: low temperatures, the influenza epidemic, and air pollution.

Methods

We used a case-crossover, time-stratified study design. Mortality data were collected on all people aged > 65 years who died of natural causes, due to respiratory diseases or cardiovascular diseases, between December 1, 2016 and February 15, 2017. Environmental data were extracted from the Regional Environmental Protection Agency. The National Surveillance Network provided data on influenza epidemic.

Results

Among the 7590 natural deaths in people aged > 65 years, 965 (13%) were caused by respiratory conditions, and 2688 (35%) were caused by cardiovascular conditions. There were statistically significant associations between the minimum recorded temperature and deaths due to natural causes (OR = 0.966, 95% CI: 0.944–0.989), and cardiovascular conditions (OR = 0.961, 95% CI: 0.925–0.999). There were also statistically significant association between the influenza epidemic and deaths due to natural causes (OR = 1.198, 95% CI: 1.156–1.241), cardiovascular conditions (OR = 1.153, 95% CI: 1.088–1.223), and respiratory conditions (OR = 1.303, 95% CI: 1.166–1.456). High levels of PM10 (60 and 70 μg/m3) were associated with a statistically significant increase in natural and cause-specific mortality. There were statistically significant interactions between PM10 and influenza for cardiovascular-related mortality, and between influenza and temperature for deaths due to natural causes.

Conclusions

Excess of mortality in Milan during winter 2016–2017 was associated with influenza epidemic and concomitant environmental exposures, specifically, the combined effect of air pollution and low temperatures. Policies mitigating the effects of environmental risk factors should be implemented to prevent future excess mortality.
Effects of applying a standardized assessment and evaluation protocol in housing adaptation implementation – results from a quasi-experimental study
Authors: Malmgren Fänge A. , Carlsson G. , Axmon A. , Thordardottir B. , Chiatti C. , Nilsson M. H. , Ekstam L.
Published: November 2019

Background

Standardized, research-based strategies to guide the implementation and evaluate the effects of housing adaptations (HA) on client outcomes are rare. We hypothesized that, compared to ordinary practice, a standardized assessment and evaluation protocol for HA implementation would better maintain or improve client outcomes over 1 year.

Method

Using a cluster design, South Swedish municipalities were recruited to an intervention or control group. Data on activities of daily living, usability of the home, health related quality of life, and participation frequency and satisfaction were collected at home visits 1 month before the HA (baseline; T1), and at 3 (T2), 6 (T3) and 12 (T4) months after. In the intervention group (n = 112) data were collected according to a standardized protocol while in the control group (n = 129) ordinary routines were applied. Changes from baseline to subsequent time points were categorized as no deterioration (i.e. improvement or no change) or deterioration, for each outcome item separately. Differences in “no deterioration” between the groups were assessed using logistic regression.

Results

Little effect of using the standardized protocol was detected. For activities of daily living, statistically significant differences between the groups were found for toileting (T1-T4; OR 3.14), dressing (T1-T4; OR2.89) and cooking (T1-T3 and T1-T4; OR 3.14). For usability of the home differences were found in personal hygiene (T1-T2; OR 2.32) using a wheelchair (T1-T2 and T1-T3; OR 9.50), picking up the mail (T1-T3; OR 4.06), and in participation, helping others (T1-T3 and T1-T4; OR 2.33 and 3.36).

Conclusion

The applied standardized protocol for HA implementation did not show any convincing effect, possibly due to the complexity of the intervention itself, and the implementation process. A process evaluation might generate in-depth knowledge about the reasons behind the findings.

Trial registration

ClinicalTrials.gov. NCT01960582.
gRNA validation for wheat genome editing with the CRISPR-Cas9 system
Authors: Arndell Taj , Sharma Niharika , Langridge Peter , Baumann Ute , Watson-Haigh Nathan S. , Whitford Ryan
Published: November 2019

Background

The CRISPR-Cas9 system is a powerful and versatile tool for crop genome editing. However, achieving highly efficient and specific editing in polyploid species can be a challenge. The efficiency and specificity of the CRISPR-Cas9 system depends critically on the gRNA used. Here, we assessed the activities and specificities of seven gRNAs targeting 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in hexaploid wheat protoplasts. EPSPS is the biological target of the widely used herbicide glyphosate.

Results

The seven gRNAs differed substantially in their on-target activities, with mean indel frequencies ranging from 0% to approximately 20%. There was no obvious correlation between experimentally determined and in silico predicted on-target gRNA activity. The presence of a single mismatch within the seed region of the guide sequence greatly reduced but did not abolish gRNA activity, whereas the presence of an additional mismatch, or the absence of a PAM, all but abolished gRNA activity. Large insertions (≥20 bp) of DNA vector-derived sequence were detected at frequencies up to 8.5% of total indels. One of the gRNAs exhibited several properties that make it potentially suitable for the development of non-transgenic glyphosate resistant wheat.

Conclusions

We have established a rapid and reliable method for gRNA validation in hexaploid wheat protoplasts. The method can be used to identify gRNAs that have favourable properties. Our approach is particularly suited to polyploid species, but should be applicable to any plant species amenable to protoplast transformation.
1,25-dihydroxyvitamin D3 suppresses lipopolysaccharide-induced interleukin-6 production through aryl hydrocarbon receptor/nuclear factor-κB signaling in oral epithelial cells
Authors: Li Hao , Li Wei , Wang Qi
Published: November 2019

Background

Antiinflammatory effect of 1,25-dihydroxyvitamin D3 (1,25D3) has been reported in periodontitis, but the exact mechanisms remain unclear. Oral epithelial cells are recently highlighted as an important regulator of inflammation in this disease. This in vitro study was established to investigate the effect of 1,25D3 on key proinflammatory cytokine IL-6 production and aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB) signaling in oral epithelial cells upon the stimulation of lipopolysaccharide (LPS) from periodontal pathogens.

Methods

OKF6/TERT-2 oral keratinocytes were incubated with LPS and different concentrations of 1,25D3, and levels of IL-6 production were determined using enzyme-linked immunosorbent assay (ELISA). Expression of vitamin D receptor (VDR), and activation of AhR was examined using western blot analysis, and phosphorylation of NF-κB was detected using cell-based protein phosphorylation ELISA.

Results

1,25D3 inhibited LPS-induced IL-6 overexpression in OKF6/TERT-2 cells. Additionally, 1,25D3 increased VDR expression and AhR activation, and repressed NF-κB phosphorylation. Furthermore, 1,25D3 suppressed IL-6 expression and enhanced VDR expression and regulated AhR/NF-κB signaling activation in a dose-dependent manner after 48 h treatment.

Conclusions

These results suggest that 1,25D3 may inhibit LPS-induced IL-6 overexpression in human oral epithelial cells through AhR/NF-κB signaling. Our findings may provide an explanation for the antiinflammatory effect and therapeutic benefit of 1,25D3 in periodontitis.
The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study
Authors: Stohs Sidney J. , Chen C. Y. O. , Preuss Harry G. , Ray Sidhartha D. , Bucci Luke R. , Ji Jin , Ruff Kevin J.
Published: November 2019

Background

Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined.

Methods

Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis.

Results

Hydrolysis of blood plasma samples prior to extraction and reporting the results as “curcumin” obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed.

Conclusions

When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products.

Trial registration

ClinicalTrails.gov, trial identifying number NCT04103788, September 24, 2019. Retrospectively registered.
Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study
Authors: Santos S. , Haslinger C. , Mennet M. , von Mandach U. , Hamburger M. , Simões-Wüst A. P.
Published: November 2019

Background

The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ).

Methods

Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1–41 cell lines.

Results

BPJ (2.5 μg/mL), atosiban (0.27 μg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability.

Conclusions

BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.
Increased average number of medical publications per interviewee from 2009 to 2018: a study of 100 interviewees to an academic gastroenterology fellowship program
Authors: Imam Zaid , Cappell Mitchell S.
Published: November 2019

Background

Gastroenterology fellowship candidates may strive to improve their qualifications for this extremely competitive fellowship.

Objective

To analyze whether extreme competitiveness of gastroenterology fellowship positions has affected fellowship interview selection by statistically analyzing 13 parameters of interviewees to identify statistically significant time changes during last 10 years.

Methods

Retrospective time-trend-analyses (performed 2018) on thirteen prospectively-obtained-parameters of 47 interviewees (2009–2011) vs. 53 interviewees (2016–2018) for gastroenterology fellowship. SETTING: William-Beaumont-Hospital, Royal-Oak: academic fully-accredited gastroenterology fellowship, teaching hospital of Oakland-University-William-Beaumont-School-of-Medicine, tertiary-care hospital, GI fellowship since 1973.

Results

Statistically significant increases occurred from 2009 to 2011 vs. 2016–2018 in number of publications, including mean number of: abstracts (1.69 ± 0.37 vs. 7.54 ± 1.16, p < 0.0001); peer-reviewed articles (1.48 ± 0.30 vs. 6.13 ± 1.29, p < 0.0001); and total publications (3.17 ± 0.48 vs. 12.76 ± 1.99, p < 0.0001). Increased publications were associated with graduating from foreign medical schools (correlation coefficient = 0.26, p = .03), and were, surprisingly, correlated with lower letters-of-recommendation-scores (Kruskal-Wallis-statistic = 5.82, p = .002). USMLE-Step-1 scores significantly increased from 2009 to 2011 to 2016–2018 (235 ± 14.1 vs. 244.9 ± 13.5, p = 0.001) (previously reported finding). Nine other parameters did not significantly change with time.

Conclusions

Current report of >four-fold-increase in publications by gastroenterology fellowship interviewees at one academic-medical-center is novel. Increased focus on scholarship by applicants may be explained by their having only three parameters to improve their credentials during residency: publications, letters-of-recommendation, and honors awarded during residency (other parameters determined before residency and immutable). Current findings may benefit medical residents/medical-residency-program-directors by focusing more on publications for applications. Association between research productivity and medical promotions likely strongly motivates medical research of residents and may motivate academic faculty. Increased exposure to research/publications may improve the clinical acumen of GI fellowship applicants by enhancing their skills in critically reading the medical literature.
Perceptions about trust: a phenomenographic study of clinical supervisors in occupational therapy
Authors: Lundh Pernilla , Palmgren Per J. , Stenfors Terese
Published: November 2019

Background

Finding the best way to facilitate student learning in clinical practice can be challenging for clinical supervisors. While high levels of trust might jeopardize patient safety, low trust might hinder student learning; however, carrying out professional activities is necessary for students to develop professional competence. There is a dearth of scholarly literature regarding the concept of trust among clinical supervisors in occupational therapy education. A better understanding of how trust is created between the supervisor and student may thus aid in facilitating student learning. The aim of this study, therefore, was to explore occupational therapy clinical supervisors’ perception of trust and how it is formed.

Methods

A qualitative method deploying a phenomenographic approach was chosen. Twelve clinical supervisors were interviewed, and the data were analyzed according to the seven-step phenomenographic approach.

Results

Three qualitatively different ways of thinking about trust were found: (1) that trust is about the student and is rather static; (2) trust as a dynamic process based on student performance; and (3) trust as something mutual and interrelated. The findings indicate that trust can be understood in various ways, such as being something inherent in the student or, alternatively, about the student, the supervisor, the relationship between them, and the surrounding context, including the tasks performed. Furthermore, the study shows that trust can be seen either as something static or as a dynamic process.

Conclusions

This study contributes to a deeper understanding of the variation of ways in which the concept of trust is understood among clinical supervisors in occupational therapy. The study corroborates the prior research finding that trust can be understood as a multifaceted construct. It contributes novel insights about the role of the supervisor as an influential factor in the trust-building process. A deep understanding of the possible differences in the ways of conceptualizing something can help supervisors support learning by building on this understanding. The results from this study contribute to our knowledge of the drivers behind entrusted decisions in clinical education in various professional contexts. We suggest that the results be used in the continuing professional development of clinical supervisors.
Identifying risks areas related to medication administrations - text mining analysis using free-text descriptions of incident reports
Authors: Härkänen Marja , Paananen Jussi , Murrells Trevor , Rafferty Anne Marie , Franklin Bryony Dean
Published: November 2019

Background

Some medications carry increased risk of patient harm when they are given in error. In incident reports, names of the medications that are involved in errors could be found written both in a specific medication field and/or within the free text description of the incident. Analysing only the names of the medications implicated in a specific unstructured medication field does not give information of the associated factors and risk areas, but when analysing unstructured free text descriptions, the information about the medication involved and associated risk factors may be buried within other non-relevant text. Thus, the aim of this study was to extract medication names most commonly used in free text descriptions of medication administration incident reports to identify terms most frequently associated with risk for each of these medications using text mining.

Method

Free text descriptions of medication administration incidents (n = 72,390) reported in 2016 to the National Reporting and Learning System for England and Wales were analysed using SAS® Text miner. Analysis included text parsing and filtering free text to identify most commonly mentioned medications, followed by concept linking, and clustering to identify terms associated with commonly mentioned medications and the associated risk areas.

Results

The following risk areas related to medications were identified: 1. Allergic reactions to antibacterial drugs, 2. Intravenous administration of antibacterial drugs, 3. Fentanyl patches, 4. Checking and documenting of analgesic doses, 5. Checking doses of anticoagulants, 6. Insulin doses and blood glucose, 7. Administration of intravenous infusions.

Conclusions

Interventions to increase medication administration safety should focus on checking patient allergies and medication doses, especially for intravenous and transdermal medications. High-risk medications include insulin, analgesics, antibacterial drugs, anticoagulants, and potassium chloride. Text mining may be useful for analysing large free text datasets and should be developed further.
Intracranial haemorrhage detected by cerebral computed tomography after falls in hospital acute medical wards
Authors: Stephen Shiny , Wong Elena W. W. , Idris Adam M. , Lim Andy K. H.
Published: November 2019

Background

There is little published data on brain imaging and intracranial haemorrhage after hospital inpatient falls. Imaging protocols for inpatient falls have been adopted from head injury guidelines developed from data in patients presenting to the Emergency Department. We sought to describe the use of brain computed tomography (CT) following inpatient falls, and determine the incidence and potential risk factors for intracranial haemorrhage.

Methods

We identified inpatient falls in acute medical wards at Monash Health, a large hospital network in the southeast region of Melbourne in Australia, from the incident reporting system during a 32 month period. We examined the post-fall medical assessment form, neurological observation chart and the diagnostic imaging system for details of the fall and brain CT findings. We used survival analysis to evaluate the timeliness of brain imaging and determined potential risk factors for intracranial haemorrhage by logistic regression.

Results

From 934 falls in 789 medical inpatients, 191 brain CT scans were performed. The median age of patients was 77 years. Only 55% of falls were from standing height and 24% experienced a head strike. Less than 10% of patients received an urgent scan within one hour, and timeliness of imaging was influenced by anticoagulation status rather than guideline determination of urgency. The overall incidence of intracranial haemorrhage was 0.9%. The factors associated with intracranial haemorrhage were head strike, anticoagulation, loss of consciousness or amnesia, drop in Glasgow Coma Scale and advanced chronic kidney disease.

Conclusions

The incidence of intracranial haemorrhage was low as most inpatient falls were at low risk for head injury. Research is needed to determine if guidelines specific for hospital inpatients may reduce unnecessary scans without compromising case detection, and improve timeliness of urgent scans.
Molecular epidemiology of canine parvovirus type 2 in Italy from 1994 to 2017: recurrence of the CPV-2b variant
Authors: Battilani Mara , Modugno Francesco , Mira Francesco , Purpari Giuseppa , Di Bella Santina , Guercio Annalisa , Balboni Andrea
Published: November 2019

Background

Canine parvovirus type 2 (CPV-2) is the most important enteric virus infecting canids. It is a rapidly evolving virus; after its emergence in the 1970s, new antigenic variants (called CPV-2a, 2b and 2c) emerged and replaced the original antigenic type. The three antigenic variants are globally distributed with different frequencies and levels of genetic variability. This study focused on VP2 gene sequence analysis and the phylodynamics of CPV-2 which were detected in 123 dogs showing clinical signs of gastroenteritis collected in Italy from 1994 to 2017.

Results

For the most part, the sick dogs were young, and a third of them (32.5%) had been vaccinated. No statistical association was found between the CPV-2 antigenic variants, and sex, age, breed and vaccination status. Sequence analysis showed that all three antigenic types circulated in Italy; the CPV-2a type was the prominent genotype, followed by CPV-2c and CPV-2b, with notable differences regarding regional bases and significant fluctuations over time. Nucleotide sequence data showed high genetic heterogeneity with 67 nucleotide sequence types (ntSTs) identified, corresponding to 21 amino acid sequence types (aaSTs). The aaSTs and ntSTs obtained were distributed differently among the three CPV-2 antigenic variants: CPV-2a grouped 12/21 (57.1%) aaSTs and 41/67 (61.2%) ntSTs; CPV-2b grouped 5/21 (23.8%) aaSTs and 6/67 (8.9%) ntSTs, and CPV-2c grouped 4/21 (19.1%) aaSTs and 20/67 (29.9%) ntSTs. Canine parvovirus 2a was characterised by the highest genetic variability while CPV-2c was characterised by notable stability with a predominant amino acid profile during the entire sampling time. Canine parvovirus 2b re-emerged in recent years, showing a new and distinctive amino acid profile of the VP2 protein.

Conclusions

The findings of the present study provided new insights regarding the phylodynamics and evolution of CPV-2 in Italy, pointing out notable differences at the local level in the distribution of the CPV-2 variants and the selection of genetic subtypes. The evolution of CPV-2 has raised questions regarding the efficacy of vaccination; therefore, continuous monitoring regarding the evolution and spread of new CPV-2 variants should be a key aim of ongoing research.