bluuebunny/crossref_metadata_2025 huggingface dataset:
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells
Authors: Benzing Christian , Lam Hoyin , Tsang Chi Man , Rimmer Alexander , Arroyo-Berdugo Yoana , Calle Yolanda , Wells Claire M.
Published: December 2019

Background

Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established.

Methods

To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay.

Results

Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity.

Conclusions

Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.
DNA methylation of SFRP1, SFRP2, and WIF1 and prognosis of postoperative colorectal cancer patients
Authors: Liu Xinyan , Fu Jinming , Bi Haoran , Ge Anqi , Xia Tingting , Liu Yupeng , Sun Hongru , Li Dapeng , Zhao Yashuang
Published: December 2019

Background

As biomarkers, DNA methylation is used to detect colorectal cancer (CRC) and make assessment of CRC prognosis. The published findings showed the association between the methylation of SFRP1, SFRP2, and WIF1, located in the Wnt signaling pathway, and the prognosis of CRC were not consistent. Our study aimed to explore the potential possibility of SFRP1, SFRP2, and WIF1 concomitant promoter methylation as prognostic biomarkers of postoperative CRC patients.

Methods

As a total of 307 sporadic postoperative CRC patients were followed up, we detected SFRP1, SFRP2, and WIF1 methylation obtained from tumor tissues and adjacent non-tumor tissues respectively on the basis of methylation-sensitive high resolution melting analysis. Univariate and multivariate Cox regressions were carried out so as to assess the potential possibility of SFRP1, SFRP2, and WIF1 promoter methylation as predictors of prognosis. Confounders in our study were controlled by Propensity Score (PS) analysis.

Results

The SFRP1, SFRP2, and WIF1 methylation levels in tumor tissues were significantly higher than that in adjacent non-tumor tissues (P < 0.001). SFRP2 hypermethylation was significantly associated with a favorable clinical outcome at the hazard ratio (HR) of 0.343 [95% confidence intervals (CI): 0.164–0.718, P = 0.005] and 0.410 (95% CI: 0.200–0.842, P = 0.015) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1 and SFRP2 was significantly associated with a favorable clinical outcome at the HR of 0.333 (95% CI: 0.159–0.694, P = 0.003) and 0.398 (95% CI: 0.192–0.821, P = 0.013) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1, SFRP2 and WIF1 was significantly associated with a favorable clinical outcome at the HR of 0.326 (95% CI: 0.117–0.908, P = 0.032) and 0.401 (95% CI: 0.146–1.106, P = 0.077) in multivariate Cox regression and PS analysis, respectively.

Conclusions

SFRP1, SFRP2, and WIF1 were frequently hypermethylated in CRC tumor tissues. It was apparent that the promoter hypermethylation of SFRP2 and co-hypermethylation of SFRP1 and SFRP2 might be considered as independent prognostic predictors for survival advantage of postoperative CRC patients.
Significant impact of three-dimensional volumetry of perinephric fat on the console time during robot-assisted partial nephrectomy
Authors: Motoyama Daisuke , Matsushita Yuto , Watanabe Hiromitsu , Tamura Keita , Ito Toshiki , Sugiyama Takayuki , Otsuka Atsushi , Miyake Hideaki
Published: December 2019

Background

To assess the impact of volumetry of perinephric fat (PNF) on the perioperative outcomes of robot-assisted partial nephrectomy (RAPN).

Methods

Between 2016 and 2019, a single surgeon performed RAPN for 128 patients with clinical T1a-b renal tumors at our institution, and the 70 most recent patients were included in this study to minimize the effects of surgical experience. PNF was defined as a fatty area around the kidney within the anatomical structures, including the lateroconal fascia, fusion fascia, psoas muscle, lumbar quadrate muscle and diaphragm, and its volume was calculated based on reconstructed three-dimensional computed tomography images using the SYNAPSE VINCENT system.

Results

In this series, the trifecta and MIC (margin, ischemia and complications) score system outcomes were achieved in 69 (98.6%) and 64 patients (91.4%), respectively. The median PNF volume in the 70 patients was 166.05 cm3, which was significantly correlated with both the body mass index (BMI) and Mayo adhesive probability (MAP) score (correlation coefficient = 0.68 and 0.74, respectively). There was no significant difference in the R.E.N.A.L. nephrometry score, PNF volume or console time during RAPN among 5 groups consisting of 14 consecutive patients. Of several factors examined, the console time was significantly affected by the sex, MAP score and PNF volume, and only the PNF volume was independently associated with the console time.

Conclusion

Even if performed by an experienced robotic surgeon beyond the initial learning curve, the PNF volume may influence the console time during RAPN.
Trueness of CAD/CAM digitization with a desktop scanner – an in vitro study
Authors: Joós-Kovács G. , Vecsei B. , Körmendi Sz. , Gyarmathy V. A. , Borbély J. , Hermann P.
Published: December 2019

Background

Desktop scanners are devices for digitization of conventional impressions or gypsum casts by indirect Computer-Aided Design/Computer-Assisted Manufacturing (CAD/CAM) in dentistry. The purpose of this in vitro study was: 1, to investigate whether virtual models produced by the extraoral scanner have the same trueness as sectioned casts; and 2, to assess if digitization with an extraoral scanner influences the surface information.

Methods

A polimethyl-methacrilic acid (PMMA) cast and a reference scanner (TwoCam 3D, SCAN technology A/S, Ringsted, Denmark; field of view 200 mm, resolution 0.1 mm ± 0.025 mm) were used to create the reference data in standard tessellation format (STL). According to the extraoral CAD/CAM digitization steps, impressions, mastercasts, and sectioned casts were made, and STL files were generated with the reference scanner. The pivotal point of the study was to digitalize these sectioned casts with the extraoral scanner (Straumann CARES Scan CS2 Visual 8.0 software, InstitutStraumann AG, Basel, Switzerland) and STL files were exported. Virtual caliper measurements were performed. Absolute deviations were compared using multilevel mixed-effects linear regression. Relative distortions were calculated with mean absolute errors and reference values.

Results

Differences were observed in measurements of tooth sizes. All four prepared teeth were affected. No relationship was observed in relative deviations. Absolute differences between all the indirect digitization steps considering arch distances were: impressions, − 0.004 mm; mastercasts, 0.136 mm; sectioned casts, − 0.028 mm; and extraoral scanner, − 0.089 mm. Prepared dies on the virtual casts (extraoral scanner) were closer to each other than those on the sectioned gypsum casts. Relative deviation calculations revealed no relationship with the position of the dies in the arch.

Conclusion

The trueness of the virtual models generated by the extraoral scanner system used in this study was different from the dimensions of the sectioned casts. The digitization of gypsum casts changes both the dimensions of dies and the distances between the dies. The virtual casts had smaller distances than any distances measured at previous steps. Either bigger dies or longer distances did not result in greater distortions. We cannot, however, generalize our results to all scanners available on the market, because they might give different results.
A 13-Week Repeated Oral Dose Toxicity Study of ChondroT in Sprague-Dawley Rats
Authors: Jeong Jiwon , Bae Kiljoon , Kim Jihoon , Choi Chanhun , Na Changsu , Park Myeongkyu , Kim Youngran , Seo Chang-Seob , Kim Seon-Jong
Published: December 2019

Background

ChondroT, a new herbal medication, consists of Angelica grosseserrata Maxim., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis terniflora var. manshurica (Rupr.) Ohwi, and Phellodendron amurense Rupr. (6:4:4:4:3). Our previous studies have shown that ChondroT exhibits significant anti-arthritic and anti-inflammatory effects. In this study, we aimed to assess the toxicological safety assessment of ChondroT.

Methods

This study was designed to assess the safety of ChondroT after repeated oral administration.

Male and female Sprague-Dawley rats were treated with ChondroT at oral doses of 0, 500, 1000, and 2000 mg/kg for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmological findings, urinalysis, hematological and blood-chemical parameters, necropsy findings, organ weights, and histological markers were recorded throughout the study period. Rats were also monitored for an additional 4 weeks to determine the recovery time.

Results

No death occurred and no significant changes in food consumption, ophthalmologic findings, and urinalysis were found. Although there were alterations in clinical signs, body weights, hematological parameters, blood-chemical parameters, necropsy findings, organ weights, and histological markers, they were not considered to be toxicologically significant.

Conclusions

The results suggest that the no-observed adverse effects level (NOAEL) was 2000 mg/kg/day for the test substance. ChondroT, a new complex herbal medication composed of five plants, can therefore be used safely at the NOAEL.
A new single nucleotide polymorphism affects the predisposition to thoracic ossification of the posterior longitudinal ligament
Authors: Wang Peng , Teng Ze , Liu Xiaoguang , Liu Xiao , Kong Chao , Lu Shibao
Published: December 2019

Background

Thoracic ossification of the posterior longitudinal ligament (T-OPLL) is one of the common factors that cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. Our previous study first reported rs201153092A site mutation in the collagen 6A1 (COL6A1) gene as a potentially pathogenic locus for T-OPLL. We aimed to determine whether the rs201153092A site mutation causes abnormal expression of the COL6A1 in Han Chinese patients with T-OPLL and whether this locus is also associated with cervical-OPLL.

Methods

Peripheral blood was collected from a total of 60 patients with T-OPLL disease (30 patients carrying the rs201153092A site mutation in COL6A1 and 30 wild-type patients) and 400 northern Chinese individuals (200 cervical-OPLL patients and 200 control subjects) using the Sequenom system. The expression of COL6A1 was analyzed by enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, and Western blotting.

Results

rs201153092A mutation resulted in markedly increased COL6A1 gene expression levels in peripheral blood samples. The allele frequency and genotype frequency results showed that this locus is no difference between cervical-OPLL patients and controls.

Conclusions

The rs201153092A site mutation of COL6A1 can significantly increase the expression of COL6A1. The COL6A1 gene rs201153092A site polymorphism is a potential pathogenic mutation in T-OPLL disease, which may be only associated with the occurrence of T-OPLL.
Expanding the clinical and genetic spectrum of Heimler syndrome
Authors: Gao Feng-Juan , Hu Fang-Yuan , Xu Ping , Qi Yu-He , Li Jian-Kang , Zhang Yong-Jin , Chen Fang , Chang Qing , Song Fang , Shen Si-Mai , Xu Ge-Zhi , Wu Ji-Hong
Published: December 2019

Background

Heimler syndrome (HS) is a rare hereditary systemic disorder, partial clinically overlapping with Usher syndrome. So far, our knowledge of HS is very limited, many cases are misdiagnosed or may not even be diagnosed at all. This study aimed to analyze the clinical and genetic characteristics of HS, and to evaluate potential phenotype–genotype correlations.

Results

Two HS cases caused by PEX1 mutations were identified, and a novel likely pathogenic mutation, PEX1 c.895_896insTATA, was found. The main ophthalmic finding of the two patients was consistent with retinitis pigmentosa accompanied by cystoid macular edema, but short axial length and hyperopia were also observed as two previously unreported ocular phenotypes. Analysis of the literature showed that of the 29 HS patients previously reported, 12 had PEX6 mutations, 10 had PEX1 mutations, two had PEX26 mutations, and the remaining patients were not genetically tested. Three novel genotype–phenotype correlations were revealed from analysis of these patients. First, most genotypes of every HS patient include at least one missense variant; second, at least one mutation in PEX1 or PEX6 gene affects the AAA-ATPase region in every HS patient with retinal dystrophy, suggesting AAA-ATPase region is a hypermutable region in patients with a retinal dystrophy; third, there are no significant differences between PEX1-, PEX6-, and PEX26-associated phenotypes.

Conclusion

Next-generation sequencing is important for the diagnosis of HS. This study expands the clinical and genetic spectrum of HS, and provides additional insights into genotype–phenotype correlations, which is vital for accurate clinical practice, genetic counseling, and pathogenesis studies.
Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study
Authors: Nakajima Mikio , Kojiro Morita , Aso Shotaro , Matsui Hiroki , Fushimi Kiyohide , Kaita Yasuhiko , Goto Hideaki , Yamaguchi Yoshihiro , Yasunaga Hideo
Published: December 2019

Background

Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds.

Methods

We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality.

Results

Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068).

Conclusions

High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.
Increasing sensor reliability through confidence attribution
Authors: Scheffel Roberto M. , Fröhlich Antônio A.
Published: December 2019

The reliability of wireless sensor networks (WSN) is getting increasing importance as this kind of networks are becoming the communication base for many cyber-physical systems (CPS). Such systems rely on sensor data correctness to make decisions; therefore, faulty data can lead such systems to take wrong actions. Errors can be originated by sensor’s hardware failures or software bugs and also from the intentional interference of intruders. The gateways that connect such WSN to the Internet are natural intruders’ targets as they usually run conventional operating systems and communication protocols. This work proposes a confidence attribution scheme, based on lightweight predictors running on the sensors. The solution also proposes a parameterizable formula, in order to stamp every value sent by a sensor with aconfidence level, calculated upon the values of a subset of correlated sensors. This work also presents an algorithm that can identify a defective sensor into its subset. The use of predictors and confidence attribution are proposed as the basis of a mechanism that increases the WSN resilience against sensor failure or bad data injection by intruders. Several simulations were performed to evaluate the detection efficiency against different types of sensor errors. This work also analyses mechanisms to deal with concept drifts in the WSN lifetime.
Iris metastasis as the initial presentation of upper gastrointestinal tract carcinoma: a case report
Authors: Siddiqui M. A. Rehman , Hussain Syed Zohaib Maroof , Mubarak Muhammed
Published: December 2019

Background

We report a case of a patient with iris metastasis as the initial manifestation of a systemic cancer: upper gastrointestinal tract carcinoma.

Case presentation

A 24-year-old Asian man presented to our hospital with complaints of red left eye, decreased visual acuity, pain, and photophobia for about 3 weeks with no prior history of cancer or any other medical abnormality. Ocular examination showed a pinkish white lesion on the superonasal part of the iris. The patient’s intraocular pressure was progressively increasing despite medications, followed by lymphadenopathy 4 weeks later. Comprehensive examination was performed along with a complete systemic workup, which detected systemic malignancy. Histopathology and immunohistochemistry revealed signet ring cells, which indicated an upper gastrointestinal tract tumor as a primary source of iris metastasis. The systemic condition of the patient deteriorated rapidly thereafter and led to his death in the 12th week of the disease.

Conclusion

A red eye with iris lesions in otherwise healthy individuals should be considered as a possible initial manifestation of underlying systemic malignancy. Prompt referral of such patients to an oncologist is warranted.
Graves disease-induced thrombotic thrombocytopenic purpura: a case report
Authors: Chaughtai Saira , Khan Ijaz , Gupta Varsha , Chaughtai Zeeshan , Ong Raquel , Asif Arif , Hossain Mohammad A.
Published: December 2019

Background

Thrombotic thrombocytopenic purpura is an autoimmune disease that carries a high mortality. Very few case reports in the literature have described a relationship between Graves disease and thrombotic thrombocytopenic purpura. We present a case of a patient with Graves disease who was found to be biochemically and clinically hyperthyroid with concurrent thrombotic thrombocytopenic purpura.

Case presentation

Our patient was a 30-year-old African American woman with a history of hypertension and a family history of Graves disease who had recently been diagnosed with hyperthyroidism and placed on methimazole. She presented to our hospital with the complaints of progressive shortness of breath and dizziness. Her vital signs were stable. On further evaluation, she was diagnosed with thrombotic thrombocytopenic purpura, depending on clinical and laboratory results, and also was found to have highly elevated free T4 and suppressed thyroid-stimulating hormone. She received multiple sessions of plasmapheresis and ultimately had a total thyroidectomy. The patient’s hospital course was complicated by pneumonia and acute respiratory distress syndrome. Her platelets stabilized at approximately 50,000/μl, and her ADAMTS13 activity normalized despite multiple complications. The patient ultimately had a cardiac arrest with pulseless electrical activity and died despite multiple attempts at cardiopulmonary resuscitation.

Conclusion

Graves disease is an uncommon trigger for the development of thrombotic thrombocytopenic purpura, and very few cases have been reported thus far. Therefore, clinicians should be aware of this association in the appropriate clinical context to comprehensively monitor hyperthyroid patients during treatment.
The vaginal and fecal microbiomes are related to pregnancy status in beef heifers
Authors: Deng Feilong , McClure Maryanna , Rorie Rick , Wang Xiaofan , Chai Jianmin , Wei Xiaoyuan , Lai Songjia , Zhao Jiangchao
Published: December 2019

Background

The greatest impact on profitability of a commercial beef operation is reproduction. However, in beef heifers, little is known about the vaginal and fecal microbiota with respect to their relationship with fertility. To this end, we followed heifers through gestation to examine the dynamics of vaginal and fecal microbial composition throughout pregnancy.

Results

Heifers were exposed to an estrus synchronization protocol, observed over a 12-day period, artificially inseminated 12 h to 18 h after observed estrus, and subsequently exposed to bulls for a 50-day breeding season. Vaginal samples were taken at pre-breeding (n = 72), during the first (n = 72), and second trimester (n = 72) for all individuals, and third trimester for individuals with confirmed pregnancies (n = 56). Fecal samples were taken at pre-breeding (n = 32) and during the first trimester (n = 32), including bred and open individuals. Next generation sequencing of the V4 region of the16S rRNA gene via the Illumina MiSeq platform was applied to all samples. Shannon indices and the number of observed bacterial features were the same in fecal samples. However, significant differences in vaginal microbiome diversity between gestation stages were observed. No differences in beta-diversity were detected in vaginal or fecal samples regarding pregnancy status, but such differences were seen with fecal microbiome over time. Random Forest was developed to identify predictors of pregnancy status in vaginal (e.g.,Histophilus, Clostridiaceae,Campylobacter) and fecal (e.g., Bacteroidales,Dorea) samples.

Conclusions

Our study shows that bovine vaginal and fecal microbiome could be used as biomarkers of bovine reproduction. Further experiments are needed to validate these biomarkers and to examine their roles in a female’s ability to establish pregnancy.
Call for Data Standardization: Lessons Learned and Recommendations in an Imaging Study
Authors: Basu Amrita , Warzel Denise , Eftekhari Aras , Kirby Justin S. , Freymann John , Knable Janice , Sharma Ashish , Jacobs Paula
Published: December 2019

PURPOSE

Data sharing creates potential cost savings, supports data aggregation, and facilitates reproducibility to ensure quality research; however, data from heterogeneous systems require retrospective harmonization. This is a major hurdle for researchers who seek to leverage existing data. Efforts focused on strategies for data interoperability largely center around the use of standards but ignore the problems of competing standards and the value of existing data. Interoperability remains reliant on retrospective harmonization. Approaches to reduce this burden are needed.

METHODS

The Cancer Imaging Archive (TCIA) is an example of an imaging repository that accepts data from a diversity of sources. It contains medical images from investigators worldwide and substantial nonimage data. Digital Imaging and Communications in Medicine (DICOM) standards enable querying across images, but TCIA does not enforce other standards for describing nonimage supporting data, such as treatment details and patient outcomes. In this study, we used 9 TCIA lung and brain nonimage files containing 659 fields to explore retrospective harmonization for cross-study query and aggregation. It took 329.5 hours, or 2.3 months, extended over 6 months to identify 41 overlapping fields in 3 or more files and transform 31 of them. We used the Genomic Data Commons (GDC) data elements as the target standards for harmonization.

RESULTS

We characterized the issues and have developed recommendations for reducing the burden of retrospective harmonization. Once we harmonized the data, we also developed a Web tool to easily explore harmonized collections.

CONCLUSION

While prospective use of standards can support interoperability, there are issues that complicate this goal. Our work recognizes and reveals retrospective harmonization issues when trying to reuse existing data and recommends national infrastructure to address these issues.
Patterns of Care of Cancers and Radiotherapy in Ethiopia
Authors: Rick Tara , Habtamu Biruk , Tigeneh Wondemagegnhu , Abreha Aynalem , van Norden Yvette , Grover Surbhi , Assefa Mathewos , Incrocci Luca
Published: December 2019

PURPOSE

Radiotherapy (RT) is an essential component of cancer treatment. There is a lack of RT services in sub-Saharan Africa as well as limited knowledge regarding clinical practices. The purpose of this study was to identify and describe the patterns for RT treatment in Ethiopia.

METHODS AND MATERIALS

We performed a retrospective analysis of 1,823 patients treated with cobalt RT at a large referral hospital in Addis Ababa, Ethiopia, from May 2015 through January 2018. Paper charts were reviewed for patient and treatment characteristics. Descriptive statistics were computed using SPSS (IBM, Armonk, NY).

RESULTS

Among patients treated for cancer, 98% (n = 1,784) were adults, 78% (n = 1,426) were female, 5% (n = 85) were HIV positive, 30% (n = 555) were from Addis Ababa, and the median age was 48 years (interquartile range [IQR], 38-58 years). Cervical cancer was the most frequent cancer treated (47%, n = 851), followed by breast cancer (15%, n = 274) and head and neck cancer (10%, n = 184). Seventy-three percent of patients (n = 1,339) presented at a late stage, and 62% (n = 1,138) received palliative RT. The wait times were the shortest for patients receiving palliative treatment (median, 0 days; IQR, 0-15 days; n = 1,138), whereas wait times were longer for patients receiving curative treatment (median, 150 days; IQR, 60-210 days; n = 685). Three percent of patients (n = 56) had documented grade 3 or 4 acute toxicity; of these, 59% (n = 33) were patients with head and neck cancer.

CONCLUSION

Cervical cancer accounted for half of patients treated; thus, a majority of patients were adult females. Most patients had advanced-stage cancer, and goals of care were palliative. Wait times were long for patients with curative-intent cancer as a result of low capacity for RT services.
Identifying and Prioritizing Family Education Needs at Pediatric Oncology Centers in Central America and Mexico
Authors: McCann Erin , Fuentes-Alabí Soad , Antillón Federico , Vega-Vega Lourdes , Sanchez Maria Sabina , Albanti Irini
Published: December 2019

PURPOSE

The educational needs of parents at the time of their child’s cancer diagnosis are often unclear, and research on this topic in low- and middle-income countries is limited. This study evaluated the educational needs of families at major pediatric oncology centers in Central America and Mexico.

METHODS

A qualitative study involving 72 in-person interviews and 4 focus groups was conducted using a semistructured interview guide. Key informants included family members, physicians, nurses, psychosocial providers, foundation leadership, volunteers, and communication professionals. The study sites included pediatric oncology centers in El Salvador, Guatemala, Mexico, and Panama. NVivo was used for thematic analysis.

RESULTS

Across all sites, parents had common questions and educational needs. Questions from families focused on their child’s likelihood of dying from cancer and feelings of guilt that were based on their perception that they caused the disease. The origin of cancer, nutrition, and psychosocial support were the most important educational themes. However, the prioritization of different educational themes varied on the basis of cultural or social influences unique to each site. Some of these differences included a need for education surrounding amputations, sibling support, and alternative or traditional healers.

CONCLUSION

This study demonstrates that although many educational needs were consistent across hospitals, some of the educational priorities differed by site despite geographic proximity and shared language. Developing an educational program in resource-limited settings can be challenging, but it is an important contributor to improving childhood cancer outcomes that should be tailored to the specific needs of a site. This study can be used as a guide for other programs with limited resources wanting to develop relevant educational materials for families.
AMPK Subunits Harbor Largely Nonoverlapping Genetic Determinants for Body Fat Mass, Glucose Metabolism, and Cholesterol Metabolism
Authors: Randrianarisoa Elko , Lehn-Stefan Angela , Krier Johannes , Böhm Anja , Heni Martin , Hrabě De Angelis Martin , Fritsche Andreas , Häring Hans-Ulrich , Stefan Norbert , Staiger Harald
Published: December 2019

Context

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme and central regulator of cellular energy metabolism. The impact of single nucleotide polymorphisms (SNPs) in all 7 AMPK subunit genes on adiposity, glucose metabolism, and lipid metabolism has not yet been systematically studied.

Objective

To analyze the associations of common SNPs in all AMPK genes, and of different scores thereof, with adiposity, insulin sensitivity, insulin secretion, blood glucose, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides.

Study Design and Methods

A cohort of 2789 nondiabetic participants from the Tübingen Family study of type 2 diabetes, metabolically characterized by oral glucose tolerance test and genotyped by genome-wide SNP array, was analyzed.

Results

We identified 6 largely nonoverlapping SNP sets across 4 AMPK genes (PRKAA1, PRKAA2, PRKAG2, PRKAG3) associated with adiposity, insulin sensitivity, insulin secretion, blood glucose, total/LDL cholesterol, or HDL cholesterol, respectively. A genetic score of body-fat-increasing alleles revealed per-allele effect sizes on body mass index (BMI) of +0.22 kg/m2 (P = 2.3 × 10–7), insulin sensitivity of −0.12 × 1019 L2/mol2 (P = 9.9 × 10–6) and 2-hour blood glucose of +0.02 mmol/L (P = 0.0048). Similar effects on blood glucose were observed with scores of insulin-sensitivity-reducing, insulin-secretion-reducing and glucose-raising alleles, respectively. A genetic cholesterol score increased total and LDL cholesterol by 1.17 mg/dL per allele (P = 0.0002 and P = 3.2 × 10–5, respectively), and a genetic HDL score decreased HDL cholesterol by 0.32 mg/dL per allele (P = 9.1 × 10–6).

Conclusions

We describe largely nonoverlapping genetic determinants in AMPK genes for diabetes-/atherosclerosis-related traits, which reflect the metabolic pathways controlled by the enzyme. Formation of trait-specific genetic scores revealed additivity of allele effects, with body-fat-raising alleles reaching a marked effect size. (J Clin Endocrinol Metab 105: 14–25, 2020)
Maternal Adipose Tissue Expansion, A Missing Link in the Prediction of Birth Weight Centile
Authors: Jarvie Eleanor M , Stewart Frances M , Ramsay Jane E , Brown E Ann , Meyer Barbara J , Olivecrona Gunilla , Griffin Bruce A , Freeman Dilys J
Published: December 2019

Context

Maternal body mass index (BMI) is associated with increased birth weight but does not explain all the variance in fetal adiposity.

Objective

To assess the contribution of maternal body fat distribution to offspring birth weight and adiposity.

Design

Longitudinal study throughout gestation and at delivery.

Setting

Women recruited at 12 weeks of gestation and followed up at 26 and 36 weeks. Cord blood was collected at delivery.

Patients

Pregnant women (n = 45) with BMI 18.0 to 46.3 kg/m2 and healthy pregnancy outcome.

Methods

Maternal first trimester abdominal subcutaneous and visceral adipose tissue thickness (SAT and VAT) was assessed by ultrasound.

Main Outcome Measures

Maternal body fat distribution, maternal and cord plasma glucose and lipid concentrations, placental weight, birth weight, and fetal adiposity assessed by cord blood leptin.

Results

VAT was the only anthropometric measure independently associated with birth weight centile (r2 adjusted 15.8%, P = .002). BMI was associated with trimester 2 and trimesters 1 through 3 area under the curve (AUC) glucose and insulin resistance (Homeostatic Model Assessment). SAT alone predicted trimester 2 lipoprotein lipase (LPL) mass (a marker of adipocyte insulin sensitivity) (11.3%, P = .017). VAT was associated with fetal triglyceride (9.3%, P = .047). Placental weight was the only independent predictor of fetal adiposity (48%, P < .001). Maternal trimester 2 and AUC LPL were inversely associated with fetal adiposity (r = -0.69, P = .001 and r = -0.58, P = .006, respectively).

Conclusions

Maternal VAT provides additional information to BMI for prediction of birth weight. VAT may be a marker of reduced SAT expansion and increased availability of maternal fatty acids for placental transport.
The incidence and diagnostic relevance of chemical shift artefact in the magnetic resonance imaging characterisation of superficial soft tissue masses
Authors: Saifuddin Asif , Siddiqui Shuaib , Pressney Ian , Khoo Michael
Published: December 2019

Objective:

Chemical shift artefact (CSA) is often encountered during MRI evaluation of superficial soft tissue masses. The study aim was to determine the incidence and diagnostic relevance of CSA in a consecutive series of superficial soft tissue masses referred to a specialist musculoskeletal sarcoma service.

Methods:

All patients referred over a 6 month period with a non-lipomatous superficial soft tissue mass were prospectively analysed. Patients characteristics (age, gender), lesion features (anatomical location, size, relationship to the skin and deep fascia), presence of CSA and final histopathological diagnosis were collected. The presence of CSA was statistically analysed against these clinical, imaging and histopathological variables.

Results:

128 patients fulfilled the inclusion criteria [63 males, 65 females; mean age = 50.6 years (7–96 years)]. CSA was present in 50 cases (39.1%) overall, but in 39 (41.5%) of 94 cases with histological diagnosis. There was no statistically significant relationship to any assessed variable apart from relationship to the deep fascia, CSA being more frequent in lesions contacting the fascia compared to lesions contacting both skin and fascia (p-value 0.02). In particular, the presence of CSA did not allow differentiation between non-malignant and malignant lesions.

Conclusion:

The presence of CSA is a not infrequent finding in the MRI assessment of superficial soft tissue masses but does not appear to be of any significance in differentiating between non-malignant and malignant lesions.

Advances in knowledge:

CSA is a relatively common finding in association with superficial soft tissue masses, but does not indicate a particular histological diagnosis or help in the differentiation of non-malignant from malignant lesions.
Recent advances in understanding frontotemporal degeneration
Authors: Borroni Barbara , Benussi Alberto
Published: December 2019

Frontotemporal degeneration (FTD) is a heterogeneous spectrum of neurodegenerative disorders characterized by diverse clinical presentations, neuropathological characteristics, and underlying genetic causes. In the last few years, several advances in the knowledge of clinical and biological aspects have been accomplished and three major scenarios have emerged that will represent the core issues in the FTD scene over the next few years. Foremost, the development of cerebrospinal fluid and blood biomarkers as well as neuroimaging techniques will aid the pursuit of new diagnostic and prognostic markers able to identify the ongoing proteinopathy and predict disease progression, which is key in identifying and stratifying patients for enrolment in clinical trials as well as evaluating response to treatment. On the other hand, current research has focused on the first attempts to slow down or revert disease progression, with the identification of disease modulators associated with disease onset and the ongoing development of the first pharmacological treatments for both sporadic and genetic FTD. Future research will certainly improve our knowledge of FTD and possibly open up a new era of disease-modifying therapies for this still-orphan disorder.
Family planning financing: tracking domestic family planning budget allocations at national and sub-national level in Kenya and Uganda
Authors: Ongwae Joshua
Published: December 2019

Background: The Abuja Declaration committed African Union countries to allocate at least 15% of their budget to improving the health sector. Consequently, Deutsche Stiftung Weltbevoelkerung (DSW) has been undertaking annual budget studies in Kenya and Uganda to track financial allocation for health and family planning (FP).

Methods: This study, carried out between the months of May and October 2017, involved budget analysis of general health and FP funding at national and sub-national level. The study covered the fiscal year 2017/18. However, for comparison purposes, fiscal years 2015/16 and 2016/17 were included in the analysis.

Results: In Uganda, during the 2017/18 fiscal year, the government allocated 0.73% ($3.7 million) of its health sector budget ($506.7 million) to FP; of which 98.8% ($3.6 million) was allocated to National Medical Stores (NMS), mainly for the supply of reproductive health commodities. Analysis of four districts shows that only 0.5% ($7,966), 0.8% ($10,046), 0.9% ($9,663) and 1.9% ($35,395) of the health sector budget was allocated to FP in Kamuli, Mityana, Mukono and Tororo, respectively, during the 2017/18 fiscal year. In Kenya, the FP budget allocation at the national level reduced from $6.05 million in 2015/16 to $2.93 million in 2017/18. At the subnational level, there were combined increases in the estimated sub-national FP budget allocations in all eleven counties of 21.8% ($2.1 million), from $9.6 million (2016/17) to $11.7 million (2017/2018).

Conclusions: The findings indicate an overall increase in FP allocations over the last three years in the two countries of study. Advocacy personnel should be enlightened on the budget making process, as it provides an excellent platform for advocating for budgetary increases.
Botany
Authors: Koryagina Natal'ya , Koryagin Yuriy
Published: December 2019

The manual is compiled in accordance with the program of the course "Botany" for agricultural universities. Theoretical questions and practical tasks on Cytology, histology, vegetative and generative organs of plants, systematics, as well as the basics of ecology and geography of plants are presented.
For University students studying in enlarged groups of specialties and directions 35.03.00 "Agriculture, forestry and fisheries", 06.03.00 "Biological Sciences".
Plato's elitology (ancient aspects of the philosophy of the chosen)
Authors: Karabuschenko Pavel
Published: December 2019

The monograph is devoted to the history of the development of ancient elitist thought and reveals the essence of Plato's philosophy of selectivity, which stands at the origins of modern elitist science. He was one of the first ancient thinkers who gave a comprehensive analysis of the phenomenon of election, describing its ontological, cultural-historical and socio-political essence. The ideas formulated by him back then and the problematic issues raised have not lost their relevance to this day. The monograph reconstructs Plato's system of views on the problem of good as a chosen value, analyzes the influence of his elitist ideas on the subsequent development of this scientific knowledge about the phenomenon of elite and elitism.
Designed for professionals and anyone interested in the history of philosophy and elitism.
New Answers for Old Questions in the Treatment of Severe Infections from Injection Drug Use
Authors: Serota David P , Vettese Theresa
Published: December 2019

Hospitalists are increasingly responsible for the management of infectious consequences of opioid use disorder (OUD), including increasing rates of hospitalization for injection drug use (IDU)‐associated infective endocarditis, osteomyelitis, and soft tissue infections. Management of IDU‐associated infections poses unique challenges: symptoms of the underlying addiction can interfere with care plans, patients often have difficult psychosocial circumstances in addition to their addiction, and they are often stigmatized by the healthcare system. Although there are few randomized trial data to support one particular approach to management, the literature suggests that successful treatment of IDU‐associated infections requires appropriate antimicrobial and surgical interventions in addition to acknowledgment and treatment of the underlying OUD. In this narrative review, the best available evidence is used to answer several of the most commonly encountered questions in the management of IDU‐associated infections. These data are used to develop a framework for hospitalists to approach the care of patients with IDU‐associated infections.
Medical Comanagement of Hip Fracture Patients Is Not Associated with
Superior Perioperative Outcomes: A Propensity Score-Matched Retrospective Cohort Analysis of the National Surgical Quality mprovement Project
Authors: Maxwell Bryan G , Mirza Amer
Published: December 2019

BACKGROUND: Medical comanagement entails a significant commitment of clinical resources with the aim of improving perioperative outcomes for patients admitted with hip fractures. To our knowledge, no national analyses have demonstrated whether patients benefit from this practice.
METHODS: We performed a retrospective cohort analysis of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) targeted user file for hip fracture 2016-2017. Medical comanagement is a dedicated variable in the NSQIP. Propensity score matching was performed to control for baseline differences associated with comanagement. Matched pairs binary logistic regression was then performed to determine the effect of comanagement on the following primary outcomes: mortality and a composite endpoint of major morbidity.
RESULTS: Unadjusted analyses demonstrated that patients receiving medical comanagement were older and sicker with a greater burden of comorbidities. Comanagement did not have a higher proportion of patients participating in a standardized hip fracture program (53.6% vs 53.7%; P > .05). Comanagement was associated with a higher unadjusted rate of mortality (6.9% vs 4.0%, odds ratio [OR] 1.79: 1.44-2.22; P < .0001) and morbidity (19.5% vs 9.6%, OR 2.28: 1.98-2.63; P < .0001). After propensity score matching was used to control for baseline differences associated with comanagement, patients in the comanagement cohort continued to demonstrate inferior mortality (OR 1.36: 1.02-1.81; P = .033) and morbidity (OR 1.82: 1.52-2.20; P < .0001).
CONCLUSIONS: This analysis does not provide evidence that dedicated medical comanagement of hip fracture patients is associated with superior perioperative outcomes. Further efforts may be needed to refine opportunities to modify the significant morbidity and mortality that persists in this population.
Influência da caminhada na cognição e composição corporal de mulheres idosas
Authors: Oliveira Rafael Afonso de , Soares Vinícius Nagy , Sampaio Ricardo Aurélio Carvalho , Fernandes Paula Teixeira
Published: December 2019

O objetivo deste estudo foi verificar a influência da caminhada em variáveis cognitivas e antropométricas de mulheres idosas. Foram recrutadas 30 mulheres destreinadas, sem doenças neurodegenerativas, com média de idade de 64,40 ± 3,71 anos, divididas por conveniência em grupo de intervenção (n = 16) e controle (n = 14). O grupo de intervenção foi submetido à prática de jogos desportivos, caminhada e alongamento, em ambientes abertos, durante três meses, duas vezes por semana. O grupo controle não participou de nenhum programa de atividade física. Antes e após a intervenção, todas as idosas foram submetidas aos testes Códigos WAIS-III, Color Trail Test (CTT-A e CTT-B), e medidas de massa corporal e estatura (determinação do índice de massa corporal – IMC), circunferência da cintura e do quadril (razão cintura-quadril – RCQ). O grupo de intervenção melhorou o desempenho no teste Códigos WAIS-III (Δ = 8,68; IC95%: 6,7; 10,7) e reduziu os tempos de execução dos testes CTT-A (Δ = -7,94; IC95%: -13,1; -2,8) e CTT-B (Δ = -18,59; IC95%: -31,4; -5,8). As modificações do grupo controle não foram estatisticamente significativas (p > 0,05). Conclui-se que a prática de caminhada pode melhorar habilidades cognitivas de mulheres idosas destreinadas.
Facing fear and embracing change
Authors: Elsey Abbygail
Published: December 2019

With the unpredictable nature of the work of a paramedic, Abbygail Elsey looks back on her first year as a Newly Qualified Paramedic and realises that perhaps the only constant is change, and the only way to approach the fear of change is to face it and embrace it
Drug breakdown: Spironolactone
Authors: Rees Sharon
Published: December 2019

In this column, Sharon Rees aims to refresh knowledge and interest in some of the commonly used drugs in a series of tweets. This month she is talking about #spironolactone
Ethics and pharmacy
Authors: Winter George
Published: December 2019

With the increasing importance of the pharmacy professional, George Winter discusses the ethical considerations that pharmacists now have to make as both medical health advisers and indpendent prescribers
Effective pharmaceutical management of Acute Otitis Externa: guidance and prescribing considerations
Authors: Savania Prad
Published: December 2019

Acute Otitis Externa is a common condition observed by physicians, particularly in primary care. The condition usually occurs due to bacterial infection, so antibiotic therapy is frequently indicated. Oral antibiotics are rarely necessary but are still being prescribed, despite a wide range of available topical preparations. Choosing a topical preparation can sometimes be challenging for prescribers, however, consideration of a range of different factors is necessary. This article provides a review of the currently recommended prescribing practice and outlines key topical antibiotic ear preparations available in the UK for treatment of Acute Otitis Externa. As no one topical ear preparation is more effective than another, a consideration of the benefits and risks of each treatment is needed to enable therapeutic resolution of Acute Otitis Externa. Furthermore, patient compliance should be adequately considered to increase the likelihood of patient adherence to treatment.