bluuebunny/crossref_metadata_2025 huggingface dataset:
Zirconia crowns cemented on titanium bars using CAD/CAM: a five-year follow-up prospective clinical study of 9 patients
Authors: Scarano Antonio , Stoppaccioli Marco , Casolino Tommaso
Published: December 2019

Background

The purpose of this prospective clinical study was to evaluate clinical results of the passive fit of the substructure in the Toronto bridge and the chipping or delamination of the ceramic veneering on the zirconia-support, after 5 years, in nine patients rehabilitated with zirconia crowns cemented on titanium bars using CAD/CAM technology.

Methods

A total of nine healthy patient fully edentulous in the upper and lower jaws with non-contributory past medical anamnesis needing full fixed total prosthesis maxilla and mandible were included in this clinical study, where a total 9 mandibles and 9 jaws were treated. The inclusion criteria in order for a patient to participate in the study were: a signed consent form, fully edentulous in the upper and lower jaws, required a full fixed total prosthesis restoration. The exclusion criteria were age limitation of less than 18 years old, chemotherapy, head and neck radiation therapy, diabetes or periodontal disease, smoking and severe illness. All patients received zirconia crowns cemented on titanium bars using CAD/CAM technology. The primary outcome of this study was to examine the survival rate of the zirconia crowns cemented on titanium bars using CAD/CAM technology during the observation period. Any chipping or delamination of the zirconia crowns of the restorations was considered as failure. The secondary outcome was to evaluate the passive fit of the substructure on the implants, loose of occlusal screws, implant survival and satisfactory occlusion.

Results

In 5 years of follow-up no evidence of chipping or delamination of the ceramic veneering on the zirconia crown supported were observed. Fifteen finished protesis (93.75%) showed satisfactory occlusion and only one case (6.25%) required significant occlusal adjustment. During the first year recall all bars were stable (100%) no mobility of protheses was recorded. After 5 years all bars were stable (100%) and no mobility of protheses was recorded.

Conclusion

The computerized workflow for the process of building bar and prosthesis ensures reproducible results and excellent adaptation and passive insertion of them, as well as conditions for avoiding mechanical complications and guarantees stability of screw-implant abutments.
Evaluating global and local sequence alignment methods for comparing patient medical records
Authors: Huang Ming , Shah Nilay D. , Yao Lixia
Published: December 2019

Background

Sequence alignment is a way of arranging sequences (e.g., DNA, RNA, protein, natural language, financial data, or medical events) to identify the relatedness between two or more sequences and regions of similarity. For Electronic Health Records (EHR) data, sequence alignment helps to identify patients of similar disease trajectory for more relevant and precise prognosis, diagnosis and treatment of patients.

Methods

We tested two cutting-edge global sequence alignment methods, namely dynamic time warping (DTW) and Needleman-Wunsch algorithm (NWA), together with their local modifications, DTW for Local alignment (DTWL) and Smith-Waterman algorithm (SWA), for aligning patient medical records. We also used 4 sets of synthetic patient medical records generated from a large real-world EHR database as gold standard data, to objectively evaluate these sequence alignment algorithms.

Results

For global sequence alignments, 47 out of 80 DTW alignments and 11 out of 80 NWA alignments had superior similarity scores than reference alignments while the rest 33 DTW alignments and 69 NWA alignments had the same similarity scores as reference alignments. Forty-six out of 80 DTW alignments had better similarity scores than NWA alignments with the rest 34 cases having the equal similarity scores from both algorithms. For local sequence alignments, 70 out of 80 DTWL alignments and 68 out of 80 SWA alignments had larger coverage and higher similarity scores than reference alignments while the rest DTWL alignments and SWA alignments received the same coverage and similarity scores as reference alignments. Six out of 80 DTWL alignments showed larger coverage and higher similarity scores than SWA alignments. Thirty DTWL alignments had the equal coverage but better similarity scores than SWA. DTWL and SWA received the equal coverage and similarity scores for the rest 44 cases.

Conclusions

DTW, NWA, DTWL and SWA outperformed the reference alignments. DTW (or DTWL) seems to align better than NWA (or SWA) by inserting new daily events and identifying more similarities between patient medical records. The evaluation results could provide valuable information on the strengths and weakness of these sequence alignment methods for future development of sequence alignment methods and patient similarity-based studies.
Diagnostic efficacy of imaging and biopsy methods for peritoneal mesothelioma in a calf
Authors: Morita Yasuhiro , Sugiyama Sadamu , Tsuka Takeshi , Okamoto Yoshiharu , Morita Takehito , Sunden Yuji , Takeuchi Takashi
Published: December 2019

Background

Peritoneal mesothelioma is a rare abdominal disease; that occasionally occurs congenitally in younger calves. Cytologic examination of peritoneal effusion (PE) was utilized to diagnose this disease, and was not diagnostic. Diagnostic accuracy has been elevated by recent use of ultrasonography (US), despite most diagnoses have been obtained post-mortem in slaughter houses or during clinical necropsy. In humans, ante-mortem diagnosis is highly associated with clinical use of computed tomography (CT) and laparoscopy together with imaging-assisted biopsy. The present report evaluates the diagnostic applicability of CT and laparoscopy as well as US via the practical application of these imaging modalities in an affected calf, and compares the cytologic and histologic findings among in PE, and specimens obtained from fine-needle aspiration and core-needle biopsy. In addition, the present results were reviewed in comparison with those of previous bovine and human reports.

Case presentation

A 58-day-old male Japanese black calf presented first with scrotal swelling, followed by progressive abdominal distention. Abnormalities of the case included: 1) accumulation of anechoic PE inside the swollen scrotum and abdomen; 2) formation of multiple echogenic nodules within the peritoneal membrane based on US images; 3) presence of hyper-dense spots (suspected calcification) along the margins of the nodules; 4) anatomic connections between intra-abdominal nodular lesions and the swollen tunica vaginalis via the inguinal region based on CT images; 5) serosanguineous-colored and less-turbid characteristics of PE; and 6) formation of multiple nodules over all of the serosa of the rumen as well as the peritoneal wall based on laparoscopic views. Fine-needle aspiration and core-needle biopsy were successfully performed under US and laparoscopic observations, respectively. Histology findings of the core-needle biopsy specimen appeared more indicative (characterization of tubular structures comprised of cubical or columnar abnormal mesothelial cell linings) diagnostically of peritoneal mesothelioma than did findings of the fine-needle aspiration specimen.

Conclusions

To the best of our knowledge, this report is the first description of clinical applications of CT and laparoscopy to diagnose peritoneal mesothelioma in a calf. Laparoscopy enhanced the diagnostic accuracy due to clear gross visualization of the intra-abdominal abnormalities and applicability to imaging-guided core-needle biopsy.
Imaging and pathological findings of intramedullary inflammatory pseudotumour in a miniature dachshund: a case report
Authors: Yamashita Masamichi , Osaki Tomohiro , Murahata Yusuke , Sunden Yuji , Morita Rinko , Imagawa Tomohiro , Okamoto Yoshiharu
Published: December 2019

Background

Inflammatory pseudotumours (IPTs) are distinctive lesions consisting of myofibroblastic spindle cells and a variety of inflammatory cells. The aetiology of IPTs is unknown. Reports of IPTs in veterinary medicine have been scarse. Moreover, only one case of intradural extramedullary IPT has been previously reported. In this report, we introduce the first known case of canine IPT, which occurred in the parenchyma of the spinal cord.

Case presentation

A 10-year-old female Miniature Dachshund presented with a 2-month-long history of progressively worsening ataxia and tetraparesis. Neurological examination was consistent with a lesion involving the cervical spinal cord. Magnetic resonance imaging revealed an intradural space-occupying lesion in the region of the fourth cervical vertebra. Dorsal laminectomy and resection of the mass were performed. Histopathological examination revealed the proliferation of immature spindle cells (fibroblasts/myofibroblasts and glial cells) and a highly cellular mixture of neutrophils, macrophages and lymphocytic cells. The mass was located in the parenchyma of the spinal cord and was diagnosed as an IPT occurring in the parenchyma of the spinal cord. No causative pathogen was detected. The dog’s symptoms improved, during the first month after surgery. However, neurological symptoms, such as laboured breathing and dysuria, subsequently worsened and the dog died 42 days after surgery.

Conclusions

The present study describes a canine case of IPT occurring in the parenchyma of the spinal cord. The diagnosis and determination of the site of the mass was difficult solely based on preoperative imaging in the present case. The outcome of this case was poorer than that observed in cases of canine extramedullary IPT and human intramedullary IPT, in which the patients exhibited recovery. The prognosis after surgical resection cannot be decided from the present case alone. However, patients should be monitored for potential serious complications and recurrence.
RNA-seq from archival FFPE breast cancer samples: molecular pathway fidelity and novel discovery
Authors: Pennock Nathan D. , Jindal Sonali , Horton Wesley , Sun Duanchen , Narasimhan Jayasri , Carbone Lucia , Fei Suzanne S. , Searles Robert , Harrington Christina A. , Burchard Julja , Weinmann Sheila , Schedin Pepper , Xia Zheng
Published: December 2019

Background

Formalin-fixed, paraffin-embedded (FFPE) tissues for RNA-seq have advantages over fresh frozen tissue including abundance and availability, connection to rich clinical data, and association with patient outcomes. However, FFPE-derived RNA is highly degraded and chemically modified, which impacts its utility as a faithful source for biological inquiry.

Methods

True archival FFPE breast cancer cases (n = 58), stored at room temperature for 2–23 years, were utilized to identify key steps in tissue selection, RNA isolation, and library choice. Gene expression fidelity was evaluated by comparing FFPE data to public data obtained from fresh tissues, and by employing single-gene, gene set and transcription network-based regulon analyses.

Results

We report a single 10 μm section of breast tissue yields sufficient RNA for RNA-seq, and a relationship between RNA quality and block age that was not linear. We find single-gene analysis is limiting with FFPE tissues, while targeted gene set approaches effectively distinguish ER+ from ER- breast cancers. Novel utilization of regulon analysis identified the transcription factor KDM4B to associate with ER+ disease, with KDM4B regulon activity and gene expression having prognostic significance in an independent cohort of ER+ cases.

Conclusion

Our results, which outline a robust FFPE-RNA-seq pipeline for broad use, support utilizing FFPE tissues to address key questions in the breast cancer field, including the delineation between indolent and life-threatening disease, biological stratification and molecular mechanisms of treatment resistance.
SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/β-catenin signaling pathway
Authors: Han Lizhang , Li Zhonggang , Jiang Yuquan , Jiang Zheng , Tang Ling
Published: December 2019

Background

Glioblastoma has been seen as the most common malignancy of brain tumor. Emerging reports has claimed that SNHG29 (LRRC75A-AS1) was involved in several biological processes via modulation of signaling pathway, and served as an malignant facilitatorin osteosarcoma. However, the specific role of SNHG29 in glioblastoma remains unknown.

Methods

RT-qPCR and microarray were operated to measure genes expression. Western blot was performed to examine protein expression. CCK-8 and colony formation assays were used to evaluate cell proliferation. Cell migration was tested by transwell assay. Nuclear-cytoplasmic fractionation was conducted to locate SNHG29. The binding capacity of miR-223-3p to SNHG29 or CTNND1 3′UTR was verified by RIP and luciferase reporter assay.

Results

SNHG29 presented high expression in glioblastoma to boost cell proliferation, migration and EMT process. In addition, miR-223-3p was validated to bind with SNHG29 after prediction and screening. Furthermore, miR-223-3p was proved to be a negative regulator for its target CTNND1. Then, the inhibition on cell proliferation, migration and EMT process resulted from SNHG29 knockdown was recovered by CTNND1 overexpression. At last, the inhibitive impacts on cell proliferation, migration and EMT process of CTNND1 deficiency was abrogated by LiCl.

Conclusions

In conclusion, SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/β-catenin signaling pathway, offering a potential therapeutic point for glioblastoma patients.
TGF-β1 stimulates epithelial–mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer
Authors: Wang Li , Xu Cong , Liu Xia , Yang Yang , Cao Lu , Xiang Guomin , Liu Fang , Wang Shuling , Liu Jing , Meng Qingxiang , Jiao Jiao , Niu Yun
Published: December 2019

Background

The progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC) is prevented by normal breast myoepithelial cells. Studies have suggested that EMT-associated genes were enriched in IDC in contrast to DCIS. This paper explored the relationship and potential mechanism between myoepithelial cells and EMT-associated genes in facilitating the transformation from DCIS to breast cancer.

Methods

EMT markers and myoepithelial phenotypic markers in IDC, DCIS, and healthy breast tissue were characterized using immunohistochemical assay. Both in vivo and in vitro models were created to mimic the various cell–cell interactions in the development of invasive breast cancer.

Results

We found that EMT markers were more abundant in invasive carcinomas than DCIS and adjacent normal breast tissue. Meanwhile, TGF-β1 regulated the morphology of MCF-7 (epithelial cells substitute) migration and EMT markers during the transformation from DCIS to invasive breast cancer. Additionally, TGF-β1 also regulated invasion, migration and cytokines secretion of MDA-MB-231 (myoepithelial cells substitute) and epithelial cells when co-cultured with MCF-7 both in vitro and in vivo.

Conclusions

In conclusion, these findings demonstrated that both EMT phenotypes and cancer-associated myoepithelial cells may have an impact on the development of invasive breast cancer.
The 2019 Isdell:Flowers Cross Border Malaria Initiative Round Table: community engagement in the context of malaria elimination
Authors: Gordon Alexandra , Vander Meulen Rebecca J. , Maglior Alysse
Published: December 2019

Government officials, representatives from malaria endemic communities, and nonprofit, academic, and private sector partners convened at the 2019 Isdell:Flowers Cross Border Malaria Initiative Round Table in Livingstone, Zambia from February 28–March 1, 2019 to discuss the necessity of community engagement and the involvement of those directly affected by malaria in malaria elimination efforts. Participants shared practical examples and principles of successful community engagement over the course of the Round Table. Three core principles of effective community engagement emerged: (1) there is no “one size fits all” community engagement strategy, (2) community engagement must be a bidirectional activity, and (3) community members must be at the heart of malaria elimination efforts.
Developmental fluoride neurotoxicity: an updated review
Authors: Grandjean Philippe
Published: December 2019

Background

After the discovery of fluoride as a caries-preventing agent in the mid-twentieth century, fluoridation of community water has become a widespread intervention, sometimes hailed as a mainstay of modern public health. However, this practice results in elevated fluoride intake and has become controversial for two reasons. First, topical fluoride application in the oral cavity appears to be a more direct and appropriate means of preventing caries. Second, systemic fluoride uptake is suspected of causing adverse effects, in particular neurotoxicity during early development. The latter is supported by experimental neurotoxicity findings and toxicokinetic evidence of fluoride passing into the brain.

Method

An integrated literature review was conducted on fluoride exposure and intellectual disability, with a main focus on studies on children published subsequent to a meta-analysis from 2012.

Results

Fourteen recent cross-sectional studies from endemic areas with naturally high fluoride concentrations in groundwater supported the previous findings of cognitive deficits in children with elevated fluoride exposures. Three recent prospective studies from Mexico and Canada with individual exposure data showed that early-life exposures were negatively associated with children’s performance on cognitive tests. Neurotoxicity appeared to be dose-dependent, and tentative benchmark dose calculations suggest that safe exposures are likely to be below currently accepted or recommended fluoride concentrations in drinking water.

Conclusion

The recent epidemiological results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes.
LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription
Authors: Xiu Bingqiu , Chi Yayun , Liu Lei , Chi Weiru , Zhang Qi , Chen Jiajian , Guo Rong , Si Jing , Li Lun , Xue Jingyan , Shao Zhi-Ming , Wu Zhao-Hui , Huang Shenglin , Wu Jiong
Published: December 2019

Background

The majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown.

Methods

lncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment.

Results

We identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo.

Conclusions

Our findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.
Further content validation of the 18-item NCCN/FACT Ovarian Symptom Index and its Disease Related Symptom-Physical (DRS-P) subscale for use in advanced ovarian cancer clinical trials
Authors: Shaunfield Sara , Jensen Sally , Fisher Allison P. , Webster Kimberly , Shahabi Shohreh , Ganguli Arijit , Cella David
Published: December 2019

Background

This study evaluated pre-defined aspects of content validity of the 18-item NCCN FACT-Ovarian Symptom Index (NFOSI-18) and its Disease-Related Symptoms-Physical (DRS-P) subscale, as clinical trial outcome tools for patients with advanced ovarian cancer.

Methods

Twenty-one women (mean age 59.5 years) diagnosed with advanced ovarian cancer completed the NFOSI-18 and participated in a cognitive interview to explore: (1) whether ‘pain’ and ‘cramps’ are considered redundant; (2) whether ‘fatigue’ and ‘lack of energy’ are overlapping concepts; (3) whether patients consider severity when responding to the item “I am bothered by constipation;” and (4) factors considered when responding to the item “I am sleeping well.” Interviews were audio-recorded, transcribed, and analyzed qualitatively.

Results

Pain was associated with discomfort, hurt, and life interference; ‘cramps’ was associated with pain, muscle tightening, and menstrual or digestive issues. Most (81%) considered the items “I have pain” and “I have cramps in my stomach area” to be more different than similar. Participants associated ‘fatigue’ with intense tiredness and ‘lack of energy’ with motivation and capability to complete daily activities. Item comparisons revealed a majority (65%) considered the items to be more different than similar. When responding to “I am bothered by constipation,” patients indicated constipation severity was related to bother. Finally, patients considered disease, treatment, and other factors when responding to “I am sleeping well.”

Conclusions

Findings support content validity of the NFOSI-18 and its DRS-P as originally constructed. We propose an alternative scoring option that excludes the item “I am sleeping well” from the DRS-P when used as a symptom-focused index for clinical research in a regulatory context.
Strengthening capacity to use research evidence in health sector policy-making: experience from Kenya and Malawi
Authors: Oronje Rose N. , Murunga Violet I. , Zulu Eliya M.
Published: December 2019

Background

Among the many barriers to evidence use in decision-making, weak capacity for evidence use has attracted a lot of focus in the last decade. The study aims to inform and enrich ongoing and future efforts to strengthen capacity for evidence use by presenting and discussing the experiences and lessons of a project implemented in Kenya and Malawi to strengthen individual and institutional capacity for evidence use within the ministries of health (MoHs).

Methods

This paper draws on the internal and external evaluations of a 3-year project funded by the United Kingdom’s Department for International Development, the Strengthening Capacity to Use Research Evidence in Health Policy (SECURE Health). To strengthen individual capacity, the project implemented a training and mentorship programme for 60 mid-level policy-makers in the two MoHs. To strengthen institutional capacity, the project conducted sustained advocacy with top leaders to strengthen structures that enable evidence-informed decision-making (EIDM), supported Kenya to develop research-for-health policies and priorities, supported Malawi to review the implementation of its health research agenda, developed EIDM guidelines for both MoHs, and supported bi-annual evidence dialogues to improve interactions and raise the profile of evidence. Internal evaluation included baseline and endline surveys (93 baseline and 92 endline interviews), 60 in-depth interviews, and intervention-specific evaluations (pre–post tests for training workshops, feedback forms for policy dialogues and tracking effects of advocacy efforts). The external evaluation was implemented alongside project implementation, conducting three annual evaluations.

Results

The results show that training and mentorship programmes in EIDM were effective in improving competencies of civil servants. However, such programmes need to train a critical mass to be effective in enhancing EIDM practice at the MoHs. On strengthening institutional capacity for EIDM, while the project achieved some success, it did not realise long-lasting effects because of its limited time of implementation and limited focus on sustained political economy analysis, which meant that the intervention was negatively affected by frequently changing interests within the MoHs.

Conclusions

Although training and mentorship are effective in improving EIDM competencies, they need to be incorporated in existing pre-service and in-service training programmes for sustainability. Strengthening institutional capacity for evidence use is complex and needs sustained political commitment and long-term investments.
EOS, an Ikaros family zinc finger transcription factor, interacts with the HTLV-1 oncoprotein Tax and is downregulated in peripheral blood mononuclear cells of HTLV-1-infected individuals, irrespective of clinical statuses
Authors: Naito Tadasuke , Ushirogawa Hiroshi , Fukushima Takuya , Tanaka Yuetsu , Saito Mineki
Published: December 2019

Background

EOS plays an important role in maintaining the suppressive function of regulatory T cells (Tregs), and induces a regulated transformation of Tregs into T helper-like cells, which are capable of secreting proinflammatory cytokines in response to specific inflammatory signals. Meanwhile, significant reduction in Treg activity along with production of proinflammatory cytokines has been reported in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Methods

In this study, to examine whether there is an alteration in EOS expression in peripheral blood mononuclear cells (PBMCs) derived from HTLV-1-infected individuals especially HAM/TSP, we investigated the expression of HTLV-1 tax genotype, proviral load (PVL), and the mRNA expression of tax, HBZ and EOS in HTLV-1 infected individuals including adult T-cell leukemia/lymphoma (ATL), HAM/TSP, or asymptomatic carriers. The expression levels of EOS mRNA and protein in various HTLV-1-infected or uninfected human T-cell lines were also investigated.

Results

EOS was highly expressed at the protein level in most HTLV-1 infected T-cell lines, and was augmented after the HTLV-1 regulatory factor Tax was induced in a Tax-inducible JPX-9 cell line. Immunoprecipitation experiments demonstrated a physical interaction between EOS and the viral regulatory protein Tax, but not HBZ. Meanwhile, there was a significant decrease in EOS mRNA levels in PBMCs of HTLV-1 infected individuals irrespective of their clinical statuses. We found an inverse correlation between EOS mRNA levels and HTLV-1 PVL in ATL patients, and positive correlations between both EOS mRNA load and PVL, and EOS and HBZ mRNA load in HAM/TSP patients, whereas this correlation was not observed in other clinical statuses.

Conclusions

These findings suggest that both Tax and HBZ can alter the expression of EOS through undetermined mechanisms, and dysregulated expression of EOS in PBMCs of HTLV-1 infected individuals may contribute to the pathological progression of HTLV-1-associated diseases, such as ATL and HAM/TSP.
Mental health profile and its relation with parental alcohol use problems and/or the experience of abuse in a sample of Moroccan high school students: an explorative study
Authors: Zouini Btissame , Sfendla Anis , Hedman Ahlström Britt , Senhaji Meftaha , Kerekes Nóra
Published: December 2019

Background

Studies on mental health are scarce from Arab countries, especially studies focusing on adolescents. In addition to the neurobiological and physiological changes that occur during adolescent development, psychological, societal and cultural influences have strong effects on adolescents’ behavior and on their somatic and mental health. The present study aimed (1) to describe the mental health profile, operationalized as psychological distress, of a sample of Moroccan adolescents, and (2) to investigate how specific psychosocial factors (parental alcohol use problems and the experience of physical and/or psychological abuse) may affect adolescents’ mental health.

Methods

The sample included 375 adolescents from conveniently selected classes of four high schools in the city of Tetouan in Morocco. The participants responded to an anonymous survey containing, beside other inventories, the Brief Symptom Inventory (BSI) and identified those reporting parental alcohol use problems and/or the previous experience of abuse. The sample characteristics were defined using descriptive statistics. The effects of the defined psychosocial factors were identified using the Kruskal–Wallis test, followed by the post hoc Fisher’s least significant difference test.

Results

The most common problems found in high school students from an urban region of Morocco were memory problems, concentration difficulties, restlessness, fear, nervosity and feelings of inadequacy during interpersonal interactions. The female students reported significantly higher psychological distress levels when compared to the male students (p < 0.001). The adolescents reporting parental alcohol use problems and the experience of physical/psychological abuse showed significantly higher levels of psychological distress (p = 0.02), especially symptoms of somatization (p < 0.001), hostility (p = 0.005) and anxiety (p = 0.01), than those not reporting any of these psychosocial factors.

Conclusion

The mental health profile of female adolescents from an urban area of Morocco is worse than that of their male fellow students. Adolescents reporting parental alcohol use problems and/or the experience of physical/psychological abuse need synchronized support from social- and healthcare services.
Improving blood product utilization at an ambulatory surgery center: a retrospective cohort study on 50 patients with lumbar disc replacement
Authors: Dorenkamp Benjamin C. , Janssen Madisen K. , Janssen Michael E.
Published: December 2019

Background

There is minimal literature discussing anterior lumbar spine surgery in ambulatory surgery centers (ASCs). The main concern with the anterior approach to the lumbar spine is the potential for injury to great vessels. In our facility, there are two units of crossmatched blood available in addition to cell saver during the procedure. We retrospectively looked at 50 cases of lumbar total disc arthroplasty (TDA) in our ASC to determine utilization of blood products.

Methods

Medical records of 50 consecutive patients who underwent a lumbar TDA at a single ASC were reviewed. Surgeries completed at the ASC were all transferred from the post anesthesia care unit to an attached convalescence care center which allows up to 3 days of observation. Patients who had either a 1 or 2 level lumbar TDA were included in the study. Data consisting of demographics, American Society of Anesthesiologist Physical Status Classification System, length of stay, estimated blood loss, cell saver volume, transfusion, perioperative and postoperative complications were recorded. Preoperative, perioperative and postoperative medical records were reviewed.

Results

Medical records of 50 consecutive patients were reviewed. The mean age was 40.86 ± 9.45. Of these, 48 (96%) had a 1-level lumbar TDA, 1(2%) had a 2-level lumbar TDA, 1 (2%) had a lumbar TDA at L4/5 and an anterior lumbar interbody fusion at L5/S1. There were no mortalities; no patient had recorded perioperative complications. No patients received allogeneic blood transfusion, 4 (8%) were re-transfused with cell saver (2 receiving approximately 400 ml and 2 receiving approximately 200 ml of re-transfused blood). All 50 (100%) were discharged home in stable condition. We had 30-day follow-up data on 35 of 50 patients. Of the 35 patients reviewed, three (8.5%) of the patients were readmitted to the hospital. One additional patient was seen in the emergency department and discharged home after negative testing. No patient was readmitted for post-operative anemia.

Conclusion

The routine use of both cell saver and crossmatched blood in the operating suite for lumbar TDA may be an over-utilization of healthcare resources. In our review of 50 patients, we had no need for transfusion of allogeneic packed red blood cells (PRBCs) and only four of the 50 patients had enough blood output for re-transfusion from the cell saver. This opens the conversation for alternatives to crossmatched PRBCs being held in the operating room. Such alternatives may be the use of cell salvage, only type O blood in a cooler for each patient or keeping type O blood on constant hold in ASCs.
A novel 14q13.1–21.1 deletion identified by CNV-Seq in a patient with brain-lung-thyroid syndrome, tooth agenesis and immunodeficiency
Authors: Hu Xuyun , Liu Jun , Guo Ruolan , Guo Jun , Zhao Zhipeng , Li Wei , Xu Baoping , Hao Chanjuan
Published: December 2019

Background

Chromosome 14q11-q22 deletion syndrome (OMIM 613457) is a rare genomic disorder. The phenotype heterogeneity depends on the deletion size, breakpoints and genes deleted. Critical genes like FOXG1, NKX2–1, PAX9 were identified.

Case presentation

We performed whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) for a patient with mild speech and motor developmental delay, short stature, recurrent pulmonary infections, tooth agenesis and triad of brain-lung-thyroid syndrome. By using CNV-seq, we identified a 3.1 Mb de novo interstitial deletion of the 14q13.2q21.1 region encompassing 17 OMIM genes including NKX2–1, PAX9 and NFKBIA. Our patient’s phenotype is consistent with other published 14q13 deletion patients.

Conclusion

Our results showed the combination of WES and CNV-seq is an effective diagnostic strategy for patients with genetic or genomic disorders. After reviewing published patients, we also proposed a new critical region for 14q13 deletion syndrome with is a more benign disorder compared to 14q11-q22 deletion syndrome.
Severe congenital RYR1-associated myopathy complicated with atrial tachycardia and sinus node dysfunction: a case report
Authors: Hayakawa Itaru , Abe Yuichi , Ono Hiroshi , Kubota Masaya
Published: December 2019

Background

Cardiac arrhythmias are sometimes encountered in patients with hereditary myopathies and muscular dystrophies. Description of arrhythmias in myopathies and muscular dystrophies is very important, because arrhythmias have a strong impact on the outcomes for these patients and are potentially treatable.

Case presentation

A girl with severe congenital RYR1-related myopathy exhibited atrial tachycardia and sinus node dysfunction during infancy. She was born after uncomplicated caesarian delivery. She showed no breathing, complete ophthalmoplegia, complete bulbar paralysis, complete facial muscle paralysis, and extreme floppiness. At 5 months old, she developed persistent tachycardia around 200–210 beats per minutes. Holter monitoring revealed ectopic atrial tachycardia during tachyarrhythmia and occasional sinus pauses with junctional escape beats. Propranolol effectively alleviated tachyarrhythmia but was discontinued due to increased frequency and duration of the sinus pauses that led to bradyarrhythmia. There was no evidence of structural heart diseases or heart failure. The arrhythmia gradually resolved spontaneously and at 11 months old, she showed complete sinus rhythm.

Conclusions

Although supraventricular arrhythmia is sometimes encountered in congenital myopathies, this is the first report of cardiac arrhythmia requiring drug intervention in RYR1-associated myopathy.
A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial
Authors:   On behalf of the CLEAR study group, Bradley Judy Martina , Anand Rohan , O’Neill Brenda , Ferguson Kathryn , Clarke Mike , Carroll Mary , Chalmers James , De Soyza Anthony , Duckers Jamie , Hill Adam T. , Loebinger Michael R. , Copeland Fiona , Gardner Evie , Campbell Christina , Agus Ashley , McGuire Alistair , Boyle Roisin , McKinney Fionnuala , Dickson Naomi , McAuley Danny F. , Elborn Stuart
Published: December 2019

Background

Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care.

Methods

This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum.

Discussion

This trial’s pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE.

Trial registration

EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017).

ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018.

Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01).

Sponsor: Belfast Health and Social Care Trust.

Ethics Reference Number: 17/NE/0339.

Protocol version: v3.0 Final_14052018.
Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to activity management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): amendment to the published protocol
Authors: Anderson Emma , Gaunt Daisy , Metcalfe Chris , Rai Manmita , Hollingworth William , Mills Nicola , Beasant Lucy , Parslow Roxanne , Kessler David , Macleod John , Stallard Paul , Knoop Hans , Van de Putte Elise , Nijhof Sanne , Bleijenberg Gijs , Crawley Esther
Published: December 2019

The FITNET-NHS Trial is a UK, national, trial investigating whether an online cognitive behavioural therapy program (FITNET-NHS) for treating chronic fatigue syndrome/ME in adolescents is clinically effective and cost-effective in the NHS. At the time of writing (September 2019), the trial was recruiting participants. This article presents an update to the planned sample size and data collection duration previously published within the trial protocol.

Trial registration

ISRCTN, ID: 18020851. Registered 8 April 2016.
Pharmacodynamics of Pre-Operative PD1 checkpoint blockade and receptor activator of NFkB ligand (RANKL) inhibition in non-small cell lung cancer (NSCLC): study protocol for a multicentre, open-label, phase 1B/2, translational trial (POPCORN)
Authors: Ahern Elizabeth , Cubitt Annette , Ballard Emma , Teng Michele W. L. , Dougall William C. , Smyth Mark J. , Godbolt David , Naidoo Rishendran , Goldrick Amanda , Hughes Brett G. M.
Published: December 2019

Background

Neoadjuvant immunotherapy targeting immune checkpoint programmed death-1 (PD-1) is under investigation in various tumour settings including non-small-cell lung cancer (NSCLC). Preclinical models demonstrate the superior power of the immunotherapy provided in a neoadjuvant (pre-operative) compared with an adjuvant (post-operative) setting to eradicate metastatic disease and induce long-lasting antigen-specific immunity. Novel effective immunotherapy combinations are widely sought in the oncology field, targeting non-redundant mechanisms of immune evasion. A promising combination partner with anti-PD1 in NSCLC is denosumab, a monoclonal antibody blocking receptor activator of NF-κB ligand (RANKL). In preclinical cancer models and in a large retrospective case series in NSCLC, anti-cancer activity has been reported for the combination of immune checkpoint inhibition (ICI) and denosumab. Furthermore, clinical trials of ICI and denosumab are underway in advanced melanoma and clear-cell renal cell carcinoma. However, the mechanism of action of combination anti-PD1 and anti-RANKL is poorly defined.

Methods

This open-label multicentre trial will randomise by minimisation 30 patients with resectable stage IA (primary > 2 cm) to IIIA NSCLC to a neoadjuvant treatment regime of either two doses of nivolumab (3 mg/kg every 2 weeks) or two doses of nivolumab (same regimen) plus denosumab (120 mg every 2 weeks, following nivolumab). Each treatment arm is of equal size and will be approximately balanced with respect to histology (squamous vs. non-squamous) and clinical stage (I-II vs. IIIA). All patients will receive surgery for their tumour 2 weeks after the final dose of neoadjuvant therapy. The primary outcome will be translational research to define the tumour-immune correlates of combination therapy compared with monotherapy. Key secondary outcomes will include a comparison of rates of the following between each arm: toxicity, response (pathological and radiological), and microscopically complete resection.

Discussion

The POPCORN study provides a unique platform for translational research to determine the mechanism of action of a novel proposed combination immunotherapy for cancer.

Trial registration

Prospectively registered on Australian New Zealand Clinical Trials Registry (ACTRN12618001121257) on 06/07/2018.
Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol
Authors:   for the Thai Renal Outcomes Research (THOR) Investigators, Nochaiwong Surapon , Ruengorn Chidchanok , Noppakun Kajohnsak , Panyathong Setthapon , Dandecha Phongsak , Sood Manish M. , Saenjum Chalermpong , Awiphan Ratanaporn , Sirilun Sasithorn , Mongkhon Pajaree , Chongruksut Wilaiwan , Thavorn Kednapa
Published: December 2019

Background

Current international guidelines recommend the use of a daily topical exit-site antimicrobial to prevent peritoneal dialysis (PD)-related infections. Although nonantibiotic-based therapies are appealing because they may limit antimicrobial resistance, no controlled trials have been conducted to compare topical antimicrobial agents with usual exit-site care for the prevention of PD-related infections among the Thai PD population. We propose a controlled three-arm trial to examine the efficacy and safety of a daily chlorhexidine gluconate-impregnated patch versus mupirocin ointment versus usual exit-site care with normal saline for the prevention of PD-related infections.

Methods/Designs

This study is a randomized, double-blind, multicenter, active-controlled, clinical trial. Adult patients aged 18 years or older who have end-stage kidney disease and are undergoing PD will be enrolled at three PD Centers in Thailand. A total of 354 PD patients will be randomly assigned to either the 2% chlorhexidine gluconate-impregnated patch, mupirocin ointment, or usual exit-site care with normal saline dressing according to a computer-generated random allocation sequence. Participants will be followed until discontinuation of PD or completion of 24 months. The primary study outcomes are time to first PD-related infection (exit-site/tunnel infection or peritonitis) event and the overall difference in PD-related infection rates between study arms. Secondary study outcomes will include (i) the rate of infection-related catheter removal and PD technique failure, (ii) rate of nasal and exit-site Staphylococcus aureus colonization, (iii) healthcare costs, and (iv) skin reactions and adverse events. We plan to conduct a cost-utility analysis alongside the trial from the perspectives of patients and society. A Markov simulation model will be used to estimate the total cost and health outcome in terms of quality-adjusted life years (QALYs) over a 20-year time horizon. An incremental cost-effectiveness ratio in Thai Baht and U.S. dollars per QALYs gained will be illustrated. A series of probabilistic sensitivity analyses will be conducted to assess the robustness of the cost-utility analysis findings.

Discussion

The results from this study will provide new clinical and cost-effectiveness evidence to support the best strategy for the prevention of PD-related infections among the Thai PD population.

Trial registration

ClinicalTrials.gov, NCT02547103. Registered on September 11, 2015.
High genetic diversity but no geographical structure of Aedes albopictus populations in Réunion Island
Authors: Latreille Anne C. , Milesi Pascal , Magalon Hélène , Mavingui Patrick , Atyame Célestine M.
Published: December 2019

Background

In recent years, the Asian tiger mosquitoAedes albopictushas emerged as a species of major medical concern following its global expansion and involvement in many arbovirus outbreaks. On Réunion Island,Ae. albopictuswas responsible for a large chikungunya outbreak in 2005–2006 and more recently an epidemic of dengue which began at the end of 2017 and is still ongoing at the time of writing. This dengue epidemic has seen a high number of human cases in south and west coastal regions, while few cases have been reported in the north and east of the island. To better understand the role of mosquito populations in such spatial patterns of dengue virus transmission in Réunion Island, we examined the genetic diversity and population structure ofAe. albopictussampled across the island.

Results

Between November 2016 and March 2017, a total of 564 mosquitoes were collected from 19 locations in three main climatic regions (West, East and Center) of Réunion Island and were genotyped using 16 microsatellite loci. A high genetic diversity was observed with 2–15 alleles per locus and the average number of alleles per population varying between 4.70–5.90. Almost allFISvalues were significantly positive and correlated to individual relatedness within populations using a hierarchical clustering approach based on principal components analyses (HCPC). However, the largest part of genetic variance was among individuals within populations (97%) while only 3% of genetic variance was observed among populations within regions. Therefore, no distinguishable population structure or isolation by distance was evidenced, suggesting high rates of gene flow at the island scale.

Conclusions

Our results show high genetic diversity but no genetic structure ofAe. albopictuspopulations in Réunion Island thus reflecting frequent movements of mosquitoes between populations probably due to human activity. These data should help in the understanding ofAe. albopictusvector capacity and the design of effective mosquito control strategies.