bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified Weaver-Dunn Procedure for Type 3 Acromioclavicular Joint Dislocation: Functional and Radiological Outcomes
Authors: Galasso Olimpio , Tarducci Lorenzo , De Benedetto Massimo , Orlando Nicola , Mercurio Michele , Gasparini Giorgio , Castricini Roberto
Published: March 2020

Background

Controversy surrounds the indication for treatment of type 3 acromioclavicular joint dislocation, and the optimal reconstructive technique has not yet been defined. Since the first description of the Weaver-Dunn procedure, several studies have described the clinical and radiological results that can be expected postoperatively; however, few studies have evaluated the outcomes of this technique for chronic type 3 acromioclavicular joint dislocation.

Purpose/Hypothesis

The purpose of this study was to evaluate the functional and radiographic mid- to long-term outcomes of a modified Weaver-Dunn procedure for chronic Rockwood type 3 acromioclavicular joint dislocation. We hypothesized that (1) functional outcomes comparable with sex- and age-matched healthy individuals could be achieved with the modified Weaver-Dunn procedure and (2) joint stability could be restored after surgery.

Study Design

Case series; Level of evidence, 4.

Methods

Out of 30 patients who sustained a chronic type 3 acromioclavicular joint dislocation, 27 had a minimum 12-month follow-up and were included in the study. All patients underwent a modified Weaver-Dunn procedure. The Constant-Murley score was used to assess patient postoperative function. Subjective evaluation of patient satisfaction with surgery was also recorded. Radiological assessment was performed postoperatively to evaluate superoinferior and anteroposterior joint stability.

Results

After a mean follow-up period of 51.6 months, the mean Constant-Murley score was 90.1, which was 97.2% that of a group of sex- and age-matched healthy individuals. In the multivariate analysis, higher Constant-Murley score was associated with male sex (β = 0.385; P = .043) and higher subjective satisfaction scale (β = 0.528; P = .003). All patients returned to their previous work and sport activity levels having high satisfaction with surgery. Successful vertical acromioclavicular joint reduction was obtained in all but 1 patient; however, horizontal joint stability was not completely restored with the modified Weaver-Dunn procedure. No intraoperative complications occurred, and the postoperative complication rate was 7.4%.

Conclusion

In patients with chronic type 3 acromioclavicular joint dislocation, the modified Weaver-Dunn procedure is an effective technique to restore vertical but not horizontal joint stability 4 years after surgery. High levels of satisfaction with surgery and functional outcomes comparable with sex- and age-matched healthy individuals can be achieved.
Research paradigms in international human resource management: An epistemological systematisation of the field
Authors: Bonache Jaime , Festing Marion
Published: March 2020

The explicit consideration of Research Paradigms in International Human Resource Management, the title of this Special Issue, helps us in analysing and systematising the field to show how research in international human resource management is typically conducted, what preferred perspectives prevail and which approaches have been rather neglected so far. In this introduction, we map the field, and after defining the contours of international human resource management, we use the distinction between positivism and interpretivism to outline implications for the goals of international human resource management studies and associated ontological and epistemological assumptions. Next, we analyse research methods, ways to construct research questions, researchers’ roles, sampling procedures, data collection techniques, key theoretical contributions, focus on context in theory construction, quality indicators of data analysis and evaluation criteria in each of the two key research paradigms when studying international human resource management issues. In so doing, we offer a framework for the contributions made to this Special Issue, including literature reviews focusing on the systematisation of international human resource management research, using various paradigm lenses and specific methods. We sincerely hope that the notions, typologies and contributions included in this Special Issue, all based on extensive literature reviews, will help advance research in international human resource management.
Successful Treatment of Full-Thickness Macular Hole in Polypoidal Choroidal Vasculopathy With Anti-VEGF Therapy
Authors: Lindeke-Myers Aaron , Kokame Gregg T. , Yeh Steven , Shantha Jessica
Published: March 2020

Purpose:

This report discusses the case of an 86-year-old man with a full-thickness macular hole (FTMH) secondary to polypoidal choroidal vasculopathy (PCV) treated with bevacizumab.

Methods:

A case report is presented.

Results:

An 86-year-old man presented with a 5-month history of metamorphopsia and decreased vision in his right eye and was found to have active exudation secondary to PCV with a concurrent FTMH. After 4 treatments with intravitreal bevacizumab, the FTMH resolved without surgical intervention.

Conclusions:

The patient’s FTMH resolved with solely pharmacologic treatment as a result of treating his PCV with intravitreal bevacizumab. Macular hole formation secondary to PCV is a rare finding, but may be successfully treated with pharmacologic therapy without surgical intervention.
Identification of germline variants in adults with hemophagocytic lymphohistiocytosis
Authors: Miller Peter G. , Niroula Abhishek , Ceremsak John J. , Gibson Christopher J. , Taylor Martin S. , Birndt Sebastian , Perner Florian , Arnason Jon , Sperling Adam S. , Agrawal Mridul , Schram Alison M. , Nikiforow Sarah , Pihan German , Hasserjian Robert P. , Aster Jon C. , La Rosée Paul , Morgan Elizabeth A. , Berliner Nancy , Ebert Benjamin L.
Published: March 2020

Key Points

Some germline variants are predicted to disrupt protein function in HLH-associated genes. Such variants are neither enriched in adult-onset HLH nor associated with specific clinical or laboratory features of HLH.
Quality and safety of municipal drinking water in Addis Ababa City, Ethiopia
Authors: Wolde Amsalu Mekonnen , Jemal Kemal , Woldearegay Gebru M. , Tullu Kassu Desta
Published: March 2020

Background

In low resourced countries, water-associated diseases have still impact on public health. Poor quality of water can cause waterborne diseases through bacteria, viruses, protozoa, and parasites that has been responsible for millions of morbidity and mortality. Therefore, this study aimed to assess quality and safety of public municipal drinking water in Addis Ababa City.

Methods

Descriptive epidemiological study design that used quantitative approach was carried out at Addis Ababa City Administration from June 2016 to October 2016. Pre-tested and standardized aseptic sample collection technique was utilized to collect a total of 2976 samples (2951 water samples for bacteriological analysis by Presence-Absence (P-A) culturing method and 25 samples for parasites identification through direct microscopy examination). Descriptive data were summarized and cleaned by the SPSS version 20 software and presented in table and graph.

Results

The study revealed that 10%, 7% and 3% were positive for bacteriological, total coliforms, and fecal coliforms respectively through Presence-Absence Broth test. The bacterial distribution trends from 1st to 13th weeks of wet season were slight increment of total coliforms and slight decrement for fecal coliforms. All tested for parasitological samples from selected reservoirs were free from parasitological species.

Conclusion

This study reflects that there were positive for bacterial, total coliforms, and fecal coliforms during the study period. It needs continuous screening and treating water sources to utmost important for prevention and control waterborne disease.
Short and long-term barriers and facilitators of skin self-examination among individuals diagnosed with melanoma
Authors: Coroiu Adina , Moran Chelsea , Bergeron Catherine , Drapeau Martin , Wang Beatrice , Kezouh Abbas , Ernst Jochen , Batist Gerald , Körner Annett
Published: March 2020

Background

Melanoma can be lethal if not detected early and treated. Early detection can be facilitated via skin self-examination (SSE) and as such, SSE is part of melanoma follow-up care for individuals with a prior history, who face a life-long risk of reoccurrence. The objective of the current study was to identify short- and long-term predictors of SSE among melanoma survivors to inform future prevention interventions in high-risk groups.

Method

This is an observational study with longitudinal assessments conducted with adult melanoma patients in active follow-up care.

Primary outcome measures

Behavioral outcomes, comprehensive SSE (checking up to 5 body areas in the last 3 months) and optimal SSE (checking the entire body at least monthly in the last 3 months) were assessed at 3, 12, and 24 months post a dermatological educational session on skin cancer prevention. T tests and chi square analyses were used to examine changes in outcomes from 3 to 12 and 24 months. Linear and logistic regression models were used to examine the association between predictors and the primary outcomes.

Results

Comprehensive SSE did not decrease significantly from 3 (M = 2.7, SD = 1.1) to 12 (M = 2.6, SD = 1.2) and 24 months (M = 2.4, SD = 1.2) post the education session, with the stronger predictor at all timepoints being intentions to perform SSE. Optimal SSE was higher at 3 months (59%) compared to 12 (46%) and 24 months (34%), with key predictors including self-efficacy and intentions to perform SSE and male sex at 3 months post; self-efficacy and reliance on medical advice at 12 months; and (lower) education and self-efficacy at 24 months.

Conclusions

The key findings of this study are that 1) survivors maintain SSE behaviour over time, but rates of SSE performed in agreement with medical recommendations are higher immediately post standard dermatological education (i.e. usual care) and decrease somewhat over a 24-month period; and 2) the strongest psycho-social predictors of SSE are intentions and self-efficacy to perform the behavior, which are highly modifiable, for example via motivational interviewing and goal setting health interventions.
Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts
Authors: Ardah Mustafa T. , Ghanem Simona S. , Abdulla Sara A. , Lv Guohua , Emara Mohamed M. , Paleologou Katerina E. , Vaikath Nishant N. , Lu Jia-Hong , Li Min , Vekrellis Konstantinos , Eliezer David , El-Agnaf Omar M. A.
Published: March 2020

Background

Recent studies indicated that seeded fibril formation and toxicity of α-synuclein (α-syn) play a main role in the pathogenesis of certain diseases including Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy bodies. Therefore, examination of compounds that abolish the process of seeding is considered a key step towards therapy of several synucleinopathies.

Methods

Using biophysical, biochemical and cell-culture-based assays, assessment of eleven compounds, extracted from Chinese medicinal herbs, was performed in this study for their effect on α-syn fibril formation and toxicity caused by the seeding process.

Results

Salvianolic acid B and dihydromyricetin were the two compounds that strongly inhibited the fibril growth and neurotoxicity of α-syn. In an in-vitro cell model, these compounds decreased the insoluble phosphorylated α-syn and aggregation. Also, in primary neuronal cells, these compounds showed a reduction in α-syn aggregates. Both compounds inhibited the seeded fibril growth with dihydromyricetin having the ability to disaggregate preformed α-syn fibrils. In order to investigate the inhibitory mechanisms of these two compounds towards fibril formation, we demonstrated that salvianolic acid B binds predominantly to monomers, while dihydromyricetin binds to oligomeric species and to a lower extent to monomers. Remarkably, these two compounds stabilized the soluble non-toxic oligomers lacking β-sheet content after subjecting them to proteinase K digestion.

Conclusions

Eleven compounds were tested but only two showed inhibition of α-syn aggregation, seeded fibril formation and toxicity in vitro. These findings highlight an essential beginning for development of new molecules in the field of synucleinopathies treatment.
Silibinin prevents depression-like behaviors in a single prolonged stress rat model: the possible role of serotonin
Authors: Lee Bombi , Choi Gwang Muk , Sur Bongjun
Published: March 2020

Background

Post-traumatic stress disorder (PTSD) is an extreme mood disorder that occurs after experiencing extreme stress, and patients with this disorder are known to accompany with symptoms of depression, anxiety, and memory impairments. Silibinin (SIL) is a natural polyphenolic flavonoid and is the main active ingredient of silymarin, which is primarily extracted from the milk thistle. Although some studies have assessed the properties of this flavonoid, the potential of SIL as a treatment for PTSD patients and its mechanisms of action have yet to be fully elucidated.

Methods

After exposure to a model of single prolonged stress (SPS), the open field test (OFT) and forced swimming test (FST), were used to investigate the effects of SIL on anxiety- and depression-like symptoms in male rats. The rats received of SIL (25, 50, and 100 mg/kg) for 14 days following exposure to SPS.

Results

Administration of SIL significantly improved anxiety-like behaviors in the OFT, depression-like behaviors in the FST, and freezing behavior in fear conditioning test. SIL also increased levels of serotonin in the hippocampus (Hipp) and amygdala, and enhanced expression of tryptophan hydroxylase-1 mRNA in the Hipp. The administration of SIL also inhibited SPS-induced decreases dopamine levels and increases norepinephrine levels in the Hipp.

Conclusions

Taken together, the present findings suggest that SIL can be a useful therapeutic ingredient for the treatment of trauma stress-associated symptoms, including PTSD-induced anxiety and depression caused by PTSD.
A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology
Authors: Wang Le , Tan Nana , Wang Huan , Hu Jingbo , Diwu Wenbo , Wang Xiaoling
Published: March 2020

Background

Flavonoids from plant medicines are supposed to be viable alternatives for the treatment of type 2 diabetes (T2D) as less toxicity and side effects.Radix scutellariae(RS) is a widely used traditional medicine in Asia. It has shown great potential in the research of T2D. However, the pharmacological actions remain obscured due to the complex chemical nature of plant medicines.

Methods

In the present study, a systematic method combining ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology was developed to screenα-glucosidase inhibitors from flavonoids ofRS, and explore the underlying mechanism for the treatment of T2D.

Results

Then-butanol part of ethanol extract fromRSshowed a strongα-glucosidase inhibition activity (90.55%, IC500.551 mg/mL) against positive control acarbose (90.59%, IC501.079 mg/mL). A total of 32 kinds of flavonoids were identified from the extract, and their ESI-MS/MS behaviors were elucidated. Thirteen compounds were screened asα-glucosidase inhibitors, including viscidulin III, 2′,3,5,6′,7-pentahydroxyflavanone, and so on. A compound-target-pathway (CTP) network was constructed by integrating theseα-glucosidase inhibitors, target proteins, and related pathways. This network exhibited an uneven distribution and approximate scale-free property. Chrysin (k = 87), 5,8,2′-trihydroxy-7-methoxyflavone (k = 21) and wogonin (k = 20) were selected as the main active constituents with much higher degree values. A protein-protein interaction (PPI) weighted network was built for target proteins of theseα-glucosidase inhibitors and drug targets of T2D. PPARG (Cd = 0.165,Cb = 0.232,Cc = 0.401), ACACB (Cd = 0.155,Cb = 0.184,Cc = 0.318), NFKB1 (Cd = 0.233,Cb = 0.161,Cc = 0.431), and PGH2 (Cd = 0.194,Cb = 0.157,Cc = 0.427) exhibited as key targets with the highest scores of centrality indices. Furthermore, a core subnetwork was extracted from the CTP and PPI weighted network. Type II diabetes mellitus (hsa04930) and PPAR signaling pathway (hsa03320) were confirmed as the critical pathways.

Conclusions

These results improved current understanding of natural flavonoids on the treatment of T2D. The combination of ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology provides a novel strategy for the research of plant medicines and complex diseases.
Reducing ignorance about who dies of what: research and innovation to strengthen CRVS systems
Authors: Lopez Alan D. , McLaughlin Deirdre , Richards Nicola
Published: March 2020

The Sustainable Development Goal (SDG) agenda offers a major impetus to consolidate and accelerate development in civil registration and vital statistics (CRVS) systems. Strengthening CRVS systems is an SDG outcome in itself. Moreover, CRVS systems are the best – if not essential – source of data to monitor and guide health policy debates and to assess progress towards numerous SDG targets and indicators. They also provide the necessary documentation and proof of identity for service access and are critical for disaster preparedness and response. While there has been impressive global momentum to improve CRVS systems over the past decade, several challenges remain. This article collection provides an overview of recent innovations, progress, viewpoints and key areas in which action is still required – notably around the need for better systems and procedures to notify the fact of death and to reliably diagnose its cause, both for deaths in hospital and elsewhere.
Transcriptome analysis of HPV-induced warts and healthy skin in humans
Authors: AL-Eitan Laith N. , Tarkhan Amneh H. , Alghamdi Mansour A. , Al-Qarqaz Firas A. , Al-Kofahi Hadeel S.
Published: March 2020

Background

The human papillomaviruses (HPV) are a group of viruses that, depending on the strain, can cause cancer or the formation of benign growths known as warts. Scarce information exists with regard to the genetic nature of non-genital cutaneous warts induced by the human papillomavirus (HPV).

Methods

The main purpose of this study is to investigate the differences between the gene expression profiles of common warts and healthy skin in HPV-positive individuals by RNA sequencing on the Illumina HiSeq 2500. After obtaining shave biopsies of common warts and healthy skin from twelve Arab males, we were able to analyze the transcriptomes of 24 paired cases and controls.

Results

Common warts were found to possess a highly significant and unique molecular signature. Many of the most up-regulated (KRT16, EPGN, and ABCG4) and down-regulated genes (C15orf59, CYB561A3, and FCGRT) in warts were the subject of little investigation in the published literature. Moreover, the top 500 differentially expressed genes were found to be associated with immune and autoimmune pathways, such as the neutrophil degranulation, toll-like receptor 7/8 (TLR 7/8) cascade, toll-like receptor 9 (TLR9) cascade, and toll-like receptor 10 (TLR10) pathways, among others.

Conclusions

Our findings are particularly important because they serve as the most comprehensive to date with regard to the modulation of human skin gene expression by HPV infection.
Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production
Authors: Wu Geng-Chin , Peng Chung-Kan , Liao Wen-I , Pao Hsin-Ping , Huang Kun-Lun , Chu Shi-Jye
Published: March 2020

Background

It is well known that ventilation with high volume or pressure may damage healthy lungs or worsen injured lungs. Melatonin has been reported to be effective in animal models of acute lung injury. Melatonin exerts its beneficial effects by acting as a direct antioxidant and via melatonin receptor activation. However, it is not clear whether melatonin receptor agonist has a protective effect in ventilator-induced lung injury (VILI). Therefore, in this study, we determined whether ramelteon (a melatonin receptor agonist) can attenuate VILI and explore the possible mechanism for protection.

Methods

VILI was induced by high tidal volume ventilation in a rat model. The rats were randomly allotted into the following groups: control, control+melatonin, control+ramelteon, control+luzindole, VILI, VILI+luzindole, VILI + melatonin, VILI + melatonin + luzindole (melatonin receptor antagonist), VILI + ramelteon, and VILI + ramelteon + luzindole (n = 6 per group). The role of interleukin-10 (IL-10) in the melatonin- or ramelteon-mediated protection against VILI was also investigated.

Results

Ramelteon treatment markedly reduced lung edema, serum malondialdehyde levels, the concentration of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), NF-κB activation, iNOS levels, and apoptosis in the lung tissue. Additionally, ramelteon treatment significantly increased heat shock protein 70 expression in the lung tissue and IL-10 levels in BALF. The protective effect of ramelteon was mitigated by the administration of luzindole or an anti-IL-10 antibody.

Conclusions

Our results suggest that a melatonin receptor agonist has a protective effect against VILI, and its protective mechanism is based on the upregulation of IL-10 production.
Ubiquitous neurocognitive dysfunction in familial adenomatous polyposis: proof-of-concept of the role of APC protein in neurocognitive function
Authors: Cruz-Correa Marcia Roxana , Sala Ana Cecilia , Cintrón Beatriz , Hernández Jessica , Olivera Myrta , Cora Adrian , Moore Constance M. , Luciano Carlos A. , Soto-Salgado Marievelisse , Giardiello Francis M. , Hooper Stephen R.
Published: March 2020

Background

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene. Patients with FAP have multiple extraintestinal manifestations that follow a genotype-phenotype pattern; however, few data exist characterizing their cognitive abilities. Given the role of the APC protein in development of the central nervous system, we hypothesized that patients with FAP would show differences in cognitive functioning compared to controls.

Methods

Matched case-control study designed to evaluate cognitive function using the Test of Nonverbal Intelligence-4, the Bateria III Woodcock-Munoz, and the Behavior Rating Inventory of Executive Functions-Adult. Twenty-six individuals with FAP (mean age = 34.2 ± 15.0 years) and 25 age-gender and educational level matched controls (mean age = 32.7 ± 13.8 years) were evaluated.

Results

FAP-cases had significantly lower IQ (p = 0.005). Across all tasks of the Batería III Woodcock-Muñoz, FAP-cases performed significantly lower than controls, with all of the summary scores falling in the bottom quartile compared to controls (p < 0.0001). Patients with FAP scored within the deficient range for Long-Term Retrieval and Cognitive Fluency.

Conclusion

APC protein has an important role in neurocognitive function. The pervasive nature of the observed cognitive dysfunction suggests that loss or dysfunction of the APC protein impacts processes in cortical and subcortical brain regions. Additional studies examining larger ethnically diverse cohorts with FAP are warranted.
Sustainable, healthy cities: protocol of a mixed methods evaluation of a cluster randomized controlled trial for Aedes control in Brazil using a community mobilization approach
Authors: Zinszer Kate , Caprara Andrea , Lima Antonio , Degroote Stéphanie , Zahreddine Monica , Abreu Kellyanne , Carabali Mabel , Charland Katia , Dantas Mayana Azevedo , Wellington José , Parra Beatriz , Fournet Florence , Bonnet Emmanuel , Pérez Denis , Robert Emilie , Dagenais Christian , Benmarhnia Tarik , Andersson Neil , Ridde Valéry
Published: March 2020

Background

Dengue is increasing in its global presence with an estimated 4 billion people at-risk of infection in at least 128 countries. Despite the promising results of EcoHealth and community mobilization approaches to Aedes reduction, more evidence of their efficacy on reducing dengue risk is needed. The principal research question is to determine if interventions based upon community mobilization reduce the risk of dengue virus infection among children 3 to 9 years old compared to usual dengue control practice in Fortaleza, Brazil.

Methods

The present study will follow a pragmatic cluster randomized controlled trial (cRCT) design with randomization at the census tract level with equal allocation to the two arms. In each arm, there will be 34 clusters of 86 children between 3 to 9 years old for an expected total of 5848 children enrolled in the study, assuming a risk reduction of 29.5% based upon findings from a previous multi-site cRCT. The primary outcomes are rates of anti-dengue Immunoglobulin G (IgG) seroconversion and adult female Aedes density. The intervention is based upon a participatory health research approach, Socializing Evidence for Participatory Action (SEPA), where the research evidence is used to foster community engagement and ownership of the health issue and solution. Following allocation, intervention communities will develop and implement their own solutions that will likely include a wide variety of collective events and media approaches. Data collection activities over a period of 3 years include household visits for blood collection, household surveys, and entomological surveys; and qualitative activities including focus groups, in-depth interviews, and document analysis to evaluate the process, acceptability, fidelity, and sustainability of the intervention. Study participants will be aware of their assignment and all research staff will be blinded although the intervention assignment will likely be revealed to field staff through interaction with participants.

Discussion

The results of our study will provide evidence on community mobilization as an intervention for dengue control. We anticipate that if community mobilization is effective in Fortaleza, the results of this study will help develop evidence-based vector control programs in Brazil, and also in other countries struggling with Aedes-transmitted diseases.

Trial registration

ISRCTN66131315, registration date: 1 October 2018.
Correction to: Impact of resettlement scheme on vegetation cover and its implications on conservation in Chewaka district of Ethiopia
Authors: Abera Alemayehu , Yirgu Teshome , Uncha Abera
Published: March 2020

Unfortunately, in the original version of this article figure 5 was repeated in Fig. 4.
Crystallization of calcium carbonate in a large-scale push–pull heat storage test in the Upper Jurassic carbonate aquifer
Authors: Ueckert Martina , Wismeth Carina , Baumann Thomas
Published: March 2020

Crystallization of carbonates is a key process affecting the operation of geothermal facilities and aquifer heat storage systems. The crystals formed in an aquifer heat storage test in the Upper Jurassic carbonate aquifer were investigated at injection temperatures of $$65\,^{\circ }\hbox {C}$$65∘C to $$110\,^{\circ }\hbox {C}$$110∘C, with varying $$\hbox {CO}_{2}$$CO2 partial pressures, and varying Mg/Ca ratios. Water samples were directly filtrated, and analyzed by SEM/EDX. Complementary autoclave experiments were run. In the autoclave experiments with tap water, aragonite crystals dominated at all temperatures (45–110$$\,^{\circ }\hbox {C}$$∘C). In the autoclave experiments with ultra-pure water, calcite crystals dominated at the same temperatures. In the field test, mainly calcite crystals were found up to temperatures of $$90\,^{\circ }\hbox {C}$$90∘C. Only at very high temperatures of $$110\,^{\circ }\hbox {C}$$110∘C aragonite crystallization prevailed. $$\hbox {CO}_{2}$$CO2 partial pressure varied especially between injection and production stages. Mg/Ca ratio varied through all stages, and depended on the dissolution of the rock matrix. Together with the autoclave experiments, this study suggest that temperature and Mg/Ca ratio had no influence on the crystallization, and only supersaturation affected the $$\hbox {CaO}_{3}$$CaO3 polymorphs. We further assume that we produced initially injected crystals back during the following production stage. That results in the assumption that existing particles can maintain an equilibrium in the dispersion, and reduce precipitation on surfaces like pipes and heat exchangers.
EANM Dosimetry Committee series on standard operational procedures for internal dosimetry for 131I mIBG treatment of neuroendocrine tumours
Authors:   In collaboration with the EANM Dosimetry Committee, Gear Jonathan , Chiesa Carlo , Lassmann Michael , Gabiña Pablo Mínguez , Tran-Gia Johannes , Stokke Caroline , Flux Glenn
Published: March 2020

The purpose of the EANM Dosimetry Committee Series on “Standard Operational Procedures for Dosimetry” (SOP) is to provide advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This SOP describes image and data acquisition parameters and dosimetry calculations to determine the absorbed doses delivered to whole-body, tumour and normal organs following a therapeutic administration of131I mIBG for the treatment of neuroblastoma or adult neuroendocrine tumours. Recommendations are based on evidence in recent literature where available and on expert opinion within the community. This SOP is intended to promote standardisation of practice within the community and as such is based on the facilities and expertise that should be available to any centre able to perform specialised treatments with radiopharmaceuticals and patient-specific dosimetry. A clinical example is given to demonstrate the application of the absorbed dose calculations.
Measurement of crystalline lens tilt in high myopic eyes before cataract surgery using swept-source optical coherence tomography
Authors: Lu Qiang , He Wenwen , Qian Dongjin , Lu Yi , Zhu Xiangjia
Published: March 2020

Background

To measure the crystalline lens tilt in eyes with various degrees of myopia before cataract surgery using swept-source optical coherence tomography (SS-OCT).

Methods

We used SS-OCT (IOLMaster 700) to scan 131 emmetropic eyes (axial length < 24.5 mm), 25 mild/moderate myopic eyes (axial length 24.5–26 mm), and 123 high myopic eyes (52, 29, and 42 eyes with axial lengths of 26–28, 28–30, and > 30 mm, respectively) as part of the routine preoperative examination before cataract surgery. SS-OCT involved B-scans along six meridians. The data were analyzed to assess the magnitude and orientation of the lens tilt and their correlation with other optical biometric parameters.

Result

The mean tilt was 3.36 ± 0.98° in emmetropic eyes, 3.07 ± 1.04° in mild/medium myopic eyes, and 2.35 ± 1.01° in high myopic eyes. Tilt correlated significantly and inversely with axial length (Pearson’s r = − 0.427, P < 0.001). The crystalline lens tilt predominantly faced the upper outer quadrant relative to the visual axis, symmetrically in both eyes, with mean angles of 24.32° and 147.36° in the right and left eyes, respectively. The variability in the lens tilt direction increased with increasing axial length (χ2 test, P < 0.001).

Conclusion

The magnitude of crystalline lens tilt decreased with increasing axial length. The direction of tilt was predominantly towards the upper outer quadrant in both eyes. The variability in the tilt orientation increased with increasing axial length.

Trial registration

NIH (clinicaltrial.gov), NCT03062085. Registered 23 February 2017.
Age of the earliest transgressive event in the Krishna-Godavari Basin, India: evidence from dinoflagellate cysts and planktonic foraminifera biostratigraphy
Authors: Mishra Ashish Kumar , Malarkodi Nallamuthu , Singh Arun Deo , Babu Dinesh , Prasad Vandana
Published: March 2020

A combined biostratigraphic study of dinoflagellate cysts and foraminifera was carried out on Early Cretaceous subsurface well cutting sediments from well A (DNG) (2800–2746 m depth) from the Krishna-Godavari Basin, India. The last appearance datum of marker species of dinoflagellate cysts and planktonic foraminifera was considered for the construction of the biostratigraphic framework. The study shows dominance of Early Cretaceous marker dinoflagellate cystsCassiculosphaeridia magna, Cribroperidinium perforans, Hystrichodinium voigtii, Kleithriasphaeridium eoinodes, and planktonic foraminiferaHedbergella aptiana, Hedbergella mitra, Hedbergella praelippa, Hedbergella tardita, Microhedbergella miniglobularisandHedbergella mitraspecies. In addition to this, the dinoflagellate cyst data were compared with the dinoflagellate biozones of Austral and Tethyan provinces. Based on earlier micropalaeontological records from the Krishna-Godavari Basin and the present study, a latest Barremian-early Aptian age has been determined for the earliest marine transgression in the Krishna-Godavari Basin. The early marine incursion during late Barremian-earliest Aptian in the Krishna-Godavari Basin compared to Albian age in Cauvery Basin suggests the opening of east coast from north to south.
Anti-inflammatory effects of Jingshu Keli capsule and its components on human synoviocyte MH7A cells
Authors: Meng Xiangbo , Cheng Wenxiang , Zhong Shan , Zhang Peng , Qin Ling , Wang Xinluan
Published: March 2020

Background

Jingshu Keli (JSKL), a traditional Chinese medicine (TCM) formula consisting of multiple active compounds, has been officially approved by National Medical Products Administration (NMPA) for treatment of cervical radiculopathy. It relieves pain, according to TCM theory, by activating blood circulation to dissipate blood stasis. The pain mainly stems from neurogenic inflammation caused by mechanical compression of the cervical nerve root. In addition, inflammation mediators also cause the development of other joint diseases, such as osteoarthritis (OA). The purpose of this paper was to evaluate the anti-inflammatory effects of JSKL and identify the biologically active herbs and compounds in vitro.

Methods

Enzyme-linked immunosorbent assay (Elisa) was used to determine the expression of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin 8 (IL-8), in the culture medium of human MH7A cells stimulated by lipopolysaccharides (LPS).

Results

JSKL and three single-herb capsules, Cinnamomum cassia Presl (C.C.), Angelica Sinensis (Oliv.) Diels (A.S.) and Carthamus tinctorius L. (C.T.), significantly inhibited the secretion of TNF-α. If one of these three herbal components was removed, suppressing effect of the single-herb-deleted JSKL on TNF-α was abolished. Cinnamaldehyde (CIN) from C.C. was the most potent ingredient that inhibited the expression of IL-6 and IL-8 in the culture medium of both LPS-stimulated MH7A cells and primary synovial cells.

Conclusions

JSKL was found to possess anti-inflammatory effect in vitro; C.C., A.S. and C.T. were the principal and essential herbal components responsible for such activity; CIN from C.C. is one the most potent single compound among indicator components of JSKL recorded in 2015 Chinese pharmacopoeia. This study provided scientific evidence for the clinical application of JSKL as an agent for targeted treatment of cervical radiculopathy. Furthermore, CIN has potential to be used for the treatment of some inflammation-related orthopedic diseases, such as rheumatic arthritis and osteoarthritis.
Antiproliferative effects on tumor cells of the synthesized gold nanoparticles against Hep2 liver cancer cell line
Authors: Priya M R Kamala , Iyer Priya R.
Published: March 2020

Background

Currently, nanomaterials (NMs) research and development is at a fastest pace due to the enhanced implication in different areas of applications. The synthesis of such NMs through biosynthesis methods is gaining much importance because of low cost involved and environment-friendly approach. In this present study, the nanoparticles (NPs) are synthesized using a medicinal plant, with anticancer properties so as to incorporate the therapeutic activity within the NPs, such that the NPs will have the attributes of NMs alongside the phytoactivity.

Results

The synthesis of gold nanoparticles (AuNPs) using Graviola, the fruit of Annona muricata (Ramaphal fruit) commonly referred as Mullu seetha fruit (Tamil), was successfully carried out. The initial confirmations of the NPs were using UV-vis spectra, which showed the characteristic peak for the NPs. HRSEM analysis gave an insight on the size and morphology of the NPs. The zeta potential was measured to check the stability of the NPs. The cytotoxicity was carried out in VERO cell line and anticancer study in Hep2 liver cancer cell line. The surface plasmon resonance (SPR) band showed the characteristic peak at 536 nm for the AuNPs. In SEM micrographs, the size was ranging between 20 and 30 nm, on an average of 15 nm with spherical morphology. On the various tested concentrations in VERO cell line, the nanoparticles were non-toxic to the cells. The anticancer study gave an IC50 value at 10.94 μg/ml.

Conclusions

The NPs showed anticancer activity in treated Hep2 liver cancer cell line and as well as commendable non-toxic effect on normal VERO cell line. The results pose a positive impact to expand further studies in the development of potential drug molecules to tackle the disease of interest.
Intratumoral mRNA levels predict clinical outcome in patients with metastatic colorectal cancer treated in a prospective clinical trial with 5-FU and oxaliplatin
Authors: Yang D. , Vallböhmer D. , Zhang W. , Iqbal S. , El-Khoueiry A. , Gordon M. , Park D. , Azuma M. , Groshen S. , Danenberg K. D. , Lenz H.
Published: March 2020

10010

Background: 5-flurouracil (5-FU) and Oxaliplatin-based therapy is one of the most frequently used combinations in the treatment of advanced colorectal cancer (CRC). There are no validated and established predictive factors for clinical outcome following 5-FU/Oxaliplatin treatment. We had shown an association between intratumoral mRNA levels of TS and ERCC1 involved in 5-FU metabolism and DNA repair, respectively, and survival to 5-FU/Oxaliplatin chemotherapy in advanced CRC in a retrospective study. Now we investigated whether intratumoral mRNA levels of these two genes and others involved in 5-FU metabolism (DPD, TP, dUTPase), DNA repair (ERCC2, XRCC1), angiogenesis (COX-2, EGFR, IL-8, PLA2), and drug detoxification (GSTP-1) predict the clinical outcome of patients with CRC in a prospectively designed biomarker study. Methods: 85 patients with metastatic CRC treated with second-line 5-FU/Oxaliplatin from the prospective trial were included. mRNA levels of 12 genes were assessed from paraffin- embedded tissue samples using laser capture microdissection and quantitative Real-time PCR. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), response, and toxicity were the secondary endpoints. Results: There were 40 women and 45 men (median age 60 years; range 29–87), median survival of 9.7 ms, median PFS of 4.2 ms, CR in 1 (1%) patient, PR in 15 (18%), SD in 36 (43%) and PD in 32 (38%) patients. High intratumoral mRNA levels of PLA2, TP, GSPTP-1 and low mRNA levels of COX-2 were each significantly associated with shorter OS (P≤0.05, log-rank test). There was a trend in the association between high mRNA levels of PLA2 and shorter PFS (P=0.08). In addition, high mRNA levels of XRCC1 and IL-8 were each significantly associated with high risk of cumulative grade 3+ toxicity (P≤0.05). No significant association was found between mRNA levels and response to 5-FU/Oxaliplatin. Conclusions: This study suggests that mRNA levels of PLA2, TP, GSTP-1, COX-2, XRCC1, and IL-8 may be useful to predict the outcome of patients with metastatic CRC with second-line 5-FU/Oxaliplatin chemotherapy. These findings should be validated with future basic sciences studies and prospective clinical trials.

[Table: see text]
Childhood cancer in families with and without germline BRCA1/2 mutations ascertained at a high-risk breast cancer clinic
Authors: Brooks G. A. , Stopfer J. E. , Erlichman J. , Davidson R. , Nathanson K. L. , Domchek S. M.
Published: March 2020

10013

Background: Germline mutations in the BRCA1 and BRCA2 genes (BRCA1/2) are associated with breast cancer, ovarian cancer and other malignancies. Biallelic mutations of BRCA2 are a cause of Fanconi anemia and characteristic childhood cancers. We undertook this study to evaluate the contribution of familial heterozygous BRCA1/2 mutations to childhood cancer in hereditary breast cancer families. Methods: We conducted a retrospective cohort study to compare the prevalence of childhood cancers among 379 families with BRCA1/2 mutations and 426 families without known mutations. All families were ascertained at a high-risk breast cancer clinic. Our study and comparison cohorts included first- through fourth-degree relatives of cancer-affected mutation carriers and cancer-affected individuals with negative full sequencing for BRCA1/2 mutations. The primary endpoint was any case of childhood cancer (diagnosed <age 21) as recorded in the family history. Results were analyzed using Fisher’s exact test. Results: 20 cases of childhood cancer were observed in 379 families with BRCA1/2 mutations and 35 cases of childhood cancer were observed in 426 families with negative mutation testing (p = 0.12). Apart from two very early-onset breast cancers, the types of childhood cancers occurring in the BRCA1/2 mutation positive families were similar to those occurring in the mutation negative families and in the general population. Nine childhood cancers occurred in 240 families with BRCA1 mutations, and 11 childhood cancers occurred in 141 families with BRCA2 mutations (p=0.1). 13 of 18 BRCA1/2 mutation positive families with cases of childhood cancer (72%) and 13 of 31 families with childhood cancer cases and negative mutation testing (42%) met the Birch clinical criteria for Li-Fraumeni like syndrome (LFL); no individual has undergone testing for germline TP53 mutations. Conclusions: Heterozygous BRCA1/2 mutations do not appear to be a significant risk factor for childhood cancer in hereditary breast cancer families. This observation supports the current practice of delaying BRCA1/2 mutation testing until candidates reach adulthood. Although many families in both groups met criteria for LFL, the clinical significance of this finding is uncertain.

No significant financial relationships to disclose.
Characterization of a novel founder rearrangement mutation of BRCA1 in high-risk Hispanic families
Authors: Ho J. , Herzog J. , Lagos V. , Lowstuter K. , Palomares M. , Blazer K. , MacDonald D. , Feldman N. , Weitzel J.
Published: March 2020

10015

Background: Large rearrangements are estimated to account for 5–10% of all mutations in BRCA1 and BRCA2. Prevalent founder rearrangement mutations have been described in European populations. We sought to identify rearrangements in the BRCA genes in a cohort of Hispanic patients. Methods: We identified 34 deleterious BRCA mutations via full sequence analysis among 110 unrelated high-risk Hispanic families enrolled in an IRB approved registry who underwent cancer risk assessment (CEBP 2005;14:1–6). DNA from 67 of 76 patients without an identifiable mutation was subjected to multiplexed quantitative differential PCR (MQDP, per B. Erickson and T. Scholl, Myriad Genetics Laboratory) for detection of large rearrangements. An apparent deletion of BRCA1 exons 9–12, indicated by a 50% loss of signal was identified by MQDP in 3 unrelated families (ASHG, 2005). Long range PCR resulted in the generation of a 2.7kb product in these samples, consistent with a deletion event of 15.1kb. This putative mutation was further characterized by cloning and sequencing the breakpoint in all 3 families. RNA splicing was evaluated by sequencing RT-PCR products from lymphoblastoid cell line RNA for each family. Results: Sequence analysis identified the breakpoint within Alu elements in introns 8 and 12, and all 3 unrelated families shared the same breakpoint. Analysis of cDNA demonstrated direct splicing of exons 8–13 predicting a frameshift mutation and premature truncation of the BRCA1 protein, thus confirming the deleterious nature of this mutation. Conclusion: We identified the same novel large deletion in three unrelated families of Mexican ancestry, suggesting potential founder effect. The frequency was 2.7% of the 110 high-risk Hispanic families screened for BRCA mutations, bringing the overall prevalence of deleterious mutations to 33.6%(37/110) in this cohort. This BRCA1 rearrangement may account for a substantial proportion of high-risk Hispanic families, and should be included in all subsequent studies of this ethnic group.

No significant financial relationships to disclose.
Patterns of genomic instability differentiate clinical outcomes in patients with invasive breast cancer
Authors: Ellsworth R. E. , Becker T. E. , Ellsworth D. L. , Love B. , Hooke J. A. , Shriver C. D.
Published: March 2020

10018

Background: Despite improved survival rates for women with breast cancer mainly from improved screening, aggressive therapies may result in the over treatment of many with undesirable physical and economic costs. Identification of molecular profiles in breast tumors that differentiate patients with poor prognosis from those with favorable outcomes would allow for development of effective, individualized treatment regimens with less overall morbidity. Methods: DNA was extracted from primary breast tumors representing stage I (n=75), stage II (n=42), stage III (n=24), and stage IV (n=9) after laser microdissection to isolate pure tumor cell populations. Genomic instability was detected using 52 microsatellite markers representing 26 chromosomal regions frequently altered in breast cancer. Statistical analyses were performed using Fisher’s exact tests and Student t-tests. Results: Patients with poor prognosis (15% of sample population) were defined as those dead of disease (DOD) or alive with disease (AWD), either metastatic disease or disease recurrence; all others had no evidence of disease (NED). Overall levels of genomic instability were significantly higher in tumors from patients with poor prognosis (P<0.0005). At the chromosomal level, chromosome 17p13.3 (P<0.001), 3p13 (P<0.05), and 13q14 (P<0.05) were altered significantly more frequently in patients with poor prognosis compared to NED patients. Conclusions: Chromosomes 3p13, 13q14, and 17p13.3 harbor the fragile histadine triad (FHIT), retinoblastoma 1 (RB1), and hypermethylated in cancer 1 (HIC1) genes, respectively. Alteration of the FHIT gene may promote overall genomic instability while alterations in RB1 and HIC1 has been associated with poor prognosis in patients with breast cancer. Assessment of genomic instability at these three regions may prove useful for stratifying patients by tumor aggressiveness, thus allowing more effective, customized treatment options to be developed.

No significant financial relationships to disclose.