bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiotherapy in the Caribbean: a spotlight on the human resource and equipment challenges among CARICOM nations
Authors: Alleyne-Mike Kellie , Sylvester Pearse , Henderson-Suite Vladimir , Mohoyodeen Thana
Published: July 2020

Background

There is limited data on access to radiotherapy services for CARICOM nations.

Methods

This was a descriptive mixed-methods observational study which used data collected via survey from staff working in Radiation Oncology in 14 CARICOM countries. Benchmark recommendations from the International Atomic Energy Agency were compared to existing numbers. The Directory of Radiotherapy Centers, World Bank, and Global Cancer Observatory databases were all accessed to provide information on radiotherapy machines in the region, population statistics, and cancer incidence data respectively. Both population and cancer incidence-based analyses were undertaken to facilitate an exhaustive review.

Results

Radiotherapy machines were present in only 50% of the countries. Brachytherapy services were performed in only six countries (42.9%).

There were a total of 15 external beam machines, 22 radiation oncologists, 22 medical physicists, and 60 radiation therapists across all nations.

Utilizing patient-based data, the requirement for machines, radiation oncologists, medical physicists, and radiation therapists was 40, 66, 44, and 106, respectively. Only four (28.6%) countries had sufficient radiation oncologists. Five (35.7%) countries had enough medical physicists and radiation therapists.

Utilizing population-based data, the necessary number of machines, radiation oncologists, and medical physicists was 105, 186, and 96 respectively. Only one county (7.1%) had an adequate number of radiation oncologists. The number of medical physicists was sufficient in just three countries (21.4%). There were no International Atomic Energy Agency population guidelines for assessing radiation therapists.

A lower economic index was associated with a larger patient/population to machine ratio. Consequentially, Haiti had the most significant challenge with staffing and equipment requirements, when compared to all other countries, regardless of the evaluative criteria. Depending on the mode of assessment, Haiti’s individual needs accounted for 37.5% (patient-based) to 59.0% (population-based) of required machines, 40.1% (patient-based) to 59.7% (population-based) of needed radiation oncologists, 38.6% (patient-based) to 58.3% (population-based) of medical physicists, and 42.5% (patient-based) of radiation therapists.

Conclusion

There are severe deficiencies in radiotherapy services among CARICOM nations. Regardless of the method of comparative analysis, the current allocation of equipment and staffing scarcely meets 50% of regional requirements.
Immunohistochemical analysis of sensory corpuscles in human transplants of the anterior cruciate ligament
Authors: Rebmann D. , Mayr H. O. , Schmal H. , Hernandez Latorre S. , Bernstein A.
Published: July 2020

Background

Sensory nerve endings in ligaments play an important role for the proprioceptive function. Clinical trials show that the sense of body position does not fully recover in the knee joint after reconstructive surgery of the ruptured anterior cruciate ligament. The aim of this study is to identify sensory corpuscles in autogenous and allogenous transplants of the ligament and to compare their quantity between the used allografts and autografts.

Methods

Thirty-three patients were included in this study. Three patellar tendon allografts, 14 patellar tendon autografts and 12 semitendinosus autografts were harvested during revision surgery after traumatic rerupture of the graft. The control consisted of 4 healthy anterior cruciate ligaments after fresh rupture. After haematoxylin staining, immunohistochemical analysis was performed using antibodies against S100, p75 and PGP9.5. Microscopical examination was carried out, and the number of mechanoreceptors was counted. Statistical analysis was performed using the Mann-Whitney U test.

Results

Two types of mechanoreceptors were identified in each graft: Ruffini corpuscles and free nerve endings. The number of Ruffini corpuscles per square centimeter was the highest in the control. Comparing the grafts, the highest number of receptors could be detected in the semitendinosus autograft. The amount of free nerve endings was higher in the semitendinosus and patellar tendon autografts than in the control; the allografts showed the lowest number of receptors. With increasing time after reconstruction, the number of both types of receptors showed a decrease in the semitendinosus graft, whereas it increased in the patellar tendon graft and allograft. The number of mechanoreceptors in the semitendinosus and patellar tendon graft decreased over time after graft-failure, whereas it increased slightly in the allograft.

Conclusion

This study was the first to identify mechanoreceptors in human transplants of the anterior cruciate ligament. The partial increase in the number of receptors over time after reconstruction could indicate a reinnervation of the grafts.
The relationship between acculturation and mental health of 1st generation immigrant youth in a representative school survey: does gender matter?
Authors: Klein Eva M. , Müller Kai W. , Wölfling Klaus , Dreier Michael , Ernst Mareike , Beutel Manfred E.
Published: July 2020

Background

Although gender plays a pivotal role in the psychological adaptation of immigrant youth, its association with acculturation strategy and mental health among 1st generation immigrant adolescents are still scarce and inconsistent. Therefore, the purpose of the current study was to investigate gender-related differences in acculturation patterns and their association with mental health (internalizing and externalizing problems).

Methods

Self-reported data of immigrant adolescents (N = 440) aged between 12 and 19 years (M = 16.2;SD = 1.6) was collected in a representative German school survey. Fifty-one percent of the sample were female (n = 224). Almost half of the sample was born in the Former Soviet Union, followed by Poland (9.3%). Sociodemographic variables, acculturation strategies, and internalizing as well as externalizing problems were assessed by questionnaires.

Results

Confirmatory factor analysis supported the four- dimensional model of acculturation styles (assimilation, integration, separation and marginalization). Whereas girls more often showed an integration pattern, boys scored higher on the separation and marginalization scale. After adjusting for age and educational level, regression analyses revealed for both gender that marginalization was associated with more internalizing problems. Separation was related to more externalizing problems.

Conclusion

1st generation adolescents experiencing a lack of belongingness to German society, socio-economic and educational disadvantages might be particularly vulnerable to mental distress. Findings are discussed in terms of gender-related differential socialization processes in context of immigration.
Time‑resolved transcriptome analysis during transitions of sulfur nutritional status provides insight into triacylglycerol (TAG) and astaxanthin accumulation in the green alga Chromochloris zofingiensis
Authors: Mao Xuemei , Lao Yongmin , Sun Han , Li Xiaojie , Yu Jianfeng , Chen Feng
Published: July 2020

Background

Chromochloris zofingiensis, an oleaginous microalga, is a promising feedstock for the co-production of triacylglycerol (TAG)-based biodiesel and the high-value product astaxanthin. To reveal the molecular mechanism of TAG and astaxanthin biosynthesis during transitions of sulfur nutritional status, namely sulfur-starvation (SS) and sulfur-replenishment (SR), the physiological responses and the transcriptomic dynamics ofC. zofingiensiswere examined.

Results

The results revealed a reversible TAG and astaxanthin accumulation under SS, which is correlated with the reduction of cell growth and protein content, indicating the reallocation of carbon. By correlating the data on the physiological and transcriptional responses to different sulfur nutritional status, a model for the underlying mechanism of TAG and astaxanthin accumulation inC. zofingiensiswas postulated, which involved up-regulation of key genes including diacylglycerol acyltransferase (DGTT5) and beta-carotene ketolase (BKT1), increased energy and NADPH supply by elevating the tricarboxylic acid (TCA) cycle and the oxidative pentose phosphate (OPP) pathway, and the increased carbon precursors (pyruvate and acetyl-CoA) through central carbon metabolism. In addition, the net enhancement of the de novo biosynthesis of fatty acids and the re-direction of the terpenoid precursors toward the branch catalyzed by lycopene beta cyclase (LCYb) andBKT1escalated the substrate availability for the biosynthesis of TAG and astaxanthin, respectively.

Conclusions

In this study, the time-resolved transcriptional analysis ofC. zofingiensisunder SS and SR conditions was reported for the first time to elucidate the regulatory roles of key enzymes, includingDGTT5,BKT1andLCYb, in the underlying mechanisms of TAG and astaxanthin accumulation.
Characterization of a female germline and early zygote promoter from the transcription factor bZip1 in the dengue mosquito Aedes aegypti
Authors: Kojin Bianca B. , Biedler James K. , Tu Zhijian , Adelman Zach N.
Published: July 2020

Background

The wide distribution ofAedes aegypti, the main vector of dengue and yellow fever viruses, currently puts three billion people in the world at risk of infection with these viruses. Continuous transmission of these and other viruses despite aggressive efforts to prevent this emphasizes the need to develop new control strategies. Proposals to control disease transmission based on vector engineering, including both population suppression and population replacement, rely on the development of transgenes under the control of regulatory elements able to drive molecules in a specific tissue, time and strength.

Methods

Here we report the characterization of a promoter active in both the female germline and early zygote, derived from the transcription factor bZip1 in the mosquitoAe. aegypti, using transposon-based methods and RT-qPCR.

Results

We generated seven transgenic lines carryingAabZip1-reporter constructs and observed expression in both the ovary and early embryo. RT-qPCR analysis was performed to evaluate transcript expression patterns for each line, confirming that transgenic expression from theAabZip1promoter largely recapitulated the endogenous expression pattern, albeit the strength of maternal expression appeared to be strongly influenced by chromosomal position.

Conclusions

This study provides a new regulatory sequence that can be useful for generating transgenic lines that can become a tool in vector control strategies.
Caution in studying and interpreting the lupus metabolome
Authors: Zhang Ting , Mohan Chandra
Published: July 2020

Several metabolomics studies have shed substantial light on the pathophysiological pathways underlying multiple diseases including systemic lupus erythematosus (SLE). This review takes stock of our current understanding of this field. We compare, collate, and investigate the metabolites in SLE patients and healthy volunteers, as gleaned from published metabolomics studies on SLE. In the surveyed primary reports, serum or plasma samples from SLE patients and healthy controls were assayed using mass spectrometry or nuclear magnetic resonance spectroscopy, and metabolites differentiating SLE from controls were identified. Collectively, the circulating metabolome in SLE is characterized by reduced energy substrates from glycolysis, Krebs cycle, fatty acid β oxidation, and glucogenic and ketogenic amino acid metabolism; enhanced activity of the urea cycle; decreased long-chain fatty acids; increased medium-chain and free fatty acids; and augmented peroxidation and inflammation. However, these findings should be interpreted with caution because several of the same metabolic pathways are also significantly influenced by the medications commonly used in SLE patients, common co-morbidities, and other factors including smoking and diet. In particular, whereas the metabolic alterations relating to inflammation, oxidative stress, lipid peroxidation, and glutathione generation do not appear to be steroid-dependent, the other metabolic changes may in part be influenced by steroids. To conclude, metabolomics studies of SLE and other rheumatic diseases ought to factor in the potential contributions of confounders such as medications, co-morbidities, smoking, and diet.
Clinical and histological significance of urinary CD11c+ macrophages in lupus nephritis
Authors: Kim Jihye , Lee Jung Sun , Go Heounjeong , Lim Joon Seo , Oh Ji Seon , Kim Yong-Gil , Lee Chang-Keun , Yoo Bin , Hong Seokchan
Published: July 2020

Background

Infiltration of immune cells into the kidney is one of the key features of lupus nephritis (LN). The presence of immune cells in the urine may be used as a non-invasive biomarker of LN. Here, we aimed to analyze the clinicopathologic significance of urinary CD11c+ macrophages in patients with LN.

Methods

The numbers and proportions of CD11c+ macrophages in the urine samples of patients with LN at the time of kidney biopsy were examined using flow cytometry. We also examined the association between the levels of urinary CD11c+ macrophages and the clinical and pathologic features of patients with LN.

Results

Compared with patients without LN or those with non-proliferative LN, patients with proliferative LN had significantly higher numbers and proportions of urinary CD11c+ macrophages, which were strongly correlated with the serum anti-dsDNA antibody titer. The numbers and proportions of urinary CD11c+ macrophages were significantly associated with the values of chronicity indices such as tubular atrophy and interstitial fibrosis. No significant relationships were found between the levels of urinary CD11c+ macrophages and the activity scores, degree of proteinuria, or lupus disease activity. Urinary CD11c+ macrophages were more abundant in patients who did not achieve renal response to induction treatment with immunosuppressants than in those who achieved complete or partial response. The receiver operating characteristic (ROC) curve analysis showed that the number of urinary CD11c+ macrophages was the most powerful predictor of renal response at 6 months (ROC-AUC = 1.00, p = 0.0004).

Conclusion

The urinary levels of CD11c+ macrophages were closely associated with the chronic pathologic changes of LN and renal response and may thus be used as a novel biomarker in LN.
Gender differences in quality of life in adults with long-standing type 1 diabetes mellitus
Authors: Castellano-Guerrero Ana María , Guerrero Raquel , Ruiz-Aranda Desireé , Perea Sofia , Pumar Alfonso , Relimpio Federico , Mangas Miguel Angel , Losada Fernando , Martínez-Brocca Maria Asunción
Published: July 2020

Background

To assess gender differences in Quality of life (QoL) and in sociodemographic, clinical and psychological factors associated with impaired QoL in adults with long-standing type 1 diabetes mellitus (DM1).

Methods

Cross-sectional evaluation in a random cohort of DM1 adult patients from a tertiary care hospital. QoL was evaluated using translated and validated self-administered Diabetes QoL questionnaire (Es-DQoL), and results transformed into a 0–100 scale. Psychological assessment included a planned psychological interview and self-reported questionnaires (Beck Depression Inventory II, State-Trait Anxiety Inventory Form Y, Fear of hypoglycaemia Scale, Medical Outcomes Study Social Support Survey).

Results

A total of 312 patients (51.6% male; 38.2 ± 12.7 years; HbA1c 7.5 ± 1.1% (58.5 ± 14.2 mmol/mol); 20.4 ± 12.0 years of DM1) were included in the analysis. Male and female subgroups showed similar sociodemographic and diabetes-related features and comparable social support. Among female patients, higher frequency of depression [31.7% (IC95% 26.2–40.8) vs. 14.9% (IC95% 10.1–20.8), p < 0.05] and anxiety [23.2% (IC95% 19.3–33.14) vs. 13.0% (IC95% 8.1–18.4), p < 0.05] and severity of depressive and anxious symptoms were also found. Compared to male patients, female patients showed lower QoL [75 (IC95% 73.6–77.5) vs. 80 (IC95% 75.7–83.1), p < 0.05] and scored significantly worse in subscale Diabetes-related worries [69 (IC95% 50.0–81.0) vs. 75 (IC95% 72.9–79.0), p < 0.05]. Fear of hypoglycemia and severity of depressive and anxious symptoms were factors independently associated to lower QoL in men and women while high frequency of glycemic excursions was a female-specific predictive one.

Conclusions

Adult women with long-standing DM1 showed lower QoL probably related to higher frequency and severity of psychopathological syndromes. Depressive and anxious symptoms and, among women, exposure to glycemic excursions were identified as modifiable, QoL-related variables. Educational, technological and psychological interventions are needed in order to improve QoL in DM1 patients.
Multiparametric MRI: practical approach and pictorial review of a useful tool in the evaluation of brain tumours and tumour-like lesions
Authors: Sawlani Vijay , Patel Markand Dipankumar , Davies Nigel , Flintham Robert , Wesolowski Roman , Ughratdar Ismail , Pohl Ute , Nagaraju Santhosh , Petrik Vladimir , Kay Andrew , Jacob Saiju , Sanghera Paul , Wykes Victoria , Watts Colin , Poptani Harish
Published: July 2020

MRI has a vital role in the assessment of intracranial lesions. Conventional MRI has limited specificity and multiparametric MRI using diffusion-weighted imaging, perfusion-weighted imaging and magnetic resonance spectroscopy allows more accurate assessment of the tissue microenvironment. The purpose of this educational pictorial review is to demonstrate the role of multiparametric MRI for diagnosis, treatment planning and for assessing treatment response, as well as providing a practical approach for performing and interpreting multiparametric MRI in the clinical setting. A variety of cases are presented to demonstrate how multiparametric MRI can help differentiate neoplastic from non-neoplastic lesions compared to conventional MRI alone.
Human multipotent adult progenitor cell-conditioned medium improves wound healing through modulating inflammation and angiogenesis in mice
Authors: Ahangar Parinaz , Mills Stuart J. , Smith Louise E. , Strudwick Xanthe L. , Ting Anthony E. , Vaes Bart , Cowin Allison J.
Published: July 2020

Background

Stem cell therapies have been widely investigated for their healing effects. However, the translation of these therapies has been hampered by the requirement to deliver live allogeneic or autologous cells directly to the wound in a clinical setting. Multipotent adult progenitor cells (MAPC® cells) are a subpopulation of bone marrow-derived adherent stem cells that secrete a wide range of factors known to accelerate the wound healing process. The aim of this study was to determine the impact of MAPC cells secretome on healing outcomes without the presence of MAPC cells.

Methods

The effect of MAPC-conditioned medium (MAPC-CM) on the capacity of keratinocytes, fibroblasts and endothelial cells to migrate and proliferate was determined in vitro using scratch wound closure and WST1 assay, respectively. The effect of MAPC-CM on collagen deposition and angiogenesis was also assessed using in vitro methods. Additionally, two excisional wounds were created on the dorsal surface of mice (n = 8/group) and 100 μL of 20× MAPC-CM were intradermally injected to the wound margins. Wound tissues were collected at 3, 7 and 14 days post-wounding and stained with H&E for microscopic analysis. Immunohistochemistry was performed to investigate inflammation, angiogenesis and collagen deposition in the wounds.

Results

Skin fibroblasts, keratinocytes and endothelial cells treated with MAPC-CM all showed improved rates of scratch closure and increased cellular proliferation. Moreover, fibroblasts treated with MAPC-CM deposited more collagens I and III and endothelial cells treated with MAPC-CM showed increased capillary tube formation. Murine excisional wounds intradermally injected with MAPC-CM showed a significant reduction in the wound area and an increase in the rate of reepithelialisation. The results also showed that inflammatory cell infiltration was decreased while an increase in angiogenesis, as well as collagens I and III expressions, was observed.

Conclusion

These findings suggest that factors produced by MAPC cells can have an important effect on cutaneous wound healing by affecting skin cell proliferation and migration, balancing inflammation and improving the formation of extracellular matrix and angiogenesis. Development of stem cell-free therapy for the treatment of wounds may be a more clinically translatable approach for improving healing outcomes.
A century of National Forest Inventory in Norway – informing past, present, and future decisions
Authors: Breidenbach Johannes , Granhus Aksel , Hylen Gro , Eriksen Rune , Astrup Rasmus
Published: July 2020

Past

In the early twentieth century, forestry was one of the most important sectors in Norway and an agitated discussion about the perceived decline of forest resources due to over-exploitation was ongoing. To base the discussion on facts, the young state of Norway established Landsskogtakseringen – the world’s first National Forest Inventory (NFI). Field work started in 1919 and was carried out by county. Trees were recorded on 10 m wide strips with 1–5 km interspaces. Site quality and land cover categories were recorded along each strip. Results for the first county were published in 1920, and by 1930 most forests below the coniferous tree line were inventoried. The 2nd to 5th inventories followed in the years 1937–1986. As of 1954, temporary sample plot clusters on a 3 km × 3 km grid were used as sampling units.

Present

The current NFI grid was implemented in the 6th NFI from 1986 to 1993, when permanent plots on a 3 km × 3 km grid were established below the coniferous tree line. As of the 7th inventory in 1994, the NFI is continuous, and 1/5 of the plots are measured annually. All trees with a diameter ≥ 5 cm are recorded on circular, 250 m2 plots. The NFI grid was expanded in 2005 to cover alpine regions with 3 km × 9 km and 9 km × 9 km grids. In 2012, the NFI grid within forest reserves was doubled along the cardinal directions. Clustered temporary plots are used periodically to facilitate county-level estimates. As of today, more than 120 variables are recorded in the NFI including bilberry cover, drainage status, deadwood, and forest health. Land-use changes are monitored and trees outside forests are recorded.

Future

Considerable research efforts towards the integration of remote sensing technologies enable the publication of the Norwegian Forest Resource Map since 2015, which is also used for small area estimation at the municipality level. On the analysis side, capacity and software for long term growth and yield prognosis are being developed. Furthermore, we foresee the inclusion of further variables for monitoring ecosystem services, and an increasing demand for mapped information. The relatively simple NFI design has proven to be a robust choice for satisfying steadily increasing information needs and concurrently providing consistent time series.
Re-testing reported significant SNPs related to suicide in a historical high -risk isolated population from north east India
Authors: Gupta Gaurav , Deval Ravi , Mishra Anshuman , Upadhyay Shashank , Singh Piyoosh Kumar , Rao V. R.
Published: July 2020

Background

Genetic diathesis of suicide is supported by family and twin studies. Few candidate gene pathways are known, but does not explain fully the complexity of suicide genetic risk. Recent investigations opting for Genome-Wide Association Studies (GWAS) resulted in finding additional targets, but replication remained a challenge. In this respect small isolated population approach in several complex disease phenotypes is found encouraging. The present study is an attempt to re-test some of the reported significant SNPs for suicide among a small historical high- risk isolated population from Northeast India.

Methods

Two hundred ten cases (inclusive of depressed, suicide attempter and depressed + suicide attempter) and 249 controls were considered in the present study which were evaluated for the psychiatric parameters. Sixteen reported significant SNPs for suicide behaviour were re-tested using association approach under various genetic models. Networking by GeneMANIA tool was used for function prediction of the associated genes.

Results

Seven SNPs (of 6 genes) remained significant in different genetic models. On networking genes with significant SNPs IL7, RHEB, CTNN3, KCNIP4, ARFGEF3 are found in interaction with already known candidate gene pathways while SNP rs1109089 (RHEB) gained further support from earlier expression studies. NUGGC gene is in complete isolation.

Conclusions

Small population approach in replicating significant SNPs is useful in complex phenotypes like suicide. This study explored the region-specific demographics of India by identifying vulnerable population for suicide via genetic association analysis in bringing into academic and administrative forum, the importance of suicide as a disease and its biological basis.
Replacing critical point drying with a low-cost chemical drying provides comparable surface image quality of glandular trichomes from leaves of Millingtonia hortensis L. f. in scanning electron micrograph
Authors: Bhattacharya Raktim , Saha Sulagna , Kostina Olga , Muravnik Lyudmila , Mitra Adinpunya
Published: July 2020

Sample preparation including dehydration and drying of samples is the most intricate part of scanning electron microscopy. Most current sample preparation protocols use critical-point drying with liquid carbon dioxide. Very few studies have reported samples that were dried using chemical reagents. In this study, we used hexamethyldisilazane, a chemical drying reagent, to prepare plant samples. As glandular trichomes are among the most fragile and sensitive surface structures found on plants, we used Millingtonia hortensis leaf samples as our study materials because they contain abundant glandular trichomes. The results obtained using this new method are identical to those produced via critical-point drying.
Treatment of Hodgkin Lymphoma With ABVD Chemotherapy in Rural Rwanda: A Model for Cancer Care Delivery Implementation
Authors: DeBoer Rebecca J. , Shyirambere Cyprien , Driscoll Caitlin D. , Butera Yvan , Paciorek Alan , Ruhangaza Deogratias , Fadelu Temidayo A. , Umwizerwa Aline , Bigirimana Jean Bosco , Muhayimana Clemence , Nguyen Cam , Park Paul H. , Mpunga Tharcisse , Lehmann Leslie , Shulman Lawrence N.
Published: July 2020

PURPOSE

Hodgkin lymphoma (HL) is highly curable in high-income countries (HICs), yet many patients around the world do not have access to therapy. In 2012, cancer care was established at a rural district hospital in Rwanda through international collaboration, and a treatment protocol using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiotherapy was implemented.

METHODS

We conducted a retrospective cohort study of all patients with confirmed HL seen at Butaro Hospital from 2012 to 2018 to evaluate quality indicators and clinical outcomes.

RESULTS

Eighty-five patients were included (median age, 16.8 years; interquartile range, 11.0-30.5 years). Ten (12%) were HIV positive. Most had B symptoms (70%) and advanced stage (56%) on examination and limited imaging. Of 21 specimens evaluated for Epstein-Barr virus, 14 (67%) were positive. Median time from biopsy to treatment was 6.0 weeks. Of 73 patients who started ABVD, 54 (74%) completed 6 cycles; the leading reasons for discontinuation were treatment abandonment and death. Median dose intensity of ABVD was 92%. Of 77 evaluable patients, 33 (43%) are in clinical remission, 27 (36%) are deceased, and 17 (22%) were lost to follow-up; 3-year survival estimate is 63% (95% CI, 50% to 74%). Poorer performance status, advanced stage, B symptoms, anemia, dose intensity < 85%, and treatment discontinuation were associated with worse survival.

CONCLUSION

Treating HL with standard chemotherapy in a low-resource setting is feasible. Most patients who completed treatment experienced a clinically significant remission with this approach. Late presentation, treatment abandonment, and loss to follow-up contribute to the discrepancy in survival compared with HICs. A strikingly younger age distribution in our cohort compared with HICs suggests biologic differences and warrants further investigation.
Challenges in Preventing Bone Loss Induced by Aromatase Inhibitors
Authors: Rachner Tilman D , Göbel Andy , Jaschke Nikolai P , Hofbauer Lorenz C
Published: July 2020

Context: Aromatase inhibitors have become a mainstay in the adjuvant treatment regimen in postmenopausal women with hormone receptor–positive breast cancer. While many of these patients have an excellent long-term prognosis, adverse effects on bone represent an emerging complication of aromatase inhibitor treatment, resulting in substantial bone loss and fragility fractures.

Treatment approaches to prevent aromatase inhibitor–induced bone loss typically consist of an antiresorptive approach with bisphosphonates or the RANKL antibody denosumab. However, different guidelines vary with respect to treatment thresholds, duration, and dosing.

The choice of antiresorptive regime is further complicated by comorbidities and potential disease-modifying effects of individual agents.

Objective: This review summarizes the evidence of how aromatase inhibitors affect bone health and provides an update of clinical approaches to preserve bone strength in affected women. (J Clin Endocrinol Metab XX: 0–0, 2020)
Duration of Exposure to Thyrotoxicosis Increases Mortality of Compromised AIT Patients: the Role of Early Thyroidectomy
Authors: Cappellani Daniele , Papini Piermarco , Di Certo Agostino Maria , Morganti Riccardo , Urbani Claudio , Manetti Luca , Tanda Maria Laura , Cosentino Giada , Marconcini Giulia , Materazzi Gabriele , Martino Enio , Bartalena Luigi , Bogazzi Fausto
Published: July 2020

Context

Patients with amiodarone-induced thyrotoxicosis (AIT) and severely reduced left ventricular ejection fraction (LVEF) have a high mortality rate that may be reduced by total thyroidectomy. Whether in this subset of patients thyroidectomy should be performed early during thyrotoxicosis or later after restoration of euthyroidism has not yet been settled.

Objectives

Mortality rates, including peritreatment mortality and 5-year cardiovascular mortality, and predictors of death, evaluated by Cox regression analysis.

Methods

Retrospective cohort study of 64 consecutive patients with AIT selected for total thyroidectomy from 1997 to 2019. Four groups of patients were identified according to serum thyroid hormone concentrations and LVEF: Group 1 (thyrotoxic, LVEF <40%), Group 2 (thyrotoxic, LVEF ≥40%), Group 3 (euthyroid, LVEF < 40%), Group 4 (euthyroid, LVEF ≥40%).

Results

Among patients with low LVEF (Groups 1 and 3), mortality was higher in patients undergoing thyroidectomy after restoration of euthyroidism (Group 3) than in those submitted to surgery when still thyrotoxic (Group 1): peritreatment mortality rates were 40% versus 0%, respectively (P = .048), whereas 5-year cardiovascular mortality rates were 53.3% versus 12.3%, respectively (P = .081). Exposure to thyrotoxicosis was longer in Group 3 than in Group 1 (112 days, interquartile range [IQR] 82.5-140, vs 76 days, IQR 24.8-88.5, P = .021). Survival did not differ in patients with LVEF ≥40% submitted to thyroidectomy irrespective of being thyrotoxic (Group 2) or euthyroid (Group 4): in this setting, peritreatment mortality rates were 6.3% versus 4% (P = .741) and 5-year cardiovascular mortality rates were 12.5% and 20% (P = .685), respectively. Age (hazard ratio [HR] 1.104, P = .029) and duration of exposure to thyrotoxicosis (HR 1.004, P = .039), but not presurgical serum thyroid hormone concentrations (P = .577 for free thyroxine, P = .217 for free triiodothyronine), were independent predictors of death.

Conclusions

A prolonged exposure to thyrotoxicosis resulted in increased mortality in patients with reduced LVEF, which may be reduced by early thyroidectomy.
Challenges Faced During the Ventilation of a Child With Bronchobiliary Fistula: A Case Report
Authors: Zainal Abidin Huda , Mohd Lutfi Nijar , Phang Ye Yun , Zarina Fakir Mohamed Intan , Hamidah Ismail , Saedah Ali , Wan Hassan Wan Mohd Nazaruddin
Published: July 2020

Hepatoblastoma is the most frequently occurring malignant tumor of the liver in children (ages ≤5 years). The formation of bronchobiliary fistula is a rare complication. We present a case report that describes the associated anesthetic challenges that we encountered for the treatment of this pathology.
Robert Solow’s Non-Walrasian Conception of Economics
Authors: Ballandonne Matthieu , Rubin Goulven
Published: July 2020

The neoclassical synthesis has been defined as a bridge between Keynes-ian theory and Walrasian general equilibrium theory. The aim of this article is to show that founders of the neoclassical synthesis were not homogenous in their appraisal of the importance of Walrasian theory. To do so, we focus on Robert Solow’s contributions as a case study and examine the history of his lifelong criticism of what he called “axiomatics.” According to Solow, the axiomatic approach aims at founding economics on one general and complex model based on first principles or axioms. In contrast, Solow advocated the use of a diversity of simple and partial models, which have practical utility, are realistic in their crucial assumptions, consider institutions and the evolving nature of the economy, and rely on common sense microfoundations. We conclude by suggesting that Solow can be characterized as Cournotian.
1927
Authors: Esmeir Samera
Published: July 2020

At the turn of the sixteenth century, Egyptian polymath Jalal al-Din al-Suyuti compiled a study about earthquakes he titled Kashf al-salsala ‘an wasf al-zalzala (Revealing the Chain of Echoes/Meaning in the Description of Earthquakes; shortened to Zalzala). Arguing that they constituted divine signs, al-Suyuti chronicled 130 earthquakes that occurred in the Muslim world. Curiously, Zalzala reemerged more than three centuries later in the modern world of colonial expansions. In the aftermath of the 1927 earthquake in Palestine, American seismologist and Stanford professor Bailey Willis would make use of Zalzala for his authoritative “Earthquakes in the Holy Land.” The chronological sections of Zalzala would become indispensable for future seismological scholarship. This article tracks Zalzala's journey into seismology. Seismology's reception of Zalzala was possible by splitting it into two parts (theological and factual), receiving the factual and bracketing the theological, and by converting Zalzala from a chronology of horrors to a catalog of normal quakes of a unified seismic earth. This splitting was at odds with Zalzala's own structure, which joined the two dimensions. Consequently, signs of divinity persisted in seismic factuality, engendering a seismological-theological hybrid. This hybrid tells of the enduring difficulty seismology faces in transforming the earthquake-disaster into a seismological object. It also tells of the persistence of wonder and the enduring relevance of ethical reflection.
Rabphilin involvement in filtration and molecular uptake in Drosophila nephrocytes suggests a similar role in human podocytes
Authors: Selma-Soriano Estela , Llamusi Beatriz , Fernández-Costa Juan Manuel , Ozimski Lauren Louise , Artero Rubén , Redón Josep
Published: July 2020

Drosophila nephrocytes share functional, structural and molecular similarities with human podocytes. It is known that podocytes express the rabphilin 3A (RPH3A)-RAB3A complex, and its expression is altered in mouse and human proteinuric disease. Furthermore, we previously identified a polymorphism that suggested a role for RPH3A protein in the development of urinary albumin excretion. As endocytosis and vesicle trafficking are fundamental pathways for nephrocytes, the objective of this study was to assess the role of the RPH3A orthologue in Drosophila, Rabphilin (Rph), in the structure and function of nephrocytes. We confirmed that Rph is required for the correct function of the endocytic pathway in pericardial Drosophila nephrocytes. Knockdown of Rph reduced the expression of the cubilin and stick and stones genes, which encode proteins that are involved in protein uptake and filtration. We also found that reduced Rph expression resulted in a disappearance of the labyrinthine channel structure and a reduction in the number of endosomes, which ultimately leads to changes in the number and volume of nephrocytes. Finally, we demonstrated that the administration of retinoic acid to IR-Rph nephrocytes rescued some altered aspects, such as filtration and molecular uptake, as well as the maintenance of cell fate. According to our data, Rph is crucial for nephrocyte filtration and reabsorption, and it is required for the maintenance of the ultrastructure, integrity and differentiation of the nephrocyte.
Loss of the Drosophila branched-chain α-keto acid dehydrogenase complex (BCKDH) results in neuronal dysfunction
Authors: Tsai Hui-Ying , Wu Shih-Cheng , Li Jian-Chiuan , Chen Yu-Min , Chan Chih-Chiang , Chen Chun-Hong
Published: July 2020

Maple syrup urine disease (MSUD) is an inherited error in the metabolism of branched-chain amino acids (BCAAs) caused by a severe deficiency of the branched chain keto-acid dehydrogenase (BCKDH) enzyme, which ultimately leads to neurological disorders. The limited therapies, including protein-restricted diets and liver transplants, are not as effective as they could be for the treatment of MSUD due to the current lack of molecular insights into the disease pathogenesis. To address this issue, we developed a Drosophila model of MSUD by knocking out the dDBT gene, an ortholog of the human dihydrolipoamide branched chain transacylase (DBT) subunit of BCKDH. The homozygous dDBT mutant larvae recapitulate an array of MSUD phenotypes, including aberrant BCAA accumulation, developmental defects, poor mobile behavior, and disrupted L-glutamate homeostasis. Moreover, the dDBT mutation causes neuronal apoptosis during the developmental progression of larval brains. The genetic and functional evidence generated by in vivo depletion of dDBT expression in the eye shows severe impairment of retinal rhadomeres. Further, the dDBT mutant shows elevated oxidative stress and higher lipid peroxidation accumulation in the larval brain. Therefore we conclude from in vivo evidence that the loss of dDBT results in oxidative brain damage that may led to neuronal cell death and contribute to aspects of MSUD pathology. Importantly, when the dDBT mutants were administrated with Metformin, the aberrances in BCAA levels and motor behavior were ameliorated. This intriguing outcome strongly merits the use of the dDBT mutant as a platform for developing MSUD therapies.
Estimation of the force-velocity properties of individual muscles from measurement of the combined plantarflexor properties
Authors: Javidi Mehrdad , McGowan Craig P. , Lin David C.
Published: July 2020

The force-velocity (F-V) properties of isolated muscles or muscle fibers have been well studied in humans and other animals. However, determining properties of individual muscles in vivo remains a challenge because muscles usually function within a synergistic group. Modeling has been used to estimate the properties of an individual muscle from the experimental measurement of the muscle group properties. While this approach can be valuable, the models and the associated predictions are difficult to validate. In this study, we measured the in situ F-V properties of the maximally activated kangaroo rat plantarflexor group and used two different assumptions and associated models to estimate the properties of the individual plantarflexors. The first model (Mdl1) assumed that the percent contributions of individual muscles to group force and power were based upon the muscles’ cross-sectional areas and were constant across the different isotonic loads applied to the muscle group. The second model (Mdl2) assumed that the F-V properties of the fibers within each muscle were identical, but due to differences in muscle architecture, the muscles’ contributions to the group properties changed with isotonic load. We compared the two model predictions to independent estimates of the muscles’ contributions based upon sonomicrometry (SONO) measurements of muscle lengths. We found that predictions from Mdl2 were not significantly different from SONO based estimates while those from Mdl1 were significantly different. The results of this study show that incorporating appropriate fiber properties and muscle architecture is necessary to parse the individual muscles’ contributions to the group F-V properties.
Oral and pre-absorptive sensing of amino acids relates to hypothalamic control of food intake in rainbow trout
Authors: Comesaña Sara , Conde-Sieira Marta , Velasco Cristina , Soengas José L. , Morais Sofia
Published: July 2020

To assess the putative role of taste and pre-absorptive sensing of amino acids in food intake control in fish, we carried out an oral administration with L-leucine, L-valine, L-proline or L-glutamic acid in rainbow trout (Oncorhynchus mykiss). Treatment with proline significantly reduced voluntary food intake at 2h and 3h after oral administration, while glutamic acid showed a less pronounced satiating effect at 3h. The mRNA expression of taste receptor subunits tas1r1, tas1r2a, tas1r2b, and tas1r3 was measured in the epithelium overlying the bony basyhyal of the fish (analogous to the tetrapod tongue) at 10, 20 or 30 min following treatment. No significant changes were observed, except for a tas1r down-regulation by valine at 30 mins. Of the downstream taste signalling genes that were analysed in parallel, plcb2 and possibly trpm5 (non-significant trend) were down-regulated 20 min after proline and glutamic acid treatment. The signal originated in the oropharyngeal and/or gastric cavity presumably relays to the brain since changes in genes involved in the regulation of food intake occurred in hypothalamus 10-30 min after oral treatment with amino acids. In particular, proline induced changes consistent with an increased anorexigenic potential in the hypothalamus. We have therefore demonstrated, for the first time in fish, that the peripheral (pre-absorptive) detection of an amino acid (L-proline), presumably by taste-related mechanisms, elicits a satiety signal that in hypothalamus is translated into changes in cellular signalling and neuropeptides regulating food intake, ultimately resulting in decreased food intake.
Cardiorespiratory coupling in cetaceans; a physiological strategy to improve gas exchange?
Authors: Fahlman A. , Miedler S. , Marti-Bonmati L. , Fernandez D. Ferrero , Caballero P. Muñoz , Arenarez J. , Rocho-Levine J. , Robeck T. , Blawas A.
Published: July 2020

In the current study we used transthoracic echocardiography to measure stroke volume (SV), heart rate (fH), and cardiac output (CO) in adult bottlenose dolphins (Tursiops truncatus), a male beluga calf (Delphinapterus leucas, body mass [Mb] range: 151-175 kg), and an adult female false killer whale (Pseudorca crassidens, estimated Mb: 500-550 kg) housed in managed care. We also recorded continuous electrocardiogram (ECG) in the beluga, bottlenose dolphin, false killer whale, killer whale (Orcinus orca), and pilot whale (Globicephala macrorhynchus) to evaluate cardiorespiratory coupling while breathing spontaneously under voluntary control. The results show that cetaceans have a strong Respiratory Sinus Arrythmia (RSA), during which both fH and SV vary within the interbreath interval, making average values dependent on the breathing frequency (fR). The RSA-corrected fH was lower for all cetaceans compared to similarly sized terrestrial mammals breathing continuously. As compared with terrestrial mammals, the RSA-corrected SV and CO were either lower or the same for the dolphin and false killer whale, while both were elevated in the beluga. When plotting fR against fH for an inactive mammal, cetaceans had a greater cardiac response to changes in fR as compared with terrestrial mammals. We propose that these data indicate an important coupling between respiration and cardiac function that enhances gas exchange, and that this RSA is important to maximize gas exchange during surface intervals, similar to that reported in the elephant seal.
Auditory evoked potentials of utricular hair cells in the plainfin midshipman,Porichthys notatus
Authors: Rogers Loranzie S. , Sisneros Joseph A.
Published: July 2020

The plainfin midshipman, Porichthys notatus, is a soniferous marine teleost fish that generates acoustic signals for intraspecific social communication. Nocturnally active males and females rely on their auditory sense to detect and locate vocally active conspecifics during social behaviors. Previous work showed that the midshipman inner ear saccule and lagena are highly adapted to detect and encode socially relevant acoustic stimuli, but the auditory sensitivity and function of the midshipman utricle remain largely unknown. Here, we characterize the auditory evoked potentials from hair cells in the utricle of non-reproductive type I males and test the hypothesis that the midshipman utricle is sensitive to behaviorally-relevant acoustic stimuli. Hair cell potentials were recorded from the rostral, medial and caudal regions of the utricle in response to pure tone stimuli presented by an underwater speaker. We show that the utricle is highly sensitive to particle motion stimuli produced by an underwater speaker positioned in the horizontal plane. Utricular potentials were recorded across a broad range of frequencies with lowest particle acceleration (dB re: 1 ms−2) thresholds occurring at 105 Hz (lowest frequency tested; mean threshold=-32 dB re: 1 ms−2) and highest thresholds at 605 to 1005 Hz (mean threshold range=−5 to −4 dB re: 1 ms−2). The high gain and broadband frequency sensitivity of the utricle suggests that it likely serves a primary auditory function and is well suited to detect conspecific vocalizations including broadband agonistic signals and the multiharmonic advertisement calls produce by reproductive type I males.
Under pressure: the extraordinary survival of seal lice in the depth of the sea
Authors: Leonardi Maria Soledad , Crespo José E. , Soto Florencia A. , Vera Ricardo B. , Rua Julio C. , Lazzari Claudio R.
Published: July 2020

Lice from pinnipeds, i.e. sea lions, seals, and walruses, are the only insects capable of surviving marine dives. Along their evolutionary history, they adapted to tolerate hypoxia, high salinity, low temperature and, in particular, to tolerate conditions of high hydrostatic pressure. To understand the limits of the capacity of lice to survive during host deep dives, we conducted a series of controlled experiments in the laboratory. We collected lice from elephant seals and submitted the different life stages to high pressure conditions. Lice were first exposed to one of four hydrostatic pressures: (a) 30 Kg/cm2; (b) 80 Kg/cm2; (c) 150 Kg/cm2, or (d) 200 Kg/cm2. They were then exposed a second time to higher or lower hydrostatic pressure conditions to test for the impact of the first experience, which could either be deleterious or trigger physiological adaption, allowing them a better tolerance to high pressure. We found that lice from elephant seals can tolerate hydrostatic pressures higher than 200 Kg/cm2 (close to 200 atm), equivalent to 2000 m depth. Adults exhibited lower recovery times than nymphs after immersion at high hydrostatic pressure. Our findings show that lice developed unique adaptations to endure extreme marine conditions. We discuss these extreme performances as related to the morphological characteristics and physiological responses to diving in these insects.