bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationales of Trade Mark Protection
Authors: Annette Kur , Senftleben Martin
Published: March 2021

Although trade mark law is generally regarded as forming part of the larger body of intellectual property, the protection mechanism underlying its functioning is distinct from other intellectual property rights. Patents, copyright, or design rights award creative or innovative achievements with a limited period of market exclusivity thus creating artificial scarcity of the respective commodities. This grants the proprietor of such rights the possibility to raise prices above the marginal costs so as to recoup the investments made. Whether and to what extent that strategy is successful and even allows gaining a premium is determined by the market. Trade mark law coincides with that scheme insofar as it also engages market forces to determine commercial gains or losses. However, instead of creating artificial exclusivity of the goods or services offered, it provides a communication channel for entrepreneurs, so as to identify the goods or services originating from their business, distinguish them from competing goods, and transport product-related messages they want to convey to their customers. This, by reflex, provides information to the market, guiding consumer choice towards goods satisfying their demands, and helping to avoid those they do not want, at minimal search costs (see paragraph 1.08 et seq.). Thus, instead of restricting competition on the production level, trade marks are designed as an enabling tool without which competition in today’s mass markets would not function at all.
Acquisition Of Rights
Authors: Annette Kur , Senftleben Martin
Published: March 2021

Under European trade mark law, protection is only acquired through registration (Article 6 EUTMR; Article 1 TMD). Whether the mark is actually used or not is of no relevance at this stage: neither is it a requirement for protection, nor does it grant a substantive right under the European Union Trade Mark Regulation (EUTMR) or the Trade Mark Directive (TMD). However, such protection may follow from national law. Member States are free to grant use-based trade mark protection within their jurisdiction, and in a number of them—Austria, Germany, Italy, the Nordic countries, and, in the form of passing off, the United Kingdom—such protection is available under terms that may differ from country to country. The specificities of the legal regime applying to such signs are independent from the provisions in the TMD.
Limitations, Defences, and Genuine Use
Authors: Annette Kur , Senftleben Martin
Published: March 2021

As with other intellectual property rights, the exclusive rights of the trade mark proprietor are limited in several respects. At the international level, Article 17 TRIPS offers room for the adoption of ‘limited exceptions’ in domestic legislation (see paragraphs 2.68–2.72). On this basis, Article 14 of the Trade Mark Directive (TMD) and Article 12 of the European Trade Mark Regulation (EUTMR) provide a tool for reconciling the interests of the trade mark owner with competing interests of other traders and the public at large. As explained by the Court of Justice of the European Union (CJEU), these provisions, by limiting the effects of the exclusive rights of the trade mark owner, seek ‘to reconcile the fundamental interests of trade mark protection with those of free movement of goods and freedom to provide services in the common market in such a way that trade mark rights are able to fulfil their essential role in the system of undistorted competition which the Treaty seeks to establish and maintain’.
Historical Developments
Authors: Grubb Philip W , Thomsen Peter R , Hoxie Tom , Wright Gordon
Published: March 2021

This chapter describes historical developments in patent systems and patent law. It highlights key developments in the UK from 1800–2014, in the US from 1790–2014, in other industrialized countries (Germany, France, the Netherlands, Switzerland, and Japan), and in developing countries. The final section discusses international developments such as the Paris Convention, the European Patent Convention, the Unitary Patent system in Europe, the Patent Cooperation Treaty, the TRIPs Agreement, the Convention on Biological Diversity, the Patent Law Treaty, the London Agreement, and the Substantive Patent Law Treaty. These developments, which have generally acted to strengthen patent protection, did not simply happen of their own accord; political, diplomatic, and industry lobbying activities have played a larger role than any objective analysis of the economic and social benefits of the patent system.
Filing a Patent Application
Authors: Grubb Philip W , Thomsen Peter R , Hoxie Tom , Wright Gordon
Published: March 2021

This chapter first addresses questions such as whether a patent application should be filed at all, and if so, when and where to file. As a general rule, if an invention appears patentable and may be of some commercial interest, a priority application should be filed. The applicant then has one year under the Paris Convention before significant amounts of time and money must be invested in filing in other countries. If the decision is made to file in other countries, or even to proceed to obtain a patent in the home country, the first filing gives a priority date that can be relied upon later. In other words, when in doubt, file an application. The remainder of the chapter discusses non-convention filings, European patent applications, international applications, registrations and patents of importation, and petty patents.
Drafting the Claims
Authors: Grubb Philip W , Thomsen Peter R , Hoxie Tom , Wright Gordon
Published: March 2021

This chapter explains the procedure for drafting patent claims. Claims define the scope of the subject matter for which protection is sought, and all countries that have patents require at least one. A competitor does not infringe and cannot be stopped unless he makes, sells, offers for sale, imports, or does something falling within the scope of at least one claim of the granted patent. Some countries still interpret claims more broadly than their literal wording, whereas others do not. Therefore, claims should be drafted to cover literally what should be protected, not relying upon a court to broaden protection on the applicant’s behalf. All claims fall into one of two broad categories: they claim either a product (i.e., something tangible, or a processs (i.e., a method of making, using, or testing something). The remainder of the chapter discusses the forms and scope of claims.
How to Catch the Infringer—and How Not to be Caught
Authors: Grubb Philip W , Thomsen Peter R , Hoxie Tom , Wright Gordon
Published: March 2021

This chapter considers the issue of patent infringement from the perspectives of both the patentee and the potential infringer. When the owner of a patent becomes aware of commercial activity by a competitor, he will naturally want to know if the patent can be used to stop these activities. The first and most important question is whether the competitor’s actions are tantamount to infringement. Finding an answer to this question means analysing the scope of the claims of the patent in the country in question, as there are considerable differences from country to country in the way in which claims are interpreted. Every company that puts a product on the market or uses a process is a potential infringer of one or more of thousands of patents presently in force, so a thorough search should be carried out for any patents that might be infringed.
Patents and Competition Law—United States
Authors: Grubb Philip W , Thomsen Peter R , Hoxie Tom , Wright Gordon
Published: March 2021

This chapter considers competition law in the US. Historically, the US has taken a stricter view than UK law of attempts to extend the patent monopoly beyond its legal scope, and has placed more restrictions on the freedom of a licensor. There are two main sources of US law in such matters: one is the common law doctrine of patent misuse; the other is the statute law—particularly the Sherman and Clayton antitrust Acts. The chapter discusses the following: the Sherman and Clayton antitrust Acts, patent misuse and antitrust, reverse payments, patent licence agreements, validity challenge by licensees, Justice Department guidelines, and collaboration between the US Justice Department and the European Commission.
The Nature of the Privacy Interest
Authors: Moreham N A
Published: March 2021

It has often been said that privacy is an elusive concept which defies precise definition. It has been used to protect interests as diverse as the right to the confidentiality of one’s correspondence to the right to access abortion services or to have one’s post-operative transgender identity recognized. Conceptions of what is private also differ from one individual to another—what one person will be happy to post on Facebook, another will regard as an intimate secret.
Health and Safety Regulators
Authors: Fairgrieve Duncan , Squires QC Dan
Published: March 2021

‘Health and safety regulators’ are public authorities whose primary purpose is to supervise the activities of third parties engaged in dangerous activities. Their aim is to provide protection from physical harm. This chapter examines the circumstances in which such regulators will be held liable in tort if their carelessness causes physical or economic losses to members of the public, or to those whose activities are the subject of the regulation. We consider other regulatory bodies, such as those concerned with planning and banking in Chapter 14, and we consider the potential liability of bodies concerned with providing information and warnings on health, but not with the direct regulation of potentially dangerous activities, in Chapter 18.
Physical Activity, Sedentary Behavior, and Skeletal Muscle Strength in Patients With Chronic Kidney Disease: An Isotemporal Substitution Approach
Authors: Yoshioka Masaki , Kosaki Keisei , Matsui Masahiro , Takahashi Kanako , Shibata Ai , Oka Koichiro , Kuro-O Makoto , Saito Chie , Yamagata Kunihiro , Maeda Seiji
Published: March 2021

Objective

Insufficient physical activity and excessive sedentary behavior can contribute to decreased skeletal muscle strength, which is strongly associated with increased mortality in patients with chronic kidney disease (CKD). However, the potential impact of replacing sedentary behavior with physical activity on skeletal muscle strength remains unclear in these individuals. The purpose of this study was to examine the associations of physical activity, sedentary behavior, and skeletal muscle strength in patients with CKD using an isotemporal substitution model to estimate the associations on replacing time from one behavior to another while keeping the total time and other behaviors fixed.

Methods

A total of 108 patients with CKD (mean age = 65 [SD = 9] y; mean estimated glomerular filtration rate = 57 [SD = 22] mL/min/1.73 m2) participated in this cross-sectional analysis study. The time spent in sedentary behavior, light-intensity physical activity, and moderate- to vigorous-intensity physical activity (MVPA) was assessed using a triaxial accelerometer. Handgrip strength, isometric knee extension strength, and 30-second chair stand test were used to measure skeletal muscle strength.

Results

In multivariate analyses (single-factor and partition models), the time spent in MVPA was beneficially associated with both isometric knee extension strength and 30-second chair stand test. Furthermore, the isotemporal substitution model found that replacing 10 min/d of sedentary behavior or light-intensity physical activity with equivalent MVPA time was beneficially associated with both isometric knee extension strength and 30-second chair standtest.

Conclusion

These cross-sectional findings indicate that MVPA time is beneficially associated with lower extremity muscle strength and that a slight increase in the MVPA time may contribute to maintaining skeletal muscle strength in patients with CKD.

Impact

Increasing the time spent in MVPA (10 min/d) may be a feasible strategy in patients with CKD who have a high prevalence of impaired physical function.
Sleep actigraphy time-synchronized with wind turbine output
Authors: Michaud David S , Keith Stephen E , Guay Mireille , Voicescu Sonia , Denning Allison , McNamee James P
Published: March 2021

Studies have yielded inconsistent evidence for an association between long-term average wind turbine sound pressure level (SPL) and disturbed sleep. Transient changes in sleep may be more susceptible to short-term variations in wind turbine SPL throughout the sleep period time. We analyzed sleep actigraphy data (participant sleep nights = 2,094, males = 151, females = 192) in 10 min intervals time-synchronized to wind turbine supervisory control and data acquisition. Calculated indoor wind turbine SPL was considered after adjusting for turbine rotor speed and closed/open bedroom windows. Maximum calculated nightly average wind turbine SPL reached 44.7 dBA (mean = 32.9, SD = 6.4) outdoors and 31.4 dBA (mean = 12.5, SD = 8.3) indoors. Wind turbine SPL in 10 min intervals, and nightly averages, was not statistically associated with actigraphy outcomes. However, the variability in wind turbine SPL due to changes in wind turbine operation across the sleep period time, as measured by the difference between the 10 min SPL and the nightly average SPL (∆SPL), was statistically related to awakenings (p = 0.028) and motility (p = 0.015) rates. These diminutive differences translate to less than 1 min of additional awake and motility time for a 5 dBA increase over a 450 min sleep period time. Overall results showed that wind turbine SPL below 45 dBA was not associated with any consequential changes in actigraphy-measured sleep. Observations based on ∆SPL provided some indication that a more sensitive assessment of sleep may be one that considers variations in wind turbine SPL throughout the sleep period time.
Obstructive sleep apnea treatment and dementia risk in older adults
Authors: Dunietz Galit L , Chervin Ronald D , Burke James F , Conceicao Alan S , Braley Tiffany J
Published: March 2021

Study Objectives

To examine associations between positive airway pressure (PAP) therapy, adherence and incident diagnoses of Alzheimer’s disease (AD), mild cognitive impairment (MCI), and dementia not otherwise specified (DNOS) in older adults.

Methods

This retrospective study utilized Medicare 5% fee-for-service claims data of 53,321 beneficiaries, aged 65 and older, with an obstructive sleep apnea (OSA) diagnosis prior to 2011. Study participants were evaluated using ICD-9 codes for neurocognitive syndromes (AD [n = 1,057], DNOS [n = 378], and MCI [n = 443]) that were newly identified between 2011 and 2013. PAP treatment was defined as the presence of at least one durable medical equipment (Healthcare Common Procedure Coding System [HCPCS]) code for PAP supplies. PAP adherence was defined as at least two HCPCS codes for PAP equipment, separated by at least 1 month. Logistic regression models, adjusted for demographic and health characteristics, were used to estimate associations between PAP treatment or adherence and new AD, DNOS, and MCI diagnoses.

Results

In this sample of Medicare beneficiaries with OSA, 59% were men, 90% were non-Hispanic whites and 62% were younger than 75 years. The majority (78%) of beneficiaries with OSA were prescribed PAP (treated), and 74% showed evidence of adherent PAP use. In adjusted models, PAP treatment was associated with lower odds of incident diagnoses of AD and DNOS (odds ratio [OR] = 0.78, 95% confidence interval [95% CI]: 0.69 to 0.89; and OR = 0.69, 95% CI: 0.55 to 0.85). Lower odds of MCI, approaching statistical significance, were also observed among PAP users (OR = 0.82, 95% CI: 0.66 to 1.02). PAP adherence was associated with lower odds of incident diagnoses of AD (OR = 0.65, 95% CI: 0.56 to 0.76).

Conclusions

PAP treatment and adherence are independently associated with lower odds of incident AD diagnoses in older adults. Results suggest that treatment of OSA may reduce the risk of subsequent dementia.
Proteomics characterization of mitochondrial‐derived vesicles under oxidative stress
Authors: Vasam Goutham , Nadeau Rachel , Cadete Virgilio J. J. , Lavallée‐Adam Mathieu , Menzies Keir J. , Burelle Yan
Published: March 2021

Mitochondria share attributes of vesicular transport with their bacterial ancestors given their ability to form mitochondrial‐derived vesicles (MDVs). MDVs are involved in mitochondrial quality control and their formation is enhanced with stress and may, therefore, play a potential role in mitochondrial‐cellular communication. However, MDV proteomic cargo has remained mostly undefined. In this study, we strategically used an in vitro MDV budding/reconstitution assay on cardiac mitochondria, followed by graded oxidative stress, to identify and characterize the MDV proteome. Our results confirmed previously identified cardiac MDV markers, while also revealing a complete map of the MDV proteome, paving the way to a better understanding of the role of MDVs. The oxidative stress vulnerability of proteins directed the cargo loading of MDVs, which was enhanced by antimycin A (Ant‐A). Among OXPHOS complexes, complexes III and V were found to be Ant‐A‐sensitive. Proteins from metabolic pathways such as the TCA cycle and fatty acid metabolism, along with Fe‐S cluster, antioxidant response proteins, and autophagy were also found to be Ant‐A sensitive. Intriguingly, proteins containing hyper‐reactive cysteine residues, metabolic redox switches, including professional redox enzymes and those that mediate iron metabolism, were found to be components of MDV cargo with Ant‐A sensitivity. Last, we revealed a possible contribution of MDVs to the formation of extracellular vesicles, which may indicate mitochondrial stress. In conclusion, our study provides an MDV proteomics signature that delineates MDV cargo selectivity and hints at the potential for MDVs and their novel protein cargo to serve as vital biomarkers during mitochondrial stress and related pathologies.
The microbiome in atopic patients and potential modifications in the context of the severe acute respiratory syndrome coronavirus 2 pandemic
Authors: Lee Eun , Hong Soo-Jong
Published: March 2021

Purpose of review

Data regarding the effects of coronavirus disease 2019 (COVID-19) on host–microbiome alteration and subsequent effects on susceptibility and clinical course of COVID-19, especially in atopic patients, are currently limited. Here, we review the studies regarding the microbiome of atopic patients with other respiratory infections and discuss the potential role of probiotics as therapeutic targets for COVID-19 to decrease its susceptibility and severity of COVID-19.

Recent findings

Respiratory tract virus infection affects the gut and airway microbiome structures and host's immune function. Diverse factors in atopic diseases affect the airway and gut microbiome structures, which are expected to negatively influence host health. However, response to respiratory virus infection in atopic hosts depends on the preexisting microbiome and immune responses. This may explain the inconclusiveness of the effects of COVID-19 on the susceptibility, morbidity, and mortality of patients with atopic diseases. Beneficial probiotics may be a therapeutic adjuvant in COVID-19 infection as the beneficial microbiome can decrease the viral load in the early phase of respiratory virus infection and improve the morbidity and mortality.

Application of probiotics can be a potential adjuvant treatment in respiratory virus infection to improve host immune responses and disturbed microbiome structures in atopic patients. Further related studies involving COVID-19 are warranted in near future.
Factors leading to the risk of stroke mortality: a cross-sectional study with lung cancer patient-based large sample
Authors: Chen Lei , Zhao Xinmin , Wang Sheng
Published: March 2021

To identify the risk factors for stroke mortality among lung cancer patients on the basis of the Surveillance, Epidemiology, and End Results (SEER) database. The clinical data of lung cancer patients diagnosed between 2004 and 2016 were collected in the SEER database. The stroke mortality of lung cancer patients was compared with the general population using standardized mortality ratios (SMRs). COX proportional hazard model was applied to analyze the risk factors for stroke mortality among lung cancer patients. Among 82 454 patients, 4821 (5.85%) died of stroke. The stroke mortality rate in lung cancer patients significantly increased compared with the general population [SMR: 1.73, 95% confidential interval (95% CI), 1.69–1.78]. Differences were pronounced between the patients with stroke death and those without regarding all the basic characteristics (P < 0.001). Multivariate COX analysis showed that the risk factors for stroke mortality among lung cancer patients included increasing age, males, the black, grade II–III, distant metastasis and higher American Joint Committee on Cancer (AJCC) TNM stage, whereas adenocarcinoma was found to be a protective factor compared with squamous cell carcinoma. Increasing age, males, the black, grade II–III, distant metastasis and higher TNM stage are associated with an increased risk of stroke mortality among lung cancer patients, but adenocarcinoma with a lowered risk.
Health Care Costs of Target Attainment for Beta-Lactam Antibiotics in Critically Ill Patients: A Retrospective Analysis of the EXPAT Study
Authors: Ewoldt Tim M. J. , Abdulla Alan , Hunfeld Nicole G. M. , Muller Anouk E. , Gommers Diederik , Polinder Suzanne , Koch Birgit C. P. , Endeman Henrik
Published: March 2021

Background:

Optimizing beta-lactam antibiotic treatment is a promising method to reduce the length of intensive care unit (ICU) stay and therefore reduce ICU costs. We used data from the EXPAT trial to determine whether beta-lactam antibiotic target attainment is a cost determinant in the ICU.

Methods:

Patients included in the EXPAT trial were divided into target attainment and target nonattainment based on serum antibiotic levels. All hospital costs were extracted from the hospital administration system and categorized.

Results:

In total, 79 patients were included in the analysis. Target attainment showed a trend toward higher total ICU costs (€44,600 versus €28,200, P = 0.103). This trend disappeared when correcting for ICU length of stay (€2680 versus €2700). Renal replacement therapy was the most important cost driver.

Conclusions:

Target attainment for beta-lactam antibiotics shows a trend toward higher total costs in ICU patients, which can be attributed to the high costs of a long stay in the ICU and renal replacement therapy.
Assisted reproductive technology for women with endometriosis, a clinically oriented review
Authors: Ata Baris , Telek Savci Bekir
Published: March 2021

Purpose of review

To discuss optimal management of an assisted reproductive technology (ART) cycle in women with endometriosis.

Recent findings

New studies involving euploid embryo transfers provide more insight on the etiology of endometriosis-associated infertility. Oocyte competence to reach live birth seems unlikely to be affected by the disease. Routine medical or surgical treatment prior to an ART cycle does not appear beneficial. Short gonadotropin releasing hormone (GnRH) antagonist or progestin primed ovarian stimulation protocols seem to be proper first choices, depending on the intention for a fresh embryo transfer. Low-quality evidence supports frozen thawed over fresh embryo transfer. Ovarian stimulation for ART does not seem to be associated with symptom progression or recurrence.

How endometriosis affects fertility is still unclear, but ART is an effective pragmatic treatment. Each woman with endometriosis must be assessed with a holistic approach, and in the absence of an indication for otherwise, ART cycles can be kept simple with patient-friendly protocols. Whether a frozen embryo transfer is better than a fresh one should be investigated.
Diagnoses and Outcomes of Prosthetic Replacement of the Ocular Surface Ecosystem Treatment—A Canadian Experience
Authors: Wong Bryan M. , Garg Anubhav , Trinh Tanya , Mimouni Michael , Ramdass Stephanie , Liao Jennifer , Chandrakumar Manokaraananthan , Chan Clara C. , Slomovic Allan R.
Published: March 2021

Objectives:

To investigate underlying diagnoses and outcomes of patients undergoing Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) treatment at the first Canadian PROSE center.

Methods:

A retrospective chart review was conducted on patients referred for PROSE treatment and fitted with PROSE devices from 2018 to 2020. Data were collected on diagnoses, presenting symptoms, previous lens modalities attempted, best-corrected visual acuities (BCVAs) pre-PROSE and post-PROSE, daily wear time, and failure rates. Best-corrected visual acuities pre-PROSE and post-PROSE were compared to evaluate visual improvement.

Results:

In total, 78 patients (126 eyes) were analyzed. The most common diagnoses were keratoconus (n=39 eyes) and postcorneal graft (n=15) in the distorted cornea group, and limbal stem cell deficiency (n=17) and graft versus host disease (n=15) in the ocular surface disease (OSD) group. Most frequent symptoms included blur, photophobia, and pain. Most common lens modalities attempted pre-PROSE were conventional scleral lenses and glasses. The overall mean BCVA improvement was 0.40 logarithm of the minimal angle of resolution (logMAR) (4-lines Snellen) (P<0.0001). Best-corrected visual acuities improvement in the distorted cornea group (0.52 logMAR, 5-lines) was significantly greater than in the OSD group (0.29 logMAR, 3-lines) (P=0.004).

Conclusions:

Prosthetic replacement of the ocular surface ecosystem treatment can provide significant visual improvement for patients with distorted corneal surfaces and OSDs who failed other lens modalities.
Comparative Analysis of Two Clinical Diagnostic Methods of the Corneoscleral Geometry
Authors: Bataille Laurent , Molina-Martin Ainhoa , Piñero David P.
Published: March 2021

Purpose:

To compare the sagittal height (SH) measurements and best fit sphere (BFS) scleral curvature obtained with two different diagnostic technologies.

Methods:

Prospective, nonrandomized, and comparative study analyzing 23 healthy eyes of 23 patients (age, 14–52 years) was conducted. A complete eye examination was performed including a corneoscleral topographic analysis with the Scheimpflug camera–based system Pentacam (Oculus GmbH, Wetzlar, Germany) and afterward with the Fourier domain profilometer Eye Surface Profiler (ESP) (Eaglet-Eye, Houten, the Netherlands). Differences between devices in temporal SH (TSH), nasal SH (NSH), and mean SH (MSH) measurements at 13- and 15-mm chord length and in scleral BFS were analyzed.

Results:

Statistically significant differences were found in TSH, NSH, and MSH obtained with Pentacam and ESP (P≤0.017), with a range of agreement from 0.21 to 1.28 mm, and a clear trend of the Pentacam system to provide higher SH measurements. Significant differences were found between Pentacam scleral BFS and ESP outer BFS (P<0.001) (range agreement, 3.57 mm). Significant correlations were found between spherical equivalent and differences between devices in 15-mm TSH (r=0.485; P=0.048), as well as between the difference between devices for some SH measurements and the magnitude of such SH values (r≥0.504; P≤0.014).

Conclusion:

Sagittal height and scleral BFS measurements obtained with the two devices are not interchangeable, with an increased difference in SH measures between devices in eyes with less myopic refractive error and increased SH values.
Depressive Symptoms and Blood Pressure in African American Women
Authors: Gao Xiaosong , Barcelona Veronica , DeWan Andrew , Prescott Laura , Crusto Cindy , Sun Yan V. , Taylor Jacquelyn Y.
Published: March 2021

Background

Depression is a risk factor for hypertension, yet few studies have been conducted in African American women.

Objective

We conducted a secondary analysis of depressive symptoms and high blood pressure among African American women from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure longitudinal study (N = 250).

Methods

Logistic regression was used to examine depressive symptoms and blood pressure, adjusting for education, employment, and racism/discrimination. Growth curve modeling was used to investigate longitudinal associations between depressive symptoms and systolic (SBP) and diastolic (DBP) blood pressures at 4 time points (T1–T4).

Results

Depressive symptoms at baseline were not prospectively associated with hypertension prevalence. Participants with Beck Depression Inventory scores higher than 10 had higher estimated marginal SBP and DBP over time compared with participants with lower scores.

Conclusion

Depressive symptoms were not associated with hypertension prevalence at T4, but they were associated with higher estimated marginal SBP and DBP. Future research is needed to elucidate mechanisms and implications for clinical care and prevention.
Downsizing of a Pulsatile Total Artificial Heart—The Effect on Hemolysis
Authors: Brockhaus Moritz K. , Hildebrand Stephan , Diedrich Mario , Lowes Marvin , De Ben Heiko , Schmitz-Rode Thomas , Steinseifer Ulrich , Jansen Sebastian V.
Published: March 2021

A downsized version of the ReinHeart total artificial heart (TAH) was developed. Hemocompatibility needs to be revised since the operating point of the downsized TAH has changed to a higher pump frequency to accomplish the same cardiac output. A mock circulation loop was designed, containing a left side for hemocompatibility testing and a right side to mimic realistic work conditions. A protocol for hemolysis testing was established using pooled porcine blood with an operation point of 5 L/min, a mean outlet pressure of 100 mm Hg and a mean inlet pressure of 12 mm Hg. Six trials were performed testing two downsized TAH (one with a compliance chamber [CC] connected, necessary for a pneumatic decoupling of both membranes and one open to atmosphere) and a BPX-80 as reference pump. The average modified index of hemolysis and normalized index of hemolysis (NIH in mg/100L) from six individual trials of the reference pump were 0.34 (0.07) and 3.21 (0.61) and of the TAH open to atmosphere 4.18 (1.19) and 38.85 (10.59), respectively. In between TAH with and without CC, there was no significant difference. A NIH ratio of TAH and reference pump was calculated to minimize variation of the different blood batches used in individual trials. Due to the downsizing, the ReinHeart’s hemolysis level increased by around 22% compared with the original size version. Comparing the results to clinically approved left ventricular assist devices, the level of hemolysis can still be considered acceptable.
The Unique Balancing Act of Managing Children With Cancer and COVID-19 Infection: A Single Center Experience From South India
Authors: Totadri Sidharth , Srinivasan Hema N. , Joseph Leenu L. , Boddu Deepthi , Suresh Kochath Parvathy , Moorthy Mahesh , Mathew Leni G. , John Rikki R.
Published: March 2021

Children with cancer are vulnerable to severe infections. Balancing the intensive treatment of cancer, with the potential risk of coronavirus disease-2019 (COVID-19) related morbidity and mortality is a unique challenge. Children with cancer testing positive for severe acute respiratory syndrome coronavirus 2 virus by reverse-transcription polymerase chain reaction at our center were studied. Thirty-seven children tested positive for COVID-19 during the study period. The severity of the illness was mild, moderate, severe, and critical in 10 (27%), 13 (35%), 12 (32%), and 2 (5%) patients, respectively. Of the 14 patients with a severe/critical illness, 2 had oncological emergencies, 4 had dengue co-infection, and 1 had an inguinal bacterial abscess. All patients were discharged in a stable condition. Modification of the treatment protocol was performed in 11 (33%) of 33 patients who were on active treatment for cancer. There was a median delay of 32.5 days to administer the next cycle of chemotherapy in patients who acquired COVID-19 during cancer treatment. Six of 7 patients who were retested after 14 days remained positive by reverse-transcription polymerase chain reaction. Children with cancer with COVID-19 recover with good supportive care. Curative chemotherapy can be administered safely with appropriate modifications in children with cancer with COVID-19.
Eudemonia and Mental Bienaise in the Wake of COVID-19!
Authors: Naguy Ahmed , Moodliar-Rensburg Seshni , Alamiri Bibi
Published: March 2021

In the aftermath of COVID-19, it sounds equally important, on the part of mental health providers to undertake the onerous duty of promoting resilience, to empower individuals, foster their own natural strengths, and help them incorporate new coping strategies into their everyday lives at this exceptional moment of hardship.
Progression of Postural Asymmetry in Young Adults With Cerebral Palsy Who Are Not Walking: An Exploratory Study
Authors: Holmes Carlee , Brock Kim , Morgan Prue
Published: March 2021

Purpose:

Young adults with cerebral palsy (CP) who are not walking are at risk of developing or increasing musculoskeletal asymmetries affecting the rib cage, spine, pelvis, and hips. This longitudinal study aimed to explore postural change using the Goldsmith Indices of Body Symmetry (GIofBS) over an 18-month period in adults with CP who are not walking.

Methods:

Demographic and medical data were accessed from participant's history. Posture was recorded using the GIofBS to collect data during an 18-month period following skeletal maturity.

Results:

All participants had postural asymmetry at study onset with evidence of minimal change in some GIofBS outcome measures and fluctuations in other outcomes over 18 months.

Conclusions:

Physical therapists may use the GIofBS across the lifespan to screen for deterioration in musculoskeletal status or in assessing longer-term outcomes of interventions impacting posture in this complex population.

Video Abstract:

For more insights from the authors, see Supplemental Digital Content 1, available at: http://links.lww.com/PPT/A314.
An Unusual Presentation of Chest Pain in a Patient With Cystic Fibrosis: A Case Report
Authors: Traylor Amanda , DiPilla-George Denee , Tirakitsoontorn Pornchai
Published: March 2021

Purpose:

This case report describes the identification and treatment of costochondritis with suspected neural entrapment in a 14-year-old individual diagnosed with cystic fibrosis.

Summary of Key Points:

The individual discussed in this report had resolution of his chest pain with additional improvement in pulmonary function test results.

Statement of Conclusion and Recommendations for Clinical Practice:

This case supports the need for musculoskeletal and neuromuscular screening and intervention for patients with cystic fibrosis. The success of the intervention suggests that when traditional approaches to treatment of costochondritis fail, use of myofascial release at the accessory muscles of breathing could be beneficial.
Blood Pressure Treatment in Kidney Transplant Recipients—Can We Improve?
Authors: Onsøien Mari O. , Midtvedt Karsten , Reisæter Anna V. , Aasarød Knut , Waldum-Grevbo Bård , Vikse Bjørn Egil , Eriksen Bjørn Odvar , Åsberg Anders
Published: March 2021

Background.

Hypertension in kidney transplant (KTx) recipients is common, affecting both patient and graft survival. Annual data from the Norwegian Renal Registry reveal that <50% of adult (>18 y) KTx recipients reach target blood pressure (BP) ≤130/80 mm Hg. The aim of this study was to identify the determinants of failure to achieve BP control.

Methods.

In conjunction with the 2018 annual data reporting, additional questions were added for recipients with BP >130/80 mm Hg (treating physician´s target BP for each patient, reasons for not achieving target, method of measurement).

Results.

Annual forms were received from 98% (3407 of 3486) of KTx recipients, with 1787 (52%) reporting a BP >130/80 mm Hg (“above-target” group). These recipients were older, mostly male, with higher body mass index and serum creatinine levels (P < 0.05) compared with patients with controlled hypertension (“on-target” group). Valid survey answers were available for 84% of the “above-target” group (Survresp) with no significant demographic differences versus nonresponders (Survnonresp). Among Survresp, 32% were under antihypertensive dose titration, whereas dose-limiting side effects were reported in 7%. Target BP was confirmed to 130/80 mm Hg for 60% of Survresp. In recipients for whom the treating physician set target BP >130/80 mm Hg, 51% did not reach these individual targets. The number of antihypertensive drugs was significantly higher in the “above-target” group versus “on-target” group (mean 2.1 ± 1.2 versus 1.8 ± 1.3) and 36% versus 25% used ≥3 antihypertensive drugs (P < 0.05). Automatic attended BP measurement was utilized by 51%.

Conclusions.

In KTx recipients, a higher BP target achievement seems possible, potentially in the range of 75%-80%.
Odor Identification Testing Can Assist in the Clinical Distinction Between Psychiatric Disorders and Neurological/Neurodegenerative Disorders
Authors: Pachi Ioanna , Evans Andrew H. , Loi Samantha M. , Eratne Dhamidhu , Malpas Charles B. , Walterfang Mark , Farrand Sarah , Kelso Wendy , Stefanis Leonidas , Velakoulis Dennis
Published: March 2021

Background/Objectives:

The aim was to identify whether performance on olfactory identification can distinguish neurological/neurodegenerative disorders (NNDs) from primary psychiatric disorders (PPDs).

Methods:

This is a cross-sectional retrospective study of inpatients assessed in Neuropsychiatry, Royal Melbourne Hospital. Data extracted from the admission records included: demographics, tobacco use, medical comorbidities, cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), and odor identification using the Sniffin’ Sticks Screening 12 test. The final diagnosis for patients was informed by established diagnostic criteria.

Results:

A total 121 patients were included. Eighty-eight patients (73%) were diagnosed with neurological or neurodegenerative disease, including Alzheimers dementia, frontotemporal dementia, Lewy body parkinsonian-related dementias (Parkinson disease, multiple system atrophy, dementia with Lewy bodies) and other neurological causes of dementia; 33 patients (27%) were diagnosed with PPDs (including mood and psychotic disorders). Patients who scored ≤8 on the Sniffin’ Sticks Screening 12 test were more likely to have NND than PPD, even after adjustment for age, sex and tobacco use (P=0.009, adjusted odds ratios=3.85, 95% confidence interval=1.40-10.62). Receiver operating characteristic curve analyses demonstrated that a score of ≤8 differentiated NND from PPD with sensitivity of 57% and specificity of 73% (receiver operating characteristic area under the curve of 0.67, P=0.004).

Conclusions:

Patients with neuropsychiatric difficulties who score 8 or less on Sniffin’ Sticks are more likely to have a neurodegenerative illness. A cut-off score of 8 is potentially a “red flag” for clinicians faced with the diagnostic question of PPD versus NND.
Dapagliflozin: an effective adjunctive treatment in type 1 diabetes
Authors: Yadegarfar Ghasem , Livingston Mark , Cortes Gabriela , Alshames Ramadan , Leivesley Kate , Metters Ann , Horne Linda , Steele Tom , Heald Adrian H.
Published: March 2021

Introduction

Many people with type 1 diabetes (T1DM) continue to run high HbA1c levels with an associated elevated risk of cardiovascular events and increased mortality. We describe here how adjunctive prescription of an SGLT2 inhibitor has improved the glycaemic control of several people with T1DM, where the new technology has been intensively deployed.

Methods

We report outcomes of six adults with T1DM who have been given dapagliflozin in East Cheshire, UK. Initiation was with education/support from the diabetes specialist nurses. All had an HbA1c of 70 mmol/mol (8.6%) or more before this was initiated. All had been monitoring glycemia with a FreeStyle Libre monitor for at least 6 months prior to this.

Results

The age range was 30–68 years. The mean duration of T1DM was 23.3 ± 5.5 years. All were on a basal-bolus regime. Over a 6 month period, HbA1c fell from 78.5 mmol/mol (9.3%) to 55 mmol/mol (7.2%). The greatest reduction in HbA1c was 57 mmol/mol (7.4%). Analysis of the FreeStyle Libre blood glucose records showed that the proportion of blood glucose readings on target (4–10 mmol/L) increased from 33.1 to 65.2% with the addition of dapagliflozin(P = 0.007). The proportion of blood glucose readings above target (>10 mmol/L) decreased from 68.0 to 26.4%, 6 months after initiation of dapagliflozin (P = 0.005). There was no increase in symptomatic hypoglycemia.

Conclusion

Dapagliflozin as adjunctive therapy to basal-bolus regime insulin in individuals with T1DM was well tolerated and improved glycemic control with no increase in hypoglycemia. We provide further evidence of the value of this intervention.
Acute cardiac overload does not induce cardiac or skeletal expression of fibroblast growth factor 23 in rats
Authors: Fajol Abul , Komaba Hirotaka , Ishioka Chigusa , Wada Takehiko , Fukagawa Masafumi
Published: March 2021

Objective

Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular events, particularly heart failure. Although FGF23 has been reported to induce cardiac hypertrophy, recent studies demonstrated that cardiac hypertrophy and myocardial infarction induce FGF23 production by cardiomyocytes. We aimed to explore whether acute cardiac overload increases cardiac and skeletal FGF23 expression and circulating FGF23 levels.

Methods

We administered 30 μL/g bodyweight of isotonic saline intraperitoneally in rats to induce acute cardiac overload. We measured serum FGF23 levels and other parameters of mineral metabolism at 2, 6, and 24 h after saline or sham injection. We also analyzed gene expression in the heart, calvarium, femur, and kidney at 2 and 24 h after injection.

Results

Acute saline injection induced cardiac overload as evidenced by a significant upregulation of brain natriuretic peptide along with a trend towards increased expression of atrial natriuretic peptide and mild hyponatremia. However, there were no changes in serum FGF23 levels or FGF23 expression in the heart, calvarium, or femur.

Conclusions

Acute cardiac overload by saline injection in rats did neither induce FGF23 expression in the heart or bone nor did it increase serum FGF23 levels. These findings suggest that more severe or long-term cardiac damage is required for induction of FGF23 expression.
Model selection reveals the butyrate-producing gut bacteriumCoprococcus eutactusas predictor for language development in three-year-old rural Ugandan children
Authors: Kort Remco , Schlösser Job , Vazquez Alan R. , Atukunda Prudence , Muhoozi Grace K.M. , Wacoo Alex Paul , Sybesma Wilbert F.H. , Westerberg Ane C. , Iversen Per Ole , Schoen Eric D.
Published: March 2021

Introduction

The metabolic activity of the gut microbiota plays a pivotal role in the gut-brain axis through the effects of bacterial metabolites on brain function and development. In this study we investigated the association of gut microbiota composition with language development of three-year-old rural Ugandan children.

Methods

We studied the language ability in 139 children of 36 months in our controlled maternal education intervention trial to stimulate children’s growth and development. The dataset includes 1170 potential predictors, including anthropometric and cognitive parameters at 24 months, 542 composition parameters of the children’s gut microbiota at 24 months and 621 of these parameters at 36 months. We applied a novel computationally efficient version of the all-subsets regression methodology and identified predictors of language ability of 36-months-old children scored according to the Bayley Scales of Infant and Toddler Development (BSID-III).

Results

The best three-term model, selected from more than 266 million models, includes the predictorsCoprococcus eutactusat 24 months of age,Bifidobacteriumat 36 months of age, and language development at 24 months. The top 20 four-term models, selected from more than 77 billion models, consistently includeCoprococcus eutactusabundance at 24 months, while 14 of these models include the other two predictors as well. Mann-Whitney U tests further suggest that the abundance of gut bacteria in language non-impaired children (n= 78) differs from that in language impaired children (n= 61) at 24 months. While obligate anaerobic butyrate-producers, includingCoprococcus eutactus, Faecalibacterium prausnitzii, Holdemanella biformis, Roseburia hominisare less abundant, facultative anaerobic bacteria, includingGranulicatella elegans, Escherichia/ShigellaandCampylobacter coli, are more abundant in language impaired children. The overall predominance of oxygen tolerant species in the gut microbiota of Ugandan children at the age 24 months, expressed as the Metagenomic Aerotolerant Predominance Index (MAPI), was slightly higher in the language impaired group than in the non-impaired group (P= 0.09).

Conclusions

Application of the all-subsets regression methodology to microbiota data established a correlation between the relative abundance of the anaerobic butyrate-producing gut bacteriumCoprococcus eutactusand language development in Ugandan children. We propose that the gut redox potential and the overall bacterial butyrate-producing capacity could be factors of importance as gut microbiota members with a positive correlation to language development are mostly strictly anaerobic butyrate-producers, while microbiota members that correlate negatively, are predominantly oxygen tolerant with a variety of known adverse effects.
Changes in live births, preterm birth, low birth weight, and cesarean deliveries in the United States during the SARS-CoV-2 pandemic
Authors: Gemmill Alison , Casey Joan A. , Catalano Ralph , Karasek Deborah , Bruckner Tim
Published: March 2021

Background

The SARS-CoV-2 pandemic and associated social, economic, and clinical disruption have been widely speculated to affect pregnancy decision-making and outcomes. While a few US-based studies have examined subnational changes in fertility, preterm birth, and stillbirth, there remains limited knowledge of how the pandemic impacted childbearing and a broader set of perinatal health indicators at the national-level throughout 2020. Here, we use recently released national-level data to fill this gap. Importantly, we, unlike earlier work, use time-series methods to account for strong temporal patterning (e.g., seasonality, trend) that could otherwise lead to spurious findings.

Methods

For the years 2015 to 2020, we obtained national monthly counts of births and rates (per 100 births) for six perinatal indicators: preterm birth (<37 weeks gestation), early preterm birth (<34 weeks gestation), late preterm birth (34-36 weeks gestation), low birth weight birth (<2500 g), very low birth weight birth (<1500 g), and cesarean delivery. We use an interrupted time-series approach to compare the outcomes observed after the pandemic began (March 2020) to those expected had the pandemic not occurred.

Results

For total births as well as five of the six indicators (i.e., all but the rate of cesarean delivery), observed values fall well below expected levels (p<.0001 for each test) during the entire pandemic period. Declines in preterm birth and low birth weight were largest in magnitude in both early and later stages of the 2020 pandemic, while those for live births occurred at the end of the year.

Discussion

Our findings provide some of the first national evidence of substantial reductions in live births and adverse perinatal outcomes during the SARS-CoV-2 pandemic. Only cesarean delivery appeared unaffected. These declines were not uniform across the pandemic, suggesting that several mechanisms, which require further study, may explain these patterns.