bluuebunny/crossref_metadata_2025 huggingface dataset:
Doxycycline-Coated Silicone Breast Implants Reduce Acute Surgical-Site Infection and Inflammation
Authors: Baker Jennifer E. , Seitz Aaron P. , Boudreau Ryan M. , Skinner Mitchell J. , Beydoun Ahmed , Kaval Necati , Caldwell Charles C. , Gulbins Erich , Edwards Michael J. , Gobble Ryan M.
Published: August 2020

Background:

Surgical-site infection after implant-based breast reconstruction remains a leading cause of morbidity. Doxycycline is an antibiotic used to treat soft-tissue infections. The authors hypothesize that doxycycline-coated breast implants will significantly reduce biofilm formation, surgical-site infection, and inflammation after bacterial infection.

Methods:

Pieces of silicone breast implants were coated in doxycycline. In vitro studies to characterize the coating include Fourier transmission infrared spectroscopy, elution data, and toxicity assays (n = 4). To evaluate antimicrobial properties, coated implants were studied after methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa inoculation in vitro and in a mouse model at 3 and 7 days (n = 8). Studies included bacterial quantification, cytokine profiles, and histology.

Results:

Coated silicone breast implants demonstrated a color change, increased mass, and Fourier transmission infrared spectroscopy consistent with a doxycycline coating. Coated implants were nontoxic to fibroblasts and inhibited biofilm formation and bacterial adherence after MRSA and P. aeruginosa incubation in vitro, and measurable doxycycline concentrations at 24 hours were seen. In a mouse model, a significant reduction of MRSA and P. aeruginosa bacterial colonization after 3 and 7 days in the doxycycline-coated implant mice was demonstrated when compared to the control mice, control mice treated with intraperitoneal doxycycline, and control mice treated with a gentamicin/cefazolin/bacitracin wash. Decreased inflammatory cytokines and inflammatory cell infiltration were demonstrated in the doxycycline-coated mice.

Conclusions:

A method to coat silicone implants with doxycycline was developed. The authors’ doxycycline-coated silicone implants significantly reduced biofilm formation, surgical-site infections, and inflammation. Further studies are needed to evaluate the long-term implications.
Indocyanine Green Angiography Predicts Tissue Necrosis More Accurately Than Thermal Imaging and Near-Infrared Spectroscopy in a Rat Perforator Flap Model
Authors: Han Tinglu , Khavanin Nima , Wu Jinlin , Zang Mengqing , Zhu Shan , Chen Bo , Li Shanshan , Liu Yuanbo , Sacks Justin M.
Published: August 2020

Background:

Clinical examination alone is neither sensitive nor specific for predicting flap necrosis, so several technologies, including indocyanine green angiography, thermal imaging (using the FLIR ONE), and near-infrared spectroscopy, have been developed to supplement perfusion assessment. This study aims to compare the accuracy of these three methods for intraoperatively predicting clinical flap necrosis in a rat perforator flap model. The authors hypothesized that near-infrared spectroscopy, assessing oxygenation rather than direct perfusion, would yield significantly different predictions.

Methods:

A 10 × 3-cm epigastric perforator flap was elevated in 14 adult male rats weighing 250 ± 50 g. Flap perfusion was assessed immediately after flap elevation using thermal imaging, near-infrared spectroscopy, and indocyanine green angiography. Measurements were correlated to the clinical endpoint and gold standard of flap necrosis on postoperative day 7.

Results:

All three technologies detected significant differences in perfusion along flap length (all p < 0.001), and were associated with significant differences in the odds of developing flap necrosis (all p < 0.001). The areas under the receiver operating characteristic curves were 0.948 for indocyanine green angiography as an absolute value, 0.873 for relative changes with thermal imaging, and 0.792 for tissue oxygenation. The sensitivity, specificity, and accuracy for indocyanine green angiography measured as an absolute value were the highest at 97.8, 87.5, and 92 percent, respectively.

Conclusions:

Indocyanine green angiography most accurately predicted flap necrosis in this study; however, tissue oximetry and thermal imaging were also capable of predicting necrosis and represented potentially less expensive or more readily available alternatives for objective perfusion assessment. Additional research can further delineate their roles and cost-efficacy in clinical practice.
The Medial Sural Artery Perforator Flap: Lessons Learned from 200 Consecutive Cases
Authors: Deek Nidal F. AL , Hsiao Jo-Chun , Do Nicolas T. , Kao Huang-Kai , Hsu Chung-Chen , Lin Chih-Hung , Lin Cheng-Hung
Published: August 2020

Background:

The medial sural artery perforator flap is a versatile option in reconstructive microsurgery. However, most reports of this flap have been limited by sample size. This study reviews the experience of a single large-volume center using the medial sural artery perforator flap and its variants for a variety of reconstructive purposes.

Methods:

A retrospective review of all patients who received the medial sural artery perforator flap reconstruction between March of 2006 and July of 2014 was performed.

Results:

Two-hundred medial sural artery perforator flaps were used at three anatomical regions: head and neck (n = 129), upper extremity (n = 47), and lower extremity (n = 24). Flaps were transferred as free (n = 189) and pedicled (n = 11). Overall flap survival was 96 percent. Flap variants used included chimeric flap (n = 11) and dual skin paddle (n = 2). Plantaris tendon and saphenous/sural nerve graft were harvested in conjunction in 20 and seven patients, respectively. In 5 percent of the cases harvested in the conventional manner, a reliable perforator could not be found.

Conclusions:

The medial sural artery perforator flap is a reliable, alternative workhorse flap for nearly any small- to medium-size defect. It can be harvested as free or pedicled and the option to include multiple tissue components further expands its versatility.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Telemedicine and Plastic and Reconstructive Surgery: Lessons from the COVID-19 Pandemic and Directions for the Future
Authors: Saad Noah H. , AlQattan Husain T. , Ochoa Oscar , Chrysopoulo Minas
Published: August 2020

Telemedicine holds vast amounts of potential in changing the way outpatient plastic and reconstructive surgery is practiced. Before the coronavirus disease 2019 (COVID-19) pandemic, video conferencing was used by a small fraction of medical specialties. However, since the start of the pandemic, the Centers for Medicare and Medicaid Services and the largest private health insurance companies have relaxed regulations to allow the majority of specialties to use video conferencing in lieu of in-person visits. Most importantly, video conferencing minimizes patient and physician exposure in situations such as these, and decreases risk in the immunocompromised population. Video conferencing, which has been shown to be just as safe and efficacious in treating patients, offers the ability to follow up with physicians while saving travel time and travel-related expenses. This in turn correlates with increased patient satisfaction. Video conferencing also allows physicians to expand their reach to patients in rural areas seeking advanced professional advice. Incorporating video conferencing into existing practices will make for a more efficient practice, improve patient satisfaction, and decrease cost to patients and the health care system.
The Western Trauma Association at 50: Still about trauma care, friendship, family, and snow
Authors: Metzdorff Mark T. , Livingston David H. , Esrig Barry C. , Sherman Harold F.
Published: August 2020

This article is a synopsis of a book created for the 50th anniversary meeting of the Western Trauma Association in February 2020. On the occasion of the 50th Anniversary of the Western Trauma Association, a review of the organization’s history, its contribution to trauma care and the development of leaders in the field, and its enduring unique culture reveals a vibrant association grounded in the values of its founders and well-positioned to continue successfully into the next 50 years.
Major Thromboembolic Complications in Liver Transplantation: The Role of Rotational Thromboelastometry and Cryoprecipitate Transfusion
Authors: Nguyen-Buckley Christine , Gao Wei , Agopian Vatche , Wray Christopher , Steadman Randolph H. , Xia Victor W.
Published: August 2020

Background.

Although hemorrhage is a major concern during liver transplantation (LT), the risk for thromboembolism is well recognized. Implementation of rotational thromboelastometry (ROTEM) has been associated with the increased use of cryoprecipitate; however, the role of ROTEM-guided transfusion strategy and cryoprecipitate administration in the development of major thromboembolic complications (MTCs) has never been documented.

Methods.

We conducted a study on patients undergoing LT before and after the implementation of ROTEM. We defined MTC as intracardiac thrombus, pulmonary embolism, hepatic artery thrombosis, and ischemic stroke in 30 d after LT. We used a propensity score to match patients during the 2 study periods.

Results.

Among 2330 patients, 119 (4.9%) developed MTC. The implementation of ROTEM was significantly associated with an increase in cryoprecipitate use (1.1 ± 1.1 versus 2.9 ± 2.3 units, P < 0.001) and MTC (4.2% versus 9.5%, P < 0.001). Further analysis demonstrated that the use of cryoprecipitate was an independent risk factor for MTC (odds ratio 1.1, 95% confidence interval 1.04-1.24, P = 0.003). Patients with MTC had significantly lower 1-y survival.

Conclusions.

Our study suggests that the implementation of ROTEM and the use of cryoprecipitate play significant roles in the development of MTC in LT. The benefits and risks of cryoprecipitate transfusion should be carefully evaluated before administration.
Triphasic Waves Are Generated by Widespread Bilateral Cortical Networks
Authors: Kural Mustafa Aykut , Fabricius Martin , Christensen Jakob , Kaplan Peter W. , Beniczky Sándor
Published: August 2020

Purpose:

Triphasic waves (TWs) have been observed in the EEG recorded in patients with various types of encephalopathy, yet their genesis and significance is still debated. The aim of this study was to elucidate the localization of the cortical generators of TWs using EEG source imaging.

Methods:

In 20 consecutive patients who had encephalopathy with TWs, EEG source imaging of the first negative and the positive phases of the TW was performed. Three different approaches were used: equivalent current dipoles, a distributed source model, and a recently described spatial filtration method for visualizing EEG in source space.

Results:

Equivalent current dipole models failed to provide valid solutions. The distributed source model and the spatial filtration method suggested that TWs were generated by large, bilateral cortical networks, invariably involving the anterior frontal and the temporo-polar areas.

Conclusions:

Source imaging localized TWs to anterior frontal and temporo-frontal structures. Involvement of these regions is consistent with the typical pathophysiological changes of altered consciousness and cognitive changes observed in patients with TW encephalopathy.
Clinical and Electrophysiological Features of Chronic Motor Axonal Neuropathy
Authors: Zhang Dong , Geng Hongzhi , Cao Lili , Li Wei
Published: August 2020

Purpose:

To determine the clinical and electrophysiological characteristics of chronic motor axonal neuropathy (CMAN) and identify the associated similarities and differences between CMAN, acute motor axonal neuropathy (AMAN), and motor neuropathy secondary to amyotrophic lateral sclerosis.

Methods:

The study described clinical and electrophysiological features of five patients with CMAN and compared with 20 AMAN patients, 42 amyotrophic lateral sclerosis patients and 41 healthy controls. To compare the distribution of different nerve involvement in the same limb, split ratio was introduced. Split ratio of upper limb = amplitude of compound muscle action potential abductor pollicis brevis (APB)/amplitude of compound muscle action potential abductor digiti minimi, and split ratio of lower limb = amplitude of compound muscle action potential extensor digitorum brevis/amplitude of compound muscle action potential abductor hallucis.

Results:

Chronic motor axonal neuropathy patients manifested lower motor neuron syndrome with positive IgG anti-monosialoganglioside antibodies and good outcome. The CMAN patients shared similar clinical manifestation with AMAN patients except for disease course and higher Medical Research Council scores. Compared with healthy controls, the split ratio of lower limb was higher in both CMAN and AMAN, despite comparable split ratio of upper limb. There was significant difference between CMAN group and amyotrophic lateral sclerosis group in nerve involvement presented as split hand and split leg signs in amyotrophic lateral sclerosis and reverse split leg sign in CMAN.

Conclusions:

Chronic motor axonal neuropathy associated with monosialoganglioside might be a “mild” AMAN with chronic onset by similar clinical and electrophysiological features. There was a unique pattern of nerve involvement presenting as reverse split leg sign in both CMAN and AMAN.
Functional difference between the ventral visual cortex and the intraparietal sulcus in visual working memory of material properties
Authors: Fujimichi Munendo , Yamamoto Hiroki , Saiki Jun
Published: August 2020

A recent study showed that objects’ roughness (smooth or rough) was held in visual working memory (VWM) in the ventral visual cortex and the intraparietal sulcus (IPS). Here, we investigated the functional differences between these areas in the context of VWM of material properties. We focused on the process in which participants accurately extracted and maintained in their memories the glossiness and roughness of a sphere. Human participants performed two types of delayed material (glossiness or roughness) discrimination tasks in which they judged which task was to be performed based on the differences in the material properties of two sequentially presented sample spheres. This task allowed us to investigate how the visual system in the human brain could properly extract a material property and hold the information in VWM. By decoding the task information (glossiness or roughness) from the brain activity patterns in the delay period, we found that both the ventral visual cortex and the IPS contributed to maintenance in memory of material properties. We also showed different decoding patterns in the areas over the course of each trial; the ventral visual cortex performed at levels above chance performance in extracting a material property, and the IPS performed at levels above chance performance in maintaining the property in memory. These results suggest that, in VWM, material properties are visually processed in the ventral visual cortex, and the visual information is sent to the IPS to be robustly maintained.
A paraphyletic ‘Silesauridae' as an alternative hypothesis for the initial radiation of ornithischian dinosaurs
Authors: Müller Rodrigo Temp , Garcia Maurício Silva
Published: August 2020

Whereas ornithischian dinosaurs are well known from Jurassic and Cretaceous deposits, deciphering the origin and early evolution of the group remains one of the hardest challenges for palaeontologists. So far, there are no unequivocal records of ornithischians from Triassic beds. Here, we present an alternative evolutionary hypothesis that suggests consideration of traditional ‘silesaurids' as a group of low-diversity clades representing a stem group leading to core ornithischians (i.e. unambiguous ornithischians, such as
Heterodontosaurus tucki
). This is particularly interesting because it fills most of the ghost lineages that emerge from the Triassic. Following the present hypothesis, the lineage that encompasses the Jurassic ornithischians evolved from ‘silesaurids' during the Middle to early Late Triassic, while typical ‘silesaurids' shared the land ecosystems with their relatives until the Late Triassic, when the group completely vanished. Therefore, Ornithischia changes from an obscure to a well-documented clade in the Triassic and is represented by records from Gondwana and Laurasia. Furthermore, according to the present hypothesis, Ornithischia was the first group of dinosaurs to adopt an omnivorous/herbivorous diet. However, this behaviour was achieved as a secondary step instead of an ancestral condition for ornithischians, as the earliest member of the clade is a faunivorous taxon. This pattern was subsequently followed by sauropodomorph dinosaurs. Indeed, the present scenario favours the independent acquisition of an herbivorous diet for ornithischians and sauropodomorphs during the Triassic, whereas the previous hypotheses suggested the independent acquisition for sauropodomorphs, ornithischians, and ‘silesaurids'.
Mathematical modelling of breast cancer cells in response to endocrine therapy and Cdk4/6 inhibition
Authors: He Wei , Demas Diane M. , Conde Isabel P. , Shajahan-Haq Ayesha N. , Baumann William T.
Published: August 2020

Oestrogen receptor (ER)-positive breast cancer is responsive to a number of targeted therapies used clinically. Unfortunately, the continuous application of any targeted therapy often results in resistance to the therapy. Our ultimate goal is to use mathematical modelling to optimize alternating therapies that not only decrease proliferation but also stave off resistance. Toward this end, we measured levels of key proteins and proliferation over a 7-day time course in ER+ MCF-7 breast cancer cells. Treatments included endocrine therapy, either oestrogen deprivation, which mimics the effects of an aromatase inhibitor, or fulvestrant, an ER degrader. These data were used to calibrate a mathematical model based on key interactions between ER signalling and the cell cycle. We show that the calibrated model is capable of predicting the combination treatment of fulvestrant and oestrogen deprivation. Further, we show that we can add a new drug, palbociclib, to the model by measuring only two key proteins, cMyc and hyperphosphorylated RB1, and adjusting only parameters associated with the drug. The model is then able to predict the combination treatment of oestrogen deprivation and palbociclib. We illustrate the model's potential to explore protocols that limit proliferation and hold off resistance by not depending on any one therapy.
Learning from plant movements triggered by bulliform cells: the biomimetic cellular actuator
Authors: Mader Anja , Langer Max , Knippers Jan , Speck Olga
Published: August 2020

Within the framework of a biomimetic top-down approach, our study started with the technical question of the development of a hinge-free and compliant actuator inspired by plant movements. One meaningful biological concept generator was the opening and closing movements of the leaf halves of grasses. Functional morphological investigations were carried out on the selected model plant
Sesleria nitida
. The results formed the basis for further clarifying the functional movement principle with a particular focus on the role of turgor changes in bulliform cells on kinetic amplification. All findings gained from the investigations of the biological model were incorporated into a finite-element analysis, as a prerequisite for the development of a pneumatic cellular actuator. The first prototype consisted of a row of single cells positioned on a plate. The cells were designed in such a way that the entire structure bent when the pneumatic pressure applied to each individual cell was increased. The pneumatic cellular actuator thus has the potential for applications on an architectural scale. It has subsequently been integrated into the midrib of the facade shading system Flectofold in which the bending of its midrib controls the hoisting of its wings.
Structure and function in human and primate social networks: implications for diffusion, network stability and health
Authors: Dunbar R. I. M.
Published: August 2020

The human social world is orders of magnitude smaller than our highly urbanized world might lead us to suppose. In addition, human social networks have a very distinct fractal structure similar to that observed in other primates. In part, this reflects a cognitive constraint, and in part a time constraint, on the capacity for interaction. Structured networks of this kind have a significant effect on the rates of transmission of both disease and information. Because the cognitive mechanism underpinning network structure is based on trust, internal and external threats that undermine trust or constrain interaction inevitably result in the fragmentation and restructuring of networks. In contexts where network sizes are smaller, this is likely to have significant impacts on psychological and physical health risks.
Pace and stability of embryonic development affect telomere dynamics: an experimental study in a precocial bird model
Authors: Stier Antoine , Metcalfe Neil B. , Monaghan Pat
Published: August 2020

Prenatal effects on telomere length are increasingly recognized as a potential contributor to the developmental origin of health and adult disease. While it is becoming clear that telomere length is influenced by prenatal conditions, the factors affecting telomere dynamics during embryogenesis remain poorly understood. We manipulated both the pace and stability of embryonic development through varying incubation temperature and its stability in Japanese quail. We investigated the impact on telomere dynamics from embryogenesis to adulthood, together with three potential drivers of telomere shortening, growth rate, oxidative damage and prenatal glucocorticoid levels. Telomere length was not affected by our prenatal manipulation for the first 75% of embryogenesis, but was reduced at hatching in groups experiencing faster (i.e. high temperature) or less stable embryonic development. These early life differences in telomere length persisted until adulthood. The effect of developmental instability on telomere length at hatching was potentially mediated by an increased secretion of glucocorticoid hormones during development. Both the pace and the stability of embryo development appear to be key factors determining telomere length and dynamics into adulthood, with fast and less stable development leading to shorter telomeres, with the potential for adverse associated outcomes in terms of reduced longevity.
The status of the genus Prolinoborus (Pot et al. 1992) and the species Prolinoborus fasciculus (Pot et al. 1992)
Authors: Glaeser Stefanie P. , Pulami Dipen , Blom Jochen , Eisenberg Tobias , Goesmann Alexander , Bender Jennifer , Wilharm Gottfried , Kämpfer Peter
Published: August 2020

On the basis of two other publications (Yarza et al. 2013; Nemec et al. 2019) and on the basis of resequencing of the 16S rRNA gene of

Prolinoborus fasciculus

CIP 103579T it is concluded that

Prolinoborus fasciculus

CIP 103579T, which is the only available strain of the species from culture collections, does not conform to the original description given by Pot et al. (1992). The strain investigated is a member of the genus

Acinetobacter

within the

Moraxellaceae

, a family of the

Gammaproteobacteria

and not a member of the

Betaproteobacteria

as originally proposed.

Prolinoborus fasciculus

CIP 103579T shared 99.8 % 16S rRNA gene sequence similarity with

Acinetobacter lwoffii

DSM 2403T. The two strains clustered together by rpoB- and core genome-based phylogenetic analyses and shared an average nucleotide identity of 96.47% (reciprocal, 96.56 %) and a digital genome distance calculation (GGDC) value of 66.9 %. Furthermore, the two strains shared matrix-assisted laser desorption/ionization time of flight MS profiles to a high extent and showed highly similar cellular fatty acid profiles and physiological substrate utilization patterns. It is proposed that the Judicial commission consider (1) that the strain currently deposited as CIP 103579 be recognized as a member of

Acinetobacter lwoffii

; (2) placing

Prolinoborus fasciculus

(Pot et al. 1992) on the list of rejected names if a suitable replacement strain, or a neotype strain cannot be found within 2 years of publication of this request; and (3) place the genus name

Prolinoborus

(Pot et al. 1992) on the list of rejected names [Recommendation 20D (3) of the Code].
Can Public Libraries Be Leveraged to Expand Access to Telehealth? Exploration of a Strategy to Mitigate Rural Health Disparities
Authors: DeGuzman Pamela B. , Jain Neha
Published: August 2020

In the U.S., those who lack broadband internet have limited ability to connect to care providers over a telemedicine video visit (VV). During the coronavirus disease pandemic, VVs have become increasingly common, but are not equitably accessible, which may exacerbate existing health disparities. Widening health disparities are of particular concern in the rural U.S. where broadband is lacking. We term this inequity in healthcare access due to limited internet access the “digital health divide.” Because public libraries typically offer free use of broadband internet to patrons, they can help bridge the digital health divide and assist patrons with VVs. However, no guidelines currently exist for care providers and libraries to implement this needed, but potentially complex undertaking. Individual programs in which community members have used public libraries as a place from which to connect to a VV may offer insight into guidance needed. Thus, we conducted a scoping review to explore interventions reporting use of public libraries for community members to connect to a healthcare provider via telemedicine. One article was found describing the use of a public library for community members to connect to a telemedicine VV. The use of public libraries as spaces from which patrons can participate in VVs with providers is promising, but research is urgently needed to guide implementation.
Patient-specific hemodynamics of new coronary artery bypass configurations
Authors: Rezaeimoghaddam Mohammad , Oguz Gokce Nur , Ates Sanser , Bozkaya Tijen Alkan , Piskin Senol , Lashkarinia S. Samaneh , Tenekecioglu Erhan , Karagoz Haldun , Pekkan Kerem
Published: August 2020

Purpose

This study aims to quantify the patient-specific hemodynamics of complex conduit routing configurations of coronary artery bypass grafting (CABG) operation which are specifically suitable for off-pump surgeries. Coronary perfusion efficacy and local hemodynamics of multiple left internal mammary artery (LIMA) with sequential and end-to-side anastomosis are investigated. Using a full anatomical model comprised of aortic arch and coronary artery branches the optimum perfusion configuration in multi-vessel coronary artery stenosis is desired.

Methodology

Two clinically relevant CABG configurations are created using a virtual surgical planning tool where for each configuration set, the stenosis level, anastomosis distance and angle were varied. A non-Newtonian computational fluid dynamics solver in OpenFOAM incorporated with resistance boundary conditions representing the coronary perfusion physiology was developed. The numerical accuracy is verified and results agreed well with a validated commercial cardiovascular flow solver and experiments. For segmental performance analysis, new coronary perfusion indices to quantify deviation from the healthy scenario were introduced.

Results

The first simulation configuration set; - a CABG targeting two stenos sites on the left anterior descending artery (LAD), the LIMA graft was capable of 31 mL/min blood supply for all the parametric cases and uphold the healthy LAD perfusion in agreement with the clinical experience. In the second end-to-side anastomosed graft configuration set; -the radial artery graft anastomosed to LIMA, a maximum of 64 ml/min flow rate in LIMA was observed. However, except LAD, the obtuse marginal (OM) and second marginal artery (m2) suffered poor perfusion. In the first set, average wall shear stress (WSS) were in the range of 4 to 35 dyns/cm2 for in LAD. Nevertheless, for second configuration sets the WSS values were higher as the LIMA could not supply enough blood to OM and m2.

Conclusion

The virtual surgical configurations have the potential to improve the quality of operation by providing quantitative surgical insight. The degree of stenosis is a critical factor in terms of coronary perfusion and WSS. The sequential anastomosis can be done safely if the anastomosis angle is less than 90 degrees regardless of degree of stenosis. The smaller proposed perfusion index value, O(0.04-0)×102, enable us to quantify the post-op hemodynamic performance by comparing with the ideal healthy physiological flow.
In-house assembled protective devices in laboratory safety against SARS-nCoV-2 in clinical biochemistry laboratory of a COVID dedicated hospital
Authors: Dubey Abhishek , Bansal Aastha , Sonkar Subash Chandra , Goswami Binita , Makwane Naina , Manchanda Vikas , Koner Bidhan Chandra
Published: August 2020

Health Care Workers (HCWs) of diagnostic laboratory handling COVID positive samples are at risk and need to take protective measures. Many protective materials were not available when the pandemic reached India forcing laboratory managers to take innovative measures to protect the laboratory staffs. We made face shields from OHP sheets and substitute of biosafety cabinets from cardboard boxes fitted with hypochlorite spraying devices. Here we present if these two in-house developed safety devices when incorporated in standard operating procedure (SOP) of laboratory safety were effective in clinical biochemistry laboratory of dedicated COVID hospitals. We assessed contamination of laboratory surfaces (n=6) and rate of SARS-nCov-2 positivity from their nasal and throat swab by RT-PCR among laboratory personnel (n=18) after 14 days of their use along with other routine safety devices like use of gloves, surgical masks, OT gowns etc. These HCWs were checked regularly for signs and symptoms of COVID-19 and none had any signs and symptoms during these 14days. The SARS-nCov-2 test report was negative for the staff members and no surface contamination was detected. We conclude that innovative and cost effective protective devices can be built in-house with locally available resources and are effective in preventing the spread of COVID 19 among the staff working in clinical biochemistry laboratories. Laboratory managers in resource scarce areas need to be innovative to face such sudden safety challenges like COVID-19 pandemic.

The highlight of the manuscript are

Strengthening the Basics Approaches to protect the lab personnel in dedicated COVID hospital of Low-Resource Settings.

Designed and developed in-house standard operating procedure (SOP) to fill the gap and evaluate the effect in dedicated COVID-19 hospitals.

Innovative protective devices made from OHP sheets and cardboard boxes fitted with hypochlorite spraying devices as alternatives to biosafety cabinets on contamination of laboratory surfaces.

Performance of the devices were clinically validated and it can be used as alternative in low resources settings.
Remote digital measurement of visual and auditory markers of Major Depressive Disorder severity and treatment response
Authors: Galatzer-Levy Isaac R. , Abbas Anzar , Yadav Vijay , Koesmahargyo Vidya , Aghjayan Allison , Marecki Serena , Evans Miriam , Sauder Colin
Published: August 2020

Objectives

Multiple machine learning-based visual and auditory digital markers have demonstrated associations between Major Depressive Disorder (MDD) status and severity. The current study examines if such measurements can quantify response to antidepressant treatment (ADT) with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine uptake inhibitors (SNRIs).

Methods

Visual and auditory markers were acquired through an automated smartphone task that measures facial, vocal, and head movement characteristics across four weeks of treatment (with timepoints at baseline, 2 weeks, and 4 weeks) on ADT (n = 12). The Montgomery-Asberg Depression Rating Scale (MADRS) was collected concordantly through clinical interviews to confirm diagnosis and assess changes in MDD severity.

Results

Patient responses to ADT demonstrated clinically and statistically significant changes in the MADRS F(2,34) = 51.62, p <.0001. Additionally, patients demonstrated significant increases in multiple digital markers including facial expressivity, head movement, and amount of speech. Finally, patients demonstrated significant decreased frequency of fear and anger facial expressions.

Conclusion

Digital markers associated with MDD demonstrate validity as measures of treatment response.
Tracheal aspirate with closed suction device: a modified technique developed during COVID-19 outbreak
Authors: Schverdfinger Sofia , Bisso Indalecio Carboni , Famiglietti Romina , Grazia Marcelo Di , Stefano Sabrina Di , Heras Marcos Las
Published: August 2020

Background

Bacterial superinfection as well as ventilation associated pneumonia (VAP) are both frequent events in critical care. During COVID-19 pandemic, usual diagnostic practices such as bronchoalveolar lavage and tracheal aspirate are limited due to their associated high risk of exposure for the operator. In order to set primary focus on the protection of health care personnel, a modified tracheal aspiration (M-TA) technique is developed and used for acquiring a lower respiratory tract of microbiological samples with a closed suction device.

Methods

Retrospective observational study to evaluate effectiveness of M-TA is conducted.

Results

A total of 33 M-TA samples were analyzed. In 66,6% of the cases, results led to a change in medical decision making. A 100% accuracy was achieved regarding COVID-19 diagnosis and a 56% bacterial growth-rate in cultives where VAP was suspected. No health care personnel have developed symptoms nor tested positive for COVID-19 during or after sample collection.

Conclusion

M-TA technique presented could be considered as a safe and effective procedure with low percentage of complications.
Systematic bias in studies of consumer functional responses
Authors: Novak Mark , Stouffer Daniel B.
Published: August 2020

Functional responses are a cornerstone to our understanding of consumer-resource interactions, so how to best describe them using models has been actively debated. Here we focus on the consumer dependence of functional responses to evidence systematic bias in the statistical comparison of functional-response models and the estimation of their parameters. Both forms of bias are universal to nonlinear models (irrespective of consumer dependence) and are rooted in a lack of sufficient replication. Using a large compilation of published datasets, we show that – due to the prevalence of low sample size studies – neither the overall frequency by which alternative models achieve top rank nor the frequency distribution of parameter point estimates should be treated as providing insight into the general form or central tendency of consumer interference. We call for renewed clarity in the varied purposes that motivate the study of functional responses, purposes that can compete with each other in dictating the design, analysis, and interpretation of functional-response experiments.
Stimulation of the human mitochondrial transporter ABCB10 by zinc-mesoporphrin
Authors: Martinez Melissa , Fendley Gregory A. , Saxberg Alexandra D. , Zoghbi Maria E.
Published: August 2020

Heme biosynthesis occurs through a series of reactions that take place within the cytoplasm and mitochondria, thus intermediates need to move across these cellular compartments. However, the specific membrane transport mechanisms involved in the process are not yet identified. The ATP-binding cassette protein ABCB10 is essential for normal heme production, as knocking down this transporter in mice is embryonically lethal and accompanied by severe anemia plus oxidative damage. The role of ABCB10 is unknown, but given its location in the inner mitochondrial membrane, it has been proposed as a candidate to export either an early heme precursor or heme. Alternatively, ABCB10 might transport a molecule important for protection against oxidative damage. To help discern between these possibilities, we decided to study the effect of heme analogs, precursors and antioxidant peptides on purified human ABCB10. Since substrate binding increases the ATP hydrolysis rate of ABC transporters, we have determined the ability of these molecules to activate purified ABCB10 reconstituted in lipid nanodiscs using ATPase measurements. Under our experimental conditions, we found that the only heme analog increasing ABCB10 ATPase activity was Zinc-mesoporphyrin. This activation of almost seventy percent was specific for ABCB10, as the ATPase activity of a negative control bacterial ABC transporter was not affected. The activation was also observed in cysteine-less ABCB10, suggesting that Zinc-mesoporphyrin’s effect did not require binding to typical heme regulatory motifs. Furthermore, our data indicate that ABCB10 was not directly activated by neither the early heme precursor delta-aminolevulinic acid nor glutathione, downsizing their relevance as putative substrates for this transporter. Although additional studies are needed to determine the physiological substrate of ABCB10, our findings reveal Zinc-mesoporphyrin as the first tool compound to directly modulate ABCB10 activity and raise the possibility that some actions of Zinc-mesoporphyrin in cellular and animal studies could be mediated by ABCB10.
Group I p21-activated kinases in leukemia cell adhesion to fibronectin
Authors: Kuželová Kateřina , Obr Adam , Röselová Pavla , Grebeňová Dana , Otevřelová Petra , Brodská Barbora , Holoubek Aleš
Published: August 2020

P21-activated kinases (PAK) regulate many processes associated with cytoskeleton dynamics, including cell adhesion, migration, and apoptosis. PAK function is frequently altered in cancer, and PAK were proposed as therapy targets both in solid tumors and in hematological malignancies. However, current knowledge about PAK function in cell adhesion is mainly based on adherent cell models. Moreover, existing functional differences among the individual PAK family members are unsufficiently characterized.

We measured expression of PAK group I members in leukemia cell lines and in primary leukemia cells, both on protein and mRNA levels. In functional assays, we analyzed the effect of two PAK inhibitors with different mechanisms of action, IPA-3 and FRAX597. Changes in cell interaction with fibronectin were monitored through impedance measurement and by interference reflection microscopy. Cytotoxic effects of inhibitors were assessed by Annexin V/propidium iodide test. PAK intracellular localization was analyzed by confocal microscopy.

PAK2 transcript was dominant in cell lines, whereas primary leukemia cells also expressed comparable amount of PAK1, which was detected as two transcription isoforms: PAK1-full and PAK1Δ15. PAK1Δ15 and PAK2 transcript levels correlated with surface density of integrins β1 and αVβ3. PAK1-full, but not PAK2, was present in membrane protrusions. The inhibitors had partly opposed effects: IPA-3, which prevents PAK activation, induced cell contraction in semi-adherent HEL cells only. FRAX597, which inhibits PAK kinase activity, increased cell-surface contact area in all leukemia cells. Both inhibitors reduced the stability of cell attachment and induced cell death. Although many cells accumulated high FRAX597 amounts, low doses were sufficient to kill sensitive cells. FRAX597-induced cell death was fast in the MV4-11 cell line and in primary AML cells.

Although PAK group I seem to be essential for leukemia cell adhesion and survival, and might thus serve as therapy targets, many PAK functions still remain to be attributed to individual isoforms and to their functional domains.
Tumor-educated monocyte-dendritic progenitors promote a metastatic switch
Authors: Magidey-Klein Ksenia , Kveler Ksenya , Cooper Tim J. , Normand Rachelly , Zhang Tongwu , Timaner Michael , Raviv Ziv , James Brian , Gazit Roi , Ronai Ze’ev A. , Shen-Orr Shai S. , Shaked Yuval
Published: August 2020

Myeloid skewing of hematopoietic cells is a prominent promoter of metastasis. However, little is known about their education and differentiation pattern from hematopoietic stem and progenitor cells (HSPCs) during tumor progression and metastasis. Here we show that metastatic tumors dictate a unique differentiation pattern of HSPCs towards a specific myeloid progeny. Using single cell RNA-sequencing analysis integrated with proteomic screen of tumor secretome, we demonstrate that highly metastatic tumors dictate a long-lived differentiation of HSPCs towards monocyte-dendritic progenitors (MDPs) while low-metastatic tumors promote their differentiation into granulocyte-monocyte progenitors (GMPs). This effect is driven by IL-6 axis that is highly active in metastatic tumors. Consequently, loss and gain of function of IL-6 in tumor cells resulted in decreased and increased metastasis and corresponding MDP levels, respectively. Consistently, IL-6-educated MDPs but not GMPs obtained from highly metastatic tumors, adoptively transferred into mice bearing low metastatic tumors resulted in increased metastasis due to their further differentiation into immunosuppressive (M2) macrophages. Overall, our study reveals a new role for tumor-derived IL-6 that hijacks HSPC differentiation program towards myeloid cells that contribute to metastasis.
Precision digital mapping of endogenous and induced genomic DNA breaks by INDUCE-seq
Authors: Dobbs Felix M , van Eijk Patrick , Fellows Mick D , Loiacono Luisa , Nitsch Roberto , Reed Simon H.
Published: August 2020

Understanding how breaks form and are repaired in the genome depends on the accurate measurement of the frequency and position of DNA double strand breaks (DSBs). This is crucial for identification of a chemical’s DNA damage potential and for safe development of therapies, including genome editing technologies. Current DSB sequencing methods suffer from high background levels, the inability to accurately measure low frequency endogenous breaks and high sequencing costs. Here we describe INDUCE-seq, which overcomes these problems, detecting simultaneously the presence of low-level endogenous DSBs caused by physiological processes, and higher-level recurrent breaks induced by restriction enzymes or CRISPR-Cas nucleases. INDUCE-seq exploits an innovative NGS flow cell enrichment method, permitting the digital detection of breaks. It can therefore be used to determine the mechanism of DSB repair and to facilitate safe development of therapeutic genome editing. We discuss how the method can be adapted to detect other genomic features.
Discovery of 5,5’-methylenedi-2,3-cresotic acid as a potent inhibitor of chemotactic activity of the HMGB1•CXCL12 heterocomplex using Virtual Screening and NMR validation
Authors: De Leo F. , Quilici G. , De Marchis F. , Mantonico M. V. , Bianchi M. E. , Musco G.
Published: August 2020

HMGB1 is a key molecule that both triggers and sustains inflammation following infection or injury, and is involved in a large number of pathologies, including cancer. HMGB1 participates to the recruitment of inflammatory cells forming a heterocomplex with the chemokine CXCL12 (HMGB1•CXCL12), herewith activating the G-protein coupled receptor CXCR4. Thus, identification of molecules that disrupt this heterocomplex can offer novel pharmacological opportunities to treat inflammation related diseases. To identify new HMGB1•CXCL12 inhibitors we have performed a study on the ligandability of the single HMG boxes of HMGB1 followed by a virtual screening campaign on both HMG boxes using Zbc Drugs and three different docking programs (Glide, AutoDock Vina, AutoDock 4.2.6). The best poses in terms of scoring functions, visual inspection and predicted ADME properties were further filtered according to a pharmacophore model based on known HMGB1 binders and clustered according to their structures. Eight compounds representative of the clusters were tested for HMGB1 binding by NMR. We identified 5,5’-methylenedi-2,3-cresotic acid (2a) as binder of both HMGB1 and CXCL12; 2a also targets the HMGB1•CXCL12 heterocomplex. In cell migration assays 2a inhibited the chemotactic activity of HMGB1•CXCL12 with IC50 in the subnanomolar range, the best documented up to now. These results pave the way for future structure activity relationship studies to optimize the pharmacological targeting of HMGB1•CXCL12 for anti-inflammatory purposes.
The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission
Authors: Zhu Yunkai , Feng Fei , Hu Gaowei , Wang Yuyan , Yu Yin , Zhu Yuanfei , Xu Wei , Cai Xia , Sun Zhiping , Han Wendong , Ye Rong , Chen Hongjun , Ding Qiang , Cai Qiliang , Qu Di , Xie Youhua , Yuan Zhenghong , Zhang Rong
Published: August 2020

The global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. This idea was supported by the identification of a suite of endosomal entry factors specific to Sdel virus by a genome-wide CRISPR-Cas9 screen. A panel of host factors regulating the surface expression of ACE2 was identified for both viruses. Using a hamster model, animal-to-animal transmission with the Sdel virus was almost completely abrogated, unlike with Sfull. These findings highlight the critical role of the S1/S2 boundary of the SARS-CoV-2 spike protein in modulating virus entry and transmission.
The genusMicroniphargus(Crustacea, Amphipoda): evidence for three lineages distributed across northwestern Europe and transfer to Pseudoniphargidae
Authors: Weber Dieter , Stoch Fabio , Knight Lee R.F.D. , Chauveau Claire , Flot Jean-François
Published: August 2020

Microniphargus leruthiSchellenberg, 1934 (Amphipoda: Niphargidae) was first described based on samples collected in Belgium and placed in a monotypic genus within the family Niphargidae. However, some details of its morphology as well as recent phylogenetic studies suggest thatMicroniphargusmay be more closely related toPseudoniphargus(Amphipoda: Pseudoniphargidae) than toNiphargus.Moreover,M. leruthiranges over 1,469km from Ireland to Germany, which is striking since only a few niphargids have confirmed ranges in excess of 200km. To find out the phylogenetic position ofM. leruthiand check whether it may be a complex of cryptic species, we collected material from Ireland, England and Belgium then sequenced fragments of the mitochondrial cytochromecoxidase subunit 1 gene as well as of the nuclear 28S ribosomal gene. Phylogenetic analyses of both markers confirm thatMicroniphargusis closer toPseudoniphargusthan toNiphargus, leading us to reallocateMicroniphargusto Pseudoniphargidae. We also identify three congruent mito-nuclear lineages present respectively in Ireland, in both Belgium and England, and in England only (with the latter found in sympatry at one location), suggesting thatM. leruthiis a complex of at least three species with a putative centre of origin in England.