Publications by authors named "Jose Rodriguez"

1,183 Publications

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Beyond Left Ventricular Ejection Fraction Improvement in the Optimization of Cardiac Resynchronization Therapy.

Angiology 2021 May 12:33197211015551. Epub 2021 May 12.

Division of Cardiovascular Medicine, Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, USA.

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http://dx.doi.org/10.1177/00033197211015551DOI Listing
May 2021

Imaging Features of Primary Immunodeficiency Disorders.

Radiol Cardiothorac Imaging 2021 Apr 25;3(2):e200418. Epub 2021 Mar 25.

Faculty of Medical Sciences, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras (J.A.R.); Department of Radiology, Division of Cardiopulmonary Imaging, University of Colorado School of Medicine, 12401 E 17th Ave, Aurora, CO 80045 (T.J.B., D.V.); Department of Radiology, University of Texas Health Science Center, San Antonio, Tex (C.S.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (D.B.G.); and Department of Radiology, Children's Hospital Colorado, Aurora, Colo (L.P.B.).

Primary immunodeficiency disorders (PIDs), which are humoral, combined, and innate defects of the immune system, are relatively uncommon and may go undiagnosed in patients experiencing recurrent infections, resulting in increased morbidity and mortality. PIDs are clinically characterized by a broad spectrum of disorders, including repeated infections, autoimmune disorders, lymphoproliferative diseases, congenital anomalies, and increased risk of malignancy. Cardiothoracic imaging plays a crucial role in the diagnosis of PIDs owing to the high rates of repeated respiratory infections leading to bronchiectasis and other forms of chronic lung disease. Although PIDs as a group may seem similar in terms of radiologic features and clinical manifestations, there are specific entities that are pertinent to each PID on an individual level. For example, patients with common variable immunodeficiency may develop a unique granulomatous lymphocytic interstitial lung disease, and Good syndrome is associated with thymoma. Familiarity with the imaging characteristics of these disorders may expedite diagnosis and prognostication, and better direct therapy. Reviewing the thoracic manifestations of all PIDs is beyond the scope of this article; thus, the focus herein is on discussing the thoracic manifestations of the most common PIDs and their imaging features. © RSNA, 2021An earlier incorrect version appeared online. This article was corrected on March 25, 2021.
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http://dx.doi.org/10.1148/ryct.2021200418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098094PMC
April 2021

How Does Contact Length Impact Titanium Tapered Splined Stem Stability: A Biomechanical Matched Pair Cadaveric Study.

J Arthroplasty 2021 Apr 22. Epub 2021 Apr 22.

Stavros Niarchos Foundation Complex Joint Reconstruction Center, Hospital for Special Surgery, New York, NY.

Background: Titanium tapered stems (TTS) achieve fixation in the femoral diaphysis and are commonly used in revision total hip arthroplasty. The initial stability of a TTS is critical, but the minimum contact length needed and impact of implant-specific taper angles on axial stability are unknown. This biomechanical study was performed to better guide operative decision-making by addressing these clinical questions.

Methods: Two TTS with varying conical taper angles (2° spline taper vs 3.5° spline taper) were implanted in 9 right and left matched fresh human femora. The proximal femur was removed, and the remaining femoral diaphysis was prepared to allow for either a 2 cm (n = 6), 3 cm (n = 6), or 4 cm (n = 6) cortical contact length with each implanted stem. Stepwise axial load was then applied to a maximum of 2600N or until the femur fractured. Failure was defined as either subsidence >5 mm or femur fracture.

Results: All 6 femora with 2 cm of stem-cortical contact length failed axial testing, a significantly higher failure rate (P < .02) than the 4 out of 6 femora and all 6 femora that passed testing at 3 cm and 4 cm, respectively, which were not statistically different from each other (P = .12). Taper angle did not influence success rates, as each matched pair either succeeded or failed at the tested contact length.

Conclusion: 4 cm of cortical contact length with a TTS demonstrates reliable initial axial stability, while 2 cm is insufficient regardless of taper angle. For 3 cm of cortical contact, successful initial fixation can be achieved in most cases with both taper angle designs.
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http://dx.doi.org/10.1016/j.arth.2021.04.013DOI Listing
April 2021

Effects of implant rotational malposition on contact surface area after implantation of the augmented glenoid baseplate in the setting of glenoid bone loss.

Int Orthop 2021 Apr 20. Epub 2021 Apr 20.

Department of Orthopaedic Surgery, University of Illinois at Chicago, 835 S. Wolcott Ave, Rm 270, IL, Chicago, USA.

Aim Of The Study: Augmented glenoid baseplates are utilized in reverse total shoulder arthroplasty in the setting of glenoid bone loss. These implants permit lateralization of the joint line and correction of bony version abnormalities. To allow bone preservation in the setting of abnormal bony version or deficiency, the backside of the augmented glenoid baseplate is not perpendicular to the axis of the central post/screw. Thus, if the baseplate is implanted with any rotational malposition, this could affect the backside contact area available for ingrowth. The purpose of this study was to assess if rotational malpositioning of a full-wedge augmented baseplate alongside the axis of the central screw significantly affects the glenoid implant backside contact area.

Methods: Seven synthetic scapulas (Sawbones, Vashon, WA) were used to implant a 15° full-wedge glenoid baseplate (Wright Medical, Memphis, TN) according to the manufacturer's technique. The contact pressure between the baseplate and the glenoid surface at rotational positions 5°, 10°, and 15° clockwise (CW) and counterclockwise (CCW) from the central axis was measured with Extreme Low Fujifilm Prescale (Tekscan, Boston, MA). The data was analyzed digitally to obtain a percentage of contact surface area. To evaluate gross contact, a computed tomography (CT) scan was performed and manual measurements of contact between the glenoid and the baseplate were conducted using a standardized axial CT slice.

Results: The average contact area at zero degrees of malrotation was 37.26 ± 3.27%. Average contact areas for the simulated malposition cases were 13.99 ± 9.39% at 15° CCW, 24.89 ± 5.11% at 10° CW, and 19.32 ± 3.13% at 15° CW. Each of these results was significant (p < 0.003). On computed tomography, at 15° CCW, the contact area decreased by 39%; at 15° CW, the contact area decreased by 38%.

Discussion: The use of augmented glenoid baseplates presents a technical challenge. It is difficult to avoid implant malrotation along the axis of the central peg/screw, because the final rotation of the baseplate must be chosen while the implant is several centimeters away from the bone. This study found that 10° and 15° malrotation about the glenoid baseplate's central axis leads to significant decreases in the implant-bone contact area.

Conclusions: When implanting an augmented baseplate for total shoulder arthroplasty, it is important to minimize baseplate malrotation to decrease the risk of baseplate loosening.
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http://dx.doi.org/10.1007/s00264-021-05047-9DOI Listing
April 2021

Assessing variability in the ratio of metal concentrations measured by DGT-type passive samplers and spot sampling in European seawaters.

Sci Total Environ 2021 Apr 9;783:147001. Epub 2021 Apr 9.

Lancaster University, Lancaster Environment Centre, Lancaster LA1 4YQ, United Kingdom.

The current study evaluates the effect of seawater physico-chemical characteristics on the relationship between the concentration of metals measured by Diffusive Gradients in Thin films (DGT) passive samplers (i.e., DGT-labile concentration) and the concentrations measured in discrete water samples. Accordingly, Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to measure the total dissolved metal concentrations in the discrete water samples and the labile metal concentrations obtained by DGT samplers; additionally, lead and cadmium conditional labile fractions were determined by Anodic Stripping Voltammetry (ASV) and total dissolved nickel was measured by Cathodic Stripping Voltammetry (CSV). It can be concluded that, in general, the median ratios of DGT/ICP and DGT/ASV(CSV) were lower than 1, except for Ni (median ratio close to 1) and Zn (higher than 1). This indicates the importance of speciation and time-integrated concentrations measured using passive sampling techniques, which is in line with the WFD suggestions for improving the chemical assessment of waterbodies. It is the variability in metal content in waters rather than environmental conditions to which the variability of the ratios can be attributed. The ratios were not significantly affected by the temperature, salinity, pH, oxygen, DOC or SPM, giving a great confidence for all the techniques used. Within a regulatory context such as the EU Water Framework Directive this is a great advantage, since the simplicity of not needing to use corrections to minimize the effects of environmental variables could help in implementing DGTs within monitoring networks.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147001DOI Listing
April 2021

LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton.

Front Cell Dev Biol 2021 1;9:624089. Epub 2021 Apr 1.

Center for Cooperative Research in Biosciences (CIC BioGUNE), Basque Research and Technology Alliance, Bizkaia Technology Park, Derio, Spain.

LUZP1 is a centrosomal and actin cytoskeleton-localizing protein that regulates both ciliogenesis and actin filament bundling. As the cytoskeleton and cilia are implicated in metastasis and tumor suppression, we examined roles for LUZP1 in the context of cancer. Here we show that exhibits frequent genomic aberrations in cancer, with a predominance of gene deletions. Furthermore, we demonstrate that CRISPR/Cas9-mediated loss of in mouse fibroblasts promotes cell migration and invasion features, reduces cell viability, and increases cell apoptosis, centriole numbers, and nuclear size while altering the actin cytoskeleton. Loss of also induced changes to ACTR3 (Actin Related Protein 3, also known as ARP3) and phospho-cofilin ratios, suggesting regulatory roles in actin polymerization, beyond its role in filament bundling. Our results point to an unprecedented role for LUZP1 in the regulation of cancer features through the control of actin cytoskeleton.
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http://dx.doi.org/10.3389/fcell.2021.624089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049182PMC
April 2021

Intraoperative Complications and Early Return to the Operating Room in Total Hip Arthroplasty Performed Through the Direct Anterior and Posterior Approaches. An Institutional Experience of Surgeons After Their Learning Curve.

J Arthroplasty 2021 Mar 26. Epub 2021 Mar 26.

Department of Orthopaedic Surgery, Division of Adult Reconstruction and Joint Rerplacement, Hospital for Special Surgery, New York, NY.

Background: Proponents of the direct anterior approach (DAA) for total hip arthroplasty (THA) claim a faster recovery, whereas critics claim an increased risk of early femoral complications. This study analyzed intraoperative and postoperative complications requiring reoperation within one year after THA through the DAA and posterior approach (PA).

Methods: A total of 2348 elective, unilateral DAA THAs in patients with osteoarthritis performed between 2016 and 2019 were matched 1:1 for age (±5 years), gender, body mass index (±5), and femoral fixation with 2348 patients who underwent PA THA during the same period. Mixed-effects logistic regression was used. Odds ratios were reported for the occurrence of intraoperative femoral fracture, postoperative femoral fracture, infection, dislocation, and other etiologies requiring reoperation within one year.

Results: Intraoperative femoral fracture occurred in 12 DAA (0.5%) and 14 PA (0.6%) patients. Twenty-five patients (1.06%) in the DAA and 28 (1.19%) in the PA group underwent reoperation within the first year. Reoperations were due to periprosthetic fracture (40%), infection (28%), dislocation (23%), and other (9%). Regression analysis revealed no difference in intraoperative femoral fracture (odds ratio (OR): 0.86, 95% confidence interval (CI): 0.40-1.86, P = .69), postoperative femoral fracture (OR: 1.10, 95% CI: 0.47-2.60, P = .83), infection (OR: 1.50, 95% CI: 0.53-5.23, P = .44), or reoperation within one year for other reasons (OR: 1.50, 95% CI: 0.25-9.00, P = .65). DAA had fewer dislocations requiring reoperation (OR: 0.20, 95% CI: 0.04-0.91, P = .02).

Conclusion: This comparative study did not find differences in intraoperative or postoperative fracture or infection between DAA and PA. DAA was associated with a lower likelihood of reoperation for dislocation within one year of surgery.
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http://dx.doi.org/10.1016/j.arth.2021.03.046DOI Listing
March 2021

The dystrophia myotonica WD repeat-containing protein DMWD and WDR20 differentially regulate USP12 deubiquitinase.

FEBS J 2021 Apr 12. Epub 2021 Apr 12.

Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.

Despite its potential clinical relevance, the product of the DMWD (dystrophia myotonica, WD repeat containing) gene is a largely uncharacterized protein. The DMWD amino acid sequence is similar to that of WDR20, a known regulator of the USP12 and USP46 deubiquitinases (DUBs). Here, we apply a combination of in silico and experimental methods to investigate several aspects of DMWD biology. Molecular evolution and phylogenetic analyses reveal that WDR20 and DMWD, similar to USP12 and USP46, arose by duplication of a common ancestor during the whole genome duplication event in the vertebrate ancestor lineage. The analysis of public human gene expression datasets suggests that DMWD expression is positively correlated with USP12 expression in normal tissues and negatively correlated with WDR20 expression in tumors. Strikingly, a survey of the annotated interactome for DMWD and WDR20 reveals a largely nonoverlapping set of interactors for these proteins. Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct coimmunoprecipitation of epitope-tagged proteins. We found that DMWD and WDR20 share the same binding interface in USP12, suggesting that their interaction with the DUB may be mutually exclusive. Finally, we show that both DMWD and WDR20 promote USP12 enzymatic activity, but they differentially modulate the subcellular localization of the DUB. Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires.
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http://dx.doi.org/10.1111/febs.15875DOI Listing
April 2021

Aseptic Tibial Implant Loosening After Total Knee Arthroplasty: Preventable?

J Am Acad Orthop Surg 2021 Apr;29(8):326-330

From the Hospital for Special Surgery, Adult Reconstruction and Joint Replacement (Menken and Rodriguez), CUNY School of Medicine (Fleuriscar), New York, NY, University of Michigan, Ann Arbor, MI (Weiner), and the Department of Orthopaedic Surgery, Boston University School of Medicine, Boston, MA (Berliner).

Aseptic loosening is a considerable complication that affects the longevity of total knee arthroplasty (TKA) implants. Surgeon technique may help minimize aseptic loosening after TKA. Meticulous cementation of the prosthesis and the bone surface during various stages of cement polymerization will maximize cement adherence to the prosthesis and the bone, respectively. Pressurization of the cement in the canal and at the cut surface to achieve at least 2 mm of cement depth penetration has been reported to increase TKA implant longevity.
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http://dx.doi.org/10.5435/JAAOS-D-20-00452DOI Listing
April 2021

Oral and topical extra-label administration of fipronil to laying hens: Assessment of the egg residue patterns.

J Vet Pharmacol Ther 2021 Mar 24. Epub 2021 Mar 24.

Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN, UNCPBA-CICPBA-CONICET, Facultad de Ciencias Veterinarias, Tandil, Argentina.

This experimental work reproduces the fipronil extra-label administration performed by producers in laying hens. The scientific goal was to characterize the residual concentrations in eggs from treated hens and suggest the withdrawal periods that should be respected to avoid risk for consumers. Thirty-four laying hens were allocated into two groups: Group A was treated with fipronil in feed, two single doses of 1 mg kg day ; Group B was administered a single dose of 1 mg kg by the topical route. Fipronil egg residues were quantified by HPLC-MS/MS. Fipronil and its sulphone metabolite (fipronil-SO ) were measured in egg after both treatments. The highest egg residual profile was always for fipronil-SO . Mean maximum egg concentrations (C ) of 228.5 ± 79.8 ng/g (fipronil) and 1,849 ± 867 ng/g (fipronil-SO ) were found after fipronil administration in feed. The lowest residual levels were quantified after the topical treatment with C of 27.1 ± 4.9 and 163 ± 26 ng/g for fipronil and fipronil-SO . Mean fipronil marker residues and established MRLs allowed calculating the withdrawal periods, the shortest being 74 days after topical administration. Such a long withdrawal period is difficult to meet in egg production systems. Thus, the extra-label use of fipronil in laying hens should not be recommended under any circumstances.
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http://dx.doi.org/10.1111/jvp.12965DOI Listing
March 2021

Correction to: Sharing the Power of White Privilege to Catalyze Positive Change in Academic Medicine.

J Racial Ethn Health Disparities 2021 Mar 15. Epub 2021 Mar 15.

Research Group for Underrepresented Minorities in Academic Medicine, Brody School of Medicine, Division of Academic Affairs, East Carolina University, 600 Moye Blvd AD-47, Greenville, NC, 27834, USA.

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http://dx.doi.org/10.1007/s40615-021-01002-xDOI Listing
March 2021

Selection of Embedding Dimension and Delay Time in Phase Space Reconstruction via Symbolic Dynamics.

Entropy (Basel) 2021 Feb 11;23(2). Epub 2021 Feb 11.

Departamento Metodos Cuantitativos, Ciencias Juridicas y Lenguas Modernas, Universidad Politecnica de Cartagena, 30201 Cartagena, Spain.

The modeling and prediction of chaotic time series require proper reconstruction of the state space from the available data in order to successfully estimate invariant properties of the embedded attractor. Thus, one must choose appropriate time delay τ∗ and embedding dimension for phase space reconstruction. The value of τ∗ can be estimated from the Mutual Information, but this method is rather cumbersome computationally. Additionally, some researchers have recommended that τ∗ should be chosen to be dependent on the embedding dimension by means of an appropriate value for the time delay τw=(p-1)τ∗, which is the optimal time delay for independence of the time series. The C-C method, based on Correlation Integral, is a method simpler than Mutual Information and has been proposed to select optimally τw and τ∗. In this paper, we suggest a simple method for estimating τ∗ and τw based on symbolic analysis and symbolic entropy. As in the C-C method, τ∗ is estimated as the first local optimal time delay and τw as the time delay for independence of the time series. The method is applied to several chaotic time series that are the base of comparison for several techniques. The numerical simulations for these systems verify that the proposed symbolic-based method is useful for practitioners and, according to the studied models, has a better performance than the C-C method for the choice of the time delay and embedding dimension. In addition, the method is applied to EEG data in order to study and compare some dynamic characteristics of brain activity under epileptic episodes.
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http://dx.doi.org/10.3390/e23020221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916852PMC
February 2021

Malaria mortality in Colombia from 2009 to 2018: a descriptive study.

Rev Soc Bras Med Trop 2021 26;54:e04412020. Epub 2021 Feb 26.

Instituto Nacional de Salud, Parasitology Team, Bogotá, Colombia.

Introduction: Colombia has an endemo-epidemic for malaria, with a downward trend in mortality over the last few decades. This study describes the malaria mortality rates from 2009-2018.

Methods: We obtained data from the Colombian Mortality Information System and calculated the case fatality and crude and age-adjusted mortality rates.

Results: During the study, 148 malaria-related deaths were registered. The average annual mortality rate was 0.032 deaths/100,000. Two peaks were observed in 2010 and 2016. Choco contributed to the highest number of deaths (27.7%).

Conclusions: The unstable downward trend of malaria mortality rates calls for greater emphasis on surveillance and interventions.
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http://dx.doi.org/10.1590/0037-8682-0441-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008904PMC
March 2021

Maximizing Black applicant matriculation in U.S. PA programs: associations between the number of submitted applications and likelihood of matriculation.

BMC Med Educ 2021 Feb 23;21(1):127. Epub 2021 Feb 23.

Division of Physician Assistant Studies Department of Family and Preventive Medicine, University of Utah, UT, Salt Lake City, USA.

Background: Physician Assistants (PA) are important members of the medical team, and increasing diversity in healthcare professionals has been consistently associated with improved health outcomes for underrepresented minority patients. In this study of a national cohort of PA program applicants, we investigated whether the number of programs a student applied to (Application Number, AN) was significantly associated with increased likelihood of matriculation into a PA program.

Methods: We examined all applications (n = 27,282) to the 2017-2018 admissions cycle of the Central Application Service for Physician Assistants, which is utilized by over 90% of accredited PA programs in the US. As we a priori hypothesized that associations would be non-linear, we used natural cubic splines to estimate the associations between matriculation and AN, controlling for multiple metrics of academic achievement, experience, and applicant demographics. We subsequently used segmented regression analyses (modified poisson regression with robust error variance) to investigate log-linear associations above and below inflection points identified in the spline analyses. Additionally, we explored for effect modification by race/ethnicity.

Results: The strongest associations were observed between application number 2-7, and a threshold effect was observed at > 16 applications, beyond which there was no significant, incremental benefit in matriculation likelihood. Associations differed by race, particularly for application number 2-7, wherein the incremental benefit from each additional application was highest for Black applicants (Likelihood Ratio [LR]: 1.243, 95% CI: 1.136 to 1.360) vs non-Latinx White (LR: 1.098, 95% CI: 1.072 to 1.125), with no additional, incremental benefit beyond 7 program applications. For all other races, significant increased likelihoods of matriculation were observed until 16 program applications.

Conclusions: These findings can help guide pre-PA advisors and PA programs, providing recommended thresholds to applicants on the most cost effective ways to increase their likelihood of admissions, and the PA profession as a whole by providing actionable information that can potentially increase Race/Ethnic diversity in the PA profession and, by extension, medical teams.
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http://dx.doi.org/10.1186/s12909-021-02563-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901109PMC
February 2021

Humanitarian Surgical Missions in Times of COVID-19: Recommendations to Safely Return to a Sub-Saharan Africa Low-Resource Setting.

World J Surg 2021 05 20;45(5):1297-1305. Epub 2021 Feb 20.

Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, IMIB-Arrixaca, El Palmar, Murcia, Spain.

Background: Since the declaration of the pandemic, humanitarian medicine has been discontinued. Until now, there have been no general recommendations on how humanitarian surgical missions should be organized.

Methods: Based on our experience in the field of humanitarian surgical missions to Sub-Saharan Africa, a panel of recommendations in times of COVID-19 was developed. The fields under study were as follows: (1) Planning of a multidisciplinary project; (2) Organization of the infrastructure; (3) Screening, management and treatment of SARS-COV-2; (4) Diagnostic tests for SARS-COV-2; (5) Surgical priorization and (6) Context of patients during health-care assistance. We applied a risk bias measurement to obtain a consensus among humanitarian health-care providers with experience in this field.

Results: A total of 94.36% of agreement were reached for the approval of the recommendations. Emergency surgery must be a priority, and elective surgery adapted. For emergency surgery, we established a priority level 1a (< 24 h) and 1b (< 72 h). For an elective procedure, according our American College of Surgeon adaptation score, process with more than 60 points should be reconsidered. Due to the low life expectancy in many African countries, we consider 45-50 years as age of risk. In case of SARS-COV-2 active infection or high clinical suspicion, the screening, management and treatment should be following the international guidelines adapted to duration of the stay, available infrastructure, size of the cooperation team and medical resources.

Conclusions: Humanitarian surgical mission in times of COVID-19 is a challenge that must extrapolate the established recommendations to the local cooperation environment.
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http://dx.doi.org/10.1007/s00268-021-06001-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896831PMC
May 2021

Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx.

Eur J Cancer 2021 Mar 16;146:135-144. Epub 2021 Feb 16.

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France; INSERM U900 Research Unit, Saint-Cloud, France; Paris-Saclay University, Paris, France. Electronic address:

Purpose: This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation.

Methods: Patients with stage III or IVA (American Joint Committee on Cancer (AJCC) guidelines, 7th edition, 2010) HNSCC of the oral cavity or oropharynx, aged ≥70 or ≥65 years and ineligible to receive cisplatin, amenable to radiotherapy (RT) with curative intent, received NBTXR3 as a single intratumoural (IT) injection followed by activation by intensity-modulated radiation therapy (IMRT; 70 Gy). The NBTXR3 dose corresponded to a percentage of the baseline tumour volume, measured by magnetic resonance imaging. The primary objectives were to determine the recommended phase II dose (RP2D), dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Safety and tolerability were assessed using National Cancer Institute CTCAE version 4.0. Antitumour activity was assessed by Response Evaluation Criteria in Solid Tumours 1.1.

Results: Nineteen patients were enrolled: 3 at the dose level of 5%, 3 at the dose level of 10%, 5 at the dose level of 15% and 8 at the dose level of 22% of the tumour volume. The MTD was not reached, and no DLTs or serious adverse event (SAEs) related to NBTXR3 were observed. Four adverse events related to NBTXR3 and/or the IT injection were reported (grade I-II). NBTXR3 remained in the injected tumour throughout RT, with no leakage in the surrounding healthy tissues. Specific RT-related toxicity was as expected with IMRT. The RP2D was determined as 22% baseline tumour volume. Preliminary signs of antitumour activity were observed.

Conclusion: Intratumoural injection of NBTXR3 followed by IMRT is feasible and demonstrated a good safety profile, supporting further evaluation at the RP2D in this patient population.

Trial Registration: ClinicalTrials.govNCT01946867.
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http://dx.doi.org/10.1016/j.ejca.2021.01.007DOI Listing
March 2021

The multifunctional role of SPANX-A/D protein subfamily in the promotion of pro-tumoural processes in human melanoma.

Sci Rep 2021 Feb 11;11(1):3583. Epub 2021 Feb 11.

Department of Physiology, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain.

Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes encode a protein family (SPANX-A, -B, -C and -D), whose expression is limited to the testis and spermatozoa in normal tissues and various tumour cells. SPANX-A/D proteins have been detected in metastatic melanoma cells, but their contribution to cancer development and the underlying molecular mechanisms of skin tumourigenesis remain unknown. Combining functional and proteomic approaches, the present work describes the presence of SPANX-A/D in primary and metastatic human melanoma cells and how it promotes pro-tumoural processes such as cell proliferation, motility and migration. We provide insights into the molecular features of skin tumourigenesis, describing for the first time a multifunctional role of the SPANX-A/D protein family in nuclear function, energy metabolism and cell survival, considered key hallmarks of cancer. A better comprehension of the SPANX-A/D protein subfamily and its molecular mechanisms will help to describe new aspects of tumour cell biology and develop new therapeutic targets and tumour-directed pharmacological drugs for skin tumours.
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http://dx.doi.org/10.1038/s41598-021-83169-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878863PMC
February 2021

The "STK38-XPO1 axis": its general relevance and mechanistic underpinnings remain to be further characterized.

Cell Mol Life Sci 2021 Feb 9. Epub 2021 Feb 9.

Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain.

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http://dx.doi.org/10.1007/s00018-021-03778-xDOI Listing
February 2021

Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific translation in epithelial cells.

Gut 2021 Feb 1. Epub 2021 Feb 1.

Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV-EHU), Leioa, Spain

Objectives: Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5'UTR of in the inflammatory environment characteristic of the coeliac intestinal epithelium.

Design: The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (mA)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD.

Results: Individuals harbouring the risk allele had higher mA methylation in the 5'UTR of RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall mA methylation in humans as well as in in vitro and in vivo models.

Conclusion: We identify a novel mA-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at mA proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.
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http://dx.doi.org/10.1136/gutjnl-2020-322566DOI Listing
February 2021

COVID-19 Coinfection with in a Patient with Multiple Myeloma.

Case Rep Infect Dis 2021 15;2021:8840536. Epub 2021 Jan 15.

Division of Infectious Disease, Memorial Regional Hospital, Memorial Healthcare System, Hollywood, FL, USA.

Background: Coronavirus disease (COVID-19) is a worldwide pandemic causing multiple fatalities and morbidities worldwide. We report a case of severe pneumonia causing acute respiratory distress syndrome due to a coinfection with SARS-CoV-2 and in an elderly patient with multiple myeloma in Florida, USA. . An 84-year-old male with a medical history significant for multiple myeloma not in remission was sent to the emergency department to rule out COVID-19 infection prior to continuing his chemotherapy sessions. At presentation, he had nonspecific mild symptoms and an unremarkable physical examination. He had significant blood test findings including serum lactate dehydrogenase 373 U/L, high sensitive C-reactive protein 17.40 mg/l, and ferritin 415 ng/ml. Xpert-SARS-CoV-2 was positive. Chest radiograph revealed patchy areas of interstitial infiltrates in mid to lower lung zones. During his hospitalization course, his oxygenation deteriorated, requiring mechanical intubation. Repeat chest radiograph showed worsening bilateral infiltrates. He was started on broad-spectrum antibiotics and eventually weaned off mechanical intubation and extubated. On the 11 day of admission, he was found to be bradycardic and in shock, and he was reintubated. His labs showed worsening inflammatory markers along with kidney dysfunction to the point of requiring renal replacement therapy. He received both convalescent plasma and remdesivir for treatment of COVID-19 pneumonia. Eventually, repeat blood cultures came back positive for the growth of acid-fast beaded bacilli. While awaiting final culture and sensitivity reports, his antibiotics were upgraded to cover possible nocardia infection. Repeat blood and sputum cultures resulted in growth of AFB bacilli 1 week after.

Conclusions: This case report highlights the importance of keeping a broad differential and considering multiple coinfections, including atypical ones during this COVID-19 pandemic, such as the one that was discussed above, , in order to provide goal-directed therapy.
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http://dx.doi.org/10.1155/2021/8840536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814410PMC
January 2021

Genomic Diversity of Burkholderia pseudomallei Isolates, Colombia.

Emerg Infect Dis 2021 Feb;27(2):655-658

We report an analysis of the genomic diversity of isolates of Burkholderia pseudomallei, the cause of melioidosis, recovered in Colombia from routine surveillance during 2016-2017. B. pseudomallei appears genetically diverse, suggesting it is well established and has spread across the region.
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http://dx.doi.org/10.3201/eid2702.202824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853579PMC
February 2021

Sharing the Power of White Privilege to Catalyze Positive Change in Academic Medicine.

J Racial Ethn Health Disparities 2021 Jun 19;8(3):539-542. Epub 2021 Jan 19.

Research Group for Underrepresented Minorities in Academic Medicine, Brody School of Medicine, Division of Academic Affairs, East Carolina University, 600 Moye Blvd AD-47, Greenville, NC, 27834, USA.

White privilege can be often overlooked and poorly understood in academic medicine, by those who wield it, and by those who suffer from its deleterious effects. Dr. Peggy McIntosh, a leader in research on equity and diversity in education, described white privilege as a set of unearned benefits that white people have based on being born white in a culture that favors the white race. White people have privilege because it was given to them by other white people, and it was taken by claiming superiority over people of color, starting before the European colonizations of Africa, Asia, and the Americas, and continuing through the present day. Many white people come from impoverished communities, suffer from socioeconomic disadvantage, and struggle with unemployment. They may also suffer from inadequate housing and limited education. Because they are white, they still benefit from privilege and positive stereotypes associated with light skin color. As our nation reckons with the murders of unarmed Black people by police, recognizing that  many white people have been allies and agents of change forBlack and other minority people, discussing how the power of white privilege can be shared is needed. The authors discuss the power of white privilege and how that power can be shared to promote change in academic medicine.
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http://dx.doi.org/10.1007/s40615-020-00947-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102454PMC
June 2021

Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction.

Proc Natl Acad Sci U S A 2021 Jan;118(4)

Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136;

Therapies for heart failure with preserved ejection fraction (HFpEF) are lacking. Growth hormone-releasing hormone agonists (GHRH-As) have salutary effects in ischemic and nonischemic heart failure animal models. Accordingly, we hypothesized that GHRH-A treatment ameliorates chronic kidney disease (CKD)-induced HFpEF in a large-animal model. Female Yorkshire pigs ( = 16) underwent 5/6 nephrectomy via renal artery embolization and 12 wk later were randomized to receive daily subcutaneous injections of GHRH-A (MR-409; = 8; 30 µg/kg) or placebo ( = 8) for 4 to 6 wk. Renal and cardiac structure and function were serially assessed postembolization. Animals with 5/6 nephrectomy exhibited CKD (elevated blood urea nitrogen [BUN] and creatinine) and faithfully recapitulated the hemodynamic features of HFpEF. HFpEF was demonstrated at 12 wk by maintenance of ejection fraction associated with increased left ventricular mass, relative wall thickness, end-diastolic pressure (EDP), end-diastolic pressure/end-diastolic volume (EDP/EDV) ratio, and tau, the time constant of isovolumic diastolic relaxation. After 4 to 6 wk of treatment, the GHRH-A group exhibited normalization of EDP ( = 0.03), reduced EDP/EDV ratio ( = 0.018), and a reduction in myocardial pro-brain natriuretic peptide protein abundance. GHRH-A increased cardiomyocyte [Ca] transient amplitude ( = 0.009). Improvement of the diastolic function was also evidenced by increased abundance of titin isoforms and their ratio ( = 0.0022). GHRH-A exerted a beneficial effect on diastolic function in a CKD large-animal model as demonstrated by improving hemodynamic, structural, and molecular characteristics of HFpEF. These findings have important therapeutic implications for the HFpEF syndrome.
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http://dx.doi.org/10.1073/pnas.2019835118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848727PMC
January 2021

Catastrophic Thrombotic Storm.

Clin Imaging 2021 Jun 30;74:64-66. Epub 2020 Dec 30.

Division of Cardiovascular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address:

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http://dx.doi.org/10.1016/j.clinimag.2020.12.025DOI Listing
June 2021

Dear White People.

Ann Fam Med 2021 Jan-Feb;19(1):66-69

Overlook Family Medicine Residency Program, Summit, New Jersey.

We are living in unprecedented times. While the world is grappling with COVID-19, we find the horrors of racism looming equally large as we, yet again, confront lurid deaths in the center of the news cycle of Black and brown people from police bias and brutality. Those of us who have been championing antiracism and justice work and bearing the burden of the "minority tax" have been overwhelmed by sudden asks from our well-intentioned White colleagues of how to best respond. In the tone of the Netflix series, "Dear White People," we further emphasize that we are not alone in trying to reach out to you, our White colleagues and leaders. Please hear our story and heed our call to action.
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http://dx.doi.org/10.1370/afm.2634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800738PMC
January 2021

Chemical Composition, Fatty Acid Profile and Sensory Characteristics of Chanco-Style Cheese from Early Lactation Dairy Cows Fed Winter Brassica Crops.

Animals (Basel) 2021 Jan 7;11(1). Epub 2021 Jan 7.

Facultad de Ciencias Agrarias y Alimentarias, Instituto de Producción Animal, Universidad Austral de Chile, Independencia 631, Valdivia 5110566, Chile.

Brassica crops such as kale and swede can be supplied to cow diets during winter, however little is known about the effects of feeding those forage brassicas to lactating cows on cheese nutritional characteristics of milk and cheese. This study evaluated the effect of including kale or swede in pasture-fed lactating dairy cow diets on chemical composition, fatty acid (FA) profile, and sensory characteristics of Chanco-style cheese. Twelve early-lactation cows were used in a replicated ( = 4) 3 × 3 square Latin square design. The control diet consisted of (DM basis) 10.0 kg of grass silage, 4.0 kg of fresh grass pasture, 1.5 kg soybean meal, 1.0 kg of canola meal, and 4.0 kg of cereal-based concentrate. The other treatments replaced 25% of the diet with swede or kale. Milk yield, milkfat, and milk protein were similar between treatments as were cheese moisture, fat, and protein. Swede and kale increased total saturated cheese FA while thrombogenic index was greater in swede, but color homogeneity and salty flavor were greater while ripe cheese aroma less than for kale. Kale or swede can be used in the diet of pasture-fed lactating dairy cows without negative effects on milk production, milk composition, or cheese composition. However, kale and swede increased total cheese saturated FA.
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http://dx.doi.org/10.3390/ani11010107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825774PMC
January 2021

Improved Sexual Function After Total Hip and Knee Arthroplasty for Osteoarthritis.

Orthopedics 2021 Jan 7:1-6. Epub 2021 Jan 7.

Osteoarthritis of the hip and knee is known to affect sexual activity. For patients with osteoarthritis, pain during sexual activity can lead to decreased quality of life and other associated health issues. The authors designed a prospective study to evaluate the effect of total hip arthroplasty and total knee arthroplasty on the psychosocial and physical aspects of sexuality pre- and postoperatively. Between April 2009 and December 2011, patients received questionnaires in the mail preoperatively. They were asked to return the pre-operative questionnaire before surgery and the postoperative questionnaire 6 months after surgery. Data were analyzed to evaluate the psychosocial and physical aspects of sexuality and participants' subjective assessment of their appearance. Preoperatively, 91% and 67% of patients reported psychosocial and physical issues, respectively. After the arthroplasty procedure, 84% (P<.001) and 47% (P<.001) of patients reported improvement psychosocially and physically, respectively. Of the patients, 16% reported that arthroplasty adversely affected sexual function, with their predominant fear being joint damage (63%). A greater number of women and patients undergoing hip procedures reported improvement in sexual activity after surgery compared with men (P=.02) and patients undergoing knee procedures (P=.002). Both hip and knee osteoarthritis and arthroplasty had a significant effect on overall sexual function-psychosocially, physically, and in terms of patients' assessment of their external appearance-with higher rates of improvement seen after hip arthroplasty. Because of the effect of osteoarthritis and arthroplasty on sexual function, this topic should be addressed both pre- and postoperatively. [Orthopedics. 2021;44(x):xx-xx.].
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http://dx.doi.org/10.3928/01477447-20210104-01DOI Listing
January 2021

Iliopsoas Impingement After Direct Anterior Approach Total Hip Arthroplasty: Epidemiology, Risk Factors, and Treatment Options.

J Arthroplasty 2021 May 13;36(5):1772-1778. Epub 2020 Dec 13.

Adult Reconstruction and Joint Replacement Service, Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY.

Background: The objective of this study is to evaluate the incidence, natural history, response to treatment, and risk factors for anterior iliopsoas impingement (AIPI) after direct anterior approach (DAA) total hip arthroplasty (THA).

Methods: Between January 1, 2009 and January 4, 2014, 600 patients (655 hips) who underwent primary DAA THA were retrospectively reviewed. AIPI incidence was calculated. Natural history and response to a stepwise treatment approach was assessed. Radiographic anterior acetabular component overhang was measured. Asymptomatic controls were used to identify risk factors for the development of AIPI.

Results: In total, 518 patients (559 hips) met the inclusion criteria. The incidence of AIPI was 32/559 (5.7%). Symptom resolution occurred in 22/32 (68.8%) patients at final follow-up. Nonoperative management was successful in 15/32 (46.9%) patients. Operative intervention resulted in symptom resolution in 5/8 (62.5%) patients. On univariate analysis, female gender (odds ratio [OR] 2.79), acetabular component to native femoral head diameter ratio above 1.1 (OR 3.85), and any measurable overhang (OR 7.07) significantly raised the risk of AIPI, while increasing native femoral head diameter was protective for AIPI (OR 0.83).

Conclusion: AIPI is a cause of groin pain after DAA THA, which often improves with conservative measures. Significant predisposing factors for AIPI include female gender, small native femoral head diameter, increased acetabular component to femoral head diameter ratio, and most notably, any measurable acetabular component overhang.

Level Of Evidence: Level III, retrospective cohort study.
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http://dx.doi.org/10.1016/j.arth.2020.12.012DOI Listing
May 2021

Isolation and X-ray Crystal Structure of an Electrogenerated TEMPO-N Charge-Transfer Complex.

Org Lett 2021 Jan 6;23(2):454-458. Epub 2021 Jan 6.

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.

Advances in radical-based catalytic reactions have created a demand for understanding their mechanistic underpinnings. Here, we present the isolation, structural elucidation, and theoretical analysis of a catalytically relevant charge-transfer species formed between the azidyl radical and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO). The unusual bond angles and pancake bonding between these two fragments highlight the weak bonding interactions present in this complex. This X-ray structure validates computational predictions as well as mechanistic proposals of TEMPO-mediated radical azidation reactions.
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http://dx.doi.org/10.1021/acs.orglett.0c03966DOI Listing
January 2021