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1.
J Foot Ankle Surg ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34810085

RESUMO

In the setting of an opioid epidemic, this study aims to provide evidence on opioid use trends, risk factors for prolonged use, and complications from perioperative opioid consumption in hallux valgus surgery. A national database was queried for patients who underwent hallux valgus correction. Regression analysis identified: (1) risk factors for prolonged postoperative narcotic use; and (2) association between preoperative/prolonged postoperative narcotic use and postoperative complications. A linear regression analysis was used to determine trends. About 20,749 patients were included, of which 3464 patients were prescribed narcotics preoperatively and 4339 were identified as prolonged postoperative narcotic prescription users. Preoperative prescriptions were identified as risk factors for prolonged use. Perioperative narcotic use was observed to be a risk factor for poor outcomes. About 21% of patients were identified as prolonged postoperative narcotic prescription users. Patients undergoing hallux valgus corrective surgery should be counseled regarding their increased risk of complications when using narcotics.

2.
Crit Care Nurse ; 41(5): 41-50, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34595494

RESUMO

BACKGROUND: In patients with acute neurological injury, abrupt temperature change exacerbates increased intracranial pressures and negatively affects perfusion pressure and cerebral blood flow. Critical care nurses must provide coordinated and effective interventions to maintain normothermia without precipitating shivering immediately after acute neurological injury in pediatric patients. OBJECTIVE: To improve hyperthermia management in a 40-bed pediatric intensive care unit, an interdisciplinary pediatric critical care team developed, implemented, and evaluated a targeted temperature management protocol. METHODS: The project was guided by the organization's plan-do-study-act quality improvement process. Quality improvement was assessed retrospectively using electronic medical records of patients meeting eligibility criteria. Samples of pediatric patients who received temperature interventions were compared before and after protocol implementation. The protocol included environmental, pharmacological, and body surface cooling device interventions, as well as use of a bedside shivering assessment scale and stepwise interventions to prevent and control shivering. RESULTS: Before implementation of the targeted temperature management protocol, 64% of patients had documented temperatures higher than 37.5 °C, and body surface cooling devices were used in 10% of patients. After protocol implementation, more than 80% of patients had documented temperatures higher than 37.5 °C, and body surface cooling devices were used in 62% of patients. Four patients (6%) before and 5 patients (31%) after protocol implementation were treated with body surface cooling without requiring use of neuromuscular blockade. CONCLUSIONS: Creation and implementation of a targeted temperature management protocol increased nurses' documented use of body surface cooling to manage hyperthermia in pediatric intensive care unit patients with acute neurological injury.


Assuntos
Hipotermia Induzida , Melhoria de Qualidade , Temperatura Corporal , Criança , Humanos , Unidades de Terapia Intensiva Pediátrica , Estudos Retrospectivos
3.
Orthop J Sports Med ; 9(10): 23259671211035741, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34631903

RESUMO

Background: Recent studies have suggested that femoral tunnel drilling during anterior cruciate ligament (ACL) reconstruction (ACLR) with the use of a flexible reaming system through a standard anteromedial portal (AM-FR) may result in a different tunnel geometry compared with a rigid reamer through an accessory anteromedial portal with hyperflexion (AM-RR). Purpose: To summarize radiologic, anatomic, and clinical outcomes from available studies that directly compared the use of AM-FR versus AM-RR for independent femoral tunnel creation during ACLR. Study Design: Systematic review; Level of evidence, 4. Methods: A literature search was performed using the MEDLINE (PubMed) and Web of Science databases to identify all studies that directly compared radiologic, anatomic, and clinical outcomes between the use of AM-FR and AM-RR. The literature search, data recording, and methodological quality assessment was performed by 2 independent reviewers. The outcomes analyzed included resultant ACL graft positioning and graft bending angle; femoral tunnel positioning, aperture morphology, length, and widening; posterior wall breakage; and distance from various posterolateral knee structures. Results: A total of 13 studies met the eligibility criteria for inclusion. There was no difference in femoral tunnel aperture location between techniques. There were conflicting findings among studies regarding which technique resulted in a more acute graft bending angle. One study reported greater femoral tunnel widening upon follow-up with the use of AM-FR. AM-FR produced longer and more anteverted femoral tunnels than did AM-RR. The difference in tunnel length was significant and more prominent in lesser degrees of knee flexion. With AM-FR, femoral tunnels were farther from the lateral collateral ligament and peroneal nerve, and 1 of 5 studies had fewer reports of posterior wall breakage. There has been no literature comparing the clinical or functional outcomes of these techniques. Conclusion: Although no clinical studies exist comparing AM-FR and AM-RR for femoral tunnel creation during ACLR, both systems allow for reproducible positioning of an anatomic femoral tunnel aperture. The use of AM-FR results in longer and more anteverted femoral tunnels than using AM-RR, with exit points on the lateral femur that are different but safe. Surgeons should be aware of the technical differences with each method; however, further study is needed to identify any clinically important difference that results.

4.
Front Microbiol ; 12: 734216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646254

RESUMO

Bacteriocins are a highly diverse group of antimicrobial peptides that have been identified in a wide range of commensal and probiotic organisms, especially those resident in host microbiomes. Rising antibiotic resistance have fueled renewed research into new drug scaffolds such as antimicrobial peptides for use in therapeutics. In this investigation, we examined mung bean seeds for endophytes possessing activity against human and plant pathogens. We isolated a novel strain of Bacillus safensis, from the contents of surface-sterilized mung bean seed, which we termed B. safensis C3. Genome sequencing of C3 identified three distinct biosynthetic systems that produce bacteriocin-based peptides. C3 exhibited antibacterial activity against Escherichia coli, Xanthomonas axonopodis, and Pseudomonas syringae. Robust antimicrobial activity of B. safensis C3 was observed when C3 was co-cultured with Bacillus subtilis. Using the cell-free supernatant of C3 and cation exchange chromatography, we enriched a product that retained antimicrobial activity against B. subtilis. The peptide was found to be approximately 3.3 kDa in size by mass spectrometry, and resistant to proteolysis by Carboxypeptidase Y and Endoproteinase GluC, suggesting that it is a modified variant of an AS-48 like bacteriocin. Our findings open new avenues into further development of novel bacteriocin-based scaffolds for therapeutic development, as well as further investigations into how our discoveries of bacteriocin-producing plant commensal microorganisms may have the potential for an immediate impact on the safety of food supplies.

5.
Orthop J Sports Med ; 9(7): 23259671211019353, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34345633

RESUMO

Background: Corticosteroid injection and physical therapy remain the mainstay of treatment for idiopathic adhesive capsulitis of the shoulder; however, a certain percentage of patients will not improve using these interventions and will require manipulation under anesthesia (MUA) and/or lysis of adhesions (LOA). Purpose: To evaluate whether the immediate pain reduction after fluoroscopic-guided, mixed anesthetic-corticosteroid injection for idiopathic adhesive capsulitis is related to the eventual need for LOA/MUA or a repeat glenohumeral steroid injection. Study Design: Case-control study; Level of evidence, 3. Methods: This single-institution study involved patients undergoing fluoroscopic glenohumeral corticosteroid injection for a diagnosis of idiopathic adhesive capsulitis between 2010 and 2017. Included were patients with a minimum of 1-year postinjection follow-up and visual analog scale (VAS) pain scores from immediately before and after the injection. The primary analysis was the relationship between patients with an immediate change in VAS score after injection and those who underwent LOA/MUA. A repeat glenohumeral injection was also evaluated as an outcome. Receiver operator characteristic curves and a multivariate binomial logistic regression analysis were performed. Results: Overall, 739 shoulders in 728 patients (mean age, 52.6 years; 68% women) were included, of which 38 (5.1%) underwent LOA/MUA and 209 (28%) underwent repeat injections. The immediate change in the VAS score was not significantly associated with the eventual need for LOA/MUA. Preinjection VAS and immediate postinjection VAS scores were not significant predictors of eventual LOA/MUA or subsequent injection. For all 3 predictors, the area under the receiver operator characteristic curve classified them as extremely poor discriminators. Conclusion: The immediate pain response to a fluoroscopic-guided glenohumeral injection for idiopathic shoulder adhesive capsulitis was not predictive of the eventual need for LOA/MUA or subsequent injection. Patients can be counseled that even if their initial pain response to an injection is poor, they still have an excellent chance of avoiding surgery, as the overall rate of LOA/MUA was low (5.1%).

6.
Adv Mater ; 33(34): e2101374, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34288156

RESUMO

The organic insulator-metal interface is the most important junction in flexible electronics. The strong band offset of organic insulators over the Fermi level of electrodes should theoretically impart a sufficient impediment for charge injection known as the Schottky barrier. However, defect formation through Anderson localization due to topological disorder in polymers leads to reduced barriers and hence cumbersome devices. A facile nanocoating comprising hundreds of highly oriented organic/inorganic alternating nanolayers is self-coassembled on the surface of polymer films to revive the Schottky barrier. Carrier injection over the enhanced barrier is further shunted by anisotropic 2D conduction. This new interface engineering strategy allows a significant elevation of the operating field for organic insulators by 45% and a 7× improvement in discharge efficiency for Kapton at 150 °C. This superior 2D nanocoating thus provides a defect-tolerant approach for effective reviving of the Schottky barrier, one century after its discovery, broadly applicable for flexible electronics.

8.
bioRxiv ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34268508

RESUMO

Drug development for specific antiviral agents against coronavirus disease 2019 (COVID-19) is still an unmet medical need as the pandemic continues to spread globally. Although huge efforts for drug repurposing and compound screens have put forth, only few compounds remain in late stage clinical trials. New approaches and assays are needed to accelerate COVID-19 drug discovery and development. Here we report a time-resolved fluorescence resonance energy transfer-based assay that detects the severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) nucleocapsid protein (NP) produced in infected cells. It uses two specific anti-NP monoclonal antibodies (MAbs) conjugated to donor and acceptor fluorophores that produces a robust ratiometric signal for high throughput screening of large compound collections. Using this assay, we measured a half maximal inhibitory concentration (IC 50 ) for Remdesivir of 9.3 µM against infection with SARS-CoV-2 USA/WA1/2020 (WA-1). The assay also detected SARS-CoV-2 South African (Beta, ß), Brazilian/Japanese variant P.1 (Gamma, γ), and Californian (Epsilon, ε), variants of concern or interest (VoC). Therefore, this homogeneous SARS-CoV-2 NP detection assay can be used for accelerating lead compound discovery for drug development and for evaluating drug efficacy against emerging SARS-CoV-2 VoC.

9.
Crit Care ; 25(1): 266, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325729

RESUMO

BACKGROUND: Hyperchloremia and chloride load have been associated with worse clinical outcomes in critically ill patients. We sought to evaluate the electrolyte profile and clinical outcomes associated with a unit-wide transition from saline to balanced fluids for resuscitation and maintenance fluids in a pediatric intensive care unit (PICU). METHODS: A before and after analysis of all patients admitted to the PICU in a large, urban, academic hospital between August 2018 and March 2020. The transition from the use of saline to the use of balanced fluids for both resuscitation and maintenance fluid as standard care occurred in June 2019. The primary outcome was day 3 acute kidney injury (AKI). The secondary outcomes included mortality, ventilator-free days (VFDs), need for renal replacement therapy (RRT), hospital length of stay (LOS), and electrolyte abnormalities. RESULTS: Overall, 2863 patients (47% female) with a day 3 AKI rate of 12.9% (n = 130) and a mortality rate of 2.8% (n = 79) were included. After adjusting for confounders (age, PRISM III, mechanical ventilation, and immunocompromised state, septic shock), there were no significant differences in the odds of day 3 AKI (pre 13%, post 12.5%; adjusted odds ratio [aOR] 0.96, 95%CI 0.65-1.42). There were no differences in the secondary outcomes. The post-intervention period had fewer patients with hyperchloremia (pre 15.5% vs. post 10.4%, p = < 0.0001) and hyperkalemia (pre 3.2% vs. post 1.4%, p = 0.02) and more patients with hypochloremia (pre 9.5% vs. post 14.4%, p = < 0.0001) and hypokalemia (pre 38.2% vs. post 47.2%, p = < 0.0001). In reference to the normochloremic cohort, the hypochloremic cohort had an increase in day 3 AKI, need for RRT, hyperchloremia, and hyperkalemia, and a decrease in hypokalemia; and the hyperchloremic cohort had an increase in VFD and a decrease in hospital LOS. CONCLUSIONS: Following a unit-wide implementation of balanced fluids as standard care, there were no differences in rates of day 3 AKI or other clinical outcomes. However, there were lower rates of hyperkalemia and hyperchloremia and higher rates of hypokalemia and hypochloremia. Further evaluation of the effect of balanced fluids and the clinical significance of electrolyte abnormalities in critically ill children is needed.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Ressuscitação/normas , Desequilíbrio Hidroeletrolítico/complicações , Injúria Renal Aguda/etiologia , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos de Coortes , Estudos Controlados Antes e Depois , Estado Terminal/terapia , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/organização & administração , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Avaliação de Resultados em Cuidados de Saúde/métodos , Pediatria/métodos , Ressuscitação/métodos , Ressuscitação/estatística & dados numéricos , Estudos Retrospectivos , Estatísticas não Paramétricas
10.
Front Cardiovasc Med ; 8: 667554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34179133

RESUMO

Invasive outcomes of Group A Streptococcus (GAS) infections that involve damage to skin and other tissues are initiated when these bacteria colonize and disseminate via an open wound to gain access to blood and deeper tissues. Two critical GAS virulence factors, Plasminogen-Associated M-Protein (PAM) and streptokinase (SK), work in concert to bind and activate host human plasminogen (hPg) in order to create a localized proteolytic environment that alters wound-site architecture. Using a wound scratch assay with immortalized epithelial cells, real-time live imaging (RTLI) was used to examine dynamic effects of hPg activation by a PAM-containing skin-trophic GAS isolate (AP53R+S-) during the course of infection. RTLI of these wound models revealed that retraction of the epithelial wound required both GAS and hPg. Isogenic AP53R+S- mutants lacking SK or PAM highly attenuated the time course of retraction of the keratinocyte wound. We also found that relocalization of integrin ß1 from the membrane to the cytoplasm occurred during the wound retraction event. We devised a combined in situ-based cellular model of fibrin clot-in epithelial wound to visualize the progress of GAS pathogenesis by RTLI. Our findings showed GAS AP53R+S- hierarchically dissolved the fibrin clot prior to the retraction of keratinocyte monolayers at the leading edge of the wound. Overall, our studies reveal that localized activation of hPg by AP53R+S- via SK and PAM during infection plays a critical role in dissemination of bacteria at the wound site through both rapid dissolution of the fibrin clot and retraction of the keratinocyte wound layer.

11.
Vaccine ; 39(28): 3717-3723, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34053791

RESUMO

BACKGROUND: Outbreaks of circulating vaccine-derived polioviruses (cVDPVs) pose a threat to the eventual eradication of all polioviruses. In 2017, an outbreak of cVDPV type 2 (cVDPV2) occurred in the midst of a war in Syria. We describe vaccination-based risk factors for and the successful response to the outbreak. METHODS: We performed a descriptive analysis of cVDPV2 cases and key indicators of poliovirus surveillance and vaccination activities during 2016-2018. In the absence of reliable subnational coverage data, we used the caregiver-reported vaccination status of children with non-polio acute flaccid paralysis (AFP) as a proxy for vaccination coverage. We then estimated the relative odds of being unvaccinated against polio, comparing children in areas affected by the outbreak to children in other parts of Syria in order to establish the presence of poliovirus immunity gaps in outbreak affected areas. FINDINGS: A total of 74 cVDPV2 cases were reported, with paralysis onset ranging from 3 March to 21 September 2017. All but three cases were reported from Deir-ez-Zor governorate and 84% had received < 3 doses of oral poliovirus vaccine (OPV). After adjusting for age and sex, non-polio AFP case-patients aged 6-59 months in outbreak-affected areas had 2.5 (95% CI: 1.1-5.7) increased odds of being unvaccinated with OPV compared with non-polio AFP case-patients in the same age group in other parts of Syria. Three outbreak response rounds of monovalent OPV type 2 (mOPV2) vaccination were conducted, with governorate-level coverage mostly exceeding 80%. INTERPRETATION: Significant declines in both national and subnational polio vaccination coverage, precipitated by war and a humanitarian crisis, led to a cVDPV2 outbreak in Syria that was successfully contained following three rounds of mOPV2 vaccination.


Assuntos
Poliomielite , Poliovirus , Criança , Surtos de Doenças , Humanos , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vacina Antipólio Oral , Síria/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-33837113

RESUMO

OBJECTIVE: Low-dose oral opioids may improve severe chronic breathlessness in advanced cardiorespiratory diseases. Prescription of opioids for breathlessness occurs infrequently however, with little known about patients' attitudes towards their use in this setting. The aim of this qualitative study was to explore patients' perceptions regarding opioids for the management of severe chronic breathlessness in people with advanced cardiorespiratory disease. METHODS: A cross-sectional, qualitative study was undertaken using outpatients with severe chronic breathlessness due to either severe chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF). Indepth, semistructured interviews were audio-recorded, transcribed verbatim and coded. Thematic analysis was undertaken to extrapolate recurring ideas from the data. RESULTS: Twenty-four participants were purposively sampled from three different groups: opioid-naïve patients with COPD (n=7), opioid-naïve patients with CHF (n=7) and patients with COPD using opioids currently or previously for severe chronic breathlessness (n=10). Four major themes were shared by both the opioid-naïve and opioid-experienced cohorts: (1) stigmatised attitudes and beliefs regarding opioids, (2) limited knowledge and information-seeking behaviour regarding opioids, (3) the impact of the relationships with health professionals and continuity of care, and (4) the significance of past experiences with opioids. An additional theme that was unique to the opioid-experienced cohort was (5) the perception of benefit and improved quality of life. CONCLUSION: Lack of knowledge regarding the role of opioids in managing severe chronic breathlessness, opioid misinformation and social stigmas are major barriers to opioid therapy that may be overcome by accurate information from trusted health professionals.

13.
Arthrosc Sports Med Rehabil ; 3(1): e105-e114, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33615254

RESUMO

Purpose: To quantify intraoperative joint space widening afforded by the outside-in, percutaneous release of the medial collateral ligament (MCL) and to evaluate its impact on medial compartment width and functional outcomes at 6-week follow-up for patients undergoing a partial medial meniscectomy without postoperative bracing. Methods: Patients with posteromedial meniscus tears and no evidence of ipsilateral knee pathology, undergoing partial medial meniscectomy, were enrolled. Intraoperatively, medial compartment width was quantified with fluoroscopy before and after the percutaneous MCL release with an 18-gauge spinal needle proximal to the joint line. At 6-week follow-up, valgus stress radiographs re-evaluated medial compartment width. International Knee Documentation Committee (IKDC) and Patient-Reported Outcomes Measurement Information System (PROMIS) scores were completed preoperatively and at 6-week follow-up to evaluate functional outcomes. A paired sample t test performed at a 95% confidence interval (CI) was used to compare these variables. Results: Forty-two patients, mean (± standard deviation) age 55.3 ± 10.7 years, were available for analysis of intraoperative medial compartment widening. Medial compartment width increased from 5.95 ± 1.32 to 11.09 ± 1.74 mm intraoperatively after MCL release. At 6-week follow-up, radiographic assessment demonstrated a mean medial compartment width of 5.85 ± .99 mm, which represented an insignificant change compared with the preoperative value (CI -0.68 to .33, P = .474). PROMIS and IKDC scores significantly improved from baseline, with increases of 6.9 ± 12.4 (CI 2.0 to 11.8, P = .008) and 11.7 ± 17.8 (CI 4.7 to 18.8, P = .002), respectively. Conclusions: Percutaneous MCL release during knee arthroscopy improves visualization and facilitates instrumentation by providing an almost 2× wider working space within the medial tibiofemoral joint. In this study, the performance of percutaneous MCL release did not result in any complications. Radiographic and clinical resolution of iatrogenic laxity was demonstrated by 6-weeks postoperatively, without the use of postoperative bracing. Level of Evidence: IV, therapeutic case series.

14.
mBio ; 12(1)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593976

RESUMO

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glycoprotein (VSVΔG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n > 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week.IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We therefore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.


Assuntos
COVID-19/diagnóstico , COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Testes de Neutralização
15.
Pain Med ; 22(2): 266-272, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33166391

RESUMO

OBJECTIVE: Radiofrequency ablation (RFA) of the medial branch nerve is a commonly performed procedure for patients with facet syndrome. RFA has previously been demonstrated to provide long-term functional improvement in approximately 50% of patients, including those who had significant pain relief after diagnostic medial branch block. We sought to identify factors associated with success of RFA for facet pain. DESIGN: Active-duty military patients who underwent lumbar RFA (L3, L4, and L5 levels) over a 3-year period were analyzed. Defense and Veterans Pain Rating Scale (DVPRS) and Oswestry Disability Index (ODI) scores were assessed the day of procedure and at the 2-month and 6-month follow-up. These data were analyzed to identify associations between patient demographics, pain, and functional status and patients' improvement after RFA, with a primary outcome of ODI improvement and a secondary outcome of pain reduction. RESULTS: Higher levels of starting functional impairment (starting ODI scores of 42.9 vs. 37.5; P = 0.0304) were associated with a greater likelihood of improvement in functional status 6 months after RFA, and higher starting pain scores (DVPRS pain scores of 6.1 vs. 5.1; P < 0.0001) were associated with a higher likelihood that pain scores would improve 6 months after RFA. A multivariate logistic regression was then used to develop a scoring system to predict improvement after RFA. The scoring system generated a C-statistic of 0.764, with starting ODI, pain scores, and both gender and smoking history as independent variables. CONCLUSIONS: This algorithm compares favorably to that of diagnostic medial branch block in terms of prediction accuracy (C-statistic of 0.764 vs. 0.57), suggesting that its use may improve patient selection in patients who undergo RFA for facet syndrome.


Assuntos
Ablação por Radiofrequência , Articulação Zigapofisária , Algoritmos , Humanos , Medição da Dor , Resultado do Tratamento , Articulação Zigapofisária/cirurgia
16.
J Virol Methods ; 287: 113995, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33068703

RESUMO

Towards the end of 2019, a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV), emerged in Wuhan, Hubei province of China, and has been responsible for coronavirus disease 2019 (COVID-19) in humans. Since its first report, SARS-CoV-2 has resulted in a global pandemic, with over 10 million human infections and over 560,000 deaths reported worldwide at the end of June 2020. Currently, there are no United States (US) Food and Drug Administration (FDA)-approved vaccines and/or antivirals licensed against SARS-CoV-2. The high economical and health impacts of SARS-CoV-2 has placed global pressure on the scientific community to identify effective prophylactic and therapeutic treatments for SARS-CoV-2 infection and associated COVID-19 disease. While some compounds have been already reported to reduce SARS-CoV-2 infection and a handful of monoclonal antibodies (mAbs) have been described that neutralize SARS-CoV-2, there is an urgent need for the development and standardization of assays which can be used in high through-put screening (HTS) settings to identify new antivirals and/or neutralizing mAbs against SARS-CoV-2. Here, we described a rapid, accurate, and highly reproducible plaque reduction microneutralization (PRMNT) assay that can be quickly adapted for the identification and characterization of both neutralizing mAbs and antivirals against SARS-CoV-2. Importantly, our MNA is compatible with HTS settings to interrogate large and/or complex libraries of mAbs and/or antivirals to identify those with neutralizing and/or antiviral activity, respectively, against SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/imunologia , Antivirais/farmacologia , Testes de Neutralização/métodos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , Chlorocebus aethiops , Ensaios de Triagem em Larga Escala , Humanos , Células Vero , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacos
17.
Front Microbiol ; 11: 589666, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281785

RESUMO

The circularized bacteriocin enterocin AS-48 produced by Enterococcus sp. exhibits antibacterial activity through membrane disruption. The membrane-penetrating activity of enterocin AS-48 has been attributed to a specific alpha-helical region on the circular peptide. Truncated, linearized forms containing these domains have been shown to preserve limited bactericidal activity. We utilized the amino acid sequence of the active helical domain of enterocin AS-48 to perform a homology-based search of similar sequences in other bacterial genomes. We identified similar domains in three previously uncharacterized AS-48-like bacteriocin genes in Clostridium sordellii, Paenibacillus larvae, and Bacillus xiamenensis. Enterocin AS-48 and homologs from these bacterial species were used as scaffolds for the design of a minimal peptide library based on the active helical domain of each bacteriocin sequence. 95 synthetic peptide variants of each scaffold peptide, designated Syn-enterocin, Syn-sordellicin, Syn-larvacin, and Syn-xiamensin, were designed and synthesized from each scaffold sequence based on defined biophysical parameters. A total of 384 total peptides were assessed for antibacterial activity against Gram-negative and Gram-positive bacteria. Minimal Inhibitory Concentrations (MICs) as low as 15.6 nM could be observed for the most potent peptide candidate tested, with no significant cytotoxicity to eukaryotic cells. Our work demonstrates for the first time a general workflow of using minimal domains of natural bacteriocin sequences as scaffolds to design and rapidly synthesize a library of bacteriocin-based antimicrobial peptide variants for evaluation.

19.
ACS Pharmacol Transl Sci ; 3(6): 1233-1241, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33330840

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in urgent need of therapeutic options. High-throughput screening (HTS) offers an opportunity to rapidly identify such compounds. In this work, we have developed a homogeneous cell-based HTS system using AlphaLISA detection technology for the SARS-CoV-2 nucleocapsid protein (NP). Our assay measures both recombinant and endogenous NP from viral lysates and tissue culture supernatants (TCS) in a sandwich-based format using two monoclonal antibodies against the NP analyte. Viral NP was detected and quantified in both tissue culture supernatants and cell lysates, with large differences observed between 24 and 48 h of infection. We simulated viral infection by spiking recombinant NP into 384-well plates with live Vero-E6 cells and were able to detect the NP with high sensitivity and a large dynamic range. Antiviral agents that inhibit either viral cell entry or replication decrease the AlphaLISA NP signal. Thus, this assay can be used for high-throughput screening of small molecules and biologics in the fight against the COVID-19 pandemic.

20.
Pract Lab Med ; 22: e00184, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33145388

RESUMO

Objectives: Point-of-care testing (POCT) is testing performed outside the traditional laboratory, often at the patient bedside. In hospital settings, blood glucose is the most common POCT. Staff performing POCT are not usually laboratory trained; they are clinical staff with a primary focus on treating patients. Clinical staff find POCT quality assurance (QA) practices burdensome and are often non-compliant. In hospitals within EORLA (Eastern Ontario Regional Laboratories Association), all critically high POCT glucose results must be repeated prior to acting, according to policy. Compliance with this policy is audited regularly. Design: and methods: All POCT glucose tests performed in participating sites between January and June 2018 and June and December 2019 were audited for compliance with the critical repeat policy. The discordant repeat rate was also determined for each audit period. Between January and May 2019, there were interventions aimed at improving compliance with the repeat policy. Results: Compliance with the critical repeat policy increased from 30 to 57% in 2019 compared to 2018, following nursing education and implementation of notifications on the glucose meters themselves. The rate of discordant repeat results (>20% different from initial) also improved at most sites in 2019 compared to 2018. Nurses cited insufficient cleaning of patient hands prior to initial testing as the primary reason for discordant repeats. Conclusions: Operator compliance with POCT QA policies is an ongoing challenge requiring continual audit, feedback and education. A strong POCT multi-disciplinary committee with supports from senior and clinical leadership in an organization are key to improving compliance.

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