Disparities in osteoarthritis diagnosis and symptoms between English- and Spanish-speaking Latinas over 40 years of age in the United States: a analysis of the Behavioral Risk Factor Surveillance System.

OBJECTIVE: Osteoarthritis (OA) is a prominent musculoskeletal disorder that affects approximately 303 million people worldwide. The challenges that language barriers present to the Latina population in regard to the diagnosis and treatment of OA remain largely unknown. The objective of this study was to examine disparities in the diagnosis and treatment of arthritic conditions in English- and Spanish-speaking Latinas over 40 years of age. DESIGN: We analyzed data from the CDC's Behavioral Risk Screening and Surveillance System (BRFSS), combining the 2017-2020 cycles using sampling weights provided by BRFSS, adjusted for multiple cycles. Determination of English- or Spanish-speaking groups was based on the language of the survey submitted. We calculated population estimates for arthritis diagnosis, physical limitations, and mean joint pain among language groups and by age (40-64 and 65+) and determined associations via odds ratios. RESULTS: Rates of arthritis diagnosis between groups were similar; however we found that Spanish-speaking Latinas 65+ were statistically more likely to report being limited by pain (AOR: 1.55; 95% CI: 1.14-2.09), and among both age groups Spanish-speaking Latinas reported higher pain scores than the English-speaking group (40-64 age group: Coef: 0.74, SE = 0.14, P < .001; 65 + age group: Coef: 1.05, SE = 0.2, P < .001). CONCLUSION: Results from this study show that while there were no significant differences in rates of diagnosis, Spanish-speaking Latinas were more likely to be limited by joint pain and report higher pain scores.

First Report of Alternaria alternata Causing Leaf Spot on Broccoli in Ecuador.

In Ecuador, broccoli (Brassica oleracea var. italica) production is located in the Andean region, specifically Cotopaxi-Ecuador (INEC, 2019). A leaf pathogen has been constantly observed in this area, showing brown circular necrosis surrounded by yellowish halo-like spots causing leaf death (Fig. 1a). This pathogen was believed to be Alternaria sp.; however, the species was not determined either using classical or molecular tools. In 2021, ten leaves showing similar symptoms were collected in Cotopaxi and sent for pathogen identification. Here, leaf explants (0.25 cm2) showing disease symptoms were surface sterilized with 2% sodium hypochlorite (NaClO) and 70% ethanol (C2H6O), rinsed with sterile water, and transferred to Potato Dextrose Agar (PDA) media. Petri dishes were incubated in darkness at 25°C for five days. The single hyphal tip method was used to purify the cultures on PDA. Fifteen pure isolates were obtained after incubating for 14 days. Isolates were incubated under blacklight for two days to induce fungal sporulation. All isolates presented early white cotton-like mycelium that later became dark green (Fig 1b). Under the microscope, we observed straight primary conidia in simple or branched chains. Also, the conidia were obclavate, long ellipsoids, moderate in size (19.5-43.9 µm in length, 7.1-17.2 µm in width), and septate with few longitudinal septa. Lastly, the conidium body can narrow itself into a secondary conidia (Fig 1c) (Woudenberg et al., 2013). According to colony and conidia morphology, isolates were identified as Alternaria sp. (Woudenberg et al., 2013). Five isolates were randomly selected for DNA extraction and sequencing of ITS (internal transcribed spacer; Chou, H.H. and Wu, W.S. 2002), TEF (translation elongation factor; O'Donnell et al., 1998), and RPB2 (RNA polymerase II second largest subunit; Liu et al., 1999) gene regions. DNA sequences obtained from each marker were identical for all isolates. Consensus sequences and alignment were built using ClustalX in MEGA X (Kumar et al., 2018). Consensus sequences were deposited in GenBank with the following accession numbers: ITS, ON982232; TEF, ON983964; RPB2, ON983963. A multilocus Bayesian inference phylogenetic tree was constructed in Beast software (version 1.8.4) using the concatenated sequences (Drummond et al., 2012; Maharachchikumbura et al., 2014). The isolates in our study clustered with isolates of Alternaria alternata, confirming their identity (Figure 2). For Koch's postulates, healthy broccoli plants were grown in sterile soil for six weeks. The fungal conidia were suspended in sterile distilled water (1×106 conidia/ml), and the leaves were inoculated by spraying the spore solution. The control treatment was sprayed with sterile distilled water alone. Plants were maintained at 28°C and had more than 85% relative humidity (Sigillo et al., 2020). Seven days after inoculation, plants showed chlorosis and necrosis. Ten days later, 100% of the treated leaves presented brown circular necrosis (Fig. 1d). Control plants showed no disease symptoms. Re-isolation of the pathogen from the diseased leaf tissue was performed as previously described. The isolates presented the exact morphology of pure cultures obtained from field-diseased leaves. The pathogenicity test was performed twice. To our knowledge, this is the first report on A. alternata being the causal agent of leaf spot on broccoli in Ecuador. Disease diagnosis contributes to providing strategies against this pathogen. Further investigations are needed to find biological/chemical techniques or cultivar resistance to control this pathogen in broccoli.

Thoracic Duct Embolization Using Transabdominal Antegrade and Transcervical Retrograde Accesses.

PURPOSE: To evaluate the technical success and clinical outcomes of thoracic duct embolization (TDE) using transabdominal antegrade and transcervical retrograde accesses to treat patients with chyle leak. MATERIALS AND METHODS: This study was a retrospective, nonblinded, single-institution chart review of all patients aged 18 years or older over a 6-year time frame who underwent lymphangiography with attempted TDE for iatrogenic or spontaneous chyle leaks using transabdominal antegrade and/or transcervical retrograde accesses. RESULTS: Ninety-nine patients underwent 113 procedures. Eighty-five patients underwent 1 procedure, and 14 patients required 2 procedures. The technical success rate of TDE was 68% (72/106) with transabdominal antegrade access and 44% (15/34) with transcervical retrograde access. The overall technical success rate of TDE, including both the access methods, was 77% (87/113). The most common reasons for transabdominal access failure were small caliber of the cisterna chyli and thoracic duct (TD) occlusion. Five patients were lost to follow-up. Overall clinical success, defined as resolution of the chyle leak, was achieved in 83% (78/94) of the patients. There were 6 Society of Interventional Radiology (SIR) level 1 adverse events (AEs), 5 SIR level 2 AEs, and 2 SIR level 3 AEs. Nontarget embolization occurred in 2 patients. CONCLUSIONS: Although transcervical retrograde TDE is a challenging procedure, with a lower technical success rate than transabdominal antegrade access, retrograde access improved the technical and clinical success rates of the treatment of chyle leaks in cases of thoracic duct occlusion, small cisterna chyli, and leaks located in the abdomen.

Cellular and molecular regulation of the programmed death-1/programmed death ligand system and its role in multiple sclerosis and other autoimmune diseases.

Programmed Cell Death 1 (PD-1) receptor and its ligands (PD-Ls) are essential to maintain peripheral immune tolerance and to avoid tissue damage. Consequently, altered gene or protein expression of this system of co-inhibitory molecules has been involved in the development of cancer and autoimmunity. Substantial progress has been achieved in the study of the PD-1/PD-Ls system in terms of regulatory mechanisms and therapy. However, the role of the PD-1/PD-Ls pathway in neuroinflammation has been less explored despite being a potential target of treatment for neurodegenerative diseases. Multiple Sclerosis (MS) is the most prevalent, chronic, inflammatory, and autoimmune disease of the central nervous system that leads to demyelination and axonal damage in young adults. Recent studies have highlighted the key role of the PD-1/PD-Ls pathway in inducing a neuroprotective response and restraining T cell activation and neurodegeneration in MS. In this review, we outline the molecular and cellular mechanisms regulating gene expression, protein synthesis and traffic of PD-1/PD-Ls as well as relevant processes that control PD-1/PD-Ls engagement in the immunological synapse between antigen-presenting cells and T cells. Also, we highlight the most recent findings regarding the role of the PD-1/PD-Ls pathway in MS and its murine model, experimental autoimmune encephalomyelitis (EAE), including the contribution of PD-1 expressing follicular helper T (TFH) cells in the pathogenesis of these diseases. In addition, we compare and contrast results found in MS and EAE with evidence reported in other autoimmune diseases and their experimental models, and review PD-1/PD-Ls-targeting therapeutic approaches.

Rheumatoid meningitis: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Rheumatoid meningitis (RM) is a neurological complication of rheumatoid arthritis (RA). Current evidence is based on case reports and partial reviews. METHODS: This is a systematic review and meta-analysis following the PRISMA statement. The aim is to describe the characteristics of the disease, including clinical, imaging and laboratory findings, treatment, outcomes and prognosis reported in the literature. RESULTS: In all, 103 studies with 130 cases were included. RM affected adults with an average age of 62 years, with or without a previous RA diagnosis. RA activity and time with the disease were associated with a worse prognosis. Most common clinical manifestations were transient focal neurological signs (64.6%), systemic symptoms (51.3%), episodic headache (50.4%) and neuropsychiatric alterations (47.7%). Joint manifestations were present in only 27.4% of cases. Brain magnetic resonance imaging showed unilateral or bilateral involvement, predominantly frontoparietal. Both pachymeninges and leptomeninges were affected, the latter more frequently (82.88%). The laboratory findings included increased levels of rheumatoid factor (89.71%), anti-cyclic citrullinated peptide (89.47%), C-reactive protein (82.54%) and erythrocyte sedimentation rate (81.81%). Cerebrospinal fluid analysis showed an increase in the protein level (76.14%), with pleocytosis (85.19%) of mononuclear predominance (89.19%). Biopsy was performed in 72.52% of the patients. Corticosteroid pulse therapy was the main induction therapy. Disease relapse occurred in 31.17% of patients, whilst 54.54% had a full recovery. CONCLUSIONS: Rheumatoid meningitis must be considered in adult patients with or without RA diagnosis, high-dose corticosteroid induction therapy should be installed and maintenance therapy plays a key role. It is not recommended to use anti-TNF as an induction therapy. Nowadays, RM has a significantly better outcome. These findings may aid clinicians in timely RM diagnosis and treatment, thus improving its outcomes.

Rheumatoid meningitis: report of two cases.

Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis (RA). RM mimics many other conditions such as subdural empyema, unsteady gait, focal brain dysfunction, stroke, relapsing-remitting motor signs, headache, neuropsychiatric disorders, seizures, parkinsonism, and meningeal tumors. RM is considered a disease with poor prognosis. However, cases reported in the last decade show a good outcome. We report two cases with a favorable outcome. A 48-year-old man with a three-year history of RA admitted for headache, sensory disturbances, and speech difficulties. Brain magnetic resonance imaging (MRI) showed a left parietal subdural laminar lesion with restricted diffusion and a small left superior frontal acute infarction. A subdural empyema was originally suspected, and antimicrobials were prescribed. A follow-up MRI did not show progression of the subdural lesion and the patient was discharged 14 days after admission without focal deficits. A 44-year-old female patient with two years of seronegative RA was admitted for severe headache, confusion, nausea and vomiting. Brain MRI showed subtle supra and infratentorial leptomeningeal involvement and a left cerebellar acute infarct. A meningoencephalitis due to etanercept was initially thought and treated with dexamethasone. The patient was discharged but had to be admitted again and a new MRI showed a progression of the leptomeningeal involvement. She worsened and required endotracheal intubation. Cyclophosphamide was started and the patient became asymptomatic three months later. We propose that treatment should not be delayed waiting a biopsy when a diagnosis of RM is made and after a cerebrospinal fluid infection has been ruled out.

Intranodal Lymphangiography with Thoracic Duct Embolization for Treatment of Chyle Leak after Thoracic Outlet Decompression Surgery.

From 2015 to 2019, 9 patients underwent ultrasound-guided intranodal lymphangiography for the treatment of a chyle leak following thoracic outlet decompression surgery. Chyle leaks were identified by Lipiodol (Guerbet, Roissy, France) extravasation near the left supraclavicular surgical bed in all patients. The technical success rate of thoracic duct embolization was 67% (6 of 9), including fluoroscopic transabdominal antegrade access (n = 4) and ultrasound-guided retrograde access in the left neck (n = 2). Clinical success was achieved in 89% of patients (8 of 9). The mean interval from lymphangiography to drain removal was 6.6 days (range, 4-18 d). No patients had a chyle leak recurrence during clinical follow-up (mean, 304 d).

La Ciudad de México, cuna del primer estudio radiológico en la República Mexicana.

En agosto de 1896, el ingeniero Gilberto Crespo y Martínez publicó un artículo en el que presentó dos radiografías realizadas por Roberto Jofre y Fernando Ferrari Pérezen. Correspondieron a las dos primeras radiografías llevadas a cabo en la República Mexicana, dos meses antes de las efectuadas en la ciudad de San Luis Potosí el 24 de octubre y la del doctor Tobías Núñez en el Hospital Juárez, el 19 de octubre de ese mismo año.In August 1896, engineer Gilberto Crespo y Martinez published an article where he presented two radiographies produced by Roberto Jofre and Fernando Ferrari Perez. This corresponded to the two first radiographs carried out in the Mexican Republic, two months earlier than those produced in the city of San Luis Potosi on October 24 and the one by Doctor Tobías Núñez at the Juarez Hospital on October 19 that same year.

An Algorithm for Management After Transjugular Intrahepatic Portosystemic Shunt Placement According to Clinical Manifestations.

We propose an algorithm for management after transjugular intrahepatic portosystemic shunt (TIPS) placement according to clinical manifestations. For patients with an initial good clinical response, surveillance Doppler ultrasound is recommended to detect stenosis or occlusion. A TIPS revision can be performed using basic or advanced techniques to treat stenosis or occlusion. In patients with an initial poor clinical response, a TIPS venogram with pressure measurements should be performed to assess shunt patency. The creation of a parallel TIPS may also be required if the patient is symptomatic and the portal pressure remains high after TIPS revision. Additional procedures may also be necessary, such as peritoneovenous shunt (Denver shunt) placement for refractory ascites, tunneled pleural catheter for hepatic hydrothorax, and balloon-occluded retrograde transvenous obliteration procedure for gastric variceal bleeding. A TIPS reduction procedure can also be performed in patients with uncontrolled hepatic encephalopathy or hepatic failure.

Technically Successful Geniculate Artery Embolization Does Not Equate Clinical Success for Treatment of Recurrent Knee Hemarthrosis after Knee Surgery.

PURPOSE: To evaluate technical details, clinical outcomes, and complications in patients undergoing geniculate artery embolization for treatment of spontaneous hemarthrosis after knee surgery. MATERIALS AND METHODS: During 2009-2014, 10 consecutive patients (seven women; mean age, 57.4 y) underwent geniculate artery embolization at a single tertiary care center. All patients except one had hemarthrosis after total knee replacement (TKR). One patient presented with hemarthrosis after cartilage surgery. Two patients in the TKR group had a history of TKR revisions before the embolization. Embolization was performed with polyvinyl alcohol particles (range, 300-700 µm). In one patient requiring repeat embolization, N-butyl cyanoacrylate/ethiodized oil was used. The endpoint for embolization was stasis in the target artery and elimination of the hyperemic blush. RESULTS: In 10 patients, 14 embolizations were performed with 100% technical success. Hemarthrosis resolved in six patients. Four patients required repeat embolization for recurrent hemarthrosis, which subsequently resolved in two of four patients. Three of the four patients who required repeat embolization had serious comorbidities, either blood dyscrasias or therapeutic anticoagulation. There were two minor skin complications that resolved with conservative management. The average length of follow-up after embolization was 545 days (range, 50-1,655 d). One patient was lost to follow-up. CONCLUSIONS: Geniculate artery embolization is a safe, minimally invasive treatment option for spontaneous and refractory knee hemarthrosis after knee surgery with 100% technical success. However, limited clinical success and higher repeat embolization rates were noted in patients with serious comorbidities.

US-Guided, Direct Puncture Retrograde Thoracic Duct Access, Lymphangiography, and Embolization: Feasibility and Efficacy.

PURPOSE: To describe technical details, success rate, and advantages of direct puncture of the thoracic duct (TD) under direct ultrasound (US) guidance at venous insertion in the left neck. MATERIALS AND METHODS: All patients who underwent attempted thoracic duct embolization (TDE) via US-guided retrograde TD access in the left neck were retrospectively reviewed. Indications for lymphangiography were iatrogenic chyle leak, pulmonary lymphangiectasia, and plastic bronchitis. Ten patients with mean age 41.4 years (range, 21 d to 72 y) underwent US-guided TD access via the left neck. Technical details, procedural times, and clinical outcomes were evaluated. TD access time was defined as time from start of procedure to successful access of TD, and total procedural time was defined from start of procedure until TDE. RESULTS: All attempts at TD access via the neck were successful. Technical and clinical success of TDE was 60%. There were no complications. Mean TD access time was 17 minutes (range, 2-47 min), and mean total procedure time was 49 minutes (range, 25-69 min). Mean follow-up time was 5.4 months (range, 3-10 months). CONCLUSIONS: TDE via US-guided access in the left neck is technically feasible and safe with a potential decrease in procedure time and elimination of oil-based contrast material.

Ultralocalized thermal reactions in subnanoliter droplets-in-air.

Miniaturized laboratory-on-chip systems promise rapid, sensitive, and multiplexed detection of biological samples for medical diagnostics, drug discovery, and high-throughput screening. Within miniaturized laboratory-on-chips, static and dynamic droplets of fluids in different immiscible media have been used as individual vessels to perform biochemical reactions and confine the products. Approaches to perform localized heating of these individual subnanoliter droplets can allow for new applications that require parallel, time-, and space-multiplex reactions on a single integrated circuit. Our method positions droplets on an array of individual silicon microwave heaters on chip to precisely control the temperature of droplets-in-air, allowing us to perform biochemical reactions, including DNA melting and detection of single base mismatches. We also demonstrate that ssDNA probe molecules can be placed on heaters in solution, dried, and then rehydrated by ssDNA target molecules in droplets for hybridization and detection. This platform enables many applications in droplets including hybridization of low copy number DNA molecules, lysing of single cells, interrogation of ligand-receptor interactions, and rapid temperature cycling for amplification of DNA molecules.

Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA.

OBJECTIVES: To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha (PIK3CA) mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). STUDY DESIGN: We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Children's Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Children's Hospital. RESULTS: Most individuals from Boston Children's Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼ 80% of cases. Seventy-four percent of patients with LM from Seattle Children's Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. CONCLUSIONS: Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low.

On-chip metal/polypyrrole quasi-reference electrodes for robust ISFET operation.

To operate an ion-sensitive field-effect transistor (ISFETs) it is necessary to set the electrolyte potential using a reference electrode. Conventional reference electrodes are bulky, fragile, and too big for applications where the electrolyte volume is small. Several researchers have proposed tackling this issue using a solid-state planar micro-reference electrode or a reference field-effect transistor. However, these approaches are limited by poor robustness, high cost, or complex integration with other microfabrication processes. Here we report a simple method to create robust on-chip quasi-reference electrodes by electrodepositing polypyrrole on micro-patterned metal leads. The electrodes were fabricated through the polymerization of pyrrole on patterned metals with a cyclic voltammetry process. Open circuit potential measurements were performed to characterize the polypyrrole electrode performance, demonstrating good stability (±1 mV), low drift (∼1 mV h(-1)), and reduced pH response (5 mV per pH). In addition, the polypyrrole deposition was repeated in microelectrodes made of different metals to test compatibility with standard complementary metal-oxide-semiconductor (CMOS) processes. Our results suggest that nickel, a metal commonly used in semiconductor foundries for silicide formation, is a good candidate to form the polypyrrole quasi-reference electrodes. Finally, the polypyrrole microelectrodes were used to operate foundry fabricated ISFETs. These experiments demonstrated that transistors biased with polypyrrole electrodes have pH sensitivity and resolution comparable to ones that are biased with standard reference electrodes. Therefore, the simple fabrication, high compatibility, and robust electrical performance make polypyrrole an ideal choice for the fabrication of outstanding microreference electrodes that enable robust and sensitive operation of multiple ISFET sensors on a chip.

Electrical detection of nucleic acid amplification using an on-chip quasi-reference electrode and a PVC REFET.

Electrical detection of nucleic acid amplification through pH changes associated with nucleotide addition enables miniaturization, greater portability of testing apparatus, and reduced costs. However, current ion-sensitive field effect transistor methods for sensing nucleic acid amplification rely on establishing the fluid gate potential with a bulky, difficult to microfabricate reference electrode that limits the potential for massively parallel reaction detection. Here we demonstrate a novel method of utilizing a microfabricated solid-state quasi-reference electrode (QRE) paired with a pH-insensitive reference field effect transistor (REFET) for detection of real-time pH changes. The end result is a 0.18 µm, silicon-on-insulator, foundry-fabricated sensor that utilizes a platinum QRE to establish a pH-sensitive fluid gate potential and a PVC membrane REFET to enable pH detection of loop mediated isothermal amplification (LAMP). This technique is highly amendable to commercial scale-up, reduces the packaging and fabrication requirements for ISFET pH detection, and enables massively parallel droplet interrogation for applications, such as monitoring reaction progression in digital PCR.

Enhanced biosensing resolution with foundry fabricated individually addressable dual-gated ISFETs.

The adaptation of semiconductor technologies for biological applications may lead to a new era of inexpensive, sensitive, and portable diagnostics. At the core of these developing technologies is the ion-sensitive field-effect transistor (ISFET), a biochemical to electrical transducer with seamless integration to electronic systems. We present a novel structure for a true dual-gated ISFET that is fabricated with a silicon-on-insulator (SOI) complementary metal-oxide-semiconductor process by Taiwan Semiconductor Manufacturing Company (TSMC). In contrast to conventional SOI ISFETs, each transistor has an individually addressable back-gate and a gate oxide that is directly exposed to the solution. The elimination of the commonly used floating gate architecture reduces the chance of electrostatic discharge and increases the potential achievable transistor density. We show that when operated in a "dual-gate" mode, the transistor response can exhibit sensitivities to pH changes beyond the Nernst limit. This enhancement in sensitivity was shown to increase the sensor's signal-to-noise ratio, allowing the device to resolve smaller pH changes. An improved resolution can be used to enhance small signals and increase the sensor accuracy when monitoring small pH dynamics in biological reactions. As a proof of concept, we demonstrate that the amplified sensitivity and improved resolution result in a shorter detection time and a larger output signal of a loop-mediated isothermal DNA amplification reaction (LAMP) targeting a pathogenic bacteria gene, showing benefits of the new structure for biosensing applications.