Depolymerized Chitosan-g-[Poly(MMA-co-HEMA-cl-EGDMA)] Based Nanogels for Controlled Local Release of Bupivacaine.

This study is designed to formulate and characterize chitosan-based nanogels that provide the controlled delivery of anesthetic drugs, such as bupivacaine (BPV), for effective postoperative pain management over prolonged periods of time. Drug carriers of chitosan/poly (MMA-co-HEMA-cl-EGDMA) (CsPMH) nanogels were prepared by varying the composition of comonomers such as MMA, HEMA, and redox initiator CAN. The nanogels were then characterized using FTIR, TGA, SEM, and TEM. The CsPMH nanogels showed greater encapsulation efficiencies from 43.20-91.77%. Computational studies were also conducted to evaluate the interaction between the drug and CsPMH nanoparticles. Finally, BPV-loaded nanoparticles were used to examine their in vitro release behavior. At pH 7.4, all the drug carriers displayed the "n" value around 0.7, thus the BPV release follows anomalous diffusion. Drug carrier 7 demonstrated a steady and sustained release of BPV for approximately 24 h and released about 91% of BPV, following the K-P mechanism of drug release. On the other hand, drug carrier 6 exhibited controlled release for approximately 12 h and released only 62% of BPV.

Distinct mutational pattern of T-cell large granular lymphocyte leukemia combined with pure red cell aplasia: low mutational burden of STAT3.

T-cell large granular lymphocyte leukemia (T-LGL) is often accompanied by pure red cell aplasia (PRCA). A high depth of next generation sequencing (NGS) was used for detection of the mutational profiles in T-LGL alone (n = 25) and T-LGL combined with PRCA (n = 16). Beside STAT3 mutation (41.5%), the frequently mutated genes included KMT2D (17.1%), TERT (12.2%), SUZ12 (9.8%), BCOR (7.3%), DNMT3A (7.3%), and RUNX1 (7.3%). Mutations of the TERT promoter showed a good response to treatment. 3 of 41 (7.3%) T-LGL patients with diverse gene mutations were revealed as T-LGL combined with myelodysplastic syndrome (MDS) after review of bone marrow slide. T-LGL combined with PRCA showed unique features (low VAF level of STAT3 mutation, low lymphocyte count, old age). Low ANC was detected in a STAT3 mutant with a low level of VAF, suggesting that even the low mutational burden of STAT3 is sufficient for reduction of ANC. In retrospective analysis of 591 patients without T-LGL, one MDS patient with STAT3 mutation was revealed to have subclinical T-LGL. T-LGL combined with PRCA may be classified as unique subtype of T-LGL. High depth NGS can enable sensitive detection of concomitant MDS in T-LGL. Mutation of the TERT promoter may indicate good response to treatment of T-LGL, thus, its addition to an NGS panel may be recommended.

Polydopamine/polypyrrole-modified graphite felt enhances biocompatibility for electroactive bacteria and power density of microbial fuel cell.

The interactions between the microbes and the surface of an anode play an important role in capturing the respiratory electrons from bacteria in a microbial fuel cell (MFC). The chemical and electrochemical characteristics of the carbon material affect biofilm growth and direct electron transfer in MFCs. This study examined the electrodeposition of polydopamine (PDA) and polypyrrole (PPY) on graphite felt electrode (GF). The MFC with the modified PDA/PPY-GF reached 920 mW/m2, which was 1.5, 1.17, and 1.18 times higher than those of the GF, PDA-GF, and PPY-GF, respectively. PDA has superior hydrophilicity and adhesive force biofilm formation, while PPY provides electrochemically active sites for microbial electron transfer. Raman spectroscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller surface area measurements, and contact angle analysis revealed the enhanced physicochemical properties of the carbon electrode. These results show that co-doped PDA/PPY provides a strategy for electroactive biofilm development and improves the bioelectrochemical performance in realistic MFC reactors.

Which motor-cognitive abilities underlie the digital Trail-Making Test? Decomposing various test scores to detect cognitive impairment in Parkinson's disease-Pilot study.

Since Parkinson's disease (PD) is a heterogeneous disorder with symptoms, such as tremors, gait and speech disturbances, or memory loss, individualized diagnostics are needed to optimize treatment. In their current form, the typical paper-pencil methods traditionally used to track disease progression are too coarse to capture the subtleties of clinical phenomena. For this reason, digital biomarkers that capture, for example, motor function, cognition, and behavior using apps, wearables, and tracking systems are becoming increasingly established. However, given the high prevalence of cognitive impairment in PD, digital cognitive biomarkers to predict mental progression are important in clinical practice. This pilot study aimed to identify those components of our digital version of the TMT (dTMT) that allow discrimination between PD patients with and without cognitive deficits. A total of 30 healthy control (age 66.3 ± 8.61) and 30 participants with PD (age 68.3 ± 9.66) performed the dTMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed between and inside circles. The decomposition of cognitive abilities based on integrating additional variables in the dTMT revealed that the Parkinson's disease group was significantly more sensitive to parameters of inhibitory control. In contrast, the mild cognitive impairment group was sensitive to parameters of cognitive flexibility and working memory. The dTMT allows objective, ecologically valid, and long-term cognitive and fine-motor performance tracking, suggesting its potential as a digital biomarker in neurodegenerative disorders.

Laboratory Perspective of Concurrent Acute Myeloid Leukemia and COVID-19: a Case Report and Review of Literature.

BACKGROUND: Whether the diagnosis and treatment of coronavirus disease 2019 (COVID-19) affect the clinical course of patients with hematologic malignancies has been of interest during the COVID-19 pandemic. METHODS: We describe a 47-year-old female who was concurrently diagnosed with COVID-19 and acute myeloid leukemia (AML). RESULTS: She developed COVID-19 pneumonia which required treatment with remdesivir and dexamethasone, and induction therapy for t-AML was delayed. After her COVID-19 was resolved and isolation ended, follow-up bone marrow examination showed decreased leukemic burden. CONCLUSIONS: This case describes possible effects of COVID-19 treatment on the clinical course of patients with AML from a laboratory perspective.

The Immediate and Sustained Effects of Exercise-Induced Hemodynamic Response on Executive Function During Fine Motor-Cognitive Tasks Using Functional Near-Infrared Spectroscopy.

BACKGROUND: Several studies have shown that acute exercise has a small positive effect on cognitive performance. However, it is still unclear what type of exercise has a sustained impact on cognitive performance during post-exercise recovery. Therefore, the purpose of our study was to investigate cognitive performance at the behavioral level, and their neural correlates after a 10-minute post-exercise recovery period with two different types of exercise intervention (high-intensity interval exercise (HIIE) vs. Moderate-intensity continuous exercise (MCE)). METHODS: A total of 29 healthy young adults (7 women) between the ages of 19 and 33 with fair to good cardiovascular fitness were submitted to two different exercise protocols and a recovery session. Cognitive function was assessed using a digital Trail-Making-Test (dTMT). Cortical activity in the prefrontal and the motor cortex using functional near-infrared spectroscopy (fNIRS) was measured before, after acute exercise, and during recovery. The statistical analysis of fNIRS data was performed by comparing the slope and mean of the hemodynamic response. RESULTS: High levels of hemodynamic responses were observed in the prefrontal and motor cortex on the brain during performing the dTMT while walking from pre- to post-exercise and decreased again in post-recovery, accompanied by improvement and maintenance of cognitive performance. Notably, a high hemodynamic response in the left motor area of the brain was maintained by HIIE in post-recovery compared with MCE. CONCLUSIONS: The high cortical activation in the left motor area from post-exercise to recovery for the HIIE group may be due to the additional availability of neural resources for fine motor and postural control by high-intensity exercise-induced fatigue. Additionally, the improved cognitive performance may have effectively utilized the available neural resources in the frontal lobe, depending on the condition (sitting and walking) and the two types of exercise protocol (HIIE and MCE).

Contact system activation in disseminated intravascular coagulation: activities of prekallikrein and high-molecular-weight kininogen are significant risk factors.

The contact system activation can play a role in microthrombus formation of disseminated intravascular coagulation (DIC). This study investigated whether the activity of prekallikrein and high-molecular-weight kininogen (HMWK) correlated DIC progression. Contact system factors (prekallikrein, HMWK, activated factor XII), coagulation factors (IX, XI, XII) and tissue factor were measured in 140 patients who clinically suspected of having DIC. Prekallikrein and HMWK activity levels showed significant linear relationships with DIC score and antithrombin level, whereas prekallikrein and HMWK antigen levels did not. The activated factor XII, factor XII, factor XI and tissue factor were significant risk factors of overt-DIC. This finding suggests that consumption of prekallikrein and HMWK contributes to microvascular thrombosis in DIC. Measurements of prekallikrein and HMWK activity could be used as potential diagnostic markers for overt-DIC.

The trail-making-test: Comparison between paper-and-pencil and computerized versions in young and healthy older adults.

One of the key challenges in assessing cognitive performance is to detect not only apparent impairment but to also pick up on subtle differences. Computerized tests benefit especially from the acquisition of fine-grained outcome measures. However, the equivalency of paper-based and computerized tests cannot be assumed. The Trail-Making-Test is a paper-pencil cognitive assessment tool (ppTMT) that has been used in many research studies to evaluate visuomotor abilities and mental flexibility. A digital version of the extended TMT (including a condition measuring fine motor speed) called the dTMT has been developed. This study aims to test (1) reliability, (2) equivalence, and (3) agreement of the ppTMT and dTMT. A total of 53 healthy individuals aged 19 to 82 years of age (22 men, 31 women; mean age 42.2, SD = 22.8) completed three trials per ppTMT and dTMT condition. Part M involves following a predefined path, Part A links numbers randomly distributed in space, in ascending order, and Part B alternates between linking numbers and letters. dTMT scores were highly reproducible, correlated strongly with paper-pencil administered durations, and discriminated young from older adults. Measures of reliability, sensitivity, and clinical meaning for dTMT scores were favorable compared with ppTMT-based testing. Our findings support the comparability of TMT-indices in computerized assessments. While many digital biomarker efforts are in progress (e.g., neurodegenerative disorders), the dTMT sets itself apart through its high sensitivity, the alternate forms, and the additional component measures. In this light, it could serve as a starting point for an early diagnostic tool.

Biodegradable PCL-b-PLA Microspheres with Nanopores Prepared via RAFT Polymerization and UV Photodegradation of Poly(Methyl Vinyl Ketone) Blocks.

Biodegradable triblock copolymers based on poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) were synthesized via ring-opening polymerization of L-lactide followed by reversible addition-fragmentation chain-transfer (RAFT) polymerization of poly(methyl vinyl ketone) (PMVK) as a photodegradable block, and characterized by FT-IR and 1H NMR spectroscopy for structural analyses, and by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) for their thermal properties. Porous, biodegradable PCL-b-PLA microspheres were fabricated via the oil/water (O/W) emulsion evaporation method, followed by photodegradation of PMVK blocks by UV irradiation. The macro-chain transfer agent (CTA) synthesized by reacting a carboxylic-acid-terminated CTA-S-1-dodecyl-S'-(a,a'-dimethyl-a''-acetic acid)trithiocarbonate (DDMAT)-with a hydroxyl-terminated PCL-b-PLA block copolymer was used to synthesize well-defined triblock copolymers with methyl vinyl ketone via RAFT polymerization with controlled molecular weights and narrow polydispersity. Gel permeation chromatography traces indicated that the molecular weight of the triblock copolymer decreased with UV irradiation time because of the photodegradation of the PMVK blocks. The morphology of the microspheres before and after UV irradiation was investigated using SEM and videos of three-dimensional confocal laser microscopy, showing a change in their surface texture from smooth to rough, with high porosity owing to the photodegradation of the PMVK blocks to become porous templates.

Perineural Epinephrine for Brachial Plexus Block Increases the Incidence of Hypotension during Dexmedetomidine Infusion: A Single-Center, Randomized, Controlled Trial.

BACKGROUND: Sedation using dexmedetomidine is frequently associated with hypotension. In contrast, epinephrine, a commonly used adjunctive agent in regional anesthesia, is a potent vasopressor. We hypothesized that perineural epinephrine used in brachial plexus blockade may reduce hypotension during dexmedetomidine infusion. METHODS: Patients scheduled for upper extremity surgery were randomly allocated into a control and an epinephrine group. All patients received brachial plexus blockade, consisting of 25 mL of a 1:1 mixture of 1% lidocaine and 0.75% ropivacaine, with patients in the epinephrine group also receiving 125 µg epinephrine. Intraoperative sedation was induced using dexmedetomidine at a loading dose of 1 µg/kg and maintenance dose of 0.4 µg/kg/hr. The primary outcome was the incidence of intraoperative hypotension or hypotension in the post-anesthesia care unit (PACU). RESULTS: One hundred and thirty patients were included (65 per group). The incidence of hypotension was significantly higher in the epinephrine than in the control group (80.6% vs. 56.9%, p = 0.009). The duration of hypotension and the maximal change in blood pressure were also greater in the epinephrine group. CONCLUSIONS: Perineural epinephrine for brachial plexus blockade does not reduce hypotension due to dexmedetomidine infusion and may actually augment the occurrence of hypotensive events.

The Effects of the Combination of High-Intensity Interval Training with 3D-Multiple Object Tracking Task on Perceptual-Cognitive Performance: A Randomized Controlled Intervention Trial.

The ability to process goal-related visual information while ignoring goal-irrelevant information is essential for the human attention system. The study aimed to investigate how perceptual-cognitive performance was affected during high-intensity interval training (HIIT) using a 3D-multiple object tracking (3D-MOT) task called Neurotracker (NT). In an experimental design, 42 healthy adults (age M = 23.3 SD = 2.94, VO2max 52.8 ± 5.66 mL·kg-1·min-1) were randomly assigned to an intervention (HIIT + NT, NT, HIIT) or control group. NT performance (20 trials per session) was measured pre-and post-test (at 5, 15, and 25 min while running on the treadmill). The participants trained twice a week for a 4-week intervention period. There was a significant interaction effect between pre/post-test and groups regarding perceptual-cognitive performance, indicating similar enhancements in the HIIT + NT and the NT group during exercise. HIIT influences physical fitness but did not show any impact on perceptual-cognitive performance. Due to the specific NT task characteristics, improved physical abilities may not directly impact sport-specific perceptual-cognitive performance. Our findings suggest that training resulted in substantial task-specific gains. Therefore, combination training may be proposed as a training program to improve perceptual-cognitive, and physical performance in a time-efficient way.

The Analgesic Efficacy of Nefopam in Patient-Controlled Analgesia after Laparoscopic Gynecologic Surgery: A Randomized, Double-Blind, Non-Inferiority Study.

Opioid-sparing effects of nefopam during patient-controlled analgesia (PCA) are well demonstrated. We hypothesized that postoperative pain control with an opioid-equivalent dose of nefopam as a single analgesic agent for PCA would not be inferior to fentanyl in laparoscopic gynecologic surgery. In total, 135 patients were randomly assigned to the N (nefopam 200 mg), NF (fentanyl 500 mcg + nefopam 100 mg), and F (fentanyl 1000 mcg) groups (n = 45 patients per group). The primary outcome was the numerical rating scale (NRS) score at rest at 6 h postoperatively, and the non-inferiority limit was set to 1. Secondary outcomes were pain severity and incidence of nausea and vomiting for 48 h postoperatively. Mean differences (MD) in primary outcome between the N and F groups were 0.4 (95% confidence interval (CI) -0.5 to 1.3). The upper limit of 95% CI exceeded the non-inferiority limit. The N group showed higher pain scores than the NF group (MD, 1.1; 95% CI, 0.3-1.9) in pairwise comparisons. No significant intergroup differences were observed in the cumulative dose of PCA usage and incidence of postoperative nausea and vomiting (PONV). In laparoscopic gynecological surgery, nefopam alone showed limited efficacy for postoperative pain control.

Effects of acute exercise at different intensities on fine motor-cognitive dual-task performance while walking: A functional near-infrared spectroscopy study.

Studies on the effects of acute exercises on cognitive functions vary greatly and depend on the duration and intensity of exercise and the type of cognitive tasks. This study aimed to investigate the neural correlates that underpin the acute effects of high-intensity interval (HIIE) versus moderate-intensity continuous exercise (MCE) on fine motor-cognitive performance while walking (dual-task, DT) in healthy young adults. Twenty-nine healthy right-handers (mean age: 25.1 years ± 4.04; 7 female) performed the digital trail-making-test (dTMT) while walking (5 km/h) before and after acute exercise. During task performance, the hemodynamic activation of the frontopolar area (FPA), dorsolateral prefrontal (DLPFC), and motor cortex (M1) was recorded using functional near-infrared spectroscopy (fNIRS). Both HIIE and MCE resulted in improved dTMT performance, as reflected by an increase in the number of completed circles and a reduction in the time within and between circuits (reflecting improvements in working memory, inhibition, and decision making). Notably, HIIE evoked higher cortical activity on all brain areas measured in the present study than the MCE group. To our knowledge, these results provide the first empirical evidence using a mobile neuroimaging approach that both HIIE and MCE improve executive function during walking, likely mediated by increased activation of the task-related area of the prefrontal cortex and the ability to effectively use, among other things, high fitness levels as neural enrichment resources.

A Simple Route of Printing Explosive Crystalized Micro-Patterns by Using Direct Ink Writing.

The production of energetic crystalized micro-patterns by using one-step printing has become a recent trend in energetic materials engineering. We report a direct ink writing (DIW) approach in which micro-scale energetic composites composed of 1,3,5-trinitro-1,3,5-triazinane (RDX) crystals in selected ink formulations of a cellulose acetate butyrate (CAB) matrix are produced based on a direct phase transformation from organic, solvent-based, all-liquid ink. Using the formulated RDX ink and the DIW method, we printed crystalized RDX micro-patterns of various sizes and shapes on silicon wafers. The crystalized RDX micro-patterns contained single crystals on pristine Si wafers while the micro-patterns containing dendrite crystals were produced on UV-ozone (UVO)-treated Si wafers. The printing method and the formulated all-liquid ink make up a simple route for designing and printing energetic micro-patterns for micro-electromechanical systems.

Fabrication and Biological Activities of Plasmid DNA Gene Carrier Nanoparticles Based on Biodegradable l-Tyrosine Polyurethane.

Gene therapy is a suitable alternative to chemotherapy due to the complications of drug resistance and toxicity of drugs, and is also known to reduce the occurrence of cellular mutation through the use of gene carriers. In this study, gene carrier nanoparticles with minimal toxicity and high transfection efficiency were fabricated from a biocompatible and biodegradable polymer, l-tyrosine polyurethane (LTU), which was polymerized from presynthesized desaminotyrosyl tyrosine hexyl ester (DTH) and polyethylene glycol (PEG), by using double emulsion and solvent evaporation techniques, resulting in the formation of porous nanoparticles, and then used to evaluate their potential biological activities through molecular controlled release and transfection studies. To assess cellular uptake and transfection efficiency, two model drugs, fluorescently labeled bovine serum albumin (FITC-BSA) and plasmid DNA-linear polyethylenimine (LPEI) complex, were successfully encapsulated in nanoparticles, and their transfection properties and cytotoxicities were evaluated in LX2 as a normal cell and in HepG2 and MCF7 as cancer cells. The morphology and average diameter of the LTU nanoparticles were confirmed using light microscopy, transmission electron microscopy, and dynamic light scattering, while confocal microscopy was used to validate the cellular uptake of FITC-BSA-encapsulated LTU nanoparticles. Moreover, the successful cellular uptake of LTU nanoparticles encapsulated with pDNA-LPEI and the high transfection efficiency, confirmed by gel electrophoresis and X-gal assay transfection, indicated that LTU nanoparticles had excellent cell adsorption ability, facilitated gene encapsulation, and showed the sustained release tendency of genes through transfection experiments, with an optimal concentration ratio of pDNA and LPEI of 1:10. All the above characteristics are ideal for gene carriers designed to transport and release drugs into the cytoplasm, thus facilitating effective gene therapy.

Synthesis and Characterization of Polyfumarateurethane Nanoparticles for Sustained Release of Bupivacaine.

Biodegradable polyfumarateurethane (PFU) for use as a bupivacaine delivery vehicle, synthesized using di-(2-hydroxypropyl fumarate) (DHPF), polyethylene glycol (PEG) and 1,6-hexamethylene diisocyanate (HMDI), was designed to be degradable through the hydrolysis and enzymatic degradation of the ester bonds in its polymer backbone. Using a water-in-oil-in-water double emulsion techniques, nanoparticles encapsulating water or fluorescein isothiocyanate (FITC) were fabricated to avoid the immune system owing to the presence of PEG on their surface. The morphologies of these nanoparticles were characterized by DLS, TEM, FE-SEM, and fluorescent microscopies. The present study explored the encapsulation, loading efficiency and in vitro drug release of bupivacaine encapsulated with biodegradable PFU nanoparticles for the treatment of local anesthesia. Various concentrations of bupivacaine were encapsulated into nanoparticles and their encapsulation efficiencies and drug loading were investigated. Encapsulation efficiency was highest when 2.5% bupivacaine was encapsulated. Drug release behavior from the bupivacaine-loaded PFU nanoparticles followed a sustained release profile.

Quantitatively controllable fluid flows with ballpoint-pen-printed patterns for programmable photo-paper-based microfluidic devices.

Regulating the fluid flow in microfluidic devices enables a wide range of assay protocols for analytical applications. A programmable, photo-paper-based microfluidic device fabricated by using a method of cutting and laminating, followed by printing, is reported. The flow distance of fluid in the photo-paper-based channel was linearly proportional to time. By printing silver nanoparticle (AgNP) and poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole-co-tetrafluoroethylene] (PTFE) patterns on the surface of a photo-paper-based channel, we were able to either increase or decrease the fluid flow in the fabricated microfluidic devices, while maintaining the linearity in the flow distance-time relation. In comparison to the speed of fluid flow in a pristine channel, by using hydrophilic AgNP patterns, we were able to increase the speed in the channel by up to 15 times while we were able to slow the speed by a factor of 3 when using hydrophobic PTFE dots. We then further demonstrated a single-step protocol for detecting glucose and a multi-step protocol for detecting methyl paraoxon (MPO) with our methods in photo-paper-based microfluidic devices. This approach can lead to improved fluid handling techniques to achieve a wide range of complex, but programmable, assays without the need for any additional auxiliary devices for automated operation.

Recurrent parvovirus B19 infection-associated pure red cell aplasia in a kidney transplant patient.

Posttransplant anemia is a common complication after kidney transplantation. Parvovirus B19 (PVB19) infection can induce pure red cell aplasia (PRCA) in immunosuppressed transplant patients. We herein report a case of recurrent PVB19-associated PRCA in a kidney transplant patient. A 49-year-old woman presented with anemia and normal renal function 1 year after a deceased-donor kidney transplantation for immunoglobulin A nephropathy-related end-stage renal disease. She received desensitization therapy, and 2 years later, she underwent transplantation with thymoglobulin induction. Despite repeated red cell transfusion and erythropoietin therapy, her anemia aggravated progressively. Bone marrow biopsy revealed normocytic normochromic PRCA. Real-time polymerase chain reaction detected a high plasma load of PVB19. Administration of intravenous immunoglobulin (IVIG) at 2 g/kg with adjuvant reduction of tacrolimus and discontinuation of myfortic acid effectively treated the anemia. However, the PVB19 load remained high, and PRCA recurred 7 months after the initial IVIG treatment. Tacrolimus was switched to cyclosporine in the second IVIG treatment, which successfully improved PRCA and reduced the PVB19 load. Our case suggested that PVB19-associated PRCA should be suspected when persistent anemia is observed in kidney transplant patients with heavy immunosuppression and that PVB19-associated PRCA can recur in the presence of persistent PVB19 viremia.

Cardiac Arrest from Patient Position Change after Spine Surgery on a Jackson Table.

The Jackson table has minimal effects on cardiac function because it does not elevate abdominal and thoracic pressures. In addition, it decreases venous congestion and increases exposure of the surgical field. However, the hips and knees are flexed with inappropriate padding, and venostasis is promoted and increased. Pulmonary thromboembolism (PTE) is fatal; thus immediate diagnosis and treatment are essential. However, clinical signs of intraoperative PTE are difficult to discern. Thrombolytic therapy can be considered as first-line therapy, but bleeding limits its use. The authors report a case of PTE resulting from patient positional change after spine surgery, and the use of immediate postoperative recombinant tissue-type plasminogen activator.

Programmable Paper-Based Microfluidic Devices for Biomarker Detections.

Recent advanced paper-based microfluidic devices provide an alternative technology for the detection of biomarkers by using affordable and portable devices for point-of-care testing (POCT). Programmable paper-based microfluidic devices enable a wide range of biomarker detection with high sensitivity and automation for single- and multi-step assays because they provide better control for manipulating fluid samples. In this review, we examine the advances in programmable microfluidics, i.e., paper-based continuous-flow microfluidic (p-CMF) devices and paper-based digital microfluidic (p-DMF) devices, for biomarker detection. First, we discuss the methods used to fabricate these two types of paper-based microfluidic devices and the strategies for programming fluid delivery and for droplet manipulation. Next, we discuss the use of these programmable paper-based devices for the single- and multi-step detection of biomarkers. Finally, we present the current limitations of paper-based microfluidics for biomarker detection and the outlook for their development.