The imminent risk of a fracture-existing worldwide data: a systematic review and meta-analysis.

The overall incidence of imminent fracture after a prior fragility fracture was 7.58% in the first year and 11.58% in the first 2 years. Approximately half of re-fractures occurred in the first 2 years after a fragility fracture. Older patients that have suffered from a fragility fracture should be treated promptly, with immediate care and a secondary fracture prevention to prevent the high imminent risk of a fracture. INTRODUCTION: Imminent fractures refer to the fractures that occur within 2 years of an initial fracture. It is well known that the risk of a subsequent fracture is not constant with time and occurs shortly after the initial one. This systematic review and meta-analysis aimed to present the existing data on imminent fracture worldwide. METHODS: Literature search was conducted in Pubmed, Embase, and Web of Science databases until 26 October 2021 for studies reporting the incidence of imminent osteoporotic fractures among people aged 50 years or older. The overall incidence of imminent fracture was pooled and subgroup analyses of index fracture sites and regions on incidence of imminent fracture were performed, with the 95% confidence interval (CI) being calculated. Percentage of imminent fracture occurring in follow-up period was calculated and pooled by meta-analysis. Hazard ratio (HR) was used to estimate the gender differences on the imminent risk of fracture. RESULTS: A total of 1446 articles were identified. Nineteen observational studies were eligible for our systematic review, in which 18 were used for quantitative analysis. Pooled overall incidence of imminent fracture in the first year after an osteoporotic fracture was 7.58% (95% CI 5.84 to 9.31%) and cumulative incidence in the first 2 years was 11.58% (95% CI 8.94 to 14.21%). Subgroup analysis showed that in the first 2 years, the pooled incidence in Asia was 7.30% (95% CI 3.42 to 11.18%), whilst incidence in Europe/North America was 13.17% (95% CI 10.14 to 16.20%). In included studies with follow-up period of more than 5 years, pooled imminent fracture percentage in the first 2 years was 47.24% (95% CI 26.18 to 68.30%). Hazard ratio (HR) on gender showed that women had an overall slight increase in risk of imminent fractures (HR 1.18, 95% CI 1.11 to 1.25). CONCLUSION: The incidence of imminent fracture is high globally at 11.58%. Approximately half of all refractures occur in the first 2 years after an index fragility fracture. Older patients that have suffered from a fragility fracture should be treated promptly. Also, immediate care and secondary fracture prevention are necessary to prevent the high imminent risk of a fracture, especially within the first 2 years.

Moving toward rapid and low-cost point-of-care molecular diagnostics with a repurposed 3D printer and RPA.

Traditionally, the majority of nucleic acid amplification-based molecular diagnostic tests are done in centralized settings. In recent years, point-of-care tests have been developed for use in low-resource settings away from central laboratories. While most experts agree that point-of-care molecular tests are greatly needed, their availability as cost-effective and easy-to-operate tests remains an unmet goal. In this article, we discuss our efforts to develop a recombinase polymerase amplification reaction-based test that will meet these criteria. First, we describe our efforts in repurposing a low-cost 3D printer as a platform that can carry out medium-throughput, rapid, and high-performing nucleic acid extraction. Next, we address how these purified templates can be rapidly amplified and analyzed using the 3D printer's heated bed or the deconstructed, low-cost thermal cycler we have developed. In both approaches, real-time isothermal amplification and detection of template DNA or RNA can be accomplished using a low-cost portable detector or smartphone camera. Last, we demonstrate the capability of our technologies using foodborne pathogens and the Zika virus. Our low-cost approach does not employ complicated and high-cost components, making it suitable for resource-limited settings. When integrated and commercialized, it will offer simple sample-to-answer molecular diagnostics.

Advances in microbial self-healing concrete: A critical review of mechanisms, developments, and future directions.

The self-healing bioconcrete, or bioconcrete as concrete containing microorganisms with self-healing capacities, presents a transformative strategy to extend the service life of concrete structures. This technology harnesses the biological capabilities of specific microorganisms, such as bacteria and fungi, which are integral to the material's capacity to autonomously mend cracks, thereby maintaining structural integrity. This review highlights the complex biochemical pathways these organisms utilize to produce healing compounds like calcium carbonate, and how environmental parameters, such as pH, temperature, oxygen, and moisture critically affect the repair efficacy. A comprehensive analysis of recently published peer-reviewed literature, and contemporary experimental research forms the backbone of this review with a focus on microbiological aspects of the self-healing process. The review assesses the challenges facing self-healing bioconcrete, including the longevity of microbial spores and the cost implications for large-scale implementation. Further, attention is given to potential research directions, such as investigating alternative biological agents and optimizing the concrete environment to support microbial activity. The culmination of this investigation is a call to action for integrating self-healing bioconcrete in construction on a broader scale, thereby realizing its potential to fortify infrastructure resilience and sustainability.

Development of a Colorimetric Loop-Mediated Isothermal Amplification Assay for the Detection of Trypanosoma cruzi in Low-Resource Settings.

Chagas disease is an inflammatory parasitic infection caused by Trypanosoma cruzi (T. cruzi). Early diagnosis is crucial in guiding treatment and slowing disease progression; however, current diagnostic methods have insufficient detection limits and often require skilled technicians. Molecular tests, especially isothermal nucleic acid assays, are advantageous due to their excellent sensitivity, specificity, speed, and simplicity. Here, we optimized a colorimetric loop-mediated isothermal amplification (LAMP) assay for T. cruzi. We can detect as few as 2 genomic copies/reaction using three different T. cruzi strains. We examined selectivity using other parasitic protozoans and successfully detected T. cruzi DNA extracted from parasites in human whole blood down to 1.2 parasite equivalents/reaction. We also performed a blinded study using canine blood samples and established a 100% sensitivity, specificity, and accuracy for the colorimetric LAMP assay. Finally, we used a heated 3D printer bed and an insulated thermos cup to demonstrate that the LAMP incubation step could be performed with accessible, low-cost materials. Altogether, we have developed a high-performing assay for T. cruzi with a simple colorimetric output that would be ideal for rapid, low-cost screening at the point of use.

Treatment effects, adverse outcomes and cardiovascular safety of romosozumab - Existing worldwide data: A systematic review and meta-analysis.

Background: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials. Methods: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was "(romosozumab) AND (osteoporosis OR safety)". Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale. Results: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51-12.57; p < 0.00001)), total hip (4.04 (95 % CI = 3.10-4.99; p < 0.00001)) and femoral neck bone mineral density (3.77 (95 % CI = 2.90-4.64; p < 0.00001)) at 12 months. There was significantly less likelihood of new vertebral fractures with romosozumab compared to control (odds ratio (OR) 0.42 (95 % CI = 0.20-0.89); p = 0.02) at 12 months of treatment. There was significantly less likelihood of new vertebral fracture at 24 months with 12 months of romosozumab followed by sequential treatment with anti-resorptive compared to control with only anti-resorptive agent use (OR 0.36 (95 % CI = 0.18-0.71); p = 0.003). There was no significant difference in serious adverse events and fatal adverse events with use of romosozumab compared with control in our meta-analyses. There were no significant differences in serious cardiovascular events in Asian population of romosozumab with control group with 12 months of romosozumab treatment followed by 24 months of anti-resorptive agent with OR 1.09 (95 % CI = 0.40-2.96; P = 0.86). There was no significant difference between romosozumab group and control group for the median time to radiographic healing. Our qualitative analysis on Quantitative Computed Tomography (QCT), Finite element analysis (FEA) and bone biopsy analyses demonstrated that romosozumab improved parameters and measures in these domains as well. Conclusion: In conclusion, our study showed that romosozumab was an effective agent to treat osteoporosis with high quality evidence. There were no significant differences in the adverse events, serious adverse events, fatal adverse events identified. Further subgroup analysis of cardiovascular events and cardiovascular death in the total population showed no differences either. The translational potential of this article: Given the results, romosozumab is an effective agent to treat patients with very-high risk of osteoporotic fractures.

Short-chain fatty acids enhance muscle mass and function through the activation of mTOR signalling pathways in sarcopenic mice.

BACKGROUND: Sarcopenia is a prevalent muscle disorder in old people leading to higher fracture rate, mortality, and other adverse clinical outcomes. Evidence indicates that short-chain fatty acids (SCFAs), which are beneficial gut microbial metabolites, were reduced in old people with sarcopenia. This study aimed to determine whether the use of SCFAs as a supplement can be a therapeutic strategy of sarcopenia in a pre-clinical model. METHODS: Seven-month-old pre-sarcopenic senescent accelerated mouse prone 8 (SAMP8) mice received daily SCFAs cocktail (acetate, butyrate, and propionate) for 3 months. Age-matched senescence accelerated mouse resistant 1 (SAMR1) and SAMP8 mice receiving sodium-matched drinking water were control groups. The gut microbiota composition analysis of aged mice with or without sarcopenia was conducted by 16S rDNA sequencing. Gut barrier-related proteins and lipopolysaccharide (LPS) concentration were biomarkers of gut permeability. Colon inflammation levels, circulatory SCFAs concentration, muscle quality, function, and underlying pathways were detected by cell number counting, RT-qPCR, gas chromatography-mass spectrometry, measurements of muscle wet weight and grip strength, ex vivo functional test, treadmill endurance test, transcriptomic sequencing, morphological and immunofluorescent staining, as well as western blot. To investigate the role of mTOR signalling pathways in SCFAs treatment, C2C12 myotubes were treated with rapamycin. RESULTS: Aged SAMP8 mice had different microbiota composition, and lower serum butyric acid compared with SAMR1 mice (P < 0.05). SCFAs treatment reversed the increment of colon inflammation (2.8-fold lower of il-1ß) and gut barrier permeability (1.7-fold lower of LPS) in SAMP8 mice. Increased muscle mass, myofibre cross-sectional area, grip strength, twitch and tetanic force were found in SCFAs-treated mice compared with control SAMP8 mice (P < 0.05). Anti-fatigue capacity (1.6-fold) and muscle glycogen (2-fold) also improved after SCFAs treatment (P < 0.05). Transcriptomic analysis showed that AMPK, insulin, and mTOR pathways were involved in SCFAs treatment (P < 0.05). Regulation of AKT/mTOR/S6K1 and AMPK/PGC1α pathways were found. SCFAs attenuated fat infiltration and improved mitochondria biogenesis of atrophic muscle. In vitro studies indicated that SCFAs inhibited FoxO3a/Atrogin1 and activated mTOR pathways to improve myotube growth (P < 0.05), and rapamycin attenuated the effect of SCFAs through the inhibition of mTOR pathways. CONCLUSIONS: This study demonstrated that bacterial metabolites SCFAs could attenuate age-related muscle loss and dysfunction, and protein synthesis-related mTOR signalling pathways were involved both in vivo and in vitro.

Does the regulation of skeletal muscle influence cognitive function? A scoping review of pre-clinical evidence.

Background: Cognitive impairment is a major challenge for elderlies, as it can progress in a rapid manner and effective treatments are limited. Sarcopenic elderlies have a higher risk of dementia. This scoping review aims to reveal whether muscle is a mediator of cognitive function from pre-clinical evidence. Methods: PubMed, Embase, and Web of Science were searched to Feb 2nd, 2022, using the keywords (muscle) AND (cognition OR dementia OR Alzheimer) AND (mouse OR rat OR animal). The PRISMA guideline was used in this study. Results: A total of 17 pre-clinical studies were selected from 7638 studies. 4 studies reported that muscle atrophy and injury harmed memory, functional factors, and neurons in the brain for rodents with or without Alzheimer's disease (AD). 3 studies observed exercise induced muscle to secrete factors, including lactate, fibronectin type III domain-containing protein 5 (FNDC5), and cathepsin B, which plays essential roles in the elevation of cognitive functions and brain-derived neurotrophic factor (BDNF) levels. Muscle-targeted treatments including electrical stimulation and intramuscular injections had effective remote effects on the hippocampus. 6 studies showed that muscle-specific overexpression of scFv59 and Neprilysin, or myostatin knockdown alleviated AD symptoms. 1 study showed that muscle insulin resistance also led to deficient hippocampal neurogenesis in MKR mice. Conclusions: The skeletal muscle is involved in the mediation of cognitive function. The evidence was established by the response in the brain (altered number of neurons, functional factors, and other AD pathological characteristics) with muscle atrophy or injury, muscle secretory factors, and muscle-targeted treatments. The translational potential of this paper: This study summarizes the current evidence in how muscle affects cognition in molecular levels, which supports muscle-specific treatments as potential clinical strategies to prevent cognitive dysfunction.

Deciphering the "obesity paradox" in the elderly: A systematic review and meta-analysis of sarcopenic obesity.

Aging and obesity are two global concerns in public health. Sarcopenic obesity (SO), defined as the combination of age-related sarcopenia and obesity, has become a pressing issue. This systematic review and meta-analysis summarize the current clinical evidence relevant to SO. PubMed, Embase, and Web of Science were searched, and 106 clinical studies with 167,151 elderlies were included. The estimated prevalence of SO was 9% in both men and women. Obesity was associated with 34% reduced risk of sarcopenia (odds ratio [OR] 0.66, 95% CI 0.48-0.91; p < 0.001). The pooled hazard ratio (HR) of all-cause mortality was 1.51 (95% CI 1.14-2.02; p < 0.001) for people with SO compared with healthy individuals. SO was associated with increased risk of cardiovascular disease and related mortality, metabolic disorders, cognitive impairment, arthritis, functional limitation, and lung diseases (all ORs > 1.0, p < 0.05). The attenuated risk of sarcopenia in elderlies with obesity ("obesity paradox") was dependent on higher muscle mass and strength. Apart from unifying the diagnosis of SO, more research is needed to subphenotype people with obesity and sarcopenia for individualized treatment. Meanwhile, the maintenance of proper body composition of muscle and fat may delay or attenuate the adverse outcomes of aging.

Muscle plays a more superior role than fat in bone homeostasis: A cross-sectional study of old Asian people.

Objectives: The aim of this study was to discover the role of fat and muscle in bone structures, as well as the relationship between obesity and sarcopenia on age-related osteoporosis. Methods: A total of 400 participants (65.0 ± 8.2 years old, 42.3% women) were recruited. Fat, muscle, bone parameters, basic demographics, medical history, physical performance and activity, and calcium intake of participants were obtained from datasets. The diagnosis of osteoporosis, sarcopenia, and obesity was based on current recommendations. Pearson correlation, non-linear regression models, and decision tree analyses were performed to study the relationship between fat, muscle, and bone. Logistic regression analyses were used to explore the risk of osteoporosis in old people with obesity or sarcopenia via Model 1 (unadjusted) and Model 2 (adjusted by age, physical activity, and calcium intake). Results: Correlation analysis showed that limb muscle mass and index, and age were best related to bone mineral density (BMD) (|r| = 0.386-0.632, p < 0.001). On the contrary, body mass index (BMI) and increased body fat percentage (BF%) were harmful for bone health. An increase of BMI and fat mass index slowed the increase of BMD in the spine, while skeletal muscle mass index accelerated the increase. People with sarcopenia had low muscle mass and strength. When separating subjects into sarcopenia and non-sarcopenia status, sarcopenia was independently related to higher risks of osteoporosis in both models (OR > 1, p < 0.05). BMI-defined obesity in Model 1 as well as BF%-defined obesity in both models did not reduce the risk of osteoporosis in both models (p > 0.05). The decision tree classification (85% accuracy) showed that greater body weight and larger lower limb muscle performance were negatively related to osteoporosis, while fat mass and percentage did not play roles in this prediction. Conclusion: Low muscle mass and function were harmful to bone health. Obesity defined by both BMI and BF% had limited protective roles in osteoporosis. The benefits for bone from increased muscle mass and function play a more superior role than increased fat mass in old people. Sarcopenia prevention and treatment instead of controlling obesity should be recommended as an approach to reduce the risks of age-related osteoporosis and fragility fracture for elderly people.

3D printing in orthopaedic surgery: a scoping review of randomized controlled trials.

AIMS: The use of 3D printing has become increasingly popular and has been widely used in orthopaedic surgery. There has been a trend towards an increasing number of publications in this field, but existing literature incorporates limited high-quality studies, and there is a lack of reports on outcomes. The aim of this study was to perform a scoping review with Level I evidence on the application and effectiveness of 3D printing. METHODS: A literature search was performed in PubMed, Embase, and Web of Science databases. The keywords used for the search criteria were ((3d print*) OR (rapid prototyp*) OR (additive manufactur*)) AND (orthopaedic). The inclusion criteria were: 1) use of 3D printing in orthopaedics, 2) randomized controlled trials, and 3) studies with participants/patients. Risk of bias was assessed with Cochrane Collaboration Tool and PEDro Score. Pooled analysis was performed. RESULTS: Overall, 21 studies were included in our study with a pooled total of 932 participants. Pooled analysis showed that operating time (p < 0.001), blood loss (p < 0.001), fluoroscopy times (p < 0.001), bone union time (p < 0.001), pain (p = 0.040), accuracy (p < 0.001), and functional scores (p < 0.001) were significantly improved with 3D printing compared to the control group. There were no significant differences in complications. CONCLUSION: 3D printing is a rapidly developing field in orthopaedics. Our findings show that 3D printing is advantageous in terms of operating time, blood loss, fluoroscopy times, bone union time, pain, accuracy, and function. The use of 3D printing did not increase the risk of complications. Cite this article: Bone Joint Res 2021;10(12):807-819.

Risk of community-acquired pneumonia requiring hospitalization in patients with spondyloarthritis.

AIMS: To compare the risk of community-acquired pneumonia (CAP) requiring hospitalization in spondyloarthritis (SpA) and non-specific back pain (NSBP), and to identify the risk factors for CAP in SpA. METHODS: A total of 2984 patients with SpA from 11 rheumatology centers and 2526 patients with NSBP from orthopedic units were reviewed from the centralized electronic database in Hong Kong. Incidence of CAP requiring hospitalization and demographic data including age, gender, smoking and drinking status, use of sulfasalazine, individual biological-disease modifying anti-rheumatic drugs (DMARDs) used, micro-organisms, other immunosuppressants or immunosuppressive states, use of steroid for more than ½ year, and co-morbidities were identified. Risks of CAP in SpA were compared with those in NSBP using propensity score regression method. Multivariate Cox regression model was used to identify the risk factors in SpA. RESULTS: CAP requiring hospitalization was found in 183 patients with SpA and 138 patients with NSBP. Increased risk for CAP was found in the following groups with SpA: all subgroups (hazard ratio (HR) 2.14, p < 0.001), without use of DMARDs (HR 2.64, p < 0.001), without psoriasis and not taking DMARDs (HR 2.38, p < 0.001). Infliximab (HR2.55, p = 0.04), smoking (HR 1.68, p = 0.003), comorbid psoriasis (HR 1.67, p = 0.003), and use of steroid for more than ½ year (HR 1.94, p = 0.003) were found to associate with CAP after adjustments for traditional risk factors. CONCLUSION: Risk of CAP is increased in patients with SpA. Our data favor universal influenza and pneumococcal vaccination programs in the population. Rheumatologists should also advise smoking cessation and avoid long term steroid therapy.

Hyperuricemia in Asian psoriatic arthritis patients.

AIM: It is generally accepted that hyperuricemia is commonly associated with psoriatic arthritis (PsA). However, variations in ethnicity, diet and habitat may contribute to differences in prevalence and risk factors for hyperuricemia in PsA patients. Moreover, Asian specific data is deficient. The primary objective of the present study was to determine the prevalence of hyperuricemia among PsA patients. The secondary objective was to explore its associated risk factors. METHODS: This was a multi-center, cross-sectional observational study of 160 PsA patients from local Rheumatology clinics. Serum uric acid (SUA) level and other clinical parameters were measured and hyperuricemia was defined as SUA level greater or equal to 360 umol/L in females and 420 umol/L in males. RESULTS: Forty-nine of 160 patients (30.6%) had hyperuricemia, of which 32 were men, 17 were women. Among those with hyperuricemia, mean SUA level was 500.7 ± 95.9 umol/L and 427.8 ± 83.1 umol/L in males and females, respectively. Univariate analysis found: (i) overweight status; (ii) obesity; (iii) Psoriasis Area and Severity Index; (iv) body surface area; (v) severe skin involvement, as being potentially associated with hyperuricemia. Regression model identified overweight status increased the likelihood of hyperuricemia in PsA, with an odds ratio of 4.4 (95% CI: 2.0-9.5). Furthermore, there was moderately positive correlation (r = 0.37) between body mass index (BMI) and SUA level. No associations were found between arthritis conditions and duration, lipid profile, creatinine clearance; and hyperuricemia. CONCLUSION: A significant proportion of PsA patients had asymptomatic hyperuricemia. It was closely related with BMI, which represented metabolic dysregulation; but not with severity of skin disease, joint involvement or renal function.

Diffusion-weighted imaging versus short tau inversion recovery sequence: Usefulness in detection of active sacroiliitis and early diagnosis of axial spondyloarthritis.

OBJECTIVE: To compare the utility of Diffusion weighted imaging (DWI) with short tau inversion recovery (STIR) sequence in the diagnosis of early axial spondyloarthritis (SpA). METHODS: Three hundred and five patients with chronic back pain were recruited consecutively from 3 rheumatology centers. Clinical, radiological and blood parameters were recorded. Patients with back pain duration no more than 3 years were classified as having early disease. STIR sequence and DWI of the sacroiliac joints were obtained and assessed using the Spondyloarthritis Research Consortium of Canada (SPARCC) method. The Assessment in Spondyloarthritis international Society definition was used to define positive STIR and DWI. Results were compared to expert diagnosed axial SpA. RESULTS: When compared to STIR sequence, DWI had similar sensitivity (STIR 0.29, DWI 0.30) and specificity (STIR 0.97, DWI 0.92) in diagnosing sacroiliitis. However, STIR sequence had better reliability (STIR 0.78, DWI 0.61). In early disease group, DWI was not better than STIR sequence in detecting active sacroiliitis (sensitivity DWI vs STIR: 0.34 vs 0.36; specificity DWI vs STIR: 0.93 vs 0.93; positive predictive value DWI vs STIR: 0.92 vs 0.92; negative predictive value DWI vs STIR: 0.36 vs 0.37). Using the Assessment in SpondyloArthritis international Society (ASAS) classification criteria, 67/98 patients with early disease (sensitivity 0.91 specificity 0.90) and 221/305 overall (sensitivity 0.90; specificity 0.92) were classified as axial SpA. Among the expert diagnosed axial SpA patients who did not meet the ASAS criteria, only 2 had positive DWI. CONCLUSION: DWI and STIR have similar sensitivity in diagnosing axSpA in early disease. However, the use of DWI is limited by poorer reliability when compared with STIR.

A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics.

The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low-cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC's ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC's performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell-phone-based fluorescence detector, the TTC will increase the availability of on-site molecular diagnostics in low-resource settings.

Rapid, Affordable and Portable Medium-Throughput Molecular Device for Zika Virus.

Zika virus (ZIKV) has gained global attention as an etiologic agent of fetal microcephaly and Guillain-Barré syndrome. Existing immuno-based rapid tests often fail to distinguish between Zika and related flaviviruses that are common in affected regions of Central and South Americas and the Caribbean. The US CDC and qualified state health department laboratories can perform the reverse transcription polymerase chain reaction (RT-PCR) ZIKV test using highly sophisticated instruments with long turnaround times. The preliminary results of a portable and low-cost molecular diagnostics system for ZIKV infection are reported here. In less than 15 minutes, this low-cost platform can automatically perform high quality RNA extraction from up to 12 ZIKV-spiked urine samples simultaneously. It can also perform reverse transcription recombinase polymerase amplification reaction (RT-RPA) in ≤15 minutes. The fluorescent signal produced from probe-based RT-RPA or RT-PCR assays can be monitored using LEDs and a smartphone camera. In addition, the RT-RPA and RT-PCR assays do not cross-react with dengue and chikungunya viral RNA. This low-cost system lacks complicated, sensitive and high cost components, making it suitable for resource-limited settings. It has the potential to offer simple sample-to-answer molecular diagnostics and can inform healthcare workers of patients' diagnosis promptly.