Randomized Clinical Trial Visual Abstract Display and Social Media-Driven Website Traffic.

In this study, the authors assessed whether publication of a visual abstract on social media was associated with reader engagement online.

Mycobacterium tuberculosis Rv1916 is an Acetyl-CoA-Binding Protein.

Isocitrate lyase (ICL) isoform 2 is an essential enzyme for some clinical Mycobacterium tuberculosis (Mtb) strains during infection. In the laboratory Mtb strain H37Rv, the icl2 gene encodes two distinct gene products - Rv1915 and Rv1916 - due to a frameshift mutation. This study aims to characterise these two gene products to understand their structure and function. While we were unable to produce Rv1915 recombinantly, soluble Rv1916 was obtained with sufficient yield for characterisation. Kinetic studies using UV-visible spectrophotometry and 1 H-NMR spectroscopy showed that recombinant Rv1916 does not possess isocitrate lyase activity, while waterLOGSY binding experiments demonstrated that it could bind acetyl-CoA. Finally, X-ray crystallography revealed structural similarities between Rv1916 and the C-terminal domain of ICL2. Considering the probable differences between full-length ICL2 and the gene products Rv1915 and Rv1916, care must be taken when using Mtb H37Rv as a model organism to study central carbon metabolism.

Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions.

The prevalence of myasthenia gravis (MG), an autoimmune disorder, is increasing among all subsets of the population leading to an elevated economic and social burden. The pathogenesis of MG is characterized by the synthesis of autoantibodies against the acetylcholine receptor (AChR), low-density lipoprotein receptor-related protein 4 (LRP4), or muscle-specific kinase at the neuromuscular junction, thereby leading to muscular weakness and fatigue. Based on clinical and laboratory examinations, the research is focused on distinguishing MG from other autoimmune, genetic diseases of neuromuscular transmission. Technological advancements in machine learning, a subset of artificial intelligence (AI) have been assistive in accurate diagnosis and management. Besides, addressing the clinical needs of MG patients is critical to improving quality of life (QoL) and satisfaction. Lifestyle changes including physical exercise and traditional Chinese medicine/herbs have also been shown to exert an ameliorative impact on MG progression. To achieve enhanced therapeutic efficacy, cholinesterase inhibitors, immunosuppressive drugs, and steroids in addition to plasma exchange therapy are widely recommended. Under surgical intervention, thymectomy is the only feasible alternative to removing thymoma to overcome thymoma-associated MG. Although these conventional and current therapeutic approaches are effective, the associated adverse events and surgical complexity limit their wide application. Moreover, Restivo et al. also, to increase survival and QoL, further recent developments revealed that antibody, gene, and regenerative therapies (such as stem cells and exosomes) are currently being investigated as a safer and more efficacious alternative. Considering these above-mentioned points, we have comprehensively reviewed the recent advances in pathological etiologies of MG including COVID-19, and its therapeutic management.

Risk attitude and belief updating: theory and experiment.

Despite the importance of risk attitude in decision-making, its role in belief updating has been overlooked. Using economic theory, we analyzed a dual-self equilibrium where an individual first updates her belief about an uncertain state and then takes an action to maximize her payoff. We showed that stronger risk aversion drives more conservative actions and thus decreases the instrumental value of information relative to the importance of belief-based utility. As a result, the relationship between risk attitude and belief updating depends on the nature of the belief-based utility. With self-relevant information, stronger risk aversion leads to more belief change, whereas with self-irrelevant information, stronger risk aversion leads to less belief change. Our experimental results concur with the theoretical predictions with two settings where subjects update their belief about their IQ and a randomly drawn number, respectively. We discuss implications on persuasion, advertisements, and political campaigns.

The Association of Erythropoietin and Age-Related Macular Degeneration in Hemodialysis Patients: A Nationwide Population-Based Cohort Study.

This population-based retrospective cohort study investigated the effectiveness of erythropoietin (EPO) treatment in reducing the risk of age-related macular degeneration (AMD) in hemodialysis patients, using the National Health Insurance Research Data of Taiwan. From the database, we identified 147,318 end-stage renal disease (ESRD) patients on hemodialysis who had been diagnosed in 2000−2014 to establish the propensity-score-matched EPO user cohort and non-EPO user cohort with equal sample size of 15,992. By the end of 2016, the cumulative incidence of AMD in EPO users was about 3.29% lower than that in non-EPO users (Kaplan−Meier survival p < 0.0001). The risk of AMD was 43% lower in EPO users than in non-EPO users, with an adjusted hazard ratio (aHR) of 0.57 (95% confidence interval (CI) = 0.51−0.64) estimated in the multivariate Cox model. A significant negative dose−response relationship was identified between the EPO dosage and the risk of AMD (p < 0.0001). Another beneficial effect of EPO treatment was a reduced risk of both exudative AMD (aHR = 0.48, 95% CI = 0.40−0.61) and non-exudative AMD (aHR = 0.61, 95% CI = 0.53−0.69), also in similar dose−response relationships (p < 0.0001). Our findings suggest that EPO treatment for hemodialysis patients could reduce AMD risk in a dose−response relationship.

Development of Astaxanthin-Loaded Nanosized Liposomal Formulation to Improve Bone Health.

Astaxanthin is a xanthophyll carotenoid commonly found in marine organisms. Due to its super antioxidative ability, astaxanthin has been widely applied as a human nutraceutical supplement for health benefits. In order to enhance the bioavailability of astaxanthin, we used soybean phosphatidylcholine to encapsulate astaxanthin for liposomal formation. The physical properties of astaxanthin (asta)-loaded liposomes were determined by particle size, encapsulation efficiency and polydispersity index. The results revealed that the particle sizes of asta-loaded liposomes with various concentrations exhibited mean diameters in the range of 109 to 134 nm and had a narrow PDI value. As expected, the entrapment efficiency of liposomes loaded with a low concentration of astaxanthin (0.05 µg/mL) was 89%, and that was reduced to 29% for 1.02 µg/mL asta loading. Alizarin red staining and calcium content measurement showed that there was a significant reduction in calcium deposition for 7F2 osteoblasts treated with asta-loaded liposomes (0.25-1.02 µg/mL) in comparison with the cells treated with drug-free liposomes and mineralization medium (MM). Although liposomal formulation can reduce the cytotoxicity of astaxanthin and possess antioxidant, anti-inflammatory and anti-osteoclastogenic activities in RAW264.7 macrophages, asta-loaded liposomes with high concentrations may suppress ALP activity and mineralization level in 7F2 osteoblasts. Therefore, astaxanthin extract may be able to protect bones against oxidative stress and inflammation through liposomal formulation.

Postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis: Clinical analysis of 12 clustered adults and a proposed therapeutic algorithm.

PURPOSE: Postoperative endophthalmitis caused by nontuberculous mycobacterium is a rare but devastating complication after intraocular surgery. However, optimal treatment strategies remain undetermined in view of its rarity. METHODS: We investigated the cases of culture-proven postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis in southern Taiwan, focusing on clinical manifestations and microbiological study, and aimed to describe clinical staging and to propose a therapeutic modality for this disease. RESULTS: Twelve cases, including two published cases, were treated in two medical centers in southern Taiwan between Aug. 2011 and Dec. 2016, and all ever received cataract surgery at one clinic. Their disease courses could be categorized into four distinct stages, i.e., the initial, quiescent, recurrent, and end stage, and some cases experienced 1-4 cycles of quiescent-recurrent stages. Although all eyes ended up with phthisis or were eviscerated, the affected eyes receiving pars plana vitrectomy (PPV) tended to become quiescent and survived longer than those without PPV (adjusted hazard ratio: 13.9, p < 0.05). Eight isolates of eight patients were available for microbiological study. All isolates were susceptible to amikacin, and inducible clarithromycin resistance was observed in 100% of isolates. CONCLUSION: Despite the preservation of vision in postoperative M.abscessus endophthalmitis remained a challenge, a stage-based approach is proposed, which may facilitate decision-makings for the future study.

Risk factors of synchronous multifocal necrotizing fasciitis: a case control study in comparison with monofocal necrotizing fasciitis in Taiwan.

BACKGROUND: Monofocal necrotizing fasciitis (MONF) involves a single site in a rapidly progressing infection and necrosis of the fascia and surrounding soft tissue. Synchronous multifocal necrotizing fasciitis (SMNF), the simultaneous development of NF in multiple noncontiguous sites, is rarely reported. This study aimed to compare the clinical characteristics and outcomes between patients with SMNF and MONF, and to determine the risk factors of SMNF. METHODS: Our retrospective case-control study compared the clinical characteristics and outcomes, between January 2006 and January 2013, of patients with SMNF and of patients with MONF of the extremities. RESULTS: We enrolled 144 patients with NF of the extremities: 19 with SMNF and 125 with MONF. The duration of symptoms before admission was significantly shorter for the former than for the latter (1.7 days vs. 3.3 days, p = 0.001); the prevalence of shock at the initial visit significantly higher (73.7% vs. 36%, p = 0.002); and the total-case postoperative mortality rate significantly higher (68.4% vs. 14.4%, p <  0.001). In further analysis of the total-case mortality, 9 in 13 SMNF deaths (69.2%) within 7 days after fasciotomy were in the majority while 13 with 28-day mortality (72.2%) was the majority of MONF deaths (p <  0.001). SMNF was significantly more likely to involve bacteremia (89.5% vs. 36%, p <  0.001). Independent risk factors for SMNF were liver cirrhosis (LC) (odds ratio [OR] 6.0, p = 0.001) and end-stage renal disease (ESRD) (OR 7.1, p = 0.035). Gram-negative bacteria were most common in SMNF, and Gram-positive bacteria in MONF (83.3% vs. 53.3%, p = 0.005). Vibrio species were the most common single microbial cause (35.4%) of all NF patients and were the overwhelming cause (73.7%) of SMNF. Staphylococcus aureus and group A ß-hemolytic streptococcus (45.6%) were the other predominant causes of MONF while both (10.5%) rarely caused multifocal NF. CONCLUSIONS: SMNF was more fulminant than was MONF. SMNF was attributable primarily to marine Gram-negative bacteria. Physicians should be aware of SMNF because of its extremely high mortality rate.

Rastelli Operation for D-Transposition of the Great Arteries, Ventricular Septal Defect, and Pulmonary Stenosis.

OBJECTIVES: Our preferred approach for the surgical treatment of patients with D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis has been the Rastelli operation. We herein evaluate our 30-year experience with this procedure. METHODS: Clinical records for patients who underwent the Rastelli operation between 1988 and 2017 at our institution were retrospectively reviewed. Primary outcomes included freedom from death or cardiac transplantation and freedom from conduit reintervention. RESULTS: Forty-seven patients met inclusion criteria. Mean follow-up was 11.7 ± 6.8 years. Forty-three (91.5%) patients received a palliative systemic-to-pulmonary artery shunt and/or atrial septostomy prior to the Rastelli procedure. Five (10.6%) patients required ventricular septal defect enlargement at the time of the Rastelli procedure. The overall mean right ventricle-to-pulmonary artery conduit size was 17.0 mm. Mortalities included one early and three late deaths. Freedom from death or cardiac transplantation was 93% and 84% at 5 and 25 years, respectively. Seven patients required pacemaker placement, two immediately postoperatively and five late. Freedom from conduit replacement was 85% and 25% at 5 and 15 years, respectively. Seven (14.9%) patients required a second conduit intervention. Forty-one (87.2%) patients were New York Heart Association class I or II at the most recent follow-up. CONCLUSIONS: The Rastelli operation for D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis offers excellent mid- to long-term survival. The need for conduit replacement remains the most common indication for reintervention, and further study of the optimal choice of conduit will be useful.

The relationship between age, axial length and retinal nerve fiber layer thickness in the normal elderly population in Taiwan: The Chiayi eye study in Taiwan.

AIMS: To interpret how the thickness of the peripapillary retinal nerve fiber layer (RNFL) changes with increasing age, axial length, or anterior chamber depth as measured by spectral domain optical coherence tomography (OCT) in the normal elderly population in Taiwan. METHODS: A total of 82 volunteers (143 eyes) were enrolled. Generalized estimating equations were used to evaluate the correlation. RESULTS: The RNFL was significantly thinner in the superonasal (p = 0.004), inferotemporal (p = 0.046), and temporolower (p = 0.009) segments with age. The same trend was also observed in the superotemporal (p = 0.330) segment, although it was not statistically significant. The global RNFL thickness decreased by 4.97 µm per decade (ß = -0.497; p = 0.021), and thinning was significant in the superonasal (-9.90 µm per decade, p < 0.001) and temporolower (-6.78 µm per decade, p < 0.001) segments; the same trend showed borderline significance in the superotemporal (-6.96 µm per decade, p = 0.073) and inferotemporal (-7.23 µm per decade, p = 0.059) segments. In eyes with longer axial length, the RNFLs significantly decreased in the non-temporal segments. Global RNFL thickness decreased by 3.086 µm for each additional millimeter of axial length (ß = -3.086; p < 0.001). CONCLUSIONS: Changes in RNFL thickness were correlated with age in the superonasal, superotemporal, inferotemporal, and temporolower segments, and were correlated with axial length in the non-temporal segments. Anterior chamber depth was not correlated with RNFL thickness.

Safe Sex Messages Within Dating and Entertainment Smartphone Apps: A Review.

BACKGROUND: Smartphone apps provide a new platform for entertainment, information distribution, and health promotion activities, as well as for dating and casual sexual encounters. Previous research has shown high acceptability of sexual health interventions via smartphone apps; however, sexual health promotion apps were infrequently downloaded and underused. Integrating sexual health promotion into established apps might be a more effective method. OBJECTIVE: The objective of our study was to critically review popular sex-related apps and dating apps, in order to ascertain whether they contain any sexual health content. METHODS: Part 1: In January 2015, we used the term "sexual" to search for free apps in the Apple iTunes store and Android Google Play store, and categorized the sexual health content of the 137 apps identified. Part 2: We used the term "dating" to search for free geosocial-networking apps in the Apple iTunes and Android Google Play stores. The apps were downloaded to test functionality and to determine whether they included sexual health content. RESULTS: Part 1: Of the 137 apps identified, 15 (11.0%) had sexual health content and 15 (11.0%) contained messages about sexual assault or violence. The majority of the apps did not contain any sexual health content. Part 2: We reviewed 60 dating apps: 44 (73%) targeting heterosexual users, 9 (15%) targeting men who have sex with men (MSM), 3 (5%) targeting lesbian women, and 4 (7%) for group dating. Only 9 dating apps contained sexual health content, of which 7 targeted MSM. CONCLUSIONS: The majority of sex-related apps and dating apps contained no sexual health content that could educate users about and remind them of their sexual risks. Sexual health practitioners and public health departments will need to work with app developers to promote sexual health within existing popular apps. For those apps that already contain sexual health messages, further study to investigate the effectiveness of the content is needed.

Garlic oil polysulfides: H2S- and O2-independent prooxidants in buffer and antioxidants in cells.

The health benefits of garlic and other organosulfur-containing foods are well recognized and have been attributed to both prooxidant and antioxidant activities. The effects of garlic are surprisingly similar to those of hydrogen sulfide (H2S), which is also known to be released from garlic under certain conditions. However, recent evidence suggests that polysulfides, not H2S, may be the actual mediator of physiological signaling. In this study, we monitored formation of H2S and polysulfides from garlic oil in buffer and in human embryonic kidney (HEK) 293 cells with fluorescent dyes, 7-azido-4-methylcoumarin and SSP4, respectively and redox activity with two redox indicators redox-sensitive green fluorescent protein (roGFP) and DCF. Our results show that H2S release from garlic oil in buffer requires other low-molecular-weight thiols, such as cysteine (Cys) or glutathione (GSH), whereas polysulfides are readily detected in garlic oil alone. Administration of garlic oil to cells rapidly increases intracellular polysulfide but has minimal effects on H2S unless Cys or GSH are also present in the extracellular medium. We also observed that garlic oil and diallyltrisulfide (DATS) potently oxidized roGFP in buffer but did not affect DCF. This appears to be a direct polysulfide-mediated oxidation that does not require a reactive oxygen species intermediate. Conversely, when applied to cells, garlic oil became a significant intracellular reductant independent of extracellular Cys or GSH. This suggests that intracellular metabolism and further processing of the sulfur moieties are necessary to confer antioxidant properties to garlic oil in vivo.

A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

Stepwise one-electron reduction of oxygen to water produces reactive oxygen species (ROS) that are chemically and biochemically similar to reactive sulfide species (RSS) derived from one-electron oxidations of hydrogen sulfide to elemental sulfur. Both ROS and RSS are endogenously generated and signal via protein thiols. Given the similarities between ROS and RSS, we wondered whether extant methods for measuring the former would also detect the latter. Here, we compared ROS to RSS sensitivity of five common ROS methods: redox-sensitive green fluorescent protein (roGFP), 2', 7'-dihydrodichlorofluorescein, MitoSox Red, Amplex Red, and amperometric electrodes. All methods detected RSS and were as, or more, sensitive to RSS than to ROS. roGFP, arguably the "gold standard" for ROS measurement, was more than 200-fold more sensitive to the mixed polysulfide H2Sn(n = 1-8) than to H2O2 These findings suggest that RSS may be far more prevalent in intracellular signaling than previously appreciated and that the contribution of ROS may be overestimated. This conclusion is further supported by the observation that estimated daily sulfur metabolism and ROS production are approximately equal and the fact that both RSS and antioxidant mechanisms have been present since the origin of life, nearly 4 billion years ago, long before the rise in environmental oxygen 600 million years ago. Although ROS are assumed to be the most biologically relevant oxidants, our results question this paradigm. We also anticipate our findings will direct attention toward development of novel and clinically relevant anti-(RSS)-oxidants.

Deep vein thrombosis due to continuous prone positioning after retinal detachment surgery.

In March 2014, a 56-year-old woman without previous underlying disease underwent encircling scleral buckling, 20-gauge pars plana vitrectomy, cryotherapy around a retinal tear, and gas-fluid exchange with 15% perfluoropropane flush for upper rhegmatogenous retinal detachment of the left eye. However, she developed progressive left leg swelling, pain, warmth, and redness, associated with difficulty in elevating her left leg after continuously maintaining a prone head position when either lying down or sitting for 2 days. When she arrived at the emergency room, she had an elevated D-dimer level. After undergoing Doppler ultrasound imaging, she was diagnosed as having deep vein thrombosis of the left leg. She received anticoagulation therapy with enoxaparin and warfarin overlapping for 7 days. The edema, pain, and paresthesia of her left leg were relieved. However, because of the risk of bleeding with anti-coagulation drug usage, the patient needed to be monitored for 6 months. Prone positioning for gas tamponade is important for anatomic and functional success in retinal detachment surgery; however, timely walking and rest between periods of continuous prone positioning should be encouraged to prevent deep vein thrombosis and other impaired circulation-related complications.

Rapid regression of cystoid macular edema associated with cytomegalovirus retinitis in adult acute myeloid leukemia by intravitreal methotrexate combined with oral valganciclovir: A case report with comparison of binocular outcome.

Cytomegalovirus (CMV) retinitis is a late complication of organ and hematopoietic stem cell transplant, the risk of which depends on the degree of immunosuppression. With the institution of preemptive ganciclovir therapy early after transplant, most patients survive episodes of life-threatening CMV infection during the early months (usually the first 3 months) after transplant and hence late onset of CMV disease, such as CMV retinitis, is being recognized more frequently. Direct involvement of the macula or optic head remains the leading cause of visual loss in patients with CMV retinitis, but there are few studies investigating the management of this condition. Herein, we present the case of 28-year-old man who had acute myeloid leukemia and developed CMV retinitis with bilateral cystoid macular edema and optic swelling in the right eye 6 months after bone marrow transplant. He received treatment with intravitreal methotrexate in the right eye in combination with oral valganciclovir. Visual acuity improved 1 month after four weekly injections of intravitreal methotrexate 400 µg/0.1 mL. Resolved disc swelling and regression of macular edema were also observed. By comparing binocular outcome, we present our findings and discuss the possible efficacy and safety of this treatment with respect to regression of anatomical damage and improvement in visual acuity.

Axial length and subfoveal choroidal thickness in individuals with age-related macular degeneration.

PURPOSE: To compare axial length (AL) and subfoveal choroidal thickness (SFCT) between individuals with age-related macular degeneration (AMD) and controls with no lesions. METHODS: This was a case-control study. In total, 853 eyes of 484 patients (>65 years), including 397 eyes at various AMD stages and 456 eyes with no fundus lesions (controls) were recruited. Using color fundus photography, eyes were grouped according to AMD degree. AL was automatically measured using IOL Master and SFCT was manually measured by two independent observers. The associations among age, AL, SFCT, and each AMD grade were analyzed. RESULTS: Out of 853 eyes, 456 had no lesions, 217 contained drusen only, 134 had early AMD, and 46 had late AMD. The eyes with late AMD were older (p = 0.007) and had longer AL (p ≥ 0.001) and thinner SFCT (p < 0.001) compared with groups of no fundus lesions, drusen only, and early AMD. SFCT in eyes with late AMD decreased by 19.20 µm (p = 0.049), 24.78 µm (p = 0.029), and 15.56 µm (p = 0.162) compared with groups of no fundus lesions, drusen only, and early AMD, respectively. SFCT decreased by 14.18 µm/mm increase in AL (p < 0.001). The odds ratio (OR) for late AMD by longer AL (≥25 mm) and thinner SFCT (<240 µm) was 4.54 (χ2 = 9.36; p = 0.002) and 4.86 (χ2 = 17.62; p < 0.001), respectively, and was 9.57 (χ2 = 18.07; p < 0.001) when both AL ≥ 25 ≥m and SFCT < 240 µm. CONCLUSION: Eyes with late AMD have distinct reduced SFCT and elongated AL. Eyes with thinner SFCT and longer AL showed high ORs for late AMD and even higher ORs when both factors were simultaneously present. These findings illustrate the crucial pathophysiological role of these two important ocular fac tors and arouse our attention to patients with both characteristics, especially in Asian countries where the prevalence of myopia are disturbingly high.