Saffron therapy for the ongoing treatment of age-related macular degeneration.

OBJECTIVE: To assess the long-term efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS AND ANALYSIS: Open-label, extension trial of 93 adults (>50 years) with mild/moderate AMD and vision >20/70 Snellen equivalent in at least 1 eye. Exclusion criteria included confounding visual lesions or significant gastrointestinal disease impairing absorption.Participants were given oral saffron supplementation (20 mg/day) for 12 months. Those already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these.Primary outcomes included changes in multifocal electroretinogram (mfERG) response density and latency, and changes in best-corrected visual acuity (BCVA). Secondary outcomes included safety outcomes, changes in mfERG and BCVA among participants on AREDS supplements and changes in microperimetry. RESULTS: At 12 months, mean mfERG response density was significantly higher in rings 1, 2 and overall (p<0.001 for all) but not in rings 3-6, and there was no difference in response between those taking AREDS supplements and those not (p>0.05). Mean mfERG latency was not significantly different in any of rings 1-6 or overall (p>0.05 for all), again with no difference between those taking AREDS supplements or not (p>0.05). Mean BCVA was 1.6 letters worse (p<0.05) with no difference between those on AREDS supplements or not, and this may have been related to cataract progression. No saffron-related serious adverse events were detected. CONCLUSION: Saffron supplementation modestly improved mfERG responses in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.

O-GlcNAc signaling increases neuron regeneration through one-carbon metabolism in Caenorhabditis elegans.

Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked ß-N-acetylglucosamine (O-GlcNAc) signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration. Here, we define the specific metabolic pathway by which O-GlcNAc transferase (ogt-1) loss of function mediates increased regenerative outgrowth. Performing in vivo laser axotomy and measuring subsequent regeneration of individual neurons in C. elegans, we find that glycolysis, serine synthesis pathway (SSP), one-carbon metabolism (OCM), and the downstream transsulfuration metabolic pathway (TSP) are all essential in this process. The regenerative effects of ogt-1 mutation are abrogated by genetic and/or pharmacological disruption of OCM and the SSP linking OCM to glycolysis. Testing downstream branches of this pathway, we find that enhanced regeneration is dependent only on the vitamin B12 independent shunt pathway. These results are further supported by RNA sequencing that reveals dramatic transcriptional changes by the ogt-1 mutation, in the genes involved in glycolysis, OCM, TSP, and ATP metabolism. Strikingly, the beneficial effects of the ogt-1 mutation can be recapitulated by simple metabolic supplementation of the OCM metabolite methionine in wild-type animals. Taken together, these data unearth the metabolic pathways involved in the increased regenerative capacity of a damaged neuron in ogt-1 animals and highlight the therapeutic possibilities of OCM and its related pathways in the treatment of neuronal injury.

Effectiveness of a community health worker-led low-sodium salt intervention to reduce blood pressure in rural Bangladesh: protocol for a cluster randomized controlled trial.

BACKGROUND: High blood pressure is a major public health problem in low- and middle-income countries. Low-sodium salt substitute (LSSS) is a promising population-level blood pressure-lowering intervention requiring minimal behavioral change. The optimal method of delivering LSSS to individuals, however, is currently unknown. Community health workers (CHWs) have successfully been used to implement health interventions in Bangladesh and may provide a venue for the dissemination of LSSS. METHODS: We aim to conduct a cluster-randomized controlled trial involving 309 households in rural Bangladesh previously identified and characterized by the BRAC James P Grant School of Public Health, BRAC University (BRAC JPGSPH). These households will be randomly assigned to three arms: (1) control, i.e., no intervention; (2) information only, i.e., community health workers will provide basic information on high blood pressure, the health consequences of excessive salt consumption, and feedback to the participant on the likely quantity of salt s/he consumes (estimated using a questionnaire); (3) free LSSS arm: the same information as in arm 2 will be provided, but participants will receive 6 months of free low-sodium salt along with education on the benefits of LSSS. One male and one female adult (age ≥ 18 years) in each household will be invited to participate, the exclusion criteria being households with members known to have high serum potassium levels, are taking medications known to elevate potassium levels (e.g., ACE inhibitors, ARBs, potassium-sparing diuretics), are already taking potassium supplements, or those who have known kidney disease or abnormal serum creatinine at baseline. The primary endpoint will be blood pressure at 6 months post-intervention. DISCUSSION: Recent large clinical trials of LSSS in China and India have shown not only blood pressure improvements, but also stroke, major cardiac event, and all-cause mortality reductions. Nevertheless, how to best translate this intervention to population-level effectiveness remains unclear. Our study would test whether a community health worker-based program could be effectively used to disseminate LSSS and achieve measurable blood pressure benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT05425030. Registered on June 21, 2022.

Proanthocyanidins mitigate bile acid-induced changes in GSTT2 levels in a panel of racially diverse patient-derived primary esophageal cell cultures.

Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for esophageal adenocarcinoma (EAC). Despite similar rates of GERD and other risk factors across racial groups, EAC progression disproportionately impacts Caucasians. We recently reported that elevated tissue levels of the detoxification enzyme GSTT2 in the esophagi of Blacks compared to Caucasians may contribute protection. Herein, we extend our research to investigate whether cranberry proanthocyanidins (C-PAC) mitigate bile acid-induced damage and GSTT2 levels utilizing a racially diverse panel of patient-derived primary esophageal cultures. We have shown that C-PACs mitigate reflux-induced DNA damage through GSTT2 upregulation in a rat esophageal reflux model, but whether effects are recapitulated in humans or differentially based on race remains unknown. We isolated normal primary esophageal cells from Black and Caucasian patients and assessed GSTT2 protein levels and cellular viability following exposure to a bile acid cocktail with and without C-PAC treatment. Constitutive GSTT2 levels were significantly elevated in Black (2.9-fold) compared to Caucasian patients, as were GSTT2 levels in Black patients with GERD. C-PAC treatment induced GSTT2 levels 1.6-fold in primary normal esophageal cells. GSTT2 induction by C-PAC was greatest in cells with constitutively low GSTT2 expression. Overall, C-PAC mitigated bile-induced reductions of GSTT2 and subsequent loss of cell viability regardless of basal GSTT2 expression or race. These data support that C-PAC may be a safe efficacious agent to promote epithelial fitness through GSTT2 induction and in turn protect against bile acid-induced esophageal injury.

Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury.

Although traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system. Increased C1q expression colocalized with neuron loss and chronic inflammation and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. Single-nucleus RNA sequencing demonstrated that microglia are a source of thalamic C1q. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities.

Atypical beta power fluctuation while listening to an isochronous sequence in dyslexia.

OBJECTIVE: Developmental dyslexia is a reading disorder that features difficulties in perceiving and tracking rhythmic regularities in auditory streams, such as speech and music. Studies on typical healthy participants have shown that power fluctuations of neural oscillations in beta band (15-25 Hz) reflect an essential mechanism for tracking rhythm or entrainment and relate to predictive timing and attentional processes. Here we investigated whether adults with dyslexia have atypical beta power fluctuation. METHODS: The electroencephalographic activities of individuals with dyslexia (n = 13) and typical control participants (n = 13) were measured while they passively listened to an isochronous tone sequence (2 Hz presentation rate). The time-frequency neural activities generated from auditory cortices were analyzed. RESULTS: The phase of beta power fluctuation at the 2 Hz stimulus presentation rate differed and appeared opposite between individuals with dyslexia and controls. CONCLUSIONS: Atypical beta power fluctuation might reflect deficits in perceiving and tracking auditory rhythm in dyslexia. SIGNIFICANCE: These findings extend our understanding of atypical neural activities for tracking rhythm in dyslexia and could inspire novel methods to objectively measure the benefits of training, and predict potential benefit of auditory rhythmic rehabilitation programs on an individual basis.

Inferior Auditory Time Perception in Children With Motor Difficulties.

Accurate time perception is crucial for hearing (speech, music) and action (walking, catching). Motor brain regions are recruited during auditory time perception. Therefore, the hypothesis was tested that children (age 6-7) at risk for developmental coordination disorder (rDCD), a neurodevelopmental disorder involving motor difficulties, would show nonmotor auditory time perception deficits. Psychophysical tasks confirmed that children with rDCD have poorer duration and rhythm perception than typically developing children (N = 47, d = 0.95-1.01). Electroencephalography showed delayed mismatch negativity or P3a event-related potential latency in response to duration or rhythm deviants, reflecting inefficient brain processing (N = 54, d = 0.71-0.95). These findings are among the first to characterize perceptual timing deficits in DCD, suggesting important theoretical and clinical implications.

Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.

BACKGROUND: Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. OBJECTIVE: To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). METHODS: Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. RESULTS: The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose. CONCLUSIONS: Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.

Morphomic Factors Associated With Complete Response to Neoadjuvant Therapy in Esophageal Carcinoma.

BACKGROUND: In patients undergoing neoadjuvant chemoradiotherapy (nCRT) followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC), patients with a pathologic complete response (pCR) have the greatest benefit. The purpose of this study was to identify morphomic factors obtained from pretreatment computed tomography scans associated with a pCR in ESCC. METHODS: We retrospectively analyzed patients with ESCC treated with nCRT who underwent esophagectomy between 2006 and 2016. Clinical and morphomic characteristics pre-nCRT were analyzed to identify factors associated with pCR using univariate and multivariable analyses. RESULTS: There were 183 patients with ESCC included in this study, and 45 (24.6%) patients achieved pCR. The overall survival in patients with pCR was better than that in patients without pCR (5.8 years vs 1.2 years; P < .001). On univariate analysis, increased age, radiation dose greater than or equal to 4000 cGy, and larger subcutaneous adipose tissue area were correlated with pCR. On multivariable logistic regression, increased age (odds ratio, 1.53; P = .03), radiation dose greater than or equal to 4000 cGy (odds ratio, 2.19; P = .04), and larger dorsal muscle group normal-density area (odds ratio, 1.59; P = .03) were independently associated with pCR. CONCLUSIONS: Increased age, radiation dose greater than or equal to 4000 cGy, and larger dorsal muscle group normal-density area were significantly associated with pCR. These factors may be useful in determining which patients are most likely to benefit from nCRT followed by esophagectomy.

Anti-inflammatory activities of Waltheria indica extracts by modulating expression of IL-1B, TNF-α, TNFRII and NF-κB in human macrophages.

In Hawaiian traditional medicinal practices, the indigenous 'uhaloa, Waltheria indica var. Americana is one of the most recognized plants. Waltheria is also known in various cultures as a medicinal plant for the treatment of inflammatory conditions. Results in human subjects and cell and animal models supported anti-inflammatory activity for the Waltheria flavonoid quercetin, and for crude plant extracts, limited animal studies also confirmed anti-inflammatory effects. Yet no systematic studies have examined immune or inflammatory responses affected by these extracts. In order to gain insight into inflammatory cascades modulated by Waltheria extracts, and to uncover the mechanistic bases for the effective use of this medicinal plant as a natural anti-inflammatory agent, we have undertaken analyses of LPS and TNF-α/IF-γ-stimulated human macrophages treated with Waltheria extracts using targeted qRT-PCR and Inflammation Panels to test differential mRNA expression of two hundred immune-related genes, furthermore, ELISA assays and Inflammatory Protein arrays to determine extracts-modulated intracellular and secreted levels of prominent cytokines. Results demonstrate that Waltheria extracts inhibit key inflammatory cytokines and cytokine receptors including protein levels of IL-1B, IL-1ra, IL-8 and IL-6, reduce both mRNA and protein levels of TNF-α and protein levels of its receptor, TNF RII, predicting diminished TNF-α-associated inflammatory signaling that, together with significant reduction of NF-κB mRNA and protein, can effectively diminish activities of multiple pro-inflammatory signaling pathways and mitigate key processes in diseases with inflammatory components.

A Qualitative Study of Child Nutrition and Oral Health in El Salvador.

The nutrition transition from traditional diets to processed snacks and sugary beverages has contributed to a higher burden of child malnutrition, obesity, and tooth decay. While child health interventions typically promote nutritious eating, they rarely promote oral health. Mothers' motivations for child nutrition and oral health practices need to be better understood. A convenience sample of 102 mothers in eight rural Salvadoran communities participated in focus groups addressing child nutrition and oral health. Focus groups were transcribed and coded using qualitative content analysis. Primary themes included generational changes in health environments; health knowledge, attitudes, and practices; and access and barriers to health services. Mothers noted general improvements in awareness of oral hygiene but poorer child oral health, which they attributed to widespread sales of unhealthy snacks and beverages near schools. Distance and cost limited families' access to dental services. Knowledge gaps included the belief that oral iron supplements cause tooth decay, uncertainty regarding when to start tooth brushing, and until when parents should help children brush. Maternal-child health programs should emphasize the adverse health consequences of feeding young children processed snacks and sugary drinks, and promote dental care access and regulations to ensure health-promoting environments surrounding schools.

Rhythmicity facilitates pitch discrimination: Differential roles of low and high frequency neural oscillations.

Previous studies indicate that temporal predictability can enhance timing and intensity perception, but it is not known whether it also enhances pitch perception, despite pitch being a fundamental perceptual attribute of sound. Here we investigate this in the context of rhythmic regularity, a form of predictable temporal structure common in sound streams, including music and speech. It is known that neural oscillations in low (delta: 1-3 Hz) and high (beta: 15-25 Hz) frequency bands entrain to rhythms in phase and power, respectively, but it is not clear why both low and high frequency bands entrain to external rhythms, and whether they and their coupling serve different perceptual functions. Participants discriminated near-threshold pitch deviations (targets) embedded in either rhythmic (regular/isochronous) or arrhythmic (irregular/non-isochronous) tone sequences. Psychophysically, we found superior pitch discrimination performance for target tones in rhythmic compared to arrhythmic sequences. Electroencephalography recordings from auditory cortex showed that delta phase, beta power modulation, and delta-beta coupling were all modulated by rhythmic regularity. Importantly, trial-by-trial neural-behavioural correlational analyses showed that, prior to a target, the depth of U-shaped beta power modulation predicted pitch discrimination sensitivity whereas cross-frequency coupling strength predicted reaction time. These novel findings suggest that delta phase might reflect rhythmic temporal expectation, beta power temporal attention, and delta-beta coupling auditory-motor communication. Together, low and high frequency auditory neural oscillations reflect different perceptual functions that work in concert for tracking rhythmic regularity and proactively facilitate pitch perception.

Cannulated Screw Prominence in Tension Band Wiring of Patella Fractures Increases Fracture Gapping: A Cadaver Study.

BACKGROUND: Transverse patella fractures are often treated with cannulated screws and a figure-of-eight anterior tension band. A common teaching regarding this construct is to recess the screws so that their distal ends do not protrude beyond the patella because doing so may improve biomechanical performance. However, there is a lack of biomechanical or clinical data to support this recommendation. QUESTION: In the treatment of transverse patella fractures, is there a difference between prominent and recessed cannulated screw constructs, supplemented by tension banding, in terms of gap formation from cyclic loading and ultimate load to failure? METHODS: Ten pairs of fresh-frozen cadaver legs (mean donor age, 72 years; range, 64-89 years) were randomized in a pairwise fashion to prominent or standard-length screws. In the prominent screw group, screw length was 15% longer than the measured trajectory, resulting in 4 to 6 mm of additional length. Each patella was transversely osteotomized at its midportion and fixed with screws and an anterior tension band. Gap formation was measured over 40 loaded flexion-extension cycles (90° to 5°). Ultimate load to failure was assessed with a final monotonic test after cyclic loading. Areal bone mineral density (BMD) of each patella was measured with dual energy x-ray absorptiometry (DEXA). There was no difference in BMD between the recessed (1.06 ± 0.262 g/cm) and prominent (1.03 ± 0.197 g/cm) screw groups (p = 0.846). Difference in gap formation was assessed with a Wilcoxon Rank Sum Test. Ultimate load to failure and BMD were assessed with a paired t-test. RESULTS: Patella fractures fixed with prominent cannulated screws demonstrated larger gap formation during cyclic loading. Median gap size at the end of cyclic loading was 0.13 mm (range, 0.00-2.92 mm) for the recessed screw group and 0.77 mm (range, 0.00-7.50 mm) for the prominent screw group (p = 0.039; 95% confidence interval [CI] difference of geometric means, 0.05-2.12 mm). There was no difference in ultimate failure load between the recessed screw (891 ± 258 N) and prominent screw (928 ± 268 N) groups (p = 0.751; 95% CI difference of means, -226 to 301 N). Ultimate failure load was correlated with areal BMD (r = 0.468; p = 0.046). CONCLUSIONS: In this cadaver study, when using cannulated screws and a figure-of-eight tension band to fix transverse patella fractures, prominent screws reduced the construct's ability to resist gap formation during cyclic loading testing. CLINICAL RELEVANCE: This biomechanical cadaver study found that the use of prominent cannulated screws for the fixation of transverse patella fractures increases the likelihood of interfragmentary gap formation, which may potentially increase the risk of fracture nonunion and implant failure. These findings suggest that proximally and distally recessed screws may increase construct stability, which may increase the potential for bony healing. The findings support further laboratory and clinical investigations comparing recessed screws supplemented by anterior tension banding with other repair methods that are in common use, such as transosseous suture repair.

Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial.

PURPOSE: To assess the efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS: Randomised, double-blinded, placebo-controlled crossover trial of 100 adults (> 50 years) with mild/moderate AMD and vision > 20/70 Snellen equivalent in at least one eye. Exclusion criteria included confounding visual lesions, or significant gastrointestinal disease impairing absorption. Participants were given oral saffron supplementation (20 mg/day) for 3 months or placebo for 3 months, followed by crossover for 3 months. Participants already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these. Primary outcomes included changes in best-corrected visual acuity (BCVA) and changes in multifocal electroretinogram (mfERG) response density and latency. Secondary outcomes included safety outcomes and changes in mfERG and BCVA amongst participants on AREDS supplements. RESULTS: Mean BCVA improved 0.69 letters (p = 0.001) and mean-pooled mfERG latency reduced 0.17 ms (p = 0.04) on saffron compared to placebo. Amongst participants on AREDS supplements, mean BCVA improved 0.73 letters p = 0.006) and mean-pooled mfERG response density improved 2.8% (p = 0.038). There was no significant difference in adverse event occurrence (p > 0.10). CONCLUSION: Saffron supplementation modestly improved visual function in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.

Beta oscillatory power modulation reflects the predictability of pitch change.

Humans process highly dynamic auditory information in real time, and regularities in stimuli such as speech and music can aid such processing by allowing sensory predictions for upcoming events. Auditory sequences contain information about both the identity of sounds (what) and their timing (when they occur). Temporal prediction in isochronous sequences is reflected in neural oscillatory power modulation in the beta band (∼20 Hz). Specifically, power decreases (desynchronization) after tone onset and then increases (resynchronization) to reach a maximum around the expected time of the next tone. The current study investigates whether the predictability of the pitch of a tone (what) is also reflected in beta power modulation. We presented two isochronous auditory oddball sequences, each with 20% of tones at a deviant pitch. In one sequence the deviant tones occurred regularly every fifth tone (predictably), but in the other sequence they occurred pseudorandomly (unpredictably). We recorded the electroencephalogram (EEG) while participants listened passively to these sequences. The results showed that auditory beta power desynchronization was larger prior to a predictable than an unpredictable pitch change. A single-trial correlation analysis using linear mixed-effect (LME) models further showed that the deeper the pre-deviant beta desynchronization depth, the smaller the event-related P3a amplitude following the deviant, and this effect only occurred when the pitch change was predictable. Given that P3a is associated with attentional response to prediction error, larger beta desynchronization depth indicates better prediction of an upcoming deviant pitch. Thus, these findings suggest that beta oscillations reflect predictions for what in additional to when during dynamic auditory information processing.

Heat-targeted drug delivery: A promising approach for organsparing treatment of bladder cancer.THERMODOX®. / Administración de medicamentos dirigida por el calor: un enfoque prometedor para el tratamiento órgano conservador del cáncer de vejiga. THERMODOX®.

Disease recurrence and progression remain as significant challenges for the management of non-muscle invasive bladder cancer (NMIBC). In recent years, novel drugs and delivery systems have been investigated as strategies to reduce recurrence, progression and mortality. In this review, we focus on the role of intravesical hyperthermic chemotherapy and discuss a novel approach involving a heat-activated drug delivery system (ThermoDox®) that enables local accumulation of systemic chemotherapy.

Analytic Morphomics Predict Outcomes After Lung Transplantation.

BACKGROUND: The purpose of this study was to identify morphomic factors on standard, pretransplantation computed tomography (CT) scans associated with outcomes after lung transplantation. METHODS: A retrospective review of 200 patients undergoing lung transplantation at a single institution from 2003 to 2014 was performed. CT scans obtained within 1 year before transplantation underwent morphomic analysis. Morphomic characteristics included lung, dorsal muscle group, bone, and subcutaneous and visceral fat area and density. Patient data were gathered from institutional and United Network for Organ Sharing databases. Outcomes, including initial ventilator support greater than 48 hours, length of stay, and survival, were evaluated using univariate and multivariable analyses. RESULTS: On multivariable Cox regression, subcutaneous fat/total body area (hazard ratio [HR] 0.60, p = 0.001), lung density 3 volume (HR 0.67, p = 0.013), and creatinine (HR 4.37, p = 0.010) were independent predictors of survival. Initial ventilator support more than 48 hours was associated with decreased vertebral body to linea alba distance (odds ratio [OR] 0.49, p = 0.002) and Zubrod score 4 (OR 14.0, p < 0.001). Increased bone mineral density (p < 0.001) and increased cross-sectional body area (p < 0.001) were associated with decreased length of stay, whereas supplemental oxygen (p < 0.001), bilateral transplantation (p = 0.002), cardiopulmonary bypass (p < 0.001), and Zubrod score 3 (p < 0.001) or 4 (p = 0.040) were associated with increased length of stay. CONCLUSIONS: Morphomic factors associated with lower metabolic reserve and frailty, including decreased subcutaneous fat, bone density, and body dimensions were independent predictors of survival, prolonged ventilation, and increased length of stay. Analytic morphomics using pretransplantation CT scans may improve recipient selection and risk stratification.

Multi-domain feature selection in auditory MisMatch Negativity via PARAFAC-based template matching approach.

MisMatch Negativity (MMN) is a small event-related potential (ERP) that provide an index of sensory learning and perceptual accuracy for the cognitive research. Group-level analysis plays an important role for detecting differences at group or condition level, especially when the signal-to-noise ratio is low. Tensor factorization has provided a framework for group-level analysis of ERPs by exploiting more information of brain responses in more domains simultaneously. A 4-way ERP tensor of time × frequency × channel × subjects/condition is generated and decomposed via PARAFAC. A crucial step after PARAFAC decomposition is to select the component that corresponds to the event of interest and moreover differentiates the two groups\conditions. This is usually done manually, which is tedious when the number of components is high. Here we propose a technique to select the multi-domain feature of an ERP among all extracted features by a template matching approach, that uses the MMN temporal and spectral signatures. Following a statistical test, the selected feature significantly discriminated subjects for the two experimental conditions.

Brain-Gut Axis Modulation of Acupuncture in Functional Dyspepsia: A Preliminary Resting-State fcMRI Study.

Objective. To explore acupuncture effects on brain functional connectivity in patients with functional dyspepsia (FD). Methods. Eight patients in an acupuncture treatment group and ten healthy adults in the control group participated in the study. Acupuncture effectiveness was evaluated based on changes of the gastrointestinal symptoms, gastric motility measurements, and gastrin levels and comparisons with the control group when appropriate. To investigate functional connectivity changes related to FD and potential modulation after acupuncture, a set of regions of interest (ROIs) were selected according to previous fMRI reports of acupuncture. Results. Patients showed significant improvements of FD signs and symptoms after acupuncture treatments. For all of the ROIs, we identified subportions of the networks showing reduced connectivity in patients with FD. Connectivity between the ROIs and corresponding disease targets showed significant improvement after acupuncture treatment (P < 0.05) in all ROIs except for right medial temporal lobe-hippocampus and right inferior parietal lobule. Conclusion. Functional connectivity of the brain is changed in patients with FD but approximates that in healthy control after acupuncture treatment. The relief of gastrointestinal signs and symptoms by acupuncture is likely due to the normalization of brain-gut axis associated with FD.

Dietary modification and supplementation for the treatment of age-related macular degeneration.

Age-related macular degeneration (AMD) causes a significant proportion of visual loss in the developed world. Currently, little is known about its pathogenesis, and treatment options are limited. Dietary intake is one of the few modifiable risk factors for this condition. The best-validated therapies remain oral antioxidant supplements based on those investigated in the Age-Related Eye Disease Study (AREDS) and the recently completed Age-Related Eye Disease Study 2 (AREDS2). In this review, current dietary guidelines related to AMD, along with the underlying evidence to support them, are presented in conjunction with current treatment recommendations. Both AREDS and AREDS2 are discussed, as are avenues for further research, including supplementation with vitamin D and saffron. Despite the considerable disease burden of atrophic AMD, few effective therapies are available to treat it, and further research is required.