Sedimentation strategies provide effective but limited mitigation of relative sea-level rise in the Mekong delta

The Mekong delta is experiencing rapid environmental change due to anthropogenic activities causing accelerated subsidence, sea-level rise and sediment starvation. Consequentially, the delta is rapidly losing elevation relative to sea level. Designating specific areas for sedimentation is a suggested strategy to encourage elevation-building with nature in deltas. We combined projections of extraction-induced subsidence, natural compaction and global sea-level rise with new projections of fluvial sediment delivery to evaluate the potential effectiveness of sedimentation strategies in the Mekong delta to 2050. Our results reveal that with current rates of subsidence and sediment starvation, fluvial sediments alone can only preserve elevation locally, even under optimistic assumptions, and organic sedimentation could potentially assume a larger role. While sedimentation strategies alone have limited effectiveness in the present context, combined with enhanced organic matter retention and interventions reducing anthropogenic-accelerated subsidence, they can considerably delay future relative sea-level rise, buying the delta crucial time to adapt.

Evaluation of a Smectite Adsorption-Based Electrostatic System to Decontaminate F− Rich Thermal Waters

Several studies have shown the presence of fluoride levels much higher than the 1.5 mg/L threshold concentration recommended by WHO in the spring waters and wells of the Ethiopian Rift Valley. Available defluoridation techniques can be costly, present complicated technical aspects, and show limited effectiveness. Therefore, it is necessary to devise innovative, sustainable, and effective solutions. This study proposes an alternative method of intervention to the known techniques for removing fluoride from water, particularly suitable for smaller rural communities. In particular, in this work, the possibility to use electromagnetic fields as a physical method for removing the excess fluoride was investigated. The study was carried out by developing a multiphysics model used for studying and envisaging the design of a device. In this framework, the combination of this approach with the use of highly reactive smectite clay was numerically studied. The results obtained, although preliminary, indicate that the proposed system could significantly impoverish the waters of the Rift Valley from fluoride, with the consequence of obtaining a resource suitable for human consumption, in particular for rural communities. However, further theoretical investigations and experimental phases will be necessary to achieve the desired results.

HomeCoRe for Telerehabilitation in Mild or Major Neurocognitive Disorders: A Study Protocol for a Randomized Controlled Trial

Background: Given the limited effectiveness of pharmacological treatments for cognitive decline, non-pharmacological interventions have gained increasing attention. Evidence exists on the effectiveness of cognitive rehabilitation in preventing elderly subjects at risk of cognitive decline and in reducing the progression of functional disability in cognitively impaired individuals. In recent years, telerehabilitation has enabled a broader application of cognitive rehabilitation programs. The purpose of this study is to test a computer-based intervention administered according to two different modalities (at the hospital and at home) using the tools CoRe and HomeCoRe, respectively, in participants with Mild or Major Neurocognitive Disorders.Methods: Non-inferiority, single-blind randomized controlled trial where 40 participants with Mild or Major Neurocognitive Disorders will be assigned to the intervention group who will receive cognitive telerehabilitation through HomeCoRe or to the control group who will receive in-person cognitive intervention through CoRe, with the therapist administering the same computer-based exercises. The rehabilitative program will last 6 weeks, with 3 sessions/week, each lasting ~45 min. All the participants will be evaluated on an exhaustive neuropsychological battery before (T0) and after (T1) the intervention; follow-up visits will be scheduled after 6 (T2) and 12 months (T3).Discussion: The results of this study will inform about the comparability (non-inferiority trial) of HomeCoRe with CoRe. Their equivalence would support the use of HomeCoRe for at distance treatment, favoring the continuity of care.Ethics and Dissemination: This study has been approved by the Local Ethics Committee and registered in https://clinicaltrials.gov (NCT04889560). The dissemination plan includes the scientific community through publication in open-access peer-reviewed scientific journals and presentations at national and international conferences.Trial Registration:Clinicaltrials.govhttps://clinicaltrials.gov/ct2/show/NCT04889560 (registration date: May 17, 2021).

Effect on the reduction of bacterial load after surgical hand antisepsis with triclosan 0.5% compared to triclosan 0.5% followed by 70% alcoholic solution

Triclosan 0.5% by scrubbing does not meet the UNE-EN12791 criteria to be used in the surgical hand preparation (SHP). Triclosan 0.5% by scrubbing followed by ethanol 70% hand rubbing is suitable without the additional characteristic of sustained effect. This limited effectiveness implies that triclosan should be avoided in SHP given the restrictions on its use in consumer antiseptic products. The trial was registered at ClinicalTrials.gov (ID: NCT04538365).

Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities

Background: Despite decades of research efforts, current treatments for Alzheimer’s disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition. Objective: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities. Methods: Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group). Results: The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up. Conclusion: These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.

Prediction of Real-World Long-Term Outcomes of People with CF Homozygous for the F508del Mutation Treated with CFTR Modulators

The clinical response to cystic fibrosis transmembrane conductance regulator (CFTR) modulators is variable within people with cystic fibrosis (pwCF) homozygous for the F508del mutation. The prediction of clinical effect in individual patients would be useful to target therapy to those who would benefit from it. A multicenter observational cohort study was conducted including 97 pwCF (F508del/F508del), who started lumacaftor/ivacaftor (LUM/IVA) treatment before June 2018. In order to assess the associations of individual in vivo and in vitro biomarkers with clinical outcomes, we collected clinical data regarding sex, age, and sweat chloride concentration (SwCl) at baseline and after six months of LUM/IVA; the percent predicted forced expiratory volume in 1 s (ppFEV1) and the number of pulmonary exacerbations (PEx) during the three years before up to three years after modulator initiation; and the forskolin-induced swelling (FIS) responses to LUM/IVA, quantified in intestinal organoids. On a group level, the results showed an acute change in ppFEV1 after LUM/IVA initiation (2.34%, 95% CI 0.85–3.82, p = 0.003), but no significant change in annual ppFEV1 decline in the three years after LUM/IVA compared to the three years before (change: 0.11% per year, 95%CI: −1.94–2.19, p = 0.913). Neither of these two outcomes was associated with any of the candidate predictors on an individual level. The median number of pulmonary exacerbations (PEx) per patient year did not significantly change in the three years after LUM/IVA compared to the years before (median: 0.33/patient year, IQR: 0–0.67 before vs. median: 0/patient year, IQR: 0–0.67 after p = 0. 268). The PEx rate after modulator initiation was associated with the PEx rate before (IRR: 2.26, 95%CI: 1.67–3.08, p < 0.001), with sex (males vs. females IRR: 0.36, 95%CI: 0.21–0.63, p = 0.001) and with sweat chloride concentration (SwCl) at baseline (IRR: 0.96, 95%CI: 0.94–0.98, p = 0.001). The change in SwCl was also significant (−22.9 mmol/L (95%CI: −27.1–−18.8, p < 0.001) and was associated with SwCl at baseline (−0.64, 95%CI: −0.90–−0.37, p < 0.001) and with sex (males vs. females 8.32, 95%CI: 1.82–14.82, p = 0.013). In conclusion, ppFEV1 decline after CFTR modulator initiation remains difficult to predict in individual patients in a real-world setting, with limited effectiveness for double CFTR modulator therapies. The PEx rate prior to CFTR modulator treatment initiation, sex and SwCl at baseline could be potential predictors of long-term PEx rate and of changes in SwCl after modulator initiation.

A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose solution was performed. After 1 week, we conducted a urodynamic test, bladder staining, and ECM-related gene expression analysis to examine the treatment’s efficacy. We found that dextrose treatment could recover the instability of the bladder, reduce frequent urination, and improve the glycosaminoglycan layer regeneration and the bladder wall thickness along with a significant intense expression of CD44 receptors. Furthermore, we enrolled 29 IC/BPS patients with previous hyaluronic acid/Botox treatment for more than 6 months with remained unchanged condition. In this study, they received intravesical injections of 10% dextrose solution followed by assessments for up to 12 weeks. Patient characteristics and a 3-day voiding diary before treatment were recorded. Patient responses were examined using IC/BPS-related questionnaires. Moreover, expressions of growth factors and cytokines were analyzed. The results demonstrated that dextrose prolotherapy in patients with IC/BPS reduced the frequency of treatment over time, with the mean number of treatments being 3.03 ± 1.52, and significantly reduced the incidence of nocturia and questionnaire scores associated with symptoms. Dextrose prolotherapy significantly enhanced EGF level and, in contrast, reduced the level of HGF, PIGF-1, and VEGF-D after several weeks following treatment. The cytokine analysis showed that the expressions of IL-12p70 and IL-10 were significantly up-regulated after dextrose prolotherapy in IC/BPS patients. The levels of most growth factors and cytokines in IC/BPS patients had no significant difference and showed a similar tendency as time progressed when compared to healthy controls. Overall, the alteration of growth factors and cytokines exhibited safe treatment and potential stimulation of tissue remodeling. In summary, our study demonstrated that dextrose prolotherapy is a promising treatment strategy for IC/BPS disease management.

A Pipelined Tracer-Aware Approach for Lesion Segmentation in Breast DCE-MRI

The recent spread of Deep Learning (DL) in medical imaging is pushing researchers to explore its suitability for lesion segmentation in Dynamic Contrast-Enhanced Magnetic-Resonance Imaging (DCE-MRI), a complementary imaging procedure increasingly used in breast-cancer analysis. Despite some promising proposed solutions, we argue that a “naive” use of DL may have limited effectiveness as the presence of a contrast agent results in the acquisition of multimodal 4D images requiring thorough processing before training a DL model. We thus propose a pipelined approach where each stage is intended to deal with or to leverage a peculiar characteristic of breast DCE-MRI data: the use of a breast-masking pre-processing to remove non-breast tissues; the use of Three-Time-Points (3TP) slices to effectively highlight contrast agent time course; the application of a motion-correction technique to deal with patient involuntary movements; the leverage of a modified U-Net architecture tailored on the problem; and the introduction of a new “Eras/Epochs” training strategy to handle the unbalanced dataset while performing a strong data augmentation. We compared our pipelined solution against some literature works. The results show that our approach outperforms the competitors by a large margin (+9.13% over our previous solution) while also showing a higher generalization ability.

In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.

Effect of CKD-MBD therapies on the gastrointestinal expression of phosphate transporters

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is prevalent and encompasses biochemical abnormalities, bone alterations, and vascular calcifications. CKD-MBD treatments include phosphate binders and calcimimetics that effectively lower phosphorus and PTH, respectively, but the impact of these treatments on phosphate transporters in the gastrointestinal tract is still unknown. NaPi2B is considered the primary intestinal phosphate transporter. However, NaPi2B inhibition shows limited effectiveness, thus the importance of PIT1 and PIT2 requires further investigation. Methods: We tested the effects phosphate binders (ferric citrate (FC) and calcium gluconate (Ca)) and the calcimimetic KP2326 (KP) in (Cy/+ male rat; CKD) and untreated normal littermates (NL). Treatments lasted 10 weeks until euthanasia at 28 weeks (moderate-to-advanced CKD), where we collected mucosa samples from duodenum, jejunum, and ileum. Blood was collected for biochemistry measurements. Total RNA was isolated, and qPCR performed to assess phosphate transporters expression (NaPi2B, PIT1, PIT2) normalized to b-actin. Results were analyzed via 2-way ANOVA. Results: As expected, CKD had abnormal plasma concentrations of phosphorus, PTH, and FGF23. FC and KP effectively lowered phosphorus. KP and Ca lowered PTH, but Ca increased FGF23. NaPi2B was expressed in the duodenum and jejunum but not in the ileum, and its expression was upregulated with FC compared to NL. PIT1 was expressed in all segments, but the expression was the highest in the ileum, while PIT2 was constitutively expressed in all segments. Ca led to higher PIT1 and PIT2 expression in the duodenum and jejunum compared to NL, CKD, or KP. KP led to higher expression of PIT1 in the ileum compared to CKD, FC, and Ca. Conclusions: CKD-MBD therapies differentially impacted biochemistries and phosphate transporters expression. The effect of Ca on gastrointestinal expression of PIT1 and PIT2 may explain the higher plasma phosphorus and should be further explored.