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A method of overcoming barriers associated with implementing lifestyle interventions in CKD may be through the use of eHealth technologies. The aim of this review was to provide an up-to-date overview of the literature on this topic. Four bibliographical databases, two trial registers, and one database for conference proceedings were searched from inception to August 2023. Studies were eligible if they reported a lifestyle intervention using eHealth technologies. A narrative synthesis of the findings from the included studies structured around the type of eHealth intervention was presented. Where a sufficient number of studies overlapped in terms of the type of intervention and outcome measure these were brought together in a direction of effect plot. There were 54 included articles, of which 23 were randomised controlled trials (RCTs). The main component of the intervention for the included studies was mobile applications (n = 23), with the majority being in the dialysis population (n = 22). The majority of eHealth interventions were reported to be feasible and acceptable to participants. However, there was limited evidence that they were efficacious in improving clinical outcomes with the exception of blood pressure, intradialytic weight gain, potassium, and sodium. Although eHealth interventions appear acceptable and feasible to participants, there is insufficient evidence to make recommendations for specific interventions to be implemented into clinical care. Properly powered RCTs which not only demonstrate efficacy, but also address barriers to implementation are needed to enhance widespread adoption.

Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75–0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85–0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality. CI, confidence intervals; CV, cardiovascular; HFH, heart failure hospitalization; RCTs, randomized controlled trials; RR, risk ratios. [Display omitted] • 9 RCTs evaluated outcomes of IV iron in patients with heart failure and anemia. • IV iron lowers risk of heart failure hospitalization or cardiovascular death by 16 %. • IV iron leads to a significant reduction in heart failure hospitalization by 25 %. • No significant difference in cardiac or mortality, GI events, or infection. • Benefits of IV iron were consistent across trials. [ABSTRACT FROM AUTHOR]

Abstract Neuromorphic computing has emphasized the need for memristors with non-volatile, multiple conductance levels. This paper demonstrates the potential of hexagonal boron nitride (hBN)/graphene heterostructures to act as memristors with multiple resistance states that can be optically tuned using visible light. The number of resistance levels in graphene can be controlled by modulating doping levels, achieved by varying the electric field strength or adjusting the duration of optical illumination. Our measurements show that this photodoping of graphene results from the optical excitation of charge carriers from the nitrogen-vacancy levels of hBN to its conduction band, with these carriers then being transferred to graphene by the gate-induced electric field. We develop a qualitative model to describe our observations. Additionally, utilizing our device architecture, we propose a memristive crossbar array for vector-matrix multiplications.

Abstract Spatially resolved molecular assays provide high dimensional genetic, transcriptomic, proteomic, and epigenetic information in situ and at various resolutions. Pairing these data across modalities with histological features enables powerful studies of tissue pathology in the context of an intact microenvironment and tissue structure. Increasing dimensions across molecular analytes and samples require new data science approaches to functionally annotate spatially resolved molecular data. A specific challenge is data-driven cross-sample domain detection that allows for analysis within and between consensus tissue compartments across high volumes of multiplex datasets stemming from tissue atlasing efforts. Here, we present MILWRM (multiplex image labeling with regional morphology)—a Python package for rapid, multi-scale tissue domain detection and annotation at the image- or spot-level. We demonstrate MILWRM’s utility in identifying histologically distinct compartments in human colonic polyps, lymph nodes, mouse kidney, and mouse brain slices through spatially-informed clustering in two different spatial data modalities from different platforms. We used tissue domains detected in human colonic polyps to elucidate the molecular distinction between polyp subtypes, and explored the ability of MILWRM to identify anatomical regions of the brain tissue and their respective distinct molecular profiles.

Introduction: There is much debate over the best choice of restorative material and the placement method for the most successful treatment. Many teeth that have undergone endodontic treatment may not have enough structure to support a restoration or crown. To improve retention for the restorative material, ferrule may be used. Adhesive techniques have transformed the way we restore teeth after root canal treatment, starting with the shift from using cast post-and-core to using fibre post. The use of fibre-reinforced posts has been found to prevent irreparable root fractures thereby improving the longevity of the treatment. Aim: To compare two different types of aesthetic fibre posts for 12 months. Materials and Methods: A prospective interventional study was carried out in the Department of Prosthodontics, Manav Rachna Dental College (Faridabad) for a period of 12 months from Nov 2022- Oct 2023. Forty participants with single rooted, endodontically treated, maxillary anterior teeth in the age bracket of 15-55 years, both males and females of the north Indian population were included in the study. Teeth were selected where a post-retained crown was indicated and post space was prepared using a piezo reamer drill at 5000 rpm. At least 4 mm of obturation is left in the canal to maintain the apical seal. Furthermore, Zircon-enriched silicon fibre and glass fibre-reinforced posts were cemented into the prepared post space. Metal-ceramic crowns were cemented and baseline periapical radiographs were obtained. At the interval of one month, three months, six months and one year, the patients were evaluated.The Fischer’s exact test was utilised to establish the association between categorical variables and the level of significance (p-value

Abstract Crohn’s disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as ‘LND’) with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn’s ileitis and colitis.

Purpose: To compare the quality of complete dentures and quality of life of participants rehabilitated by using TENS (Transcutaneous electric nerve stimulation) facilitated impression making with manual impressions. Material and methods: Ten completely edentulous participants were enrolled in the crossover, pilot study. Participants were randomized in 2 groups. Five participants in each group were rehabilitated by dentures fabricated with TENS facilitated definitive impression technique (group T) and conventional impression technique (group C). In group T, Bioelectric border molding was done for the participants, that uses electric stimulation of the nerves supplying the muscles. In group C, incremental border molding using modeling plastic impression compound was carried out. Participants in each group used the dentures for 3 months. After 3 months, OHIP-EDENT questionnaire responses were obtained from the participants to observe the oral health related quality of life. A dental specialist recorded denture quality by Kapur scoring criteria. After one month wash period, the treatment was swapped between the groups. OHIP-EDENT scores and Kapur score were recorded for the alternate dentures after 3 months of use. Descriptive analysis was followed by Mann Whitney test to compare the overall scores between group T and group C for OHIP-EDENT, the scores for individual domains of OHIP-EDENT, and Kapur score for denture evaluation (α = 0.05). Results: The overall OHIP-EDENT scores within each domain were less in group T when compared with the scores in group C and Kapur score for group T was more than group C. The difference was statistically significant i.e. P = 0.002 & 0.003 respectively. Conclusions: Less OHIP-EDENT scores in group T imply better perception of quality of life of individuals due to better performance of stomatognathic system. The higher Kapur scores in group T signifies better quality of dentures when TENS was used for definitive impression making.

Key Clinical Message Early recognition and management of familial hypercholesterolemia (FH) are crucial, especially in patients with extensive xanthomas and premature coronary artery disease. Prompt diagnosis and aggressive lipid‐lowering therapy can significantly reduce morbidity and mortality rates. Careful clinical assessment in resource‐limited settings is essential for optimal outcomes. Abstract Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder that causes chronically elevated levels of low‐density lipoprotein (LDL) cholesterol. Based on LDL levels, FH can be heterozygous or homozygous, further established through clinical features, laboratory findings, and genetic analysis. Elevated cholesterol levels cause atherosclerosis, coronary artery disease, myocardial infarction, and sudden death. Xanthomas are a clinical manifestation of FH that reveal the underlying systemic genetic disease. We present the case of a 47‐year‐old male with triple vessel coronary artery disease and widespread xanthomas, diagnosed with homozygous FH based on “The Dutch Lipid Clinic Network Diagnostic Criteria for Familial Hypercholesterolemia.” Lifelong therapy with lipid‐lowering medications and lifestyle changes is necessary in such cases.

The objective is to minimize the inaccuracies in two-step impressions by homogenizing the polymerization shrinkage of elastomeric impression material in fixed prosthesis fabrication. The objective is accomplished by the technique of spacer adaptation and custom tray fabrication for two-step impressions. The technique makes the use of two vacuum-adapted spacers, selected based on the viscosity of elastomeric impression, and a vacuum-adapted custom tray. The procedure of using the specially fabricated custom tray for impression making is also presented. Consistent thickness of the two different viscosities of impression material is maintained due to vacuum adaptation of the spacers. This homogenizes the polymerization shrinkage of the elastomeric material in different regions of impression, as uniform space is occupied by the material in the space created by the spacer. The procedure of vacuum adaption of the tray material also limits the dimensional change of the tray. The technique minimizes the inaccuracies of impression by homogenizing the polymerization shrinkage of the elastomeric impression, thus promising a well-fitting prosthesis.

Abstract Basal cell carcinoma (BCC) is the most common skin cancer. Skin cancers may present either as a non-invasive tumor or an invasive malignancy. The terminology of carcinoma in situ is used when the tumor is either just limited to epidermis or not present as single cells or nests in the dermis. However, currently the terminology superficial BCC is inappropriately used instead of BCC in situ when the skin cancer is limited to epidermis. In this study we compare the pathologic changes of superficial, nodular, and infiltrative BCCs using electron microscopy to identify the ultrastructural characteristics and validate the previously proposed terminology. Three cases of BCC (superficial BCC, nodular BCC, and infiltrative BCC) diagnosed by dermatopathologists at our institute were selected for review. Paraffin block tissues from these cases were sent for electron microscopy studies which demonstrated disruption of basal lamina in both nodular and infiltrative type of BCC, while it remains intact in BCC superficial type after extensive examination. Therefore, similar to other in situ skin cancers, there is no invasion of the neoplasm in superficial BCC into the dermis. Hence, the older term superficial BCC should be appropriately replaced with the newer terminology BCC in situ.

Abstract Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2–3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial. Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Introduction: Providing complete denture therapy to patients with atrophic residual alveolar ridges is challenging, because these patients suffer ongoing resorption of the denture foundation; regardless of contemporary treatment options, physiologically optimal denture contours and appropriate denture tooth arrangement should be achieved to maximize prosthesis stability, comfort and function for patients. One of the methods used to achieve the stability is the neutral zone technique. Aim: It is in this zone that the natural dentitions lie and this is where the artificial teeth should be positioned. This article describes a preview of faciolingual positioning of denture teeth along with a novel approach of recording the neutral zone. Conclusion: The neutral zone is the area where the displacing forces of the lips, cheeks and tongue are in balance. Physiologic recording of the neutral zone aids in stability to the prosthesis.

Background: Mucormycosis is a fungal infection that can affect multiple organs. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is not well documented. Aim: The objective of this study was to describe the detailed cytomorphologic features of mucormycosis on FNAC samples. Materials and Methods: A retrospective analysis of all cases diagnosed as mucormycosis on FNAC between January 2014 and July 2021 was performed for detailed cytomorphological evaluation and correlation to clinical data and microbiological studies wherever available. FNA was computed tomography-guided (n = 38), ultrasonography-guided (n = 31) or palpation-guided (n = 12), and slides were reviewed in two cases. Results: A total of 83 cases of mucormycosis were evaluated. An immunocompromised setting was observed in 48 cases. The most common site of FNA was the lung (n = 57) followed by liver, soft tissue, palate, mediastinum, orbital/ocular region, and lymph node. Isolated renal involvement, a unique feature, was seen in seven cases. The aspirates were necrotic to pus-like or blood-mixed particulate. Broad, nonseptate, foldable, ribbon-like fungal hyphae showing right-angled branching were seen. The tissue reaction was predominantly necro-inflammatory (n = 36), bland necrotic (n = 22), mixed inflammatory (n = 16), suppurative (n = 5), necrotizing granulomatous (n = 3), and granulomatous (n = 1). Immunocompromised patients showed mixed inflammatory responses more frequently. Fungal culture was positive for Rhizopus species in 2/13 cases and molecular testing in two additional cases corresponding to Rhizopus and Syncephalastrum spp. Conclusion: FNA provides quick and conclusive diagnosis of mucormycosis from varied anatomic sites enabling prompt institution of therapy. The tissue response is variable and to some extent dependent on the immune status of the patient.

Multidrug-resistant yeast Candida auris is a serious threat to public health with documented survival in various hospital niches. The dynamics of this survival benefit and its trade off with drug resistance are still unknown for this pathogen. In this study we investigate the oxidative stress response (OSR) in fluconazole-resistant C. auris and compare its relative fitness with fluconazole-susceptible strains. A total of 351 C. auris clinical isolates (61 fluconazole-susceptible and 290 fluconazole-resistant) were screened for stress tolerance by spot assay and 95.08 % fluconazole-susceptible isolates were hyper-resistant to oxidative stress while majority (94.5 %) fluconazole-resistant isolates had lower oxidative tolerance. Expression of Hog1 and Cta1 gene transcript levels and cellular catalase levels were significantly higher in fluconazole-susceptible isolates and a corresponding higher intracellular reactive oxygen species level (iROS) was accumulated in the fluconazole-resistant isolates. Biofilm formation and cell viability under oxidative stress revealed higher biofilm formation and better viability in fluconazole-susceptible isolates. Fluconazole-resistant isolates had higher basal cell wall chitin. On comparison of virulence, the % cytotoxicity in A549 cell line was higher in fluconazole-susceptible isolates and the median survival of the infected larvae in G. mellonella infection model was higher in fluconazole-resistant (5; IQR:4.5–5 days) vs. fluconazole-susceptible C. auris (2; IQR:1.5–2.5 days). All organisms evolve with changes in their environmental conditions, to ensure an optimal balance between proliferation and survival. Development of tolerance to a certain kind of stress example antifungal exposure in yeast can leads to a compensatory decrease in tolerance for other stresses. This study provides useful insights into the comparative fitness and antifungal susceptibility trade off in C. auris. We report a negative association between H2O2 tolerance and fluconazole susceptibility. Using in-vitro cell cytotoxicity and in-vivo survival assays we also demonstrate the higher virulence potential of fluconazole-susceptible C. auris isolates corroborating the negative correlation between susceptibility and pathogen survival or virulence. These findings could also be translated to clinical practice by investigating the possibility of using molecules targeting stress response and fitness regulating pathways for management of this serious infection.

As professional phagocytes, macrophages represent the first line of defence against invading microbial pathogens. Various cellular processes such as programmed cell death, autophagy and RNA interference (RNAi) of macrophages are involved directly in elimination or assist in elimination of invading pathogens. However, parasites, such as Leishmania, have evolved diverse strategies to interfere with macrophage cell functions, favouring their survival, growth and replication inside hostile and restrictive environments of macrophages. Therefore, identification and detailed characterization of macrophage-pathogen interactions is the key to understanding how pathogens subvert macrophage functions to support their infection and disease process. In recent years, great progress has been achieved in understanding how Leishmania affects with critical host macrophage functions. Based on latest progress and accumulating knowledge, this review exclusively focuses on macrophage-Leishmania interaction, providing an overview of macrophage cellular processes such as programmed cell death, autophagy and RNAi during Leishmania infection. Despite extensive progress, many questions remain and require further investigation.

The intracellular protozoan parasite Leishmania causes leishmaniasis in humans, leading to serious illness and death in tropical and subtropical areas worldwide. Unfortunately, due to the unavailability of approved vaccines for humans and the limited efficacy of available drugs, leishmaniasis is on the rise. A comprehensive understanding of host-pathogen interactions at the molecular level could pave the way to counter leishmaniasis. There is growing evidence that several intracellular pathogens target RNA interference (RNAi) pathways in host cells to facilitate their persistence. The core elements of the RNAi system are complexes of Argonaute (Ago) proteins with small non-coding RNAs, also known as RNA-induced silencing complexes (RISCs). Recently, we have shown that Leishmania modulates Ago1 protein of host macrophages for its survival. In this study, we biochemically characterize the Ago proteins' interactome in Leishmania-infected macrophages compared to non-infected cells. For this, a quantitative proteomic approach using stable isotope labelling by amino acids in cell culture (SILAC) was employed, followed by purification of host Ago-complexes using a short TNRC6 protein-derived peptide fused to glutathione S-transferase beads as an affinity matrix. Proteomic-based detailed biochemical analysis revealed Leishmania modulated host macrophage RISC composition during infection. This analysis identified 51 Ago-interacting proteins with a broad range of biological activities. Strikingly, Leishmania proteins were detected as part of host Ago-containing complexes in infected cells. Our results present the first report of comprehensive quantitative proteomics of Ago-containing complexes isolated from Leishmania-infected macrophages and suggest targeting the effector complex of host RNAi machinery. Additionally, these results expand knowledge of RISC in the context of host-pathogen interactions in parasitology in general.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure–activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.