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Objective: To rate athletes' functional ability and return to sport (RTS) success at the end of their individual, formal, medically prescribed rehabilitation after anterior anterior cruciate ligament (ACL) reconstruction. Methods: In our prospective multicenter cohort study, 88 (42 females) adults aged 18-35 years after acute unilateral ACL rupture and subsequent hamstring grafting were included. All patients were prospectively monitored during their rehabilitation and RTS process until the end of their formal rehabilitation and RTS release. As outcome measures, functional hop and jump tests (front hop, balance hops, and drop jump screening test) and self-report outcomes (Knee Injury and Osteoarthritis Outcome Score, ACL-RTS after injury) were assessed. Literature-based cut-off values were selected to rate each performance as fulfilled or not. Results: At 7.5 months (SD 2.3 months) after surgery, the percentage of participants meeting the functional thresholds ranged from 4% (Knee Injury and Osteoarthritis Outcome Score SPORT) and over 44% (ACL-RTS after injury sum score) to 59% (Knee Injury and Osteoarthritis Outcome Score activities of all daily living) in the self-report and from 29% (Balance side hop) to 69% (normalized knee separation distance) in performance testing. Only 4% fulfilled all the cut-offs, while 45% returned to the same type and level of sport. Participants who successfully returned to their previous sport (type and level) were more likely to be "over-cut-off-performers." Conclusions: The low share of the athletes who fulfilled the functional RTS criteria highlights the importance of continuing the rehabilitation measures after the formal completion to assess the need for and success of, inter alia, secondary-preventive therapies. [ABSTRACT FROM AUTHOR]

Generating highly organized skeletal muscle tissues that mimics the cellular alignment, maturation, and contraction of native skeletal muscle remains a challenge in disease modeling and regenerative therapies. Existing methodologies are constrained by complexity in fabrication and difficulty in achieving aligned 3D myofibers. Here, a functional skeletal muscle organoid‐on‐a‐chip (SMO) is engineered by establishing mechanical boundary constraints at either end of the cell‐laden extracellular matrix hydrogel within polydimethylsiloxane microstructures to promote the formation of an anisotropic biophysical microenvironment in tissues. The linearly aligned tissue, featuring multinucleated myofibers with distinct cross‐striations, exhibited a positive force‐frequency relationship and stable calcium transients under electrical stimulation. SMOs applicability is demonstrated by systematically evaluating muscle response to varying degrees of intermittent hypoxia. Murine‐ or human‐derived SMOs revealed that, with increasing hypoxia severity, muscles transitioned from a compensatory phase‐characterized by enhanced contractile function, vacuolation and hypertrophic‐like changes in myofibers, fiber type switching, and metabolic shift, to a decompensatory stage, paralleling in vivo muscle responses and highlighting interspecies differences. Human‐derived SMOs are also utilized to assess self‐repair capabilities and pharmaceuticals protective effects on damaged muscle. Together, the platform, with its simplicity of operation and reliable phenotypic readouts, demonstrates significant potential for future disease modeling and regenerative therapies. [ABSTRACT FROM AUTHOR]

Summary Immune responses to primary COVID‐19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016–004010‐10). COVID‐19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide‐based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS‐CoV‐2 spike protein using the Abbott Architect and interferon‐gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T‐cell responses. Within the FL cohort, multivariable analysis identified low pre‐treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T‐cell responses, and bendamustine and high/intermediate FLIPI‐2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID‐19 vaccines in FL patients is influenced by multiple disease‐ and treatment‐related factors, among which B‐cell depletion showed differential effects on antibody and T‐cell responses. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a type of non-coding RNA (ncRNA) that possesses a unique single-stranded circular structure. They are primarily formed through alternative splicing of pre-mRNA (messenger RNA). The primary biological function of circRNAs is to regulate gene expression at both the transcriptional and post-transcriptional levels. Recent studies have increasingly demonstrated a close association between the dysregulation of circRNAs and the progression of diverse cancers, where they can function as either tumor suppressors or oncogenes. circWHSC1 (circNSD2) is a circular ncRNA that originates from the first 2 exons of the Wolf-Hirschhorn syndrome candidate gene (WHSC1). As Chen 2019 discovery that circWHSC1 (circNSD2) functions as a sponge for miRNAs and promotes cancer, this circRNA has garnered significant interest among researchers. circWHSC1 (circNSD2) has been found to be up-regulated in various malignant tumors, including nasopharyngeal carcinoma, lung cancer, breast cancer, liver cancer, colorectal cancer, ovarian cancer, cervical cancer, and endometrial cancer. It exerts its effects on cancer by either inhibiting or promoting the expression of related genes through direct or indirect pathways, ultimately affecting cancer proliferation, invasion, and prognosis. This article provides a comprehensive review and discussion of the biological roles of circWHSC1 (circNSD2) and its target genes in various cancers, as well as the latest research progress on related molecular biological regulatory mechanisms. Furthermore, the potential significance of circWHSC1 (circNSD2) in future clinical applications and transformations is thoroughly analyzed and discussed. [ABSTRACT FROM AUTHOR]

Modulating cellular functions at the dental implant‐tissue interface to augment integration and prevent bacterial ingress is crucial for achieving early stability and long‐term implant success. Nano‐engineering strategies, such as anodized titanium implants with titania (TiO2) nanotubes/nanopores, are emerging as a promising dental implant surface modification approach to enhance integration and prevent infection. Achieving on‐demand therapy through electrical stimulation therapy (EST, supply of voltage/current to local tissue) may be advantageous but has not been explored for dental implants. Further, anodized implants with TiO2 nanotubes/nanopores represent a semi‐conducting modification that can impede EST effectiveness. In this pioneering study, TiO2 nanopores are converted into conducting Ti nanopores to perform EST to achieve superior soft‐tissue integration and antibacterial efficacy. In‐depth surface characterizations are followed by assays investigating the effect of EST on cultured human salivary biofilm and gingival fibroblasts. Significant bactericidal efficacy is demonstrated for EST (1.5 V for 5 min per day) using Ti nanopores. Further, EST enhanced fibroblast proliferation and collagen secretion. In summary, EST applied to Ti nanoporous implants promotes soft‐tissue healing and antibacterial functions and is proposed as a next‐generation approach in implant dentistry to achieve on‐demand therapy. [ABSTRACT FROM AUTHOR]

Dropout from psychotherapy among adolescents is a common occurrence. Adolescents’ need for independence can be in direct conflict with therapeutic relationships, particularly in open-ended psychotherapy where endings need to be negotiated. The present study was a service evaluation, which aimed to identify how open-ended once-weekly psychoanalytic psychotherapy ends with adolescents, and whether dropout could be predicted from a range of adolescent and treatment factors. The sample comprised 443 adolescents, aged 14–24, who had received psychoanalytic psychotherapy in a community-based clinic. Logistic regression was used to estimate the effects of predictors on the odds of dropout. Adolescents were categorised based on how treatment ended: adolescents’ unilateral decision (43%), mutually agreed between adolescent and therapist (27%), initiated by changed external circumstances such as relocation (23%) or a referral to another service (6%). Younger adolescents and those from more disadvantaged backgrounds were most at risk of dropout. Missed sessions early in treatment were also predictive of dropout. Neither therapist change nor the number of services was significantly associated with dropout. This study shows that dropout is a frequent occurrence in open-ended psychoanalytic psychotherapy. Further research is needed to explore how young people at risk of dropout can be better supported to attend treatment to ensure they receive the maximum benefits. Moreover, research is required to identify how therapists can optimally respond to missed sessions, to avoid subsequent dropout and to facilitate positive and appropriate treatment endings. [ABSTRACT FROM AUTHOR]

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles. [ABSTRACT FROM AUTHOR]

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles. [ABSTRACT FROM AUTHOR]

Rewiring of cellular metabolism is now fully recognized as a hallmark of cancer. Tumor cells reprogram metabolic pathways to meet the energetic and macromolecular demands to support unrestricted growth and survival under unfavorable conditions. It is becoming apparent that these adaptations underpin most of the traits that define a cancer cell's identity, including the ability to avoid immune surveillance, endure nutrient and oxygen restrictions, detach and migrate from their natural histological niche, and avert human‐made aggressions (i.e., therapy). In a recent study, Benichou and collaborators identify carbohydrate‐responsive element‐binding protein (ChREBP), a master regulator of physiological glucose metabolism, as an oncogene in hepatocellular carcinoma (HCC) development. Upregulation of ChREBP expression results in a self‐stimulatory loop interconnecting PI3K/AKT signaling and glucose metabolism to feed fatty acid and nucleotide synthesis supporting tumorigenesis. Importantly, pharmacological inhibition of ChREBP activity quells in vivo HCC tumor growth without causing systemic toxicity. This study identifies novel oncometabolic pathways and open up new avenues to improve the treatment of a deadly tumor. [ABSTRACT FROM AUTHOR]

In this cross-sectional study, we examined the relations between perceived LGBTQ+ community support for psychotherapy and both willingness to seek counseling and use of mental health services in the past year among 721 sexual minority persons. At the bivariate level, we found that LGBTQ+ community support for psychotherapy was positively correlated with both willingness to seek counseling and use of mental health services in the past year. Further, LGBTQ+ community support for psychotherapy was directly and indirectly related to willingness to seek counseling via less public stigma, less self-stigma, and more positive attitudes toward help-seeking in serial. LGBTQ+ community support for psychotherapy was indirectly related to use of mental health services in the past year via these same explanatory variables. Finally, we provide psychometric support for the LGBTQ+ Community Support for Psychotherapy Scale that we developed for this study. Our findings indicate the important role that contextual factors can have on psychological help-seeking attitudes, intentions, and behaviors for sexual minority persons. [ABSTRACT FROM AUTHOR]

Tuft cells are more than guardian chemosensory elements of the digestive tract. They produce a variety of immunological effector molecules in response to stimulation; moreover, they are essential for defense against protozoa and nematodes. Beyond the description of their characteristics, this review aims to elucidate the potential pathogenic and therapeutic roles of colonic tuft cells in inflammatory bowel disease and colorectal cancer, focusing on their primarily immunomodulatory action. Regarding inflammatory bowel disease, tuft cells are implicated in both maintaining the integrity of the intestinal epithelial barrier and in tissue repair and regeneration processes. In addition to maintaining intestinal homeostasis, they display complex immune-regulatory functions. During the development of colorectal cancer, tuft cells can promote the epithelial-to-mesenchymal transition, alter the gastrointestinal microenvironment, and modulate both the anti-tumor immune response and the tumor microenvironment. A wide variety of their biological functions can be targeted for anti-inflammatory or anti-tumor therapies; however, the adverse side effects of immunomodulatory actions must be strictly considered. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small RNA molecules that regulate more than 30% of genes in humans. Recent studies have revealed that miRNAs play a crucial role in tumorigenesis. Large sets of miRNAs in human tumors are under-expressed compared to normal tissues. Furthermore, experiments have shown that interference with miRNA processing enhances tumorigenesis. Multiple studies have documented the causal role of miRNAs in cancer, and miRNA-based anticancer therapies are currently being developed. This review primarily focuses on two key points: (1) miRNAs and their role in human cancer and (2) the regulation of tumor suppressors by miRNAs. The review discusses (a) the regulation of the tumor suppressor p53 by miRNA, (b) the critical role of the miR-144/451 cluster in regulating the Itch-p63-Ago2 pathway, and (c) the regulation of PTEN by miRNAs. Future research and the perspectives of miRNA in cancer are also discussed. Understanding these pathways will open avenues for therapeutic interventions targeting miRNA regulation. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common malignant extracranial solid tumor of childhood. Recent studies involving the application of advanced high-throughput "omics" techniques have revealed numerous genomic alterations, including aberrant coding-gene transcript levels and dysfunctional pathways, that drive the onset, growth, progression, and treatment resistance of neuroblastoma. Research conducted in the past decade has shown that long non-coding RNAs, once thought to be transcriptomic noise, play key roles in cancer development. With the recent and continuing increase in the amount of evidence for the underlying roles of long non-coding RNAs in neuroblastoma, the potential clinical implications of these RNAs cannot be ignored. In this review, we discuss their biological mechanisms of action in the context of the central driving mechanisms of neuroblastoma, focusing on potential contributions to the diagnosis, prognosis, and treatment of this disease. We also aim to provide a clear, integrated picture of future research opportunities. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) causes a significant challenge to global healthcare systems, with limited effective treatments available. This review examines the landscape of novel therapeutic strategies for AD, focusing on the shortcomings of traditional therapies against amyloid-beta (Aβ) and exploring emerging alternatives. Despite decades of research emphasizing the role of Aβ accumulation in AD pathogenesis, clinical trials targeting Aβ have obtained disappointing results, highlighting the complexity of AD pathophysiology and the need for investigating other therapeutic approaches. In this manuscript, we first discuss the challenges associated with anti-Aβ therapies, including limited efficacy and potential adverse effects, underscoring the necessity of exploring alternative mechanisms and targets. Thereafter, we review promising non-Aβ-based strategies, such as tau-targeted therapies, neuroinflammation modulation, and gene and stem cell therapy. These approaches offer new avenues for AD treatment by addressing additional pathological hallmarks and downstream effects beyond Aβ deposition. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) has become one of the leading causes of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT) have been recently added to the clinical armamentarium of stage II/III diseases. Moreover, the improvement of a patient's telomere status may have a synergistic effect along with ICIs/ACT. This can be achieved either via lifestyle modifications with increased physical activity or with new promising treatments such as those acting on telomerase. Therefore, this review aims to comprehensively summarize the current data on immunotherapy in order to facilitate clinicians' familiarity with this relatively new therapeutic approach. Cancer of the colon and rectum (CRC) has been identified among the three most prevalent types of cancer and cancer-related deaths for both sexes. Even though significant progress in surgical and chemotherapeutic techniques has markedly improved disease-free and overall survival rates in contrast to those three decades ago, recent years have seen a stagnation in these improvements. This underscores the need for new therapies aiming to augment patient outcomes. A number of emerging strategies, such as immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), have exhibited promising outcomes not only in preclinical but also in clinical settings. Additionally, a thorough appreciation of the underlying biology has expanded the scope of research into potential therapeutic interventions. For instance, the pivotal role of altered telomere length in early CRC carcinogenesis, leading to chromosomal instability and telomere dysfunction, presents a promising avenue for future treatments. Thus, this review explores the advancements in CRC immunotherapy and telomere-targeted therapies, examining potential synergies and how these novel treatment modalities intersect to potentially enhance each other's efficacy, paving the way for promising future therapeutic advancements. [ABSTRACT FROM AUTHOR]

Tigilanol tiglate (TT, also known as EBC-46) is a novel, plant-derived diterpene ester possessing anticancer and wound-healing properties. Here, we show that TT-evoked PKC-dependent S985 phosphorylation of the tyrosine kinase MET leads to subsequent degradation of tyrosine phosphorylated p-Y1003 and p-Y1234/5 MET species. PKC inhibition with BIM-1 blocked S985 phosphorylation of MET and led to MET cell surface accumulation. Treatment with metalloproteinase inhibitors prevented MET-ECD release into cell culture media, which was also blocked by PKC inhibitors. Furthermore, unbiased secretome analysis, performed using TMT-technology, identified additional targets of TT-dependent release of cell surface proteins from H357 head and neck cancer cells. We confirm that the MET co-signalling receptor syndecan-1 was cleaved from the cell surface in response to TT treatment. This was accompanied by rapid cleavage of the cellular junction adhesion protein Nectin-1 and the nerve growth factor receptor NGFRp75/TNFR16. These findings, that TT is a novel negative regulator of protumorigenic c-MET and NGFRp75/TNFR16 signalling, as well as regulating Nectin-1-mediated cell adhesion, further contribute to our understanding of the mode of action and efficacy of TT in the treatment of solid tumours. [ABSTRACT FROM AUTHOR]

Cysteine cathepsins F and W are members of the papain-like cysteine protease family, which have distinct structural features and functional roles in various physiological and pathological processes. This review provides a comprehensive overview of the current understanding of the structure, biological functions, and pathological implications of cathepsins F and W. Beginning with an introduction to these proteases, we delve into their structural characteristics and elucidate their unique features that dictate their enzymatic activities and substrate specificity. We also explore the intricate involvement of cathepsins F and W in malignancies, highlighting their role as potential biomarkers and therapeutic targets in cancer progression. Furthermore, we discuss the emerging roles of these enzymes in immune response modulation and neurological disorders, shedding light on their implications in autoimmune and neurodegenerative diseases. Finally, we review the landscape of inhibitors targeting these proteases, highlighting their therapeutic potential and challenges in clinical translation. This review brings together the diverse facets of cysteine cathepsins F and W, providing insights into their roles in health and disease and guiding future investigations for therapeutic advances. [ABSTRACT FROM AUTHOR]

Managing primary amoebic meningoencephalitis, induced by Naegleria fowleri poses a complex medical challenge. There is currently no specific anti-amoebic drug that has proven effectiveness against N. fowleri infection. Ongoing research endeavours are dedicated to uncovering innovative treatment strategies, including the utilization of drugs and immune modulators targeting Naegleria infection. In this study, we explored the potential of imidazo[2,1-b]thiazole and imidazooxazole derivatives that incorporate sulfonate and sulfamate groups as agents with anti-amoebic properties against N. fowleri. We assessed several synthesized compounds (1f, 1m, 1q, 1s, and 1t) for their efficacy in eliminating amoebae, their impact on cytotoxicity, and their influence on the damage caused to human cerebral microvascular endothelial (HBEC-5i) cells when exposed to the N. fowleri (ATCC 30174) strain. The outcomes revealed that, among the five compounds under examination, 1m, 1q, and 1t demonstrated notable anti-parasitic effects against N. fowleri (P ≤ 0.05). Compound 1t exhibited the highest anti-parasitic activity, reducing N. fowleri population by 80%. Additionally, three compounds, 1m, 1q, and 1t, significantly mitigated the damage inflicted on host cells by N. fowleri. However, the results of cytotoxicity analysis indicated that while 1m and 1q had minimal cytotoxic effects on endothelial cells, compound 1t caused moderate cytotoxicity (34%). Consequently, we conclude that imidazo[2,1-b]thiazole and imidazooxazole derivatives containing sulfonate and sulfamate groups exhibit a marked capacity to eliminate amoebae viability while causing limited toxicity to human cells. In aggregate, these findings hold promise that could potentially evolve into novel therapeutic options for treating N. fowleri infection. [ABSTRACT FROM AUTHOR]

Ventilator-associated pneumonia (VAP) is a major health care associated infection which usually emanates from aspiration, immigration of pathogens from aerodigestive tract, adulterated appliance uses or medications. The mortality rate due to VAP is approximately 13% and the causative organisms are bacteria, viruses, and fungi. Many studies have investigated the causative organisms as Pseudomonas spp., Acinetobacter spp., Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus with varying prevalence. Intensive Care Unit (ICU) admitted patients who are ventilated, are more prone to the infections where the pathogens adhere to the mucosa of lower respiratory tract of mechanically ventilated patients and start infections. Clinical diagnosis based on Clinical Pulmonary Infection Score (CPIS) has poor specificity and microbiological findings takes 48-72 hrs, that can delay the treatment of patients. Lymphopenia on complete blood count is a predictor of mortality in VAP patients, but decreased lymphocyte count occurs in various other infections too. Multiplex PCR is a better diagnostic technique for VAP which can even diagnose atypical bacteria along with other etiological agents. Effectively employing sampling techniques is a vital step in the diagnosis of VAP, enabling the identification of pathogens responsible for lung infections. Furthermore, the emergence of novel therapeutic options approved by regulatory bodies, adds significant advancements in VAP treatment. In this review article, we have performed an in-depth study on the pathogenesis, diagnosis and therapeutic strategies involved in VAP. This study will help the researchers working in this area to design their work appropriately with the updated knowledge on VAP. [ABSTRACT FROM AUTHOR]

Background: Speech and language therapy can reduce the level of impairment and disability caused by aphasia (Brady et al., 2016). Selecting a therapy can be challenging for clinicians who may struggle to stay abreast of the best evidence to support therapy selection (Rose et al., 2014). Once a therapy is selected, accessing relevant resources is a significant barrier to implementation (Shrubsole et al., 2019). The Aphasia Therapy Finder (ATF) is proposed to be an online repository of therapy resources designed to aid selection of evidence-based aphasia therapies and to bridge the evidence-practice gap in aphasia rehabilitation. Aims: In this study, we aimed to explore speech pathologists’ selection and use of aphasia therapy approaches, and access to aphasia therapy resources in clinical practice. We further aimed to explore speech pathologists’ perspectives on the proposed ATF. Methods & Procedures: A cross-sectional, mixed-methods, survey design was employed. A 22-item web-based survey was developed and disseminated to speech pathologists via professional networks internationally. Data analyses included descriptive statistics and conventional content analysis. Outcomes & Results: Eligible responses from 176 speech pathologists across 19 countries were included in the analyses (86.3% completion rate). Speech pathologists reported using a range of therapy approaches (n = 43) in aphasia rehabilitation, consistent with previous findings (Rose et al., 2014). Information regarding new therapy approaches was predominantly obtained from academic sources including conferences, research literature, and professional development workshops. Speech pathologists placed high importance on research evidence when selecting therapy approaches. Resource limitations, including time and budget constraints, were identified as key barriers to implementing evidencebased aphasia therapy approaches in clinical practice. There was strong support for development of the ATF; 91.7% of respondents indicated they would use it in clinical practice. Recency of research, equity of access with the inclusion of linguistically and culturally diverse resources, and usability of resources were identified as priorities when developing the ATF. Conclusions: While speech pathologists report using a range of aphasia therapy approaches in clinical practice and consider research evidence when selecting therapy approaches, resource limitations continue to present a barrier to the implementation of evidence-based practice. The development of the ATF may support the translation of research evidence into clinical practice. [ABSTRACT FROM AUTHOR]

Summary: Obstructive sleep apnea is a common comorbidity that occurs in individuals with obesity. It classically manifests with excessive daytime sleepiness, resulting in reduced quality of life, workplace productivity, and an increased risk of motor vehicle accidents. Weight gain plays an important role in its pathogenesis through worsening upper airway collapsibility, and current treatment options are targeted towards mechanically overcoming upper airway obstruction and weight loss. Continuous positive airway pressure therapy remains the most widely prescribed treatment for obstructive sleep apnea but poor tolerance is a common barrier to effective treatment. Sustainable weight loss is an important treatment option but can be difficult to achieve without bariatric surgery. The recent advances in incretin‐based pharmacotherapies represent a promising avenue not only in achieving long‐term weight loss but also in treating obstructive sleep apnoea and alleviating the burden of its symptoms and comorbidities. [ABSTRACT FROM AUTHOR]

The Enneagram is a personality framework with ancient philosophical underpinnings and cross cultural roots. It outlines nine different pathways of growth for nine different personalities. In recent years, it has started to gain traction in the peer reviewed level of research. Since the Enneagram has a conceptual versatility in addressing various levels and dimensions of the human psyche, it can both contribute and benefit from cross pollinating its insights with the latest scientific research on how the human mind works. One area of research that has the potential for this type of symbiotic partnership with the Enneagram is the study of the interaction between the conscious and unconscious mind. There is rich potential for the multi-leveled integration of contemporary findings on how the conscious and unconscious mind mutually interact with one another along with insights into personality structures from the Enneagram. These integrative insights have clinical implications and create possible directions for future research. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disease. Despite being considered the gold standard treatment scheme, inhaled nitric oxide (iNO) is not readily available in settings with limited resources. Therefore, in recent years, research on related drugs is being actively pursued. Herein, we aimed to use random-effects network meta-analysis to evaluate the efficacy and associated mortality of different PPHN therapies. DATA SOURCES: We electronically searched the PubMed, Embase, and Cochrane Library for data up to January 27, 2023. STUDY SELECTION: Randomized controlled trials involving neonates with PPHN assessing efficacy and mortality of various treatments. DATA EXTRACTION: Details of study population, treatments, and outcomes were extracted. DATA SYNTHESIS: Direct pairwise comparisons and a network meta-analysis was performed under random effects. The ranking probability was further assessed based on the surface under the cumulative ranking curve (SUCRA). We analyzed 23 randomized clinical trials involving 902 newborns with PPHN. Sixteen different treatment strategies were compared with each other and conventional therapy (CON). A median concentration of 10-20 parts per million (ppm) iNO (MNO) coupled with sildenafil orally administered at a dose of 1-3 mg/kg/dose every 6-8 hours (OSID) demonstrated the best efficacy (MNO + OSID vs. CON: odds ratio [OR] = 27.53, 95% CI, 2.36-321.75; SUCRA = 0.818, ranking first; moderate quality). OSID combined with milrinone administered IV also performed well in terms of efficacy (OSID + milrinone vs. CON: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.811, ranking second; low quality) and mortality reduction (CON vs. OSID + milrinone: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.786, ranking last; low quality). CONCLUSIONS: MNO + OSID is the most effective PPHN treatment. If iNO is not available, OSID + milrinone is preferred. [ABSTRACT FROM AUTHOR]

Background: The use of artificial intelligence (AI) is increasing in many areas of healthcare, including mental healthcare. The automated nature of such technologies has the potential to be developed to work with large numbers of people. This paper examines the way that student therapists experience using an interactive text‐based machine client as a training tool. Methodology: Chatbot technology has been used to develop an emotionally responsive interactive client (ERIC). This introduces individuals to concepts of person‐centred therapy (empathy, congruence and unconditional positive regard) by using a series of pre‐programmed scenarios. Twenty‐eight student therapists evaluated ERIC's potential as a learning tool. Individuals were recruited from one university from a postgraduate and an undergraduate counselling programme. Findings: Feedback was generally positive, with all reporting that they enjoyed engaging with ERIC as a learning method. ERIC helped individuals consider their understanding of counselling skills in a non‐judgemental environment. Participants felt the scenarios were realistic and engaging, with many reporting that they felt they were engaging with a real client/person due to ERIC's ability to express emotions. Discussion: ERIC is at the proof‐of‐concept phase. From the feedback presented here, it is evident that it can be a useful learning tool. Further development of ERIC with feedback from a larger sample is, however, required. ERIC is currently a text‐based client, and further development would like to see the intervention be voice‐activated to enhance the experience. ERIC can be further enhanced and adapted to be a useful learning platform for student therapists, as well as for students in other (healthcare‐related) disciplines, whereby a client or patient is required. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present research was to test the feasibility of a randomised controlled trial comparing five consecutive days of regular online jigsaw puzzling (JP) against a no‐treatment control group in improving mental well‐being outcomes in older adults. Methods: Eighteen older adults (65–80 years) were randomly assigned to either the JP (9) or control (9) group and completed a range of mental health and well‐being measures for five consecutive days. We assessed recruitment rates, completion rates and participants' experiences of the intervention. Results: Recruitment issues meant that 18 of the 32 intended participants took part in the trial. All participants completed the trial. Qualitative analysis indicated that participants experienced the JP intervention as accepted, with indications of enhanced enjoyment and self‐esteem at study completion. Conclusion: The present pilot study indicates that testing the efficacy of JP is feasible. A full‐scale clinical trial of this intervention should be considered, which can determine the efficacy of the JP intervention. [ABSTRACT FROM AUTHOR]

Introduction: Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a "real-life" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up. Methods: Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6 months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR. Results: A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5 years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6 months, a significant reduction of DAPSA was observed (β − 15.47, p = 0.001, 95% CI − 23.15 to − 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1 months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs. Conclusion: The "real-life" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18 months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs. [ABSTRACT FROM AUTHOR]

Improvement in the therapeutics for multiple myeloma (MM) has been continuously developed owing to the application of novel drugs and technologies in the last 20 years. The standard first-line therapy for MM consists of a three-drug induction regimen based on immunomodulatory drugs and proteasome inhibitors combined with autologous stem cell transplantation. However, MM remains incurable; therefore, therapies for relapsed/refractory MM (RRMM) are emerging and evolving rapidly. This study aimed to summarize and review the results of RRMM trials over the past 5 years to provide a holistic overview and insights for practitioners in related fields and to provide additional ideas for clinical trialists. This study shows that daratumumab and isatuximab continue to significantly advance as treatment options. Additionally, novel antibody drugs, such as elotuzumab and selinexor, as well as bispecific antibodies, teclistamab and talquetamab, are currently undergoing clinical research with promising outcomes. However, chimeric antigen receptor-T cell therapy targeting B-cell maturation antigen remains the optimal approach for MM treatment. [ABSTRACT FROM AUTHOR]

Pathogenic variants in genes encoding ion channels are causal for various pediatric and adult neurological conditions. In particular, several epilepsy syndromes have been identified to be caused by specific channelopathies. These encompass a spectrum from self-limited epilepsies to developmental and epileptic encephalopathies spanning genetic and acquired causes. Several of these channelopathies have exquisite responses to specific antiseizure medications (ASMs), while others ASMs may prove ineffective or even worsen seizures. Some channelopathies demonstrate phenotypic pleiotropy and can cause other neurological conditions outside of epilepsy. This review aims to provide a comprehensive exploration of the pathophysiology of seizure generation, ion channels implicated in epilepsy, and several genetic epilepsies due to ion channel dysfunction. We outline the clinical presentation, pathogenesis, and the current state of basic science and clinical research for these channelopathies. In addition, we briefly look at potential precision therapy approaches emerging for these disorders. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of European descent. The interplay between environmental factors and genetic predisposition plays a crucial role in MS etiopathogenesis. We searched recent relevant literature on reputable databases, which include, PubMed, Embase, Web of Science, Scopus, and ScienceDirect using the following keywords: multiple sclerosis, pathogenesis, autoimmunity, demyelination, therapy, and immunotherapy. Various animal models have been employed to investigate the MS etiopathogenesis and therapeutics. Autoreactive T cells within the CNS recruit myeloid cells through chemokine expression, leading to the secretion of inflammatory cytokines driving the MS pathogenesis, resulting in demyelination, gliosis, and axonal loss. Key players include T cell lymphocytes (CD4+ and CD8+), B cells, and neutrophils. Signaling dysregulation in inflammatory pathways and the immunogenetic basis of MS are essential considerations for any successful therapy to MS. Data indicates that B cells and neutrophils also have significant roles in MS, despite the common belief that T cells are essential. High neutrophil-to-lymphocyte ratios correlate with MS severity, indicating their contribution to disease progression. Dysregulated signaling pathways further exacerbate MS progression. MS remains incurable, but disease-modifying therapies, monoclonal antibodies, and immunomodulatory drugs offer hope for patients. Research on the immunogenetics and immunoregulatory functions of gut microbiota is continuing to provide light on possible treatment avenues. Understanding the complex interplay between genetic predisposition, environmental factors, and immune dysregulation is critical for developing effective treatments for MS. [ABSTRACT FROM AUTHOR]

Endovascular reperfusion therapy is the primary strategy for acute ischemic stroke. No-reflow is a common phenomenon, which is defined as the failure of microcirculatory reperfusion despite clot removal by thrombolysis or mechanical embolization. It has been reported that up to 25% of ischemic strokes suffer from no-reflow, which strongly contributes to an increased risk of poor clinical outcomes. No-reflow is associated with functional and structural alterations of cerebrovascular microcirculation, and the injury to the microcirculation seriously hinders the neural functional recovery following macrovascular reperfusion. Accumulated evidence indicates that pathology of no-reflow is linked to adhesion, aggregation, and rolling of blood components along the endothelium, capillary stagnation with neutrophils, astrocytes end-feet, and endothelial cell edema, pericyte contraction, and vasoconstriction. Prevention or treatment strategies aim to alleviate or reverse these pathological changes, including targeted therapies such as cilostazol, adhesion molecule blocking antibodies, peroxisome proliferator-activated receptors (PPARs) activator, adenosine, pericyte regulators, as well as adjunctive therapies, such as extracorporeal counterpulsation, ischemic preconditioning, and alternative or complementary therapies. Herein, we provide an overview of pathomechanisms, predictive factors, diagnosis, and intervention strategies for no-reflow, and attempt to convey a new perspective on the clinical management of no-reflow post-ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. Methods: We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. Results: The median age of the patients was 55.0 (39.0–64.0) years, and the median tumor size was 40.0 (33.0–60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3–81.0) months. Unfortunately, 2 patients died from the disease. Conclusion: NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery. [ABSTRACT FROM AUTHOR]

Background: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis. Outcomes of RDEB-cSCC therapies have primarily been described in case reports. Systematic studies are scarce. This systematic review aims to assess the pathophysiology, clinical characteristics, and outcomes of RDEB-cSCCs, with a focus on results and mechanisms of recent immunotherapies and anti-EGFR treatments. Results: A systematic literature search of epidermolysis bullosa and cSCC was performed in February 2024, using PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EudraCT databases. Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors. Data extraction and risk of bias assessment was performed by two independent reviewers. Of 1132 references in the original search, 163 relevant articles were identified, representing 59 case reports, 7 cohort studies, 49 abstracts, 47 in-vitro/in-vivo experiments, and 1 bioinformatic study. From these, 157 cases of RDEB-cSCCs were included. The majority of RDEB-cSCCs were well-differentiated (64.1%), ulcerated (59.6%), and at least 2 cm in size (77.6%), with a median age at diagnosis of 30 years old (range 6–68.4). Surgery was the primary form of treatment (n = 128), followed by chemotherapy and radiotherapy. Anti-EGFR therapy and immunotherapy was also reported beginning in 2009 and 2019, respectively. Survival time from first cSCC diagnosis to death was available in 50 cases. When stratified by their treatment regimen, median survival time was 1.85 years (surgery + chemotherapy, n = 6), 2 years (surgery only, n = 19), 4.0 years (+ anti-EFGR therapy, n = 10), 4 years (surgery + radiotherapy, n = 9), 4.6 years (+ immunotherapy, n = 4), and 9.5 years (surgery + chemotherapy + radiotherapy; n = 2). Treatment-related adverse events were primarily limited to impaired wound healing for immunotherapies and nausea and fatigue for anti-EGFR therapies. Conclusions: Despite the challenges of a limited sample size in a rare disease, this systematic review provides an overview of treatment options for cSCCs in RDEB. When surgical treatment options have been exhausted, the addition of immunotherapy and/or anti-EGFR therapies may extend patient survival. However, it is difficult to attribute extended survival to any single treatment, as multiple therapeutic modalities are often used to treat RDEB-cSCCs. [ABSTRACT FROM AUTHOR]

Chronic low back pain (cLBP) is a major cause of disability and healthcare expenditure worldwide. Its prevalence is increasing globally from somatic and psychosocial factors. While non-pharmacological management, and in particular physiotherapy, has been recommended as a first-line treatment for cLBP, it is not clear what type of physiotherapeutic approach is the most effective in terms of pain reduction and function improvement. This analysis is rendered more difficult by the vast number of available therapies and a lack of a widely accepted classification that can effectively highlight the differences in the outcomes of different management options. This study was conducted according to the PRISMA guidelines. In January 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All the randomised controlled trials (RCTs) which compared the efficacy of physiotherapy programs in patients with cLBP were accessed. Studies reporting on non-specific or mechanical cLPB were included. Data concerning the Visual Analogic Scale (VAS) or numeric rating scale (NRS), Roland Morris Disability Questionnaire (RMQ) and Oswestry Disability Index (ODI). Data from 12,773 patients were collected. The mean symptom duration was 61.2 ± 51.0 months and the mean follow-up was 4.3 ± 5.9 months. The mean age was 44.5 ± 9.4 years. The mean BMI was 25.8 ± 2.9 kg/m2. The Adapted Physical Exercise group evidenced the lowest pain score, followed by Multidisciplinary and Adapted Training Exercise/Complementary Medicine. The Adapted Physical Exercise group evidenced the lowest RMQ score followed by Therapeutic Exercises and Multidisciplinary. The Multidisciplinary group evidenced the lowest ODI score, followed by Adapted Physical Exercise and Physical Agent modalities. Within the considered physiotherapeutic and non-conventional approaches to manage nonspecific and/or mechanic cLBP, adapted physical exercise, physical agent modalities, and a multidisciplinary approach might represent the most effective strategy to reduce pain and disability. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) poses a significant public health problem, affecting millions of people across the world. Despite decades of research into therapeutic strategies for AD, effective prevention or treatment for this devastating disorder remains elusive. In this review, we discuss the potential of photobiomodulation (PBM) for preventing and alleviating AD-associated pathologies, with a focus on the biological mechanisms underlying this therapy. Future research directions and guidance for clinical practice for this non-invasive and non-pharmacological therapy are also highlighted. The available evidence indicates that different treatment paradigms, including transcranial and systemic PBM, along with the recently proposed remote PBM, all could be promising for AD. PBM exerts diverse biological effects, such as enhancing mitochondrial function, mitigating the neuroinflammation caused by activated glial cells, increasing cerebral perfusion, improving glymphatic drainage, regulating the gut microbiome, boosting myokine production, and modulating the immune system. We suggest that PBM may serve as a powerful therapeutic intervention for AD. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) is a major cause of newborn brain damage stemming from a lack of oxygenated blood flow in the neonatal period. Twenty-five to fifty percent of asphyxiated infants who develop HIE die in the neonatal period, and about sixty percent of survivors develop long-term neurological disabilities. From the first minutes to months after the injury, a cascade of events occurs, leading to blood-brain barrier (BBB) opening, neuronal death and inflammation. To date, the only approach proposed in some cases is therapeutic hypothermia (TH). Unfortunately, TH is only partially protective and is not applicable to all neonates. This review synthesizes current knowledge on the basic molecular mechanisms of brain damage in hypoxia-ischemia (HI) and on the different therapeutic strategies in HI that have been used and explores a major limitation of unsuccessful therapeutic approaches. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14–19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c‐Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/β‐catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The microenvironment of hepatocellular carcinoma is a really complex milieu, containing a wide variety of cells with specific tasks, belonging to both the mesenchimal and immunitary systems, the extracellular matrix, growth factors, proinflammatory cytokines, and translocated bacterial products. This intricate environment represents a source of potential targets in order to establish a wide and multitask therapeutic strategy for hepatocellular carcinoma. Hepatocellular carcinoma is a malignant tumor that originates from hepatocytes in an inflammatory substrate due to different degrees of liver fibrosis up to cirrhosis. In recent years, there has been growing interest in the role played by the complex interrelationship between hepatocellular carcinoma and its microenvironment, capable of influencing tumourigenesis, neoplastic growth, and its progression or even inhibition. The microenvironment is made up of an intricate network of mesenchymal cells, immune system cells, extracellular matrix, and growth factors, as well as proinflammatory cytokines and translocated bacterial products coming from the intestinal microenvironment via the enterohepatic circulation. The aim of this paper is to review the role of the HCC microenvironment and describe the possible implications in the choice of the most appropriate therapeutic scheme in the prediction of tumor response or resistance to currently applied treatments and in the possible development of future therapeutic perspectives, in order to circumvent resistance and break down the tumor's defensive fort. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic strategies. NB-02 is a novel botanical drug that has shown promise as a protective and therapeutic treatment for AD in an APP/PS1 preclinical mouse model. In this paper, we investigate the underlying mechanisms by which NB-02 provides these therapeutic advantages using in vitro neuron-astrocyte co-cultures. Pretreatment with NB-02 prevented pathological calcium elevations in neurons and astrocytes after application of toxic soluble amyloid-β (Aβ) oligomers. NB-02 also prevented cell death associated with the addition of soluble Aβ oligomers suggesting NB-02 is effective at protecting both neurons and astrocytes from Aβ-mediated damage. [ABSTRACT FROM AUTHOR]

The use of nanomaterials in medicine offers multiple opportunities to address neurodegenerative disorders such as Alzheimer's and Parkinson's disease. These diseases are a significant burden for society and the health system, affecting millions of people worldwide without sensitive and selective diagnostic methodologies or effective treatments to stop their progression. In this sense, the use of gold nanoparticles is a promising tool due to their unique properties at the nanometric level. They can be functionalized with specific molecules to selectively target pathological proteins such as Tau and α-synuclein for Alzheimer's and Parkinson's disease, respectively. Additionally, these proteins are used as diagnostic biomarkers, wherein gold nanoparticles play a key role in enhancing their signal, even at the low concentrations present in biological samples such as blood or cerebrospinal fluid, thus enabling an early and accurate diagnosis. On the other hand, gold nanoparticles act as drug delivery platforms, bringing therapeutic agents directly into the brain, improving treatment efficiency and precision, and reducing side effects in healthy tissues. However, despite the exciting potential of gold nanoparticles, it is crucial to address the challenges and issues associated with their use in the medical field before they can be widely applied in clinical settings. It is critical to ensure the safety and biocompatibility of these nanomaterials in the context of the central nervous system. Therefore, rigorous preclinical and clinical studies are needed to assess the efficacy and feasibility of these strategies in patients. Since there is scarce and sometimes contradictory literature about their use in this context, the main aim of this review is to discuss and analyze the current state-of-the-art of gold nanoparticles in relation to delivery, diagnosis, and therapy for Alzheimer's and Parkinson's disease, as well as recent research about their use in preclinical, clinical, and emerging research areas. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions Long COVID is a global health concern which has debilitating effects on the individual experiencing it. In the United Kingdom, psychological therapies are being offered to people with long COVID, although the evidence for these therapies is yet to be demonstrated. This research aimed to understand how therapists and clients define and understand recovery from long COVID, and use hope theory to interpret the results.An online Q‐methodology was employed, where participants sorted a range of statements pertaining to long COVID recovery based on their level of agreement with them. These arranged statements (Q‐sorts) were collated and factor analysed to explore and compare underlying perspectives.Sixteen participants were recruited for the study, including eleven clients, four IAPT therapists and one therapist working in the broader long COVID pathway. A four‐factor model is reported, including (1) Psychological Pathways to Recovery, (2) Social Context and Agency, (3) Physiological Goals of Recovery and (4) Personal Meaning Making. All IAPT therapists loaded onto the psychological pathways factor, whereas the remaining participants shared more diverse perspectives.The belief that long COVID recovery was possible, taken as an indicator of hopefulness, was rated highest for Factor 1, Psychological Pathways to Recovery, and Factor 3, Physiological Recovery Goals. This suggested that having a clear definition of recovery, or clear guidance on how to intervene, promoted hopefulness and, theoretically, well‐being. However, clients reported experiences of being invalidated and disbelieved by health professionals, with psychological explanations sometimes being experienced as dismissive and invalidating. Clinical implications and future research directions are discussed. [ABSTRACT FROM AUTHOR]

This article describes a novel methodology for involving the public in a creative co-produced project about grief, which invited bereaved people to work together to create a fictional story about loss and then reflect on the experience in focus groups. Devised by Crowded Room Theatre Company and researchers at the University of Bristol, the project aimed to explore the risks and benefits of collaborative storytelling about emotionally charged subjects. Thematic analysis of the focus group transcripts generated seven themes: storytelling as protective and enabling; support and understanding; new perspectives; connecting to grief and loved ones who have died; complicated emotions; workshop anxiety; and anticipating the audio story. These findings corroborate research that suggests storytelling can provide a safe space to explore and make meaning from difficult emotions and experiences; it may also appeal to bereaved individuals who are less likely to attend conventional support groups. The audio story created from the workshop recordings is available online (https://www.spreaker.com/episode/the-colours-of-loss--53334166). [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a dynamic disease where patients progress through several stages defined by HBV e‐antigen (HBeAg) status, HBV‐DNA levels and transaminase elevations, with antiviral therapy indicated only in specific stages. However, some patients cannot be classified into one of the stages and are said to fall into an ‘indeterminate phase’ or ‘grey zone’. Exact definitions of the indeterminate phase vary from guideline to guideline as a result of different cut‐off values for biomarker measurements. Data suggest that as many as 50% of HBV patients may be in an indeterminate phase and may not rapidly transition out of this phase. Clinical data that suggest these patients are at increased risk of hepatocellular carcinoma (HCC) are complemented by molecular evidence of integrations of HBV‐DNA into the host genome, chromosomal translocations and immune activation despite liver enzymes that may suggest lack of inflammation. Antiviral therapy reduces these hepatocarcinogenic mechanisms and is reflected in a reduction of fibrosis and HCC risk. We review key data on patients in the indeterminate phase, with emphasis on HCC as an outcome. We take a holistic approach and link new biological data with clinical observations as well as examine the potential role of antiviral therapy in reducing HCC risk among patients in the indeterminate phase. With the availability of safe and effective oral antivirals, consideration must be given as to how much residual risk of HCC should be tolerated among patients in the indeterminate phase. [ABSTRACT FROM AUTHOR]

In recent times, the intersection of nanotechnology and biomedical research has given rise to nanobiomedicine, a captivating realm that holds immense promise for revolutionizing diagnostic and therapeutic approaches in the field of cancer. This innovative fusion of biology, medicine, and nanotechnology aims to create diagnostic and therapeutic agents with enhanced safety and efficacy, particularly in the realm of theranostics for various malignancies. Diverse inorganic, organic, and hybrid organic–inorganic nanoparticles, each possessing unique properties, have been introduced into this domain. This review seeks to highlight the latest strides in targeted glioblastoma therapy by focusing on the application of inorganic smart nanoparticles. Beyond exploring the general role of nanotechnology in medical applications, this review delves into groundbreaking strategies for glioblastoma treatment, showcasing the potential of smart nanoparticles through in vitro studies, in vivo investigations, and ongoing clinical trials. [ABSTRACT FROM AUTHOR]

The KDIGO guideline for acute rejection treatment recommends use of corticosteroids and suggests using lymphocyte-depleting agents as second line treatment. Aim of the study was to determine the current practices of detection and treatment of TCMR of kidney allografts amongst European kidney transplant centres. An invitation was sent through ESOT/EKITA newsletters and through social media to transplant professionals in Europe for taking part in the survey. A total of 129 transplant professionals responded to the survey. There was equal representation of small and large sized transplant centres. The majority of centres treat borderline changes (BL) and TCMR (Grade IA-B, IIA-B) in indication biopsies and protocol biopsies with corticosteroids as first line treatment. Thymoglobulin is used mainly as second line treatment for TCMR Grade IA-B (80%) and TCMR IIA-B (85%). Treatment success is most often evaluated within one month of therapy. There were no differences observed between the large and small centres for the management of TCMR. This survey highlights the common practices and diversity in clinics for the management of TCMR in Europe. Testing new therapies for TCMR should be in comparison to the current standard of care in Europe. Better consensus on treatment success is crucial for robust study designs. [ABSTRACT FROM AUTHOR]

Purpose: The exact molecular and cellular processes that cause benign urological diseases in the stromal and epithelial components of the urinary tract are yet unknown. Reviewing and analyzing the data linking microRNAs (miRNAs) expression in the pathophysiology of benign urological conditions, including overactive bladder (OAB), bladder outlet obstruction (BOO), bladder pain syndrome/interstitial cystitis (BPS/IC), and Lower urinary tract dysfunction (LUTD) is the objective of the current systematic review. Materials and Methods: Evidence including all case-control, cohort, and cross-sectional studies that measure participants' MicroRNA as a biomarker for benign urological diseases has been gathered On January 2024, through searching MEDLINE via PubMed, Scopus, Web of Science, Embase, and ProQuest databases. Studies considered eligible that present information on the reference Gene, profile type, and serum levels of microRNA from patients diagnosed with benign urological disease including benign prostate hyperplasia (BPH) or benign prostate enlargement (BPE), overactive bladder (OAB), and bladder outlet obstruction (BOO). These studies appraised by the quality assessment checklist of Joanna Briggs Institute (JBI). Results: A total of 4,587 records related to miRNAs in urological diseases were retrieved. Of these, we identified 28 records for our systematic study. The most frequently associated miRNA was 92a-3p identified which was found upregulated in OAB diagnosis. In BOO, miR-146a-5p was identified to be upregulated. miR-146a-5p was upregulated in BO, and for other benign conditions, different miRNAs were reported. 491-5p miRNAs were found deregulated in OAB-related studies. We expected other miRNAs to have the same trend in the OAB studies. InSUI miR-93 was the most frequent downregulated miRNA. The other reported miRNAs had similar frequencies. Conclusion: When it comes to the early detection and treatment of benign urological conditions, 92a-3p, miR-21, miR-199a-5p, and miR-146a-5p, and 491-5p have the potential to be employed as both a biomarker and a therapeutic target. The creation of pre-RNA or anti-RNA molecules within carrier vehicles that may be safely administered to patients should be made possible by technological advancements. [ABSTRACT FROM AUTHOR]

Multiple myeloma bone disease (MBD) is a common clinical complication in patients with multiple myeloma (MM), and the occurrence of bone-related events seriously affects the quality of survival and prognosis of patients. The pathogenesis of MBD involves an imbalance in physiologic bone remodeling: overactivation of osteoclasts, suppression of osteoblasts, and multiple cell-cytokine interactions in the microenvironment, including osteoblasts, bone marrow stromal cells, and immune cells. The current treatment of MBD is based on standard antimyeloma therapy to control tumor progression, along with the use of bone-related drugs acting on bone remodeling within the indications. To prevent bone destruction. In order to prevent bone destruction, it is essential to induce new bone formation to repair the existing lesions while resisting bone resorption, and a variety of novel bone-targeting drugs are currently demonstrating anti-osteopathic effects in preclinical and clinical trials. This article summarizes new advances in the mechanisms of bone remodeling and treatment of MBD. [ABSTRACT FROM AUTHOR]

Wounds are breaks in the continuity of the skin and underlying tissues, resulting from external causes such as cuts, blows, impacts, or surgical interventions. Countless individuals suffer minor to severe injuries, with unfortunate cases even leading to death. In today's scenario, several commercial products are available to facilitate the healing process of wounds, although chronic wounds still present more challenges than acute wounds. Nevertheless, the huge demand for wound-care products within the healthcare sector has given rise to a rapidly growing market, fostering continuous research and development endeavors for innovative wound-healing solutions. Today, there are many commercially available products including those based on natural biopolymers, stem cells, and microRNAs that promote healing from wounds. This article explores the recent breakthroughs in wound-healing products that harness the potential of natural biopolymers, stem cells, and microRNAs. A comprehensive exploration is undertaken, covering not only commercially available products but also those still in the research phase. Additionally, we provide a thorough examination of the opportunities, obstacles, and regulatory considerations influencing the potential commercialization of wound-healing products across the diverse markets of Europe, America, and Asia. [ABSTRACT FROM AUTHOR]

Organosulfur-based polymers have unique properties that make them useful for targeted and managed drug delivery, which can improve therapy while reducing side effects. This work aims to provide a brief review of the synthesis strategies, characterization techniques, and packages of organosulfur-based polymers in drug delivery. More importantly, this work discusses the characterization, biocompatibility, controlled release, nanotechnology, and targeted therapeutic aspects of these important structural units. This review provides not only a good comprehension of organosulfur-based polymers but also an insightful discussion of potential future prospectives in research. The discovery of novel organosulfur polymers and innovations is highly expected to be stimulated in order to synthesize polymer prototypes with increased functional accuracy, efficiency, and low cost for many industrial applications. [ABSTRACT FROM AUTHOR]

In the present study, preparation of [188Re]Re-Tricine-HYNIC-Tyr3-octreotide, stability in human serum, internalization, cell viability analysis, and in vivo tissue biodistribution in rats bearing C6 glioma tumor were investigated. Radiolabeled peptide exhibited a molar activity of 8.60 ± 0.76 GBq/µmol, with over 90% (n = 3) of radiochemical yield. The findings indicated significant internalization of radiolabeled peptide into glioma cells and the ability to reduce cancerous cell viability in MTT analysis. High tumor-to-muscle ratios were observed at various time points following injection. The results suggest that the radiolabeled peptide could be considered for treating tumors expressing somatostatin receptors. [ABSTRACT FROM AUTHOR]