Therapeutic Assessment Research Articles

Comparative Evaluation of Antibiotic Therapies for Subclinical Staphylococcal Mastitis in Goats

Subclinical mastitis (SCM) is characterized by inflammation of the udder without visible signs of inflammation in the animal, udder and milk and hence could be diagnosed by laboratory examination only. Effective treatment of SCM in goats is crucial for maintaining quality milk production. This study was conducted at the Department of Veterinary Medicine, College of Veterinary Science and Animal Husbandry, Nanaji Deshmukh Veterinary Science University, Jabalpur (M.P.), India. A total of 236 lactating goats irrespective of age, breed, parity and stage of lactation, from both organized and unorganized sectors in and around Jabalpur, were screened over a period of six month. Based on modified California mastitis test scores, 83 goats tested positive for subclinical mastitis resulting in an overall occurrence of 35.17% (83/236). A total of 48 milk samples that tested positive for modified California mastitis test were further analyzed for bacterial isolation and identification. Among them, 34 (70.83%) samples were positive for only Staphylococcus spp., while 12 (25%) samples exhibited mixed infection with Staphylococcus spp. and Gram-positive bacilli. Then, 18 goats, positive for subclinical Staphylococcal mastitis were divided into three groups i.e. G1, G2 and G3 with six goats in each group for therapeutic study and six apparently healthy goats were taken as healthy control group (G4). G1 Goats were treated with Inj. Enrofloxacin LA @ 7.5 mg/kg b. wt. I/M single dose; G2 with Inj. Ceftizoxime @ 10 mg/kg b. wt. I/V single dose and G3 with Inj. Oxytetracycline LA @ 20 mg/kg b. wt. I/M single dose. The responses of therapeutic assessment were evaluated on the basis of somatic cell count and modified California mastitis test score. The most effective response for subclinical Staphylococcal mastitis in goats was observed with Ceftizoxime followed by Enrofloxacin LA and the least with Oxytetracycline LA.

Results of a randomized controlled superiority trial of the effect of modified collaborative assessment vs. standard assessment on patients’ readiness for psychotherapy (CO-ASSM-RCT)

BackgroundAvoidant personality disorder (AvPD) and social phobia (SP) are associated with high personal and societal costs. While psychotherapy can be efficient, many patients drop out during treatment. Little is known about what can be done to increase a patient’s readiness for psychotherapy. However, research highlights the fields of collaborative and therapeutic assessment as a possible means to enhance readiness for psychotherapy.MethodsWe conducted a randomized controlled feasibility and superiority trial on patients with SP or AvPD who were to initiate psychotherapeutic treatment in outpatient mental health services. Patients were randomized 1:1 to either assessment as usual or modified collaborative assessment (MCA), provided as a pre-treatment intervention before psychotherapy initiation. MCA included the collaborative administration of a battery of psychological tests designed to assess the patient’s psychopathology more systematically. The tests were administered in collaboration with the patient, and detailed oral and written feedback was provided. We investigated the feasibility of the MCA intervention regarding acceptability, patient satisfaction, and adherence. We also investigated MCA’s effect on readiness for psychotherapy, as assessed with the University of Rhode Island Change Assessment Scale (URICA), and outcomes relating to symptomatology and dropout rates.ResultsAll three prespecified feasibility outcomes were met. At the end of treatment, no significant difference was observed in any other outcome, except client satisfaction, which favored MCA (− 7.42 (95% CI − 11.75; − 3.09; p = 0.002)).DiscussionWe found that MCA was feasible, and patients were highly satisfied with the intervention. It is relevant to investigate another implementation of MCA.Trial registrationClinicalTrials.gov NCT05018312. Registered on August 24, 2021.

Systematic Review and Meta-Analysis of Intervention Techniques in Occupational Therapy for Babies and Children with Obstetric Brachial Plexus Palsy.

(1) Background: Obstetric brachial plexus palsy (OBPP) is an unpredictable and unpreventable neurological injury, caused by shoulder dystocia during birth, that affects the brachial plexus and leads to motor and sensory deficits in the child's upper extremity. The limited literature on early therapeutic assessment of newborns with OBPP highlights a gap in specialized care that, if filled, could enhance decision-making and support timely treatment. The objective of this paper is to analyze the therapeutic intervention techniques used at an early stage and their functional impact, from the occupational therapy discipline in the treatment of the upper extremity in babies and children with OBPP. (2) Method: Systematic review design and meta-analysis. A systematic review is a comprehensive analysis of existing research on a specific topic, using rigorous methods to identify, evaluate, and synthesize studies. Meta-analysis, often part of a systematic review, combines results from multiple studies to identify overall trends and enhance reliability, providing a clearer summary of evidence. Articles that included pediatric patients (from birth to 12 years of age) with a diagnosis of OBPP were reviewed. The results of the techniques used were analyzed according to each study, with the scale or method of assessment considered by the study for the presentation of data. The articles were assessed for methodological quality using the "PEDro Validity Scale". (3) Results: A total of 2190 articles were found, with 108 analyzed and 22 fully meeting this study's standards. Fourteen had a quantitative design, while the others included clinical guidelines. The most statistically reliable intervention techniques were CIMT (constraint-induced movement therapy) and splinting (dynamic and static), with second-tier techniques like joint manipulation, NMES, early infant management education, and serial casting used when needed. This study focused on children from birth to eight years old, with assessment tools primarily measuring upper limb range of motion, external rotation, supination, and impairment levels, though bimanual activity assessment was less common. (4) Conclusions: The early implementation of the techniques that provide us with the most data are CIMT, splinting, NMES, and joint manipulation linked to health education for families. In second place, we have the use of TB infiltrations and serial casts, when the treatment of the previous techniques fails in some cases.

Malignant Rhabdoid Tumor masquerading as Neuroblastoma: A rare Case-report

Abstract Introduction/Objective Malignant rhabdoid tumors (MRT) predominantly impact infants and young children, typically occurring around the age of 15 months. While they can emerge from soft tissues throughout the body, but commonly initiate in the kidneys. Neuroblastoma-like characteristics are seldom observed within the varied phenotypes of malignant rhabdoid tumors. Here, we present an exceptionally rare and distinctive subtype of malignant rhabdoid tumor exhibiting features akin to neuroblastoma localized within the unusal parapharyngeal space. Methods/Case Report A 2-month-old female presented to the ED with an enlarging right cervical neck mass. The mother reported a one-week history of upper respiratory tract symptoms and noticed an enlarging mass of her right neck. CT reported a “parapharyngeal abscess with airway compression”. The patient was started on Augmentin with no significant improvement. Repeat CT with contrast demonstrated an enlarging rim-enhancing 3 cm mass involving the right parapharyngeal space, trachea, and right carotid arteries. Laryngoscopy and incisional biopsy of right neck lymph nodes demonstrated a high-grade malignancy with prominent nucleoli, high N/C ratio and scant cytoplasm. The tumor tested positive for CD 99, synaptophysin, and neurofilament, leading to the initial diagnosis of neuroblastoma. However, molecular analysis uncovered the loss of INI-1 on 22q11.2, prompting a reevaluation and a final diagnosis of MRT with neuroblastoma-like characteristics was made. Results (if a Case Study enter NA) NA Conclusion A range of tumors displaying distinct “rhabdoid” cytological features are collectively termed as malignant rhabdoid tumors (MRTs). Conventional immunohistochemistry (IHC) staining for CD99, synaptophysin, neurofilament, and myogenin might suggest neuroblastoma, Ewing sarcoma, or rhabdomyosarcoma. However, the absence of INI-1 expression provides a definitive diagnosis. INI-1 loss, a purported tumor suppressor gene located on chromosome 22q11.2, solidifies the tumor’s classification as malignant rhabdoid tumor (MRT). Additionally, a positive neurofilament stain in MRT is crucial for diagnostic and therapeutic assessments. This differentiation is vital, given the dismal prognosis of MRT with a 5-year survival rate of less than 10%.

Anti-Shrinkage Technique for Feline Skin Samples

Surgical resection of subcutaneous neoplasms with clear margins is crucial for preventing local recurrence and avoiding adjuvant treatments. However, the evaluation of surgical margins often differs significantly from the histopathological assessment due to tissue shrinkage, which can result in inaccurate therapeutic assessments and unreliable patient prognoses. In this study, ten feline cadavers were utilized. Six 50 mm diameter specimens were collected from three regions (thorax, flank, femur) and measured at three time points: T0 (excision time), T1 (10 min after incision), and T2 (at least 48 h after sample collection and formalin fixation). Samples in the study group were stretched and fixed on a cork plate with pinpoint needles after excision to restore their original dimensions. All specimens exhibited a similar trend. After 48 h of formalin fixation, the control specimens showed significant shrinkage, with a reduction of 25.73% in radius and 26.32% in diameter. In contrast, the study specimens demonstrated minimal changes, with a radius reduction of −0.28% and no change in diameter. The results indicate that all feline skin specimens experienced significant shrinkage of approximately one-quarter from their pre-incisional size. Stretching and pinning the excised tissues allowed for the restoration and maintenance of original dimensions even after formalin fixation. This technique represents a valid and practical approach to minimize tissue shrinkage.

Yap Is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates the Expression of Ctgf in Cardiomyocytes.

Myocardial infarction and reperfusion constitute a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival and adaptation. Cell signalling, which is essential to cardiac development, also presents potential disease-modifying opportunities to recover and limit myocardial injury or maladaptive remodelling. Here, we hypothesized that Yap signalling could be sensitive to one or more molecular stress patterns associated with early acute ischemia. We found that Yap, and not Taz, expression patterns differed in a post-myocardial infarct compared to a peri-infarct region of rat hearts post-myocardial infarction, suggesting cell specificity that would be challenging to resolve for causation in vivo. Using H9c2 ventricular myotubes in vitro as a model, Yap levels were determined to be more sensitive to nutrient deprivation than other stress patterns typified by ischemia within the first hour of stress. Moreover, this is mediated by amino acid availability, predominantly L-isoleucine, and influences the expression of connective tissue growth factor (Ctgf)-a major determinant of myocardial adaptation after injury. These findings present novel opportunities for future therapeutic development and risk assessment for myocardial injury and adaptation.

Development and Psychometric Properties of the Therapeutic Relationship Assessment Scale-Patient (TRAS-Patient).

The therapeutic relationship plays a crucial role in nursing care for people with mental illness. Adopting a systemic and person-centred approach that considers the individual experiences and needs of the person is paramount. However, no instruments were found in the literature designed to evaluate the nurse-patient therapeutic relationship from the perspective of a person with mental illness. This study aimed to develop and evaluate the psychometric properties of an instrument for assessing the quality of the nurse-patient therapeutic relationship from the patient's perspective. An e-Delphi study was conducted to develop the assessment tool, and a psychometric study was carried out to examine its psychometric properties. The sample comprised 240 adults with mental illness. Internal consistency was assessed using Cronbach's alpha and the Omega coefficient. The final structure of the assessment instrument included 24 items distributed across two factors, explaining 64.2% of the variance. Cronbach's alpha was 0.94, and the Omega coefficient was 0.96. The intraclass correlation coefficient was 0.84 (95% CI: 0.66-0.92). The therapeutic relationship assessment scale (TRAS-Patient) shows good psychometric properties. This is a relevant tool for assessing the quality of the nurse-patient therapeutic relationship from the patient's perspective, thus promoting a patient-centred approach and responding to the patient's needs. Mental health nurses can access a tool for evaluating the nurse-patient therapeutic relationship centred on disciplinary knowledge. This enables patient involvement in care, enhanced care and person-centred practice.

Co-freezing localized CRISPR-Cas12a system enables rapid and sensitive nucleic acid analysis

Rapid and sensitive nucleic acid detection is vital in disease diagnosis and therapeutic assessment. Herein, we propose a co-freezing localized CRISPR-Cas12a (CL-Cas12a) strategy for sensitive nucleic acid detection. The CL-Cas12a was obtained through a 15-minute co-freezing process, allowing the Cas12a/crRNA complex and hairpin reporter confined on the AuNPs surface with high load efficiency, for rapid sensing of nucleic acid with superior performance to other localized Cas12a strategies. This CL-Cas12a based platform could quantitatively detect targets down to 98 aM in 30 min with excellent specificity. Furthermore, the CL-Cas12a successful applied to detect human papillomavirus infection and human lung cancer-associated single-nucleotide mutations. We also achieved powerful signal amplification for imaging Survivin mRNA in living cells. These findings highlight the potential of CL-Cas12a as an effective tool for nucleic acid diagnostics and disease monitoring.Graphical abstract

Effectiveness of surgical approach in the management of non-traumatic corneal perforations

ABSTRACT Clinical relevance Non-traumatic aetiologies are one of the leading causes of corneal perforations. The management of corneal perforation is quite challenging and complex for anterior segment surgeons. The appropriate surgical approach for each case is usually determined on the basis of a combination of many different parameters. Background The study aimed to evaluate surgical approach options and outcomes in the treatment of non-traumatic corneal perforations. Methods Patient data who underwent surgery for non-traumatic corneal perforation between 2016 and 2023 were retrospectively evaluated. Medical records were assessed in terms of age, gender, perforation aetiology, the first and last examination notes, surgical approach, follow-up time, and additional surgeries and outcomes according to anatomical, therapeutic and functional success. Anterior segment photographs were investigated for thorough explanation of the examinations. Results Forty-five eyes of 45 patients were included (mean age 61.2 ± 22.4 (90-2), female/male ratio 20/25). Surgical approaches applied according to the size and location of the perforation site included fibrin glue application (6), amniotic membrane transplantation (AMT) (9), corneal patch graft application(15), and tectonic keratoplasty (15). The ratio of inflammatory and infectious causes as the two main indications was 29/16. Globe integrity was ensured with the first surgery in 27 eyes. However, 17 eyes required secondary surgical attempts due to failure of the first approach and 1 eye underwent evisceration. AMT was the least successful method among other methods in anatomical, therapeutic, and functional assessment. Conclusion There are various surgical approaches for repairing non-traumatic corneal perforations, each with its own advantages and disadvantages. These include high tissue resistance, the ability to remove necrotic tissue, ease of access, and anti-inflammatory activity. It is possible to successfully repair corneal perforations with single and combined methods, considering the above-mentioned features, especially depending on the size and location of the defect. While AMT is a viable and time-saving choice − especially in the lack of donor tissues − further interventions are necessary in most circumstances.

Correction: Synergistic effect of “methyl cellulose-dextran” on oral curcumin delivery via casein nanomicelle: fabrication, characterization, and cancer therapeutic efficacy assessment

Correction: Synergistic effect of “methyl cellulose-dextran” on oral curcumin delivery via casein nanomicelle: fabrication, characterization, and cancer therapeutic efficacy assessment

An innovative tool to prioritize the assessment of investigational COVID-19 therapeutics: A pilot project.

As the COVID-19 pandemic unfolded, hundreds of investigational COVID-19 therapeutics emerged. Maintaining situational awareness of this extensive and rapidly evolving therapeutic landscape represented an unprecedented challenge for the Public Health Agency of Canada, as it worked to promote and protect the health of Canadians. A tool to triage and prioritize the assessment of these therapeutics was needed. The objective was to develop and conduct an initial validation of a tool to identify investigational COVID-19 therapeutics for further review based on an efficient preliminary assessment, using a systematic and reliable process that would be practical to validate, implement and update. Phase 1 of this pilot project consisted of a literature search to identify existing COVID-19 therapeutic assessment prioritization tools, development of the Rapid Scoring Tool (RST) and initial validation of the tool. No tools designed to rank investigational COVID-19 therapeutics for the purpose of prioritizing their assessment were identified. However, a few publications provided criteria to consider and therapeutic ranking methods, which helped shape the development of the RST. The RST included eight criteria and several descriptors ("characteristics"). A universal characteristic scoring scale from -10 to 10 was developed. The sum of all the characteristic scores yielded an overall benefit score for each therapeutic. The RST appropriately ranked therapeutics using a systematic, reliable and practical approach. Phase 1 was successfully completed. The RST presents several distinct aspects compared with other tools, including its scoring scale and method, and capacity to factor in incomplete or pending information. It is anticipated that the framework used for the RST will lend itself to use in other dynamic situations involving many interventions.

Comprehensive Evaluation of the Genetic Basis of Keratoconus: New Perspectives for Clinical Translation.

Keratoconus (KC) is a corneal disorder with complex etiology, apparently involving both genetic and environmental factors, characterized by progressive thinning and protrusion of the cornea. We aimed to identify novel genetic regions associated with KC susceptibility, elucidate relevant genes for disease development, and explore the translational implications for therapeutic intervention and risk assessment. We conducted a genome-wide association study (GWAS) that integrated previously published data with newly generated genotyping data from an independent European cohort. To evaluate the clinical translation of our results, we performed functional annotation, gene prioritization, polygenic risk score (PRS), and drug repositioning analyses. We identified two novel genetic loci associated with KC, with rs2806689 and rs807037 emerging as lead variants (P = 1.71E-08, odds ratio [OR] = 0.88; P = 1.93E-08, OR = 1.16, respectively). Most importantly, we identified 315 candidate genes influenced by confirmed KC-associated variants. Among these, MINK1 was found to play a pivotal role in KC pathogenesis through the WNT signaling pathway. Moreover, we developed a PRS model that successfully differentiated KC patients from controls (P = 7.61E-16; area under the curve = 0.713). This model has the potential to identify individuals at high risk for developing KC, which could be instrumental in early diagnosis and management. Additionally, our drug repositioning analysis identified acetylcysteine as a potential treatment option for KC, opening up new avenues for therapeutic intervention. Our study provides valuable insights into the genetic and molecular basis of KC, offering new targets for therapy and highlighting the clinical utility of PRS models in predicting disease risk.

The Suicide Status Form-4 (SSF-IV) as a potentially therapeutic suicide risk assessment tool.

Empirically supported suicide risk assessment and conceptualization is a central aim of the Zero Suicide model. The Suicide Status Form (SSF) is the essential document and scaffolding of the Collaborative Assessment and Management of Suicidality-Brief Intervention (CAMS-BI) and is hypothesized as an example of a psychological assessment as therapeutic intervention (PATI). However, this hypothesis has never been directly tested. N = 57 patients deemed at risk for outpatient suicidal behavior and treated as part of an inpatient psychiatric consultation and liaison service were recruited to participate in CAMS-BI at a Level 1 trauma center in the southeastern United States. During the CAMS-BI process, patients were asked to rate their subjective units of distress (SUDS) at five time points throughout the intervention (k = 285). The omnibus random intercept multilevel model revealed a significant difference in pre- to post-session ratings of SUDS across patients. Post hoc pairwise comparisons revealed no significant differences between SSF sections (e.g., Section A, Section B, and Section C) and relative reductions in SUDS; however, there was an observable trend toward a favorable effect of Section A of the SSF. The SSF may represent an example of PATI pending replication and extension of the current results.

Atypical language organization in a Spanish-speaking adolescent with drug-resistant epilepsy: a multicultural case report

Objective: Epilepsy disproportionally affects children from Hispanic/Latino backgrounds, particularly among those born outside the U.S. Longstanding health-related disparities associated with ethnicity (e.g. language use) further contribute to gaps in care. Neuropsychologists are beginning to outline best practices when working with non-English speakers; however, the lack of appropriately normed/validated measures for pre-surgical language evaluation is a limiting factor. This report informs practices among neuropsychologists by discussing atypical language organization in a non-English speaker using a multicultural framework and collaborative therapeutic assessment process. Method: The current study presents a 16-year-old, right-handed, monolingual Spanish-speaking, Latina designated female with drug-resistant focal seizures with impaired awareness. Comprehensive presurgical epilepsy workup included: CBC, video EEG, brain MRI, functional MRI, PET, MEG, baseline neuropsychological evaluation by bilingual Spanish-English providers, and Wada testing. Results: Neuropsychological testing revealed the most pronounced deficits in language, working memory, and processing speed domains. Functional MRI showed bilateral language activation, which Wada testing confirmed along with bilateral memory representation. Conclusion: Diagnosis, treatment, surgical intervention, and post-operative status are discussed. The clinical course is examined through a multicultural lens, highlighting limitations in international health services, barriers accessing health care in the U.S., and patient-specific factors that were considered as a part of the clinical decision-making process. Targeted recommendations related to culturally-informed care are offered.

Doxorubicin-Intercalated Li-Al-Based LDHs as Potential Drug Delivery Nanovehicle with pH-Responsive Therapeutic Cargo for Tumor Treatment.

Clinical oncology is currently experiencing a technology bottleneck due to the expeditious evolution of therapy defiance in tumors. Although drugs used in chemotherapy work for a sort of cell death with potential clinical application, the effectiveness of chemotherapy-inducing drugs is subject to several endogenous conditions when used alone, necessitating the urgent need for controlled mechanisms. A tumor-targeted drug delivery therapy using Li-Al (M+/M3+)-based layered double hydroxide (LDHs) family has been proposed with the general chemical formula [M+1-x M3+x (OH)]2x+[(Am-)2x/m. n(H2O)]2x-, which is fully biodegradable and works in connection with the therapeutic interaction between LDH nanocarriers and anticancerous doxorubicin (DOX). Compositional variation of Li and Al in LDHs has been used as a nanoplatform, which provides a functional balance between circulation lifetime, drug loading capacity, encapsulation efficiency, and tumor-specific uptake to act as self-regulatory therapeutic cargo to be released intracellularly. First-principle analyses based on DFT have been employed to investigate the interaction of bonding and electronic structure of LDH with DOX and assess its capability and potential for a superior drug carrier. Following the internalization into cancer cells, nanoformulations are carried to the nucleus via lysosomes, and the mechanistic pathways have been revealed. Additionally, in vitro along with in vivo therapeutic assessments on melanoma-bearing mice show a dimensional effect of nanoformulation for better biocompatibility and excellent synergetic anticancer activity. Further, the severe toxic consequences associated with traditional chemotherapy have been eradicated by using injectable hydrogel placed just beneath the tumor site, and regulated release of the drug has been confirmed through protein expression applying various markers. However, Li-Al-based LDH nanocarriers open up new design options for multifunctional nanomedicine, which has intriguing potential for use in cancer treatment through sustained drug delivery.

Aspects of complexity in quality and safety assessment of peptide therapeutics and peptide-related impurities. A regulatory perspective

In recent years, a number of therapeutic peptides have been authorized in the EU market, and several others are in the clinical development phase or under assessment for full dossier or generic applications. Quality and safety guidelines specific to peptides are limited, and some aspects have to be considered. In particular, concerns relate to the analytical investigation for impurities and the toxicological assessment of these substances. The guidelines and the compendial pharmacopoeias provide certain references but that may be questionable if interpreted according to whether therapeutic peptides are considered chemical or biological entities, large or small. The characterization of peptide-related impurities cannot follow the small molecule approach but should consider aspects closely linked to the complex mechanisms of action that these large molecules can exert in the human body. Although direct genotoxic mechanisms cannot be excluded, hazardous interactions on biological systems cannot be ruled out, as in the case of natural peptide toxins and their specific interactions with cellular or membrane targets. From a regulatory perspective, only after specific risk identification and characterization should an equally specific safety threshold in relation to potential toxicity be defined.

Clinical Utility of Serum C-peptide Concentration for Hospitalized Patients with Hyperglycemia.

Serum C-peptide concentration is often utilized for diagnostic, prognostic, or therapeutic assessment in diabetes mellitus. However, there is limited clinical data regarding diagnostic and predictive value of C-peptide measured during hospitalizations for hyperglycemia. Adults admitted to Mayo Clinic inpatient facilities due to an acute hyperglycemic emergency between January 2017 and November 2022 were included in our study. Predictive capacity of C-peptide for discontinuation of therapeutic insulin was examined in the entire cohort and the subgroup of non-autoimmune non-pancreatitis diabetes (NANP-DM). We included 187 patients (63 women) in our study. During hospitalization, patients with type 1 diabetes antibodies displayed diminished serum C-peptide concentration (p=0.014), correlating inversely with subsequent HbA1c% [r= (-0.22), p=0.005]. Initial C-peptide concentrations did not differ between patients requiring insulin therapy during follow-up and those who did not (p=0.16). C-peptide concentrations showed limited predictive capacity for achieving glycemic control. Subgroup analyses in NANP-DM exhibited similar limited capacity for anticipating therapeutic insulin needs and achieving glycemic controls. C-peptide concentration did not exhibit a robust predictive capability for future need of insulin therapy and achieving glycemic control, limiting its utility in clinical practice within inpatient settings.

Opacity, difference and not knowing: what can psychiatry learn from the work of Édouard Glissant?

Martinican poet, novelist and cultural theorist Édouard Glissant (1928–2011) rejected contemporary simplistic notions of creole hybridity popularised in the 1980s and 1990s in favour of a unique and explicitly antiessentialist...

Rational design of a high-affinity fluorescent probe for visualizing monitoring the amyloid β clearance effect of anti-Alzheimer's disease drug candidates

Beta-amyloid (Aβ), the most pivotal pathological hallmark for Alzheimer's disease (AD) diagnosis and drug evaluation, was recognized by TZ095, a high-affinity fluorescent probe developed by rational molecular design. With a TICT mechanism, TZ095 exhibited remarkable affinity with Aβ aggregates (Kd = 81.54 nM for oligomers; Kd = 66.70 nM for fibril) and substantial fluorescence enhancement (F/F0 = 44), enabling real-time monitoring of Aβ in live cells and nematodes. Significantly, this work used TZ095 to construct a new protocol that can quickly and conveniently monitor Aβ changes at the cellular and nematode levels to evaluate the anti-AD efficacy of candidate compounds, and four reported Aβ-lowering drug candidates were administrated for validation. Imaging data demonstrated that TZ095 can visually and quantitatively track the effect of Aβ elimination after drug treatment. Furthermore, TZ095 excelled in ex vivo histological staining of 12-month-old APP/PS1 mouse brains, accurately visualizing Aβ plaques. Integrating CUBIC technology, TZ095 facilitated whole-brain, 3D imaging of Aβ distribution in APP/PS1 mice, enabling high-resolution in situ analysis of Aβ plaques. Collectively, these innovative applications of TZ095 offer a promising strategy for rapid, convenient, and real-time monitoring of Aβ levels in preclinical therapeutic assessments.

Genetic testing for inherited arrhythmia syndromes and cardiomyopathies: results of the European Heart Rhythm Association survey.

Indications and clinical impact of genetic testing for cardiac diseases have increased significantly over the past years. The aim of this physician-based European Heart Rhythm Association (EHRA) survey was to assess current clinical practice and access to genetic testing for cardiac diseases across European Society of Cardiology countries and to evaluate adherence to the 2022 EHRA/HRS/APHRS/LAHRS Expert Consensus Statement on genetic testing. An online questionnaire composed of 28 questions was submitted to the EHRA Research Network and European Reference Network GUARD-Heart healthcare partners and promoted via dedicated social media channels. There were 357 respondents from 69 countries, 40% working in a hospital setting with a cardiac genetic service and/or a dedicated clinic focusing on inherited cardiac diseases and 27% with an onsite genetic laboratory. No genetic testing or low annual rate (<10/year) was declared by 39% of respondents. The majority of respondents (78%) declared issues or limitations to genetic testing access in their clinical practice. The main reasons for not providing or limited access to genetic testing were no availability of dedicated unit or genetic laboratory (35%) or reimbursement issues (25%). The most frequently reported indication for genetic testing was diagnostic purpose (55%). Most respondents (92%) declared offering genetic testing preceded by genetic counselling and 42% regular multidisciplinary evaluations for patients with cardiac genetic diseases. The perceived value of genetic testing in the diagnostic, prognostic, and therapeutic assessment was variable (67, 39, and 29%, respectively) and primarily based on the specific inherited disease. The majority of respondents recommended cascade genetic testing for the first-degree family members in case of pathogenic/likely pathogenic variant in the proband. This survey highlights a significant heterogeneity of genetic testing access and provision and issues attributable to the availability of dedicated unit/genetic laboratory and reimbursement. However, adequate adherence to indications in the current recommendations for genetic testing in patients with cardiac diseases was observed.