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Introduction: The East African Community Medicines Regulatory Harmonisation (EAC-MRH) programme was established to address challenges faced by national regulatory authorities (NRAs) of the region. Work sharing through joint assessments and inspections was adopted to manage limited resources and capacity; however, NRA good review practices (GrevP) are also a key determinant to success. This study evaluated GReVP among the EAC-MRH NRAs and mapped required strategies for countries to align themselves with the African Medicines Agency (AMA). Methods: A validated questionnaire (Optimising Efficiency in Regulatory Agency-OpERA) that standardises and captures review processes was completed by the head of the medicines registration division in each NRA. A country report based on the completed questionnaire was developed for each NRA and validated by the heads of the respective authorities. Results: The population and size of the NRAs vary and four of the countries have semi-autonomous authorities and three NRAs are autonomous. The Burundi and South Sudan authorities were fully government funded, Kenya and Uganda entirely from fees, while Rwanda, Tanzania and Zanzibar were partially funded from different sources. All authorities except South Sudan, which does not receive or review applications had backlogs. Authority fees varied based on the different application categories. Key milestones for standardised regulatory processes are implemented in all authorities. Queue times range from a few weeks to about one year. Three NRAs use internal technical agency staff for scientific assessments and three use both internal and external experts. Clock stop time varies and target timelines for review committee range from one day to three months. All the NRAs implement some best practices on quality measures, transparency and communication. Some have activities for transparency improvement but with minimal attention to training and education. Most employ some quality decision-making practices. Discussion: GrevP in EAC-MRH NRAs still needs to be improved and it is imperative that these authorities streamline and harmonise their practices. Increasing human resources and an investment in training and education of staff will enable the implementation of all measures for GRevP. This is vital, as the effectiveness and efficiency of the AMA will depend on the strength of these NRAs.

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OBJECTIVES: This study investigated the potential of the slow-developing blastocysts using preimplantation genetic testing-aneuploidy (PGT-A) in patients undergoing frozen-thawed embryo transfer, stratified by age. METHODS: A retrospective analysis was performed including a total of 743 cycles, the first frozen embryo transfer (FET) cycle with single embryo transfer, who underwent treatment between January 2020 and July 2023 in a single fertility centre, Gangnam CHA Fertility Center. A total of 743 cycles, in which we performed intracellular sperm injection and freeze-all strategy, from 743 patients were included. The patient group was divided into 4 groups as follows: group 1 (G1), 208 FET on day 5; group 2 (G2), 177 FET with PGT-A on day 5; group 3 (G3), 220 FET on day 6; group 4 (G4), 138 FET with PGT-A on day 6. We also divided into 2 groups-under 35 years of age and over 35 years of age-and performed the analysis separately for each group. RESULTS: In the under 35 years of age group, there were no significant differences in clinical pregnancy and miscarriage rates in G1 and G2 (67.2% vs. 63.8%, not statistically significantly different). Also, G4 had a higher clinical pregnancy rate than G3, but it was not significant (51.8% vs. 54.7%, not statistically significantly different). In the 35 years or older group, G2 had higher pregnancy rates than G1 and lower miscarriage rates (clinical pregnancy rate: 43.3% vs. 67.7%, P = 0.001, miscarriage rate: 22.5% vs. 3.4%, P = 0.001). In addition, G4 had a higher pregnancy rate than G3 and a lower miscarriage rate (clinical pregnancy rate: 31.8% vs. 46.9%, P = 0.003, miscarriage rate: 22.9% vs. 2.2%, P = 0.023). CONCLUSIONS: In the under-35-year-old group, PGT-A on day 5 and day 6 showed a high pregnancy rate and a low miscarriage rate. Therefore, using PGT-A seems advantageous for patients of an advanced maternal age.

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The apical membrane antigen-1 (AMA-1) is a crucial target for malaria management and prevention strategies. While the immunogenicity of AMA-1 has been extensively studied for Plasmodium falciparum and Plasmodium vivax, there is a notable scarcity of information for Plasmodium malariae. In this study, recombinant PmAMA-1 was expressed in Escherichia coli, and its integrity was confirmed via western blotting and indirect immunofluorescence assays. Immunization of BALB/c mice with rPmAMA-1 emulsified in Freund's adjuvant resulted in significantly elevated specific IgG antibodies, predominantly IgG1. The immune response exhibited Th1, Th2, and Th17 phenotypes, with a notable Th1 bias. Antisera from immunized mice effectively recognized native PmAMA-1 on P. malariae. These results suggest that PmAMA-1 is a promising target for both vaccine development and diagnostic applications for P. malariae infections, offering dual preventive and diagnostic benefits in malaria control.

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Anticuerpos Antiprotozoarios , Antígenos de Protozoos , Malaria , Proteínas de la Membrana , Plasmodium malariae , Proteínas Protozoarias , Animales , Femenino , Ratones , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Escherichia coli/genética , Inmunoglobulina G/sangre , Malaria/diagnóstico , Malaria/prevención & control , Malaria/inmunología , Vacunas contra la Malaria/inmunología , Vacunas contra la Malaria/administración & dosificación , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , Plasmodium malariae/inmunología , Plasmodium malariae/genética , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética

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Against Medical Advice (AMA) discharges pose significant challenges to the healthcare system, straining patient-clinician relationships while contributing to avoidable morbidity and mortality. Furthermore, though these discharges culminate in patients' departure from hospitals, their effects reverberate long after, propagated by clinician notes stored in patients' medical records. These notes capture exceptionally fraught interactions between patients and providers, describing the circumstances surrounding breakdowns in clinical relationships. Additionally, they represent just one side of complex, contentious social interactions, for in describing AMA discharges, clinician notewriters quite literally have the last word. For these reasons, notes documenting AMA discharges provide insight into the ways in which clinicians conceptualize, characterize, and propagate power differentials in the contemporary healthcare system. Here, we present a qualitative thematic analysis of 185 notes documenting AMA discharges from a large urban US medical center, interpreting note dynamics through three sociological models of power analysis: (i) the distributive model of power promulgated by Max Weber, (ii) the collectivist power model characterized by Talcott Parsons and Hannah Arendt, and (iii) structural interpretations of power developed by Michel Foucault. We argue that in documenting AMA discharges, clinicians appear to conceive of their relationship with patients in almost exclusively distributive terms, which in turn contributes to an adversarial dynamic whereby both patients and clinicians ultimately suffer disempowerment. We furthermore argue that by facilitating clinicians' recognition of power's collectivist and structural dimensions, we may help transform breakdowns in patient-clinician relationships into opportunities for collaboration.

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Alta del Paciente , Poder Psicológico , Humanos , Alta del Paciente/estadística & datos numéricos , Relaciones Médico-Paciente , Investigación Cualitativa , Negativa del Paciente al Tratamiento/psicología , Negativa del Paciente al Tratamiento/estadística & datos numéricos , Femenino , Masculino , Persona de Mediana Edad , Estados Unidos

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DNA methylation at the N6 position of adenine (N6-methyladenine, 6 mA), which refers to the attachment of a methyl group to the N6 site of the adenine (A) of DNA, is an important epigenetic modification in prokaryotic and eukaryotic genomes. Accurately predicting the 6 mA binding sites can provide crucial insights into gene regulation, DNA repair, disease development and so on. Wet experiments are commonly used for analyzing 6 mA binding sites. However, they suffer from high cost and expensive time. Therefore, various deep learning methods have been widely used to predict 6 mA binding sites recently. In this study, we develop a framework based on multi-scale DNA language model named "iDNA6mA-MDL". "iDNA6mA-MDL" integrates multiple kmers and the nucleotide property and frequency method for feature embedding, which can capture a full range of DNA sequence context information. At the prediction stage, it also leverages DNABERT to compensate for the incomplete capture of global DNA information. Experiments show that our framework obtains average AUC of 0.981 on a classic 6 mA rice gene dataset, going beyond all existing advanced models under fivefold cross-validations. Moreover, "iDNA6mA-MDL" outperforms most of the popular state-of-the-art methods on another 11 6 mA datasets, demonstrating its effectiveness in 6 mA binding sites prediction.

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Adenina , ADN , Sitios de Unión , Adenina/química , Adenina/metabolismo , ADN/química , ADN/genética , Metilación de ADN , Oryza/genética , Biología Computacional

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Against medical advice (AMA) discharges are practically and emotionally challenging for both patients and clinicians. Moreover, they are common after admissions for respiratory conditions such as COPD and asthma, and they are associated with poor outcomes. Despite the challenges presented by AMA discharges, clinicians rarely receive formal education and have limited guidance on how to approach these discharges. Often, the approach to AMA discharges prioritizes designating the discharge as "AMA," whereas effective coordination of discharge care receives less attention. Such an approach can lead to stigmatization of patients and low-quality care. Although evidence for best practices in AMA discharges remains lacking, we propose a set of strategies to improve care in AMA discharges by focusing on respect, in which clinicians treat patients as equals and honor differing values. We describe five strategies, including (1) preventing an AMA discharge; (2) conducting a patient-centered and truthful discussion of risk; (3) providing harm-reducing discharge care; (4) minimizing stigma and bias; (5) educating trainees. Through a case of a patient discharging AMA after a COPD exacerbation, we highlight how these strategies can be applied to common issues in respiratory-related hospitalizations, such as prescribing inhalers and managing oxygen requirements. We argue that, by using these strategies, clinicians can deliver respectful and higher-quality care to an often-marginalized population of patients with respiratory disease.

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BACKGROUND: Aureobasidium pullulans is a generalist polyextremotolerant black yeast fungus. It tolerates temperatures below 0 °C or salt concentrations up to 18%, among other stresses. A. pullulans genome sequencing revealed a high potential for producing bioactive metabolites. Only few molecular tools exist to edit the genome of A. pullulans, hence it is important to make full use of its potential. Two CRISPR/Cas9 methods have been proposed for the protoplast-based transformation of A. pullulans. These methods require the integration of a marker gene into the locus of the gene to be deleted, when the deletion of this gene does not yield a selectable phenotype. We present the adaptation of a plasmid-based CRISPR/Cas9 system developed in Aspergillus niger for A. pullulans to create deletion strains. RESULTS: The A. niger CRISPR/Cas9 plasmid led to efficient genomic deletions in A. pullulans. In this study, strains with deletions ranging from 30 to 862 bp were obtained by using an AMA1 plasmid-based genome editing strategy. CONCLUSION: The CRISPR/Cas9 transformation system presented in this study provides new opportunities for strain engineering of A. pullulans. This system allows expression of Cas9 and antibiotic resistance while being easy to adapt. This strategy could open the path to intensive genomic engineering in A. pullulans.

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Increasing pursuit of subspecialized training has quietly revolutionized physician training, but the potential impact on physician workforce estimates has not previously been recognized. The Physicians Specialty Data Reports of the Association of American Medical Colleges, derived from specialty designations in the American Medical Association (AMA) Physician Professional Data (PPD), are the reference source for US physician workforce estimates; by 2020, the report for pathologists was an undercount of 39% when compared with the PPD. Most of the difference was due to the omission of pathology subspecialty designations. The rest resulted from reliance on only the first of the AMA PPD's 2 specialty data fields. Placement of specialty designation in these 2 fields is sensitive to sequence of training and is thus affected by multiple or intercalated (between years of residency training) fellowships. Both these phenomena have become progressively more common and are not unique to pathology. Our findings demonstrate the need to update definitions and methodology underlying estimates of the US physician workforce for pathology and suggest a like need in other specialties affected by similar trends.

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BACKGROUND: Elevated FSH often occurs in women of advanced maternal age (AMA, age ≥ 35) and in infertility patients undergoing controlled ovarian stimulation (COS). There is controversy on whether high endogenous FSH contributes to infertility and whether high exogenous FSH adversely impacts patient pregnancy rates. METHODS: The senescence-accelerated mouse-prone-8 (SAMP8) model of female reproductive aging was employed to assess the separate impacts of age and high FSH activity on the percentages (%) of viable and mature ovulated oocytes recovered after gonadotropin treatment. Young and midlife mice were treated with the FSH analog equine chorionic gonadotropin (eCG) to model both endogenous FSH elevation and exogenous FSH elevation. Previously we showed the activin inhibitor ActRIIB:Fc increases oocyte quality by preventing chromosome and spindle misalignments. Therefore, ActRIIB:Fc treatment was performed in an effort to increase % oocyte viability and % oocyte maturation. RESULTS: The high FSH activity of eCG is ootoxic to ovulatory oocytes, with greater decreases in % viable oocytes in midlife than young mice. High FSH activity of eCG potently inhibits oocyte maturation, decreasing the % of mature oocytes to similar degrees in young and midlife mice. ActRIIB:Fc treatment does not prevent eCG ootoxicity, but it restores most oocyte maturation impeded by eCG. CONCLUSIONS: FSH ootoxicity to ovulatory oocytes and FSH maturation inhibition pose a paradox given the well-known pro-growth and pro-maturation activities of FSH in the earlier stages of oocyte growth. We propose the FOOT Hypothesis ("FSH OoToxicity Hypothesis), that FSH ootoxicity to ovulatory oocytes comprises a new driver of infertility and low pregnancy success rates in DOR women attempting spontaneous pregnancy and in COS/IUI patients, especially AMA women. We speculate that endogenous FSH elevation also contributes to reduced fecundity in these DOR and COS/IUI patients. Restoration of oocyte maturation by ActRIB:Fc suggests that activin suppresses oocyte maturation in vivo. This contrasts with prior studies showing activin A promotes oocyte maturation in vitro. Improved oocyte maturation with agents that decrease endogenous activin activity with high specificity may have therapeutic benefit for COS/IVF patients, COS/IUI patients, and DOR patients attempting spontaneous pregnancies.

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Receptores de Activinas Tipo II , Oocitos , Animales , Femenino , Oocitos/efectos de los fármacos , Ratones , Receptores de Activinas Tipo II/metabolismo , Ovulación/efectos de los fármacos , Gonadotropina Coriónica/farmacología , Hormona Folículo Estimulante/sangre , Oogénesis/efectos de los fármacos , Inducción de la Ovulación/métodos , Fragmentos Fc de Inmunoglobulinas/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Embarazo , Activinas

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Background: How antimitochondrial antibody (AMA)-positive patients evolve to have primary biliary cholangitis (PBC) in viral hepatitis-endemic areas is unknown. Objectives: We aimed to investigate this evolution in Taiwan. Design/methods: A 16-year medical center-based cohort study of 2,095,628 subjects was conducted in Taiwan, an Asian country endemic to viral hepatitis. AMA-positive subjects were those with positive AMA with alkaline phosphatase (ALP) ⩽1.5 times the upper limit of normal (ULN), and PBC was defined as positive AMA with ALP >1.5 × ULN. Results: AMA-positive subjects had a lower average age- and sex-adjusted prevalence than PBC patients (4.68/105 versus 11.61/105, p = 0.0002), but their incidence was comparable (0.99/105 versus 1.12/105, p = 0.36). The former group had a borderline significantly lower mean age (56.59 years versus 58.10 years, p = 0.06) and a lower female-to-male ratio (2.85:1 versus 5.44:1, p < 0.0001). Both AMA-positive subjects (prevalence change: 20.0%, p < 0.01; incidence change: -9.2%, p < 0.01) and PBC patients (prevalence change: 14.6%, p < 0.01; incidence change: -4.7%, p < 0.01) prevalence rate increased but the incidence rate decreased. Among the 423 AMA-positive subjects, 77 (18.2%) developed PBC, for a mean duration of 1.757 years. Compared with AMA-positive subjects, PBC patients had similar concurrent chronic hepatitis B (CHB) rates (2.7% versus 4.3%, p = 0.197) but lower chronic hepatitis C (CHC) rates (3.69% versus 15.60%, p < 0.01). Conclusion: PBC was more prevalent than AMA-positive subjects, and PBC patients had a higher female-to-male ratio than AMA-positive subjects, of whom 18.2% developed PBC (mean lag: 1.757 years). Upward trends in prevalence rates and downward trends in incidence rates were noted for both AMA-positive subjects and PBC. CHB was rare, CHC was more prevalent among PBC patients than the general population, and CHC was less prevalent among PBC than among AMA-positive subjects.

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Evolutionary relationship between AMA positivity and PBC in Taiwan PBC was more prevalent than AMA-positive subjects, and PBC patients had a higher female-to-male ratio than AMA-positive subjects, of whom 18.2% developed PBC (mean lag: 1.757 years). Upward trends in prevalence rates and downward trends in incidence rates were noted for both AMA-positive subjects and PBC. CHB was rare, CHC was more prevalent among PBC patients than the general population, and CHC was less prevalent among PBC than among AMA-positive subjects.

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American Medical Association , Current Procedural Terminology , Dermatología , Estados Unidos , Humanos

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Clay colloids in the subsurface environment have a strong adsorption capacity for radionuclides, and the mobile colloids will carry the nuclides for migration, which would promote the movability of radionuclides in the groundwater environment and pose a threat to the ecosphere. The investigations of the adsorption/desorption behaviors of radionuclides in colloids and porous media are significant for the evaluation of the geological disposal of radioactive wastes. To illustrate the adsorption/desorption behaviors of 241Am(Ⅲ) in Na-montmorillonite colloid and/or quartz sand systems at different pH (5, 7 and 9), ionic strengths (0, 0.1 and 5 mM), colloid concentrations (300 and 900 mg/L), nuclide concentrations (500, 800, 1100 and 1400 Bq/mL) and grain sizes (40 and 60 mesh), a series of batch sorption-desorption experiments were conducted. Combining the analysis of the physical and chemical properties of Na-montmorillonite with the Freundlich model, the influencing mechanism of different controlling factors is discussed. The experimental results show that the adsorption/desorption behaviors of 241Am(Ⅲ) in Na-montmorillonite colloid and/or quartz sand strongly are influenced by the pH value and ionic strength of a solution, the colloid concentration as well as quartz sand grain size. The adsorption and desorption isotherms within all the experimental conditions could be well-fitted by the Freundlich model and the correlation coefficients (R2) are bigger than 0.9. With the increase in pH, the adsorption partition coefficient (Kd) at 241Am(Ⅲ)-Na-montmorillonite colloid two-phase system and 241Am(Ⅲ)-Na-montmorillonite colloid-quartz sand three-phase system presents a trend which increases firstly followed by decreasing, due to the changes in the morphology of Am with pH. The Kd of 241Am(Ⅲ) adsorption on montmorillonite colloid and quartz sand decreases with increasing in ionic strength, which is mainly attributed to the competitive adsorption, surface complexation and the reduction of surface zeta potential. Additionally, the Kd increases with increasing colloid concentrations because of the increase in adsorption sites. When the mean grain diameter changes from 0.45 to 0.3 mm, the adsorption variation trends of 241Am(Ⅲ) remain basically unchanged. The research results obtained in this work are meaningful and helpful in understanding the migration behaviors of radionuclides in the underground environment.

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Americio , Bentonita , Coloides , Cuarzo , Bentonita/química , Concentración Osmolar , Adsorción , Concentración de Iones de Hidrógeno , Coloides/química , Cuarzo/química , Americio/química , Americio/análisis , Contaminantes Radiactivos del Agua/química , Contaminantes Radiactivos del Agua/análisis , Contaminantes Radiactivos del Suelo/análisis , Contaminantes Radiactivos del Suelo/química , Modelos Químicos , Tamaño de la Partícula , Arena/química

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OBJECTIVE: To investigate the feasibility of performing frozen-thawed high-quality single blastocyst transfer in women of different ages. METHODS: A total of 1,279 women were divided into four groups: a 38-40-year-old group (n = 147), 35-37-year-old group (n = 164), 30-34-year-old group (n = 483), and < 30-year-old group (n = 485). Intergroup comparisons of baseline characteristics and pregnancy and neonatal outcomes were made. RESULTS: The clinical pregnancy rate (47.6%), and live birth rate (34.0%) in the 38-40-year-old group were significantly lower than those in the 30-34-year-old group (64.4%, 50.9%, respectively; all P < 0.001) and < 30-year-old group (62.9%, 50.7%, respectively; all P < 0.001). However, the 35-37-year-old group did not differ from the other three groups in these two dimensions (all P > 0.05). Moreover, there were no differences in the rates of biochemical pregnancy, miscarriage, or obstetric or neonatal complications among the four groups (all P > 0.05). According to the multivariate logistic regression analysis, the 35-37-year-old group was not associated with non-live birth outcomes, adverse pregnancy outcomes, or obstetric or neonatal complications. However, being 38-40 years of age was a risk factor for non-live birth (OR = 2.121, 95% CI: 1.233-3.647) and adverse pregnancy outcomes (OR = 1.630, 95% CI: 1.010-2.633). Post hoc power analysis showed that the study was sufficiently powered to detect meaningful differences. CONCLUSION: Frozen-thawed high-quality single blastocyst transfer produces the same satisfactory pregnancy outcomes for women aged 35-37 years as younger patients. Future prospective randomized controlled studies with larger populations are needed to verify the feasibility and safety of this method.

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Aborto Espontáneo , Resultado del Embarazo , Embarazo , Recién Nacido , Humanos , Femenino , Adulto , Resultado del Embarazo/epidemiología , Transferencia de Embrión/métodos , Índice de Embarazo , Tasa de Natalidad , Aborto Espontáneo/etiología , Estudios Retrospectivos , Nacimiento Vivo/epidemiología

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Dolor Abdominal , Errores Diagnósticos , Torsión Ovárica , Humanos , Femenino , Dolor Abdominal/etiología , Torsión Ovárica/diagnóstico , Adulto , Recurrencia

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OBJECTIVES: This study describes clinical, biochemical, and histological features and long-term outcomes in pediatric patients diagnosed with autoimmune hepatitis (AIH) at King Abdullah University Hospital, Jordan. DESIGN: Retrospective, single-center study. SETTING: King Abdullah University Hospital, Jordan. PARTICIPANTS: Inclusion of all pediatric patients with AIH diagnosed at our hospital from 2015 to 2023. Exclusion criteria was patients aged over 18 at time of diagnosis and those diagnosed elsewhere. OUTCOME MEASURES: Understanding clinical, biochemical, and histological AIH features in children, evaluating treatment responses, and reporting short- and long-term complications, including mortality. RESULTS: Sixteen pediatric cases were diagnosed, with an average age of 9.84 ± 4.13 years. Females comprised 75% of patients, and 31.3% presented with acute liver failure. Jaundice was the most common symptom, and hepatosplenomegaly was observed in 18% of cases. Most patients had elevated transaminase levels, along with positive anti-smooth muscle antibody (ASMA) and antinuclear antibodies (ANA). Common hematological abnormalities included anemia (56.3%) and thrombocytopenia (37.5%). All patients underwent liver biopsy, with interface hepatitis present in 81.3% of cases. Treatment mainly involved prednisone and azathioprine. Three patients died, one discontinued therapy, two patients were lost to follow-up, and 10 remained on treatment. CONCLUSION: Autoimmune hepatitis affects Jordanian children, primarily female children. Jaundice is the most common presenting symptoms. Only Type I AIH occurred in our cohort. Although of good response to conventional treatment with steroids and immunosuppression, mortality reached 18.8%.

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Hepatitis Autoinmune , Ictericia , Humanos , Niño , Femenino , Adolescente , Adulto , Preescolar , Masculino , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Estudios Retrospectivos , Jordania/epidemiología , Azatioprina/uso terapéutico , Autoanticuerpos , Anticuerpos Antinucleares/uso terapéutico

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BACKGROUND: Timely diagnosis of Toxoplasma gondii infection is necessary to prevent and control toxoplasmosis transmission. The gold immunochromatographic assay (GICA) is a means of rapidly detecting pathogen in samples. GICA-based diagnostic methods have been developed to accurately detect pathogens with high sensitivity and specificity, and their application in T. gondii diagnosis is expected to yield good results. METHODS: Colloidal gold test strips were produced using T. gondii C-terminal truncated apical membrane antigen 1 (AMA1C). Colloidal gold-AMA1C and colloidal gold-murine protein conjugate were synthesized under optimal conditions. A nitrocellulose membrane was treated with AMA1C and goat anti-mouse antibody as the test line and control line, respectively. In total, 90 cat serum samples were tested using AMA1C-GICA and a commercial enzyme linked immunosorbent assay (ELISA) kit. The GICA results were digitally displayed using a portable colloidal gold immunochromatographic test strip analyzer (HMREADER). The sensitivity, specificity, and stability of AMA1C-GICA were assessed, and this was then used to examine clinical samples, including 203 human sera, 266 cat sera, and 81 dog sera. RESULTS: AMA1C-GICA had a detection threshold of 1:32 for T. gondii-positive serum. The GICA strips specifically detected T. gondii antibodies and exhibited no reactivity with Plasmodium vivax, Paragonimus kellicotti, Schistosoma japonicum, Clonorchis sinensis, and Schistosoma mansoni. Consequently, 15 (16.7%) positive samples were detected using the AMA1C-GICA and commercial ELISA kits for each of the assays. The receiver-operating characteristic curve showed that GICA had a relative sensitivity of 85.3% and specificity of 92%, with an area under the curve of 98%. After analyzing clinical samples using HMREADER, 1.2%-23.4% of these samples were found to be positive for T. gondii. CONCLUSIONS: This study presents a novel assay that enables timely and efficient detection of serum antibodies against T. gondii, thereby allowing for its early clinical diagnosis. Furthermore, the integration of digital detection using HMREADER can enhance the implementation of GICA.

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Toxoplasma , Toxoplasmosis , Ratones , Animales , Perros , Humanos , Cromatografía de Afinidad/métodos , Sensibilidad y Especificidad , Inmunoensayo/métodos , Toxoplasmosis/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Anticuerpos Antihelmínticos , Oro Coloide/análisis , Oro Coloide/química

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The Amphibian Metamorphosis Assay (AMA) is used to determine if a tested chemical has potential to impact the hypothalamic-pituitary-thyroid (HPT) axis of Xenopus laevis tadpoles, while the Fish Short Term Reproduction Assay (FSTRA) assesses potential effects on the hypothalamic-pituitary-gonadal (HPG) axis of fish such as the fathead minnow (Pimephales promelas). Several global regulatory programs routinely require these internationally validated tests be performed to determine the potential endocrine activity of chemicals. As such, they are conducted in accordance with standardized protocols and test criteria, which were originally developed more than a decade ago. Sizeable numbers of AMA and FSTRA studies have since been carried out, which allows for the mining of extensive historical control data (HCD). Such data are useful for investigating the existence of outlier results and aberrant control groups, identifying potential confounding variables, providing context for rare diagnoses, discriminating target from non-target effects, and for refining current testing paradigms. The present paper provides histopathology HCD from 55 AMA studies and 45 fathead minnow FSTRA studies, so that these data may become publicly available and thus aid in the interpretation of future study outcomes. Histopathology is a key endpoint in these assays, in which it is considered to be one of the most sensitive indicators of endocrine perturbation. In the current review, granular explorations of HCD data were used to identify background lesions, to assess the utility of particular diagnostic findings for distinguishing endocrine from non-endocrine effects, and to help determine if specific improvements to established regulatory guidance may be warranted. Knowledge gleaned from this investigation, supplemented by information from other recent studies, provided further context for the interpretation of AMA and FSTRA histopathology results. We recommend HCDs for the AMA and FSTRA be maintained to support the interpretation of study results.

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Cyprinidae , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/toxicidad , Reproducción , Sistema Endocrino , Anfibios

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Development and validation of instruments based on concepts and clinical features described in Ayurveda is a constructive step towards translational research in Ayurveda. The clinical decisions in traditional medical practices often depend on clinical features. Such attempts from Ayurveda experts also contribute to strengthen an endeavour of integrative medicine. A recently published article in J-AIM on development and validation of Aam Assessment Instrument (AAI) to assess the disease activity in amavata is a landmark study. This study is undertaken in patients with rheumatoid arthritis (RA), a prototype of inflammatory arthritis. We suggest that the specificity and reliability of AAI in RA and amavata would increase if complemented with joint count as described in Ayurveda texts. These joint counts can be further sub-classified for different types of inflammatory arthritides. Similarly, this AAI can also be validated and used for constitutional features in other ama-dominant non-rheumatic systemic diseases. This may need development of more comprehensive ama-specific features. We also need to consider the limitations of patient-reported outcome measures (PROMs) during further development and validation of AAI. Collective, multicentric, organized efforts by Ayurveda clinicians will lead to the development of reliable, sensitive, specific, and reproducible instruments for clinical assessments in various diseases.

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Introduction and importance: Primary biliary cholangitis (PBC) is a rare immune-mediated liver disease characterized by the destruction of intrahepatic bile ducts and a positive antimitochondrial antibody (AMA), which is considered a serological hallmark for the diagnosis. Rarely, AMA can be absent/nondetectable in a few cases and is referred to as 'AMA-negative'. Case presentation: The authors present such an uncommon case of AMA-negative PBC in a 39-year-female with Sjogren's syndrome who presented with fatigue, pruritus, and dry eyes. Clinical discussion: Previously published studies state that approximately only about 5% of patients with PBC are 'AMA-negative'. For patients negative for AMA, the diagnosis has to be based on typical pathological features of this disease. Once a diagnosis of PBC is established, regardless of whether it is positive or negative for AMAs, ursodeoxycholic acid is a widely accepted treatment. Conclusion: The presence/absence of AMAs is associated with similar clinical, biochemical, and histopathological characteristics in PBC. The identification of AMAs alone should not impact the diagnosis or treatment of PBC.