Impacts of the feedback loop between sense-antisense RNAs in regulating circadian rhythms.

Antisense transcripts are a unique group of non-coding RNAs that are transcribed from the opposite strand of a sense coding gene in an antisense orientation. Even though they do not encode a protein, these transcripts play a regulatory role in a variety of biological processes, including circadian rhythms. We and others found an antisense transcript, Per2AS , that is transcribed from the strand opposite the sense transcript Period2 ( Per2 ) and exhibits a rhythmic and antiphasic expression pattern compared to Per2 in mouse. By assuming that Per2AS and Per2 mutually repress each other, our previous mathematical model predicted that Per2AS regulates the robustness and the amplitude of circadian rhythms. In this study, we revised our previous model and developed a new mathematical model that mechanistically described the mutually repressive relationship between Per2 and Per2AS via transcriptional interference. We found that the simulation results are largely consistent with experimental observations including the counterintuitive ones that could not be fully explained by our previous model. These results indicate that our revised model serves as a foundation to build more detailed models in the future to better understand the impact of Per2AS-Per2 interaction in the mammalian circadian clock. Our mechanistic description of Per2AS-Per2 interaction can also be extended to other mathematical models that involve sense-antisense RNA pairs that mutually repress each other.

The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data. METHODS: Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population. RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7). CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

Multiple juvenile xanthogranuloma.

Juvenile xanthogranuloma is the most frequent form of non-Langerhans cell histiocytosis in children. Clinically, it presents as well defined, yellowish papules that are typically located on the head, neck, upper trunk, and proximal region of the extremities. Although solitary lesions are the most common presentation, few cases of multiple juvenile xanthogranuloma have been described, more frequently associated with extracutaneous involvement. We report a 2-month-old girl with 22 cutaneous papules, clinically and histologically compatible with juvenile xanthogranulomas. Screening of visceral involvement was performed with no evidence of systemic disease. Identifying high-risk factors of systemic disease in patients with multiple juvenile xanthogranuloma is essential to perform an appropriate management of this entity.

Operative Management of Y-Shaped Metatarsal with Biphalangeal Sixth Toe.

BACKGROUND: In the literature, there is no consensus regarding the surgical management of postaxial polydactyly, and few cases of polymetatarsia with polydactyly have been reported. Treatment of the complete deformity will prevent further foot and gait disorders. OBJECTIVE: To identify literature relevant to the operative management of Y-shaped metatarsal with biphalangeal sixth toe and related skin and wound care to improve surgical treatment protocols from a clinical experience perspective. DATA SOURCES: The authors searched several electronic databases in December 2022 for articles related to postaxial polysyndactyly in the feet and polymetatarsia. Databases searched included PubMed, SciELO, ScienceDirect, Cochrane Database of Systematic Reviews, and Google Scholar gray literature. STUDY SELECTION: Two independent researchers conducted the searches and read the article titles and abstracts. Studies were included if they were narrative reviews, case studies, or observational studies; written in English or Spanish; and published between 2012 and 2022. Nonhuman studies were excluded. Studies that met the inclusion criteria were fully evaluated. Disagreements between reviewers were resolved by consensus, and when there was no consensus, a senior researcher was consulted. DATA EXTRACTION: The following data were extracted from the included studies using a standardized form: author and year of publication, study type, number of participants, sex, polydactyly location, polymetatarsia, type of polydactyly, participants' history of hereditary associated diseases or malformations, treatment, removal criteria, and timing of surgery. DATA SYNTHESIS: Authors evaluated 11 studies of postaxial polydactyly that included a total of 153 participants (64 men, 89 women). They also document their clinical experience with a surgical technique used in cases of bilateral postaxial polydactyly of the foot with a Y-shaped metatarsal with biphalangeal sixth toe. CONCLUSIONS: Surgical correction with lateral removal of the sixth toe is a resolutive treatment to improve the functionality of the foot, its aesthetic appearance, and the patient's quality of life. Case-specific treatment should be applied and tailored to meet the individual needs. The biomechanics of gait and shoe problems in these patients improve with surgical treatment, without presenting secondary aesthetic problems in skin care.

Volatiles of symbiotic bacterial origin explain ectoparasitism and fledging success of hoopoes.

BACKGROUND: Some parasites use olfactory cues to detect their hosts and, since bacterial symbionts are partially responsible for animal odours, they could influence host parasitism. By autoclaving nest materials of hoopoe (Upupa epops) nests before reproduction started, we explored the hypothetical links between host-associated bacteria, volatiles and parasitism. During the nestling stage, we (i) estimated the level of ectoparasitism by chewing lice (Suborder Mallophaga) in adult hoopoe females and by Carnus haemapterus flies in nestlings, and (ii) characterized microbial communities and volatile profiles of nest environments (nest material and nest cavity, respectively) and uropygial secretions. RESULTS: Experimental nests had less diverse bacterial communities and more diverse volatile profiles than control nests, while occupants experienced lower intensity of parasitism in experimental than in control nests. The experiment also affected beta diversity of the microbial communities of nest material and of the volatiles of the nestling uropygial secretions. Moreover, microbial communities of uropygial secretions and of nest materials covaried with their volatile profiles, while the volatile profile of the bird secretions explained nest volatile profile. Finally, a subset of the volatiles and bacteria detected in the nest material and uropygial secretions were associated with the ectoparasitism intensity of both adult females and nestlings, and with fledging success. CONCLUSIONS: These results show that a component of animal odours is linked with the microbial communities of the host and its reproductive environment, and emphasize that the associations between bacteria, ectoparasitism and reproductive success are partially mediated by volatiles of bacterial origin. Future work should focus on mechanisms underlying the detected patterns.

Oculomotor Dysfunction in Idiopathic and LRRK2-Parkinson's Disease and At-Risk Individuals.

Background: Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD). Objective: To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2. Methods: The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests. Results: We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy. Conclusions: iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers.

[Convergent and discriminative validity of the Frail-VIG index with the Pfeiffer test in people cared for in home care]. / Validez convergente y discriminativa del índice Frágil-VIG con el test de Pfeiffer en personas atendidas en atención domiciliaria.

INTRODUCTION: The Frail-VIG index-and the Pfeiffer test are measurements used in Primary Care for assessment frailty and the cognitive impairment screening. The Frail-VIG index is a multidimensional instrument that allows a rapid assessment of the degree of frailty in the context of clinical practice. OBJECTIVE: Our aim was to investigate the convergent and discriminative validity of the Frail-VIG index with regard to Pfeiffer test value. DESIGN: A cross-sectional study. SITE: Two urban Primary Health Care centres of the Catalan Institute of Health, Barcelona (Spain). PARTICIPANTS: All people included under a home care programme during the year 2018. No exclusion criteria were applied. MAIN MEASUREMENTS: We used the Frail-VIG index to measure frailty and the Pfeiffer test to cognitive impairment screening. Trained nurses administered both instruments during face-to-face assessments in a participant's home during usual care. The relationships between both instruments were examined using Pearson's correlation coefficient. RESULTS: A total of 412 participants were included. Frail-VIG score and Pfeiffer test value were moderately correlated (r=0.564; P<0.001). Non-frail people had a lower risk of developing cognitive impairment than moderate to severe frail people. The value of the Pfeiffer test increased significantly as the Frail-VIG index score also increased. CONCLUSIONS: Frail-VIG index demonstrated a convergent validity with the Pfeiffer test. Its discriminative validity was optimal, as their scores showed an excellent capacity to differentiate between people with a higher and lower risk of developing cognitive impairment. These findings provide additional pieces of evidence for construct validity of the Frail-VIG index.

Prediabetes as a risk factor for all-cause and cause-specific mortality: a prospective analysis of 115,919 adults without diabetes in Mexico City.

BACKGROUND: Prediabetes has been associated with increased all-cause and cardiovascular mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations. METHODS: We analyzed data from 115,919 adults without diabetes (diagnosed or undiagnosed) aged 35-84 years who participated in the Mexico City Prospective Study between 1998 and 2004. Participants were followed until January 1st, 2021 for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA, HbA1c 5.7% to 6.4%) and the International Expert Committee (IEC, HbA1c 6.0-6.4%) definitions. Cox regression adjusted for confounders was used to estimate all-cause and cause-specific mortality rate ratios (RR) at ages 35-74 years associated with prediabetes. FINDINGS: During 2,085,392 person-years of follow-up (median in survivors 19 years), there were 6,810 deaths at ages 35-74, including 1,742 from cardiovascular disease, 892 from renal disease and 108 from acute diabetic crises. Of 110,405 participants aged 35-74 years at recruitment, 28,852 (26%) had ADA-defined prediabetes and 7,203 (7%) had IEC-defined prediabetes. Compared with those without prediabetes, individuals with prediabetes had higher risk of all-cause mortality at ages 35-74 years (RR 1.13, 95% CI 1.07-1.19 for ADA-defined prediabetes and RR 1.28, 1.18-1.39 for IEC-defined prediabetes), as well as increased risk of cardiovascular mortality (RR 1.22 [1.10-1.35] and 1.42 [1.22-1.65], respectively), renal mortality (RR 1.35 [1.08-1.68] and 1.69 [1.24-2.31], respectively), and death from an acute diabetic crisis (RR 2.63 [1.76-3.94] and 3.43 [2.09-5.62], respectively). RRs were larger at younger than at older ages, and similar for men compared to women. The absolute excess risk associated with ADA and IEC-defined prediabetes at ages 35-74 accounted for6% and 3% of cardiovascular deaths respectively, 10% and 5% of renal deaths respectively, and 31% and 14% of acute diabetic deaths respectively. INTERPRETATION: Prediabetes is a significant risk factor for all-cause, cardiovascular, renal, and acute diabetic deaths in Mexican adults. Identification and timely management of individuals with prediabetes for targeted risk reduction could contribute to reducing premature mortality from cardiometabolic causes in this population. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, UK Medical Research Council. Instituto Nacional de Geriatría (Mexico City).

Enhancing adaptive proton therapy through CBCT images: Synthetic head and neck CT generation based on 3D vision transformers.

BACKGROUND: Proton therapy is a form of radiotherapy commonly used to treat various cancers. Due to its high conformality, minor variations in patient anatomy can lead to significant alterations in dose distribution, making adaptation crucial. While cone-beam computed tomography (CBCT) is a well-established technique for adaptive radiation therapy (ART), it cannot be directly used for adaptive proton therapy (APT) treatments because the stopping power ratio (SPR) cannot be estimated from CBCT images. PURPOSE: To address this limitation, Deep Learning methods have been suggested for converting pseudo-CT (pCT) images from CBCT images. In spite of convolutional neural networks (CNNs) have shown consistent improvement in pCT literature, there is still a need for further enhancements to make them suitable for clinical applications. METHODS: The authors introduce the 3D vision transformer (ViT) block, studying its performance at various stages of the proposed architectures. Additionally, they conduct a retrospective analysis of a dataset that includes 259 image pairs from 59 patients who underwent treatment for head and neck cancer. The dataset is partitioned into 80% for training, 10% for validation, and 10% for testing purposes. RESULTS: The SPR maps obtained from the pCT using the proposed method present an absolute relative error of less than 5% from those computed from the planning CT, thus improving the results of CBCT. CONCLUSIONS: We introduce an enhanced ViT3D architecture for pCT image generation from CBCT images, reducing SPR error within clinical margins for APT workflows. The new method minimizes bias compared to CT-based SPR estimation and dose calculation, signaling a promising direction for future research in this field. However, further research is needed to assess the robustness and generalizability across different medical imaging applications.

Insulin resistance potentiates the effect of remnant cholesterol on cardiovascular mortality in individuals without diabetes.

BACKGROUND AND AIMS: Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality. METHODS: We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality. RESULTS: We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18-1.48) and decreased at older ages (HR 0.934, 95%CI 0.918-0.959) compared to RC (HR 0.983, 95%CI 0.952-1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25-1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13-1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11-98.89) of the effect of RC levels on CVD mortality. CONCLUSIONS: Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals.

Adaptation and Validation of a Questionnaire to Measure Satisfaction With Telephone Care Among Individuals Living With Inflammatory Bowel Disease.

Background: Individuals with inflammatory bowel disease (IBD) require routine medical follow-up. The usage of telephone care (TC) appointments increased because of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to adapt a questionnaire to evaluate satisfaction with TC use and validate it among IBD individuals. Methods: A committee of experts adapted the Telehealth Usability Questionnaire to the TC context and validated its use in individuals with IBD. This committee included three IBD gastroenterology care providers (GCPs), two IBD-patient partners, and two healthcare researchers. The committee evaluated the content validity of the adapted items to measure TC satisfaction. A pilot study assessed the readability and usability of the questionnaire. Individuals with IBD in Saskatchewan completed an online survey with the adapted questionnaire between December 2021 and April 2022. Data were analyzed using descriptive and correlational techniques. Psychometric analyses were conducted to examine the reliability and validity of the questionnaire. Results: The committee of experts developed the Telephone Care Satisfaction Questionnaire (TCSQ patient), with 16 items and one overall item for TC satisfaction. After the pilot, 87 IBD individuals participated in the online survey. A strong correlation was observed between the 16-item standardized level of TC satisfaction and the overall item, r = 0.85 (95%CI 0.78-0.90, p < 0.001). The TCSQ patient had optimal internal reliability (α = 0.96). Two dimensions were identified in the exploratory factor analysis (i.e., TC usefulness and convenience). Conclusion: The TCSQ patient is a valid and reliable measure of TC satisfaction among individuals with IBD. This questionnaire demonstrated excellent psychometric properties and we recommend its use.

Development of dye-sensitized solar cells using pigment extracts produced by Talaromyces atroroseus GH2.

The identification of more efficient, clean, secure, and competitive energy supply is necessary to align with the needs of sustainable devices. For this reason, a study for developing innovative dye-sensitized solar cells (DSSCs) based on microbial pigments is reported starting from Talaromyces atroroseus GH2. The fungus was cultivated by fermentation and the extracellular pigment extract was characterized by HPLC-DAD-ESI-MS analyses. The most abundant compound among the 22 azaphilone-type pigments identified was represented by PP-O. The device's behavior was investigated in relation to electrolyte and pH for verifying the stability on time and the photovoltaic performance. Devices obtained were characterized by UV-vis measurements to verify the absorbance intensity and transmittance percentage. Moreover, photovoltaic parameters through photo-electrochemical measurements (I-V curves) and impedance characteristics by Electrochemical Impedance Spectroscopy (EIS) were determined. The best microbial device showed a short-circuit current density (Jsc) of 0.69 mA/cm2, an open-circuit photo-voltage (Voc) of 0.27 V and a Fill Factor (FF) of 0.60. Furthermore, the power conversion efficiency (PCE) of the device was 0.11%. Thus, the present study demonstrated the potential of microbial origin pigments for developing DSSCs.

Diabetes subgroups and sociodemographic inequalities in Mexico: a cross-sectional analysis of nationally representative surveys from 2016 to 2022.

Background: Differences in the prevalence of four diabetes subgroups have been reported in Mexico compared to other populations, but factors that may contribute to these differences are poorly understood. Here, we estimate the prevalence of diabetes subgroups in Mexico and evaluate their correlates with indicators of social disadvantage using data from national representative surveys. Methods: We analyzed serial, cross-sectional Mexican National Health and Nutrition Surveys spanning 2016, 2018, 2020, 2021, and 2022, including 23,354 adults (>20 years). Diabetes subgroups (obesity-related [MOD], severe insulin-deficient [SIDD], severe insulin-resistant [SIRD], and age-related [MARD]) were classified using self-normalizing neural networks based on a previously validated algorithm. We used the density-independent social lag index (DISLI) as a proxy of state-level social disadvantage. Findings: We identified 4204 adults (median age: 57, IQR: 47-66, women: 64%) living with diabetes, yielding a pooled prevalence of 16.04% [95% CI: 14.92-17.17]. When stratified by diabetes subgroup, prevalence was 6.62% (5.69-7.55) for SIDD, 5.25% (4.52-5.97) for MOD, 2.39% (1.95-2.83) for MARD, and 1.27% (1.00-1.54) for SIRD. SIDD and MOD clustered in Southern Mexico, whereas MARD and SIRD clustered in Northern Mexico and Mexico City. Each standard deviation increase in DISLI was associated with higher odds of SIDD (OR: 1.12, 95% CI: 1.06-1.12) and lower odds of MOD (OR: 0.93, 0.88-0.99). Speaking an indigenous language was associated with higher odds of SIDD (OR: 1.35, 1.16-1.57) and lower odds of MARD (OR 0.58, 0.45-0.74). Interpretation: Diabetes prevalence in Mexico is rising in the context of regional and sociodemographic inequalities across distinct diabetes subgroups. SIDD is a subgroup of concern that may be associated with inadequate diabetes management, mainly in marginalized states. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico.

Uneven response of phytoplankton-bacteria coupling under Saharan dust pulse and ultraviolet radiation in the south-western Mediterranean Sea.

The microbial carbon (C) flux in the ocean is a key functional process governed by the excretion of organic carbon by phytoplankton (EOC) and heterotrophic bacterial carbon demand (BCD). Ultraviolet radiation (UVR) levels in upper mixed layers and increasing atmospheric dust deposition from arid regions may alter the degree of coupling in the phytoplankton-bacteria relationship (measured as BCD:EOC ratio) with consequences for the C-flux through these compartments in marine oligotrophic ecosystem. Firstly, we performed a field study across the south-western (SW) Mediterranean Sea to assess the degree of coupling (BCD:EOC) and how it may be related to metabolic balance (total primary production: community respiration; PPT:CR). Secondly, we conducted a microcosm experiment in two contrasting areas (heterotrophic nearshore and autotrophic open sea) to test the impact of UVR and dust interaction on microbial C flux. In the field study, we found that BCD was not satisfied by EOC (i.e., BCD:EOC >1; uncoupled phytoplankton-bacteria relationship). BCD:EOC ratio was negatively related to PPT:CR ratio across the SW Mediterranean Sea. A spatial pattern emerged, i.e. in autotrophic open sea stations uncoupling was less severe (BCD:EOC ranged 1-2), whereas heterotrophic nearshore stations uncoupling was more severe (BCD:EOC > 2). In the experimental study, in the seawater both enriched with dust and under UVR, BCD:EOC ratio decreased by stimulating autotrophic processes (particulate primary production (PPP) and EOC) in the heterotrophic nearshore area, whereas BCD:EOC increased by stimulating heterotrophic processes [heterotrophic bacterial production (HBP), bacterial growth efficiency (BGE), bacterial respiration (BR)] in the autotrophic open sea. Our results show that this spatial pattern could be reversed under future UVR × Dust scenario. Overall, the impact of greater dust deposition and higher UVR levels will alter the phytoplankton-bacteria C-flux with consequences for the productivity of both communities, their standing stocks, and ultimately, the ecosystem's metabolic balance at the sea surface.

Comparison of prevalence estimates of pfhrp2 and pfhrp3 deletions in Plasmodium falciparum determined by conventional PCR and multiplex qPCR and implications for surveillance and monitoring.

OBJECTIVES: The accuracy of malaria rapid diagnostic tests is threatened by Plasmodium falciparum with pfhrp2/3 deletions. This study compares gene deletion prevalence determined by multiplex real time polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR) using existing samples with clonality previously determined by microsatellite genotyping. METHODS: Multiplex qPCR was used to estimate prevalence of pfhrp2/3 deletions in three sets of previously collected patient samples from Eritrea and Peru. The qPCR was validated by multiplex digital polymerase chain reaction. Sample classification was compared with cPCR, and receiver operating characteristic curve analysis was used to determine the optimal ΔCq threshold that aligned the results of the two assays. RESULTS: qPCR classified 75% (637 of 849) of samples as single, and 212 as mixed-pfhrp2/3 genotypes, with a positive association between clonality and proportion of mixed-pfhrp2/3 genotype samples. The sample classification agreement between cPCR and qPCR was 75.1% (95% confidence interval [CI] 68.6-80.7%) and 47.8% (95% CI 38.9-56.9%) for monoclonal and polyclonal infections. The qPCR prevalence estimates of pfhrp2/3 deletions showed almost perfect (κ = 0.804, 95% CI 0.714-0.895) and substantial agreement (κ = 0.717, 95% CI 0.562-0.872) with cPCR for Peru and 2016 Eritrean samples, respectively. For 2019 Eritrean samples, the prevalence of double pfhrp2/3 deletions was approximately two-fold higher using qPCR. The optimal threshold for matching the assay results was ΔCq = 3. CONCLUSIONS: Multiplex qPCR and cPCR produce comparable estimates of gene deletion prevalence when monoclonal infections dominate; however, qPCR provides higher estimates where multi-clonal infections are common.

SEOM-GEINO clinical guidelines for grade 2 gliomas (2023).

The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis. Though slow-growing and having a low proliferative index, grade 2 gliomas are incurable by surgery and complementary treatments are vital to improving prognosis. This guideline provides recommendations on the multidisciplinary treatment of grade 2 astrocytomas and oligodendrogliomas based on the best evidence available.

The Great Imitator Masquerading as Autoimmune Hepatitis and Demystifying as Fulminant Syphilitic Retinitis.

PURPOSE: Syphilis is a "Great Masquerader" because of its versatile clinical manifestations. We aim to report a patient whose first presentation was with presumed autoimmune hepatitis. Fulminant retinitis subsequently ensued, thus enabling correct diagnosis and treatment. METHODS: Case description. RESULTS: A 62-year-old male presented with bilateral drop in vision. One month earlier, right eye (RE) arteritic ischemic optic neuropathy was suspected because of severe headache, sudden drop in vision, relative afferent pupillary defect, and elevated inflammatory markers. Systemic steroids were instituted. Brain imaging and temporal artery biopsy were unyielding. Four months earlier, liver biopsy performed because of elevated cholestatic liver enzymes, revealed granulomatous hepatitis. After ruling out viral hepatitis, autoimmune etiology was presumed, and prednisone was started. On presentation, visual acuity (VA) was counting fingers in RE and 6/20 in the left eye (LE). Bilateral panuveitis with punctate inner retinitis, placoid chorioretinitis was diagnosed. Serological tests were strongly positive for syphilis. Lumbar puncture confirmed the existence of neurosyphilis. Systemic penicillin was initiated. One month later, VA improved to RE 6/10, LE 6/7.5, with marked resolution of posterior uveitis. No recurrence was observed over 27-month-period. CONCLUSION: Acquired syphilitic hepatitis is rarely reported. Administering steroids potentially aggravated the infection. The characteristic features of placoid chorioretinitis and punctate inner retinitis connected the pieces of the puzzle together to the diagnosis of ocular and neurosyphilis. Intrahepatic cholestasis with negative serological panel of hepatotropic pathogens should raise the suspicion of non-hepatotropic pathogens especially syphilis.