IntroductionMitochondrial disease (MD) is a group of disorders caused by dysfunctional mitochondria, the organelles which play an important role in the production of ATP and exist in every human cell inthe body, except for the red blood cells (1 ). Mitochondrial DNA (mtDNA) is inherited maternally and affects organs dependent on high aerobic metabolism, such as the eye, inner ear, central nervous system, skeletal and cardiac muscle. Mitochondrial diabetes mellitus (MDM), also known internationally as maternally inherited diabetes and deafness (MIDD) syndrome, is a mtDNA mutation disease, with a progressive islet β cell secretory dysfunction (2, 3 ). MIDD is associated with early onset diabetes and sensorineural deafness, but there are various other systemic features, including cardiomyopathy, renal problems, and neuropsychiatric symptoms. It was first reported by J.A. Massen et al. in 1992, who found a large pedigree with mt.3243A>G mutation, suffering from diabetes with the presence of maternal transmission, in conjunction with bilateral hearing loss in most of the carriers (4 ). From then on, there has been growing scientific evidence that a range of other point mutations in mtDNA could contribute to the pathogenesis of MIDD, such as mt-tRNA encoding genes, including MT-TI, MT-TS1, and MT-TK, and mt-proteins encoding genes, incuding MT-ND1, MT-ND4, MT-COX2, and MT-COX3. In addition, deletion and depletion of nucleotides have also been described in patients with MIDD (5 ). These novel mutations, however, are extremely rare compared to the proportion of mt.3243A>G, where there is an A to G substitution at position 3243. MIDD is currently found to be the most common type of monogenic diabetes mellitus, accounting for about 1% of all diabetes mellitus, and the incidence in China is approximately 0.6% (6 ). Because of its low incidence and irrespective of its complex clinical phenotype, MIDD is often misdiagnosed as type 1 or type 2 diabetes. Nonetheless, its treatment is different from the common types of diabetes, and incorrect diagnosis and treatment will accelerate the disease process and the occurrence of complications. Therefore, correct genetic diagnosis and treatment are crucial for patients with MIDD. This study discusses the clinical manifestations and treatment process of a typical patient with MIDD, and summarizes its clinical characteristics through a comprehensive review of the literature, with the scope of improving clinicians’ cognition of the disease and reducing misdiagnosis rate.
Introduction: Dengue virus (DENV) represents a global health concern. Symptomatic infection causes a wide range of clinical manifestations, from mild dengue fever to severe disease, characterized by vascular permeability and bleeding. Previous reports indicated that the exacerbated expression of some cytokines is implicated in the progression of the disease. The aim of this study was to assess IL-6 and IL-10 level kinetics together with the description of clinical parameters, distinguishing two phases within the febrile stage in DENV infected patients. Methods: We conducted a retrospective study on samples from 2016 and 2020 DENV outbreaks in Argentina. Viremic patients were categorized in Phase I and II, based on anti-DENV IgM presence. Cytokine levels, clinical parameters, and type of infection were analyzed. Results: Our analysis included samples from 259 patients in the febrile stage. Of these, 184 patients (71%) were classified into Phase I, while 75 patients (29%) were in Phase II. Ninety-nine patients showed secondary infection (38.2%). Notably, secondary infections exhibited earlier IL-6 and IL-10 elevation than primary infections, suggesting pre-existing immune memory priming the immune response. Thrombocytopenia and elevated AST were associated with Phase II, secondary infection, and hospitalization, and elevated IL-6 and IL-10 correlated with low platelet counts, suggesting their potential as early severity markers. Conclusion: Our findings underscore the pivotal roles played by IL-6 and IL-10 in dengue pathogenesis, with their dynamics varying by type of infection and specific phase within the febrile stage. Further research with broader cytokine panels is warranted to validate these findings.
The expansion of machine learning applications across dif- ferent domains has given rise to a growing interest in tap- ping into the vast reserves of data that are being generated by edge devices. To preserve data privacy, federated learn- ing was developed as a collaboratively decentralized privacy- preserving technology to overcome the challenges of data silos and data sensibility. This technology faces certain lim- itations due to the limited network connectivity of mobile devices and malicious attackers. In addition, data samples across all devices are typically not independent and iden- tically distributed (non-IID), which presents additional chal- lenges to achieving convergence in fewer communication rounds. In this paper, we have simulated attacks, namely Byzantine, label flipping, and noisy data attacks, besides non-IID data. We proposed Robust federated learning against poisoning attacks (RFCaps) to increase safety and accelerate conver- gence. RFCaps incorporates a prediction-based clustering and a gradient quality evaluation method to prevent attack- ers from the aggregation phase by applying multiple filters and also accelerate convergence by using the highest quality gradients. In comparison to MKRUM, COMED, TMean, and FedAvg algorithms, RFCap has high robustness in the pres- ence of attackers and has achieved a higher accuracy of up to 80% on both MNIST and Fashion-MNIST datasets.
We present the first videos depicting the consumption of bats by rusty-spotted genets (Genetta maculata) inside a cave in the Republic of Congo. Following the implementation of a camera-trap monitoring protocol of interactions between cave bats and wildlife, we identified important genet activity in one of the caves in our study. Between 2022 and 2023, we recorded four events of bat or rodent consumption (including two with certainty on bats), one hunting attempt on bats and three feeding behaviors on insects. We detail the various behaviors and discuss the potential implications of genets consuming bats, rodents and insects, and in particular scavenging on dead bats. Finally, we address the potential implications of zoonotic pathogen transmission from bats to humans via genets through the bushmeat trade.
In this paper, BSA surface-imprinted magnetic Fe-Ni bimetallic oxide shell nanorods (m-FeNi@MIPs@PCBMA) were prepared with the assistance of poly(3-[[2-(methacryloyloxy)ethyl]dimethylammonium] propionate (PCBMA) in connection with the surface-imprinting technique. The Fe-Ni bimetallic oxide shell layer nanorods (m-FeNi) with magnetic responsiveness simplified the separation and recovery process of adsorbed materials. The controlled introduction of PCBMA facilitated the reduction of protein non-specific adsorption. At the optimal encapsulation ratio of 1:0.75 (Wm-FeNi@MIPs: WCBMA), m-FeNi@MIPs@PCBMA could adsorb 122.98 ± 5 mg/g of BSA within 80 min, and the value of the imprinting factor (IF) was also increased from 1.68 (m-FeNi@MIPs) to 3.95. In the mixed protein adsorption and real sample separation experiments, m-FeNi@MIPs@PCBMA could selectively separate BSA. Meanwhile, after seven adsorption-desorption experiments, the loss of BSA adsorption by the imprinted nanorods was only 15.9%, which had good reusability. Therefore, m-FeNi@MIPs@PCBMA has a broader application prospect in the field of protein separation and purification.
Background: Ubiquitin and ubiquitin-like (UUL) modifications play pleiotropic functions and are subject to fine regulatory mechanisms frequently altered in cancer. However, the comprehensive impact of UUL modification on breast cancer remains unclear. Methods: Transcriptomic and clinical data of breast cancer were downloaded from TCGA and GEO databases. Molecular subtyping of breast cancer was conducted using the NMF and CIBERSORT algorithms. Prognostic genes were identified via univariate, lasso and multivariate Cox regression analyses. Clinical pathological features, immune cell infiltration, immune therapeutic response and chemotherapy drug sensitivity were compared between groups using the Wilcoxon test. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Results: In breast cancer, 63 UUL modification-related genes were differentially expressed, with 29 up-regulated and 34 down-regulated genes. These genes were used to generate two UUL modification patterns that exhibited significant differences in prognostic features and immune cell infiltration. The UUL modification patterns were associated with 2038 differentially expressed genes that were significantly enriched in nuclear division, chromosome segregation, neuroactive ligand-receptor interaction, cell cycle, and other biological processes. Of these genes, 425 were associated with breast cancer prognosis, which enabled the classification of breast cancer into two clusters with significantly distinct prognoses. We developed a prognostic model, UULscore, which comprised nine genes and showed a significant correlation with partial immune cell infiltration. Furthermore, UULscore demonstrated potential predictive value in breast cancer overall survival prediction, immune therapeutic response, and chemotherapy drug sensitivity. UULscore, stage, radiotherapy, and chemotherapy were identified as independent prognostic factors for breast cancer. Based on these factors, a nomogram model was constructed, which demonstrated exceptional prognostic predictive performance. Conclusion: In conclusion, we identified two UUL modification-derived molecular subtypes in breast cancer, and have successfully constructed a risk scoring model that holds potential value in prognosis, immune infiltration, immune therapeutic response, and chemotherapy sensitivity.
Recent magnetoencephalography (MEG) studies have reported that functional connectivity (FC) and power spectra can be used as neural fingerprints in differentiating individuals. Such studies have mainly used correlations between measurement sessions to distinguish individuals from each other. However, it has remained unclear whether such correlations might reflect a more generalisable principle of individually distinctive brain patterns. Here, we evaluated a machine-learning based approach, termed latent-noise Bayesian reduced rank regression (BRRR) as a means of modelling individual differences in the resting-state MEG data of the Human Connectome Project (HCP), using FC and power spectra as neural features. First, we verified that BRRR could model and reproduce the differences between metrics that correlation-based fingerprinting yields. We trained BRRR models to distinguish individuals based on data from one measurements and used the models to identify subsequent measurement sessions of those same individuals. The best performing BRRR models, using only 20 spatiospectral components, were able to identify subjects across measurement sessions with over 90% accuracy, approaching the highest correlation-based accuracies. Using cross-validation, we then determined whether that BRRR could generalize to unseen subjects, successfully classifying the measurement sessions of novel individuals with over 80% accuracy. The results demonstrate that individual neurofunctional differences can be reliably extracted from MEG data with a low-dimensional predictive model.
Meta-ecosystems are the largest and probably most complex structures investigated in ecol-ogy. Because of their complexity they are often separated into their respective ecosystems and then studied in isolation. This is often done without analysing whether an understanding of the individual ecosystems can lead to a proper understanding of the meta-ecosystem, like-ly because we lack clear guidelines when such a separation is sufficient. We here propose four conceptual models for which a separation appropriately approximates the full dynamics. For each of these models we provide empirical evidence from riparian meta-ecosystems to showcase that the terrestrial or aquatic ecosystem should likely not be studied in isolation. Finally, we provide a new theoretical framework to assess how strongly two ecosystems are linked and discuss how this framework might be applied in future empirical research.
Background: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives. Methods: We conducted a cohort study of Optum’s de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups. Results: Of the 87,130 patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95%CI 0.96–1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95%CI 0.97–1.12). Conclusions: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.
Background: The conjunctiva of the eye is a mucosal surface that is colonized by various bacteria. Following surgeries, trauma, or other underlying conditions the normal flora of these bacteria may cause some eye infections such as conjunctival, corneal infections, or endophthalmitis. Objectives: This study aimed to investigate the bacterial population and antibiotic resistance of the conjunctiva in healthy horses. Study design: Random sampling of ocular samples from 20 horse during the winter (2019). Methods: Swab samples were collected from the eyes of 20 healthy horses of different breeds, ages, and sexes in Tehran province, Iran. The swabs were cultured on blood agar and MacConkey agar and incubated at 37°C for 24-48 hours. The isolated bacteria were characterized using cellular morphology, gram-staining, and biochemical tests. Sensitivity and resistance to 10 different antibiotics were measured using an antibiogram test. Results: Results showed that the bacterial population consisted of various species, with Bacillus cereus being the most frequent. There were no significant differences in the frequency of isolated bacteria between sexes and age groups. There were no significant differences in the sensitivity of bacterial flora of the eyes to Colistin, ceftiofur, florfenicol, amoxicillin, and ampicillin between neither different age groups nor different sexes of the horses (P>0.05). However, sensitivity to enrofloxacin and ciprofloxacin was significantly correlated with the age groups of the horses (P>0.05). Significant difference in sensitivity to trimethoprim-sulfamethoxazole between various sexes of horses was observed. Main limitations: The non-uniformity of the follow-up examination reliance owners or caregiver of the horse for follow-up information and Lack of adequate financial resources to study more horses. Conclusions: The study suggests that the frequency of bacterial flora in horses’ eyes is influenced by housing and management conditions rather than age and sex. Keywords: Microbial flora, Conjunctiva, Eyes, Horse, Mucosal surface.
Accurate and efficient genotyping of microsatellite loci is essential for their application in population genetics and various demographic analysis. Protocols for next generation sequencing of microsatellite loci generate high-throughput and cross-compatible allele scoring characteristics: common issues associated with size separation on conventional capillary-based protocols. As a result, we have developed a novel, ultra-fast, all-in-one software Seq2Sat in C++ to support accurate automated microsatellite genotyping. It directly takes raw reads of microsatellite amplicons and subsequently performs read quality control before inferring genotypes based on depth of read, sequence composition and length. It does not produce any intermediate files, making I/O very efficient. Additionally, we developed a module in Seq2Sat for sex identification based on sex locus amplicons. We further developed a user-friendly website-based platform SatAnalyzer to conduct reads-to-report analyses by calling Seq2Sat to generate genotype tables and interactive genotype graphs for manual editing. SatAnalyzer also allows visualization of read quality and distribution across loci and samples to troubleshoot multiplex optimization and high-quality library preparation. To evaluate its performance, we benchmarked SatAnalyzer against conventional capillary gel electrophoresis and an existing microsatellite genotyping software MEGASAT. Results show that SatAnalyzer can achieve > 0.993 genotyping accuracy and Seq2Sat is ~ 5 times faster than MEGASAT despite many more informative tables and figures generated. Seq2Sat and SatAnalyzer are freely available at github (https://github.com/ecogenomicscanada/Seq2Sat) and dockerhub (https://hub.docker.com/r/rocpengliu/satanalyzer).
Cancer in adolescents and young adults (AYAs) is associated with an increased risk for suicidal ideation (SI). There are no reported pediatric oncology cases describing management of SI during end of life. We present a case of a 14-year-old male with relapsed, high-risk B-cell acute lymphoblastic leukemia (B-ALL) who received a haploidentical stem cell transplant (HSCT) and was acutely suicidal at the end of life. We discuss how to navigate acute suicidality in this patient population, the impact of discordant goals of care amongst family members, and potential preventative strategies for similar cases.
Objective: To develop a novel non-invasive model for CSPH, and investigate whether carvedilol could reduce the risk of decompensation in patients with high-risk CSPH stratified by the novel model. Methods: International multicenter observational study with a median follow-up time of 38 months. Three cohorts were included in study from 6 countries. In this study, a total of 1,304 patients were fulfilled diagnosis of liver cirrhosis. Patients were treated with carvedilol in longitudinal carvedilol-treating cohort. The primary outcome was the development of the first hepatic decompensation . Results: Six studies from the meta-analysis were involved (n=819), and LSM and platelet count (PLT) were identified as independent risk factors of CSPH, with pooled risk ratios of 1.10 (95% confidence interval [CI] 1.06-1.15) and 0.99 (95% CI 0.98-0.99). A novel model was established. In HVPG cohort (n=151), the areas under the receiver operating characteristic curve (AUC) of the novel model, ANTICIPATE model, and Baveno VII criteria for CSPH were 0.91 (95% CI 0.86-0.95), 0.80 (95% CI 0.73-0.87), and 0.83 (95% CI 0.77-0.89). The novel model narrows down the grey zone to 22.5%, significantly lower than 50.3%, using Baveno VII criteria (p<0.001). In follow-up cohort (n=1,102), the cumulative incidences (1.7% vs 2.5% vs 15.8%) of decompensation events were significantly different by using the novel model cutoff values of >0, 0 to -0.68 (medium-risk), and <-0.68 (p<0.001). In the carvedilol-treating cohort, the patients with high-risk CSPH stratified by the novel model (treating cohort, n=51) had significantly lower rates of decompensation than those of NSBBs untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=102 after PSM, all p<0.05). Conclusion: A novel model provides stratification for CSPH and decompensation in patients with liver cirrhosis. Treatment with carvedilol significantly reduces the risk of decompensation among high-risk CSPH patients stratified by the novel model.
Prolonged oseltamivir treatment for severe influenza pneumonia: Requirement of combination therapies. Teluguakula Narasaraju1,2 PhD, Pandareesh M2 PhD, Shivaramu MG3 MD1 Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA2 Center for Research and Innovation, Adichunchanagiri University, BG Nagara, Karnataka, India3 Department of Forensic Medicine, Adichunchanagiri Institute of Medical Sciences, BG Nagara, Karnataka, IndiaCorresponding author: Teluguakula Narasaraju email@example.comA recent article by Gerard Moreno et al. compared the efficacy of a standard oseltamivir (5 doses) versus a prolonged oseltamivir treatment (10 doses) in critically ill influenza patients admitted into intensive care units (ICUs).1 Oseltamivir was administered at 75 mg/dose twice daily, and patients were monitored for death or discharge from the hospital as primary outcomes. Overall, this retrospective multicenter cohort study provides valuable insights and important scientific rationale that patients with severe lower respiratory tract influenza infections require extended antiviral therapy to contain the virus shedding in the deeper lungs. However, this study raises several concerns about the limitations of prolonged oseltamivir therapy in ICU patients.First, although this retrospective study demonstrates the beneficial effects of prolonged oseltamivir treatment, due to the high diversity in influenza virus strains, their persistent mutative ability, and being a most common community-acquired viral pathogen, extreme caution must be taken to avoid unwanted use of extended oseltamivir and prevent the origin of resistant viral strains. Genetic fluctuations of the surface genes of the influenza virus are potent contributors for the origin of resistance via antigenic drift or spontaneous mutations2 and lacking this information is one of the major limitations of this study. Second, prolonged oseltamivir treatment in immunocompromised patients functions as a double-edged sword. It has been reported that immunocompromised patients on chemotherapy, solid organ transplantation, or under corticosteroid therapies take more extended periods for virus clearance.3-4 Although prolonged oseltamivir treatment will likely yield potent antiviral effect, extended oseltamivir therapy induce spontaneous origin of the oseltamivir-resistant mutant (H275Y) strain in immunocompromised patients.5 The origin of H275Y mutants was observed within a week when influenza-infected immunocompromised ferrets were treated with oseltamivir.5 The origin of quick resistance to oseltamivir is truly alarming, as oseltamivir will be the top choice of antiviral drug used in case of a pandemic outbreak, and there is a high chance for quick origin of the resistant viral strains due to extensive use of this drug. Further, it is not clear whether the proposed prolonged oseltamivir treatment strategy can be applied to other approved antiviral drugs, such as zanamivir, peramivir, or baloxavir in ICU-admitted patients.Third, it is critical to explore other choices of treatments to overcome the problem of the origin of resistant viral strains. One such alternative is using a combination of two or more antiviral agents.6-7 Several clinical trials have tested a combination of antiviral agents that target either the same viral protein (ex. neuraminidase, which helps in progeny virus release) or different viral proteins that interfere with different stages of virus infection (viral attachment, replication, or progeny virus release). A combination of antiviral drugs, including oseltamivir plus baloxavir marboxil (inhibitor of cap-dependent endonuclease activity), has shown synergistic effects compared to oseltamivir alone treated patients, but no significant improvements in the clinical outcomes were observed.8 Similarly, a triple combination antiviral therapy that includes oseltamivir, Amantadine (M2 ion channel inhibitor), and ribavirin (inhibitor of the viral polymerase) yielded promising results as oseltamivir and amantadine also exhibited antiviral activity against resistant viral strain in the combination therapy.9 However, although the triple combination drugs are well tolerated in the mechanically ventilated critically ill pandemic H1N1 influenza-infected patients, the clinical signatures were comparable with oseltamivir alone treated patients.10While treating critically ill influenza patients, it is critical to monitor two additional parameters including superinfections11 and host-induced immunopathology12 that could significantly exacerbate pulmonary pathology, thus worsening clinical outcome.From the history of influenza pandemics since 1918, it is known that secondary bacterial superinfections mainly contributed to devastating mortalities during influenza outbreaks.11 The failure in the clinical outcome, despite using antivirals and antibiotics in severe influenza, could be due to a lack of proper diagnosis of resistant viruses and bacterial pathogens involved in superinfections. Hence, efforts must be made to strengthen the screening and diagnostic capacities for early detection and rapid onset of antiviral treatment, together with continuous monitoring of secondary bacterial infections for selective antibiotic treatment, especially in patients admitted into ICUs.
BACKGROUNDAndrogenetic alopecia, often referred to as male pattern baldness, stands as the most prevalent form of alopecia. It is primarily characterized by a progressive reduction in hair diameter, length, and pigmentation.1 This process is driven by the influence of androgens, specifically dihydrotestosterone (DHT), in individuals genetically predisposed to this condition. The manifestation of androgenetic alopecia typically centers on the frontal and vertex regions of the scalp, while interestingly, the occipital area is usually spared from its effects.2 This localized pattern of hair loss can create distinctive patterns, such as receding hairlines and balding crowns, that are recognizable hallmarks of this condition. Beyond its mere physical impact, androgenetic alopecia exerts a profound influence on the psychological and emotional well-being of those affected. Hair is not merely a biological feature; it often carries a significant part of an individual’s identity and self-esteem.3 Consequently, the hair loss experienced in androgenetic alopecia can result in feelings of diminished self-confidence and self-image.CASE REPORTWe report the case of a 35-year-old man without comorbidities. The patient comes to the attention of the dermatologist complaining a progressive hair loss over the past 2 years. The patient reports that, at first, the hair loss was evidenced by the presence of hair on the pillow when he woke up and later, he noticed increased hair loss while showering. He initially attributed the fall to a period of work stress and did not give importance to it. However, progressive thinning in the fronto-parietal and vertex region led him to pay more attention to the problem, until he decided to book a dermatological examination with the intention of undergoing a hair transplant. At the dermatological examination, the patient presented a clinical picture compatible with androgenetic alopecia with involvement of the frontal and vertex region assessable as grade V, according to the Hamilton-Norwood scale4 (Figure 1A). Pull Test was positive and trichoscopy showed miniaturization of hair in androgen-dependent areas and hair reduction per pilo-sebaceous unit. The patient reported that hair loss had a strong impact on quality of life and personal, work, and relationship habits. In relation to the strong functional and esthetic impact of the problem, before deciding to undergo hair transplantation, the dermatologist proposed a conservative therapy: topical minoxidil 5% two times daily, oral finasteride 1 mg daily and topical application of a gel containing three oligopeptides mimicking growth factors, caffeine and taurine, and an iron chelating complex, one time per week. The patient underwent monthly follow-ups, and at 6 months after the start of the therapy, the results were striking: increased thickness of the shaft at the fronto-parietal and vertex levels and increased hair density per pilo-sebaceous unit were observed (Figure 1D). The patient was satisfied by the treatment and decided to postpone the transplantation.DISCUSSIONMale androgenetic alopecia is the most common cause of hair loss and has a strong impact on the quality of life of patients suffering from it. Currently, there are several treatments approved by the US FDA that have proven efficacy such as oral finasteride and topical minoxidil. On the other hand, some pioneering studies have demonstrated the efficacy of drugs such as dutasteride, topical finasteride, and/or oral minoxidil. Good emerging alternatives also include nondrug therapies such as platelet-rich plasma or laser therapy with wavelengths between 630 and 660 nm. In addition, studies on topical androgen receptor antagonists and topical cetirizine have provided promising results5. Recently, very promising data have been reported regarding the topical use of growth factor mimetic oligopeptides6, caffeine7, and taurine8 in individuals with androgenetic alopecia and/or telogen effluvium. Specifically, weekly use of a gel containing three growth factor mimicking oligopeptides, caffeine and taurine, and an iron chelating complex (GFmgel) has been shown to be particularly effective in subjects with androgenetic alopecia when used in combination with anti-hair loss medications such as topical minoxidil and oral finasteride9. In the case described, the patient applied a gel containing three growth factors mimicking oligopeptides, caffeine and taurine, and an iron chelating complex (GFmgel) in combination with dual therapy with minoxidil and finasteride. The patient, who initially expressed the will to undergo hair transplantation, was incredibly satisfied with the result achieved with conservative therapy six months later. Although our patient showed an excellent outcome, further real-world studies are needed to confirm the effectiveness of the combination of drug therapy and topical gel containing oligopeptides mimicking growth factors for the treatment of androgenetic alopecia.Figure 1Clinical presentation at baseline visit (Figure 1A); after 2 months (Figure 1B), after 4 months (Figure 1C) and after 6 months of therapy (Figure 1D).References:Piraccini BM, Alessandrini A. Androgenetic alopecia. G Ital Dermatol Venereol. 2014 Feb;149(1):15-24.Lolli F, Pallotti F, Rossi A et al. Androgenetic alopecia: a review. Endocrine. 2017 Jul;57(1):9-17. doi: 10.1007/s12020-017-1280-y. Epub 2017 Mar 28. PMID: 28349362.Huang CH, Fu Y, Chi CC. Health-Related Quality of Life, Depression, and Self-esteem in Patients With Androgenetic Alopecia: A Systematic Review and Meta-analysis. JAMA Dermatol. 2021 Aug 1;157(8):963-970.Rossi A, Ferranti M, Magri F et al. Clinical and Trichoscopic Graded Live Visual Scale for Androgenetic Alopecia. Dermatol Pract Concept. 2022 Apr 1;12(2):e2022078.Saceda-Corralo D, Domínguez-Santas M, Vañó-Galván S et al. What’s New in Therapy for Male Androgenetic Alopecia? Am J Clin Dermatol. 2023 Jan;24(1):15-24.Shome D, Kapoor R, Surana M et al. Neo® hair growth factor formulation for the treatment of hair loss in Covid-19-induced persistent Telogen Effluvium-A prospective, clinical, single-blind study. J Cosmet Dermatol. 2022 Jan;21(1):16-23. doi: 10.1111/jocd.14626. Epub 2021 Dec 7.Völker JM, Koch N, Becker M et al. Caffeine and Its Pharmacological Benefits in the Management of Androgenetic Alopecia: A Review. Skin Pharmacol Physiol. 2020;33(3):93-109.Kim H, Chang H, Lee DH. Simulative evaluation of taurine against alopecia caused by stress in Caenorhabditis elegans. Adv Exp Med Biol. 2013; 776:267-76.Lazzari, Tiziana & Milani, Massimo. (2019). Efficacy of Autologous Platelet-Rich Plasma alone or in Combination with a Lotion Containing Growth-Factor like Polypeptides and Taurine in the Treatment of Androgenic Alopecia: A Randomized, Prospective, AssessorBlinded Trial. Journal of Clinical & Experimental Dermatology Research.
Aim: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large inter-individual variability was found in its pharmacokinetics, and how to handle a delayed or missed dose of INH remains unclear. This study aimed to develop a population pharmacokinetics (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for non-adherent patients. Methods: A nonlinear mixed-effects modeling was used to analyze the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. A two-compartment model well described the PPK of INH. Results: N-acetyltransferase 2 (NAT2) genotype and body weight were identified as significant factors on INH PK. Monte Carlo simulations determined optimal dosage regimens for patients with different NAT2 genotype and body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. On delaying a INH dose exceed 12 h, only need to take the next single dose normally. Conclusion: PPK modeling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.