A new suture fixation technique for the Akin osteotomy of the proximal phalanx: You don't need any implant.

BACKGROUND: Various fixation methods have been described for Akin osteotomy, based on using metal implants or transosseous sutures. The aim of this study was to evaluate radiological outcomes and complications of closing wedge Akin osteotomy based on a crossed suture configuration of the joint capsule rather than using implants. The null hypothesis is that a crossed suture has comparable radiological results to other techniques, with no additional complications. METHODS: It's a retrospective study. Patients who underwent Akin osteotomy fixed either with implant or joint capsule suture between 2015 and 2018 were included. Distal articular set angle corrections in pre- and postoperative anteroposterior foot x-rays were calculated by 2 observers. Complications, such as pain, infection, non-union and need of surgery revision, was compared at 1 year follow-up. RESULTS: 89 patients, 30 in the implant group and 59 in the suture group. Mean distal articular set angle corrections were 6.43 (SD 5.54) and 7.36 (SD 5.48) degrees in the implant and suture groups, respectively, without statistically significant differences (p 0454). Complications were 2 local pain and 1 wound infection cases in the suture and implant groups, respectively (p 0138, p 0197). CONCLUSION: Akin osteotomy with suture fixation yields comparable radiological results to metal implant fixation methods without increasing the associated complications.

Effects of Plyometric Training on Running Biomechanics and Jumping Ability of U14 Athletes.

ABSTRACT: Cardiel-Sánchez, S, Rubio-Peirotén, A, Molina-Molina, A, García-Cebadera Gómez, C, Almenar-Arasanz, A, Ráfales-Perucha, A, Roche-Seruendo, LE, and Cartón-Llorente, A. Effects of plyometric training on running biomechanics and jumping ability of U14 athletes. J Strength Cond Res XX(X): 000-000, 2024-Children under the age of 14 years (U14) are particularly susceptible to musculoskeletal disorders because of growth spurts. Plyometric training has been shown to be beneficial for both injury reduction and performance enhancement. The aim of this study was to evaluate the effects of plyometric training on the jumping ability and running biomechanics of U14 track-and-field athletes. A single-blind randomized controlled trial was conducted. Thirty-five (18 female and 17 male) U14 athletes (age: 12.5 ± 1.2 years; height: 152.3 ± 7.7 cm; body mass: 47.3 ± 6.9 kg) were randomized into experimental and control groups. All subjects completed their usual training for 4 weeks, and those in the intervention group added a low-volume plyometric program twice a week. Preintervention and postintervention assessments included a countermovement jump (CMJ) to determine maximum jump height, 10-second repeated jumps to assess reactive strength index (RSI), and a 3-minute run at 12 km·h-1 to analyze running kinematics contact time, flight time, step length (SL), step frequency (SF), mean power output, vertical spring stiffness, and leg spring stiffness (LSS). The results revealed no main effect of time for any of the variables. A group-by-time interaction was found for RSI (p = 0.045) in the intervention group, whereas a significant increase in LSS was also found after the intervention (p = 0.031). However, no changes in CMJ height or other running parameters were observed. The significance level for the study was set at ρ ≤ 0.05. Plyometric-jump training may improve the stretch-shortening cycle in U14 athletes by increasing RSI and LSS. Athletes and coaches in running-related sports should be aware of these short-term effects when aiming to optimize the energy storage and release mechanism.

Integrative workflows for the characterization of hydrophobin and cerato-platanin in the marine fungus Paradendryphiella salina.

Hydrophobins (HFBs) and cerato-platanins (CPs) are surface-active extracellular proteins produced by filamentous fungi. This study identified two HFB genes (pshyd1 and pshyd2) and one CP gene (pscp) in the marine fungus Paradendryphiella salina. The proteins PsCP, PsHYD2, and PsHYD1 had molecular weights of 12.70, 6.62, and 5.98 kDa, respectively, with isoelectric points below 7. PsHYD1 and PsHYD2 showed hydrophobicity (GRAVY score 0.462), while PsCP was hydrophilic (GRAVY score - 0.202). Stability indices indicated in-solution stability. Mass spectrometry identified 2,922 proteins, including CP but not HFB proteins. qPCR revealed differential gene expression influenced by developmental stage and substrate, with pshyd1 consistently expressed. These findings suggest P. salina's adaptation to marine ecosystems with fewer hydrophobin genes than other fungi but capable of producing surface-active proteins from seaweed carbohydrates. These proteins have potential applications in medical biocoatings, food industry foam stabilizers, and environmental bioremediation.

Ehrlichiosis and anaplasmosis in solid organ transplantation: A case series and review of the literature.

Ehrlichiosis and anaplasmosis are rising tickborne infections posing significant risks to solid-organ transplant (SOT) patients. We present three cases highlighting clinical presentations, diagnostic challenges, and the benefits of microbial cell-free DNA (mcfDNA) sequencing. Emphasizing early diagnosis and preventive measures, we advocate for advanced diagnostic modalities to improve outcomes in this vulnerable population.

Acute diarrhea in the hospitalized immunocompromised patient: what is new on diagnostic and treatment?

PURPOSE OF THIS REVIEW: This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. RECENT FINDINGS: Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. SUMMARY: Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.

Tracking EEG network dynamics through transitions between eyes-closed, eyes-open, and task states.

Our study aimed to verify the possibilities of effectively applying chronnectomics methods to reconstruct the dynamic processes of network transition between three types of brain states, namely, eyes-closed rest, eyes-open rest, and a task state. The study involved dense EEG recordings and reconstruction of the source-level time-courses of the signals. Functional connectivity was measured using the phase lag index, and dynamic analyses concerned coupling strength and variability in alpha and beta frequencies. The results showed significant and dynamically specific transitions regarding processes of eyes opening and closing and during the eyes-closed-to-task transition in the alpha band. These observations considered a global dimension, default mode network, and central executive network. The decrease of connectivity strength and variability that accompanied eye-opening was a faster process than the synchronization increase during eye-opening, suggesting that these two transitions exhibit different reorganization times. While referring the obtained results to network studies, it was indicated that the scope of potential similarities and differences between rest and task-related networks depends on whether the resting state was recorded in eyes closed or open condition.

Dengue NS1 antibodies are associated with clearance of viral NS1.

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Molecular epidemiology and antimicrobial resistance in Clostridioides difficile strains isolated from children and adolescents in a tertiary referral pediatric hospital in Fortaleza, Brazil.

BACKGROUND: C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon. Only two pediatric research groups reported the presence of C. difficile infection in Brazilian children, but no previous research has examined C. difficile infection among children in northeastern Brazil. This prospective cross-sectional study investigated the molecular epidemiology and antimicrobial resistance of C. difficile strains isolated from children and adolescents with diarrhea referred to a tertiary pediatric hospital in Brazil while exploring the associated risk factors. RESULTS: Toxin positivity or C. difficile isolation was found in 30.4 % (17/56) samples. C. difficile was isolated from 35 % (6/17) samples. Four toxigenic strains were identified (tpi+, tcdA+, tcdB+, cdtB-, without tcdC deletions) belonging to PCR ribotypes and PFGE-pulsotypes: 046 (new pulsotype 1174), 106 (NAP11), 002 (new pulsotype 1274), 012 (new pulsotype NML-1235). Two of the six isolates belonging to ribotypes 143 and 133 were non-toxigenic. All toxigenic strains were sensitive to metronidazole and vancomycin. Regarding the clinical manifestation, diarrhea lasted an average of 11 days, ranging from 3 to 50 days and was often associated with mucus and/or blood. All six patients from whom the C. difficile was isolated had a chronic disease diagnosis, with these comorbidities as the main risk factors. CONCLUSION: Our study enhances our understanding of the present epidemiological landscape of C. difficile-associated diarrhea (CDI) among children in northeastern Brazil, reveling a substantial CDI frequency of 30.4 %, with toxigenic strains detected in 76.4 % of cases, highlighting a higher prevalence compared to earlier Brazilian studies. In the globalized world, an understanding of disease-generating strains, the associated risk factors, clinical manifestation, and antimicrobial sensitivity has fundamental epidemiological importance and draws attention to preventive measures, allowing for more decisive action.

Continuous measurements of respiratory muscle blood flow and oxygen consumption using noninvasive frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy.

Prior studies of muscle blood flow and muscle-specific oxygen consumption have required invasive injection of dye and magnetic resonance imaging, respectively. Such measures have limited utility for continuous monitoring of the respiratory muscles. Frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy (FD-NIRS & DCS) can provide continuous surrogate measures of blood flow index (BFi) and metabolic rate of oxygen consumption (MRO2). This study aimed to validate sternocleidomastoid FD-NIRS & DCS outcomes against electromyography (EMG) and mouth pressure (Pm) during incremental inspiratory threshold loading (ITL). Six female and six male healthy adults (means ± SD; 30 ± 7 yr, maximum inspiratory pressure 118 ± 61 cmH2O) performed incremental ITL starting at low loads (8 ± 2 cmH2O) followed by 50-g increments every 2 min until task failure. FD-NIRS & DCS continuously measured sternocleidomastoid oxygenated and deoxygenated hemoglobin + myoglobin (oxy/deoxy[Hb + Mb]), tissue saturation of oxygen (StO2), BFi, and MRO2. Ventilatory parameters including inspiratory Pm were also evaluated. Pm increased during incremental ITL (P < 0.05), reaching -47[-74 to -34] cmH2O (median [IQR: 25%-75%]) at task failure. Ventilatory parameters were constant throughout ITL (all P > 0.05). Sternocleidomastoid BFi and MRO2 increased from the start of the ITL (both P < 0.05). Deoxy[Hb + Mb] increased close to task failure, concomitantly with a constant increase in MRO2, and decreased StO2. Sternocleidomastoid deoxy[Hb + Mb], BFi, StO2, and MRO2 obtained during ITL via FD-NIRS & DCS correlated with sternocleidomastoid EMG (all P < 0.05). In healthy adults, FD-NIRS & DCS can provide continuous surrogate measures of respiratory BFi and MRO2. Increasing sternocleidomastoid oxygen consumption near task failure was associated with increased oxygen extraction and reduced tissue saturation.NEW & NOTEWORTHY This study introduces a novel approach, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy (FD-NIRS & DCS), for noninvasive continuous monitoring of respiratory muscle blood flow and metabolic rate of oxygen consumption. Unlike prior methods involving invasive dye injection and magnetic resonance imaging, FD-NIRS & DCS offers the advantage of continuous measurement without the need for invasive procedures. It holds promise for advancing muscle physiology understanding and opens avenues for real-time monitoring of respiratory muscles.

Age-related changes in brain oscillatory patterns during an n-back task in children and adolescents.

The development of brain oscillatory responses and their possible role in the working memory (WM) performance of children, adolescents and young adults was investigated. A set of 0- and 1-back tasks with letter stimuli were administered to a final sample of 131 subjects (between 6 and 20 years of age). A decrease in response times (RTs) and an increase of the sensitivity index d-prime (d') were seen with increased age. RTs increased and d' decreased with load, indicating higher difficulty for higher loads. Event-related synchronization (ERS) and event-related desynchronization (ERD) were obtained by the convolution of Morlet wavelets on the recorded EEG. Statistical analyses were performed of the absolute and relative power of brain oscillations defined by topography, frequency and latency. Posterior alpha and beta ERD, and frontocentral theta ERS, were induced by the stimuli presented during the n-back task. While relative theta ERS increased with age, absolute theta ERS, absolute and relative alpha and, absolute beta ERD, decreased with age. Age-related improvement in behavioral performance was mediated by relative theta. Alpha and beta ERD were more pronounced for the most difficult task (1-back) and for the target condition. Globally, there was high consistency of the effects of target type and task load across development. Theta ERS maturation is a crucial step for improving WM performance during development, while alpha and beta ERD maturation seem to be less critical for behavioral performance improvement with age, possibly due to a sufficient level of alpha-beta ERD for good performance in young children.

Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment.

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

Robust genetic codes enhance protein evolvability.

The standard genetic code defines the rules of translation for nearly every life form on Earth. It also determines the amino acid changes accessible via single-nucleotide mutations, thus influencing protein evolvability-the ability of mutation to bring forth adaptive variation in protein function. One of the most striking features of the standard genetic code is its robustness to mutation, yet it remains an open question whether such robustness facilitates or frustrates protein evolvability. To answer this question, we use data from massively parallel sequence-to-function assays to construct and analyze 6 empirical adaptive landscapes under hundreds of thousands of rewired genetic codes, including those of codon compression schemes relevant to protein engineering and synthetic biology. We find that robust genetic codes tend to enhance protein evolvability by rendering smooth adaptive landscapes with few peaks, which are readily accessible from throughout sequence space. However, the standard genetic code is rarely exceptional in this regard, because many alternative codes render smoother landscapes than the standard code. By constructing low-dimensional visualizations of these landscapes, which each comprise more than 16 million mRNA sequences, we show that such alternative codes radically alter the topological features of the network of high-fitness genotypes. Whereas the genetic codes that optimize evolvability depend to some extent on the detailed relationship between amino acid sequence and protein function, we also uncover general design principles for engineering nonstandard genetic codes for enhanced and diminished evolvability, which may facilitate directed protein evolution experiments and the bio-containment of synthetic organisms, respectively.

Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.

Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus.

BACKGROUND: Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressant-like effects of an NPY1R agonist and Ketamine, targeting their neurobiological interactions within the ventral hippocampus. RESEARCH DESIGN AND METHODS: Utilizing a preclinical model, this study administered Neuropeptide Y receptor 1 (NPY1R) agonist and Ketamine, both separately and in combination, through intracerebroventricular (icv) and intranasal (i.n.) routes. The Forced Swimming Test (FST) was employed to assess antidepressant-like activity, while in situ Proximity Ligation Assay and immunohistochemistry were used to examine NPY1R/TrkB heteroreceptor complexes and BDNF expression in the ventral dentate gyrus (DG), along with neurogenesis markers. RESULTS: The combined treatment significantly reduced immobility in the FST, indicative of enhanced antidepressant-like effects, correlated with increased formation of NPY1R/TrkB complex and brain-derived neurotrophic factor (BDNF) expression in the ventral DG. These molecular alterations were associated with increased neurogenesis. CONCLUSIONS: The coadministration of an NPY1R agonist and Ketamine in a rodent model demonstrated potentiated antidepressant responses through synergistic neurobiological pathways, including TrkB signaling and hippocampal neurogenesis. This indicates a novel therapeutic strategy for MDD, warranting further clinical investigation to fully understand its implications.

Effect of the Photoexcitation Wavelength and Polarization on the Generated Heat by a Nd-Doped Microspinner at the Microscale.

Thermal control at small scales is critical for studying temperature-dependent biological systems and microfluidic processes. Concerning this, optical trapping provides a contactless method to remotely study microsized heating sources. This work introduces a birefringent luminescent microparticle of NaLuF4:Nd3+ as a local heater in a liquid system. When optically trapped with a circularly polarized laser beam, the microparticle rotates and heating is induced through multiphonon relaxation of the Nd3+ ions. The temperature increment in the surrounding medium is investigated, reaching a maximum heating of ≈5 °C within a 30 µm radius around the static particle under 51 mW laser excitation at 790 nm. Surprisingly, this study reveals that the particle's rotation minimally affects the temperature distribution, contrary to the intuitive expectation of liquid stirring. The influence of the microparticle rotation on the reduction of heating transfer is analyzed. Numerical simulations confirm that the thermal distribution remains consistent regardless of spinning. Instead, the orientation-dependence of the luminescence process emerges as a key factor responsible for the reduction in heating. The anisotropy in particle absorption and the lag between the orientation of the particle and the laser polarization angle contribute to this effect. Therefore, caution must be exercised when employing spinning polarization-dependent luminescent particles for microscale thermal analysis using rotation dynamics.

Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development.

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.

Interstitial needles versus intracavitary applicators only for locally advanced cervical cancer: results from real-life dosimetric comparisons.

Background and purpose: Image-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy. Materials and methods: We included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT. Results: Ninety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4). Conclusion: HR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

Enhancing Cognitive Functions and Neuronal Growth through NPY1R Agonist and Ketamine Co-Administration: Evidence for NPY1R-TrkB Heteroreceptor Complexes in Rats.

This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male Sprague-Dawley rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized. The results demonstrated that co-administration significantly enhanced memory consolidation and increased neuronal proliferation, specifically neuroblasts, without affecting quiescent neural progenitors and astrocytes. These effects were mediated by the potential formation of NPY1R-TrkB heteroreceptor complexes, as suggested by receptor co-localization studies, although further investigation is required to conclusively prove this interaction. The findings also highlighted the pivotal role of brain-derived neurotrophic factor (BDNF) in mediating these effects. In conclusion, this study presents a promising avenue for enhancing cognitive functions and neuronal proliferation through the synergistic action of the NPY1R agonist and Ketamine, potentially via NPY1R-TrkB heteroreceptor complex formation, offering new insights into therapeutic strategies for neurodegenerative diseases.

Fatal outcome of a corticosteroid resistant IgG4-related autoimmune hepatitis and IgG4-primary sclerosing cholangitis.

33-year-old woman, previously hospitalized for self-limited migratory bile duct strictures, presented with jaundice three months after giving birth. Blood analysis revealed elevated levels of aspartate aminotransaminase 1064U/L, alanine aminotransaminase 1097U/L, gamma-glutamyl transferase 194U/L, alkaline phosphatase 284U/L, bilirubin 27mg/dL and prothrombin time of 19.3s. Magnetic resonance-cholangiopancreatography revealed intrahepatic bile duct dilation with a stenosis in the common hepatic duct, not detected on endoscopic retrograde cholangiopancreatography. Additionally, diffuse signal abnormalities were observed in the liver parenchyma on T2 sequences. An early liver biopsy showed moderate-severe interface hepatitis with IgG4-positive plasma cell infiltration (IgG4-PPC) of 8-20cells/HPF, hepatocellular ballooning and focal rosette formation, yielding 6 points of the simplified-score for autoimmune hepatitis and treatment with methylprednisolone was initiated. Despite treatment, there was no improvement after two weeks and the patient received rituximab as a rescue treatment, but three days later, developed candida sepsis with rapid progression to multiorgan failure, ultimately resulting in death.