While the necessity of a concept of "self" for understanding human behavior remains subject to debate, it evidently has significance in everyday life: Lay individuals ascribe selves to humans but also to animals and technical systems, shaping their interactions accordingly. The literature suggests that there are distal behavioral cues eliciting this perception of selfhood and they may be as minimal as simple movement observed as causal. We aimed to identify which types of behavioral cues increase selfhood-attribution to other agents such as robots. Specifically, we compared behavior of nonhumanoid robots suggesting either the presence or absence of behavioral cues for one of the characteristics of causality, equifinality, behavioral efficiency, learning sensitivity, and context sensitivity. Results showed a consistent pattern of increased selfhood-attribution toward robots exhibiting any one of the examined minimal characteristics. Furthermore, most perceived sentient characteristics of the robot were triggered by any single characteristic's cue. These results reflect a Halo effect like pattern: Even a single perceived cue of selfhood-related characteristics may be sufficient to trigger a change in overall selfhood-attribution to robots. We suggest two versions of a Brunswikian model of selfhood-judgment, wherein selfhood is attributed based on the perception of (probably loosely defined) self-related characteristics. We propose that not all characteristics are directly perceived by their corresponding behavioral cues; rather, that the characteristics interact with each other and/or distal cues trigger the perception of more than one characteristic. We term this a Pars-Pro-Toto account as people go way beyond the perceived information when attributing selfhood.
Frankenia hirsuta (FH) is an underexplored halophytic plant used for managing inflammatory and metabolic disorders. However, its phytochemical composition and pharmacological mechanisms remain largely uncharacterized. Thus, this study aimed to comprehensively elucidate the phytochemical profile, molecular mechanisms, and pharmacological efficacy of FH using an integrated approach combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolite characterization, in vitro bioassays, in-vivo validation, and computational analyses. Metabolite profiling was performed using LC-MS/MS, followed by molecular docking and network pharmacology analyses to predict potential targets involved in neuropathic, inflammatory, and metabolic pathways. In vitro cytotoxicity and anticoagulant activities of the aerial and root ethanolic extracts were assessed using MTT and activated partial thromboplastin time (aPTT) assays, respectively. The in vivo antidiabetic and neuroprotective effects were evaluated in streptozotocin-induced diabetic mice, using behavioral assays (hot plate and von Frey filaments), biochemical markers of oxidative stress and inflammation, and histopathological and immunohistochemical (IHC) examinations. LC-MS/MS analysis revealed a diverse bioactive constituents, including phenolic acids, flavonoid glycosides, and feruloyl derivatives. Network pharmacology and docking studies highlighted strong binding affinities toward key enzymes such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2, and AKT1, indicating multimodal anti-inflammatory and neuroprotective potential. In vitro, FH extracts exhibited significant cytoprotective effects and prolonged aPTT in a dose-dependent manner, confirming their safety and mild anticoagulant properties. In vivo, FH root extract (75 mg/kg) and its isolated feruloyl glycoside (FG) (5-10 mg/kg) significantly restored nociceptive thresholds, improved glycemic control, normalized oxidative and inflammatory biomarkers, and preserved pancreatic and sciatic nerve histoarchitecture. IHC analyses further demonstrated downregulation of TNF-α and IL-6 and upregulation of IL-10 in treated groups, confirming their anti-inflammatory and regenerative effects. This study provides the first comprehensive evidence that FH exerts potent neuroprotective and antidiabetic effects mediated through antioxidant, anti-inflammatory, and cytokine-modulating pathways. The integrated LC-MS/MS, computational, and experimental validation framework highlights FH and its FG as promising candidates for developing safe, plant-derived therapeutics targeting diabetic neuropathy and related metabolic dysfunctions.
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Single sign-on (SSO), tap-on-tap-off (TOTO) and virtual desktops (VD) are increasingly being used in hospitals to reduce the burden and risks of password management, but we know little about how these systems are used in practice. We aimed to understand whether, and if so, how and why a TOTO and VD solution supported clinical work in an emergency department (ED). Qualitative descriptive design comprising interviews (n = 17) and work observations (~ 7 h) with doctors and nurses in an Australian ED. Data collection and analysis were informed by the unified theory of acceptance and use of technology (UTAUT). Some participants perceived the TOTO-VD system as useful, however, most questioned the value of the system for ED work. Time to login was relatively long for the needs of the ED, which contributed to the system not being used as intended. Workarounds led to users being automatically logged out mid-task, which further contributed to clinicians' negative experience with the system. There appeared to be limited use for, and potentially new risks introduced with a VD solution, where ED clinicians perceived there to be redundant control of access to computers. The ED work context presented barriers to TOTO-VD adoption. The system did not support clinical work in an ED and so was worked around by clinicians. We recommend examining and understanding clinician work, including when and how computers are used and what systems are accessed, prior to implementation of any technological solution. Not applicable.
We report the case of a high-risk patient with candidemia and obstructive uropathy caused by renal fungal balls. Initial management with systemic antifungals and stenting was insufficient. Given the patient's dual antiplatelet therapy, we opted for flexible ureterorenoscopy utilizing a bendable ureteral access sheath with an integrated suction device. This enabled in toto removal of fungal balls and efficient clearance of a concomitant stone using laser lithotripsy. To our knowledge, this is the first report demonstrating in toto removal of renal fungal balls using suction-assisted URS in a high-risk patient, offering a minimally invasive alternative to PNL.
Tonsil stones or tonsilloliths are mineralised concretions in the crypts of palatine tonsils. They are usually small and asymptomatic. Sometimes, they can be recurrent, large in size and produce symptoms like a sense of foreign body in throat, mild pain and heaviness in throat and halitosis. In such cases, a surgical intervention may be required for permanent cure. We came across one such patient with massive tonsillolith which mimicked a peritonsillar abscess initially. Eventually, the large tonsillolith was surgically removed in toto. It measured 5.2 × 2.5 × 2.5 cm which makes it the largest tonsillar stone ever to be successfully removed till date.
Chylous Mesenteric Cyst is an uncommon benign abdominal cyst that can arise anywhere along the mesentery of the gastrointestinal tract, from the duodenum to the rectum. It is often asymptomatic but can rarely present with abdominal discomfort or a palpable abdominal mass. Final diagnosis typically relies on histopathology examination following laparoscopic or open excision. We present a 54 years old male who initially presented with right lower abdominal discomfort and lump. Computed Tomography (CT) demonstrated a large thin walled cystic lesion abutting and displacing the right ureter. Pre-operative ureteric stenting and laparoscopic excision of the cyst was planned. The cyst contained 700 mL of chylous fluid and was excised in toto. Histopathological examination was consistent with chylous mesenteric cyst. The ureteric stent was removed at the end of surgery. The patient was discharged with favorable outcome in second post-operative day. Mesenteric cysts are rare entities and appropriate planning is essential for a favorable outcome. Our case report demonstrates successful management of this rare condition with the use of minimally invasive surgery.
Castleman disease constitutes a rare spectrum of conditions with rheumatologic, hematologic, and oncologic features. Orbital involvement is extremely rare with only several cases involving the lacrimal gland. This report describes Castleman disease in a 15-year-old patient who presented with progressive left eye bulging and intermittent periorbital pain. Neuroimaging demonstrated a well-defined, enhancing, homogeneous left lacrimal gland mass with decreased diffusivity, smooth bone remodeling, and anteromedial globe displacement, and no other systemic findings. The lesion was excised in toto and histopathology revealed features of hyaline vascular-type Castleman disease. This is the first reported case of Castleman disease in a pediatric patient with an isolated lacrimal gland lesion. It emphasizes the importance of considering Castleman disease among other lymphoproliferative diseases in the differential diagnosis for patients presenting with a well-circumscribed, homogeneous orbital mass associated with decreased diffusivity and bone remodeling.
Angiomyxoma is a rare, benign mesenchymal tumor rarely encountered in the infantile hard palate. This case report describes the presentation, diagnostic workup, and successful management of an angiomyxoma in an 11-month-old male infant. An 11-month-old male was presented to the ENT department with a slowly enlarging, asymptomatic palatal swelling first noticed at 9 months of age. Intraoral examination revealed a 2 cm × 2 cm, soft, nontender mass on the anterior hard palate. A contrast-enhanced computed tomography scan identified a well-defined, oval, heterogeneously enhancing cystic lesion (8 mm × 15 mm × 18 mm) with no bony erosion. The patient underwent complete surgical excision under general anesthesia. The lesion was excised in toto via an intraoral approach, revealing a well-encapsulated, gelatinous mass. Histopathological examination confirmed the diagnosis of angiomyxoma, showing spindle cells in a myxoid stroma with numerous thin-walled vessels. The postoperative course was uneventful, and the child resumed feeding normally. At the 6-month follow-up, there was no evidence of recurrence, and both functional and cosmetic outcomes were excellent. This case underscores that angiomyxoma, though rare, should be considered in the differential diagnosis of pediatric palatal masses. A combination of cross-sectional imaging and complete surgical excision is the cornerstone of management, leading to a favorable prognosis with low recurrence risk. RésuméL’angiomyxome est une tumeur mésenchymateuse rare et bénigne, exceptionnellement rencontrée au niveau du palais dur chez le nourrisson. Ce rapport de cas décrit la présentation clinique, le bilan diagnostique et la prise en charge chirurgicale réussie d’un angiomyxome chez un nourrisson de 11 mois de sexe masculin. Le patient a été adressé au service d’oto-rhino-laryngologie pour une tuméfaction palatine d’évolution progressive et asymptomatique, remarquée pour la première fois à l’âge de 9 mois. L’examen endobuccal a mis en évidence une masse de 2 cm × 2 cm, souple et indolore, localisée au niveau du palais dur antérieur. Une tomodensitométrie avec injection de produit de contraste a objectivé une lésion kystique bien limitée, ovalaire, à rehaussement hétérogène (8 mm × 15 mm × 18 mm), sans lyse osseuse associée. Le patient a bénéficié d’une exérèse chirurgicale complète sous anesthésie générale par voie endobuccale, permettant l’ablation en monobloc d’une masse bien encapsulée à contenu gélatineux. L’examen anatomopathologique a confirmé le diagnostic d’angiomyxome, révélant une prolifération de cellules fusiformes au sein d’un stroma myxoïde richement vascularisé par de nombreux vaisseaux à paroi fine. Les suites opératoires ont été simples, avec une reprise rapide de l’alimentation. Au recul de six mois, aucune récidive n’a été constatée, avec d’excellents résultats fonctionnels et esthétiques. Ce cas souligne que l’angiomyxome, bien que rare, doit être intégré dans le diagnostic différentiel des masses palatines pédiatriques. L’association d’une imagerie en coupe et d’une exérèse chirurgicale complète constitue le pilier de la prise en charge, offrant un pronostic favorable avec un faible risque de récidive.
How embryos of different sizes generate reproducible body plans remains a central question in developmental biology. Do larger embryos contain more cells, or preserve conserved organizational principles that ensure robust tissue patterning independent of scale? Here, we address this question through whole-embryo quantitative mapping of cell number, tissue allocation, and spatial organization during early development in Xenopus. Using optimized in-toto 3D imaging, tissue clearing, and deep-learning for nuclei segmentation, we quantified cell numbers and reconstructed the spatial distribution of cells in early embryonic stages. Although X. laevis embryos exhibited substantially larger embryo volumes and higher total cell numbers than X. tropicalis, the proportional allocation of cells among ectoderm, mesoderm, and endoderm remained highly conserved between species. In addition, quantitative analysis of local cellular neighborhoods revealed striking conservation of spatial order, packing geometry, and large-scale tissue architecture despite major differences in embryo size and cellular density. Together, these findings demonstrate that early vertebrate embryos follow shared quantitative design principles in which embryonic scaling occurs without disruption of the underlying cellular blueprint of the body plan. Our study establishes a quantitative framework for comparing embryonic architecture across species and provides evidence that developmental organization is governed by conserved scale-invariant topological principles.
Does the degree of extravillous trophoblast (EVT) invasion influence decidual tissue architecture and immune cell distribution in first-trimester decidua? Areas of pronounced morphological changes have been identified at sites of strong EVT invasion in the decidua basalis-defined as 'remodeling lesions'-and are associated with a substantially reshaped immune cell landscape. During early human placental development, EVTs invade the decidua to facilitate placental attachment and nutrient supply to the fetus. EVT-driven decidual tissue restructuring and vascular adaptation are essential for establishing a functional fetal-maternal interface, to which the decidual microenvironment is thought to contribute substantially. However, the precise impact of the degree of EVT invasion on decidual architecture and immune cell distribution remains poorly understood, underscoring the need to elucidate how varying EVT abundances shape the morphological and cellular landscape of the decidual microenvironment. First-trimester decidual tissue (n = 23, gestational age Weeks 7-9) was analyzed from women undergoing elective terminations of pregnancy between 2011 and 2023. Additionally, hematoxylin and eosin-stained sections from archival specimens (n = 11), obtained from three different sources, were included in the study. Matched first-trimester decidua basalis and decidua parietalis samples from the same donors were analyzed through a comprehensive approach combining spatial transcriptomics, histomorphological characterization, and quantitative image analysis. Decidua sections were (i) categorized according to the degree of invasion, (ii) subjected to spatial transcriptomics, including integration with a previously published single-cell RNA-seq dataset, and (iii) quantitatively assessed on the protein level for selected immune cell populations with immunostaining and semi-automated image analysis. The study was complemented by (iv) an observer-based histological evaluation and (v) comprehensive staining series of consecutive decidua sections. Analyses revealed a characteristic tissue restructuring of the decidua and distinct spatial patterns of immune cell abundance in relation to the degree of EVT invasion. In strongly invaded decidual areas, we identified regions with pronounced morphological changes-defined as 'remodeling lesions'. These remodeling lesions typically displayed compromised tissue integrity, eroded blood vessels, extravasal erythrocytes, fibrin deposits, and a distinct gene expression profile, reflecting coagulation, fibrinolysis, and tissue restructuring. While we observed a decline in local immune cell populations-specifically T cells, macrophages, and decidual natural killer cells-with increasing EVT density, neutrophils were almost exclusively located within or in close proximity to remodeling lesions, indicating a substantially reshaped immune landscape. Spatial transcriptomics data are available in the Gene Expression Omnibus repository under accession number GSE301306. Studies using first-trimester placental tissues from elective terminations are inherently limited by surgical disruption of the intact (in toto) anatomical architecture of the tissue and the unknown pregnancy outcome. Spatial transcriptomics was performed on a limited number of tissue sections, and histological tissue sections represent just a snapshot, highlighting the limitations of such tissue-based analyses. While blood leakage into the stromal tissue compartment has typically been documented for pathological conditions-such as large atherosclerotic plaques and tumors-we report such a scenario under physiological conditions for the early invaded decidua. We propose that strong EVT invasion induces remodeling lesions in the decidua basalis and also shapes the surrounding immune cell landscape. We further suggest that the occurrence of these remodeling lesions contributes to the establishment of a stable yet flexible basal plate and is thus necessary for a reliable connection between mother and placenta/fetus. It can be speculated that inadequate decidual tissue restructuring and vascular adaptation lead to pregnancy pathologies and complications such as placental abruption. G.M. was supported by the Austrian Science Fund (FWF): PAT9611123. M.G. was supported by the Austrian Science Fund (FWF): 10.55776/P35118 and 10.55776/I6907. This project has received funding from the European Union's Horizon Europe research and innovation programme under the Marie Skłodowska-Curie grant agreement No 101169308 (funding supported M.G.). M.G., G.M., and J.F. were supported by the Medical University of Graz through the PhD program MolMed. J.F. and G.M. were supported by the COMET center acib: Next Generation Bioproduction (Project #98.311 and #95.802) is funded by BMIMI, BMWET, SFG, Standortagentur Tirol, Government of Lower Austria and Vienna Business Agency in the framework of COMET-Competence Centers for Excellent Technologies. The COMET-Funding Program is managed by the Austrian Research Promotion Agency FFG. The authors declare that they have no conflicts of interest related to this work.
The RVLM (rostral ventral lateral medulla) region of the brainstem is implicated as a controller of both systemic and cerebral blood flow (CBF). Past studies leave open the question of how the RVLM stabilizes CBF in awake animals. Here, we focus on CBF regulation by the adenergic subpopulation of RVLM neurons (RVLMDβh). Hypoxic challenge increases the variability of the activity of RVLMDβh neurons along with increased CBF. Experimental photoactivation of RVLMDβh neurons leads to rapid vasodilation of pial arterioles across the cortical mantle and increased CBF, which is only then followed by an increase in cortical activity. No significant changes in systemic physiology are observed. Virus tracing establishes disynaptic pathways from the RVLM to neocortex with predominant relays involving the lateral hypothalamus and the zona incerta subthalamic nuclei. Chemogenetic inhibition of those nuclei led to a 70 % reduction in the ability of photoactivated RVLMDβh neurons to induce cortical vasodilation and increase CBF. In toto, these findings reveal a major RVLM subcortical pathway to drive transcortical increases in CBF and represent an adaptive mechanism to inform the cerebral vasculature about environmental shifts in pO2.
Obesity prevalence continues to rise in the United States, with a disproportionate burden falling to West Virginia. To investigate the metabolic effects of region-specific dietary patterns, we developed the West Virginia Obesogenic Diet (WV-OD), a compositionally defined rodent diet based on nutritional analyses of meals consumed by obese individuals in the state. The WV-OD closely mirrors the macronutrient profile of the average American diet while incorporating regional features such as a greater sodium level and significantly less fiber. We compared the metabolic effects of the WV-OD to a matched control diet (WV-CD) and to a widely used high-fat diet (HFD, 60% of calories derived from fat) in male and female C57BL/6J mice. After 19 weeks, WV-OD-fed males exhibited weight gain and adiposity comparable to HFD-fed counterparts, along with glucose intolerance and hepatic triglyceride accumulation confirming the obesogenic and metabolically disruptive properties of the WV-OD. Unlike HFD-fed mice, WV-OD-fed males also displayed elevated circulating cholesterol and cholesterol esters without corresponding increases in hepatic total cholesterol. When compared to the HFD, the WV-OD did not increase uric acid or xanthine oxidoreductase (XOR) content of liver or circulation; however, both males and females on the WV-OD demonstrated trends towards elevated plasma uric acid. Interestingly, while exhibiting a similar caloric intake on either diet, the WV-OD females did not demonstrate significant fat accretion or metabolic dysfunction compared to females subjected to the 60% HFD. In toto, these findings: 1) establish the WV-OD as a regionally-grounded, yet broadly representative tool for modeling diet-induced obesity and metabolic dysfunction, 2) offer a physiologically relevant alternative to extreme-fat dietary models in preclinical research and 3) highlight sex-based differences in response to diet-induced obesity.
The use of programmable nucleases has transformed genome editing and functional genomics. Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) was developed such that targeted genomic lesions [usually DNA double-stranded breaks (DSBs)] could be introduced in vivo with ease and precision. In the presence of homology donors, these lesions facilitate high-efficiency precise genome editing (PGE) via homology-directed repair (HDR) pathways. Because DSBs can lead to genomic instability, however, a large amount of effort has been invested in methodologies (e.g., base editors) that only require nicking the chromosomal DNA on one strand. Indeed, we have demonstrated in human cells that oligodeoxynucleotide (ODN)-mediated PGE using nickase variants of Cas9 can proceed by at least two HDR subpathways termed synthesis-dependent strand annealing (SDSA) and single-stranded DNA incorporation (ssDI). Which pathway is utilized is determined by which chromosomal strand (sense or anti-sense/Watson or Crick) is nicked and by the strandedness (sense or anti-sense/Watson or Crick) of the donor ODN. While the mechanism of mammalian SDSA is moderately well understood, that of ssDI is not. To gain genetic insight into ssDI, we carried out a genome-wide CRISPR knockout screen to identify those genes which, when absent, enable increased ssDI. This screen identified the protein lysine methyl transferase (PKMT) Su(var)3-9, enhancer-of-zeste and trithorax (SET) domain bifurcated histone lysine methyltransferase 1 (SETDB1):activating transcription factor 7-interacting protein (ATF7IP) heterodimer and the downstream human silencing hub (HUSH) complex as strong negative regulators of ssDI. Consistent with their well-known biological effects, the negative regulation of ssDI by SETDB1/ATF7IP and HUSH was specific for transgenic reporters and for a HUSH-regulated single-copy gene, but was not observed at other (non-HUSH regulated) single-copy endogenous loci. In toto, these experiments underscore the profound impact that chromatin modifiers - and by extension, chromatin structure - have on PGE outcomes. Specifically, we have identified SETDB1/ATF7IP and the HUSH complex as major negative regulators of the HDR subpathway, ssDI, when the target is a transgene. These experiments are a proof-of-principle that chromatin can act as a potent barrier to genetic recombination and they strongly support the feasibility of extending similar chromatin modulating strategies to enhance PGE efficiency at endogenous single-copy loci.
Malignant peripheral nerve sheath tumour (MPNST) is a rare, aggressive sarcoma with high mortality. MPNST can develop sporadically, after radiation therapy or in association with neurofibromatosis type 1 (NF1). The treatment is challenging especially if surgical removal is not possible. NF1 is an autosomal-dominant genetic disorder most often caused by a germline pathogenic variant in the NF1 gene and in rare cases a deletion of the NF1 gene. Patients with NF1 have a higher risk of developing several different cancers, of which MPNST is one of the most frequent. MPNST in individuals with NF1 often presents with large MPNST which are often not accessible for surgery. Several studies have shown that patients with NF1-associated MPNST (nfMPNST) have an overall inferior survival than those with sporadic MPNST (sMPNST). Despite this, NF1 status alone may not be a causative factor for poor prognosis, which might rather be due to the incidence of larger tumours, which are more challenging to resect in toto. A systematic research protocol was made using the PRISMA-P model and the review question and inclusion and exclusion criteria were defined using the PICO model. The study characteristics defined by PICO include patients with NF1 as the population of interest. The development of MPNST was considered as the intervention, patients with sMPNST were chosen for comparison and the primary outcome of interest was survival. The literature search was performed on 12 October 2024 and 4,394 studies were eligible for screening, of which 36 studies were included in this study. Meta-analysis of eight studies found NF1 status to be a risk factor for the survival of MPNST. The reported survival rates varied between studies, but the 5-year overall survival (OS) remained poor in general, Awith 15 studies showing a significantly inferior survival for nfMPNST. Only four studies have a worse survival for sMPNST, but none with a significant difference. The findings in this systematic review and meta-analysis of 36 studies indicates that patients with nfMPNST have a worse survival compared to sMPNST.
The Toto Bora trial tested whether a course of azithromycin reduced rates of re-hospitalization or death in the 6 months following hospitalization among Kenyan children. We hypothesized that azithromycin would reduce enteric bacteria and increase carriage of macrolide resistance in the subsequent 3 months. Kenyan children (1-59 months) hospitalized and subsequently discharged for non-traumatic conditions provided fecal samples before and 3 months after randomization to a 5-day course of azithromycin or placebo. Quantitative PCR identified enteropathogens and AMR-conferring genes in fecal samples. Generalized estimating equations assessed the impact of the randomization arm on pathogen and resistance gene detection, accounting for baseline presence and site. Among 1,393 baseline stools, 12.4% had at least one bacterial enteropathogen, 94.7% had at least one macrolide-resistance gene, and 92.6% had at least one beta-lactamase-resistance gene identified. At month 3, children randomized to azithromycin had a 6.1% higher likelihood of carrying a macrolide resistance gene compared to placebo (adjusted prevalence ratio [aPR], 1.06; 95% Cl, 1.04-1.08; PcO.OOl). Specifically, azithromycin randomization was associated with a higher relative prevalence of erm(B) (aPR, 1.09 [95% Cl, 1.04-1.15]; P=0.001), erm(C) (aPR, 1.23 [95% Cl, 1.14-1.31]; P<0.001), msr(A) (aPR, 1.14 [95% Cl, 1.04-1.25]; P=0.007), and msr(D) (aPR, 1.07 [95% Cl, 1.03-1.11]; P=0.001). There was no difference in overall bacterial pathogen prevalence (18.9% vs 17.3%) between randomization arms, but a slightly lower proportion of children had Shigella after randomization in the azithromycin arm (3% vs. 5%, aPR, 0.79 [95% Cl, 0.62, 1.01]; P=0.063). Azithromycin at hospital discharge was associated with higher carriage of macrolide-resistance-conferring genes in the post-discharge period compared with placebo, without significant declines in enteric pathogen carriage other than modest changes to Shigella. The potential benefits and risks of empiric azithromycin need to be considered, as children are increasingly exposed to this broad-spectrum antibiotic.
In the Forensic Collection of the Institute of Forensic Medicine in Belgrade there is an autopsy specimen of a man who underwent total reconstruction of the penis he had previously lost due to war injury, collected in the year 1929 by Professor Milovan Milovanović (1884-1948). The museum exhibit No. 453, labeled as Penis Arteficialis, is a specimen of in toto dissected male pubic region, including the grossly altered male external genitalia - the mechanical injury that completely destroyed the penis was partially overcome by a procedure of total phalloplasty: abdominal skin flap was used to create a bulky phalloid structure, with autologous rib cartilage fragment incorporated in its proximal part to provide sufficient rigidity for sexual intercourse. The procedure left an acquired hypospadia, since its inherent limitation was the inability to reconstruct the urethra through the artificial penis. The unaltered autopsy specimen was analyzed using multi-detector computed tomography and magnetic resonance imaging to reveal the complete anatomy of the pioneering total phalloplasty, while preserving the museum specimen. So, we demonstrated the essential elements of what was a successful reconstructive procedure of the time: the artificial penis with cartilage proximally embedded into the root portion of the erectile tissue, enabling stimulation, arousal, and rigidity, and the unobstructed urethra that opened on the skin below the neophallus. Milovanović sought to preserve this achievement in reconstructive surgery, and today, with imaging, we can directly observe the pioneering surgical approach to total penile reconstruction, appreciating its achievements and limitations in terms of morphology.
To describe the histological findings 7 weeks and 18 months after subretinal implantation of the PRIMA photovoltaic array in eyes with geographic atrophy. Comparative case series SUBJECTS: and controls: Four globes of two deceased study participants from the prospective PRIMAvera study were analyzed. The subretinal implant was removed after horizontal sectioning of the globe. Serial sections were performed and stained with hematoxylin-eosin, Masson trichrome as well as periodic acid Schiff for histopathologic analysis. Selected sections were immunohistochemically stained for CD68, CD163, GFAP, CD31, CK18, ARR3, RPBMS, and TRPM1. Both study and fellow eyes were analyzed. The histopathological analysis focused on the anatomical implant localization, wound healing processes, potential inflammatory reactions adjacent to the implant and at the retinotomy site, the development of retinal gliosis and retinal atrophy as well as a potential encapsulation. Both implants could be removed in toto without obvious retinal trauma. Histologically, the implants were located at the level of the outer plexiform layer, as intended, close to the inner nuclear layer. A tissue layer was identified beneath the implant, consisting of a basement membrane deposit and cellular components. A small rupture of Bruch's membrane was detected (in the globe with an 18 months follow-up) associated with localized subretinal fibrosis. At the implant-retina interface, there was only a minimal tissue response without pseudocapsule formation. Furthermore, no significant inflammatory response was detected. The retina overlying the implant was comparable to the fellow eyes in most areas, with limited focal atrophy of the inner retina 18 months after PRIMA implantation. At the retinotomy site, a full thickness scar was noted with mild atrophic changes in the implant insertion area. The wireless subretinal PRIMA implant demonstrated good biocompatibility with no significant encapsulation or surrounding inflammatory response. At seven weeks and eighteen months after implantation, retina overlying the implant was viable and layered as in control areas. Histopathologic analysis following innovative surgical techniques can provide important information in addition to in vivo findings.
Cavernous hemangioma is the most common benign vascular lesion of the adult orbit, typically located in the intraconal compartment. Extraconal and medial locations are rare. We report the case of a 59-year-old male presenting with a 10-year history of progressive right eye proptosis associated with diminution of vision. Examination revealed abaxial (down and out) proptosis with mild restriction of ocular motility. Magnetic resonance imaging of the orbit showed a well-defined intraconal retrobulbar mass compressing the optic nerve. The lesion was completely excised via an endoscopic transnasal approach under general anesthesia. Intraoperatively, a vascular, encapsulated intraconal mass was identified beneath the medial and inferior rectus muscles and removed in toto. Histopathology confirmed cavernous hemangioma. Postoperatively, proptosis reduced from 26 mm to 22 mm, and final visual acuity improved from hand movements close to the face to 6/18. The suboptimal recovery in vision was due to foveal thinning owing to the compressive effect of the mass over the years. This case highlights the efficacy of the endoscopic transnasal approach in managing medially located intraconal cavernous hemangiomas. This approach provides excellent visualization, minimal morbidity, and superior cosmetic outcomes.
Air pollution is the biggest environmental factor impacting the health of people worldwide contributing significantly to mortality. This study has been conducted to investigate the strategies of air pollution policies suggested by multilateral organisations to mitigate the adverse impact of air pollution on populations' health. This study was a qualitative document analysis of health policies and strategies related to air pollution. For this purpose, READ's 4-step approach (Ready material, Extract findings, Analyse data and Distil findings) was used. This approach entails systematic method for collating documents and extracting information from them. This was done with respect to air pollution and health policy studies at global, national and local levels. After extraction of related documents, the content analysis of the obtained documents was done. Cumulatively 12 documents were considered for analysis. In toto, 810 codes, 27 subcategories and 9 categories were extracted by content analysis. The categories included strategies for emission reduction, strategies for exposure reduction, strategies for education & communication, strategies for high-risk groups, strategies for research, strategies for capacity building, strategies for policymaking, implementation and enforcement, strategies for collaboration and coordination, and strategies for evaluation. Mitigating health impacts of air pollution needs to go beyond emission reduction at the sources of pollution. They could encompass comprehensive and holistic measures addressed to population affected by pollution. Health sector strengthening, policy advocacy by health sector, health sector awareness, policy enforcement and implementation through cross sectoral and geographical collaboration and coordination also needs to be the focus for improving the health of the population.