The mosquito, Aedes aegypti, is the principal vector for several arboviruses. The mosquito midgut is the initial tissue that gets infected with an arbovirus acquired along with a blood meal from a vertebrate host. Blood meal ingestion leads to midgut tissue distention thereby increasing the pore size of the surrounding basal lamina. This allows newly synthesized virions to exit the midgut by traversing the distended basal lamina to infect secondary tissues of the mosquito. We conducted a quantitative label-free proteomic time course analysis with saline meal-fed Ae. aegypti females to identify host factors involved in midgut tissue distention. Around 2000 proteins were detected during each of the seven sampling time points and 164 of those were uniquely expressed. Forty-five of 97 differentially expressed proteins were upregulated during the 96-h time course and most of those were involved in cytoskeleton modulation, metabolic activity, and vesicle/vacuole formation. The F-actin-modulating Ae. aegypti (Aa)-gelsolin was selected for further functional studies. Stable knockout of Aa-gelsolin resulted in a mosquito line, which showed distorted actin filaments in midgut-associated tissues likely due to diminished F-actin processing by gelsolin. Zika virus dissemination from the midgut of these mosquitoes was diminished and delayed. The loss of Aa-gelsolin function was associated with an increased induction of apoptosis in midgut tissue indicating an involvement of Aa-gelsolin in apoptotic signaling in mosquitoes. Here, we used proteomics to discover a novel host factor, Aa-gelsolin, which affects the midgut escape barrier for arboviruses in mosquitoes and apoptotic signaling in the midgut.

Background: Vestibular schwannoma (VS) is a relatively common tumor that arises from the vestibulocochlear nerve (CN VIII) and represents 80% of cerebellopontine angle (CPA) masses. CPA tumors are mostly benign, slow growing with low malignant potential (~1%). VS have rarely been reported, and there is a lack of in-depth discussion on the experience of management of massive acoustic neuromas in ICU. It represents the case in which the patient presented with obstructive hydrocephalus and progressive neurological deficits. The purpose of this case report is to understand the management of post-operative patients with VS with several comorbidities in the ICU.Case: We present a 53 years old woman with a giant VS and obstructive hydrocephalus. An imaging findings revealed a brain tumor in the CPA region and obstructive hydrocephalus. Consequently, she relieved her hydrocephalus with a ventriculoperitoneal shunt (VP shunt). After 1.5 years, her mental condition deteriorated, and her left limb muscle strength gradually decreased. Under a joint consultation with Department of Neurosurgery and Anesthesiology, she underwent tumor removal. Upon discharge, the previously observed neurological deficits, which were reversible had been successfully resolved. The neuroimaging confirmed the complete tumor removal, while the neuropathologic examination revealed a VS.Discussion: If untreated, an acoustic neuroma can grow large enough to cause pressure on the brain stem. The tumor can block the flow of cerebrospinal fluid (CSF) between the brain and the spinal cord, causing a buildup of the fluid in the brain. Because the skull is a closed structure, excess fluid in the brain (hydrocephalus) can press against the brain, causing unsteady movement and lack of coordination (ataxia), headaches and confusion. Patients with brainstem compression had significantly longer mean LOS than patients without. Also, the dissection of the facial nerve from the tumor in order to preserve it can sometimes cause swelling, which can result in weakness or paralysis (complete or partial loss of muscle function). This is usually temporary but can take weeks to months to recover. After the operation, the patient was treated in the ICU, a ventilator was installed,insulin was given to regulate blood sugar and anti-hypertension medication for maintaining blood pressure. During treatment in the ICU, adequate fluids and nutrition are provided. Monitoring is carried out on cardiovascular function, hemodynamics and respiration by monitoring blood pressure, electrocardiogram (ECG), oxygen saturation. The patient was moved to high care unit (HCU) after being treated for 3 days in the ICU.Conclusion: Postoperative therapy is more focused on supportive therapy, including maintaining the airway, regulating blood sugar, blood pressure and providing mechanical ventilation to maintain adequate oxygenation.

Background: Management of presenile cataracts with nystagmus and chronic kidney (CKD) disease is a separate problem in anesthetic procedures. The risk of anesthesia in patients with chronic kidney disease is accumulation of nephrotoxic metabolites, unstable hemodynamic during intraoperative, and fluid overload.Case: A 43-year-old man with a diagnosis of immature presenile cataract with nystagmus and comorbid CKD was planned for phacoemulsification and intraocular lens. The anesthetic technique used was regional anesthesia with peribulbar block. Site injections in the inferotemporal and medial canthus with local anesthetic drugs levobupivacaine 0.5% 5 ml and lidocaine 2% 3 ml.Discussion: Combination of peribulbar block and mild sedation provides effective analgesic and anxiolytic effects. Peribulbar blocks in nystagmus besides sensory blocks can also block motoric function so that the position of the eyeball is in center.Conclusion: The peribulbar blockade anesthetic technique can be considered as an alternative safe anesthetic technique for cataract surgery with nystagmus and CKD.

Limb-Girdle Muscular Dystrophy R1/2A (LGMD R1/2A) is caused by mutations in the CAPN3 gene encoding Calpain 3, a skeletal-muscle specific, Ca2+-dependent protease. Localization of Calpain 3 within the triad suggests it contributes to Ca2+ homeostasis. Through live-cell Ca2+ measurements, muscle mechanics, immunofluorescence, and electron microscopy (EM) in Capn3 deficient (C3KO) and wild-type (WT) mice, we determined whether loss of Calpain 3 altered Store-Operated Calcium Entry (SOCE) activity. Direct Ca2+ influx measurements revealed loss of Capn3 elicits elevated resting SOCE and increased resting cytosolic Ca2+, supported by high incidence of calcium entry units (CEUs) observed by EM. C3KO and WT mice were subjected to a single bout of treadmill running to elicit SOCE. Within 1HR post-treadmill running, C3KO mice exhibited diminished force production in extensor digitorum longus muscles and a greater decay of Ca2+ transients in flexor digitorum brevis muscle fibers during repetitive stimulation. Striking evidence for impaired exercise-induced SOCE activation in C3KO mice included poor colocalization of key SOCE proteins, stromal-interacting molecule 1 (STIM1) and ORAI1, combined with disappearance of CEUs in C3KO muscles. These results demonstrate that Calpain 3 is a key regulator of SOCE in skeletal muscle and identify SOCE dysregulation as a contributing factor to LGMD R1/2A pathology.

Introduction: Surgical treatment including intramedullary K wire fixation is desirable for unstable pediatric both bone fracture to avoid angulation, rotational deformity and refracture ensuring optimal functional outcomes. However, it is debatable to leave free end of K wire exposed or to bury underneath the skin. The aim of the study is to assess the functional outcomes and complications after intramedullary K wire buried under the skin for pediatric both bone fracture. Method: This is a prospective analytical study performed from 15 August 2021 to 15 February 2023. This study included unstable closed diaphyseal forearm facture in children aged between 5 and 13 years treated with intramedullary K wires which were buried inside the skin. Study variables included demographical profiles, fracture pattern, time for surgical intervention, Modified Flynn et al criteria, time to unite the fracture and any associated complications). Results: Mean age of the patient in our study was 8.70±2.17 years. Average time required to unite the fracture was 3.15±0.62 months. Thirty-Four (97.2%) patients had excellent outcomes; one (2.8%) patient had good functional outcomes based on Modified Flynn et al criteria. Nine (25.7%) patients had bursa formation at proximal aspect of ulnar K wire while one patient (2.8%) had superficial infection at olecranon site. Conclusion: Intramedullary K wire for pediatric diaphyseal both bone fractures is excellent surgical technique. Even though controversy exist between exposed K wires and those buried underneath the skin, buried K wires have reasonable advantages and less side effects in terms of infection and overall functional outcomes. Keywords: Both bone; Bury; Forearm fracture; Functional outcomes; Intramedullary K wire

Osteofibrous dysplasia (OFD) is a rare, benign, fibro-osseous lesion that occurs most commonly in the tibia of children. Tibial involvement leads to bowing and predisposes to the development of a fracture which exhibit significantly delayed healing processes, leading to prolonged morbidity. We previously identified gain-of-function mutations in the MET gene as a cause for OFD. In our present study, we test the hypothesis that gain-of-function MET mutations impair bone repair due to reduced osteoblast differentiation. A heterozygous Met exon 15 skipping (MetΔ15-HET) mouse was created to imitate the human OFD mutation. The mutation results in aberrant and dysregulation of MET-related signaling determined by RNA-seq in the murine osteoblasts extracted from the wide-type and genetic mice. Although no gross skeletal defects were identified in the mice, fracture repair was delayed in MetΔ15-HET mice, with decreased bone formation observed 2-week postfracture. Our data are consistent with a novel role for MET-mediated signaling regulating osteogenesis.

This paper examines the evolution of Iranian architectural magazines, focusing on discernible shifts in the involvement and portrayal of women during three distinct periods spanning from 1946 to 2001. From 1946 to 1969, female contributions to the magazines were markedly scarce initially, with depictions limited to non-progressive representations of women in traditional roles and endorsements directed towards the Queen. Along with the modern cultural initiatives of the Pahlavi state in the 1970s, the magazines transitioned from a prior disregard for female figures to occasionally recognising them as equally capable professionals. In contrast to this shift and the gradual growth in the number of educated and professional women before and after the 1979 revolution, the Islamic Republic embarked on a systematic effort to marginalise women and censor their images from public view. Challenging the post-revolutionary moments of limitation and censorship, few charismatic figures succeeded in redefining their roles and images in architectural magazines, especially after the revivals of 1991 and 1998 that were marked by the publication of two ground-breaking magazines. This study, supported by a comprehensive historical review, employs Theo van Leeuwen’s discourse analysis, revealing the intricate interplay of four discursive strategies in shaping women’s representation in Iranian architectural magazines across the three periods. The text underscores the impact of pre- and post-revolutionary societal and political changes. It highlights how the resilience of Iranian women led to an unprecedented redefinition of female professional roles in the 1990s.

The application of metagenomic next-generation sequencing (mNGS) in pathogens detection of cerebrospinal fluid (CSF) is limited because clinical, microbiological, and biological information are not well connected. We analyzed the 428 enrolled patients' clinical features, pathogens diagnostic efficiency of mNGS in CSF, microbial community structure and composition in CSF, and correlation of microbial and clinical biomarkers in CSF. General characteristics were unspecific but helpful in formulating a differential diagnosis. CSF mNGS has a higher detection rate (34.6%) compared to traditional methods (5.4%). mNGS detection rate was higher when the time from onset to CSF collection was ≤20 days, the CSF leukocytes count was >200 × 106/L, the CSF protein concentration was >1.3 g/L, or CSF glucose concentration was ≤2.5 mmol/L in non-postoperative bacterial CNS infections (CNSi). CSF was not strictly a sterile environment, and the potential pathogens may contribute to the dysbiosis of CSF microbiome. Furthermore, clinical biomarkers were significantly relevant to CNS pathogens. Clinical data are helpful in choosing a proper opportunity to obtain an accurate result of mNGS, and can speculate whether the mNGS results are correct or not. Our study is a pioneering study exploring the CSF microbiome in different CNSIs.

The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.