Local Reactions Research Articles

Randomized comparative study between ferric carboxymaltose and iron sucrose for correction of anemia in antenatal women

Anemia during pregnancy is a significant global health concern. This study aims to evaluate the efficacy and safety of Ferric Carboxymaltose (FCM) compared to Iron Sucrose (ISC) in treating mild to moderate iron deficiency anemia (IDA) in pregnant women. A randomized prospective control study was conducted with antenatal women suffering from mild to moderate anemia at Sri Dharmasthala Manjunatheshwara College of Medical Sciences and Hospital from December 2018 to November 2019. Participants were randomly assigned to either Group A (FCM) or Group B (ISC). A total of 128 women were randomized, with 64 in each group. The mean increase in hemoglobin was significantly higher in the FCM group (1.34 g/dl) compared to the ISC group (0.98 g/dl) (p < 0.001). FCM required fewer administrations, improving patient compliance. Both treatments were well-tolerated, with minor local reactions observed. FCM offers a more effective, convenient, and well-tolerated treatment option for IDA in pregnancy compared to ISC.

Variants of Surface Charges and Capacitances in Electrocatalysis: Insights from Density-Potential Functional Theory Embedded with an Implicit Chemisorption Model

Prevalent electrolyte effects across a wide range of electrocatalytic reactions underscore the general importance of the local reaction conditions in the electrical double layer (EDL). Compared to traditional EDLs, the electrocatalytic siblings feature partially charged chemisorbates that could blur our long-held views of surface charge densities and differential capacitances—two interrelated quantities shaping the crucial local reaction conditions. Herein, five variants of surface charge density and three variants of differential capacitance in the presence of chemisorbates are defined and compared. A semiclassical model of electrocatalytic EDLs is developed for a quantitative analysis of the differences and interrelationships between these variants of surface charge densities and differential capacitances. It is revealed that the potential- and concentration-dependent net charge on these chemisorbates dramatically changes the surface charge densities and differential capacitances. Specifically, the free surface charge density could decrease as the electrode potential becomes more positive, implying that the . The relationship between the free and total surface charge densities is analyzed with aid of the concept of electrosorption valency. By linking the electrosorption valency with the differential capacitance in the absence of chemisorbates, we explain the potential and concentration dependence of the former. The conceptual analysis presented in this work has important implications for experimental characterization and first-principles-based atomistic simulations of electrocatalysis and EDL effects. Particularly, we disclose a hidden yet potentially crucial disadvantage of widely employed atomistic simulation models that fix the coverage of chemisorbates. Proposing the self-consistent implicit model as an expedient remedy for this disadvantage, this work contributes to more realistic modeling of electrocatalytic EDLs. Published by the American Physical Society 2024

One-strength dose escalation of house dust mite depot product for subcutaneous immunotherapy is safe and tolerable.

Allergen immunotherapy (AIT) aims at modulating the immune response by administration of allergen preparations at regular intervals over several years (1). For subcutaneous AIT (SCIT), the treatment is initiated with a dose escalation phase followed by a maintenance dose administration. Over the last decade, there has been a trend towards shortening dose escalation regimens to increase patient adherence. This open-label, phase II trial aimed to investigate the safety and tolerability of a house dust mites (HDMs) SCIT product when used in a newly designed one-strength dose escalation scheme. Patients, aged 12-65, suffering from HDM-allergic rhinitis/rhinoconjunctivitis ± asthma were included. Patients were randomized to the one-strength (6 injections from the highest strength 3) or the Standard dose escalation regimen (14 injections from strengths 1 to 3) using the HDMs-SCIT product. All adverse events were reported. Tolerability was assessed on the Likert scale. One hundred and forty-three patients were randomized, 79 adults and 64 adolescents. In total, the one-strength regimen caused more adverse drug reactions (ADRs) than the Standard regimen (p = .0457). With both regimens most ADRs were local reactions which occurred more often in the one-strength group (p = .0393). But there was no significant difference in the number of patients affected by systemic or serious ADRs between both regimens. No relevant differences occurred between the two age groups and no other risks were observed for adolescents compared to adults. The safety and tolerability of both regimens can be considered comparable, as most ADRs were local reactions, primarily rated as mild in intensity. Nevertheless, the one-strength regimen caused more ADRs. Reducing the number of injections from 14 to 6 while using only one strength offers the potential to improve patient adherence which further might increase clinical efficacy. Future trials could confirm this hypothesis.

Safety and immunogenicity of freeze-dried human rabies vaccines: A phase 3 clinical trial of Zagreb and Essen regimes

ABSTRACT Recently optimized freeze-dried rabies vaccines (Vero cell) are promising for rabies prevention; however, comparisons of Essen 5-dose and Zagreb 4-dose regimens are needed for clinical applications. This phase III clinical trial aimed to assess the safety and immunogenicity of candidate freeze-dried rabies vaccines developed for human use by Shandong Yeedo Biotechnology (Registration No.: CTR20182016, http://www.chinadrugtrials.org.cn/index.html). In total, 40 participants in stage I and 1797 subjects in stage II with an age range of 10–60 years were recruited. Both 4-dose and 5-dose experimental vaccines were well-tolerated in stage 1, with similar overall adverse event (AE) rates. In stage 2, systemic fever (35.39%) and local pain (48.91%) were common, and the rate of Grade 3 AEs was approximately 2.5%. Rates of local reactions and unsolicited AEs differed among groups (p = .045 and 0.011). Immunogenicity analyses showed higher antibody levels, seroconversion rates, and pre-immune seroconversion rates in the 4-dose experimental group versus the 5-dose group (p < .001) on day 7 post-first dose, with similar GMCs (geometric mean concentrations) by day 14. Pre-immune negative subjects had comparable antibody levels in the 4-dose and 5-dose experimental groups, outperforming the 5-dose control group (p = .039). The rate difference (95% CI) for first-dose seroconversion at 14 days post-vaccination among pre-immune antibody-negative subjects indicated non-inferiority between the 5-dose experimental and control groups. Overall, the Shandong Yeedo rabies vaccine demonstrated satisfactory safety and efficacy, offering a new option for rabies prevention.

Methods for Selective Gene Expression Profiling in Single Tertiary Lymphoid Structure Using Laser Capture Microdissection.

Tertiary lymphoid structures (TLS) are de novo lymphoid formations that are induced within tissues during inflammatory episodes. TLS have been reported at various anatomic sites and in many different contexts like cancer, infections, autoimmunity, graft rejection, and idiopathic diseases. These inducible, ectopic, and transient lymphoid structures exhibit the prototypical architecture found within secondary lymphoid organs (SLO) and have been increasingly recognized as a major driver of local adaptive immune reaction. As TLS emerge within tissues, the isolation in situ and the molecular characterization of these structures are challenging to perform. Laser capture microdissection (LCM) is a powerful tool to isolate selective structural components and cells from frozen or paraffin-embedded tissues. We and other groups previously applied LCM to decipher the molecular network within TLS and uncover their intrinsic connection with the local microenvironment. In this chapter, we describe a detailed LCM method for selecting and isolating TLS in situ to perform comprehensive downstream molecular analyses.

Settler-colonialism in the Late Neocolonial Period

This essay discusses settler-colonialism in Palestine and the world system during late neocolonialism. It offers a materialist methodology for interpreting settler-colonial social formations, showing the linkage between settler-colonialism, class, imperialism, and world accumulation. It then considers how race continues to structure local reactions and condition local and international attempts at transformation. It concludes with some reflections on contemporary orientations to Palestine in the periphery, especially within racialized social formations.

CTIM-04. MODULATION OF THE INTRATUMORAL IMMUNE MICROENVIRONMENT BY LOCAL THERAPY WITH NATURAL KILLER CELLS ENGINEERED WITH A HER2-TARGETED CHIMERIC ANTIGEN RECEPTOR IN COMBINATION WITH SYSTEMIC ANTI-PD-1 CHECKPOINT INHIBITION IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract Glioblastoma (GB) is characterized by a marked immunosuppressive tumor microenvironment. In the multicenter CAR2BRAIN phase I first-in-human clinical trial, we investigated the modulation of the tumor microenvironment by repetitive local injection of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2 alone and in combination with systemic anti-PD-1 checkpoint inhibitor therapy in patients with recurrent HER2-positive GB. 6 patients were treated with repetitive doses of CAR-NK cells as monotherapy and 12 patients received a combination therapy with the anti-PD-1 checkpoint inhibitor ezabenlimab. In three of those, we were able to implement a biopsy-treat-resect-treat strategy. After initial biopsy, combination treatment was initiated before planned tumor resection, enabling analysis of the transformation of the tumor immune microenvironment by highplex multispectral fluorescent analyses and cytokine quantification. None of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Profound alterations of the immune cell distribution in the cerebrospinal fluid (CSF) and in the tumor were observed. In CSF sampled from the resection cavity, combination immunotherapy induced a local immune response with elevated pro-inflammatory cytokines and cell counts. In post-treatment tissue samples, we observed an increase of CD4+ and CD8+ T cells, and a decrease of regulatory CD4+FoxP3+ T cells. The three patients treated following the biopsy-treat-resect-treat strategy achieved a median progression-free survival (PFS) of 24 weeks, compared to 10 weeks for patients with upfront resection. Local immunotherapy with HER2-targeted CAR-NK cells is feasible and safe both as monotherapy and in combination with the systemic checkpoint inhibitor ezabenlimab and induces local immune reactions in CSF and tumor tissue. Given the signal for possible clinical benefit provided by the increase in PFS in the patients of the biopsy-treat-resect-treat cohort, further trials are warranted.

Natural History and Risk Factors of Hymenoptera Venom Allergy in Dogs.

Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSRs) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera and presented to the Vetsuisse Faculty Animal Hospital of the University of Zurich between 2018 and 2022. Dogs under two years old, dogs that weighed under 10 kg, purebred dogs, and dogs that were stung in the oral cavity were at a greater risk of developing SSRs. Almost two thirds of patients with SSRs experienced the same or worse symptoms after subsequent stings and >40% of patients with local reactions developed SSRs when stung again. Next to providing valuable clinical information about HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA.

Prebiotic and panthenol-containing dermocosmetic improves tolerance from artificial daylight photodynamic therapy: A randomized controlled trial in patients with actinic keratosis

Introduction & ObjectivesTreatment with daylight photodynamic therapy (dPDT) of actinic keratosis (AK) is associated with local skin reactions (LSR), which may affect patients’ quality of life and treatment acceptability. This study explores the potential of a prebiotic and panthenol-containing Dermocosmetic Cream (DC) to enhance tolerance and mitigate post-dPDT induced LSR in the treatment of AKs. Materials & MethodsThis randomized controlled, intra-individual trial included 20 patients with ≥10 AKs in two symmetrical areas on their face or décolleté, treated with a single session of artificial dPDT. After treatment, the two areas were randomized to DC twice daily for 14 days or No-DC. Primary outcomes included clinical signs of LSR graded from 0=none to 3=severe, calculated as a composite score, and assessed on Days 2, 7, 14, and 30 post-treatment, along with AK clearance rate. Secondary outcomes encompassed objectively measured erythema, and clinical and objective skin photoaging assessment. ResultsTopical application of DC following dPDT significantly improved post-treatment tolerance up to two weeks. By Day 2, DC-treated skin had milder LSR (median 3.0, IQR 2.0-4.8) compared to No-DC skin (median 4.0, IQR 3.0-5.0; p=0.011). This improvement continued on Day 7 (DC median 3.0, IQR 2.0-3.8 vs. No-DC median 4.5, IQR 3.0-5.8; p<0.001) and Day 14 (DC median 1.0, IQR 0.0-1.0 vs. No-DC median 1.0, IQR 1.0-2.0; p=0.004). Objective measurements showed milder erythema in DC-treated areas on Day 2 (p=0.045) and Day 7 (p=0.005). Crusting resolved more effectively in DC-treated areas by Day 7 (40% vs. 20%; p=0.039). No significant difference in complete lesion response rate was observed between DC and No-DC skin (p=0.850). By Day 30, clinical photoaging assessment demonstrated significant improvement in dyspigmentation (p=0.004) and skin texture (p<0.001) in both locations. Moreover, objective measurements revealed reduced dyspigmentation in both DC and No-DC treated skin (p≤0.001). ConclusionApplication of a prebiotic and panthenol-containing multipurpose DC significantly enhanced tolerance from artificial dPDT and accelerated healing time up to 14 days after treatment. The use of DC cream did not affect the overall treatment efficacy of dPDT, indicating its potential to enhance patient comfort following dPDT.

User practices in dealing with trouble in interactions with virtual assistants in German: Repeating, altering and insisting

Moments of trouble and miscommunication occur regularly when users interact with virtual assistants like smart speakers. To add to the understanding of how users treat moments of trouble in everyday interactions with a virtual assistant (VA) in German, this paper reports on a conversation analytic study of practices that users deploy after a request to a VA has failed. The repair sequences that we analyse show users orienting to different trouble sources and employing a range of practices to resolve trouble, including repeating, altering their formulations and formulating related (new) requests. Most often, troubles are resolved after one instance of repair. Other repair sequences include several instances of repair and show more complex and diverse practices being employed. In some of these sequences, users ‘insist’ on their initial goal and/or strategy and do not always observably orient to the VA’s local reactions. In these cases, the interactional history with the VA and previously successful requests seem to play a role as well in the users’ local conduct.

In vivo revascularization and tissue effects of uterine artery embolization with starch microspheres in sheep.

In uterine artery embolization (UAE) for the treatment of fibroids, nondegradable particles permanently occlude the uterine artery (UA). These particles remain in the vessels and can cause secondary undesirable effects, such as severe pain after embolization and fertility issues. In this prospective experimental study, we aimed to evaluate the angiographic recanalization, local and systemic reactions, and uterine damage occurring after performing UAE with newly developed degradable starch microspheres (DSMs) in sheep. Under general anesthesia, eight nonpregnant sheep underwent bilateral UAE using DSMs to achieve stasis. Angiographic evaluation was performed on days 1, 3 and 7 after embolization to assess in vivo recanalization. In addition, the angiographic series were scored via a modified embolization score. A postmortem tissue examination was performed to determine whether DSMs and foreign body inflammatory reactions were present and to assess uterine necrosis. Complete bilateral embolization of the UA and cervicovaginal branches was achieved in all treated animals. Recanalization of the occluded arteries was evident in 25 of 27 arteries during the angiographic evaluation. In all sheep, there were multifocal areas of uterine necrosis, and some uterine vessels contained intraluminal material consistent with DSMs. The average weight of both uterine horns was significantly correlated with both the number of microspheres needed for complete embolization (r = 0.69, ρ<0.01) and the average percentage of necrosis in both uterine horns (r = 0.64, ρ<0.05). Our findings demonstrated the efficacy of vascular embolization with DSM by inducing ischemic changes in the uterus and subsequent recanalization of previously occluded arteries.

Effective Treatment of Basal Cell Carcinoma with a Topical Enzymatic Mixture Enriched in Bromelain: Summary of Proof-Of Concept Clinical Studies on the First 22 Tumors.

Background/Objectives: Basal cell carcinoma (BCC), the most prevalent form of human cancer, is traditionally treated by surgical and alternative destructive or topical chemical means, each with its advantages, challenges, and drawbacks. We describe our experience treating BCCs with a topical concentrate of proteolytic enzymes enriched in bromelain (CPEEB) sourced from pineapple stems. CPEEB has strong proteolytic, antitumor-proapoptotic, and inflammation modulation activities, and is approved for debridement of deep burns and starting phase 3 trials for chronic wounds. Methods: In the first proof-of-concept (POC) study, six BCCs on three individuals were treated with five to six daily CPEEB 10% topical applications under a zinc oxide-based occlusive dressing for 9-12 h each during a period of up to 10 days. These patients were followed for up to 4 years. In an additional two POC studies, 16 patients with one BCC each were treated every other day for a total of seven applications of topical CPEEB 5% under a variety of occlusive dressings. The wounds were followed for up to 2 months before undergoing diagnostic excisional biopsy. Results: In the first study, clinical assessment of the BCCs and two excisional biopsies after 6 months suggested that all lesions were eradicated with spontaneous healing within ~2 weeks without clinical or histological recurrence for over 4 years. In the two subsequent studies, 16 histologically diagnosed superficial and nodular BCCs were treated using four application techniques. Excisional histology after 2 months confirmed BCC eradication in seven of the patients. In nine patients, with compromised occlusive dressings, histological eradication was incomplete. Treatment was well tolerated by all patients with the expected local skin reactions, which completely healed within 2-3 weeks. Conclusions: These are POC preliminary studies aimed at indicating the potential efficacy and feasibility of topical CPEEB in eradicating BCC. In these studies, topical CPEEB 10% and 5% resulted in complete eradication of the BCC when appropriately applied. CPEEB was well tolerated in all patients, and all treated sites' erosions healed without scars in <3 weeks. Further research is necessary to corroborate the results, refine the application technique, and complete the regulatory process.

The SQ tree sublingual immunotherapy tablet is effective and well tolerated in children-A pivotal phase III trial.

Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT-tablet in a paediatric population (5-17 years) with moderate-to-severe AR/C induced by pollen from birch and trees in the birch homologous group. Nine hundred and fifty-two subjects were randomized (1:1) to daily treatment with SQ tree SLIT-tablet or placebo for up to 52 weeks and had free access to AR/C symptom-relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS). SQ tree SLIT-tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment-related adverse events were mild or moderate local administration site reactions. This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT-tablet in tree pollen-induced AR/C in a paediatric population (5-17 years).

The Structural Diversity of Encapsulin Protein Shells.

Subcellular compartmentalization is a universal feature of all cells. Spatially distinct compartments, be they lipid- or protein-based, enable cells to optimize local reaction environments, store nutrients, and sequester toxic processes. Prokaryotes generally lack intracellular membrane systems and usually rely on protein-based compartments and organelles to regulate and optimize their metabolism. Encapsulins are one of the most diverse and widespread classes of prokaryotic protein compartments. They self-assemble into icosahedral protein shells and are able to specifically internalize dedicated cargo enzymes. This review discusses the structural diversity of encapsulin protein shells, focusing on shell assembly, symmetry, and dynamics. The properties and functions of pores found within encapsulin shells will also be discussed. In addition, fusion and insertion domains embedded within encapsulin shell protomers will be highlighted. Finally, future research directions for basic encapsulin biology, with a focus on the structural understand of encapsulins, are briefly outlined.

Comparative evaluation of chlorhexidine gluconate with alcohol and polyhexamethylene biguanide with Tris-EDTA as antiseptic solutions for pre-operative skin preparation in dogs

Background and Aim: Skin antisepsis plays a crucial role in pre-operative skin preparation, with chlorhexidine gluconate and alcohol being historically the preferred choice. However, concerns have risen regarding the development of bacterial resistance to chlorhexidine. Polyhexamethylene biguanide (PHMB) combined with Tris-ethylenediaminetetraacetic acid (Tris-EDTA) has recently emerged as a skin and wound antiseptic. This study aimed to compare the antibacterial efficacy and local safety of 2% chlorhexidine gluconate with 70% alcohol (CG+Alc) and 0.3% PHMB with 6% Tris and 1.86% EDTA (PHMB+Tris-EDTA) for pre-operative skin preparation in dogs. Materials and Methods: Twenty-four adult dogs underwent aseptic preparation on both sides of their ventral abdomens, with one side receiving CG+Alc and the other side receiving PHMB+Tris-EDTA, assigned randomly. Skin swab samples were collected pre-antisepsis and at 3-, 10-, and 60-min post-antisepsis to quantify bacterial colony-forming units (CFUs). Local skin reactions (erythema and edema) were evaluated after hair clipping, pre-antisepsis, and at 3-, 10-, 30-, and 60-min post-antisepsis. Results: There was no significant difference in bacterial CFU counts between the two antiseptic groups pre-antiseptic. Both solutions significantly reduced CFU counts (p &lt; 0.05) at all post-antisepsis sampling times compared with pre-antisepsis. However, dogs treated with PHMB+Tris-EDTA showed a significantly higher incidence of edema at 10 min (p = 0.02) and 30 min (p = 0.003) and a higher incidence of erythema at 10 min (p = 0.043) post-antisepsis compared with CG+Alc. No skin reactions were observed in either group at 60 min post-antisepsis. Conclusion: CG+Alc and PHMB+Tris-EDTA reduced bacterial counts in pre-operative skin preparation in dogs. However, acute transient skin reactions were observed more frequently following the application of PHMB+Tris-EDTA. Keywords: alcohol, antisepsis, chlorhexidine gluconate, dogs, polyhexamethylene biguanide, skin preparation, tris-ethylenediaminetetraacetic acid.

Safety of immunotherapy with Alternaria alternata glutaraldehyde-polymerized allergen extract in adults and children.

Allergies to fungi, such as Alternaria alternata, are significant contributors to respiratory conditions like asthma and rhinitis. Immunotherapy with native A. alternata extracts often results in high rates of adverse reactions. This study evaluates the safety of immunotherapy using glutaraldehyde-polymerized A. alternata extracts in both pediatric and adult populations. This observational real-world study involved 738 patients (435 children and 303 adults) monosensitized to A. alternata or polysensitized together to other allergens. Patients received personalized immunotherapy containing polymerized A. alternata extract, either alone or in combination with other polymerized allergens. The concentration of each polymerized allergen in the therapeutic vaccine was 10,000 TU/mL. Side reactions were classified and recorded based on immediate and delayed onset, and their severity was graded according to the EAACI guidelines. All side reactions were expected and related to the intrinsic properties of allergens. The number of injections administered was 7392, with 4137 to children and 3255 to adults. Thirteen relevant local reactions (0.24% in children, 0.09% in adults) and seven systemic reactions (0.09% overall) were observed. Systemic reactions included mild to moderate symptoms, such as mild bronchospasm and rhinitis. Severe reactions were not reported. Immunotherapy with glutaraldehyde-polymerized A. alternata, alone or in combination with other polymerized allergens, is safe and well-tolerated in both children and adults. The polymerized extracts allow for higher concentrations and faster administration schedules, providing an effective treatment option for patients with fungal allergies, including those polysensitized to multiple allergens.

Paradoxical exacerbation of sclerouveitis following Rituximab infusion.

To report on an unexpected side effect of Rituximab (RTX), a B-cell targeting monoclonal agent, in a patient with severe sclerouveitis, leading to severe visual loss. Observational case report. A 61-year-old female was treated with RTX for a severe sclerouveitis occurring with granulomatosis with polyangiitis. Initially it responded partly to high dose of oral corticosteroids, however, her sclerouveitis recurred after two months during tapering below 20mg daily. The days following the RTX infusions, aggravation of the intraocular inflammation was seen, endangering visual acuity. No evidence for an infection or other cause were found. High doses of oral corticosteroids were started within one week, where after the ocular inflammation resolved. For persisting hypotony and chorioretinal detachment a combined pars plana vitrectomy with phacoemulsification and silicone oil tamponade was performed. The retina remained attached under oil tamponade with partial improvement of the BCVA to finger counting. Ophthalmologist should be aware of the possibility of this paradoxical local reaction to RTX infusion, particularly in bilateral and/or severe cases, which carry a risk of a poor outcome.

The Local's Reactions to Tourists Escaping to Nature After COVID-19: An Assessment on Bungalow Accommodation

This study is aimed to determine the reactions of the public towards Bungalows, which have reached significant numbers in the district as a type of accommodation preferred by tourists to escape to nature after the pandemic, and the tourists staying here. Quantitative research methods were used in the study. A questionnaire was preferred as a data collection tool. Convenience sampling technique was preferred for sampling and during the data collection process, 443 surveys were collected in Sapanca. The study findings reveal that local people support the escaping to nature behavior of tourists, which increased after the pandemic, in terms of their economic contributions, but criticize them for their environmental impacts. The environmental concerns of the locals who do not want more bungalow investments in their regions are greater than their economic gains. While the study measures the reactions of the local people regarding the increasing bungalow-type accommodation, it fills a gap in the literature by supporting the views that there may be reactions at routine times to the developments caused by COVID-19 in tourism.

Observational Study with a New Portable Cryosurgery Device, HYDROZID®, in Superficial Epidermal Lesions: An Indian Experience

Abstract Background: Cryosurgery remains an important treatment modality in dermatology practice. HYDROZID®, a new portable cryosurgery medical device using norflurane as a cryogen, was recently introduced in the Indian market. This paper reports the findings of the phase IV study conducted in India. Aims: This is a prospective phase IV study to evaluate its safety and efficacy in the treatment of superficial epidermal and dermal lesions. Methods: The study was conducted across 4 centres in India. The cryosurgery cycles were decided based on the skin lesion considered for the treatment. Safety and efficacy parameters were assessed at day 1, day 7, day 14, day 30 (±2) (end of treatment), and day 60 (±2) after the initial cryosurgery treatment. The local skin reactions scale, pain VAS scale, and Vancouver scale for assessment of pigmentation and scarring were used for the assessment of cutaneous reactions. Assessment of efficacy was done by evaluating the total disappearance of skin lesions at the end of the study visit. Results: Ninety-seven patients completed the study. The reported post-procedural pain was mild to moderate and subsided over the period of 24 hours. There was no pain observed in 84.76% of patients at the end of 24 hours. Complete disappearance of the lesion was seen in 47.4% of patients at the end of the study, while the reduction in the diameter of skin lesions by more than 50% was observed in 79.38% of patients. Conclusion: The data from this study support good clinical tolerability and safety of the Hydrozid® portable cryo device.

Safety and efficacy of placental mesenchymal stromal cells-derived extracellular vesicles in knee osteoarthritis: a randomized, triple-blind, placebo-controlled clinical trial

BackgroundKnee osteoarthritis causes pain and disability in many people worldwide, for which no definitive treatment has yet been proposed. In this study, we investigated the safety and efficacy of placental mesenchymal stromal cells-derived extracellular vesicles in patients with knee osteoarthritis.MethodsThis triple-blind, randomized clinical trial included patients suffering from bilateral knee osteoarthritis with grade 2 or 3. The knees of each patient were randomized to intervention and control. For the intervention knee, 5 cc of placental mesenchymal stromal cells-derived extracellular vesicles were injected, and for the control knee, 5 cc of normal saline was injected. The patients’ symptoms were evaluated before the intervention and 2 and 6 months after the intervention using VAS, WOMAC questionnaire, and Lequesne index. MRI was performed before the intervention and 6 months after the intervention to evaluate retropatellar and tibiofemoral cartilage volume, medial and lateral meniscal disintegrity, ACL injury, and effusion-synovitis.Results62 knees (31 patients) were enrolled in this study. There were 31 knees as intervention and 31 knees as control. Finally, the data of 58 knees (29 patients) were analyzed, including 28 women and 1 man. The mean age of the patients was 55.38 ± 6.07 years. No statistically significant difference was detected between the two groups in clinical outcomes (including VAS, WOMAC, and Lequesne scores) before treatment and 2 and 6 months after treatment. Also, no statistically significant difference was detected between the two groups in MRI findings before treatment and 6 months after treatment. No systemic complications or severe local reactions occurred in the patients.ConclusionA single intra-articular injection of placental mesenchymal stromal cells-derived extracellular vesicles (5 cc, 7 × 109 particles/cc) is safe, but does not improve clinical symptoms or MRI findings in knee osteoarthritis beyond placebo. The protocol of this study was approved on 11 May 2022 with registration number IRCT20210423051054N1.