The effect of phenylephrine hydrochloride 2.5 % and sodium hyaluronate solution on visual functions and accommodation in children with myopia and its local tolerability

Purpose: to evaluate visual functions, accommodation, and local tolerance in children instilled with Phenylephrine hydrochloride 2.5 % and sodium hyaluronate solution (Stelphrin Supra). Material and methods. 30 children (60 eyes) aged 8 to 12 (ave. 10.04 ± 0.24) with low (28 eyes) and moderate (32 eyes) myopia (ave. -2.96 ± 0.17 D) were tested. Refractometry, subjective and objective accommodation, optical biometry, anterior corneal surface examination, Norn test, and polling were performed prior to one-time instillation, 30 minutes after it, and after 1 month of daily bedtime instillations of Stelphrin Supra. Results. We noted a significant decrease in the tone of accommodation in the open field by 90 % from the initial value, an approximation of the nearest point of clear vision by 27 %, an increase in the volume of absolute accommodation by 57 % and the objective amplitude of accommodation by 20 %, which indicates an increase in the accommodation ability. The pupil width increased 30 minutes after a single instillation of Stelphrin Supra, which coincided with an increase in the relative accommodation reserve by 25 % from the initial one. After a month, the pupil width significantly decreased, and the positive relative accommodation reserve decreased to a level only 12 % higher than the original one. Tear film break time significantly increased by 0.89 sec, singular spot stainings disappeared in 2 out of 6 patients, lacrimation — in 6 out of 10, pain — in 1 out of 2, blurring in 4 out of 6, feeling of “sand” — in 7 out of 9 patients who had these symptoms before instillations. Conclusion. Regular instillations of Stelphrin Supra reduce the habitual tone of accommodation, increase the accommodation ability, and improve the condition of the eye surface.

Clinical evaluation of UrgoStart Plus dressings in real-life conditions: results of a prospective multicentre study on 961 patients

Aims: This study aimed to evaluate the performances of lipid colloid technology with nano-oligosaccharide factor (TLC-NOSF) dressings with polyabsorbent fibres in an unselected population of patients under real-life conditions. Methods: A large, prospective, multicentre, observational study with three polyabsorbent TLC-NOSF dressings (UrgoStart Plus Pad, UrgoStart Plus and UrgoStart Plus Border, Laboratoires Urgo, France) was conducted in Germany between January 2019 and June 2020. Main outcomes included wound healing rate, clinical assessment of wound healing progression, local tolerance and acceptance of dressings, and changes in health-related quality of life (HRQoL) of the patients, assessed with the validated Wound-QoL questionnaire. Results: A total of 961 patients with wounds of various aetiologies (leg ulcers (LU), diabetic foot ulcers (DFU), pressure ulcers (PU) and other types of wounds) were treated with the evaluated dressings in 105 centres for a mean duration of 62 days (standard deviation 37 days). By the last visit, a wound closure or an improvement in wound healing was reported in 92.0% of the treated wounds. The highest wound closure rates were achieved when the dressings were used as first-line treatment: 71.3% in DFUs, 52.9% in LUs, 53.6% in PUs and 61.8% in the other wounds. Improvement of the wound healing process was also associated with an 87.5% relative reduction of sloughy tissue, a decrease of the level of exudate in 68.9% of the wounds, and an improvement in the periwound skin condition in 66.4% of the patients at the final visit. The dressings were ‘very well’ or ‘well’ tolerated and ‘very well’ or ‘well’ accepted by the large majority of patients. The HRQoL questionnaires were completed both at initial and final visits by 337 patients, representative of the total cohort. Despite the relatively short duration of the wounds, the HRQoL of the patients was already impaired at baseline, with 81.6% of the patients being severely affected in at least one aspect of their HRQoL. By the final visit, significant improvements in each dimension of the patients' HRQoL were reported (p<0.001), along with a reduction of the proportion of patients in need of intervention and in the number of actions needed per patient in relation to their HRQoL. Conclusions: These results are consistent with previous clinical evidence on TLC-NOSF dressings. They confirm the good healing properties and safety profile of these dressings, and that a significant improvement in patient HRQoL is achieved in non-selected patients treated in real-life practice. These data support the use of such dressings as a first-line intervention and until wound healing in the management of chronic wounds, in association with appropriate standard of care.

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

Maternal-fetal immune-tolerance occurs throughout the whole gestational trimester, thus a mother can accept a genetically distinct fetus without immunological aggressive behavior. HLA-G, one of the non-classical HLA class I molecules, is restricted-expression at extravillous trophoblast. It can concordantly interact with various kinds of receptors mounted on maternally immune cells residing in the uterus (e.g. CD4+ T cells, CD8+ T cells, natural killer cells, macrophages, and dendritic cells) for maintaining immune homeostasis of the maternal-fetus interface. HLA-G is widely regarded as the pivotal protective factor for successful pregnancies. In the past 20 years, researches associated with HLA-G have been continually published. Indeed, HLA-G plays a mysterious role in the mechanism of maternal-fetal immune-tolerance. It can also be ectopically expressed on tumor cells, infected sites and other pathologic microenvironments to confer a significant local tolerance. Understanding the characteristics of HLA-G in immunologic tolerance is not only beneficial for pathological pregnancy, but also helpful to the therapy of other immune-related diseases, such as organ transplant rejection, tumor migration, and autoimmune disease. In this review, we describe the biological properties of HLA-G, then summarize our understanding of the mechanisms of fetomaternal immunologic tolerance and the difference from transplant tolerance. Furthermore, we will discuss how HLA-G contributes to the tolerogenic microenvironment during pregnancy. Finally, we hope to find some new aspects of HLA-G in fundamental research or clinical application for the future.

Toxicity and Local Tolerance of COVID- eVax, a Plasmid DNA Vaccine for SARS-CoV-2, Delivered by Electroporation

COVID-19 is a rapidly spreading disease, posing a huge hazard to global health. The plasmid vaccine pTK1A-TPA-SpikeA (named COVID- eVax) encodes the severe acute respiratory syndrome coronavirus 2 S protein receptor-binding domain, developed for intramuscular injection followed by electroporation (EP). The aim of this study was to assess the systemic toxicity and local tolerance of COVID- eVax delivered intramuscularly followed by EP in Sprague Dawley (SD) rats. The animals were killed 2 days and 4 weeks after the last injection (30-day and 57-day, respectively). No mortality was observed, and no signs of toxicity were evident, including injection site reactions. A lasting and specific immune response was observed in all treated animals, confirming the relevance of the rat as a toxicological model for this vaccine. Histopathological evaluation revealed muscle fiber necrosis associated with subchronic inflammation at the injection sites (at the 30-day time point), with a clear trend for recovery at the 57-day time point, which is expected following EP, and considered a desirable effect to mount the immune response against the target antigen. In conclusion, the intramuscular EP-assisted DNA vaccine, COVID- eVax showed an excellent safety profile in SD rats under these experimental conditions and supports its further development for use in humans.

Inverted Human Umbilical Artery as a 3D Scaffold for Sciatic Nerve Regeneration in Rats.

Background: Treatment of peripheral nerve injuries (PNIs) remains a challenge. Interposing a graft delivers better regenerative outcomes. Autografts present major drawbacks which have given rise to the development of alternatives such as artificial scaffolds, some of which are very promising. This study was designed to investigate the potential use of an inverted human umbilical cord artery (iHUA) as a 3D scaffold nerve chamber, for nerve regeneration after transection of the sciatic nerve (SN) in rats.Methods: Rats underwent surgical SN transection in their right hindlimb, followed by suture of the device at the resected stumps. Local tolerance, insert biodegradability and nerve reconstruction over time were thoroughly studied by histopathological and morphometric analysis, completed by functional test assessment of sensitivity and motricity recovery.Results: We have demonstrated that nerve reconstruction in the presence of an iHUA insert is effective. The device is well tolerated and highly biodegraded. Although the regenerated nerve is still immature at the end of our study, signs of sensitivity and partial functional recovery were witnessed, confirming our histological findings. Conclusions: Our results support the potential clinical use of iHUA as a 3D scaffold to bridge nerve discontinuity and guide axonal regrowth in selected cases of PNIs.

Non-inferiority evaluation of preservative-free latanoprost/timolol eye drops solution versus preserved latanoprost/timolol eye drops in patients with high intraocular pressure and open-angle glaucoma

Background: This study aimed to evaluate the non-inferiority and safety of a newly developed preservative-free (PF) multi-dose latanoprost/timolol ophthalmic solution, compared with the benzalkonium chloride (BAK)-preserved fixed combination, in patients with open-angle glaucoma and ocular hypertension.Methods: A Phase III randomized multi-center observer-blind parallel-group clinical trial was conducted. A total of 210 adult patients (aged over 18 years) were randomly treated with the PF- or the BAK-preserved latanoprost/timolol solution once daily in the affected eye(s) for 12 weeks. Follow-up visits were scheduled at weeks 2, 6, and 12; intraocular pressure (IOP) was recorded at 8:00 AM, 12:00 PM, and 4:00 PM. The primary efficacy endpoint to prove non-inferiority was the IOP change at 8:00 AM (± 1 hour) from the baseline to the end of treatment (week 12) in the studied eye. Safety parameters were also assessed.Results: In total, 196 patients completed the study. The pressure-lowering effect of the PF eye drops was comparable to that of the preserved formulation at all time points. Latanoprost/timolol PF formulation was non-inferior to the BAK-preserved solution as shown by the change in IOP from day 0 to week 12. The point estimate of the inter-treatment difference was 0.624 mmHg (95% CI: -0.094, 1.341). Both treatments were well-tolerated during the study, and they had similar adverse event profiles.Conclusions: PF-latanoprost/timolol combination was found to be non-inferior to the BAK-preserved formulation based on the efficacy at all times, with similar local tolerance.

Human-Elephant Conflict Around Moukalaba-Doudou National Park in Gabon: Socioeconomic Changes and Effects of Conservation Projects on Local Tolerance

Human-elephant conflict (HEC) poses a serious problem in Africa for both local livelihoods and elephant conservation. Elephant damage is the price local people pay for coexisting with this species, and is assumed to reduce tolerance for elephants. However, conservation-related projects, through the benefits they offer may enhance local tolerance toward elephants. This study aimed to examine how crop damage by elephants and the benefits gained from conservation activities affect local people’s tolerance toward elephants around Moukalaba-Doudou National Park in southwest Gabon based on long-term ethnographic research and interview surveys in two periods (2010 and 2019). Based on the results, crop damage by elephants had a significant negative impact on the local social economy, leading to a decrease in human population in the area and making local people highly resentful of elephants. However, in one of the villages where employment from research and conservation activities was concentrated, many acknowledged the benefits associated with wildlife and expressed high tolerance for elephants. These findings suggest that benefits from conservation activities can increase tolerance toward elephants, which is negatively affected by the crop damage they cause. However, it should also be noted that externally generated projects have limitations and drawbacks. It is important to establish a system in which the benefits of conservation are shared widely and distributed appropriately, and wherein income resources are diversified. Multisectoral interventions focusing on local socio-ecological vulnerability are needed to mitigate human-elephant conflict and advance the conservation of African elephants.

Is the local tolerance of injectable biosimilars too underestimated?

This editorial highlights the importance of carrying out comparative studies of patient tolerance to biosimilars and originator products. Minor side effects can affect their acceptability.

Balancing incomplete COVID-19 evidence and local priorities: risk communication and stakeholder engagement strategies for school re-opening

In the midst of the COVID-19 pandemic, United States (U.S.) educational institutions must weigh incomplete scientific evidence to inform decisions about how best to re-open schools without sacrificing public health. While many communities face surging case numbers, others are experiencing case plateaus or even decreasing numbers. Simultaneously, some U.S. school systems face immense infrastructure challenges and resource constraints, while others are better positioned to resume face-to-face instruction. In this review, we first examine potential engineering controls to reduce SARS-CoV-2 exposures; we then present processes whereby local decision-makers can identify and partner with scientists, faculty, students, parents, public health officials, and others to determine the controls most appropriate for their communities. While no solution completely eliminates risks of SARS-CoV-2 exposure and illness, this mini-review discusses engaged decision and communication processes that incorporate current scientific knowledge, school district constraints, local tolerance for health risk, and community priorities to help guide schools in selecting and implementing re-opening strategies that are acceptable, feasible, and context-specific.