Review of the molecular mechanisms in wound healing: new therapeutic targets?

The restoration of the skin barrier in acute and chronic wounds is controlled by several molecular mechanisms that synergistically regulate cell kinetics, enzymatic functions, and neurovascular activation. These pathways include genetic and epigenetic activation, which modulate physiological wound healing. Our review describes the genetic background of skin repair, namely transcription-independent diffusible damage signals, individual variability, epigenetic mechanism, controlled qualitative traits, post-translational mechanisms, antioxidants, nutrients, DNA modifications, bacteria activation, mitochondrial activity, and oxidative stress. The DNA background modulating skin restoration could be used to plan new diagnostics and therapeutics.

Next-generation sequencing confirms the implication of SLC24A1 in autosomal-recessive congenital stationary night blindness.

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder which represents rod photoreceptor dysfunction or signal transmission defect from photoreceptors to adjacent bipolar cells. Patients displaying photoreceptor dysfunction show a Riggs-electroretinogram (ERG) while patients with a signal transmission defect show a Schubert-Bornschein ERG. The latter group is subdivided into complete or incomplete (ic) CSNB. Only few CSNB cases with Riggs-ERG and only one family with a disease-causing variant in SLC24A1 have been reported. Whole-exome sequencing (WES) in a previously diagnosed icCSNB patient identified a homozygous nonsense variant in SLC24A1. Indeed, re-investigation of the clinical data corrected the diagnosis to Riggs-form of CSNB. Targeted next-generation sequencing (NGS) identified compound heterozygous deletions and a homozygous missense variant in SLC24A1 in two other patients, respectively. ERG abnormalities varied in these three cases but all patients had normal visual acuity, no myopia or nystagmus, unlike in Schubert-Bornschein-type of CSNB. This confirms that SLC24A1 defects lead to CSNB and outlines phenotype/genotype correlations in CSNB subtypes. In case of unclear clinical characteristics, NGS techniques are helpful to clarify the diagnosis.

Cross-linked hyaluronic acid in pressure ulcer prevention.

OBJECTIVE: Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. METHOD: All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. RESULTS: There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus reducing the exogenous pressure stress: thus, the induction of a thick hydrophilic substrate supports adequate mesenchymal and blood cells traffic to immediately restore any early or impending damage to the skin. DECLARATION OF INTEREST: The authors certify that there is no conflict of interest with any financial organisation regarding the material discussed in the manuscript.

Risk assessment in ginecology and obstetrics in Sicily: an approach based on Wolff's Criteria.

OBJECTIVES: To apply Wolff's Criteria to hospital discharge records (HDR) in order to detect adverse events worthy of further study. METHODS: Gynecology and Obstetrics Units of three Sicilian hospitals were considered and HDR regarding ordinary and day hospital admissions in 2008 were collected. A matched case-control study was designed, by random selection of 10 controls at maximum for each case. Matching was performed on the variables age and speciality of admission (gynecology or obstetrics). RESULTS: Out of a total of 7011 HDR examined, 114 cases were identified with Wolff's Criteria. Multivariate analysis confirmed a statistically significant association with the origin of admission, diagnosis at the acceptance and length of stay: there was a decreased risk of Wolff's event in patients having urgent admission compared to elective (OR = 0.47, 95% CI = [0.28-0.78]), an increased risk in patients reporting tumor (OR = 5:41, 95 % CI [1.89-15.47]) and other causes (OR = 2.16, 95% CI [1.10-4.24]) compared to delivery diagnosis at acceptance and in patients whose length of stay was more than 6 days (OR = 23.17, 95% CI = [12.56-42.7]) compared to less or equal than 3 days CONCLUSION: Wolff's Criteria can be applied for the analysis of clinical risk in hospitals with different structural characteristics, on condition that the HDR database is complete and good quality.

The role of Carcinine treatment on glico-lipidic imbalance of patients with altered blood glucose pattern.

Objective: Several studies support the active role of Carcinine, an L-carnosine metabolite, in insulin resistance and dyslipidaemia, to modulate the insulinemic/glycaemic profile and fat metabolism. Materials and methods: 100 (50 women and 50 men) volunteers, aged between 40 and 85 years with a body mass index (BMI) between 25 and 34,9 kg/m2, spontaneously addressed to our "Second Opinion Medical Consulting Network" (Modena, Italy) between 2019 and 2020, were included in this anecdotal, observational, retrospective trial. The aim of the study was to find an adequate possibly natural treatment for unbalanced insulin resistance pattern notwithstanding ongoing administration of statins, and hypoglycaemic chemical agents in healthy overweight/obese subjected. All the patients were divided in two groups: 1) the first group included 50 patients that were admi-nistered with a specific galenic nutraceutical product containing 20 mg of carcinine, and 2) the second group included 50 patients, which were administered with lithothamnion calcareum alga (190 mg) and three-time day for two months. The waist circumference, glycaemia, homeostasis model asses-sment (HOMA-IR), glycated haemoglobin, total cholesterol values were detected at time 0, and time 1 (after treatment). At the same time, the pre versus post treatment, Advanced Glycation End products (AGEs), that play an important role in the development of diabetic va-scular complications, were instrumentally measured at time 1 and 2. Results: After 60 mg/day of Carcinina treatment, glycaemia (p=0,001), glycated haemoglobin (p<0,001), total cholesterol (p<0,003), serum insulin (p<0.05) were significantly reduced, respect to placebo period. Abdominal circumference (p<0.2), HOMA index (p<0.03) progressively were reduced as well. No cardiovascular risk and untoward effects were observed at the prescribed dosages. The AGE reader test showed a statistically meaningful reduced risk due to reduced amount. Conclusions: Carcinine, at the daily dose of 60 mg/day, was able to modify, safely, the AGEs that induced cardiovascular risk, the waist circumference, and some glycolipid-metabolic parameters in over-weight/obese patients with altered blood glucose pattern, improving significantly the impending metabolic syndrome.

Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss.

Objectives: Ten million new cases of dementia are recorded annually worldwide, with agitation and idiopathic weight loss being the most common symptoms. Several pharmacological therapies have emerged in recent years, but the clinical use of cannabis extracts in older patients with AD is constantly growing. This retrospective, analytical, observational, spontaneous trial aimed to enhance the clinical action of THC: CBD cannabis extract administration in AD patients with severe symptoms such as agitation, weight loss, cognitive impairment, and sleep disturbance. Methods: Thirty patients (9 men and 21 women) diagnosed with mild, moderate, or severe AD, aged 65-90 years, appealing to our Second Opinion Medical Consultation (Modena, Italy), were enrolled and required to use oil-diluted cannabis extract, Bedrocan® (22% THC, 0.5% CBD, Olive Oil 50 ml), twice a day for 12 weeks. The efficacy of cannabinoid therapy was evaluated at baseline and 12 weeks after therapy, employing three self-administered questionnaires completed by the parents of the enrolled patients: NPI-Q, CMAI, and MMSE. Key findings: The NPI-Q demonstrated a reduction (p<0.0001) in agitation, apathy, irritability, sleep disturbances, and eating disturbances, consequently improving caregiver distress. Levels of physically and verbally aggressive behaviours, measured using the CMAI questionnaire, were lower (p<0.0001) in all patients. The MMSSE questionnaire confirmed a significant decrease (p<0.0001) in cognitive impairment in 45% of the patients. Conclusion: Our anecdotical, spontaneous, and observational study demonstrated the efficacy and safety of oil-diluted cannabis extract in patients with AD. The limitations of our study are: 1) small patient cohort, 2) absence of control group, 3) self-administered questionnaires that are the most practical but not objective instruments to assess the neurologic functions of AD patients.

Poly(vinyl alcohol) freeze casts with nano-additives as potential thermal insulators.

Freeze-casting consists of freezing a liquid suspension (aqueous or other), followed by sublimation of the solidified state to the gas state under reduced pressure, and subsequent sintering of the remaining scaffold to consolidate and densify the struts and walls. The structure is very porous with the pores being a replica of the solvent crystals. The technique is rather versatile and the use of a liquid solvent (water most of the time) as a pore forming agent is a strong asset. Freeze-casting has also been developed as a near net shape forming route yielding dense ceramics. In this work we report on porous composite materials synthesized via the ice templating method. Poly(vinyl alcohol) (PVA) is used as matrix and nano-silica (SiO2), nanoclay (NC) and microfibrillated cellulose (MFC) are used as fillers to improve the mechanical stability of the PVA scaffold. We show our results on the porosity and mechanical stability and consider these porous nanocomposites as potential insulation materials with low thermal conductivity and superior mechanical properties.

Experience on biocompatible artificial hair implant.

OBJECTIVE: In Europe, a great number of investigations and studies followed up to develop safer techniques performed by physicians only. Successful dedicated medical protocols included the implant of single fibers with extractable root. The aim of our study was to evaluate the efficacy of biocompatible artificial hair implants in patients with androgenetic alopecia. PATIENTS AND METHODS: 682 patients (488 males and 184 females) aged between 25 and 70 years old, with diagnosed AGA, requiring no invasive nor surgical hair restoration, with problems of baldness and refusing surgical options appealed to the Second Opinion Medical Consulting (Modena, Italy), and were included in the present protocol. Before the treatment, all patients underwent a test implant to rule out hypersensitivity by implanting 100 fibers on a selected skin spot. If no reaction was detected, five weeks later 500-1,200 fibers were further implanted per session at a minimum interval of 5 weeks until the required aesthetic result was achieved. RESULTS: The average number of sessions for each patient was 5. The average number of implanted fibers was 2,100 (ranging from 800 to 12,000). The treated scalp area returned to normal appearance and tenderness in 3 days. CONCLUSIONS: The socio-phycological benefit and the life quality improvement of our patients have been the focus of the study. On our side, the accurate selection, small hair units for each implant session, customized dermatological consultation and the use of highly biocompatible fibers have been the proper strategy to achieve the goal.

Insomnia treatment: a new multitasking natural compound based on melatonin and cannabis extracts.

OBJECTIVES: Our main aim was to investigate the short-term thera-peutic effects, safety/tolerability of natural compound, composed of melatonin (1,5 mg) and cannabis extracts (2.5 mg CBD) in patients with sleep disorders. METHODS: In this spontaneous, anecdotal, retrospective, "compas-sionate-use," observational, open-label study, 20 patients (age 43-96 years) were appealed to our "Second Opinion Medical Consulting Net-work" (Modena, Italy), because of a variable pattern of sleep disorders and anxiety and were instructed to take sublingually the compound (20 drops) overnight for 3 months of treatment. Tolerability and adverse effects were assessed monthly during the treatment period through direct contact (email or telephone) or visit if required. RESULTS: PSQUI and HAM-A scores evidenced reduction in mood alterations, including anxiety, panic, paranoia, depression (P < 0.03), in pain (P < 0.02) and good general health perceptions. CONCLUSIONS: These data suggest that the formula CBD-melatonin could be competitive with the classic hypnotic synthetic drugs, the antioxidant activity of melatonin offers a further benefit to the brain network, restoring the biological clock functions, while CBD, redu-cing chronic pain perception, helps to complete the neuromuscular relaxation and to relieve anxiety fulfilling a very balanced sensation of wellbeing during the sleep.

A Proposal for Clinical Biomarkers in Multiple Chemical Sensitivity.

Multiple chemical sensitivity (MCS) is increasingly widespread disease, characterized by non-specific and recurring symptoms from various organs associated with exposure to common chemicals, even if inhaled at low concentrations, usually harmless for normal people. MCS is not yet well recognized from common point of view and for this reason affected patients risk marginalization and their symptoms are often trivialized. It is actually a devastating chronic disease that affects not only the patients in the daily routine but partly conditions their survival. Despite more than 50 years of research, the action mechanisms of MCS is still undefined. In this study we examine the theories about the etiopathogenesis of multiple chemical sensitivity that include genetic susceptibility factors, immunological factors, neurological factors and psychiatric factors. Since no specific diagnostic markers are currently available for the MCS, the diagnosis can only be supposed on the basis symptomatic criteria and patient's medical history. However new biochemical markers and diagnostic imaging techniques have emerged, useful to postulate at least the clinical-diagnostic hypothesis of MCS and in this paper we discuss a list of biomarkers studied for the diagnosis of MCS, based on the available scientific literature. At last but not least, we propose four-levels MCS tests that could help the clinician in the diagnosis of the pathology both through the use of quantifiable serological parameters, both through diagnostic tools, genetic testing and through clinical observation of symptoms.

Skin scars and wrinkles temporary camouflage in dermatology and oncoesthetics: focus on acetyl hexapeptide-8

OBJECTIVE: The aim of study is to evaluate the aesthetic outcome of specific formulated cosmeceutical product to mask and reduce the appearance surgical scars or unappealing skin tags in chronic diseases, such as cancer METHODS: In a spontaneous, anecdotal, retrospective study, 26 patients with skin disorders appealed to Second Opinion Medical Network (Modena, Italy), required masking and improving the skin appearance. To evaluate the aesthetic improvement of skin imperfections, a gelcream containing 10% of acetyl hexapeptide-8 (registered trademark Argireline®) was selected, that can be applied directly upon the lesion, followed by a light massage in the treated area for a few minutes RESULTS: The skin quality parameters (hydration, elasticity, sebum), photographs and investigators clinical assessment have been performed before and after the treatment and demonstrated that this cream significantly improved the skin values and the self-image expectation of each patient. No allergic reactions were documented during the period treatment CONCLUSIONS: The topical administration of this cosmeceutical cream is a safe and effective alternative to the invasive procedures, to improve the quality of life in patients with some skin disorders such as cancer, surgical scars, hidradenitis, aging wrinkles

A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars.

OBJECTIVE: To investigate the therapeutic effect of CBD-ointment administered on severe skin chronic diseases and/or on their outcome scars. METHODS: A spontaneous, anecdotal, retrospective study of 20 patients with two most frequent skin disorders: psoriasis (n: 5 patients), atopic dermatitis (n: 5) and resulting outcome scars (n: 10). The subjects were instructed to administer topical CBD-enriched ointment to lesioned skin areas twice daily for three months treatment. RESULTS: Based on skin evaluations (hydration, TEWL, elasticity), clinical questionnaires (SCORAD, ADI, PASI), and supported by photographic data and investigators' clinical assessment, the results showed that topical treatment with CBD-enriched ointment significantly improved the skin parameters, the symptoms and also the PASI index score. No irritant or allergic reactions were documented during the period treatment. CONCLUSIONS: The topical administration of CBD ointment, without any THC, is a safe and effective non-invasive alternative for improve the quality of life in patients with some skin disorders, especially on inflammatory background.

Heterobifunctional poly(ethylene oxide) oligomers containing carboxylic acids.

Syntheses of vinylsilyl alcohols having one to three vinyl moieties and their use as initiators for ethylene oxide polymerizations are discussed. Poly(ethylene oxide) oligomers with vinylsilanes at one end and a hydroxyl group at the other were prepared in base-catalyzed reactions. Molecular weights determined from 1H NMR and gel permeation chromatography were close to the targeted values. Carboxylic acid functional poly(ethylene oxide) oligomers were prepared from ene-thiol addition reactions of mercaptoacetic acid across the vinylsilane terminus. It is anticipated that these carboxylic acid functional oligomers will complex to magnetite nanoparticles to afford complexes that can be dispersed in aqueous media.

Dogs'olfactory diagnostics applied on human species: state of the art and clinical perspectives.

Dogs'smell ability is about 10000-100000 more developed than humans' one. Dogs smell is usually exploited in forensic medicine, to find missing people and specific substances showing peculiar sensorial features. In clinic, there is the possibility to take advantage of dogs smell, which are conveniently trained, for the screening of cancers and other diseases. The common feature is the presence of molecules in organic samples that may be considered as biomarkers of a specific pathology. In cancer, scientific evidences exist about screening of melanoma, lung, breast, rectum, ovarian, prostate and bladder cancer. Instead, other pathologies manifest the presence of organic volatile compounds in biologic materials, such as spit, faeces and urine that may be studied by dogs smell in order to identify the presence of a specific disease. This review shows the state of the art of actual dogs' olfactory ability based on scientific principles and the advantages and the disadvantages of this method. The authors also reveal some potential pathologies joined by the presence of organic volatile compounds, which may be investigated by dogs smell.

Correlation between bioprotective effectiveness and dynamic properties of trehalose-water, maltose-water and sucrose-water mixtures.

The aim of the present work is to link the bioprotective effectiveness to the dynamic properties of a class of homologous disaccharides, that is, trehalose, maltose and sucrose, and their mixtures in water. The findings obtained by elastic neutron scattering point out a harmonic-anharmonic transition for all the three disaccharide mixtures. Using a new operative definition of 'fragility', the different degrees of 'strength' of the investigated systems are determined. The links existing between the degree of fragility and the cryptoprotective action are also discussed.

[From algae to "functional foods"]. / Dalle alghe ai "functional foods" .

In the recent years, a growing interest for nutraceutical algae (tablets, capsules, drops) has been developed, due to their effective health benefits, as a potential alternative to the classic drugs. This review explores the use of cyanobacterium Spirulina, the microalgae Chlorella, Dunaliella, Haematococcus, and the macroalgae Klamath, Ascophyllum, Lithothamnion, Chondrus, Hundaria, Glacilaria, Laminaria, Asparagopsis, Eisenia, Sargassum as nutraceuticals and dietary supplements, in terms of production, nutritional components and evidence-based health benefits. Thus, our specific goals are: 1) Overview of the algae species currently used in nutraceuticals; 2) Description of their characteristics, action mechanisms, and possible side effects; 3) Perspective of specific algae clinical investigations development.

Uveal effusion syndrome complicated by anterior ischemic optic neuropathy.

We report on a case of idiopathic uveal effusion syndrome complicated by AION. To our knowledge such an association hasn't been previously described. We suggest that scleral thickening caused obstruction of vortex veins followed by uveal effusion and compression of posterior ciliary arteries within their intrascleral tract, leading to AION. Nevertheless is can't be excluded that AION was the result of mechanical compression on ciliary vessels of optic disc by choroidal detachment.

Multifocal choroiditis: indocyanine green angiographic features.

The aim of this study is to retrospectively evaluate the indocyanine green (ICG) angiographic features in 13 patients affected by multifocal choroiditis. We identified two clinical and angiographic patterns. The 'active' pattern showed hypofluorescence up to the late phases and more extensive choroidal involvement than presumed by ophthalmoscopy and fluorescein angiography. In the 'inactive' pattern, ICG angiography showed hypofluorescence during all the phases: no increase in lesion number was observed between early and late phases. Choroidal neovascularization was present in 10 patients, and it was bilateral in 2 of these: it occurred only in the inactive stage. The appearance of choroidal lesions in IGC angiography supports the hypothesis of inflammatory involvement of the choriocapillaris as the pathophysiological mechanism of the disease.