Binding without variables: Solving the under-generation problems

The variable-free semantics of Jacobson (1999, 2000, 2014) derives binding relations by the local application of the z-rule. This rule, however, under- generates binding. This paper makes two contributions: (i) replacing the z-rule with a more flexible rule called i (a la the W-combinator of Szabolcsi 1992), which allows for more binding relations; (ii) enriching Jacobson’s variable-free system and proposing a two-dimensional analysis to account for the interactions between scoping and binding. Issues to be covered include binding into adjuncts, possessor binding, scope ambiguity, inverse linking, weak crossover, and ‘paycheck pronouns’.

Comparison of Efficacy and Safety of Calcipotriol and Apremilast Combination Against Cacipotriol Monotherapy in Psoriasis

Background Potentiating activity of tablet apremilast 30mg BD against psoriasis in combination with 0.005% calcipotriol ointment was studied in comparison with calcipotriol monotherapy. Methods Single centre, prospective, parallel group, open label study compared efficacy and safety of calcipotriol+apremilast combination with calcipotriol monotherapy. Patients of mild to severe psoriasis in age group 18-60 years were randomized to two groups – calcipotriol+apremilast group and calcipotriol group. Calcipotriol+apremilast group received apremilast 30 mg BD p.o. and 0.005% calcipotriol ointment local application BD for 8 weeks. While calcipotriol group received 0.005% calcipotriol ointment local application BD for 8 weeks. Primary endpoint for efficacy was percentage of patients in whom mPASI decreased by 75% from baseline. Safety was also monitored throughout. Results 106 patients were randomized: calcipotriol+apremilast (n = 56) and calcipotriol group (n = 53). More patients of calcipotriol+apremilast achieved treatment success compared to calcipotriol was also higher (51.85% vs 34.61%; p < 0.001). Similar percentage of patients reported adverse events: Calcipotriol+apremilast 45.49% (n = 23) and calcipotriol 42.30% (n = 22) Conclusion Addition of apremilast to calcipotriol is significantly more efficacious than calcipotriol monotherapy. This combination is as safe as monotherapy.

AYURVEDIC MANAGEMENT OF KITIBH KUSHTHA (SCALP PSORIASIS) – A CASE REPORT

People suffering from Autoimmune diseases is increasing day by day. The exact cause of the autoimmune disease is still unknown. Psoriasis is one such disease. Dry thick raised itchy patches on the skin are the sign of psoriasis. They are covered with silvery-white scales. It is triggered by infection stress and cold. There is no known cure but with proper management, serious flares can be avoided. It generally affects the scalp, sole, palm, elbows and knees. Such diseases can be effectively managed by Ayurveda. Ayurveda defines the major- ity of skin diseases under the category of Kushtha. Clinically we can compare scalp psoriasis to Kitibha Kush- tha mentioned in the granthas. In the present study, a 53-year-old male patient was treated for scalp psoriasis. He presented himself with itching, dry scales, flake formation and whitish-pink patches on the scalp. He was treated with Arogyavardhini, Sukshma Triphala, Panchatikta Ghrut, Jatamansi choorna internally and Karan- ja Tel for local application. The treatment was given for seven months. The case report is presented here to share effective management of scalp psoriasis by Ayurveda. Keywords: Psoriasis, Kitibha Kushtha, autoimmune diseases, Arogyavardhini, Ayurveda.

The Effectiveness of Local Application of Melatonin in the Original Dermal Film in Experimental Thermal Trauma

Background: The development and pathogenetic substantiation of the new agents used for local therapy of thermal trauma (TT) is an urgent problem in medicine. Melatonin (MT) is an endogenous factor of homeostasis regulation with pleiotropic potential. The aim of our study was to assess the morphology, expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), indicators of repair, oxidative destruction of lipids in the skin lesion focus in the dynamics of experimental TT under the conditions of using the original dermal film (DF) with MT. Methods and Results: The experiment was performed on 104 male Wistar rats weighing 200-240 g. For modeling TT II degree according to ICD-10 a relative area of 3.5% of the body surface, an interscapular region isolated from the surrounding tissues, was immersed in distilled water at 98-99 °C for 12 sec. DF based on sodium carboxymethylcellulose with an area of 12 cm2 with MT at a concentration of 5 mg/g was applied daily for five days. The wound area and epithelialization rate were calculated. The content of MMP-9 and VEGF in the burn wound was assessed by an immunohistochemical method. In the homogenate of the burn wound, the content of LPO products was assessed. Morphological and biochemical studies were performed on Days 5, 10 and 20 after TT induction. With experimental TT from Day 5 to Day 20, the absolute area of the burn wound decreases by 35%, the rate of epithelialization increases, the number of neutrophils in the focus of thermal damage decreases, while the representation of lymphocytes, histiocytes, and fibroblasts increases; the expression of MMP-9 and VEGF increases; predominantly secondary and final LPO products in the heptane phase accumulate, the final products of LPO in the isopropanol phase of the lipid extract. The use of MT in the composition of DF daily for 5 days with experimental TT leads to a decrease in the area of the wound defect (by 46% of the original area on Day 20), an increase in the rate of its epithelialization, an increase in the content of lymphocytes and fibroblasts in the burn wound on Days 5, 10 and 20 of TT, a decrease in the representation of neutrophils and macrophages on Days 5 and 10, as well as an increase in VEGF expression on Days 5 and 10, MMP-9 - on Day 5 and a decrease in MMP-9 expression on Days 10 and 20 of TT. In addition, the use of MT in the composition of DF leads to a decrease in the content of predominantly secondary and end products of LPO in the heptane and isopropanol phases of the burn wound on Days 10 and 20 of TT. Correlation analysis revealed that a decrease in the burn surface area under a local application of MT occurs with an increase in the content of VEGF in the wound area and a decrease in the content of MMP-9 and secondary and final LPO products in the heptane phase and the isopropanol phase. On Day 20, there were direct moderate correlations between the absolute burn surface area, on one hand, and secondary and final LPO products, on the other, in the heptane phase (R=0.51, R=0,68; P<0.05) and the isopropanol phase (R=0.44, R=0.46; P<0.05), respectively. Conclusion: The results obtained expand the existing understanding of the role of changes in the expression of MMP-9 and VEGF in the pathogenesis of TT. We believe that the repair-stimulating effect of MT in the DF, which we established during TT at the preclinical stage, is associated with the LPO-limiting effect of MT and a change in the expression of MMP-9 and VEGF in the burn wound and is a prerequisite for further study of the mechanism of action and the effectiveness of MT application in clinical conditions in TT.

THE USE OF ANTISEPTIC PREPARATIONS IN THE COMPLEX TREATMENT OF TROPHIC ULCER OF THE VENOUS ETIOLOGY IN LOWER LIMBS

For the last decades despite the rapid development of medicine and its significant achievements there is a tendency towards an increase in the number of patients with trophic ulcers. Globally, the number of people suffering from chronic trophic ulcers ranges from 600 thousands to 2 million. Venous pathology is reported as the most common cause of trophic ulcers of lower extremities. Taking into account considerable prevalence of trophic ulcers, which can impede many aspects of life quality of patients, insufficient efficiency of existent conservative methods of treatment, no tendency to the decline in the prevalence of the disease, its prolonged treatment, which mostly lasts 2 – 3 months, and in some patients trophic ulcers do not heal over years, propensity to the frequent relapses in 60 – 70% of patients, considerable economic losses due to the loss of working capacity or disability of patients that ranger from 10 to 67%, and the large expenses for medication pose the trophic ulcer management as a challenging socioeconomic issue. Therefore, the search of new methods of local treatment of trophic ulcers of venous aetiology is remaining as one of the important problems of modern medicine. The article presents the clinical examination findings and treatment outcomes of 47 patients with the trophic ulcers of venous etiology. The participants took the course of treatment at the surgical department, II Municipal Clinical Hospital of Poltava. The treatment included local application of antiseptics. We investigated the clinical parameters of wound healing and check microbiological contamination of wounds. The results of clinical and laboratory investigations have demonstrated that local application of antiseptics in the management of trophic ulcers of venous aetiology of lower extremities promotes healing of trophic ulcers and can considerably reduce the term of treatment and hospital staying.