Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

The pathophysiological changes underlying impairment of cognition in Parkinson's disease (PD) are complex and not fully understood till date. Hence, understanding the structural changes responsible for cognitive decline in PD is essential for early diagnosis and to offer effective treatment. In this review, we discuss the neuroanatomical changes in major brain structures responsible for cognition in PD. We have included the key findings of various studies to provide up-to-date information for better understanding of pathophysiology of PD, which will help researchers and clinicians in planning and developing new treatment methods for the benefit of PD patients.

Thai mango cultivars are classified into six groups plus one miscellaneous group according to germplasm database for mango. Characterization is important for conservation and the development of Thai mango cultivars. This study investigated macroscopic, microscopic leaf characteristics, and genetic relationship among 17 cultivars selected from six groups of mango in Thailand. Selected mango samples were obtained from three different locations in Thailand (n = 57). They were observed for their leaf and fruit macroscopic characteristics. Leaf measurement for the stomatal number, veinlet termination number, and palisade ratio was evaluated under a microscope attached with digital camera. DNA fingerprint was performed using CTAB extraction of DNA and inter-simple sequence repeat (ISSR) amplification. Forty-five primers were screened; then, seven primers that amplified the reproducible band patterns were selected to amplified and generate dendrogram by Unweighted Pair-Group Method with Arithmetic Average. These selected 17 Thai mango cultivars had individually macroscopic characteristics based on fruits and leaves. For microscopic characteristics, the stomatal number, veinlet termination number, and palisade ratio were slightly differentiable. For genetic identification, 78 bands of 190-2660 bps were amplified, of which 82.05% were polymorphic. The genetic relationship among these cultivars was demonstrated and categorized into two main clusters. It was shown that ISSR markers could be useful for Thai mango cultivar identification.

Zanthoxylum limonella (Dennst.) Alston. (Rutaceae) or Ma-khwaen is one of the medicinal plants in Thai traditional medicine. To investigate the pharmacognostic specifications and chemical constituents of Z. limonella fruits and seeds. Fruits and seeds of Z. limonella were collected from 15 sources throughout Thailand; then examined the pharmacognostic specification following WHO guideline of quality control method for medicinal plant materials. Microscopic determination of Z. limonella powders demonstrated fragment of mesocarp, fragment of brown vitta, oil glands, fragment of endocarp, and endosperm containing oil globule, trichome and pale brown stone cells. Stomatal index and pellucid dots in mm ² were 19.87 and 4.2 respectively. Physico-chemical parameters unveiled that loss on drying, water content, total ash, and acid-insoluble ash should be not >17.90%, 9.18%, 4.50%, and 0.60% of dried weight respectively; while ethanol, water, and hexane extractive values and volatile oil content should be not <2.24%, 2.27%, 1.57% and 9.63% of dried weight respectively. R _f values of thin-layer chromatographic fingerprint of Z. limonella fruits and seeds ethanolic extract were 0.38, 0.45, 0.90, and 0.97 detected ultraviolet (UV) light 254 nm, 0.30, 0.44, 0.67, and 0.77 detected UV light 366 nm, and 0.24, 0.73, 0.78, and 0.93 detected 10% sulfuric acid. There are three main chemical compounds in Z. limonella oil including limonene (43.63%), (+)-sabinene (16.72%), and terpinen-4-ol (10.95%). The result gained from pharmacognostic specifications and chemical fingerprints could be used as standardization data of Z. limonella fruits and seeds to apply or provide for guarantee of quality.

The periodontal therapies along with systemic antibiotic therapy aim at eliminating the subgingival microbiota to arrest the progression of periodontal diseases. The complete elimination is often difficult, and thus the probability of repopulation after periodontal therapy is also high. The objectives of the study are to develop in situ thermoreversible gelling system of green tea catechins suitable for periodontal pocket administration, which would act as an adjunct to mechanical periodontal therapy. Gel is prepared on a weight basis using a cold process. In vitro drug release pattern is observed through spectrophotometer analysis at 277 nm. The gel is subjected to serial dilution analysis to determine the minimum inhibitory concentration (MIC) and disc diffusion analysis to determine the in vitro antibacterial effectiveness. Release pattern studies showed a complete release of drug from gel occurred by 36 h. A volume of 1.25 mg/ml was determined as MIC required against the periodontal pathogens. Disc diffusion analysis showed a 14 mm zone of inhibition is present around the 75 µl well for all the four species and 12 mm zone of inhibition around the 50 µl well. The advantage of F-127 is its thermoreversible nature that used for in situ gel formulation. Pluronic gel proved to be a promising carrier for prolong and effective release of green tea catechin.

Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder among preschool children but the number of controlled clinical trials regarding psychopharmacological treatment in this age group is limited. The aim of this study was to compare methylphenidate with the combination of methylphenidate and risperidone in preschool children with ADHD. Forty-two preschool children, aged 3-6 years, diagnosed with ADHD by a child and adolescent psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-Text Revision criteria, were enrolled in a 6-week, single-blind clinical trial and administered with methylphenidate (5-30 mg/dl) or the combination of methylphenidate and risperidone (0.25-2 mg/dl) in Iran. Treatment outcomes were assessed using the Conners' Rating Scale and Clinical Global Impression (CGI) Scale at baseline and 3 and 6 weeks after starting the drugs administration. Side effects were rated by a checklist and body weight was measured at each visit. There were no significant differences between the two protocols in Parent Conners' Rating Scale scores (P > 0.05) and CGI scores (P > 0.05). Both groups showed a significant improvement in ADHD symptoms over the 6 weeks of treatment for Parent Conners' Rating Scale (P < 0.001). The combination group used significantly lower doses of methylphenidate compared to the other group (P = 0.002). The most common adverse effects were anorexia (21.7%) and daytime drowsiness (17.4%) in combination treatment group and insomnia (33.3%) and anorexia (25%) in methylphenidate group. Risperidone and methylphenidate may be effective and well tolerated in preschool children with ADHD, and adding risperidone to methylphenidate may decrease the occurrence of some side effects of methylphenidate such as insomnia and anorexia and lower the dose of methylphenidate may be needed to control symptoms.

Dental caries and periodontal diseases have historically been considered the most important global oral health burdens. Many chemicals and synthetic drugs have marked the side effects. Hence, there has been a paradigm shift from the use of modern drugs to the age-old herbs. Achyranthes aspera is one such important plant with various established pharmaceutical properties. The aim of this study was to assess the antibacterial activity of the A. aspera extract against Streptococcus mutans. Aqueous extract of A. aspera was prepared. Different concentrations of the root and stem extracts of A. aspera were transferred to the agar plates, which had been streaked with the bacterium S. mutans. The plates were incubated aerobically at 37°C for 24 h, and the zones of inhibition were measured using cup plate method. A. aspera extract showed statistically significant zones of inhibition. A. aspera showed marked antibacterial activity against S. mutans.

Polygonatum verticillatum (Mahameda) is an important ingredient of Ashtawarga and Ayurvedic formulations. Nowadays, it comes under the category of endangered plants due to large scale and indiscriminate collection of wild material. To overcome the scarcity, substitutes of Mahameda are also commonly used in market. These additives are different from the authentic plant by Ayurvedic and pharmacological theory of drug action, thereby resulting in substitution/adulteration. Substitution is a critical issue in isolation and quantification of the therapeutically active ingredients that can be used as markers in the identification of substitution/adulteration. Methanolic extract of the rhizomes of P. verticillatum was subjected to preliminary phytochemical screening for the detection of phytoconstituents, followed by column chromatography for isolation of the marker. The column was first eluted with pure hexane, and polarity of the solvent was gradually increased. A total of 1180 fractions were collected and pooled on the basis of thin-layer chromatography profile. The single compound was isolated and confirmed by chemical test, melting point, spectral analysis, and comparison with literature. Phytochemical screening of the extract shows the presence of alkaloids, flavonoids, carbohydrates, terpenoids, and phenolics. A pure white crystalline powder was isolated by column chromatography which was characterized as (6-methoxyquinolin-4-yl-8-vinylquinuclidin-2-yl) methanol, i.e. Quinine. The isolated compound, Quinine, was identified as a novel compound in Mahameda as it has not been reported in the genus Polygonatum, till now. It can be used as a marker for the identification of substitution/adulteration and standardization of P. verticillatum.

Wrightia tinctoria Roxb. (R.Br.) is an Ayurvedic remedy, ethnomedically used in the treatment of various ailments. The present work was carried out to evaluate the anticancer and antioxidant activity as well as total phenolic and phytochemical contents of W. tinctoria bark methanolic extract (WTBM) by high-performance liquid chromatography (HPLC)-diode array detector. Antiproliferative activity of WTBM was evaluated against MDA-MB-231 and MCF-7 cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation, and Hoechst staining. In addition, the antioxidant potential was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and 2,2- azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation decolorization assay. Total phenolic content was assessed by Folin-Ciocalteu method. The results demonstrated that WTBM exhibited significant antiproliferative effect against MDA-MB-231 (IC ₅₀ = 88.9 ± 1.27 μg/ml) and MCF-7 (IC ₅₀ = 45.71 ± 7.74 μg/ml) cancer cells in time- and dose-dependent manner. WTBM significantly suppresses colony formation and induces apoptosis in both MDA-MB-231 and MCF-7 cells as evident by morphological assessment, clonogenic assay, and Hoechst staining. The total phenolic content of WTBM was found to be 30.3 gallic acid equivalent mg/g dry weight of bark extract while IC ₅₀ value for DPPH and ABTS radical scavenging activity was 72.2 ± 2.8 μg/ml and 45.16 ± 1.95 μg/ml, respectively. HPLC analysis showed the presence of gallic acid, rutin, and quercetin in WTBM. These findings demonstrated that WTBM significantly inhibited proliferation of breast cancer cells and induced apoptosis, suggesting the potential chemopreventive activity of W. tinctoria bark.