Australasian Medical Journal
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Systems multiple molecule drug design with less side-effects via drug data mining and genome-wide data identification
Get PDFBackgroundDrugs fail in the clinic for two main reasons; one is that they do not work and another is that they are not safe. As such, two of the most important steps in developing new drugs should be drug targets identification and side-effect validation.AimsThe identification of drug targets and their restoration of cellular dysfunctions to normal cellular functions with less side-effects are considered as drug design specifications of systems medicine discovery. Since the effect on the normal expression of house-keeping genes and proteins is also considered as a restriction on drug design, the proposed multi-molecules drug strategy might be helpful for systems drug design with less-side effects.Methods By systems biology method, genetic and epigenetic networks (GENs) are constructed to identify network biomarker for drug targets of diseases by genome-wide high throughput data. An integration of computational network- based approach for multiple drug targets with drug data mining is also proposed for systems drug discovery with more precise medicine and less side-effects. Finally, some systematic drug design specifications for drug design are proposed to restore to the normal functions of multiple drug targets with less side-effects.Results A systematic method is introduced to find multiple drug targets based on pathogenic mechanism investigated by network identification through genome-wide high- throughput data. Then a multi-molecule drug design strategy is also proposed to select a set of multi-molecule drugs with less side-effects via drug data mining method.ConclusionSystematic engineering design methods seem applicable to systems drug discovery and design
Native human dermis versus human acellular dermal matrix: A comparison of biaxial mechanical properties
Get PDFBackgroundHuman Acellular Dermal Matrices (HADMs), thanks to its mechanical resistance and it’s not immunogenic response, is used in reconstructive surgery such as breast reconstruction procedures and hernia repairs. There is the need to investigate the mechanical response of HADMs when subjected to in vivo-like stresses. AimsIn order to supply additional guidance to surgeons, in this work equi-biaxial experimental curves of native and decellularized human dermis are presented because it is essential to investigate the engineered tissue response when subjected to stresses comparable to those that occur in vivo. Methods HADMs specimens were biaxially characterized exploiting a customized biaxial conversion device entirely realized through rapid prototyping methods, and the HADM response to mechanical stimuli comparable to the in vivo deformation state was explored. From the derived data, stress-strain curves were evaluated, and the elastic moduli were extracted from the curve toe-region. As an indication of the fibre rearrangement rate, the slope of the stress-strain curve at higher strains was evaluated in a semi-log plane. Results The mean elastic modulus at low strains for the medio-lateral direction (along Langer lines) resulted from 35 per cent to 87 per cent higher than the cranio-caudal one. Furthermore, medio-lateral specimens show lower rearrangement velocities at higher strains. Considering both directions, the decellularization process leads to a deterioration of the mechanical properties of the matrix.ConclusionThe tested HADMs maintained the typical anisotropic dermis behaviour, dependent on the collagen network predominantly oriented along the Langer lines. Moreover, comparisons among HADMs and the native human reticular dermis demonstrated the mechanical strength loss at lower strains caused by the decellularization process
Why volubility can predict the success of cochlear implantation
Get PDFBackgroundWe sought to identify potential communication markers predicting the success of cochlear implantation, that might be observed within the first year of life. According the last ten years literature review volubility can be considered as a potentially important vocal measure predicting later language development.AimsThe present review aims to review existing evidence related with: (i) why volubility posits a plausible marker of cochlear implantation success in infancy, and (ii) presents the clinical usefulness of volubility data in predicting later language trajectory. Methods Rate of vocalization or volubility measured in terms of frequency of syllable production and it is clearly affected by parental interactivity. A low percentage of volubility can be predictive of significant communication impairment. Vocalization growth during the first year of life, as demonstrated in publications examining sound production characteristics of normally hearing (NH) and hearing impaired (HI) infants fitted with CI, were reviewed. Results Literature results revealed differences in linguistic performance among NH and CI infants which are typically attributed to auditory deprivation. Infants received late CI, produce fewer syllables (low volubility) and exhibit late-onset babbling, especially those who underwent the procedure as late as the age of 12 months or thereafter. Early recipients (implanted before the age of 12-months) related with more vocalizations, which is thought to stem from CI-initiated auditory feedback. In sum, total syllables produced (volubility) demonstrate the developmental trajectory of language acquisition which in turn is a crucial factor related with the success of cochlear implantation.ConclusionContemporary findings collectively endorse volubility as a plausible criterion of differentiation between successful and non-successful early CI. It is argued that volubility measures predict language development and, in doing so, carry vast implications on designing efficient clinical assessment and intervention practices
Utility of sphenoid ostium in relation to posterior wall of maxillary sinus in CT scan
Get PDFBackgroundIn the past many rough guides and estimates have been used to localize the face of sphenoid sinus for FESS due to the bony anatomical variations of sphenoid sinus as well as its relationship with adjacent vital structures.AimsThe current study was performed to find out an easiest fixed bony landmark on computerized tomographic scans for localizing the sphenoid sinus ostium before embarking on to the FESS and Pituitary Surgery.Methods It was a retrospective study in which computerized tomographic (CT) scan axial cut of sinuses from 166 patients were reviewed to determine average distance between Posterior Maxillary Wall (PMW) and the Front of Sphenoid (FOS) in both right and left sides.Results Mean age of the patients was 41.18±14.75 (95 per cent CI=38.92–43.44) years. Males (n=88, 53.01 per cent) and females (n=78, 46.99 per cent) were almost equally participated in the study. The average anterior-posterior distance from the PMW to the FOS was on the right side 7.1mm and on the left side 7.9mm, the average in both right and left respectively was 7.5mm in the CT scans.ConclusionThe posterior maxillary sinus wall may act as a concrete and unmistakable bony landmark on CT scan to localize the face of sphenoid sinus for the sinus surgeons performing FESS and pituitary surgery
Gallbladder polyps between ultrasound and histopathology
Get PDFBackgroundGallbladder polyps (GBP) are rare. Ultrasound is the most widely used screening method for Gallbladder pathology.AimsWe aim to analyse polyps identified in gallbladders removed by laparoscopy over a 14-year period, and to assess the ability of conventional ultrasound to differentiate GBPs from stones.MethodsThis is a retrospective study of 11,391 patients who underwent laparoscopic cholecystectomy from 2002–2016. Data concerning patients' characteristics, preoperative ultrasound findings, number and size of lesions, histologic features of polyps and gallbladder were collected.ResultsForty-six patients had GBP(s) (0.4 per cent). Mean age was 54(range 17-85), 67.4 per cent were females. Body mass index (BMI) was 30 (range 19-43). GBP(s) were single in 63 per cent of cases. Polyp size ranged between 0.2 and 2.2cm (average 1cm). Preoperative ultrasound successfully differentiated polyps from stones in nine cases (20 per cent). The most common histopathologic pattern was hyperplastic polyps in 18 cases (39.1), followed by cholesterol polyps (28.3 per cent), adenomyoma (13 per cent) and adenoma (8.7 per cent). The rest (10.9 per cent) were malignant polyps (adenocarcinoma). Polyps were associated with chronic cholecystitis in 40/46 patients.ConclusionGBPs are rare. Hyperplastic polyps are the commonest in our region, probably due to chronic inflammation induced by gallstones. Although ultrasound seems to be sensitive to gallbladder lesions; its utility to differentiate polyps from stones is relatively low. Since one tenth of polyps were hiding malignancy, cholecystectomy is advised especially in elderly people
A study of the prevalence and risk factors for cardiovascular disorders among patients registered with the primary health centres
Get PDFBackgroundCardiovascular disorders (CVDs) are considered among the most common co-morbidities especially in developed countries that are easily preventable by controlling its risk factors and developing a healthy life style.AimsTo identify the magnitude and risk factors of CVDs among PHC patients in Majmaah, Saudi Arabia.Methods This was an interviewee based cross-sectional study conducted among the patients who were chosen through a one–stage cluster sampling method. Data was collected through a pre – structured close ended questionnaire.Results The study included 397 participants with mean age of 44.5±13.7 years. About 22 per cent of the participants had one of the CVDs and hypertension was the most commonly recorded one (20.4 per cent). Statistically significant risk factors associated with CVDs were smoking (Odds ratio – 2.9), DM (OR–2.1) and obesity (OR–3.5). Triglycerides readings were higher among those having CVDs as compared to those who were healthy.ConclusionIt was found that one out of five participants were affected with CVDs in spite of their young age. Obesity, smoking, age, diabetes mellitus and elevated blood pressure were the most important predictors
Sources of information in health education: A cross-sectional study in Portuguese university students
Get PDFBackgroundLiteracy is a public health priority. The way people access health information is changing. It’s crucial to understand this movement towards new communication tools, to better deal with it.AimsTo describe the sources of health information in younger population.Methods Cross-sectional study of a sample of Portuguese university students, by survey, asking for the sources of information in health issues, and crossing it with the literacy levels.Results We surveyed 485 participants (77.5 per cent females; median age 23 years). The main source of information was the internet (78.8 per cent; 95 per cent CI:75.1–82.4 per cent), followed by health providers and by family. A linear regression model adjusted for age, gender and having education in health issues, showed that using the internet is adversely associated with the literacy score.ConclusionThe internet is preferred to search for health information, but ineffective to improve the literacy rate, making us to conclude for the need of increasing the quality of available resources
Clinical report about the effectiveness of andriol, tamoxifen, vitamin A and lecithin on low acrosome
Get PDFBackgroundAcrosin is the most important proteolytic enzyme in fertilization, acrosome dysfunction affects fertilization. Recently, our group found that the treatment of andriol, tamoxifen, vitamin A and lecithin helped to improve acrosome function.AimsTo assess the effectiveness of andriol, tamoxifen, vitamin A and lecithin on low acrosome.MethodsSeventy-eight infertility males in my hospital were enrolled. Kenedy test was used to test acrosome function. Andriol, tamoxifen, vitamin A and lecithin were used for one to four months.ResultsSperm concentration (t=5.05, P=0.000) raised while seminal volume (t=1.93, P=0.057), normal morphology (t=0.24, P=0.811) and progressive sperm (t=2.14, P=0.036) did not show statistical difference after treatment. Acrosin was (37.62±11.07)μIU/106 sperm before treatment and raised to (52.68±15.68)μIU/106 sperm after treatment and showed statistical difference (t=8.18, P=0.00). In all the 78 males, the acrosin of seven men (11 per cent) bellowed after treatment while the acrosin of 71 males (91 per cent) raised and ten couples (13 per cent) got pregnant.ConclusionThe combined treatment of andriol, tamoxifen, vitamin A and lecithin were effective on low acrosin
Intermittent fasting for cardiovascular disease risk factor reduction: A narrative review of current evidence
Get PDFBackgroundThe metabolic syndrome (MetSy), which is defined by the spectrum of obesity, insulin resistance and dyslipidaemia, is recognised as a major contributor to the overall risk of developing cardiovascular disease. Intermittent fasting (IF), which encompasses dieting plans with varying schedules of fasting, may be an effective method of reducing the burden of MetSy and the consequent cardiovascular events in the face of a worsening obesity epidemic in the contemporary society.AimsDespite the widespread public interest there is a serious lack of scientific understanding of the evidence base and the safe, optimal recommendations. This has created a level of public confusion that we endeavour to address by this narrative review of the published literature.Methods This narrative literature review summarises the current findings and suggests which regimens may be more effective and where future research in this area should be focused.Results Although the ideal regimen for IF remains unclear, there is promising evidence that alternate day fasting or modified fasting regimens, paired with or without continuous caloric restriction, may be more effective than continuous caloric restriction alone.ConclusionIF has been shown in the small number of human clinical trials discussed here to be an alternative to continuous caloric restriction in reducing the factors that contribute to the development of cardiovascular disease.Long-term randomised, controlled trials comparing continual caloric restriction and IF are required to objectively assess energy intake, energy expenditure, adherence, disease outcomes and metabolic factors