Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular diagnostics and personalised medicine in wound care: assessment of outcomes.

OBJECTIVE This large, level A, retrospective cohort study set out to compare healing outcomes in three large cohorts of wound patients managed universally for bioburden: standard of care group, who were prescribed systemic antibiotics on the basis of empiric and traditional culture-based methodologies; treatment group 1, who were prescribed an improved selection of systemic antibiotics based on the results of molecular diagnostics; treatment group 2 who received personalised topical therapeutics (including antibiotics) based on the results of molecular diagnostics. METHOD Apart from the differences in diagnostic methods and antibiotic treatments described above, all three cohorts were subjected to the same biofilm-based wound care protocol, which included evaluation of the host and bioburden, frequent sharp debridement, use of wound dressings and comprehensive standard care (reperfusion therapy, nutritional support, offloading, compression and management of comorbidities). RESULTS In all, 1378 patients were recruited into the study. In the standard of care group 48.5% of patients (244/503) healed completely during the 7-month study period. This increased to 62.4% (298/479) in treatment group 1 and 90.4% (358/396) in treatment group 2. Cox proportional hazards analysis revealed the time to complete closure decreased by 26% in treatment group 1 (p<0.001) and 45.9% in treatment group 2 (p<0.001) compared with the standard of care group. Patients in treatment group 2 had >200% better odds of healing at any given time point compared with the other cohorts. CONCLUSION Implementation of personalised topical therapeutics guided by molecular diagnosis resulted in statistically and clinically significant improvements in outcome. The integration of molecular diagnostics and personalised medicine provides a directed and targeted approach to wound care. CONFLICT OF INTEREST SED and RDW are owners of PathoGenius Laboratories, a clinical diagnostic laboratory. SED and RDW are owners of Research and Testing Laboratory, which develops molecular diagnostics. CJ and JK are clinical advisors for PathoGenius. CJ and JK are owners of Southeastern Medical Compounding, Savannah, GA and Southeastern Medical Technologies, Savannah, GA.
Epidemiological survey of hypertension in Anambra state, Nigeria.

BACKGROUND Hypertension is a major public health problem worldwide. Estimating the prevalence of disease in populations of Nigeria would be useful in developing intervention programs to control it and prevent its consequences. OBJECTIVE This survey was carried out to assess the prevalence, awareness, treatment, detection and risk factors of hypertension in three major populations - Onitsha, Nnewi and Awka cities of Anambra State. METHODS The study was a church based cross sectional study involving 912 participants randomly selected from the three major zones in Anambra State. The age range of the participants was 17-79 years. Participants were administered with a well-structured questionnaire and their blood pressures (BP) as well as anthropometric measurements were taken using standard instruments. RESULTS The study population (n = 912) consists, 476 (52.16%) females and 436 (47.81%) males; sampled randomly from Awka, Onitsha and Nnewi. The overall crude prevalence of hypertension and prehypertension in the study population were 22.81% and 42.54% respectively. The crude prevalence of hypertension in the three cities - Onitsha, Awka and Nnewi were 32.56%, 19.665 and 16.40% respectively. The prevalence of hypertension was significantly higher in Onitsha (P = 0.0001). The prevalence of hypertension in both sexes was not statistically different (male, 22.01% and female, 23.5% P = 0.587). Mean BMI, Systolic, and Diastolic BP for the study population was 25.43 ± 4.2, 120.7 ± 18.39 and 78.21 ± 12.57 respectively. Systolic and diastolic BP correlated with age and anthropometric measures such as waist circumference, BMI, Hip circumference, weight and height. The following factors were strongly associated with the prevalence of hypertension in our study population: Age (χ2 = 110.87, P = 0.000); Zone (χ2 = 25.19, P = 0.000); BMI (χ2 = 45.51, P = 0.000); Physical Activity(χ2 = 58.08, P = 0.000); Alcohol Consumption (χ2 = 32.27, P = 0.000); Smoking (χ2 = 7.892, P = 0.000); General Health status (χ2 = 46,62, P= 0.000); Consumption of fatty food (χ2 = 29.35, P = 0.000). A low percentage of the population, 9.76% reported previous diagnosis of high BP and 34.59% of 910 of the participants also reported previous BP diagnosis of any relative. Our result shows that the prevalence of hypertension and prehypertension in this population was high and associated with some modifiable risk factors. In addition, poor detection, treatment and control of hypertension in this population were observed. This underscores the need for comprehensive evaluation of the prevalence of hypertension and other cardiovascular diseases in Nigeria.
Motor simulation does not underlie action perception: evidence from upper limb dysmelia.

Every day, we interact with people synchronously, immediately understand what they are doing, and easily infer information about their mental state and the likely outcome of their action from their kinematics. According to motor theories of perception, such efficient perceptual processing of others' actions is achieved within the motor system by a process of "motor simulation", i.e., an unconscious covert imitation of the observed movements. On this hypothesis, individuals incapable of simulating observed movements in their motor system should have difficulties perceiving and interpreting observed actions. Contrary to this prediction, we found across eight sensitive experiments that five individuals born without upper limbs (i.e., upper limb dysmelia) perceived, anticipated, predicted, comprehended and memorized upper limb actions (i.e., that they cannot simulate) as accurately and as rapidly as age- and education- matched typically developed participants. We also found that, like the typically developed participants, the dysmelic participants systematically perceived the position of moving upper limbs slightly ahead of their real position but only when the anticipated position would be biomechanically possible. Such anticipatory bias and its modulation by implicit knowledge of the body biomechanical constraints were previously considered as indexes of motor contribution to perception. Our findings undermine this assumption and, together, show instead that efficient action perception does not rely on a motor simulation process. Meeting abstract presented at VSS 2015.
Sex differences in carbohydrate metabolism

During submaximal endurance exercise, women oxidize more lipid and less carbohydrate as metabolic substrates than men. This is reflected in a lower glycogen utilization in skeletal muscle and lower hepatic glucose production for women compared with men. These latter observations may explain the lower leucine oxidation observed during endurance exercise in women. Animal and preliminary human study evidence suggests that 17-β-estradiol may be a major determinant of the sex dimorphic response in carbohydrate metabolism during exercise. From a practical standpoint, it appears necessary for women to increase their dietary energy intake (and percentage derived from carbohydrates) for four days before a sporting event in order to supercompensate muscle glycogen concentrations. Sex differences in carbohydrate metabolism may have future implications for the care of patients with diabetes and inborn errors of lipid metabolism.
Antioxidant effects of gamma-oryzanol on human prostate cancer cells.

BACKGROUND To assess the antioxidant effects of gamma-oryzanol on human prostate cancer cells. MATERIALS AND METHODS Cytotoxic activity of gamma-oryzanol on human DU145 and PC3 prostate cancer cells was determined by proliferation assay using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reagent. mRNA levels of genes involved in the intracellular antioxidant system, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GSR) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Cancer cell lysates were used to measure lipid peroxidation using thiobarbituric acid reactive substance (TBARS). Glutathione contents of the cell lysates were estimated by the reaction between sulfhydryl group of 5, 5'-dithio (bis) nitrobenzoic acid (DTNB) to produce a yellow- color of 5-thio-2-nitrobenzoic acid using colorimetric assay. Catalase activity was also analysed by examining peroxidative function. Protein concentration was estimated by Bradford's assay. RESULTS All concentrations of gamma-oryzanol, 0.1-2.0mg/ml, significantly inhibited cell growth in a dose- and time-dependent fashion in both prostate cancer cell lines, DU145 and PC3. Gene expression of catalase in DU145 and PC3 exposed to gamma-orizanol at 0.5mg/ml for 14 days was down regulated, while mRNA of GPX was also down regulated in PC3. The MDA and glutathione levels including catalase activity in the cell lysates of DU145 and PC3 treated with gamma-oryzanol 0.1 and 0.5mg/ml were generally decreased. CONCLUSIONS This study highlighted effects of gamma-oryzanol via the down-regulation of antioxidant genes, catalase and GPX, not cytotoxic roles. This might be interesting for adjuvant chemotherapy to make prostate cancer cells more sensitive to free radicals. It might be useful for the reduction of cytotoxic agents and cancer chemoprevention.
Detection of orbicularis oris muscle defects in first degree relatives of cleft lip children using ultrasound.

OBJECTIVE The severity of cleft lip (CL) varies considerably from complete bilateral CL and palate at one end of the spectrum to a minimal CL at the other. In some cases of microform clefting, there may be no visible manifestation of the defect on the lip surface (i.e., the defect is occult) and no residual functional deficit. This study used high resolution ultrasonography to detect subclinical anomalies of orbicularis oris muscle (OOM) in first degree relatives of CL +- cleft palate children and compared it with controls. MATERIALS AND METHODS Thirty relatives of 25 children with non-syndromic CL or CL+ CP were identified for the study. Thirty subjects having negative family history of CL/P in three generations and absence of any minimal cleft features were taken as controls. Ultrasound scans of OOM of all the controls and relatives were taken. Statistical analysis was performed using standard χ2 tests with Yates correction. RESULTS Defects were seen in 13.3% of relatives and no defects were seen in controls, this was not statistically significant. CONCLUSION The data support the hypothesis that subclinical CL cases with subepithelial OOM defects do exist and Orbicularis oris discontinuities represent the mildest form of CL.
The management of episiotomy technique and its effect on pelvic floor muscles during a malposition childbirth

Abstract Vaginal childbirth is the leading cause of pelvic floor muscles injury, which contributes to pelvic floor dysfunction, being enhanced by fetal malposition. Therefore, the aim of the present study is to verify the influence of mediolateral episiotomies in the mechanics of the pelvic floor with the fetus in occiput posterior position when compared to the occiput anterior position. Numerical simulations of vaginal deliveries, with and without episiotomy, are performed based on the Finite Element Method. The biomechanical model includes the pelvic floor muscles, a surface to delimit the anterior region of the birth canal and a fetus. Fetal malposition induces greater extension of the muscle compared to the normal position, leading to increases of stretch. The faster enlargement may be responsible for a prolonged second stage of labor. Regarding the force required to achieve delivery, the difference between the analyzed cases are 35 N, which might justify the increased need of surgical interventions. Furthermore, episiotomy is essential in reducing the damage to values near the ones obtained with normal position, making the fetal position irrelevant. These biomechanical models have become extremely useful tools to provide some understanding of pelvic floor function during delivery helping in the development of preventative strategies.
Physical activity and risk of cardiovascular disease by weight status among U.S adults

Purpose We sought to determine whether the association between physical activity and 10-year cardiovascular disease (CVD) risk varies among normal weight, overweight, and obese adults in a nationally-representative sample of the United States. Methods Data were from the National Health and Nutrition Examination Survey 2007–2016. A subset of 22,476 participants aged 30–64 years was included with no CVD history. Physical activity level was self-reported and stratified into sedentary (0 min/week), inactive (1–149 mins/week), or active (≥150 mins/week) of moderate or vigorous activities. Framingham risk scores were classified as low/intermediate (<20%) or high 10-year CVD risk (≥20%). Results The average age of the population was 45.9 years, 52.3% were female, 33.6% were overweight (BMI 25.0–29.9kg/m2), and 35.7% were obese (BMI≥30kg/m2). Individuals who were overweight and obese had a higher 10-year CVD risk compared to those with normal weight (9.5 vs. 10.1 vs. 6.3%, P<0.001). The association of physical activity and high 10-year CVD risk differed by weight status. Among overweight and obese adults, individuals engaged in any physical activity had lower odds ofhigh 10-year CVD risk compared to sedentary individuals (overweight: OR active = 0.48, 95% CI: 0.36–0.64; OR inactive = 0.53, 95% CI: 0.45–0.86; obese: OR active = 0.50, 95% CI: 0.37–0.68; OR inactive = 0.66, 95% CI: 0.49–0.89). Among normal weight adults, individuals who were physically active had lower odds of high 10-year CVD risk (OR = 0.59, 95% CI: 0.28–0.87). When compared the joint effects of physical activity level and weight status, physical activity was associated with a larger magnitude of reduced odds of 10-year CVD risk than weight status. Conclusion Participation in any level of physical activity is associated with a lower 10-year CVD risk for overweight and obese adults. Future studies are needed to identify effective modes and doses of exercise that offer optimal CVD benefits for populations with different weight statuses.
Short Communication Identification of Chromosome 9 Alterations and p53 Accumulation in Isolated Carcinoma in Situ of the Urinary Bladder versus Carcinoma in Situ Associated with Carcinoma

Carcinoma in situ (CIS) of the urinary bladder is a flat, aggressive lesion and may be the most common precursor of invasive bladder cancer. Although chromosome 9 alterations are among the earliest and most prevalent genetic alterations in bladder cancer, discrepancy exists about the frequency of chromosome 9 losses in CIS. We analyzed 22 patients with CIS of the bladder (15 patients with isolated CIS, 7 patients combined with synchronous pTa or pT1 carcinomas) for gains and losses of chromosome (peri)centromere loci 1q12, 7p11-q11, 9p11-q12, and 9p21 harboring the INK4A/ARF locus (p16/p14) and INK4B (p15) by multiple-target fluorescence in situ hybridization, and for p53 protein accumulation by immunohistochemistry. In 15 of 20 (75%) CIS lesions analyzed p53 overexpression was detected, whereas aneusomy for chromosomes 1 and 7 was identified in 20 of 22 (91%) CIS. In 13 of 22 (60%) CIS cases analyzed, 12 of which were not associated with a synchronous pTa or pT1 carcinoma, no numerical losses for chromosome 9 (p11-q12 and 9p21) were detected as compared with chromosomes 1 and 7. Furthermore 6 of 12 (50%) patients showed a metachronous invasive carcinoma within 2 years. In the remaining nine biopsies CIS lesions (40%) were recognized that showed losses of chromosome 9p11-q12 and 9p21, six of these were associated with a synchronous pTa or pT1 carcinoma. Three of these carcinomas were pTa and exhibited loss of 9q12 as well as a homozygous deletion of 9p21. The others were invasive carcinomas in which CIS lesions were also recognized that showed no numerical loss of chromosome 9, but did show an accumulation of p53. In conclusion our data demonstrate that predominantly isolated CIS lesions contained cells with no specific loss of chromosome 9, as opposed to CIS lesions with synchronous carcinomas that showed evidence of chromosome 9 loss. Furthermore our data strengthen the proposition that p53 mutations (p53 overexpression) precede loss of chromosomes 9 and 9p21 in CIS as precursor for invasive bladder cancer, as opposed to noninvasive carcinomas where chromosome 9 (9p11-q12) losses are early and frequently combined with homozygous deletions of 9p21. (Am J Pathol 2002, 161:1119–1125)
Differentiation of proliferated NG2‐positive glial progenitor cells in a remyelinating lesion

Cells that express the NG2 proteoglycan (NG2+ cells) constitute a large cell population in the adult mammalian central nervous system (CNS). They give rise to mature oligodendrocytes in culture and are thus considered to be oligodendrocyte progenitor cells (OPCs). They proliferate in response to a variety of insults to the CNS, but their ability to differentiate into oligodendrocytes in vivo has not been established. We used bromodeoxyuridine (BrdU) to trace the fate of NG2+ cells that proliferated in response to a chemically induced demyelinating lesion in the adult rat spinal cord. Cells that were proliferating 24 hr after lesioning were labeled by a single injection of BrdU, and their antigenic phenotype was examined at various times up to 28 days post‐lesioning (28 dpl). Initially, at 2 dpl, NG2+/BrdU+ cells were found almost exclusively at the periphery of the lesion. At 7 dpl, the number of NG2+/BrdU+ cells increased in the lesion center and decreased from the surrounding areas. The number of NG2+/BrdU+ cells inside the lesion further decreased with time, concomitant with progression of remyelination and appearance of BrdU+ mature oligodendrocytes. Double labeling with 3H‐thymidine and BrdU combined with NG2 immunohistochemistry showed that some NG2+ cells in the lesion had undergone at least two rounds of cell division. These observations strongly suggest that NG2+/BrdU+ cells that appeared in response to the demyelinating insult gave rise to mature remyelinating oligodendrocytes, providing an in vivo evidence for the differentiation of NG2+ cells into oligodendrocytes. © 2002 Wiley‐Liss, Inc.
Granulocyte-macrophage colony-stimulating factor expression is regulated at transcriptional and posttranscriptional levels in a murine bone marrow stromal cell line.

We have reported modulation, by cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) and by hormonal cyclic-adenosine-monophosphate (cAMP) agonists, of hematopoietic growth factor production in the murine marrow adherent cell line +/+(-)1.LDA11. Previously, we reported that increased intracellular cAMP levels inhibited bioactive granulocyte-macrophage colony-stimulatory factor (GM-CSF) production stimulated by IL-1 or by the synergistic stimulus of IL-1 plus TNF-alpha. On the other hand, increased intracellular cAMP stimulated IL-6 synthesis in +/+(-)1.LDA11 cells. In addition, cAMP was additive with either IL-1 or IL-1 plus TNF-alpha in inducing production of soluble IL-6. In the present study, these observations were pursued mechanistically at the level of messenger RNA (mRNA) production. Northern blot analysis of steady-state mRNA for GM-CSF revealed induction by treatment of +/+(-)1.LDA11 cells with IL-1 or with TNF-alpha. The combined stimulation by IL-1 plus TNF-alpha resulted in supra-additive increases in GM-CSF expression by +/+(-)1.LDA11. Addition to stromal cells of the soluble cAMP agonist 8-bromo-cAMP (8BrcAMP) at 0.5 to 1 mM stimulated IL-6 mRNA expression acting alone, and it was additive with IL-1 or IL-1 plus TNF-alpha in stimulating IL-6 expression. On the other hand, 8BrcAMP inhibited GM-CSF mRNA expression stimulated by IL-1 or IL-1 plus TNF-alpha. Inhibition of GM-CSF mRNA by 8BrcAMP was time-dependent, starting 120 to 180 minutes posttreatment. In addition, inhibition of GM-CSF transcript expression in +/+(-)1.LDA11 by 8BrcAMP required the expression of a labile protein. Nuclear run-on assays revealed that GM-CSF and IL-6 genes were transcriptionally induced in +/+(-)1.LDA11 by incubation with IL-1 plus TNF-alpha. IL-6 transcription was further enhanced by 8BrcAMP co-incubation. More sensitive experiments using a luciferase reporter vector containing the GM-CSF promoter region were necessary to convincingly establish the role of TNF-alpha and 8BrcAMP on transcriptional induction of the GM-CSF gene in +/+(-)1.LDA11 stromal cells. Considering these results and an effect of 8BrcAMP on decreasing GM-CSF transcript stability in actinomycin-D (act-D) decay experiments, we conclude that the inhibitory effect of 8BrcAMP on GM-CSF expression is exerted at the posttranscriptional level. These data demonstrate that the intracellular level of cAMP has an important discriminatory role on expression of the cytokines GM-CSF and IL-6 in a model stromal cell line.
Validity of using pallor to detect children with mild anemia

Background: The World Health Organization recommends the assessment of pallor as an indicator for the presence of anemia in children under 5 years of age at a primary care level where anemia is prevalent. The aim of the present study was to study the validity and interobserver agreement of pallor examination in recognition of anemia in children under 2 years of age.
Roles of the locus coeruleus and adrenergic receptors in brain-mediated hypothalamic-pituitary-adrenal axis responses to intracerebroventricular alcohol.

BACKGROUND Alcohol activates the hypothalamic-pituitary-adrenal (HPA) axis through its actions in both the periphery and the central nervous system (CNS). The studies presented here were designed to test the CNS-specific noradrenergic mechanisms by which alcohol stimulates HPA activity in the male rat. METHODS We used an experimental paradigm in which a small, nontoxic amount (5 μl) of alcohol was slowly microinfused intracerebroventricularly (icv). Alcohol was administered icv to animals with lesions of the locus coeruleus (LC) or in animals pretreated with α- or β-adrenergic receptor antagonists. Hormonal HPA activation was determined by measuring secretion of the pituitary stress hormone adrenocorticotropin (ACTH). Neuronal activation was determined by quantification of the expression of the transcription factor c-fos (Fos). RESULTS As expected, icv alcohol stimulated ACTH secretion from the pituitary and Fos expression in the paraventricular nucleus of the hypothalamus (PVN). Bilateral electrolytic LC lesions blocked the ability of icv alcohol to stimulate ACTH secretion. Pretreatment with icv propranolol increased basal ACTH secretion levels, but icv alcohol did not increase this effect. Propranolol also blunted icv alcohol-induced PVN Fos expression. A low dose of phenoxybenzamine, an α-adrenergic receptor antagonist, did not affect the ability of icv alcohol to stimulate ACTH release. However, a higher dose of the drug was able to block the ACTH response to icv alcohol. Despite this, phenoxybenzamine did not inhibit alcohol-induced Fos expression. Icv pretreatment with corynanthine, a selective α-1 adrenergic receptor antagonist, modestly raised basal ACTH levels and blocked the icv alcohol-induced secretion of this hormone. CONCLUSIONS These results indicate that the LC and norepinephrine play important roles in HPA activation caused by icv alcohol administration, but that the specific adrenergic receptor subtypes involved in this phenomenon still need to be identified.