Individual Variation In Response Research Articles

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia.

Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses. Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures (P0.1) were evaluated. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E, APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoE knock-in rats were performed to test causality. AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3/4) compared to individuals with other APOE genotypes (P = 0.048) and the other tested SNPs. Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (P = 0.004). Additionally, age was inversely related with change in P0.1 (P = 0.007). In hApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3 controls (P < 0.05). APOE4 genotype, sex, and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults. AIH is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative disease. Figure 5 Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, AIHH, in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.

RENAL SYMPATHETIC DENERVATION AND NEURO-HORMONAL EVALUATION BY SELECTIVE VENOUS CATHETERIZATION: THE RESIDENCY STUDY

Objective: Renal denervation (RD) is effective in reducing blood pressure (BP) in hypertensive patients, but the pathophysiologic mechanisms underlying the variable individual response are unclear and early markers of procedural success are lacking. The aim of the study was to evaluate intra-/peri-operative effects of RD on the renin-angiotensin-aldosterone system (RAAS) either as determinants and markers of efficacy. Design and method: Patients with resistant hypertension and eGFR&gt;45 ml/min underwent radiofrequency-RD (Medtronic Symplicity-Spyral) with simultaneous sampling of the renal veins (RV), left adrenal vein and pre-renal inferior vena cava (IVC). Samples were collected before (t0) and 15’ after RD from each sequentially-approached side. Additional peripheral blood samples collected on the morning before RD and 3h, 24h and 7 days after the procedure were tested for renin, aldosterone and cortisol. During this timeframe, antihypertensive therapy remained unchanged. Results: Ten patients were recruited (61±11yo; 30%F; BP = 149/84 ±11/12 mmHg on 4 (range 3-6) antihypertensive drugs). Peripheral renin concentration showed no significant changes during/immediately after RD and up to 7 days after, in spite of the observed BP reduction (136/78 ±17/15 mmHg; p&lt;0.05). Similarly, RV renin was unaffected by ipsilateral RD compared to the corresponding t0 values (p = 0.899). Aldosterone and cortisol increased in the adrenal vein during RD (p&lt;0.001), but their IVC-corrected ratio and their peripheral plasma concentrations at follow-up did not, likely reflecting a self-limiting stress reaction. Conclusions: These results do not suggest any direct blunting effect of RD on RAAS, and do not support the contention of monitoring acute RAAS changes as proxies for procedural effectiveness.

Pharmacogenomics of Hypertension in Africa: Paving the Way for a Pharmacogenetic-Based Approach for the Treatment of Hypertension in Africans.

In Africa, the burden of hypertension has been rising at an alarming rate for the last two decades and is a major cause for cardiovascular disease (CVD) mortality and morbidity. Hypertension is characterised by elevated blood pressure (BP) ≥ 140/90 mmHg. Current hypertension guidelines recommend the use of antihypertensives belonging to the following classes: calcium channel blockers (CCB), angiotensin converting inhibitors (ACEI), angiotensin receptor blockers (ARB), diuretics, β-blockers, and mineralocorticoid receptor antagonists (MRAs), to manage hypertension. Still, a considerable number of hypertensives in Africa have their BP uncontrolled due to poor drug response and remain at the risk of CVD events. Genetic factors are a major contributing factor, accounting for 20% to 80% of individual variability in therapy and poor response. Poor response to antihypertensive drug therapy is characterised by elevated BPs and occurrence of adverse drug reactions (ADRs). As a result, there have been numerous studies which have examined the role of genetic variation and its influence on antihypertensive drug response. These studies are predominantly carried out in non-African populations, including Europeans and Asians, with few or no Africans participating. It is important to note that the greatest genetic diversity is observed in African populations as well as the highest prevalence of hypertension. As a result, this warrants a need to focus on how genetic variation affects response to therapeutic interventions used to manage hypertension in African populations. In this paper, we discuss the implications of genetic diversity in CYP11B2, GRK4, NEDD4L, NPPA, SCNN1B, UMOD, CYP411, WNK, CYP3A4/5, ACE, ADBR1/2, GNB3, NOS3, B2, BEST3, SLC25A31, LRRC15 genes, and chromosome 12q loci on hypertension susceptibility and response to antihypertensive therapy. We show that African populations are poorly explored genetically, and for the few characterised genes, they exhibit qualitative and quantitative differences in the profile of pharmacogene variants when compared to other ethnic groups. We conclude by proposing prioritization of pharmacogenetics research in Africa and possible adoption of pharmacogenetic-guided therapies for hypertension in African patients. Finally, we outline the implications, challenges, and opportunities these studies present for populations of non-European descent.

Is it all in the baseline? Trajectories of chair stand performance over 4 years and their association with grey matter structure in older adults.

Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time-points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K-means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel-based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re-assigned to one of four trajectory-based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory-based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later.

Balancing the beautiful and the good in pursuit of biomarkers for depression.

Balancing the beautiful and the good in pursuit of biomarkers for depression.

Cannabis Pharmacogenomics: A Path to Personalized Medicine

Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids and the incidence of side effects are still difficult to determine. Pharmacogenomics may provide the answers to many questions and concerns regarding the cannabis/cannabinoid treatment and help us to understand the variability in individual responses and associated risks. Pharmacogenomics research has made meaningful progress in identifying genetic variations that play a critical role in interpatient variability in response to cannabis. This review classifies the current knowledge of pharmacogenomics associated with medical marijuana and related compounds and can assist in improving the outcomes of cannabinoid therapy and to minimize the adverse effects of cannabis use. Specific examples of pharmacogenomics informing pharmacotherapy as a path to personalized medicine are discussed.

Maternal immune activation as an epidemiological risk factor for neurodevelopmental disorders: Considerations of timing, severity, individual differences, and sex in human and rodent studies.

Epidemiological evidence suggests that one's risk of being diagnosed with a neurodevelopmental disorder (NDD)-such as autism, ADHD, or schizophrenia-increases significantly if their mother had a viral or bacterial infection during the first or second trimester of pregnancy. Despite this well-known data, little is known about how developing neural systems are perturbed by events such as early-life immune activation. One theory is that the maternal immune response disrupts neural processes important for typical fetal and postnatal development, which can subsequently result in specific and overlapping behavioral phenotypes in offspring, characteristic of NDDs. As such, rodent models of maternal immune activation (MIA) have been useful in elucidating neural mechanisms that may become dysregulated by MIA. This review will start with an up-to-date and in-depth, critical summary of epidemiological data in humans, examining the association between different types of MIA and NDD outcomes in offspring. Thereafter, we will summarize common rodent models of MIA and discuss their relevance to the human epidemiological data. Finally, we will highlight other factors that may interact with or impact MIA and its associated risk for NDDs, and emphasize the importance for researchers to consider these when designing future human and rodent studies. These points to consider include: the sex of the offspring, the developmental timing of the immune challenge, and other factors that may contribute to individual variability in neural and behavioral responses to MIA, such as genetics, parental age, the gut microbiome, prenatal stress, and placental buffering.

Motivational decline and proactive response under thermal environmental stress are related to emotion- and problem-focused coping, respectively: Questionnaire construction and fMRI study.

Despite the diversity of human behavioral and psychological responses to environmental thermal stress, the major dimensions of these responses have not been formulated. Accordingly, the relevance of these responses to a framework of coping with stress (i.e., emotion- and problem-focused) and the neural correlates are unexplored. In this study, we first developed a multidimensional inventory for such responses using social surveys and a factor analysis, and then examined the neural correlates of each dimension using a functional magnetic resonance imaging; we manipulated the ambient temperature between uncomfortably hot and cold, and the correlations between the inventory factor scores and discomfort-related neural responses were examined. We identified three factors to construct the inventory: motivational decline, proactive response, and an active behavior, which appeared to reflect inefficient emotion-focused coping, efficient problem-focused coping, and positive appreciation of extreme environmental temperatures, respectively, under environmental thermal stress. Motivational decline score was positively associated with common neural response to thermal stress in the frontal and temporoparietal regions, implicated in emotion regulation, while proactive response score negatively with the neural responses related to subjective discomfort in the medial and lateral parietal cortices, implicated in problem-solving. We thus demonstrated that two of three major dimensions of individual variation in response to and coping with environmental thermal stress conform to an influential two-dimensional framework of stress coping. The current three-dimensional model may expand the frontiers of meteorological human science in both basic and application domains.

Enabling and restricting functions of the overjet in orthodontic treatment

The aim is to evaluate the functions of the overjet in mediating, aggravating, and enabling the expression of jaw growth in growing patients with Class II division 1 and Class III malocclusions. Beside malocclusion severity and treatment timing, treatment duration warrants special consideration, contrasting shorter-term (2-3 years) and longer-term (5-7 years) responders to treatment, both encompassing the contribution of the adolescent growth spurt. Analysis of the genetic and environmental components affecting the development of malocclusion and growth modification indicates that varying critical periods of growth among the craniofacial components account for the variable individual responses to treatment. Clinical implications include keeping the overjet off the path of mandibular horizontal movement during orthopedic treatment, recognizing gender differences in the potential response to treatment, and assessing the value of longer treatment in slow responders.

An Individuality of Response to Cannabinoids: Challenges in Safety and Efficacy of Cannabis Products.

Since legalization, cannabis/marijuana has been gaining considerable attention as a functional ingredient in food. ∆-9 tetrahydrocannabinol (THC), cannabidiol (CBD), and other cannabinoids are key bioactive compounds with health benefits. The oral consumption of cannabis transports much less hazardous chemicals than smoking. Nevertheless, the response to cannabis is biphasically dose-dependent (hormesis; a low-dose stimulation and a high-dose inhibition) with wide individuality in responses. Thus, the exact same dose and preparation of cannabis may be beneficial for some but toxic to others. The purpose of this review is to highlight the concept of individual variations in response to cannabinoids, which leads to the challenge of establishing standard safe doses of cannabis products for the general population. The mechanisms of actions, acute and chronic toxicities, and factors affecting responses to cannabis products are updated. Based on the literature review, we found that the response to cannabis products depends on exposure factors (delivery route, duration, frequency, and interactions with food and drugs), individual factors (age, sex), and susceptibility factors (genetic polymorphisms of cannabinoid receptor gene, N-acylethanolamine-hydrolyzing enzymes, THC-metabolizing enzymes, and epigenetic regulations). Owing to the individuality of responses, the safest way to use cannabis-containing food products is to start low, go slow, and stay low.

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease

In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022). Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority). Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. ClinicalTrials.gov Identifier: NCT02579499.

Graph Theory Measures and Their Application to Neurosurgical Eloquence.

Improving patient safety and preserving eloquent brain are crucial in neurosurgery. Since there is significant clinical variability in post-operative lesions suffered by patients who undergo surgery in the same areas deemed compensable, there is an unknown degree of inter-individual variability in brain 'eloquence'. Advances in connectomic mapping efforts through diffusion tractography allow for utilization of non-invasive imaging and statistical modeling to graphically represent the brain. Extending the definition of brain eloquence to graph theory measures of hubness and centrality may help to improve our understanding of individual variability in brain eloquence and lesion responses. While functional deficits cannot be immediately determined intra-operatively, there has been potential shown by emerging technologies in mapping of hub nodes as an add-on to existing surgical navigation modalities to improve individual surgical outcomes. This review aims to outline and review current research surrounding novel graph theoretical concepts of hubness, centrality, and eloquence and specifically its relevance to brain mapping for pre-operative planning and intra-operative navigation in neurosurgery.

Farmakogenetika kardiovaskularnih lekova

Individual variations in the patient's response to the administered drugs are a frequent and important clinical problem in medicine and pharmacology. It is especially important to consider these issues when counting cardiovascular disease (CVD) treatment, since CVD is characterized by high incidence in the population, making cardiovascular drugs the most prescribed medication. Currently used medical therapies are adapted to best fit the needs of a wide population of patients who can benefit from them, despite the fact that a certain number of individuals will suffer from inadequate therapeutic effects or even intoxication. By examining the genetic basis that causes individual variations in the response to drugs, pharmacogenetics enables the personalization of drug therapy, with the aim to identify patients who are exposed to an increased risk of serious drug side effects and those missing the maximum drug effectiveness. Polymorphisms of genes that encode protein units of enzymes involved in the drug metabolism, mainly cytochrome P450 enzymes, receptors and drug transporters, affect both pharmacokinetics and pharmacodynamics of drugs often prescribed for CVD, such as beta-blockers, ACE inhibitors, warfarin, clopidogrel, and statins. This approach in cardiological practice would enable adjusting the therapy for patients based on gene polymorphisms, by changing the dose of the existing drugs or using another drug of choice. Although including pharmacogenetics in daily clinical practice would bring along large diagnostic costs, as well as potential legal and ethical dilemmas, a substantial number of patients, overall society, and the health system, in general, could benefit from enhanced therapeutic effects as well as decreased side effects of the applied therapy.

Effects of helicopter net gunning on the survival and movement behaviour of nilgai antelope

Context Research on large, terrestrial mammals often requires physical captures to attach tags or collars, collect morphological data, and collect biological samples. Choice of capture method should minimise pain and distress to the animal, minimise risk to personnel, and consider whether the method can achieve study objectives without biasing results. Aims We studied how capture via helicopter net-gunning affected survival, post-capture movement patterns, and space use of exotic nilgai (Boselaphus tragocamelus) in southern Texas, USA. Methods We estimated daily survival rates for 101 collared nilgai over 28 days, following 125 captures. We calculated mean daily movement rates and net-squared displacement for 21 recaptured nilgai for 60 days, starting 30 days before capture. Key results The survival probability of 125 nilgai individuals was 0.97 (95% CI = 0.92–0.99) over the 28 days following capture, with the lowest daily survival for the day after capture ( x ¯ WR22049_IE1.gif = 0.99; 95% CI = 0.96–1.00). We observed an increase of ~65% in the mean daily movement rate of 134 m/h on the first 2 days since capture, followed by a period of reduced movement out to the 5th day before returning to pre-capture levels. Analysis of net-squared displacement for 21 nilgai showed that 17 resumed pre-capture space-use patterns within a week, whereas four individuals did not return to the pre-capture range for ≥1 month. Conclusions Capture-related mortality rates for nilgai using helicopter net-gunning in our study (3%) were similar or lower than those reported for similar species captured using the same method. While we were able to detect a period of elevated movement rates, followed by a recovery period of diminished movement as a result of capture, nilgai appeared to return to typical behaviour ~6 days post-capture. Most nilgai in our study also resumed typical space-use patterns within a week of capture; however, our results suggest high individual variability in their response. Implications We recommend using net-gunning from a helicopter as a method for capturing nilgai when conditions and where vegetation and topography allow. We suggest censoring data for a minimum of 7 days following capture for analyses related to survival and movement rates. For analyses relating to space use, we suggest inspecting net-squared displacement or some similar displacement analysis for each animal separately to account for individual variation in response and exclude data accordingly.

Impact of Aerobic Training on Cardiovascular Function, Fitness, and Patient Reported Outcomes During Anthracycline Chemotherapy: A Case Series in Women With Breast Cancer.

Chemotherapy for breast cancer can increase the risk of cancer therapy related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD, however, research to date has indicated high degrees of individual variability following exercise interventions in this population. This study aimed to explore the impact of regular, individualized aerobic exercise on CTRCD incidence (defined by global longitudinal strain [GLS]) during and immediately upon the completion of dose-dense anthracycline (DDAC) chemotherapy in 5 women with breast cancer. Five women receiving DDAC with stage I-III breast cancer enrolled. Participants underwent resting echocardiography and exercise testing before, during, upon the completion of, and 3 months after the completion of DDAC treatment to measure GLS and aerobic fitness (VO2peak). Participants opted-in to an individualized 8-week aerobic exercise intervention (3 sessions per week, 24 sessions total) or standard care for the duration of their DDAC treatment. Data for each participant were presented descriptively. Four of the 5 participants completed the exercise intervention during DDAC treatment (adherence 79.2%-91.7%). Mild asymptomatic CTRCD occurred in 2 of the 4 exercising participants, of whom both were at an increased risk (one was >65 years of age and diagnosed with hypertension, with the other receiving trastuzumab prior to DDAC treatment). Varied responses in VO2peak were observed and did not align with changes in GLS. The only participant not to complete the exercise intervention reported poorer health related quality of life and increased cancer related fatigue at all measurement timepoints. This study details the individual variability in cardiovascular responses to exercise that can occur during DDAC treatment in women with breast cancer, which can inform exercise professionals and researchers when designing individualized exercise programs for this population.

The ecological scale mediates whether trees experience drought legacies in radial growth

The impact of lag effects produced by disturbances on primary production has been a major concern among ecologists during the last decade. Sudden and extreme climatic events are imposing drastic reductions in radial growth of trees as evidenced in tree-rings series Dendrochronological samples are obtained at tree level but analyzed at an aggregated scale (i.e., mean chronologies), although aggregating tree-ring chronology on a regional scale may reduce the possibility of studying the variability of individual tree response to drought, by amplifying the average population response. Here, we conducted experimental research in which 370 trees of 5 species were analyzed to assess the potential statistical and scaling issues that may occur when using regression-based methods to analyze ecosystem responses to disturbances. Drought legacy effects were quantified using individual and aggregated scales. Then, lag effects were validated using confidence and prediction intervals to identify values falling outside the certainty of the climate-growth model Individual scale legacy effects contrasted with confidence intervals were commonly distributed across species but were scarce when compared with prediction intervals. The analysis of aggregated scale legacies detected significant growth reductions when validated using prediction intervals; however, individual scale legacy lag effects were not detected. This finding directly contrasts the results obtained when using an aggregated scale. Our results provide empirical evidence on how aggregating ecological data to infer processes that emerge from an individual scale can lead to distorted conclusions. We therefore encourage the use of individual based statistical and ecological procedures to analyze tree rings as a means of further understanding the ecosystem responses to disturbances.

Comparison of health-related quality of life in patients with traumatic brain injury, subarachnoid haemorrhage and cervical spine disease

Purpose The degree of disability that is acceptable to patients following traumatic brain injury (TBI) continues to be debated. While the dichotomization of outcome on the Glasgow Outcome Score (GOSE) into ‘favourable’ and ‘unfavourable’ continues to guide clinical decisions, this may not reflect an individual’s subjective experience. The aim of this study is to assess how patients’ self-reported quality of life (QoL) relates to objective outcome assessments and how it compares to other debilitating neurosurgical pathologies, including subarachnoid haemorrhage (SAH) and cervical myelopathy. Method A retrospective analysis of over 1300 patients seen in Addenbrooke’s Hospital, Cambridge, UK with TBI, SAH and patients pre- and post- cervical surgery was performed. QoL was assessed using the SF-36 questionnaire. Kruskal-Wallis test was used to analyse the difference in SF-36 domain scores between the four unpaired patient groups. To determine how the point of dichotomization of GOSE into ‘favourable’ and ‘unfavourable’ outcome affected QOL, SF-36 scores were compared between GOSE and mRS. Results There was a statistically significant difference in the median Physical Component Score (PCS) and Mental Component Score (MCS) of SF-36 between the three neurosurgical pathologies. Patients with TBI and SAH scored higher on most SF-36 domains when compared with cervical myelopathy patients in the severe category. While patients with Upper Severe Disability on GOSE showed significantly higher PC and MC scores compared to GOSE 3, there was a significant degree of variability in individual responses across the groups. Conclusion A significant number of patients following TBI and SAH have better self-reported QOL than cervical spine patients and patients’ subjective perception and expectations following injury do not always correspond to objective disability. These results can guide discussion of treatment and outcomes with patients and families.

Treatment of Primary Dysmenorrhea Affecting Menstruating Women Using Herbs: A Review

Abstract: Primary dysmenorrhea is a common condition that affects menstruating women, especially young women. Painful cramping in the lower abdominal area, nausea, vomiting, headache, and fatigue is associated with primary dysmenorrhea, which restricts women from normal living life. The productivity and work performance of women are heavily affected by the symptoms of primary dysmenorrhea. Non-steroidal anti-inflammatory drugs (NSAIDs) and low dose oral contraceptive pills (OCPs) are commonly prescribed for the treatment of primary dysmenorrhea. However, variability in individual response to the drugs and their side effects hinder their long-term use among women. Complementary medicine such as herbs is a promising alternative for the treatment of primary dysmenorrhea, but it lacks scientific evidence. The pharmacological and clinical studies of 9 herbs were included in this review. Although excellent analgesic effects of herbs were reported by clinical studies, the detailed mechanism of action of most herbs remains unelucidated. Several studies discovered that herbs exert analgesic effects through direct uterine muscle relaxation effect, inhibition of cyclooxygenase-2 (COX-2), inhibition of intracellular calcium level, and reduction of prostaglandin synthesis. Further investigation of pharmacological action and the recommended dosages of the herbs for the optimal analgesic effect is needed.

Impact of the built, social, and food environment on long-term weight loss within a behavioral weight loss intervention.

Behavioral weight loss interventions can lead to an average weight loss of 5%-10% of initial body weight, however there is wide individual variability in treatment response. Although built, social, and community food environments can have potential direct and indirect influences on body weight (through their influence on physical activity and energy intake), these environmental factors are rarely considered as predictors of variation in weight loss. Evaluate the association between built, social, and community food environments and changes in weight, moderate-to-vigorous physical activity (MVPA), and dietary intake among adults who completed an 18-month behavioral weight loss intervention. Participants included 93 adults (mean±SD; 41.5±8.3years, 34.4±4.2kg/m2, 82% female, 75% white). Environmental variables included urbanicity, walkability, crime, Neighborhood Deprivation Index (includes 13 social economic status factors), and density of convenience stores, grocery stores, and limited-service restaurants at the tract level. Linear regressions examined associations between environment and changes in body weight, waist circumference (WC), MVPA (SenseWear device), and dietary intake (3-day diet records) from baseline to 18months. Grocery store density was inversely associated with change in weight (β=-0.95; p=0.02; R 2=0.062) and WC (β=-1.23; p<0.01; R 2=0.109). Participants living in tracts with lower walkability demonstrated lower baseline MVPA and greater increases in MVPA versus participants with higher walkability (interaction p=0.03). Participants living in tracts with the most deprivation demonstrated greater increases in average daily steps (β=2048.27; p=0.02; R 2=0.039) versus participants with the least deprivation. Limited-service restaurant density was associated with change in % protein intake (β=0.39; p=0.046; R 2=0.051). Environmental factors accounted for some of the variability (<11%) in response to a behavioral weight loss intervention. Grocery store density was positively associated with weight loss at 18months. Additional studies and/or pooled analyses, encompassing greater environmental variation, are required to further evaluate whether environment contributes to weight loss variability.

Next-Generation Sequencing and Bioinformatics-Based Protocol for the Full-Length CYP2E1 Gene Polymorphism Analysis.

Pharmacogenetics studies provide clinically relevant information on the identified associations between genetic variants and individual variability in drug response, which, in turn, offers great promise for guiding personalized drug therapy and clinical trial design. However, there is a lack of information concerning the evidence-based clinical annotations of specific CYP2E1 genetic variants. To design and evaluate the next-generation sequencing-based method for full-length CYP2E1 gene polymorphism analysis. Seven gene-specific oligonucleotide primer pairs targeting overlapping CYP2E1 gene fragments spanning all nine gene exons with interleaving introns, untranslated (UTR) and intergenic regions were designed. Human DNA samples (n = 3) were used as a training set to check the primer performance and to optimize the PCR conditions. The effectiveness of the developed target amplification and sequencing protocol was evaluated using the test set comprising human DNA samples (n = 3) obtained from tuberculosis patients. Sequencing data analysis was performed on the Galaxy online-based platform. The sequencing data quality was sufficient for the detection of genetic variants dispersed throughout the CYP2E1 gene with a high degree of confidence in fully covered regions achieving optimal reading depth of the targeted fragment with high base call accuracy. Developed protocol can be applied in subpopulation-level association studies to determine whether single nucleotide variants (SNVs) or variant combinations from multiple regions of the CYP2E1 gene are of clinical significance.