ATP1A1-linked diseases require a malfunctioning protein product from one allele.

Heterozygous germline variants in ATP1A1, the gene encoding the α1 subunit of the Na+/K+-ATPase (NKA), have been linked to diseases including primary hyperaldosteronism and the peripheral neuropathy Charcot-Marie-Tooth disease (CMT). ATP1A1 variants that cause CMT induce loss-of-function of NKA. This heterodimeric (αß) enzyme hydrolyzes ATP to establish transmembrane electrochemical gradients of Na+ and K+ that are essential for electrical signaling and cell survival. Of the 4 catalytic subunit isoforms, α1 is ubiquitously expressed and is the predominant paralog in peripheral axons. Human population sequencing datasets indicate strong negative selection against both missense and protein-null ATP1A1 variants. To test whether haploinsufficiency generated by heterozygous protein-null alleles are sufficient to cause disease, we tested the neuromuscular characteristics of heterozygous Atp1a1+/- knockout mice and their wildtype littermates, while also evaluating if exercise increased CMT penetrance. We found that Atp1a1+/- mice were phenotypically normal up to 18 months of age. Consistent with the observations in mice, we report clinical phenotyping of a healthy adult human who lacks any clinical features of known ATP1A1-related diseases despite carrying a plasma-membrane protein-null early truncation variant, p.Y148*. Taken together, these results suggest that a malfunctioning gene product is required for disease induction by ATP1A1 variants and that if any pathology is associated with protein-null variants, they may display low penetrance or high age of onset.

ATP1A1 -linked diseases require a malfunctioning protein product from one allele.

Heterozygous germline variants in ATP1A1 , the gene encoding the α1 subunit of the Na + /K + -ATPase (NKA), have been linked to diseases including primary hyperaldosteronism and the peripheral neuropathy Charcot-Marie-Tooth disease (CMT). ATP1A1 variants that cause CMT induce loss-of-function of NKA. This heterodimeric (αß) enzyme hydrolyzes ATP to establish transmembrane electrochemical gradients of Na + and K + that are essential for electrical signaling and cell survival. Of the 4 catalytic subunit isoforms, α1 is ubiquitously expressed and is the predominant paralog in peripheral axons. Human population sequencing datasets indicate strong negative selection against both missense and protein-null ATP1A1 variants. To test whether haploinsufficiency generated by heterozygous protein-null alleles are sufficient to cause disease, we tested the neuromuscular characteristics of heterozygous Atp1a1 +/- knockout mice and their wildtype littermates, while also evaluating if exercise increased CMT penetrance. We found that Atp1a1 +/- mice were phenotypically normal up to 18 months of age. Consistent with the observations in mice, we report clinical phenotyping of a healthy adult human who lacks any clinical features of known ATP1A1 -related diseases despite carrying a protein-null early truncation variant, p.Y148*. Taken together, these results suggest that a malfunctioning gene product is required for disease induction by ATP1A1 variants and that if any pathology is associated with protein-null variants, they may display low penetrance or high age of onset.

Exploration of arm weight effects on hemiparetic stroke participants' gait performance.

BACKGROUND: This study explores the potential benefits of an arm weight intervention for improving gait performance in stroke survivors. Consistent with an interlimb neural coupling mechanism, the investigators hypothesized that arm weight would improve gait performance. METHODS: Nine stroke and nine healthy participants (1 female; age: 58.0 ± 6.8 years) participated. Participants walked over-ground at their preferred speed in four conditions: no weight (C1), non-hemiparetic (healthy: dominant) side weights (C2), hemiparetic (non-dominant) side weights (C3), and bilateral weights (C4). Statistical analyses included repeated analysis of variance (ANOVA) and paired t-test planned comparisons to explore the effects of added weight on gait speed, step width, step length, cadence, and arm swing amplitude. Single-subject analyses used randomization tests to delineate further the weight's effect on gait speed. FINDINGS: The stroke group walked significantly faster with arm weight (p = 0.048), exhibiting large ANOVA (η2p = 0.28) and C1 vs. C4 planned comparison (p = 0.021; dD = 0.95) effect sizes. Four of nine stroke participants significantly increased gait speed in at least one condition, and seven of nine exhibited large effect size increases (d = 0.85-4.71). The stroke group's hemiparetic-side step length and cadence significantly (p = 0.008) increased in C4 compared to C1, exhibiting large effect size increases (rb = 0.96). Four of nine healthy participants significantly increased gait speed in at least one condition, with five of nine exhibiting large effect size increases (d = 0.80-6.63). INTERPRETATION: This study's exploratory results demonstrate arm weight's potential for improving higher-functioning stroke survivors' gait performance. Arm weight addition merits further investigation as a possible rehabilitation intervention in the stroke population.

International consensus conference recommendations on ultrasound education for undergraduate medical students.

OBJECTIVES: The purpose of this study is to provide expert consensus recommendations to establish a global ultrasound curriculum for undergraduate medical students. METHODS: 64 multi-disciplinary ultrasound experts from 16 countries, 50 multi-disciplinary ultrasound consultants, and 21 medical students and residents contributed to these recommendations. A modified Delphi consensus method was used that included a systematic literature search, evaluation of the quality of literature by the GRADE system, and the RAND appropriateness method for panel judgment and consensus decisions. The process included four in-person international discussion sessions and two rounds of online voting. RESULTS: A total of 332 consensus conference statements in four curricular domains were considered: (1) curricular scope (4 statements), (2) curricular rationale (10 statements), (3) curricular characteristics (14 statements), and (4) curricular content (304 statements). Of these 332 statements, 145 were recommended, 126 were strongly recommended, and 61 were not recommended. Important aspects of an undergraduate ultrasound curriculum identified include curricular integration across the basic and clinical sciences and a competency and entrustable professional activity-based model. The curriculum should form the foundation of a life-long continuum of ultrasound education that prepares students for advanced training and patient care. In addition, the curriculum should complement and support the medical school curriculum as a whole with enhanced understanding of anatomy, physiology, pathophysiological processes and clinical practice without displacing other important undergraduate learning. The content of the curriculum should be appropriate for the medical student level of training, evidence and expert opinion based, and include ongoing collaborative research and development to ensure optimum educational value and patient care. CONCLUSIONS: The international consensus conference has provided the first comprehensive document of recommendations for a basic ultrasound curriculum. The document reflects the opinion of a diverse and representative group of international expert ultrasound practitioners, educators, and learners. These recommendations can standardize undergraduate medical student ultrasound education while serving as a basis for additional research in medical education and the application of ultrasound in clinical practice.

Intravenous thrombolysis for the management of acute ischemic stroke in patients therapeutically anticoagulated with heparin: A review.

BACKGROUND: Intravenous thrombolysis (IVT) with alteplase is effective in acute ischemic stroke (AIS). However, its use rate remains low due to the many exclusion criteria. Recent guidelines recommend excluding patients suffering AIS with an elevated aPTT secondary to heparin exposure from receiving IVT. The purpose of this review is to explore the safety and efficacy of IVT in patients therapeutically anticoagulated with heparin. We also propose a treatment algorithm for IVT in patients with AIS that are therapeutically anticoagulated with heparin. METHODS: We performed a systematic review of PubMed and Embase through March 2020 to identify the literature regarding AIS in patients exposed to heparin, followed by IVT treatment, emphasizing safety, efficacy, and clinical outcome using PRISMA guidelines. RESULTS: We included thirteen articles in the final analysis, including three retrospective studies, two observational studies, one randomized trial, five case reports, and two case series. CONCLUSION: There is limited information about the off-label use of IVT in patients with elevated aPTT. Patients with AIS are excluded from IVT if they have recent exposure to heparin. Our review indicates that this population of patients may benefit from IVT as the cases of active bleeding after IVT are few, and functional outcomes are favorable in the long term suggesting that IVT in therapeutically anticoagulated patients may be safe and efficacious.

Effects of arm weight on gait performance in healthy subjects.

Previous studies have investigated how additional arm weights affect gait. Although light weights (0.45 kg) seemed to elicit performance improvements in Parkinsonian patients, it was not studied how light weights affect gait parameters in healthy individuals. It is important to understand normal responses in a healthy population so that clinical effects might be better understood. Therefore, the purpose of this study was to investigate the effects of arm weights on arm swing amplitude, gait performance, and muscle activity in healthy people. Twenty-two subjects walked overground at their preferred speed under different weight carriage conditions (C1: no weight; C2: unilateral arm weight; C3: bilateral arm weights; C4: waist weights). Gait speed increased in C2 (p = 0.018) and C4 (p = 0.013) when compared with C1(C1: 1.21 ±â€¯0.08; C2: 1.25 ±â€¯0.11; C3: 1.24 ±â€¯0.11; C4: 1.25 ±â€¯0.11 m/s) with an increase in cadence during C2 (p < 0.001), C3 (p = 0.008), and C4 (p < 0.001) (C1: 105.5 ±â€¯5.2; C2: 108.5 ±â€¯5.6; C3: 107.9 ±â€¯5.6; C4: 108.5 ±â€¯5.3 steps/min) and in tibialis anterior electromyographic activity on the unweighted side in C2 (p = 0.048) (C1: 21.05 ±â€¯4.59; C2: 25.10 ±â€¯6.10; C3: 23.93 ±â€¯4.75; C4: 24.33 ±â€¯6.32 µV). The results indicate that an additional sensory input with the application of the weights may result in an overcompensation with the whole body and facilitate faster walking speed when applied on one arm or around the waist. The locations of the weights and amount of the weights may elicit different responses. Various strategies of adding weights should be further investigated as a potential intervention to improve performance in individuals with various gait impairments. Although there is evidence for benefits of this intervention in Parkinsonian patients, further study is warranted in other patient populations, such as stroke patients, who might benefit from this intervention to improve gait performance.

Energy metabolism and whole-exome sequencing-based analysis of Sasang constitution: a pilot study.

BACKGROUND: Traditional Korean Sasang constitutional (SC) medicine categorizes individuals into four constitutional types [Tae-eum (TE), So-eum (SE), Tae-yang (TY), or So-yang (SY)] based on biological and physiological characteristics. As these characteristics are closely related to the bioenergetics of the human body, we assessed the correlation between SC type and energy metabolism features. METHODS: Forty healthy, young (22.3 ± 1.4 years) males volunteered to participate in this study. Participants answered an SC questionnaire, and their face shape, voice tone, and body shape were assessed using an SC analysis tool. Thirty-one participants (10 TE, 10 SE, 3 TY, and 8 SY) were selected for further analysis. Collected blood samples were subjected to blood composition analysis, mitochondrial function analysis, and whole-exome sequencing. RESULTS: The SY type showed significantly lower total cholesterol and high-density lipoprotein cholesterol levels than the SE type. Cellular and mitochondrial Adenosine triphosphate (ATP) levels were similar across types. All types showed similar basal mitochondrial oxygen consumption rates, whereas the TE type showed a significantly lower ATP-linked oxygen consumption rate than the other types. Whole-exome sequencing identified several genes variants that were exclusively detected in particular SC types, including 19 for SE, seven for SY, 11 for TE, and six for TY. CONCLUSION: SC type-specific differences in mitochondrial function and gene mutations were detected in a small group of healthy, young Korean males. These results are expected to greatly improve the accurate screening and utilization of SC medicine.

Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.

Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke.

Pupil to limbus ratio: Introducing a simple objective measure using two-box method for measuring early anisocoria and progress of pupillary change in the ICU.

INTRODUCTION: Measurement of static pupillary size in the ICU is of importance in cases of acutely expanding intracranial mass lesions. The inaccuracies with subjective assessment of pupillary size by medical personnel preclude its use in emergent neurological situations. OBJECTIVE: To determine if the ratio of pupil to limbus diameter (PLD ratio) measured by a two-box method is a reliable measure of pupil size for detecting early anisocoria and measuring pupillary changes. MATERIALS AND METHODS: The PLD ratio was defined as the ratio of the pupillary diameter measured at a para-horizontal axial plane with the limbus diameter measured at the same or parallel axial plane. A two-box method was used to estimate the diameters of imaged pupils. Eyes were imaged using an iPhone 4S cellphone camera. Background illumination was measured and kept constant. The pupils of a 78-year-old woman, who presented with a large intra-axial parenchymal hemorrhage, were imaged. The patient had left pupillary miosis in dark but not in bright light. After presenting this case along with the images of the pupillary examination, a group of 21 medical staff were asked several questions on the pupillary examination. Reliability of PLD ratio were assessed via standard error of mean (S.E.M) of PLD ratios for 3 different subjects each imaged under constant illumination and fixation but from different angles to the optical axis. RESULTS: Analysis of questionnaire data together with PLD ratios revealed that ~ 14% and 10% of participants could estimate the pupillary size in darkness and bright light respectively but none were simultaneously accurate indicating that subjective assessment of pupillary size was unreliable. The approach towards a systematic pupillary examination was inconsistent among the participants. The PLD ratio was found to be a reliable measure of pupillary size with standard error of mean below 0.1 mm for the three subjects tested. CONCLUSION: Static pupillary sizes can be objectively and consistently evaluated using PLD ratios using a two-box method. PLD ratios are resistant, within limits, to changes in imaging angle or choice of para-horizontal axes for measurement.

Is initial preservation of deep tendon reflexes in West Nile Virus paralysis a good prognostic sign?

Typical West Nile virus paralysis is characterized by muscle weakness, decreased tone, and loss of deep tendon reflexes attributed to destruction of anterior horn cells. Two cases in which deep tendon reflexes were initially preserved in the presence of profound and persistent muscle weakness are presented here. In both cases, deep tendon reflexes were later severely attenuated or lost, while weakness of the involved muscles remained profound and unchanged. Both patients showed good motor recovery at 6 months. Initial preservation of deep tendon reflexes in the presence of persistent muscle weakness indicates that in the early stages of disease, the muscle weakness in these two cases was not caused by destruction of anterior horn cells. Pathology involving anterior horns preceding AHC destruction could potentially disrupt upper motor neuron pathways to anterior horn cells, causing weakness with initial preserved deep tendon reflexes.

Heritabilities of facial measurements and their latent factors in korean families.

Genetic studies on facial morphology targeting healthy populations are fundamental in understanding the specific genetic influences involved; yet, most studies to date, if not all, have been focused on congenital diseases accompanied by facial anomalies. To study the specific genetic cues determining facial morphology, we estimated familial correlations and heritabilities of 14 facial measurements and 3 latent factors inferred from a factor analysis in a subset of the Korean population. The study included a total of 229 individuals from 38 families. We evaluated a total of 14 facial measurements using 2D digital photographs. We performed factor analysis to infer common latent variables. The heritabilities of 13 facial measurements were statistically significant (p < 0.05) and ranged from 0.25 to 0.61. Of these, the heritability of intercanthal width in the orbital region was found to be the highest (h (2) = 0.61, SE = 0.14). Three factors (lower face portion, orbital region, and vertical length) were obtained through factor analysis, where the heritability values ranged from 0.45 to 0.55. The heritability values for each factor were higher than the mean heritability value of individual original measurements. We have confirmed the genetic influence on facial anthropometric traits and suggest a potential way to categorize and analyze the facial portions into different groups.

Transcranial Doppler velocities in a large, healthy population.

BACKGROUND: Transcranial Doppler (TCD) ultrasonography has been extensively used in the evaluation and management of patients with cerebrovascular disease since the clinical application was first described in 1982 by Aaslid and colleagues TCD is a painless, safe, and noninvasive diagnostic technique that measures blood flow velocity in various cerebral arteries. Numerous commercially available TCD devices are currently approved for use worldwide, and TCD is recognized to have an established clinical value for a variety of clinical indications and settings. Although many studies have reported normal values, there have been few recently, and none to include a large cohort of healthy subjects across age, race, and gender. As more objective, automated processes are being developed to assist with the performance and interpretation of TCD studies, and with the potential to easily compare results against a reference population, it is important to define stable normal values and variances across age, race, and gender, with clear understanding of variability of the measurements, as well as the yield from various anatomic segments. METHODS: To define normal TCD values in a healthy population, we enrolled 364 healthy subjects, ages 18-80 years, to have a complete, nonimaging TCD examination. Subjects with known or suspected cerebrovascular disorders, systemic disorders with cerebrovascular effects, as well as those with known hypertension, diabetes, stroke, coronary artery disease, or myocardial infarction, were excluded. Self-reported ethnicity, handedness, BP, and BMI were recorded. A complete TCD examination was performed by a single experienced sonographer, using a single gate nonimaging TCD device, and a standardized protocol to interrogate up to 23 arterial segments. Individual Doppler spectra were saved for each segment, with velocity and pulsatility index (PI) values calculated using the instrument's automated waveform tracking function. Descriptive analysis was done to determine the mean velocities and PI, and all data were analyzed for changes by decade of age, sex race, handedness, BMI, and BP. RESULTS: Among the key intracranial segments, mean blood flow velocities (MBFV) were highest in the MCA and lowest in the PCA across all ages, sexes, and ethnic groups. There was no difference in the MBFVs between left and right side segments of the Circle of Willis, with the exception of the distal M1 (P = .022) and the C1 (P < .0001), both slightly higher on the left. MBFV were higher among women than men in all segments except for the OA. MBFV decreased with advancing age in both men and women, but this was specific to Caucasian subjects. There were lower velocities in the OA for non-Caucasians. The PI was lower in the left VA (P < .0001), and for most segments was lower in women than men. The PI increased with age in all segments for women, but only in some segments for men, and this finding was also specific to Caucasian subjects. The yield of usable data ranged from 99.7% for the VA and BA, to 88.2% for C2. CONCLUSION: Our study provides normal, reference TCD values for a large cohort of healthy subjects across a wide range of age, sex, and race groups. We observed decreased MBFV and increased PI with aging, and higher MBFV in women. There were few differences in MBFV related to side or ethnicity, but the MFBV and PI changes with age were specific to Caucasians. We provide means and standard deviations of MBFVs across various demographic groups in key intracranial arteries. Such normal TCD values across age, gender, and ethnic groups in healthy subjects represent a useful reference tool for detecting individuals with TCD values outside normal limits and at increased vascular risk. TCD studies in large multiethnic populations are still required to determine differences in brain hemodynamics across various ethnic groups.

Pathways involved in sasang constitution from genome-wide analysis in a Korean population.

OBJECTIVE: Sasang constitution (SC) medicine, a branch of Korean traditional medicine, classifies the individual into one of four constitutional types (Taeum, TE; Soeum, SE; Soyang, SY; and Taeyang, TY) based on physiologic characteristics. The authors of the current article recently reported individual genetic elements associated with SC types via genome-wide association (GWA) analysis. However, to understand the biologic mechanisms underlying constitution, a comprehensive approach that combines individual genetic effects was applied. DESIGN: Genotypes of 1222 subjects of defined constitution types were measured for 341,998 genetic loci across the entire genome. The biologic pathways associated with SC types were identified via GWA analysis using three different algorithms--namely, the Z-static method, a restandardized gene set assay, and a gene set enrichment assay. RESULTS: Distinct pathways were associated (p<0.05) with each constitution type. The TE type was significantly associated with cytoskeleton-related pathways. The SE type was significantly associated with cardio- and amino-acid metabolism-related pathways. The SY type was associated with enriched melanoma-related pathways. TY subjects were excluded because of the small size of that sample. Among these functionally related pathways, core-node genes regulating multiple pathways were identified. TJP1, PTK2, and SRC were selected as core-nodes for TE; RHOA, and MAOA/MAOB for SE; and GNAO1 for SY (p<0.05), respectively. CONCLUSIONS: The current authors systematically identified the biologic pathways and core-node genes associated with SC types from the GWA study; this information should provide insights regarding the molecular mechanisms inherent in constitutional pathophysiology.

Subacute Neurological Deterioration with Selective Axonal Injury in Patients with Acute Ischemic Stroke following Reperfusion of Middle Cerebral Artery Occlusion.

To date, the long-term effects of reperfusion on the salvaged brain tissues have not been addressed in the literature. We report 4 cases presenting subacute neurological deteriorations with selective axonal injury following reperfusion therapies for acute ischemic stroke. Our case series based on 4 patients showed common features distinct from those of early reperfusion injury in that (1) the neurological symptoms developed after 1-2 months of reperfusion therapies, (2) these symptoms were accompanied by the subcortical white matter changes on brain MRI, and (3) these findings were mostly reversible with time. This suggests that axons in the reperfused brain may be vulnerable to further neurological injury.

Reliability and validity of a cold-heat pattern questionnaire for traditional Chinese medicine.

OBJECTIVE: The aim of this study was to develop and evaluate a questionnaire for Cold and Heat pathologic pattern identification in the context of Traditional Chinese Medicine (TCM). This questionnaire was intended to classify subjects into Cold or Heat pattern groups, a distinction that is useful in clinical trials of both herbal and acupuncture treatments. METHODS: A questionnaire that had been developed in a previous study was completed by 63 patients (Group A) and 64 patients (Group B) from TCM hospitals. Each patient was diagnosed by a TCM doctor as one of three patterns: Cold, Heat, and Complex. The questionnaire results were analyzed for internal reliability and validity based on the doctor's diagnosis. RESULTS: Cronbach's alpha coefficients were 0.579 for the 10 Cold items and 0.718 for the 10 Heat items. There were significant differences in the mean questionnaire scores between the Cold and Heat groups. The classification accuracy of this questionnaire for Group A was 94.9%, and for Group B it was 92.3%. CONCLUSIONS: Our results suggest that the questionnaire meets certain basic and fundamental requirements and that it may be useful as an adjunct diagnostic tool. Further studies using a greater number and variety of patients will be needed to evaluate its usefulness in clinical trials and in basic physiologic research.

Association of asymptomatic peripheral arterial disease with vascular events in patients with stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Patients with stroke and patients with transient ischemic attack (TIA) are at high risk for vascular events and may not exhibit the signs and symptoms of peripheral arterial disease (PAD). We investigated if asymptomatic PAD detected by ankle brachial index <0.9 is independently associated with recurrent vascular events in patients with stroke or TIA. METHODS: In this prospective longitudinal hospital-based cohort study, asymptomatic PAD was detected by ankle brachial index measurement in consecutive patients with stroke and patients with TIA. They were assessed for stroke risk factors, ankle brachial index measurement, and laboratory parameters known to be associated with stroke risk. These patients were followed for composite vascular events, including stroke, TIA, myocardial infarction, and vascular death. RESULTS: In a 1-year period, 102 patients were evaluated, of whom 26% had asymptomatic PAD. All patients were followed for a median period of 2.1 years from the index stroke/TIA (range, 1.0 to 2.7 years) for vascular events. Kaplan-Meier curve showed fewer patients with asymptomatic PAD remained free of composite vascular events (48% compared with 84% in the no-PAD group; log rank, P=0.0001). Asymptomatic PAD was significantly associated with composite vascular events before (hazard ratio, 4.2; 95% CI, 1.9 to 9.3; P=0.0003) and after adjustment for confounders (hazard ratio, from Model 1, 2.8; 95% CI, 1.1 to 7.2; P=0.03 and Model 2, 3.4; 95% CI, 1.4 to 8.2, P=0.006). Asymptomatic PAD was also significantly associated with stroke before (hazard ratio, 6.5; 95% CI, 2.1 to 19.9; P=0.001) and after adjustment for confounders (hazard ratio from Model 1, 4.8; 95% CI, 1.5 to 15.3; P=0.009 and Model 2, 5.2; 95% CI, 1.5 to 17.6; P=0.008). CONCLUSIONS: In patients with stroke or TIA, asymptomatic PAD is independently associated with recurrent vascular events and stroke.

A genome-wide scan for the Sasang constitution in a Korean family suggests significant linkage at chromosomes 8q11.22-23 and 11q22.1-3.

OBJECTIVES: We aim to identify the genetic loci responsible for Sasang constitution type, which is important for effective personalized treatments in traditional Korean medicine. SUBJECTS: Forty (40) individuals in a Korean family were recruited for linkage analysis and 310 unrelated individuals for association analysis to confirm the linkage result. OUTCOME MEASURES: Genome-wide linkage analysis was performed for the Korean family using the Affymetrix 500K arrays. MERLIN software was used for multipoint nonparametric linkage (NPL) analysis. The significant candidate regions in linkage analysis were also investigated with association analysis of independent 310 individuals. RESULTS: Linkage analysis showed four significant peaks, 3q27.3, 8p11.21, 8q11.22-23, and 11q22.1-3, whose NPL Z scores are greater than 5.0. Among the significant loci, the 8q11.22-23 and 11q22.1-3 regions were supported by independent association analysis at the level of p < 0.05. CONCLUSIONS: The 8q11.22-23 and 11q22.1-3 regions were suggested as the candidate region for significant linkage to Sasang constitution.

Bacterial, archaeal, and eukaryal diversity in the intestines of Korean people.

The bacterial, archaeal, and eukaryal diversity in fecal samples from ten Koreans were analyzed and compared by using the PCR-fingerprinting method, denaturing gradient gel electrophoresis (DGGE). The bacteria all belonged to the Firmicutes and Bacteroidetes phyla, which were known to be the dominant bacterial species in the human intestine. Most of the archaeal sequences belonged to the methane-producing archaea but several halophilic archarea-related sequences were also detected unexpectedly. While a small number of eukaryal sequences were also detected upon DGGE analysis, these sequences were related to fungi and stramenopiles (Blastocystis hominis). With regard to the bacterial and archaeal DGGE analysis, all ten samples had one and two prominent bands, respectively, but many individual-specific bands were also observed. However, only five of the ten samples had small eukaryal DGGE bands and none of these bands was observed in all five samples. Unweighted pair group method and arithmetic averages clustering algorithm (UPGMA) clustering analysis revealed that the archaeal and bacterial communities in the ten samples had relatively higher relatedness (the average Dice coefficient values were 68.9 and 59.2% for archaea and bacteria, respectively) but the eukaryal community showed low relatedness (39.6%).

Variations in non-invasive radial artery pulse waveform at different measuring positions.

Noninvasive radial artery pulse wave has been widely not only for the pulse wave analysis (PWA) itself but also for assessment of arterial stiffness with estimated aortic pulse wave from peripheral pulse wave. In this study, we tested the differences between the extracted parameters, including AIx, from radial artery pulse waves measured at three different positions preliminarily. A 30 years old female involved in this experiment and this subject has no evidence about cardiovascular diseases. Radial pulse waves were recorded at three different positions on left lower arm ten times for each position. These positions are widely used in pulse diagnosis of traditional medicine.As results of repeated measures ANOVA analysis, 9 parameters were found which had significantly differences in between measuring positions (P<0.05). These parameters wereP_AIx, PP_Amp, A_T1, A_Tr, AIx, AIx_@HR75, ESP, MP_Sysand MP_Dia. And, by Spearman correlation test at P2, it was observed that P_AIx (r =0.894), PP_Amp (r=-0.765),AIx_@HR75 (r=0.929), ESP (r=0.893) and MP_Dia (r=0.792)were highly correlated with AIx. Elaborately, the correlation coefficients between each parameter were high in similar degrees (r>0.70).Further studies on what make differences in these parameters between measuring positions are need. And, ultimately, we need to determine the best measuring process, including measuring position, hold-down pressure, signal quality validation and so on,so to achieve the optimal waveform which represents subject's health condition for both western medicine and traditional medicine.