Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the endotracheal tube ( ett ) should be placed at the optimal level to avoid inadvertent complication .
if the ett is too deep , it increases the risk of unintended single lung ventilation .
on the other hand , if the ett is too shallow , it may cause vocal cord injury by the ett balloon or accidental extubation .
there are many methods for determining the appropriate depth of ett in adults ; fixed insertion depth according to sex ( 23 and 21  cm from the upper incisors in adult males and females , respectively ) , the use of depth marks on the ett , suprasternal palpation of the ett tip or cuff , and bilateral auscultation .
although chest radiography and bronchoscopy are considered an accurate method , they are not always feasible and the costs are considerable . considering the individual variation in the length of the trachea , using fixed depths or marks on the ett may result in inadequate placement of the ett . to reduce the risk of single lung ventilation or vocal cord injury , the segment between the proximal edge of the cuff and the ett tip should be placed at the mid - trachea level . if the length of the trachea can be predicted at bedside before intubation , the ett can be placed at a safe depth for each patient .
the purpose of this study was to determine whether surface anatomical landmarks can be used to predict the mid - tracheal level in adult patients .
neck computed tomography ( ct ) images of adults obtained between 2009 and 2014 were reviewed by a single reviewer after obtaining approval form seoul national university hospital institutional review board ( july 17 , 2015/no .
patients with laryngeal , tracheal , or thoracic abnormalities , tracheostomy or significant tracheal deviation caused by mass lesions were excluded .
in addition , poor ct image quality , absent sagittal ct images , ct images that did not cover the entire trachea , or ct images taken in neck hyperextension ( boidin angle > 130 on scout view ) or hyperflexion ( boidin angle < 110 on scout view ) position were also excluded .
levels of subglottic and tracheal airway segments that include the vocal cords ( vc ) , the cricoid cartilage ( cc ) , and the carina were identified using the method described by sirisopana et al .
the vocal cords were identified as the most cranial level of the upper airway , with a teardrop shape below the laryngeal ventricle . anatomic level of suprasternal notch ( ssn )
the level of manubriosternal junction ( msj ) was defined as the middle level between the manubrium and the body of the sternum where the second rib attaches to the sternum .
the level of carina was defined as the bifurcation of right and left main bronchus and identified by the figure 8 shaped lumen .
the external locations of the cc , ssn , and msj were defined on the skin surface .
the distances between the external points of the cc and the ssn ( extcc - ssn ) , and those of the ssn and the msj ( extssn - msj ) were measured .
the distances between the subglottic structures at the levels of the vc , the cc , ssn , and carina were measured .
tracheal length was calculated as the summation of the distances measured from the vc to the carina .
the mid - trachea level was calculated from tracheal length and the ideal position of ett is shown in fig .
2 . identification of subglottic segments on axial view ( right ) , and defining the distances between subglottic segments on sagittal view ( left ) in a 45-year - old male patient .
cc  =  cricoid cartilage , extcc - ssn  =  the surface distances from the cricoid cartilage to the suprasternal notch , extssn - msj  =  the surface distances from the suprasternal notch to the manubriosternal junction , msj  =  manubriosternal juction , ssn  =  suprasternal notch , vc  =  vocal cord , tracheal length  =  a  +  b  +  c  +  d. the ideal position of endotracheal tube ( ett ) to minimize the risk of endobronchial intubation and vocal cord injury .
the mid - point between the proximal edge of the cuff and the ett tip was matched to the level of the middle of the trachea ( mtl ) , which was calculated from the tracheal length .
cc  =  cricoid cartilage , ett  =  endotracheal tube , msj  =  manubriosternal juction , mtl  =  the level of the middle of the trachea , ssn  =  suprasternal notch , vc  =  vocal cord .
the correlations between age , height , weight , and tracheal length were analyzed using linear regression .
the relationships between surface measurements and the mid - tracheal level were analyzed with bland
the distance between the cc and the ssn was longer in females ( p  <  0.001 ) , whereas distances between the vc and the cc , the ssn and the carina , and the tracheal length were longer in males ( p  <  0.001 ) .
the extcc - ssn was longer in females ( p  <  0.001 ) , whereas extssn - msj was longer in males ( p  <  0.001 ) .
demographic data and measured distances between subglottic structures of trachea , external landmarks , and calculated tracheal length .
the calculated tracheal length was 131.9 ( 10.3 ) mm and ranged from 106.0 to 169.8  mm .
tracheal length showed weak correlation with height ( r  =  0.2188 ) and weaker correlation with age ( r  =  0.0004 ) and weight ( r  =  0.0466 ) ( fig .
the calculated mid - tracheal level was 66.0    5.1  mm from the vc .
altman plots showing the difference between the mid - tracheal level and the surface measurements are shown in fig .
the bias was calculated by subtracting the mid - tracheal level from the surface measurements .
the difference between the extcc - ssn and the mid - tracheal level was 6.6 ( 12.5 ) mm , and the difference between the extssn - msj and the mid - tracheal level was 19.2 ( 6.1 ) mm .
altman plots showing the agreement between the mid - tracheal level ( mtl ) and the surface measurements of surface anatomical landmarks .
( left ) the bias ( subtraction of the mid - tracheal level from the surface distance from the cricoid cartilage to the suprasternal notch ) and 95% limit of agreement as the mean difference were 6.6 [ 31.1 to 17.9 ] ( mm ) .
( right ) the bias ( subtraction of the mid - tracheal level from the surface distance from the suprasternal notch to the manubriosternal junction ) and 95% limit of agreement as the mean difference were 19.2 [ 31.1 to 7.2 ] ( mm ) .
extcc - ssn  =  the surface distances from the cricoid cartilage to the suprasternal notch , extssn - msj  =  the surface distances from the suprasternal notch to the manubriosternal junction , mtl  =  the level of the middle of the trachea .
altman plots of the difference between the extcc - ssn and the mid - tracheal level in female and male patients .
the calculated mid - tracheal level was 64.5 ( 4.6 ) mm in females and 67.9 ( 5.0 ) mm in males .
the difference between the extcc - ssn and the mid - tracheal level was 1.7 ( 11.7 ) mm in females and 12.8 ( 10.7 ) mm in males ( p  <  0.001 ) .
altman plots of female ( left ) and male ( right ) patients showing the agreement between the mid - tracheal level ( mtl ) and the surface the surface distance from the cricoid cartilage from the suprasternal notch .
( left ) the bias ( subtraction of the mid - tracheal level from the surface distance from the cricoid cartilage to the suprasternal notch ) and 95% limit of agreement as the mean difference were 1.7 [ 24.6 to 21.2 ] ( mm ) in females .
( right ) the bias ( subtraction of the mid - tracheal level from the surface distance from the cricoid cartilage to the suprasternal notch ) and 95% limit of agreement as the mean difference were 12.8 [ 33.8 to 8.2 ] ( mm ) in males .
extcc - ssn  =  the surface distances from the cricoid cartilage to the suprasternal notch , mtl  =  the level of the middle of the trachea .
this study showed that mid - tracheal level could be estimated by the surface distance between the cc and the ssn ( extcc - ssn ) . compared with males , extcc - ssn more
accurately predicts the mid - tracheal level in females . in clinical practice , physicians can use extcc - ssn to determine the depth of ett so that the segment between the proximal edge of the cuff and the ett tip lies at the mid - tracheal level .
there are several studies that used the distance between the surface anatomical landmarks to estimate the airway length and the optimal insertion depth of endotracheal tube .
lee et al showed that the distance between the upper incisor and the manubriosternal angle in the neck extension position correlates with the distance between the upper incisor and the carina in the neutral neck position .
evron et al used the sum of the 2 distances from the mouth angle to the jaw angle and from the jaw angle to the sternal manubrium to determine the depth of ett
. however , these methods are complicated than single measurement of extcc - ssn due to the difficulty in locating the sternal manubrium , more than 1 measurement , and the need for full neck extension .
the physicians can easily apply our method with a simple measurement of the extcc - ssn to estimate the mid - tracheal level , and apply this depth during endotracheal intubation .
however , according to previous studies in adults , flexion and extension of the neck from neutral position are associated with the inward and outward movements of the ett .
conrardy et al showed that the orally intubated ett can move 1.5 ( range 0.52.0 ) cm toward the carina during flexion and 2.4 ( range 1.34.3 ) cm away from the carina during extension .
kim et al showed that the ett can migrate 1.3 ( sd 0.6 ; range 0.52.5 ) cm toward the carina during flexion and 1.7 ( sd 0.8 ; range 0.43.1 ) cm during extension .
therefore , the position of the neck should be considered when determining the optimal depth of the ett .
first , this study was a retrospective analysis of ct images and the distances were measured in the neutral position .
second , since the vc is used as a baseline of the depth of intubation in our method , it can be difficult to apply our method to patients with high cormack grades .
lastly , the efficacy of this method is yet to be demonstrated in clinical practice . in conclusion ,
the mid - tracheal level , which is considered the optimal depth of ett , can be predicted by the surface distance between the cc and ssn in adults , especially in females .

Answer:
abstractendotracheal tube ( ett ) should be placed at the optimal level to avoid single lung ventilation or accidental extubation .
 this study was performed to estimate the mid - tracheal level by using surface anatomical landmarks in adult patients.neck computed tomography images of 329 adult patients between the ages of 16 and 79 years were reviewed . in the midline sagittal plane , the levels corresponding to the vocal cords , cricoid cartilage , suprasternal notch , manubriosternal junction , and carina were identified .
 the surface distances from the cricoid cartilage to the suprasternal notch ( extcc - ssn ) and that from the suprasternal notch to the manubriosternal junction ( extssn - msj ) were measured .
 the relationship between mid - tracheal level and the surface distances was analyzed using bland
 altman plot.the difference between the extcc - ssn and the mid - tracheal level was 6.6 ( 12.5 ) mm , and the difference between the extssn - msj and the mid - tracheal level was 19.2 ( 6.1 ) mm .
 the difference between the extcc - ssn and the mid - tracheal level was smaller in females compared with males [ 1.7 ( 11.7 ) mm vs 12.8 ( 10.7 ) mm ; p  <  0.001].the mid - tracheal level , which is helpful in planning the insertion depth of an ett , can be predicted by the surface distance between the cricoid cartilage and suprasternal notch in adults , especially in females .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
an increased incidence of hashimoto thyroiditis has been reported in patients with turner
 syndrome . in view of its pathogenic relationship with autoimmune thyroiditis
we report the case of a 9-yr - old girl with turner syndrome who developed graves
 disease during recombinant human gh therapy , and we discuss previous reports of this
 association .
the patient was the first child of healthy unrelated parents of normal stature , father
 175.0  cm and mother 159.0  cm .
the patient was born
 after an uncomplicated pregnancy at a gestational age of 37 wks and 1 d. her birth weight
 was 2490  g. on examination , lymphedema and webbed neck were detected .
chromosomal analysis
 of peripheral blood lymphocytes ( n=26 ) showed complete deletion of the short arm of the
 second x chromosome ( karyotype : 45 , x ) . at the age of 5 yr and 2 mo ,
her height was 98.2  cm ( 2.25 sd ) and her weight was 14.4  kg
 ( 1.48 sd ) .
a gh stimulation test was performed , and
 the peak gh values after stimulation with clonidine and arginine were 8.39 ng / ml and 5.56
 ng / ml , respectively . of note
is that diagnosis of complete gh deficiency is less than 5
 ng / ml in this assay .
recombinant human ( rh ) gh therapy ( 0.175  mg / kg / wk ) was initiated with
 success ( fig .
thyroid function tests showed a tsh level of 0.01 u / ml ( normal ,
 0.50 to 5.50 u / ml ) , a free ( f ) t4 value of 6.00 ng / dl ( normal , 0.85 to 1.80
 ng / dl ) , and a free t3 value of 21.76 pg / ml ( normal , 2.50 to 5.50 pg / ml ) .

anti - thyroglobulin antibody was 3.4 u / ml ( normal , < 0.3 u / ml ) .
anti - thyroid peroxidase
 antibody was 5.5 u / ml ( normal , < 0.3 u / ml ) .
tsh receptor antibody ( trab ) was 52% ( normal ,
 < 15% ) .
these results are compatible with a diagnosis of graves disease and treatment
 with thiamazole was started .
growth curve of the patient at the latest follow up ( 9 y old ) , the development of the patient s breast was tanner stage
 1 .
treatment with thiamazole was continued and the thyroid function has stayed within normal
 ranges .
the association of turner syndrome with graves disease was reported in english about
 1020  years ago ( 1,2,3,4,5,6,7,8,9,10 ) .
table 1table 1 graves disease in turner syndrome summarizes the historical thirteen known cases of graves disease with turner
 syndrome , including our case .
this table reveals that the clinical characteristics of
 graves disease with turner syndrome are similar to those known generally in patients
 without turner syndrome in terms of ages of the onset , symptoms and prognosis .
treatment with rhgh was
 given to 4 patients in table 1 , and it was
 continued in 3 out of the 4 patients including our case .
this continuation of gh treatment ,
 together with the successful treatment of hyperthyroidism , suggests that a direct link
 between gh treatment and graves disease is unlikely .
consistent with this hypothesis , the
 incidence of hyperthyroidism in japanese patients with turner syndrome receiving rhgh
 therapy is 0.40% , which is similar to overall incidence of hyperthyroidism in patients with
 turner syndrome , 00.5% ( 11 , 12 ) .
it is well known that hyperthyroidism in patients with turner syndrome leads to
 acceleration of height velocity ( 6 , 13 ) . in our patient ,
the height velocity was not
 increased by hyperthyroidism , probably because her growth had been already accelerated by
 rhgh therapy before the onset of hyperthyroidism .
it is important to monitor changes of thyroid function as well as growth parameters in
 patients with turner syndrome , as is recommended by sybert and mccauley ( 14 ) .

Answer:
an increased incidence of hashimoto thyroiditis has been reported in patients with
 turner syndrome , but several cases of graves disease were also described ten to 20  years
 ago .
 we report the case of a patient with turner syndrome who developed graves disease ,
 3  years after successful treatment with recombinant human growth hormone ( gh ) .
 a diagnosis
 of graves disease was made and treatment with thiamazole was started , which resulted in
 normalization of the thyroid function .
 it is important to monitor thyroid function as well
 as growth parameters in patients with turner syndrome .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
most patients are asymptomatic or suffer from mild symptoms only , ( 1 ) and many present with extraintestinal manifestations such as neurologic disorders ( 2 ) .
the anti - tissue transglutaminase antibody ( ttga ) test is a sensitive and specific tool in disclosing celiac disease with overt villous atrophy ( 3 ) with a specificity of approximately 95% , false positive tests are uncommon , and ttga may appear in serum at an early stage in the disease , in other words before the clinical manifestations and even before the development of villous atrophy ( 4 ) .
psychiatric disorders are also common in untreated celiac disease , especially depressive symptoms ( 58 ) .
hallert & derefeldt reported that nine out of 42 studied subjects had attended a psychiatric clinic because of neurotic problems and most of them are involved with depressive disorders ( 7 ) .
celiac disease was considered relatively uncommon in iran , until recently an estimated population prevalence of 1:166 was reported ( 9 ) .
greater awareness of its varying presentation and the availability of new serologic tests have shown celiac disease to be relatively common ( 10 ) .
these observations prompted us now to assess the association between celiac disease and severe chronic depression and schizophrenia .
this cross - sectional study was carried out in 2006 - 2007 . by random sampling
, 200 inpatient men comprising 100 with chronic depression and 100 with schizophrenia ( mean age 37 years , range 18 - 68 years ) were enrolled in razi hospital , tabriz , iran .
chronic depression was defined according to dsm - iv criteria , ( 11 ) diagnosed and treated by semi - structural clinical interview by two psychiatric experts .
the duration of the diseases was more than two years , and the diseases were unbearable without antipsychotic drugs .
patients with schizophrenia suffered from different types of the disease such as paranoid , phrenetic or undistinguished .
two hundred healthy males were selected as controls , matched for age and birthplace ( mean age 32 , range 4 - 77 years ) .
a written informed consent was obtained from patients ( or from next of kin if necessary ) and the study was approved by the institutional ethics committees of the research center for gastroenterology and liver disease , tabriz medical university .
iga class ttga antibody was measured by enzyme - linked immunosorbent assay using a commercially available kit ( eu - ttg iga , eurospital , trieste , italy ) .
a titer of > 7 u / ml was considered positive as recommended by the manufacturer .
a frequency of 0.6% celiac disease has been reported in iran ( 9 ) . assuming this frequency in 200 controls and a tenfold frequency in psychiatric patients ( 6% , as has been reported in many autoimmune conditions ) the statistical power of 0.80 at a significance level of 0.05
percentages were compared by rates and proportion ; 95% confidence intervals ( ci ) were reported .
a frequency of 0.6% celiac disease has been reported in iran ( 9 ) . assuming this frequency in 200 controls and a tenfold frequency in psychiatric patients ( 6% , as has been reported in many autoimmune conditions ) the statistical power of 0.80 at a significance level of 0.05
percentages were compared by rates and proportion ; 95% confidence intervals ( ci ) were reported .
none of the 200 patients had a history of chronic diarrhea and all were taking antipsychiatric drugs ( antipsychotic such as risperidone , haloperidol or perphenazine and anticholinegic for schizophrenic patients , and fluoxetine and tricyclic antidepressants for depressive patients ) .
three patients with chronic psychiatric disorders were ttga positive , in which one ( age 52 years ) with schizophrenia and two ( both 30 years of age ) with chronic depression . of these three patients ,
two refused duodenal biopsy and one died during the study period . in the control group ,
one ( age 25 years ) out of 200 individuals was positive , but duodenal histology proved normal .
the prevalence of positive celiac disease serology in patients with chronic psychiatric disorders was thus slightly but not significantly higher than in controls ; 1.5% , ( 95% ci : 0.38 - 4.03 ) and 0.5% ( 95% ci : 0.00025 - 2.44 ) , respectively ( p = 0.06 ) . clinical features and laboratory findings among the patients with schizophrenia and depression are shown in table 1 .
five in the study group and none in the control group had selective iga deficiency .

clinical and laboratory features of male patients with schizophrenia and depression
 ttga iga - class anti - tissue transglutaminase antibody ; meanstandard deviation
in our reports , the frequency of positive celiac disease serology in iranian inpatients suffering from depression or schizophrenia was 1.5% . by comparison , pynnnen et al .
have shown the prevalence of celiac disease in patients with depression to be 0.7% ( 5 ) .
the same authors have reported that in adolescent celiac disease patients the frequency of depression and disruptive behavioral disorders was higher than in controls , 31% and 7% , respectively ( 6 ) .
the present observations support earlier findings that celiac disease is not increased in patients with schizophrenia .
( 12 ) studied 7754 schizophrenia patients in denmark and found a frequency of untreated celiac disease of 0.05% . in uk , west et al . showed that in subjects with celiac disease the prevalence of schizophrenia was 0.25% , the adjusted odds ratios showing no association between the two conditions ( celiac disease vs. controls 0.76 , 95% ci : 0.41 - 1.4 ) ( 13 ) .
by contrast , a study in the uk revealed that patients with celiac disease developed schizophrenia 3 times more frequently than non - celiac controls ( 14 ) .
some studies have suggested that schizophrenia and celiac disease may be associated with similar or adjacent genes ( 15 , 16 ) .
it has indeed been reported that genetic susceptibility in schizophrenia lies in human leukocyte antigen ( hla ) dq , similarly to autoimmune disorders such as celiac disease ( 17 ) .
by contrast , a recent study showed no such hla association in schizophrenia ( 18 ) . in a case report
, the symptoms of schizophrenia were improved in a celiac patient aged 33 years after the introduction of gluten free diet ( 19 ) .
here we had no opportunity to investigate the effect of gluten - free diet , since two patients refused and one died during the study . in this present study ,
the frequency of positive celiac disease serology in patients with chronic depressive ( 2% ) and schizophrenia ( 1% ) was in fact similar to that found in healthy blood donors in iran ( 0.6% ) ( 9 ) . in the latter study ,
the frequency of celiac disease in males ( 1.8% ) was higher than in females ( 0.5% ) , although usually 60%-70% of celiac disease patients are female . we could not investigate females with psychiatric disorders , which may be considered as a limitation to the current study . on the other hand ,
all our patients were inpatients , indicating that they suffered from severe manifestations of chronic psychiatric disorders .
patients with selective iga deficiency remain negative by ttga iga class screening , and we had no opportunity to test our 5 such subjects by igg class ttga . in blood donors
there may thus be additional celiac case in our study group , but we consider that this would not change our conclusions . to conclude , mass screening for celiac disease in patients with depression or schizophrenia is not advocated . despite this , alertness to celiac disease should be high , since early diagnosis and treatment by gluten - free diet may ameliorate the symptoms and quality of life of these patients .

Answer:
aimthe aim of this study was to determine the prevalence of celiac disease in iranian patients suffering from chronic depression or schizophrenia.backgroundpsychiatric disorders are common in untreated celiac disease.patients and methodstwo hundred iranian inpatient men with in chronic phase of depressive disorders or schizophrenia , and 200 age - matched healthy male subjects were screened for celiac disease by anti - tissue transglutaminase iga antibodies .
 the mean age of the study patients was 37 years.resultsone ( 1% ) schizophrenic and two ( 2% ) depressive patients were positive for anti - tissue transglutaminase iga antibodies ; duodenal biopsy was not possible in these subjects . in the control group one ( 0.5% )
 individual was positive for anti - tissue transglutaminase iga antibodies , but had normal duodenal histology .
 the difference between patients and controls was not statistically significant.conclusionthe frequency of celiac disease serology in schizophrenic and depressive inpatients was not significantly higher than that in the general population
 . we would therefore not advocate systematic serologic screening in these patients , but alertness to celiac disease should be kept in mind .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
obesity is associated with numerous chronic diseases and , currently , its prevalence is 34% in us adults .
excess fat storage is the result of greater energy intake than expenditure for a period of time ; thus , increasing energy expenditure is an important strategy to treat obesity .
physical activity energy expenditure ( paee ) can be further divided into energy expended during structured exercise and during activities of daily living other than structured exercise .
there has been extensive research investigating the effects of various exercise and/or caloric restriction interventions for inducing weight loss .   in general ,
these programs are successful at inducing weight loss ; however , there is some evidence showing that increases in total daily energy expenditure during prescribed exercise interventions are less than expected given the amount of energy expended during the prescribed exercise sessions     [ 38 ] .
in support of this , one study showed that accelerometer counts from physical activities outside of structured exercise decreased by 8% after a 12-week training period .
this suggests that paee outside of the structured exercise may decrease as a result of the exercise treatment .
all of these prior studies examined the chronic or longer - term effects of exercise interventions on paee .
however , it is also important to determine whether there are potential changes in paee acutely on days in which the exercise is performed .
yet , to date , only one small study examined this acute effect of exercise on daily paee .
it reported that accelerometer counts from nonexercise activities were lower on days with , than without , structured exercise during a 12-week exercise program .
thus , the purpose of the present study was to determine whether performing a single exercise bout impacts daily paee in postmenopausal women and to determine whether the intensity of the exercise bout plays a role in any potential changes in daily paee .
women in this study are a subset of those enrolled in a randomized clinical trial that was designed to determine whether intensity of aerobic exercise affects the loss of abdominal adipose tissue and improvement in cardiovascular disease risk factors in postmenopausal women with abdominal obesity ( clinicaltrials.gov : nct00664729 ) .
briefly , they were : ( 1 ) older postmenopausal ( age : 5070 yr ) , ( 2 ) overweight or obese ( bmi : 2540  kgm and waist circumference > 88  cm ) , ( 3 ) nonsmoking , ( 4 ) not on hormone therapy , and ( 5 ) sedentary ( < 15 minutes of exercise , two times per wk ) in the past 6 months before enrollment .
the study was approved by the wake forest university institutional review board , and all women signed an informed consent form to participate in the study according to the guidelines for human research .
data used for the current analyses are from women who were randomized to caloric restriction plus moderate - intensity aerobic exercise ( moderate - intensity ) or caloric restriction plus vigorous - intensity aerobic exercise ( vigorous - intensity ) and completed the study interventions .
there were 18 women in the moderate - intensity and 18 women in the vigorous - intensity groups who had paee data available from before the intervention and from days with and without center - based exercise in the last month of intervention .
both the moderate - intensity and vigorous - intensity interventions were 5 months , and the energy deficit was designed to be approximately 2100  kcalwk from caloric restriction and 700  kcalwk from center - based exercise .
individual energy needs for weight maintenance were calculated from each woman 's resting metabolic rate ( indirect calorimetry after an overnight fast by using a medgraphics ccm / d cart and breeze 6.2 software , medgraphics , st .
paul , mn ) and an activity factor based on self - reported daily activity ( 1.2 - 1.3 for sedentary lifestyle ) .
individual diets were developed by a registered dietitian according to each woman 's choices from a menu designed by a registered dietitian .   throughout the course of the 5-month intervention ,
all women were provided with daily lunch , dinner , and snacks prepared by the general clinical research center ( gcrc ) metabolic kitchen .
they were asked to eat only the food that was given to them or that was approved from the breakfast menu .
energy make - up of the diet was approximately 25% from fat , 15% from protein , and 60% from carbohydrate .
women were allowed to consume as many noncaloric , noncaffeinated beverages as they liked .
they were also allowed 2 free days per month during which they were not provided food but were given guidelines for diet intake at their prescribed energy level .
all women were provided with daily calcium supplements ( 500  mg , 2  timesd ) .
they were asked to keep a log of all foods consumed , and the records were monitored by the dietitian to verify compliance .
the exercise interventions were center - based walking on treadmills ( lifefitness 9500hr , life fitness co. , il ) on 3  dwk under the supervision of an exercise physiologist .
exercise progressed from 2025 min the first week to 55 minutes by the end of the sixth week for the moderate - intensity ( 4550% of maximum oxygen consumption , vo2max ) group and it progressed from 1015 minutes the first week to 30 min by the end of the sixth week for the vigorous - intensity ( 7075% of vo2max ) group .
the target exercise intensity was determined based on each woman 's target heart rate calculated from the karvonen equation [ ( hrr  intensity ) + resting heart rate ] , where hrr is the maximal heart rate , obtained from each woman 's maximum exercise test , minus resting heart rate .
treadmill speed and grade were adjusted on an individual basis to ensure women exercised at their prescribed exercise intensity .
heart rate readings ( by polar heart rate monitors ; polar electro inc , lake success , ny ) were taken before , at least 2 times during ( to monitor compliance to the prescribed exercise intensity ) , and after the exercise .
it is about the size of a pager and is worn by clipping onto the waist .
it collects 3-dimensional data at one minute intervals and stores such data for 7 days .
activity energy expenditure was computed using the manufacturer 's software from the integrated acceleration and body mass with formula developed by the manufacturer .
daily paee was calculated using the average calories expended per minute times 1440 minutes a day .
women were asked to wear the accelerometer before and each month during the intervention , for 57 days including week days and weekend days .
women were instructed not to change their activities while wearing the accelerometer at all times , except while sleeping and bathing .
data collected from rt3 monitors were included only when there were valid data from both before the intervention and during the last month of intervention .   during the last month of intervention ,
rt3 data were considered valid when data were collected from at least 2 days with center - based exercise and at least 2 days without center - based exercise .
the average paee from days with and without center - based exercise were used for the current analyses .   of note ,
the average daily paee from days with center - based exercise included the energy expended during the exercise sessions , and none of the women performed structured exercise at baseline .
treadmill readings during the exercise sessions were recorded for each woman as a measure of energy expended during center - based exercise .
height and weight were measured before and after the 5-month intervention with shoes and jackets or outer garments removed .
all analyses were performed using sas software , version 9.1 ( sas institute , cary , nc ) .
paired t - tests were used to compare values within the same group at different measurement points .
as shown in table 1 , there were no differences in baseline characteristics such as age , racial distribution , body weight , and body mass index between the moderate - intensity and vigorous - intensity groups .
the total amount of weight loss during intervention was similar between the moderate - intensity and vigorous - intensity groups ( 12.9  4.2  kg or 14.6  4.8% and 12.6  5.1  kg or 13.5  4.6% , resp . ) .   during the last month of intervention ,
paee on days with center - based exercise was significantly higher in women performing moderate - intensity exercise than in women performing vigorous - intensity exercise ( p = .052 ) .
in contrast , paee on days without exercise was not statistically different between the two groups ( p = .135 ) .
in the moderate - intensity group , 13 of the 18 women had higher paee on days with than without center - based exercise ( figure 1 ) , and the average paee on days with exercise ( 577.7  219.7  kcald ) was higher than on days without exercise ( 450.7  140.5  kcald , p = .011 ) ( table 1 ) .   yet , the difference ( 127.0  188.1  kcald ) was much smaller than the energy expended during exercise ( 325.0  79.6 kcald ) ( figure 2 ) , suggesting that , during the 5th month of exercise training , women expended less energy on activities outside of the structured exercise when they exercised during the day .   in support of this , paee on days with center - based exercise was not different from baseline paee ( 520.8  206.5  kcald ; p > .05 for both ) in women performing moderate - intensity exercise even though energy expended during exercise was included in the daily paee on days with exercise . on the other hand , in the vigorous - intensity group , 12 of the 18 women had lower paee on days with than without center - based exercise during the last month of the intervention ( figure 1 ) .
the average daily paee on days with exercise ( 450.6  153.6  kcald ) was lower than on days without exercise ( 519.2  127.4  kcald ) ( difference = 68.6  136.1  kcald , p = .047 ) again even though energy expended during exercise ( 296.8  93.0  kcald ) was included in daily paee on days with exercise ( figure 2 ) .
this indicates that , during the 5th month of exercise training , women performing vigorous - intensity exercise were expending more total calories on nonexercise days than on exercise days .
in addition , paee on days without exercise was not different from baseline daily paee ( 543.2  164.0  kcald ; p > .05 ) ; however , paee on days with exercise ( which included energy expended during center - based exercise ) was significantly lower than baseline paee ( p = .020 ) .
this study adds information to the literature regarding how acute exercise sessions affect daily paee and whether the intensity of exercise influences the effects .
we found that , during the last month of a 5-month moderate - intensity exercise training intervention , the daily paee during days with center - based exercise was higher than days without exercise by an amount much smaller than the exercise energy expenditure .
during the 5th month of a vigorous - intensity exercise training intervention , daily paee during days with center - based exercise was lower than days without center - based exercise sessions , even with energy expended during the exercise sessions included in paee .
therefore , there was a reduction in paee outside of the center - based exercise sessions in both intervention groups , and this reduction appeared to differ based on the intensity level of the center - based exercise because it was greater in women performing vigorous - intensity , compared to moderate - intensity , exercise .
our findings are in line with those of meijer et al . , who found that accelerometer counts of total physical activity were similar between days with and without training , and that after energy expenditure during the training session was subtracted out , accelerometer counts were significantly lower on training days .   in their study ,
the training program included one aerobic exercise of 60 minutes and one cardio- and weight - stack machine exercise of 90 minutes each week for 12 weeks in men and women of 55 years and older .
we can not directly compare the magnitude of the paee responses in our study to their study because the intensity of the exercises was not specified and only accelerometer counts were reported in their study .
we also showed that exercise at vigorous intensity induced greater compensation in paee than moderate - intensity exercise .   of note ,
both exercise programs in our study are consistent with the current physical activity guidelines for adults     [ 11 , 12 ] .
the frequency of the exercise sessions was the same for the moderate - intensity and vigorous - intensity exercise groups , and the volume of exercise was also similar .
however , this does not exclude the possibility that volume or frequency of exercise of an exercise program may affect the  chronic  response in paee to the program .
further studies are needed to address these questions because these are important factors to consider when designing exercise programs to better meet an individual 's goal for participating exercise . in this study ,
thus , women were relatively trained so that paee responses to acute exercise may be somewhat different from those if women were untrained
.   however , we suspect that the compensation in paee is likely lower in the trained state .   in other words , for a person who does not participate in regular exercise , an acute session of exercise may induce greater compensation in paee
.   on the other hand , the information found in this study may be more important because with the epidemic of obesity , many individuals participating in exercise programs may think that would satisfy the goal of weight control .
thus , we should educate and encourage them to maintain higher daily activities while participating in exercise programs at the same time .
the results of this study should be interpreted in light of a few considerations .
the daily paee during days with and without center - based exercises was the average of at least two days .
although this provides a good measure of activity energy expenditure , it would be better if data from more days were available .
second , all exercise sessions were during the week .   for paee during days without exercise , we did not have enough data to determine whether there was a difference in paee between those weekdays and weekend days .
these are not accurate measures of energy expenditure ; however , we believe this will not affect our conclusion given the big difference shown between exercise energy expenditure and the difference between paee during days with and without exercise sessions ( figure 2 ) . in summary ,
the main finding of this study is that women expended more energy during physical activities outside of prescribed exercise sessions on days they did not perform center - based exercise , especially if the prescribed exercise was of a higher intensity .
more research is needed to determine what exercise prescription can minimize this  compensation  .
this phenomenon may have biological and behavioral reasons , and future research investigating the underlying mechanisms is warranted .
thus , health professionals should encourage individuals who are participating in exercise programs to maintain levels of activity in addition to the program , so that greater weight loss can be achieved .

Answer:
this study determined whether performing a single moderate- or vigorous - intensity exercise bout impacts daily physical activity energy expenditure ( paee , by accelerometer ) .
 overweight / obese postmenopausal women underwent a 5-month caloric restriction and moderate- ( n = 18 ) or vigorous - intensity ( n = 18 ) center - based aerobic exercise intervention . during the last month of intervention , in women performing moderate - intensity exercise , paee on days with exercise ( 577.7  219.7 kcald1 ) was higher ( p = .011 ) than on days without exercise ( 450.7  140.5 kcald1 ) ; however , the difference ( 127.0  188.1 kcald1 ) was much lower than the energy expended during exercise . in
 women performing vigorous - intensity exercise , paee on days with exercise ( 450.6  153.6 kcald1 ) was lower ( p = .047 ) than on days without exercise ( 519.2  127.4 kcald1 ) .
 thus , women expended more energy on physical activities outside of prescribed exercise on days they did not perform center - based exercise , especially if the prescribed exercise was of a higher intensity .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the nerves and their structures change and are subject to the law of neuroplasticity : they adapt to reflect the stimulus which is present ( mechanical , biochemical , electrical , or metabolic).1 the peripheral nervous system is subjected to a daily mechanical tensile load , as when a joint moves , undergoing compression and stretching .
compression happens when the surrounding tissues create a longitudinal force to a nerve , such as when the muscles are stretched , while stretching occurs when a force is parallel to the nerve , for example , when the elbow is flexed , the ulnar nerve is stretched.2 this mechanical stress can leave the physiological confines when there is direct trauma to the nerve or surrounding tissue.2 the physiological tensile load allows the nerve to regenerate , through autocrine and paracrine substances , generated by the same nervous structure . when the nerve is subjected to stress in elongation , the schwann cells can proliferate and synthesize many neurotrophic factors , which play roles in nerve repair and remodeling.3 the synthesized molecules are varied , with different functions depending on the site of production and the quantity and based on the combinations that occur ; their direction and propulsion force also change.4,5 the synthesized molecules from nerve structure can travel along the nerve and stimulate the various receptors , activating or switching them off , so as to or not to interact with the molecule produced ; the same molecules can behave in different modes based on the area where they were synthe - sized.4,5 in order for the nervous tissue to reshape correctly , it must have the ability to retain its elasticity .
the correct sliding of the fascial structures that make up nerves and the sliding of nerves between the various tissues that cross and innervate it become fundamental , so that the mechanical stress can be communicated properly and has the ability to adapt and regenerate the nerves.6 an impediment to this slide will lead to dysfunction and pathology.7 the biochemical information carried by the nerve does not merely have the function of operating on the nervous system , but it is also able to assist trophism and tissue function that crosses the nerve and innervates it .
nerves can carry multipotent cells for repair and remodeling of tissues and organs , which are innervated by the same nerves.8 the fascial structure of a nerve is divided into three layers : the endoneurium , perineurium , and epineurium .
all the layers are innervated and have a subtle but potentially important plexus of nociceptors.9 the epineurium is composed mainly of type i and iii collagen , fibroblasts , mast cells , and fat cells .
the inter - fascial epineurium is loosely attached to the perineurium , facilitating sliding of the various fascia .
there is abundant epineurium in larger nerves , in order to disperse most of the compressive forces .
the epineurium is attached to paraneural fascial components of the connective tissue that surrounds the nerve and is an extension of the dura mater .
the vessels enter the epineurium in rolled - up form ( to adapt better to the strain in elongation of the nerve ) and periodically along its length , forming the vasa nervorum .
therefore , the epineurium supports the blood vessels while keeping the microvascularity of the nerve constant and also supports the nervi nervorum ( sensory nerve fibers ) of the nerve itself .
it contributes to the tensile strength of the nerve and to the sliding , but it does not provide a barrier function.10,11 the perineurium surrounds the axon filaments with a dense connective tissue and the same perinerium is formed by up to 15 layers of flat perineural cells .
we can encounter collagen type i and ii , and other cells with different carriers modulating the tension recorded from the nerve , thereby regulating intraneural pressure .
perineural cells synthesize several substances and are in close contact with laminin and collagen type iv , further acting as a shock absorber .
another key task of the perineurium is to act as a blood barrier , ie , not allowing all the filtered substances to reach the endoneurium .
arterioles that reach and penetrate the perineurium form an oblique angle ; these vessels have developed little smooth muscle and therefore do not possess a great intrinsic ability to regulate blood flow .
nevertheless , the perineurium performs important functions in the repair of nerve tissue by managing the traffic of molecules inside and out of the neural environment by active transcytotic transport.10,11 a study has shown the presence of many pinocytotic vesicles for this transcytosis , but more research is needed to draw conclusions.11 molecules can also be transported via specific membrane receptors.11 the endoneurium contains individual axons wrapped several times by schwann cells ; this sheet is in turn wrapped by type iv collagen cells , fibronectin , laminin , and proteoglycans . inserted between the various filaments , collagen type i and ii with a longitudinal orientation ,
mast cells and macrophages , and endoneurial fluid ( 70% water ) can be found .
the capillaries that penetrate the endoneurium increase in size , allowing the blood flow to head in different directions .
the arterioles , however , are tightly wrapped by the endoneurium cells to create an additional barrier to the blood .
it is most likely that the blood flow comes into contact with the endoneurium by diffusion .
venules carry the blood back to the venous system . the lymphatic system , however ,
is present only in the epineurium ; there are no lymphatic drainage vessels into the nerves ( figure 1).10,11 the nervi nervorum , or a nerve s nerves , can evoke local neuroinflammation when there is nonphysiological damage or mechanical stress to the nerve tissue , to assist in its repair.9 the fascial nerve system innervated by the nervi nervorum may become a source of local pain.9 another cause of pain by the fascial nerve system , connected to axonal and physiological dysfunctions and capable of generating dysesthetic or distant pain ( for example , pain resulting from traction of the sciatic nerve , when the leg is stretched during tests ) , follows directly from the fascial structures of the axon .
these fascial structures become more sensitive to mechanical stimulation and , after a few days of local inflammation , they are able to generate potential action similar to the mechanical stimulus that causes dysfunction .
this mechanism is known as ectopic electrogen - esis.9 such nonphysiological situations may require from 1 week to 2 months to disappear and only involve the epineurium and perineurium.9 there is a strong hypothesis that impeded sliding of a nerve between its various layers and tissues that cross its fascial system will generate local and dysesthetic pain .
when there is an impediment to the sliding of a nerve , the rigidity of its fascial structures during joint movement is increased , and this is even more true when the joint is moved swiftly , which often occurs with everyday gestures.10 an elongated nerve causes a reduction in its diameter , defined as transverse contraction , with an increase in the pressure of the endoneurial compartment.10 its return to size and length at rest happens due to the elasticity of the perineural tissue , while the endoneurial tissue has less elastic compliance.10 a decrease in the nerve s ability to stretch may damage the endoneurial integrity before a lesion to the epineurium is visible.10 repetitive elongation of a nerve with reduced fascial elasticity properties brings about further inability of the nerve to slide , decreasing blood flow and likely leading to ischemic problems.10 for example , use of a computer mouse for prolonged periods leads to a reduction of the flow capacity of the median nerve at the level of the carpal tunnel , with possible pathological consequences of nerve compression , including the formation of edema , inflammation , and the production of adhesions , along with pain and reduced axonal flow ( figure 2).10 edema is found at the intraneural level and is a common response to trauma , compression , tension , or excessive vibration .
a slight trauma may give rise to edema , more superficially , at the epineural level ; this can be transformed into intraneural edema if compression continues , creating a mini - compartmental syndrome of the nerve , due also to the absence of lymphatic vessels in the endoneurium .
all this will lead to fibrous adhesions , decreasing the sliding of the intrafascicular tissue .
the fibrosis increases the compression both inside and outside the tissues with a thickening of the nerve .
this is even more noticeable when the nerve passes through small areas.12 the situation described will still generate pain symptoms .
many peripheral nerves can be palpated and directly moved , but at the same time , they are more susceptible to trauma than the central nervous system , which is protected by the cranium.9,13 many peripheral nerves can be palpated and directly moved for anatomical reasons.9
there are very few texts in the scientific literature on manual treatment of the peripheral nervous system .
such therapy is used by manual operators with the intent of allowing adequate sliding of the peripheral nerve and surrounding tissue , using two methods in particular : the sliding technique or a technique that alters the tension of the nerve path.13 studies on the human model are scarce , and there are no precise data on the method of movement that should be performed on a patient s nerve path in order to optimize the results .
specific work protocols are lacking , and a positive clinic outcome is not always observed.1419 within the field of osteopathy , there are no scientific articles that deal with palpation or manual techniques applied directly to the peripheral nerve , although there is a book that describes and shows how the osteopathic operator should palpate and treat emergencies superficial to the nerve path.20 the purpose of these therapies and treatments is to alter the mechanical properties of fascia , such as density , stiffness , and viscosity , so that the fascia can more readily adapt to physical stresses .
in fact , some osteopathic physicians and manual therapists report local tissue release after the application of a slow manual force to tight fascial areas ; these reports have been explained as a breaking of fascial cross - links , a transition from gel to sol state in the extracellular matrix , and other passive viscoelastic changes of fasciae.21 the fascial osteopathic technique is the application of a low - load , long - duration stretch into the myofascial complex that is intended to restore the optimal length of this complex.21 the operator places his or her hand on the fascial restriction identified previously by palpation , using different approaches , until the perceived resistance disappears or greatly decreases , inducing or stopping the preferential direction of the tissue.21,22 the time required for the technique varies according to the response of the patient.22 there are reports in the literature that improvement in the sliding of the different fascia layers , via manual manipulation , may decrease pain symptoms and reduce inflammation at the local level.21,23 palpation of the peripheral nerves is feasible and is also used to evaluate nerve function , because these nerves are very often superficial.24,25 our clinical experience encourages us to support osteopathic fascial treatment of the peripheral nerve , providing a strong incentive to launch new research aimed at understanding what happens to the nerve using fascial osteopathic techniques , in addition to quantifying the benefit derived by the patient .
it is important to remember that evidence - based medicine involves not only scientific research highlighted in an article , but also the patient s experience of treatment and the clinical experience of the operator.26 to provide some examples of treatment of peripheral nerve fascia , a finger or fingers are placed on the nerve emergence , either at the elbow on the cubital tunnel , where it passes the ulnar nerve ( figure 3 ) , or in the middle third lateral of the humerus , where the radial nerve passes ( figure 4).24 ulnar compression difficulties may be encountered at the cubital tunnel level , while the humeral area is subject to direct trauma that might damage the radial nerve.2729 the method of treating any emergence of the peripheral nerve is relatively simple and noninvasive .
once the fingers are in contact with the emergence and the most superficial area of the nerve branches , a fascial osteopathic technique is used , during which the operator waits for the tissues of the fabric to release under the fingers.21 it is common for the area being treated to be characterized by tissue hardness , with layers that slide with difficulty under the fingers : the technique ends when the tissue in the area has been restored , as close as possible , to a softer , more flexible tissue .
we do not know the exact scientific reasons for this fascial release , despite many studies showing that an osteopathic fascial treatment is useful in many clinical conditions.21 an in vitro study demonstrates how osteopathic techniques can influence the metabolic behavior of fibroblasts , such as proliferation and inflammatory response.21 another possible explanation is that improved sliding of the various fascial layers would allow resetting of the afferents of the free nerve endings , resulting in a physiologic response of the efferents.21 further studies are expected in order to facilitate choosing the best osteopathic approach to ensure the well - being of the patient .
the peripheral nerves are composed of several layers of fascial tissue , which can become a source of pain if they fail in their ability to slide .
it is only recently that fascial osteopathy research has been aimed at understanding what happens to the fascia following treatment and , as a result of the first studies , it has been possible to highlight some of the benefits , including a reduction in local pain and inflammation .
the osteopathic approach to the fascial system of the peripheral nerve does not have a grounding in scientific research , being based only on the clinical experience of individual operators , despite the use of peripheral nerve palpation as a method for the evaluation and testing of the nerve s function .
the authors wish to encourage the initiation of new research in the fields of academic and clinical osteopathy that is aimed at quantifying the possible benefits a patient may derive from osteopathic treatment of the peripheral nerve .

Answer:
the peripheral nerve is composed of several layers of fascia tissue , which can become a source of pain if the way they slide is impeded .
 it is only recently that fascial osteopathy research has been aimed at understanding what happens to the fascia following treatment , and as a result of previous studies , we are able to highlight some of the benefits , including a reduction in local pain and inflammation . the osteopathic approach to the fascial system of the peripheral nerve does not have a grounding in scientific research , being based instead on the clinical experience of individual operators , despite peripheral nerve palpation being used as a method to evaluate and test its function .
 the authors wish to encourage the initiation of new research in the fields of academic and clinical osteopathy that is aimed at quantifying the possible benefits a patient may derive from osteopathic treatment of the peripheral nerve .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
infarct of the anterior spinal artery is the most common subtype of spinal cord infarct , and is characterized by bilateral motor deficits with spinothalamic sensory deficits .
we experienced a case with atypical anterior - spinal - artery infarct that presented with bilateral hand weakness but without sensory deficits .
a 29-year - old man presented with sudden neck pain and bilateral weakness of the hands . magnetic resonance imaging ( mri ) of the brain did not reveal any lesion .
his motor symptoms improved rapidly except for mild weakness in his left wrist and fingers .
magnetic resonance angiography showed proximal occlusion of the left vertebral artery ; a spine mri revealed left cervical cord infarction .
bilateral or unilateral hand weakness can be the sole symptom of a cervical cord infarct .
spinal cord infarction is much less frequent than cerebral infarction , accounting for only 1% of all strokes.1 the anterior spinal artery supplies the anterior two - thirds of the spinal cord via the sulcal ( central ) artery .
this usually results in anterior spinal artery infarcts presenting with profound bilateral motor deficits , sensory disturbances , and spinothalamic sensory deficits.2,3 although the mechanisms are not completely understood , there are some case reports of restrictive clinical syndromes , such as the ' man - in - the - barrel syndrome ' and the sulcal artery syndrome.4,5 here we describe a patient who presented with bilateral hand weakness but without sensory deficits due to left vertebral artery occlusion .
a healthy 29-year - old man without any vascular risk factors presented with sudden neck pain and bilateral hand weakness . after flexing his neck while tying his shoelaces
, the patient experienced a sudden , severe pain ( with a maximum score on a visual analog scale ) that started in the posterior neck and spread rapidly across the entire head .
bilateral hand weakness that followed the pain onset prevented the patient from tying his shoelaces .
the patient 's vital signs were stable upon hospital admission , except for markedly elevated blood pressure ( 202/108 mm hg ) .
the initial neurological examination revealed weakness in both flexion and extension of the wrists and fingers bilaterally , and during left leg extension [ medical research council ( mrc ) grade 4 ] .
however , the deep tendon reflexes were normal and the patient denied hypoesthesia in any sensory modality including pain , temperature , proprioception , and vibration .
laboratory findings were normal , and chest radiography did not reveal any pathology ; an electrocardiogram also produced no evidence of ischemia or arrhythmia .
his motor symptoms improved rapidly within 1 day except for mild weakness of his left wrist ( mrc grade of flexion / extension iv / iv ) and fingers ( mrc grade of flexion / extension iv / iv ; slightly more severe in the 5th finger ) .
brain computed tomography ( ct ) and brain magnetic resonance imaging ( mri ) did not reveal any signal abnormalities or mass lesions .
however , ct aortography identified severe stenosis and occlusion of the left vertebral artery , and a pseudo lumen with mural thrombi was suspected on cervical mri ( fig .
mri of the cervical segment produced high signal intensities in the left gray matter of spinal cord at the c3 , c4 , and c6 levels on diffusion - weighted images ( fig .
magnetic resonance angiography performed 3 months after symptom onset showed persistent occlusion of the left vertebral artery .
unique features of this spinal - cord - infarct patient were bilateral hand weakness , absence of sensory deficits , and rapid improvement of motor symptoms in the right hand and left leg .
weakness of both arms has been reported previously in association with cervical cord infarcts , typically also with spinothalamic sensory deficit and vertebral artery occlusion.4,5,6,7 the mechanism that preserves leg strength in these cases is most likely collateral flow from the surrounding pial plexus.4 nevertheless , weakness of both hands without sensory deficits is rare in infarcts of the cervical spinal cord , and its mechanism remains to be determined.7,8 the anterior spinal artery forms at the level of the foramen magnum from the branches of the vertebral artery , and gives rise to the sulcal ( central ) arteries that penetrate the right and left sides of the spinal cord.3 unlike circumferential areas of the spinal cord , its interior has no anastomosis and the sulcal arteries are essentially end arteries .
therefore , the weakness of both hands in the present patient suggests that the end - arteries zone or the zone bordering the sulcal artery and circumferential artery corresponds to a region where hand motor neurons are located bilaterally.8 this would include the ventrolateral to lateral regions within the gray matter of the lower cervical spinal cord ( fig .
3).9,10 alternatively , the hand motor areas may be more vulnerable than the more proximal arm motor areas .
the hand motor area occupies a relatively large proportion of the cortical homunculus , so the hand motor area may occupy a larger area in the spinal gray matter , or require a larger blood supply.11,12 finally , the isolated unilateral hand weakness of this patient may be related to variation in the branches of the sulcal artery .
successive sulcal arteries generally alternate in their distribution to the left or right side of the spinal cord , but not both ; this would make unilateral involvement or improvement possible.5 sensory deficit was absent in the present case .
all subtypes of spinal cord infarcts are presumed to have sensory deficits , and therefore a pure motor presentation can result in misdiagnosis.2,3 anterolateral involvement could explain the present atypical presentation , and bilateral presentation without facial weakness may indicate a spinal cord infarct.5 transient ischemic attacks in the spinal cord reported occur primarily in the cervical cord , and recovery depends on the severity of the initial involvement and its collateral flow.1,2,6 cervical lesions are generally less vulnerable to ischemic insults than are thoracic or lumbar lesions due to the intensive vascularization from the vertebral and radicular arteries.3,6,13 the rapid improvement in the present case might therefore have resulted from initial distal involvement and collateral flow from the intact right vertebral artery . in conclusion , transient bilateral hand weakness can be the initial symptom of a spinal cord infarct , and unilateral hand weakness can be the sole symptom of a cervical cord infarct .

Answer:
backgroundinfarct of the anterior spinal artery is the most common subtype of spinal cord infarct , and is characterized by bilateral motor deficits with spinothalamic sensory deficits .
 we experienced a case with atypical anterior - spinal - artery infarct that presented with bilateral hand weakness but without sensory deficits.case reporta 29-year - old man presented with sudden neck pain and bilateral weakness of the hands .
 magnetic resonance imaging ( mri ) of the brain did not reveal any lesion .
 his motor symptoms improved rapidly except for mild weakness in his left wrist and fingers .
 magnetic resonance angiography showed proximal occlusion of the left vertebral artery ; a spine mri revealed left cervical cord infarction.conclusionsbilateral or unilateral hand weakness can be the sole symptom of a cervical cord infarct .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
peri - implantitis is inflammation of the peri - implant supporting tissue , which can lead to progressive loss of supporting bone , if untreated .
a history of periodontitis , poor oral hygiene , and smoking are considered risk factors for peri - implant diseases .
it is of paramount importance to treat periodontitis of the residual dentition prior to implant placement . a higher implant failure rate and elevated number of sites with peri - implant bone loss were documented in periodontally compromised patients who did not adhere to comprehensive supportive periodontal therapy . customized and correctly performed
supportive periodontal therapy is essential to enhance the long - term outcome of implant therapy .
the outcome of non - surgical periodontal treatment ( nspt ) of peri - implantitis is unpredictable .
although minor beneficial effects of laser therapy on peri - implantitis have been shown , this method requires further evaluation .
the diode laser is not an ablative instrument and can directly contact the implant surfaces without inducing melting , cracking , or crater formation .
the 810-nm diode laser , when used in accordance with appropriate parameters , does not damage titanium surfaces , which is useful when uncovering submerged implants , and can be used to treat bacterial induced peri - implantitis .
the use of laser treatment in periodontal therapy is an emerging therapeutic option , although little reliable evidence suggests that it can effectively treat peri - implantitis .
a 45-year - old male presented with pain and swelling at a mandibular implant site ( nobel biocare , sw ) . clinical examination revealed a deep pocket [ 7-mm pocket depth ( pd ) ] and bleeding on probing [ figure 1 ] , with suppuration and gingival inflammatory edema at the implant site .
the patient was in good general health , did not take any medications , and was an occasional smoker ( 4 - 5 cigarettes / day ) .
clinical examination revealed 7-mm probing depths , circumferentially around a mandibular implant , bleeding on probing , and the presence of exudate and gingival inflammatory edema no occlusal trauma or parafunctional habits were detected .
a periapical radiograph demonstrated bone loss of five fixture threads on the most distal mandibular left implant , when compared to the original radiograph [ figure 2 ] .
periapical radiography shows bone loss for five fixture threads on the most distal mandibular left implant the patient was eventually scheduled for periodontal surgery to treat the inflammatory lesion , but emergency intervention was indicated to disinfect the area by removing the bacterial biofilm and alleviating pain using an 810-nm diode laser [ figure 3 ] .
the patient was treated using an 810-nm diode laser to disinfect the area and facilitate bacterial biofilm removal by mechanical and manual periodontal instrumentation the patient was asked to rinse with undiluted chlorhexidine 0.2% for 1 min .
after insertion of the optical fiber parallel to the long axis of the implant 1 mm from the most apical portion of the pocket , the diode insert was moved in an apico - coronal and mesio - distal direction for 30 sec at each inflamed implant site .
it was used at a power of 0.5 w in a continuous wave ( cw ) [ equivalent to 1 w in pulsating mode ( pw ) for 30 s ] in duplicate on each site , for a total time of 360 sec with a fluence of 1.96 j / cm .
non - surgical periodontal instrumentation was performed with hand instrumentation using a titan curette ( roncati implant care , by martin kls ) and a piezoelectric ultrasonic device with plastic fused to a metal insert ( piezon master 700 , ems , pi insert ) , as needed .
finally , a 0.5% chlorhexidine gel was deposited into the sulcus with a disposable syringe and a blunt needle .
the area was checked for plaque removal and home care compliance for the first month on a weekly basis and was followed by routine supportive periodontal therapy at 3-month intervals .
the adjunctive use of the diode laser was included in the conventional periodontal maintenance every 6 months for the following 3 years .
periodontal indices were documented and intraoral periapical radiographs were taken at the 1-year [ figure 4 ] , and 2- , 3- , 4- , and 5-year [ figures 5 and 6 ] follow - up recall appointments .
periapical radiograph : 1-year post - non - surgical treatment periapical radiograph : 5-year follow - up clinical probing depth : 5-year follow - up satisfactory results were obtained by the application of laser - assisted non - surgical peri - implant therapy .
periodontal pocket depth was reduced from 7 to 3 mm with no bleeding upon probing .
intraoral periapical radiographs , taken for up to 5 years post - non - surgical treatment , provide evidence of some improvement of the bone level .
the reduction of periodontal pockets is probably due to re - epithelialization , with formation of a long junctional epithelial attachment .
at the 6 european workshop on periodontology , it was reported that mechanical non - surgical therapy with an adjunct of local antibiotics or laser application was effective longitudinally to reduce bleeding on probing and pds over a period of 6 - 12 months .
however , the outcome is unpredictable due to possible re - infection related to the inability to completely remove bacterial deposits from titanium implant surfaces , thus interfering with new histological bone - to - implant contact .
the primary objective of non - surgical treatment for peri - implantitis is to remove bacterial contaminants to allow resolution of the inflammatory lesion . to date , no critical probing depths in the therapy of peri - implant diseases have been defined to guide selection of a non - surgical or surgical approach .
laser treatment may serve as an alternative or adjunctive treatment to conventional periodontal mechanical therapy or peri - implantitis .
diode lasers have a bactericidal effect due to a localized increase in temperature , which has been verified in vivo using dna probes that detect periodontal pathogens .
threaded implants have a different morphology than root surfaces ; therefore , debridement instruments might be different .
the laser may be a valuable tool to detoxify the implant surface [ figure 7 ] , and significant bacterial reduction should lead to a more satisfactory recovery .
it is possible to point the diode laser insert toward the wall of the ulcerated pocket epithelium to kill virulent periodontal pathogens .
vaporization of granulomatous tissue seems to result in a more favorable effect compared to that of solo instrumentation .
threaded implants have a different morphology than root surfaces ; therefore , debridement instruments may differ .
the laser may facilitate detoxification of the implant surface the diode laser detoxifies root and implant surfaces by inactivating bacterial endotoxins .
the thermal effect weakens calculus chemical adhesion to the root and/or implant , facilitating its removal by curette or ultrasonic devices .
the diode laser also stimulates fibroblasts and osteoblasts , which , in turn , cause increased production of rna messengers , leading to significant collagen production during periodontal tissue healing .
the patient experienced no postoperative discomfort and he was able to comply with home care procedures , such as debridement , after the surgery .
in contrast , patients often have post - treatment discomfort , and compliance with home care procedures decreases because the recommended home care protocols for plaque control are painful ; this results in impaired healing .
important changes were also detected in the patient : bleeding , a marker of inflammation with a high prognostic value , was compared at baseline and at 1 year after laser - assisted periodontal therapy , and was reduced significantly to < 20% .
absence of bleeding has a negative predictive value . besides laser therapy , the following therapeutic interventions
all of these combined may have contributed to healing , complicating isolation of the most effective modality .
the laser has been used as an adjunct to many periodontal treatments , but it is not a replacement for conventional non - surgical treatment or proper home care with adequate patient compliance . the absence of attached gingiva may be an etiological factor in the development of peri - implantitis ; this issue is controversial .
traditional protocols of non - surgical periodontal therapy , in conjunction with the use of an 810-nm diode laser , can be an effective alternative treatment modality for peri - implantitis
. other treatment options may successfully enhance resolution of peri - implant soft and hard tissue inflammation , and preserve long - term periodontal health .
regardless of the method used , correctly performed supportive periodontal therapy is a key factor in successful implant therapy .

Answer:
an 810-nm diode laser was used to non - surgically treat a 7-mm pocket around an implant that had five threads of bone loss , bop+ , and exudate , and the patient was followed up for 5 years .
 non - surgical treatment , home care reinforcement , clinical indices records , and radiographic examination were completed in two consecutive 1-h appointments within 24 h. the patient was monitored frequently for the first 3 months .
 subsequently , maintenance debridement visits were scheduled at 3-month intervals .
 the patient had a decreased probing pocket depth and a negative bop index compared to initial clinical data , and the results were stable after 1 year .
 after 5 years of follow - up visits , there appeared to be rebound of the bone level radiographically . within the limits of this case report
 , conventional non - surgical periodontal therapy with the adjunctive use of an 810-nm diode laser may be a feasible alternative approach for the management of peri - implantitis .
 the 5-year clinical and radiographic outcomes indicated maintenance of the clinical improvement .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
topical bimatoprost is a popular prostaglandin analog used primarily as a powerful ocular hypotensive agent for treatment of glaucoma ( approved in 2001 ) .
it is also used cosmetically to induce hypertrichosis , approved by the us food and drug administration in 2008 as latisse ( allergan , inc , irvine , ca , usa ) .
however , it may cause complications such as periocular skin hyperpigmentation , intraocular inflammation , and conjunctival hyperemia.1 these mainly affect superficial tissues and , to date , there has been no report on involvement of deeper periocular tissues as far as we are aware .
herein , we report an unusual case of periocular muscle atrophy and weakness secondary to unilateral topical bimatoprost use .
a 58-year - old chinese female was referred to the oculoplastics services of national university hospital , singapore , for right upper eyelid ptosis of 1.5 years duration and difficulty in closing her right eye .
she had a history of bilateral primary angle closure diagnosed in 2003 , for which bilateral laser peripheral iridotomies were performed .
she was started on topical latanoprost 0.005% once every night to the right eye , as intraocular pressure ( iop ) was suboptimal .
subsequently , she underwent an uneventful right cataract extraction with intraocular lens implantation that same year .
her condition remained stable until 2008 when there were progressive defects in her right visual field with increased iop .
thus , she was started on topical bimatoprost 0.03% ( lumigan , allergan , inc ) once every night to her right eye .
however , she reported an onset of right upper eyelid drooping 2 months after starting treatment .
the ptosis did not show any diurnal variability or fatigability , and there was no diplopia . a detailed evaluation by the neuro - ophthalmology team revealed no underlying neurological cause .
four months after starting treatment , the treated eye was found to have long eyelashes and ocular pigmentation .
subsequently , the patient reported worsening of her right ptosis after 12 months on treatment and was keen for referral to the oculoplastics team . by the time the patient was reviewed by the oculoplastics team in 2010
measurements of the palpebral aperture ( pa ) of her right and left eye were 6 mm and 8 mm , respectively . measurements of marginal reflex distance 1 ( mrd1 ) for her right and left eyes were 0.5 mm and 2 mm , respectively .
levator palpebrae function was 8 mm for the right eye and 14 mm for the left eye .
lid creases measured 7 mm and 5 mm for the right and left eye , respectively . eventually , the patient underwent a surgical correction of her ptosis with levator muscle advancement in august 2011 .
seven months after the operation , her pa measured 9 mm and 8 mm while mrd1 measured 4 mm and 3 mm for the right and left eye , respectively . the pre- and postoperative clinical photos of her eyelids are shown in figures 1 and 2 , respectively .
preoperatively , she had clinically significant right ptosis obscuring her visual axis , and right lagophthalmos with orbicularis oculi muscle weakness .
topical bimatoprost is highly efficacious and superior to many other anti - glaucoma eye drops.2,3 however , it commonly causes side effects such as ocular hyperemia , periocular and iris pigmentary changes , although these are mostly reversible with cessation of use.4 periorbital lipodystrophy resulting in periorbital hollowing , eyelid retraction , and enophthalmos from chronic use of bimatoprost has also been well - documented.58 upper eyelid sulcus deepening has been shown to occur significantly more frequently ( objectively and subjectively ) with bimatoprost use than with other prostaglandin analogs , namely latanoprost , tafluprost , and unoprostone.9 aihara et al reported an increased incidence of upper eyelid sulcus deepening in patients who were switched from latanoprost to bimatoprost , suggesting that the latter has a more potent effect on periorbital fat tissue.10 the term  prostaglandin - associated periorbitopathy  ( pap ) has been coined to describe the constellation of periorbital soft - tissue changes resulting from the use of topical prostaglandin analogs .
the clinical features of pap include upper eyelid ptosis , deepening of the upper eyelid sulcus , involution of dermatochalasis , orbital fat atrophy , mild enophthalmos , flattening of lower eyelid bags , inferior scleral show , and tight orbits.11 these effects can appear after a period of several weeks to several years , and have been reported to be reversible upon cessation of use.11 most of the anatomical changes in pap are thought to be caused by orbital fat atrophy , while dehiscence of levator aponeurosis or mller muscle may account for the upper lid ptosis.11 it has been postulated that upregulation of prostaglandin f2- results in significant anti - adipogenic effect.12 prostaglandin f2- blocks adipogenesis through the activation of mitogen - activated protein kinase , resulting in the inhibitory phosphorylation of peroxisome proliferator - activated receptor - gamma , a nuclear hormone receptor central to adipocyte differentiation.13,14 topical prostaglandin analogs have been shown to downregulate the expression of peroxisome proliferator - activated receptor - gamma and inhibit the accumulation of intracytoplasmic lipid droplets.15 the reversal of fat atrophy upon cessation of use may be due to removal of this inhibition , allowing adipogenesis to recommence .
imaging of orbits ( computed tomography and magnetic resonance imaging ) has ruled out orbital pathology in the fellow eye ( resulting in pseudo - enophthalmos ) and other disease processes such as cicatrizing changes.5,6 periorbital changes may be underestimated , as they may be subtle or attributed to age - related volume depletion .
bilateral topical use of prostaglandin analog eye drops in glaucoma may lead to equivocal changes in both eyes , which may be less obvious and thus under - reported .
however , in asians , who tend to have greater upper eyelid fullness , unilateral periorbital fat atrophy may result in more obvious disfigurement.16 to date , as far as we are aware , there has been no report of topical bimatoprost use resulting in periorbital muscle atrophy .
in figure 1 , it can also be seen that the patient had deepening of her upper eyelid sulcus and dermatochalasis involution .
clinical eyelid measurements clearly showed reduced function of the right upper eyelid , suggesting that the effects of topical bimatoprost may not be limited to periorbital fat .
reduced levator function and ptosis may be masked by the more common eyelid retraction and deepening of the upper eyelid sulcus .
peplinski and albiani smith postulated that mller muscle ( smooth muscle ) may be directly affected by prostaglandin - mediated pathways , but whether there is a similar effect on levator muscle ( striated muscle ) remains unknown.17 other reasons for the induced right ptosis might have been stretching of the eyelid due to initiation of glaucoma - drop usage , disruption of the whitnall s suspensory ligament from the relative enophthalmos , or the patient s previous cataract surgery , even though there was no fixing of patient s superior rectus during the surgery .
further studies are warranted . in this case , the patient was advised to stop topical bimatoprost and right ptosis correction surgery was performed successfully . in figure 2 , it can be seen that the upper eyelid sulcus deepening was much reduced , with a marked improvement in the dermatochalasis involution after the surgery .
it may be worthwhile to note that topical bimatoprost used cosmetically can also cause unwanted side effects such as conjunctival hyperemia and iop reduction.18 therefore , while considered generally safe when applied superficially to the base of eyelashes , ocular side effects can still occur with risk of instillation onto the eye surface .
herein , we report an unusual and previously unreported case of upper eyelid ptosis secondary to levator muscle atrophy as a result of the chronic unilateral use of topical bimatoprost .
clinicians and patients should be aware of this , as it may compromise visual field and be potentially disfiguring , especially when used monocularly .
patients using latisse should similarly be warned , since the cosmetic and ophthalmic preparations are identical .
although this side effect may not be completely reversible with discontinuation of medication , this case shows that it may be successfully corrected with surgical intervention

Answer:
topical bimatoprost is a common and popular prostaglandin analog used as an ocular hypotensive agent in the treatment of glaucoma .
 side effects include ocular hyperaemia , ocular pruritus , and periocular and iris pigmentary changes .
 perioribital lipodystrophy is another well - documented outcome associated with chronic use of topical bimatoprost , which results in periorbital hallowing , upper eyelid sulcus deepening , eyelid retraction and enophthalmos .
 we report an unusual case of periocular muscle atrophy and weakness from unilateral topical bimatoprost use .
 our patient had primary angle closure and experienced a right upper eyelid ptosis 2 months after she started to use topical bimatoprost in that eye .
 clinical measurements of her eyelids clearly showed reduction in the function of her right levator muscle , suggesting that effects of topical bimatoprost may not be limited to periorbital fat .
 she was advised to stop topical bimatoprost and right ptosis correction surgery with levator muscle advancement was performed successfully .
 ophthalmologists and patients should be aware of this potential rare side effect of topical bimatoprost , as it may be potentially disfiguring , especially with monocular use .
 however , its exact mechanism of action needs to be clarified further .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity

Paper sections:
1. Introduction

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease caused by mutations in genes which encode sarcomeric proteins [1–4]. The most frequently affected genes are MYH7 [5], MYBPC3 [6], and TNNT2 [7], coding for the heavy chain of myosin, the myosin-binding protein-C, and troponin T, respectively. More than 200 mutations have been described in these genes. Furthermore, mutations in a number of other genes, for example, mitochondrial genes [8] have been associated with HCM, albeit at a much lower frequency. Among the rare causes of HCM [9] are mutations in MYL3 which encodes the myosin essential light chain (ELC) of the sarcomere [4, 10–19]. The ELC is located at the lever arm of the myosin head and stabilises this region (Figure 1) through interaction with the IQ1 motif [20, 21] at aminoacid residues 781–810 [22] in beta myosin. The N-terminus of ELC interacts with actin [23]. Although the precise functional role of ELC has not been defined [24], the protein belongs to the EF-hand family of Ca2+-binding proteins [25] and appears to be involved in force development and fine tuning of muscle contraction [26, 27]. The phosphorylation of a C-terminal serine residue has recently been shown to be of major significance for cardiac contraction [28] in zebra fish.

To date, nine HCM-causing mutations have been described in MYL3. Three missense mutations, p.E56G, p.A57G, and p.R81H, have been found in exon 3 and six, p.G128C p.E143K, p.M149V, p.E152K, p.R154H, and p.H155D in exon 4 [4, 10–19] (Figure 2).

The described phenotypes of ELC mutations vary considerably [24], from HCM with an autosomal dominant inheritance and sudden death events, as in p.A57G [13, 17] and p.M149V [10], to a recessive phenotype where only homozygosity was associated with sudden cardiac death [14]. The penetrance is high in middle-aged mutation carriers [24].

Here, we describe a family with a novel MYL3 mutation characterised by low expressivity and late onset of disease.

2. Materials and Methods

The proband and family members were subjected to a full clinical evaluation including family history, physical examination, echocardiography, stress test, and 12-lead electrocardiograph (ECG). Disease status for the proband and family members was determined using conventional diagnostic criteria [29, 30]. All family members gave informed consent for genetic testing, while for testing of children, consent was obtained from the parents.

Genomic DNA was extracted from blood samples using a QIAamp DNA purification kit (Qiagen, Germany). DNA from the proband was screened for mutations in the coding regions of MYH7, MYBPC3, TNNT2, TPM1, TNNI3, MYL3, MYL2, ACTC, TCAP, and CSRP3, and exons 3, 7, 14, 18, and 49 of TTN, as detailed in a previous study [5]. The primers and conditions used for screening MYL3 have previously been described [9]. Three-hundred ethnically matched Caucasian controls were used to establish frequencies of genetic variants.

Polyphen2 (http://genetics.bwh.harvard.edu/pph2/) was used to predict the effect of the identified ELC variant (p.V79I) [31].

The modelling of ELC and regulatory domain of MYH7 was performed using PDB Protein Workshop (http://www.rcsb.org/) and the PdB file 1WDC [32]. Homology studies and gene-structure studies were performed using BioEdit vers 7.0.9 [33] and Ensembl (http://www.ensembl.org/).

3.1. Family History

The proband, a 38-year-old obese (BMI = 44) man, was referred for clinical assessment following the identification of a cardiac murmur during routine health check. He was asymptomatic and had never experienced cardiac symptoms, systemic hypertension, or syncope. Echocardiography demonstrated asymmetrical septal ventricular hypertrophy becoming more concentric towards the apex (max WT 21 mm), a resting left ventricular outflow gradient (36 mm Hg) and left atrial dilation (54 mm) (Table 1). Genotyping of 11 sarcomere genes showed him to be heterozygous carrier of a novel missense mutation (c.235G > A), p.V79I, in MYL3, which encodes the ELC of the ventricle. PolyPhen2 prediction of the p.V79I mutation indicated this variant to be "possibly damaging". The family was offered screening for the mutation and clinical evaluation (see Figure 3 for the pedigree and Table 1 for clinical data on family members).

Examination of the family members resulted in the identification of nine additional heterozygous carriers of the p.V79I mutation, none of whom fulfilled the diagnostic criteria for HCM. Three mutation carriers, see Figure 3 and Table 1, exhibited a borderline phenotype, either based on the presence of an angulated septum in combination with T-wave inversion in AVL on the ECG or diastolic dysfunction in association with left axis deviation (LAD) or LAD and QRS deviation on the ECG. One mutation carrier, a 29-year-old male, exhibited intraventricular conduction defect (IVCD) as an isolated abnormality. The three borderline cases were 58, 55, and 36 years of age, whereas the remaining asymptomatic mutation carriers were 3, 8, 11, 17, 23, and 29 years of age. None of the family members shown in the pedigree had experienced cardiac events or sudden death, but the grandfather of the proband (I-1) was said to have died suddenly and unexpected at the age of 55 years; while a sister (II-6) to the mother had died suddenly and unexpected at the age of 19 years. No information was available as to the cause of these deaths that occurred 4-5 decades ago, and no DNA was available for analysis. As none of the mutation carriers, including the patient with HCM, had any symptoms, severe disease expression, or risk markers, the mutation was considered benign. However, all mutation carriers were offered a follow-up evaluation.

The mutation was not found in 300 controls and had not been registered as a variant in the NCBI SNP databases (dbSNP). Furthermore, there were no clinically affected or borderline cases among the nonmutation carriers.

The p.V79I is a novel variant, which is located in exon 3 in the region where two other HCM-associated missense mutations have previously been identified (Figure 2). Multiple species alignment of MYL3 in seven species indicate that valine is strongly conserved at this position (Figure 4). We examined the location of the p.V79I mutation in the three-dimensional structure of ELC by interpolating the human structure on the structure established for the scallop myosin regulatory domain (Figure 5). The mutation is located on the linker connecting the N- and C-terminal lobes and it is located just two aminoacid residues from the N-C connecting-loop interacting with the first IQ1 motif on myosin (aa 780–810) (Figure 5) [34]. It is possible that the more nonpolar, longer side chain of the isoleucine residue may disrupt interaction of ELC with the positively charged lysine and arginine residues of myosin heavy chain that interface with this ELC region [35].

4. Discussion

We have described a patient with mild HCM associated with a novel, dominantly inherited, MYL3 mutation p.V79I. The mutation segregates with disease and is absent in 600 control alleles in a family in which no other mutation was identified in known HCM-associated genes. The phenotypic presentation of the p.V79I mutation is that of classical HCM with asymmetric septal hypertrophy, just as previously described for the p.A57G mutation in two unrelated Korean families [13, 17] but distinct from the rare midcavitary obstruction previously described in patients with p.E143K [14], p.M149V, and p.R154H mutations [15]. Expression was reduced and/or the disease exhibited late occurrence, as nine mutation carriers were asymptomatic and did not fulfil diagnostic criteria for HCM, and no mutation carriers below 35 years of age were affected or even borderline affected. However, four of the mutation carriers, all >35 years of age, exhibited either a borderline phenotype or ICVD. Strictly defined, the mutation has a penetrance of 10%, but as many of the carriers are below 25 years. If we define the phenotype as borderline HCM with a late onset, we can say that all mutation carriers above the age of 35 exhibit this phenotype. However, a more precise definition of the penetrance of disease will depend on followup studies. Unfortunately, it was not possible to obtain more information about the sudden deaths occurring in the two potential mutation carriers, I-1 and II-6, 4-5 decades ago. However, their existence supports that the mutation carriers are offered clinical follow-up.

The part of beta myosin containing the IQ1 motif that interacts with the N-C-loop of ELC harbours a number of HCM-associated mutations, that are, p.S782D [36], p.S782N [35], p.R787H [4], p.L796F [1], and p.A797T [37], supporting the concept that interference with the interaction between ELC and beta myosin results in HCM. Another part of the beta myosin molecule that comes into close contact with ELC is the arginine residue at position 723 [35], and mutations here also result in HCM, for example, p.R723G [38] and p.R723C [39], which further supports the concept that interference with the interaction between ELC and myosin is a pathogenetic substrate of HCM.

Homology modelling suggests that the p.V79I mutation may interfere with the interaction between ELC and myosin heavy chain, a mechanism which is believed to be the cause of disease for a number of reported mutations. Based on this evidence we find it likely that the p.V79I mutation is disease causing. However, it can not be ruled out that the mutation may only be associated with hypertrophy when other triggering conditions are present. In this case, the proband is very obese; obesity has recently been associated with a cardiac hypertrophic response in mice fed a high-fat diet through inactivation of the Foxo3a transcription factor via the Akt pathway [40]. As the cardiac hypertrophic response in the same mouse model is associated with increased caspase activity [40] and caspase has ELC [41] as its primary substrate in the failing heart, obesity may aggravate the development of a hypertrophic phenotype in conditions with reduced ELC functionality. A less specific aggravation of hypertrophy through the leptin-induced cardiac hypertrophic response seen in neonatal rat cardiomyocytes phenotype could also explain that the proband is the only mutation carrier with clinical HCM [42].

The finding of a clinically silent mutation with low expressivity and late onset raises the question of whether it should entail a detailed followup of mutation carriers. However, as most mutations in MYL3 have been associated with sudden death [24], it would seem prudent to conduct a clinical followup of mutation carriers. The potential relation between a MYL3-based genetic predisposition, the hypertrophic phenotype and obesity in the proband should also strengthen the recommendation to the proband to lose weight.

Answer: Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations in MYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied a large family with a 38-year-old asymptomatic HCM-affected male referred because of a murmur. The patient had HCM with left ventricular hypertrophy (max WT 21 mm), a resting left ventricular outflow gradient of 36 mm Hg, and left atrial dilation (54 mm). Genotyping revealed heterozygosity for a novel missense mutation, p.V79I, in MYL3. The mutation was not found in 300 controls, and the patient had no mutations in 10 sarcomere genes. Cascade screening revealed a further nine heterozygote mutation carriers, three of whom had ECG and/or echocardiographic abnormalities but did not fulfil diagnostic criteria for HCM. The penetrance, if we consider this borderline HCM the phenotype of the p.V79I mutation, was 40%, but the mean age of the nonpenetrant mutation carriers is 15, while the mean age of the penetrant mutation carriers is 47. The mutation affects a conserved valine replacing it with a larger isoleucine residue in the region of contact between the light chain and the myosin lever arm. In conclusion, MYL3 mutations can present with low expressivity and late onset.