Studies carried out by Brainstem Evoked Auditory Potentials (BEAP) in Noise-Induced Hearing Loss (NIHL) workers show different results in relation to neuronal involvement, not involving bus drivers as study object.to use BEAP in a prospective case/control clinical study to check whether or not there is neural auditory pathway involvement in bus drivers with NIHL.we selected 50 bus drivers between 27 and 40 years with mild to moderate NIHL, and 20 individuals between 29 and 40 years with normal hearing and without prior history of noise exposure. BEAP tests were carried out and the traces were analyzed.in the NIHL group, the auditory thresholds in 3, 4 and 6 kHz were significantly higher in the left ear. In the NIHL group, potentials PI, PIII and/or PV were not present in a small number of the individuals; we observed a statistically significant increase in PI, PIII and PV absolute latencies, (LIP) LIP I-III interpeak latencies, bilaterally and LIP I-V in the left ear.in the NIHL group, besides sensorial injury, changes in BEAP latencies suggest an early functional injury of the first auditory pathway afferent neuron. Noise is one of the most prevalent noxious physical agents present in the work environment today, and one of the major problems found in factories, means of transportation and in the very getting together of people.Prolonged exposure to high intensity sounds produces successive changes to inner ear structures, initially transitional and later permanent. The final result is damage to the sensorial hair cells and its highest expression is the destruction of most of the organ of Corti, consequently causing noise-induced hearing loss (NIHL). Experimental studies showed the involvement of neural structures in NIHLThe NIHL is caused when the individual is exposed to noise intensity above 85 dB of Sound Pressure Level (SPL), eight hours per day, regularly, for a period of many years, usually setting in the first five years of exposureNIHL is seen and studied in different professional occupations – urban bus drives among them. There are many factors involved in hearing loss among these professionals, such as the engine in the front of the vehicle, and the loud noise in urban environments5. Many studies have reported NIHL among bus drives, with reported prevalences of 32.6% to 55.4%Today, tonal audiometry is the most used complementary test to detect noise induced hearing loss. When necessary, one must use other complementary tests, such as immittance, logoaudiometry, evoked otoacoustic emissions (EOE) and the Brainstem Evoked Auditory Potential (BEAP) The BEAP is a simple, objective and non-invasive text of the neural pathway which allows one to predict the psychoacoustic threshold through the electrophysiological threshold. In rare cases of simulation, it is not possible to trust the audiometric evaluation, since it depends on the patient's response. These situations require the otolaryngologist or the labor physician to perform objective tests, such as the BEAP and/or EOE. Therefore, it is fundamental to understand all the types of common electrophysiological responses found in NIHL individuals, and thus allow for a more accurate audiologic diagnosis.Numerous studies have been carried out aiming at investigating BEAP alterations in patients with NIHL. Attias, PrattThe lack of studies on the BEAP alterations in bus drivers with NIHL and the different results of the previous workers justified this study.The goal of the present investigation was to assess, by means of the brainstem evoked auditory potential, the involvement of the absolute latencies of potentials PI, PIII and PV and LIP I-III, LIP III-V and LIP I-V in a sample of urban bus drives with NIHL, compared to a group of normal-hearing individuals without noise exposure, with the aim to check whether or not there is any neural auditory pathway involvement in the study group.We carried out a prospective and controlled clinical study. This study was approved by the Research Ethics Committee of this institution under research project 16/06. After the approval we collected the data from October 2006 through January of 2008. The selection of patients was sequential for the study group and happened as the workers were referred from their bus company for a periodic audiometric test. For the control group we selected volunteers. All the subjects signed an informed consent form in order to take part in the study.The study group (NIHL group) was made up of 50 male individuals (100 ears), aged between 27 and 40 years (mean age: 37.5 years), from a population of drivers of front-engine buses and mean daily noise exposure of 85 to 93 dB (A) during a work shift of 8 hours. Noise exposure data from these patients was obtained from observing dosimeter reports carried out by the work safety and engineering staffs of the company. For the control group (C.G), 20 normal-hearing male subjects aged between 29 and 40 years (mean age: 34.2 years) without a past of noise exposure were selected.In the NIHL Group we included bus drivers according to the following inclusion criteria: 5 or more years of employment working with the company; no history of prior ear disorders; audiometry showing a sensorineural hearing loss only in sound frequencies between 3 and 6 kHz, bilaterally; tonal audiometry thresholds between 3 and 6 kHz below 45dB HL; percentage index of speech recognition above 90%; type A Jerger dynamic tympanometry with immittance and contralateral stapedial reflex of 0.5 to 4kHz; 14 hour auditory rest before auditory and BEAP tests. Exclusion criteria from the NIHL Group were: prior neurological disorders; another work and/or leisure activity with noise exposure; prior exposure to organic solvents.For the control group (C.G) we selected individuals with the following conditions: no prior history of ear disorders; no prior exposure to noise and/or sound trauma; tonal auditory thresholds of at most 25 dB HL for all audiogram frequencies (0.25 to 8 kHz); speech recognition percentage index above 90%; immittance values with type A Jerger dynamic tympanometry and the presence of contralateral stapedial reflex of 0.5 to 4kHz.The patients were evaluated by means of an interview – following a set of guidelines according to the inclusion and exclusion criteria. All the patients were submitted to otoscopy. Tonal audiometry was carried out by the ascending-descending approach, by air conduction in the frequencies of 0.25, 0.5, 1, 2, 3, 4, 6 and 8 kHz. When detected by the air conduction test a hearing threshold equal to or greater than 25 dB, a bone conduction test was carried out in the frequencies of 0.5, 1, 2, 3 and 4 kHz. The percentage index of speech recognition was studied with a comfortable intensity level for the patient, established from the mean values of the 0.5, 1, 2 kHz sound frequencies. Audiometry was carried out with the Interacoustics® AC33 audiometer and immittance values with the Interacoustics® AT 235 immittance tester, calibrated according to the Brazilian Calibration Network and the ISO 8253-1 standard. The BEAP was studied with the Smart Intelligent Hearing System® device - Siemens, inside a sound treated booth, with the patients comfortably seated in a reclining chair. We first cleaned the skin with ether and placed disposable Meditrace® electrodes in the regions corresponding to the mastoid apophysis (M1 and M2) and on the upper forehead (Fpz), according to the International System of Brain Electrodes 10/20. The maximum accepted electrical impedance between the electrodes was below 5 kOhms. For acoustic stimulation we used ER3A Insert Earphones. Stimulation was in a single ear, ipsilateral, made up of unfiltered clicks of rarefact polarity and with inter-stimulus frequency of 19.3/s to an intensity of 80 dB HL, and total number of stimuli of, at least 1.000 clicks. The rejection index accepted for the test was of a maximum of 20%. We executed two series of stimulus in each ear in order to certify BEAP reproducibility. All the tests were started on the right ear. At the end of the tests, the traces were analyzed as to the occurrence of PI, PIII and PV and as to absolute latency values and of LIPI-III, LIPIII-V and LIPI-V on the right and left ears.For all the absolute latency variables and LIPs we calculated the mean and standard deviation values. In order to analyze the statistical difference between the right and left ears in both groups we applied the Wilcoxon test. Following, the variables from the control and NIHL groups were analyzed comparatively, in the study of statistically significant differences. The analysis of the differences between the groups was evaluated by the Mann-Whitney test. We used a significance level of 5%  in all the statistical tests employed.In the NIHL group, the ear laterality by the Wilcoxon test of the tonal thresholds of the audiometric frequencies of 3, 4 and 6 kHz, showed that they were significantly higher in the left ear .Table 1MIn the control group, PI, PIII and PV potentials were identified in all the ears.In the NIHL group, PI was not seen in 18% (n=9) of the ears, of which 10% (5/50) represented the right ear and 08% (4/50) the left. PI and PIII did not occur in 10% of the ears (n=5), of which 02% (1/50) to the right and 08% (04/50) to the left. PI, PIII and PV did not happen in 02% (01/50), on the left ears. These values are represented on In order to analyze the statistical differences between right and left ear in each group, the Wilcoxon test showed that in both groups, C.G.  and NIHL G. , PI mean latency in the right ear was significantly higher than that on the left ear. In the NIHL G, the LIPI-III  mean value on the left ear was significantly higher than that on the right ear. As to comparing mean latencies between the groups according to laterality, we observed a statistically significant extension of the three variables PI, PIII and PV in both ears of the NIHL group. , Table 5As to the comparison between the groups, once we consider the ear laterality and LIPs mean values, there was a LIPI-III extension in both ears and of LIPI-V on the left ear in the NIHL group. , Table 7Experimental studies showed neural structures involvement in NIHLThe present study tried to assess a homogeneous sample, with the choice of subjects with the same occupation and, therefore, exposure to similar sound intensities; of similar audiometric profiles, characterized by mild sensorineural hearing loss, in order to avoid the difficulty in obtaining BEAP records in function of the NIHL of moderate or higher level; from a sample with age below 40 years in order to avoid influences from presbycusis eventually associated with NIHL. Immittance tests were carried out in order to check for tympanic-ossicular system functional integrity after 14 hour auditory rest, which was important to rule out transitional alterations of the auditory threshold. The work period choice above five years was based on the fact that most of the NIHL installs on the first five years of exposureThe choice of audiometric profile of the patients in this study, characterized by sensorineural hearing loss restricted to 3 to 6 kHz frequencies and with tonal thresholds below 45 dB may represent a bias on the checked results, since it did not consider the evaluation of patients with NIHL in a moderate to severe level; Nonetheless, a greater reproducibility and sensitivity than BEAP on possible neural alterations in the first years of NIHL.The mean values from the right ear PI latencies were significantly higher than those in the left ear in both groups. It is important to stress that, in the present investigation all the BEAPs were started systematically by the right ear, and such fact may have influenced the production of a potential with an extended latency in function of the most wakefulness state and or of greatest tension the patients suffer at the initial stage of trace recording.In patients with NIHL, many authors observed a significant extension of the PI, PIII, PV and LIPI-IIIIn the present investigation we identified the absence of PI in 18% of the ears, of PI and PIII in 10% and undetectable BEAP potentials in 2% of the NIHL G. This relatively low prevalence is justified by the fact that the sample was made out of patients with mild NIHL. The lack of PI and PIII was also noticed in different studiesNoorhassim et al. (1996)16 also observed PI, PIII and PV, and LIPI-V and LIPIII-V latency extensions, however, because of the age range studied (60 ± 8.7 years), the possibility of presbycusis has relevant. In the present study, in order to avoid such bias, we tried to assess subjects younger than forty years of age.In this paper, the mean LIPI-V value was significantly more extended on the left ear, when compared to the control group, as established by Thakur et al.Many factors have contributed to the development of NIHL in urban bus drivers, such as the location of the engine in the front of the bus, the lack of proper sound insulation, the very age of the buses - usually above eight ears; the lack of preventive maintenance and the high level of urban noise – which the authors described as being higher than the acoustic comfort thresholdIn the city of Salvador, most urban buses do not have air conditioning, and such condition added to the climate characteristics of the place impact this fact because the vehicles run with the windows ajar, and such factor favored the propagation of noise to inside the vehicle. This fact must be considered as a possible cause of greater noise exposure to the left ear.Thus, with this study we could infer that, besides the damage to the hair cells of the Organ of Corti, there was an early functional involvement of the neuronal auditory pathway of the lower brainstem, and these alterations were probably, proportional to the level of sound exposure.BEAP is a useful complementary test in the assessment of NIHL and shows early on that besides the sensorial damage, there is also damage to the first afferent neural pathways of the auditory system.


Upper and lower limbs can be affected by several diseases and changes related to current life habits, such as the sedentarism, technological advances, and even eating habits. This cross-sectional study investigated morphological adaptations of the biceps brachii muscle and the performance of the elbow flexors in healthy individuals in the early phase of aging. Thirty-two volunteers were separated according to age range  and sex. Smaller diameters and subtypes of fibers were evaluated using muscle biopsies, and peak torque and total work were assessed using an isokinetic dynamometer. The variables were compared considering sex and decade, using mixed-effects linear models. The smaller diameter of all fiber types did not differ significantly between age groups for either sex. The proportion of oxidative fibers was reduced in male participants in the 4th (-20%) and 5th (-6%) decades of life compared to the 3rd decade, and there was an increase in the number of oxidative fibers in women from the 4th (+14%) to the 5th decade of life. There were no significant changes in the peak torque and total work between the analyzed age groups. The early phase of aging starts with alterations in the proportion of fibers, with a decrease in oxidative fibers in men and an increase in oxidative fibers in women. Smaller diameter, torque, and total work did not change over these decades of life. The performance of many activities of daily living (ADL) requires quality of movement, and this in turn is a combination of motor skills and active range of motion, and muscle strength. Upper and lower limbs can be affected by aging  and seve-1). Regarding the elbow extension torque, a cross-sectional study reported decreases of 20 to 40% and a longitudinal study demonstrated decreases of 1 to 5% in elderly participants compared to young participants , dynamic (using a gold standard isokinetic protocol), and functional measurements , considering sex and age, would improve the understanding of human reference values for minimally required tasks related with ADL.Therefore, the purpose of this study was to examine the adaptations of the elbow flexor muscles considering the morphological approach and muscle performance evaluation using the isokinetic test at different velocities of movement in healthy individuals of both sexes in the early phase of aging: the 3rd, 4th, and 5th decades of life. We hypothesize that if muscle mass changes minimally in later aging, it is likely that in the early phase of aging, when the movement repertoire required for ADL does not change, the greatest adaptations in upper limbs are morphological rather than in the muscle performance.This cross-sectional study included 32 healthy volunteers (convenience sample), divided into groups according to age range and sex: 3rd decade ; 4th decade ; and 5th decade . The inclusion criteria were: age between 20 and 50 years, both sexes, recreational physical activity level, no immobility in the last 7 days, and presence of morphologically normal muscle samples (few artifacts or mild fiber size variability). The exclusion criteria were athletes (who competed in one or more sports), volunteers with a family history of myopathy, uncontrolled or treated hypertension or hypotension, history of fracture or recent surgery in the preferred upper limb (less than one year), history of reactions to xylocaine , and systemic diseases.The volunteers were asked about their physical activity level and health status using a simple questionnaire following the recommendations of the WHO Guidelines on Physical Activity and Sedentary Behavior in order to identify the amount of regular aerobic and/or muscle-strengthening exercise per day and per week . All volOf the 32 volunteers who participated in this study, six samples were found to have freezing artifacts that prevented morphometric analysis from being performed. Of the 26 remaining volunteers, 14 were male and 12 were female . All volunteers had previous experience with local anesthesia, i.e. for dental treatments, and showed no reaction to the anesthetic. The procedure for obtaining the muscle fragment was performed on the non-preferential upper limb and consisted of a percutaneous needle biopsy. Before the biopsy, the region was cleansed and anesthetized using 2% lidocaine without epinephrine. A #11 scalpel blade was then used to make a small incision of 0.5 cm in the skin, subcutaneous tissue, and muscle fascia. A 4.5-mm biopsy needle with suction (Bergström model) was then inserted . The fraThe biceps brachii muscle fragments were stained with hematoxylin and eosin (HE) for the general morphological evaluation and processed for detection of mATPase (E.C.3.6.1.3.) activity by pre-incubation in acid and alkaline media in order to identify the different fiber types and subtypes . A neuro®, Biodex Medical Systems, Inc., USA) from the Department of Physiotherapy, Federal University of São Carlos, Brazil.The isokinetic evaluation was performed using an isokinetic dynamometer . The mechanical axis of rotation of the dynamometer was aligned with the lateral epicondyle of the humerus. The shoulder was positioned at 30° in the plane of the scapula, 30° abduction in the frontal plane, 0° flexion, and the forearm in supination. The device for fixation of the forearm was placed in the middle third of the forearm, and the application of resistance was placed in the middle third of the metacarpals so that the individual could hold the distal part of the resistance device.-1) to measure strength and moderate to fast velocities  to evaluate power , with the level of significance set at 0.05.Descriptive statistical analysis of the anthropometric data are reported as means (SD). For morphometric analysis, mean small fiber diameter and fiber distribution were compared considering sex and age group. For isokinetic analysis, the peak torque relative to body weight (PT - in percentage) and total work  of each volunteer were obtained at the five angular velocities. TW was obtained by the average of the performance in the 15 repetitions. The following comparisons were made: between age groups for the same sex, between sexes for the same age group, and between age groups for the same velocity and sex. Data were analyzed using linear mixed-effects models . MultiplThe general characteristics of the volunteers, according to each decade of life, are summarized in the The first statistical approach explored if the mean small fiber diameter was significantly different between the sexes. Males presented higher values of all fiber types than females (P<0.05). Then, the consecutive statistical analysis separated the results of the volunteers according to sex. The comparison between the age groups showed no significant difference for all fiber types, for both males and females (data not shown). This means that the smaller diameter of type 1 fiber did not modify significantly from the 3rd to 5th decade of life for male and female volunteers. There was a significant decrease in the proportion of type 1 fibers of male participants in the 4th and 5th decades of life than of male participants in the 3rd decade of life  . We also-1 (74.98±12.30%). The lowest PT value was from female volunteers in the 5th decade, with a velocity of 180°s-1 (34.32±6.79%). In the 3rd and 5th decades and at all velocities, the mean values of PT were significantly lower in female compared to male volunteers (P<0.05)  .-1 (761.46±71.72 J). The lowest TW value was observed in females in the 5th decade, with a velocity of 60°s-1 (129.22±18.83 J). For the three decades analyzed and at all velocities, the mean values of TW were significantly lower in females compared to males (P<0.05)  .Mean PT and TW values of age groups of the same sex did not differ significantly (P>0.05).PT and TW values obtained in the concentric isokinetic test of elbow flexion at different angular velocities are presented in Supplementary Table S1. Data from the comparison of the PT and TW between age groups for the same sex, between sexes for the age group, and between age groups for the same velocity and sex are presented in the Supplementary Tables S2, S3, and S4, respectively.The present study showed that the smaller diameter of the different fiber types in the biceps brachii muscle did not differ significantly between decades, either for males or females. On the other hand, the proportion of oxidative fibers in males was lower in the 4th and 5th decades compared to the 3rd decade, and in females, there was a higher proportion of oxidative fibers in the 4th and 5th decades. Additionally, there were no changes in the performance of the elbow flexor muscle during the early phase of aging, since there were no significant changes in the PT and TW among the analyzed decades. Our hypothesis was confirmed since the morphological adjustments occurred before strength adjustments.The size of muscle fibers changes and can convert from one type to another in response to stimuli, such as training or immobilization , and alsIn male volunteers, the proportion of type 1 fibers was lower in the 4th and 5th decades compared to the 3rd decade, and the proportion of type 2C fibers was lower in the 5th decade compared to the 4th. One hypothesis is that the lower number of type 1 and type 2C fibers in males is related to the continued conversion of these fiber types to type 2 fibers, a process that begins in childhood and progresses throughout maturity. Muscle fiber type distribution was investigated in human skeletal muscle in children, adolescents, and adults in the deltoid muscle  and vastIn female volunteers, there was a significant increase in the proportion of type 1 fibers from the 4th to the 5th decade. Again, these findings can be related to the conversion of fiber types in aging muscles. The lower proportion of type 2 fibers and, secondly, the preferential atrophy of type 2 fibers leads to loss of muscle mass with advancing age and therefore a greater area with slow fibers in aging muscles ,25,28. TThe greatest age-related changes in strength occur in men , becausePart of the decrease in force or torque during aging is due to a decrease in the proportion of type 1 and type 2 fibers and preferential atrophy of type 2 fibers, causing loss of muscle mass . The maiThe early age-related process of healthy men starts with the conversion of type 1 muscle fibers into type 2 fibers and the opposite occurs in women, similar to the alterations of older people over 60 years of age . The smaThe limitations of the present study were the lack of the evaluation of the physical activity level, labor, or sporting activity of the volunteers using specific scales, and the absence of immunohistochemical analyses for MHC and PCR, which could complement the fiber conversion assessments.To the best of our knowledge, this is an original study exploring morphological and muscle performance (using different test movement velocities) of elbow flexor muscles in healthy individuals in the early phase of aging. These data allow a more precise comparison across age groups and sexes providing quantitative assessment measures to follow the progress of muscle performance and muscle morphology in athletes and (or) in patients with upper limb disabilities. Further research is suggested to explore the molecular, biochemical, and histopathology of biceps brachii and PT and TW of elbow flexors in healthy volunteers for the age group above 50 years of age.


Background & aimThe spinal cord is the continuation of the brain from the lower point of the medulla and the terminal portion of the developing neural tube. The spinal cord develops within the bony canal, called the vertebral canal, formed by the union of individual vertebrae in the vertebral column. Initially, the development of the length of the vertebral column and spinal cord are the same but later on undergo alterations. The growth of the vertebral column is faster than that of the spinal cord because the spinal cord appears to terminate early within the vertebral canal. To measure the length of the spinal cord and lowermost point of conus medullaris in the third trimester gestational age fetuses.Material and methodsThe present cross-section observational study was carried out on 30 fetuses collected from the museum of the Anatomy Department and Obstetrics and Gynecology Department. Before starting the study, permission and approval from the university's ethical committee were received. The dissection of fetuses includes the incision of the skin, removal of superficial and deep muscles, and a laminectomy. The meninges were cut and removed to note the vertebra level of the termination of the spinal cord. The spinal cord was taken out, and the total length of the spinal cord was measured. The fetuses were categorized into three groups determined by their gestational age .ObservationIn the present study, 81.8% of male fetuses were in the 36-40 weeks gestational age group, and 52.6 % of female fetuses were in the 32-35 weeks, gestational age group. The mean length of the spinal cords was 14.74±1.45cm, with a range of 10.95 cm to a maximum of 16.60 cm. In the full-term gestational age group, male fetuses had a greater length of spinal cord than female fetuses. Sixteen fetuses had a spinal cord termination at level L2, followed by eight fetuses at the L3 level and six fetuses at the L4 level. Out of 11 male fetuses, eight fetuses had spinal cord termination at the L2 vertebra level, two at the L3 level, and one fetus at the L4 level. In female fetuses, eight had a spinal cord termination at the L2 level, six at the L3 level, and five at the L4 level.ConclusionThe spinal cord length and level of conus medullaris depend on the age of the fetuses. In prenatal diagnosis for different spinal cord pathology, these values can be used as reference values in future studies. The spinal cord is the continuation of the brain from the lower point of the medulla and the terminal portion of the developing neural tube. During the development of the brain, which starts as a single tube, various curvatures are formed in the fore part of the neural tube. These curvatures form the forebrain and hindbrain. However, the midbrain remains in its primitive form, and the spinal cord retains its shape. The spinal cord develops within the bony vertebral canal formed by the union of individual vertebrae in the cervical, thoracic, lumbar, and sacrococcygeal regions united by intervertebral discs. The covering of the spinal cord is the same as the brain . Initially, the vertebral column and spinal cord length are the same. The growth of the vertebral column is faster than that of the spinal cord in developing fetuses, and the postnatal life spinal cord terminates early within the vertebral canal. This process is known as the ascent of the spinal cord, and this terminology has passed from one author to another . The exaThis cross-section observational study was conducted on 30 fetuses from January 2020 to July 2022 in the Department of Anatomy, Uttar Pradesh University of Medical Science, Saifai, UP, India. The IUD (intra-uterine death) fetuses were collected from the obstetrics and gynecology departments at the same institute. The parents and University Ethical Committee gave the necessary consent for the fetus collection (Ref. no 665/UPUMS/DEAN/2019-20/EC no 2019/20 date 08-07-2019). Gestation from 28-week to 40-week fetuses was included, while fetuses with the abnormal nervous system and spinal cord development were excluded from this study.The early dissection includes incision of skin from the external occipital protuberance up to the lower limit of the coccyx. The skin was cut in the midline and reflected laterally. The back's superficial muscles and deep muscles from the external occipital protuberance up to the lowermost point of the sacrum and coccyx were cut and removed to visualize the vertebral column. The spines and lamina of the vertebra (laminectomy) were cut with scissors and a scalpel in the midline. The surface of the spinal cord  was clean and cut from top to bottom. All the spinal nerves coming out from the spinal cord laterally were cleaned. The meanings were cut vertically throughout their length. All the nerves of the cauda equine were separated and fanned out to visualize the complete spinal cord Figures -4. A measuring scale measured the length of the spinal cord from the uppermost point  to the terminal point . Data were managed on an Excel spreadsheet. In this study, we measured the length of the spinal cord within the vertebral canal and determined the lowermost point of the spinal cord within the vertebral canal.Our study noted that the majority of 46.7% of fetuses belonged to the 36-40 weeks gestational age group, 40.0% of fetuses in the 32-35 weeks gestational age group, and 13.3% of fetuses in the 28-31 weeks gestational age group. In the present study, 63.3% of fetuses were female while 36.7% were male, and 81.8% of male fetuses came in the 36-40 weeks gestational age group while 52.6% of female fetuses were in the32-35 weeks gestational age group , the L2 level of the spinal cord was in eight fetuses, the L3 level of the spinal cord was in two fetuses, and the L4 level of the spinal cord was in one fetus. In the female (n=19) fetuses, the L2 level of the spinal cord was in eight, the L3 level of the spinal cord was in six, and the L4 level of the spinal cord was in five fetuses. We also found that the lowermost level of spinal cord termination decreases with increased gestational age; in the early third trimester (28-31 weeks), spinal cord termination was at the L4 level, whereas in the 40th week, the spinal cord was at L2 level . The lower limit of the conus medullaris was at the L2/L3 level in fetuses of 27-29 weeks gestational age. In the fetuses of 40 weeks gestational age, the level of the conus was found to be at the L12/L2 level [Sahin studied an ultrasound scan of 41 pre-perm fetuses and 64-term fetuses, and they found that in the pre-term group of fetuses, the conus medullaris level was at an L2 level of 90.4%. In the term group fetus, it was above L2 in 92.1%. The difference in the conus medullaris levels between term and pre-term neonates and genders was insignificant. They finally conclude that the ascent of the conus occurs early in fetal life .Wolf et al. did an ultrasound study on 114 healthy infants to assess the time of ascent of the conus medullaris up to the normal level (L2) and found that the tip of the conus lies between the L2 and L4 level in fetuses ranging between 30-39 gestational weeks, whereas the level of the conus falls between T12/L1 to L1/L2 in 40-63 weeks [Sun et al. suggested using an MRI as an accurate and useful method to determine the level of conus medullaris in term infants. They concluded that the conus medullaris reaches the normal adult level at birth and does not ascend afterward .Albert-Neels et al. studied newborn infants' cadavers with a sagittal MRI of children, adolescents, and young adults. The authors found a significant difference in newborn infants from other higher groups. In infants, the lower limit of the conus was found at the L2/L3 level (16%). In contrast, in the childhood stage, adolescent population, and young adult group, it was at the levels of T12/L1 and the lower third of L1 (21%), the middle third of L1, and L1/L2 (19%), and level of L1/L2 (25%), respectively. They found the difference in the conus termination in infants within one year and older than one year. In this study, the spinal cord termination was not found caudal to the L3 vertebral body . NakashiRao reported his findings on 19 South Indian fetuses and one newborn . He repoWe further noted that the lowermost level of the spinal cord termination at the L2 level increased in the gestational age group in the 40th week. It was increasingly at the L4 level in the early third trimester (28-31 weeks). Mottet et al. reported that an L4 level or greater was reached at the gestational age of 13-18 weeks from L1 to L2 at approximately 40 weeks . Levins Boon et al. stated that the difficulty in determining spinal cord termination (CMT) might be due to the presence of lumbosacral transitional vertebrae in 8-15% of subjects .We further noted that out of 11 male fetuses, eight were at the L2 level, two were at the L3 level, and only one was at the L4 level; while in females, eight fetuses were at the L2 level, six fetuses at L3 level, and five fetuses were at L4 level. According to Thomson (1894) and Needles 1935), the adult female spinal cord terminates at a lower level than that of the male . Vettive35, the aIn this study, using distinct anatomic landmarks to prevent bias, the ascent of the conus medullaris occurred throughout the gestational age. A follow-up scan and proper evaluation are required to prevent catastrophe for fetuses whose spinal cord termination levels were abnormally low (lower than the L3 to L4 levels). Early postnatal treatment through a multidisciplinary approach is recommended for patients with abnormally low-level spinal cords .


The 24-h recall (24HR) is a short-term dietary assessment instrument that is widely used in large-scale nutrition surveys. The number of survey days is critical in the accuracy of estimates. The multiple, repeated collection of 24HRs can yield reliable dietary intakes, whereas that is not always feasible due to staffing, equipment, financial, and temporal constraints. The NCI  method was developed to address this limitation by using only within-person variance to calculate usual dietary intake. However, the performance of different forms of 24HRs based on the NCI method remains unclear. The aim of this study was to explore a form of 24HR based on the NCI method that can balance accuracy and survey cost. A total of 595 subjects completed 7 consecutive 24HRs in each season, for a total of 28 24HRs. The averages of the 28 collection days were defined as the reference value to compare the performance of 24HRs for two consecutive days (C2), three consecutive days (C3), two non-consecutive days (NC2), and three non-consecutive days (NC3) for estimating the dietary intakes of Chinese adults. The equivalence test was used to evaluate whether the estimates of scenarios NC2 and NC3 were equivalent. Additionally, the accuracy of a scenario of NC2 which included a weekend was compared to that of a scenario of NC2 which included two weekdays. All results of the 24HRs in each scenario were corrected by the NCI method. Bias/relative bias and mean bias/mean relative bias were used as measures of precision and accuracy, respectively. The results showed that the precision was similar among the four scenarios, while the accuracy relationship varied among the different dietary components. In general, scenario NC3 was the most accurate, followed by scenario NC2, which was close to the former. The form using non-consecutive days was more accurate than that using consecutive days, and the main factor affecting the accuracy of the 24HRs was the continuity between multiple survey days rather than the number of days. The means and major percentiles of energy, nutrients, and frequently consumed food in scenarios NC2 and NC3 were functionally identical. The accuracy of the scenario of NC2 which included a weekend was higher than that of scenario NC2, which consisted of only weekdays. The above results indicated that the adoption of two, non-consecutive 24HRs consisting of a weekend and a weekday to collect dietary data prior to correction by the NCI method, is a feasible approach to balancing survey costs and accuracy in large-scale nutrition surveys. As an important part of a nutrition survey, the results of a dietary survey allow for the assessment of population-level food and nutrient intake and the risks of inadequate or excessive intakes. Additionally, it is an interesting exposure factor in the study of the relationship between diet and chronic diseases. The 24-h recall (24HR), a short-term dietary assessment instrument, requires the investigator to help the subject accurately recall and record the types and amounts of all of the foods consumed in the past 24 h . This meSeveral similar statistical modelling methods have been proposed to obtain usual intakes by correcting for the measurement errors of short-term 24HRs. These corrected methods include the National Cancer Institute (NCI) method , the MulThe aim of this study was to compare the performance of two consecutive 24HRs, three consecutive 24HRs, two non-consecutive 24HRs, and three non-consecutive 24HRs, using the NCI method to generate estimates of dietary intakes and the risks of nutrient deficiencies/excesses. The secondary aim was to determine which of these would be a better form of the 24HR to balance the accuracy with the cost of dietary surveys. The average of 28 24HRs administered in a single year were used as the gold standard for these purposes.The present study is a follow-up study to one conducted from December 2019 to December 2020. The participants were aged 18 to 60 years and lived in Zhejiang and Shanxi provinces in China. One rural survey site and one urban survey site were selected from each province. The selected survey sites had served as the China Nutrition and Healthy Surveillance 2015 (CNHS 2015) monitoring sites and thus had a basis for conducting dietary surveys. Purposive sampling was used to recruit 198 participants at each survey site, divided in half by gender. A total of 7 consecutive 24HRs were conducted quarterly during the one-year follow-up period. The seasons were divided into Spring (March to May), Summer (June to August), Autumn (September to November), and Winter (December to February). Finally, a total of 780 participants completed 28 24HRs. Detailed descriptions of the sampling and survey protocols are provided in the published article .In the present study, we first removed the survey days with unusual energy intake levels  . Then, 2The study protocol was approved by the Ethics Committee of the Chinese Center for Disease Control and Prevention (No. 201519-B), and all participants signed an informed consent form before participating.The design of the questionnaire for this study was based on the standard questionnaire of the CNHS 2015, which consisted of four domains: basic information, health status, dietary information, and condiment consumption. All the information was collected through face-to-face interviews. Before the investigation, all investigators received standardized training, and quality control was implemented during data collection.Individual dietary data was recorded through face-to-face household visits by investigators. Participants were asked to complete 7 consecutive 24HRs in each quarter, for a total of 28 survey days. On each visit, trained investigators used food models and picture aids to help participants recall the types, amounts, cooking methods, and locations of all the foods they had consumed in the past 24 h. The face-to-face interviews also recorded whether the respondents were working on each visit day. Daily energy and nutrient intakes for individuals were calculated according to the Chinese Food Composition Tables . For thiAccording to different forms of administering multiple 24HRs, we divided them into 4 scenarios, including C2 (2 consecutive days), C3 (3 consecutive days), NC2 (2 non-consecutive days), and NC3 (3 non-consecutive days). “Non-consecutive days” were defined as periods in which least one day passed between two adjacent survey days. Seasonal and weekend effects may lead to different results at different survey times. To fully compare the performance between the four scenarios, we generated data sets containing all possible combinations of collection days for the four scenarios. The data sets generated by the 4 scenarios over the 7 consecutive survey days are shown in The agreement between the participants’ self-reported work schedules and weekdays as defined by the date was greater than 99%. Therefore, weekdays were defined as being those days between Monday and Friday, and weekends were defined as being Saturday and Sunday.The true dietary intake was defined as the average intake of all (23 or more) 24HRs for each participant [The NCI method is a correction method created by the National Cancer Institute of the USA to reduce the measurement error found in dietary intake calculations through the removal of intra-individual variability . It is aTo compare the estimated value with the true value, we calculated the bias B for each dietary component,To demonstrate the differences between the four scenarios more visibly, the relative bias and the mean relative bias were used to compare dietary components with less than 5% of zero intake, while the bias and mean bias were used for dietary components with greater than 5% of zero intake.Equivalence testing was used to evaluate whether the parameters between scenario NC2 and NC3 were equivalent. The equivalence margin was defined as 5% of the estimates from scenario NC3 . ConfideThe NCI method and other analyses were conducted using SAS version 9.4 , and all plots were constructed using R version 4.1.2.The mean biases and mean relative biases of the means and major percentiles of the intakes for each dietary component estimated by the NCI method relative to the true values can be found in p < 0.05). In addition, most of these dietary components had an error of 2% or less. Interestingly, the 90% CIs for cholesterol, iron, magnesium, vitamin A, and vitamin C were wider than those for other nutrients. For the other 8 foods, scenarios NC2 and NC3 estimated functionally identical means and 90th percentile (p < 0.05). However, for 10th, 25th, 50th, and 75th percentiles, the 90% CI for most foods exceeded the 5% of scenario NC3. Despite this, they were mostly within the 10% error range  as a covariate in the model. The scenarios share a common problem in estimating episodically consumed foods, namely producing a large error relative to the true values, which can be addressed by including food consumption frequency as a covariate in the model . A previBased on the above results, we suggest that two non-consecutive 24HRs consisting of a weekend and a weekday using the NCI method can meet the requirements of high accuracy and low costs, and that is also the fewest number of survey days required to obtain usual intake. One way to further reduce the costs and subject burden may be to conduct a second repetition of the survey with only a part of the sample. A previous study showed that replication rates of a second 24HR greater than 40% did not lead to significant impairment in precision, and that impairment was reduced when the sample was increased, suggesting that choosing an appropriate replication rate to estimate dietary intake may help reduce costs . There aOne of the strengths of this study was the use of 28 24HR, covering the 4 seasons, as a reference standard, rather than the simulated true dietary intake. The second strength was that we considered all possible combinations of 24HRs from different seasons and different days of the week. Additionally, we included 33 dietary components to comprehensively compare the performance of different forms of 24HRs involving energy, nutrients, and foods. However, there were some limitations. First, the reasons why different dietary components have different results were not further explored in this study. Second, the population of this study was Chinese adults, aged 18–60 years, so caution is needed when extrapolating the results.In the NCI method, the continuity between multiple 24HRs is the main factor affecting the accuracy of the estimates, while the number of 24HRs has little effect on the accuracy. The precision is similar between the 4 forms of 24HR, while the order of accuracy varies across dietary components. In most cases, 3 non-consecutive 24HRs obtained the highest accuracy, followed by 2 non-consecutive 24HRs. For energy, nutrients, and frequently consumed foods, 2 non-consecutive 24HRs can replace 3 non-consecutive 24HRs to make functionally equivalent estimates. In addition, two non-consecutive 24HRs consisting of a weekend and a weekday performed better in estimating dietary intake. Therefore, we propose the use of 2 non-consecutive 24HRs, consisting of a weekend and a weekday, to collect data in large-scale nutrition surveys, and then to correct for within-person variance by the NCI method to improve accuracy while reducing survey costs and subject burden. However, this approach yielded great biases in estimating the intakes of foods consumed episodically, and further research is needed to determine how to reasonably collect food consumption frequency information under this approach so as to address this limitation.


Even if breast cancer is a severe pathology that can cause the death of a person, nowadays there are effective screening methods that could help us to discover in due time the tumor formation and thus be able to benefit from conservative breast surgery.Evaluating the feasible relationship between the noted levels of procrastination and the educational level of subjectsThe analyzed group comprises a number of 152 female subjects (n=152). They were divided in three subgroups: subgroup I(26) composed of women with lower education, subgroup II(66), women with medium education level and subgroup III(60), women with higher education. A socio-demographic questionnaire and the Tuckman Procrastination Scale have been applied.Comparing the three subgroups, the levels of procrastination were similar. Low levels of procrastination were most common in all three subgroups: in the subgroup I 57,69%, in the subgroup II 56,06% and in the subgroup III 53,33%. Average procrastination levels were observed in 34,61% of women in subgroup I, 42,42% of women in subgroup II and 45% of women in subgroup III. Concerning high levels of procrastination we can affirm that they involve a small number of subjects. Measuring the degree of connection between the two variables, we obtained as a result r=0.13, which means a very weak, non-existent correlation.The study revealed that there is no relationship between the level of education and the levels of procrastination that include postponing the presentation to the doctor.No significant relationships.


Preimplantation genetic diagnosis (PGD) has been used as an option for couples with the possibility of having a baby with a genetic disorder. The common method for performing this test involves isolating 1 cell from day 3 or a few cells from day 5 embryos and performing genetic studies on the cell-extracted DNA. This method is invasive and can cause abortion after implantation in the uterus. Because of this, 2 noninvasive methods for performing a PGD have been studied: PGD using blastocyst fluid and PGD using embryo culture medium.The aim of this study is to determine the sensitivity of the polymerase chain reaction (PCR) technique to detect the Y chromosome using cell-free DNA within a culture medium for gender prediction of blastocysts. In this study, the gender of 30 embryos on day 5 was determined using embryonic DNA extraction from the culture medium and the PCR technique to evaluate the sex-determining region Y and fragile X mental retardation genes. Then, the accuracy was assessed using ultrasound.The results of the PCR technique showed that 7 embryos were male, but an ultrasound revealed that 13 were male.The given results indicated that, because of the low amount of DNA extracted from the culture medium, the diagnosis of the existence of the Y chromosome by this method is still not accurate enough for detecting the gender of the embryo. One of the essential functions of using in vitro fertilization (IVF) techniques is to raise the possibility of having a healthy child in couples who are in danger of having a child with a genetic disease . To accomplish this, before embryo implantation in the uterus, the genetic health of the embryo produced in laboratory conditions is examined using preimplantation genetic diagnosis (PGD). The embryo is then transferred to the uterus after assuring genetic health (1-4).The common method of PGD implementation includes controlled ovarian stimulation, egg acquisition, intracytoplasmic sperm injection in the egg, keeping the embryos in a culture medium, detachment of 1 cell from an embryo on day 3 or a few cells on day 5 for genetic diagnosis, performing the necessary tests to diagnose, and finally selecting an embryo without disease and transferring it to the uterus (4-6). This method, unlike other diagnostic methods, does not cause complications that may lead to termination of pregnancy (3). However, this method of PGD, due to cell separation from the embryo, is a kind of invasive method so it can cause abortion after implantation . Recently, 2 noninvasive methods for implementing PGD for obtaining embryo genetic material have been introduced, including PGD using blastocyst fluid and PGD using embryo culture medium (7-11). In both approaches, the required embryonic DNA is obtained from matters discarded after implantation in the uterus. The main drawback of both approaches is access to a small amount of genetic material in the embryo, making the performance of genetic studies difficult . According to a study, it was estimated that 80 Due to medical reasons, gender selection is defined as preventing childbirth with a severe genetic disorder . PGD was initially introduced for selecting female embryos concerning chromosome X-related disorders . Although, currently, some families, due to several issues such as having multiple children of the same sex and wanting to have a child of different gender, request IVF implementation and pre-implantation genetic diagnosis (16).SRY) and fragile X mental retardation (FMR1) genes for diagnosis of the Y and X chromosomes, respectively, using the polymerase chain reaction (PCR) technique (17-19). Then, after the diagnosis of the gender of implanted embryos, in the 4This prospective clinical trial study attempted to determine the gender of embryos formed in the laboratory on day 5, using embryonic DNA extraction from the culture medium, and evaluation of the sex-determining region Y . PCR was performed based on the table II steps (according to the manufacturer's protocol) in a thermal cycler (Perkin Elmer 480). Electrophoresis of the PCR products was performed on 1.5% agarose gels for 60 min. The gel was then stained with ethidium bromide and observed under a UV transilluminator. Then, according to the following 4 states, the blastocysts' gender was predicted.The primers of the SRY+ / FMR1+, blastocyst has both X and Y chromosomes, blastocyst gender should be male.SRY- / FMR1+, blastocyst has only an X chromosome, blastocyst gender should be female.SRY+ / FMR1-, blastocyst has only a Y chromosome, maybe blastocyst has aneuploidy, the test should be repeated.SRY- / FMR1-, blastocyst has neither X nor Y chromosomes, the test should be repeated.In this prospective study, all the clinical information was obtained from the Fertility, Infertility Private Center. All participating couples completed the informed consent form. The clinical analysis was approved by the Ethics Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (Code: IR.AJUMS.REC.1398.990).In this study, 117 couples participated, of which 54 became pregnant. Finally, in 30 pregnancies, the sex of the fetus was determined by ultrasound, and all pregnancies were successful, and the baby was born alive.SRY and FMR1 genes were successfully amplified in a day 5 culture medium and detected with bands at 230 bp and 301 bp, respectively. Positive controls  were included in the PCR reactions. If PCR products were observed at both 230 bp and 301 bp, this result indicated that the DNA originated from a male sample. However, if samples originated from a female, a single PCR product at 301 bp was observed .The SRY gene, and sex determination was incorrect. The calculation of the sensitivity, specificity, and diagnostic accuracy of this method was done based on the `2 by 2 table' and the results were as follows (Table III):Analysis of the PCR products showed that out of the 30 embryos studied, 7 were male, and 23 were female. However, an ultrasound revealed that 13 fetuses were male and 17 were female. Thus, in 6 male embryos, the Y chromosome was not detected by the amplified FMR1 gene, the Y chromosome diagnosis by the SRY gene was not as easy, so that the PCR studies identified only 7 embryos with a Y chromosome, while the ultrasound results showed the existence of 13 boys.In this study, using embryo DNA extracted from the fetal culture medium on day 5, the authors tried to determine the presence or absence of a Y chromosome for gender determination of the studied embryo, and the sensitivity of this method was examined after the gender determination of embryos by ultrasound in the 4As a result, it can be said that although the gender of all 7 cases diagnosed by ultrasound was the same as found in the culture medium, the gender of the diagnosed girls had an accuracy of 74%. So, in case a male gender is desired, we can trust the method to determine the gender of the embryo. However, if the preferred gender is female, it should be considered that 26% of the cases diagnosed as females using this method are probably males.SRY gene, located at the Yp11.2 locus, comprises only 828 nucleotides. In contrast, the X chromosome is about 156.05 Mbp long (2.72 times the Y chromosome), and the FMR1 gene, located at locus Xq27.3, has 46,135 nucleotides (about 55.71 times larger than the SRY gene).One of the factors that can explain this result is the differences in the size and dimensions of the 2 chromosomes X and Y. The Y chromosome is one of the smallest human chromosomes with approximately 57.23 nucleotides, and the SRY (as a Y chromosome gene) and ALT1 genes (as a control). This study was performed on DNA extracted from blood cells. Its purpose was to evaluate the efficiency of the multiplex PCR technique and the sensitivity of the SRY gene to detect the male gender (18).A previous study used multiplex PCR for the detection of Another study reported that the use of cell-free DNA in the culture medium may be a viable alternative to the use of embryonic cell DNA for the diagnosis of a-thalassemia-SEA (20). The study evaluated the amount of cell-free DNA in the culture medium from the culture on day 3 and day 5, and reported that it was better to use the day 5 medium due to the higher amount of cell-free DNA.Furthermore, Li et al. showed that cell-free DNA in a culture medium or fetal blastocyst fluid could be used to assess genetic and chromosomal defects. However, the amount of DNA obtained from these methods is small, and it may be necessary to use both ways together (7).SRY gene, and it was recommended to use the day 5 embryonic culture medium (8).According to Yang et al., the amount of cell-free DNA in the day 3 embryonic culture medium was insufficient to detect the Y chromosome by the Given the huge difference in the dimensions of these 2 chromosomes, it is clear that the extraction of the Y chromosome and the study of its genes is more difficult than the extraction and study of the genes of the X chromosome, particularly in the extraction of an embryo's genetic material from the culture medium where the amount of DNA obtained for examination is small.Our findings are consistent with a study that showed that the amount of DNA obtained from culture media was not sufficient for accurately detecting the testis-specific protein Y-linked 1 gene, which is located on the Y chromosome, but was enough for detecting the TBC1 domain family member 3 gene, which is located on chromosome 17 (12).SRY gene, some of the unique sequences of this chromosome should be examined simultaneously using the multiplex PCR technique.The findings of this study suggest that simultaneous extraction of fetal DNA from the blastocyst fluid and from the embryo culture medium enhances the amount of fetal DNA obtained for examinations. Also, for increasing the accuracy of Y chromosome detection and detecting the The authors declare that there is no conflict of interest.


Although the analogues were less active than nucleozin, the loss of activity highlights the need for the piperazine ring to maintain the activity of nucleozin analogs. Interestingly, this result agrees with the prediction of anti-influenza activity made with a QSAR model presented in this work. The proposed model and the synthetic route will be useful for the further development of nucleozin analogs with antiviral activity.The infection caused by the influenza virus is a latent tret. The limited access to vaccines and approved drugs highlights the need for additional antiviral agents. Nucleozin and its analogs have gain attention for their promising anti-influenza activity. To contribute to the advancement of the discovery and design of nucleozin analogs, we analyzed piperazine-modified nucleozin analogs to increase conformational freedom. Also, we describe a new synthetic strategy to obtain nucleozin and its analogues, three molecules were synthesized and two of them were biologically evaluated  Orthomyxoviridae family. This infection affects the respiratory system of the host, affecting the nasal pharyngeal mucosa, bronchi, and pulmonary alveoli. The symptoms of influenza are similar to the common cold; however, influenza can be deadly, especially in vulnerable groups. The mutation rate of the influenza virus; the high frequency of genetic rearrangement; and the antigenic changes in viral glycoproteins challenge the control of infections, causing even zoonotic interactions, such as avian influenza (H7 and H9) and swine influenza , with high potential for a pandemic threat. Pharmacological therapy is available. Rimantadine is used to treat or prevent the infection of seasonal influenza (Influenza B), and oseltamivir, peramivir, zanamivir are preferred for influenza (influenza A) that has reached epidemic and pandemic levels heptane (DBH) system, where compound 1 corresponds to the  diastereomer and compound 2 corresponds to the  diastereomer. This system has been introduced in a variety of compounds heptane, N-BocDBH, (19), reported previously, instead of the amine 14. Compound 9 was prepared from 2-chloro-4-nitrofluorobenzene (13), and compound 10 from the compound 4-nitrofluorobenzene (18).The same synthetic strategy was employed for the synthesis of compounds 9 and 10 ; for the11. The ethylenediamine was mono protected using the Boc2O reagent to obtain compound 24 which was mixed with an acyl chloride generated in situ from the carboxylic acid 17 treated with oxalyl chloride in dry dichloromethane in the presence of triethylamine as a base, and drops of dimethylformamide, rendering compound 25. Then, for the deprotection of the N-Boc group, the compound 25 was treated with methane sulfonic acid to form the primary amine 26, followed by a nucleophilic aromatic substitution, using 13 as an electrophile for obtaining the compound 11  as solvent at 120 °C. Some observations in the laboratory indicated that it was not necessary to add DMF to the reaction mixture for the synthesis of compound 20. For this reason, we carried out the reaction grinding in a mortar with a pestle, for 15 minutes, the monoprotected diamine 19 and the compound 13, both in solid state, in the presence of five equivalents of K2CO3 as a base, without DMF. The reaction was monitored by thin-layer chromatography (TLC), comparing the reaction mixture against the previously characterized compound 20, showing that most of the raw materials were transformed. Compound 20 was obtained by the addition of 3 mL of hot ethyl acetate (AcOEt), filtered through a small layer of Celite, recrystallized, and isolated from the mother liquor. By thin layer chromatography, a product with a good degree of purity was observed, and the melting point coincided with that reported m.p. = 199.7 °C. Thus, the substitution reaction can be carried out under free-solvent conditions. Future experiments will be carried out to explore this methodology as a potential synthesis route to new nlz derivatives.Thus, here we employed a new route using 4-nitrofluroarenes as feedstock, which efficiently led to nlz and is totally inhibited at 10 μM. Under the same conditions but in the presence of analogs 9 and 10, viral growth was not inhibited, as is shown in 9 and 10 will have viral inhibitory effects at larger concentrations. These results show that constraining the core structure of nlz  results in the loss of activity. Interestingly, the QSAR model developed here predicts the analogs 9 and 10 as less active, consistent with the experimental observation.The virus load starts to decline in the presence of 1μM of nlz analogs.Additional molecular modeling studies and experimental evaluation of other analogs will provide information on structural modifications required for the improvement of antiviral activity. QSAR models developed here will aid the synthetic efforts of new S1 File(PDF)Click here for additional data file.


Breeding programs in developing countries still cannot afford the new genotyping technologies, hindering their research. We aimed to assemble an Association Mapping panel to serve as CGIAR Barley Breeding Toolbox (CBBT), especially for the Developing World. The germplasm had to be representative of the one grown in the Developing World; with high genetic variability and be of public domain. For it, we genotyped with the Infinium iSelect 50K chip, a Global Barley Panel (GBP) of 530 genotypes representing a wide range of row-types, end-uses, growth habits, geographical origins and environments. 40,342 markers were polymorphic with an average polymorphism information content of 0.35 and 66% of them exceeding 0.25. The analysis of the population structure identified 8 subpopulations mostly linked to geographical origin, four of them with significant ICARDA origin. The 16 allele combinations at 4 major flowering genes  explained 11.07% genetic variation and were linked to the geographic origins of the lines. ICARDA material showed the widest diversity as revealed by the highest number of polymorphic loci , number of private alleles and the fact that ICARDA lines were present in all 8 subpopulations and carried all 16 allelic combinations. Due to their genetic diversity and their representativity of the germplasm adapted to the Developing World, ICARDA-derived lines and cultivated landraces were pre-selected to form the CBBT. Using the Mean of Transformed Kinships method, we assembled a panel capturing most of the allelic diversity in the GBP. The CBBT (N=250) preserves good balance between row-types and good representation of both phenology allelic combinations and subpopulations of the GBP. The CBBT and its genotypic data is available to researchers worldwide as a collaborative tool to underpin the genetic mechanisms of traits of interest for barley cultivation. The new advances in genotyping technologies and genomic research applied to breeding (Genome Wide Association Studies and more recently Genomic Selection) have the potential to bring the largest yield productivity increase and stability improvement since the Green Revolution. The efficient use of these new tools is important to attain the production needed to feed the increasing population in a scenario of climate instability. These new approaches have been widely adopted thanks to new low-cost and high throughput genotyping technologies . HoweverHordeum vulgare L.) covers 50Mha worldwide, ca. 20Mha of them in developing countries  of 530 barley entries. This panel includes entries representing the different barley uses , morphophysiological traits and phenology patterns and local and regional preferences. It is using the information gathered from this Global Barley Panel that we aim to constitute a barley breeding toolbox that represents the global diversity in the GBP and: i) is representative of the germplasm grown in the Developing World; ii) covers a wide range of genetic variability, morphophysiological traits and phenology groups and iii) is of public domain or international public goods to facilitate germplasm exchange.A Global Barley Panel (GBP) of 530 genotypes mainly considered of spring-type, including elite lines, cultivars, and landraces from different geographic origins was assembled. The GBP includes a significant number of elite lines and cultivars from the ICARDA Global Barley Breeding Program of the CGIAR, both from the ICARDA program previously based in Syria, now in Morocco and Lebanon, and from the ICARDA/CIMMYT Latin-America program based in Mexico, merged during the first decade of the 2000s. The set represents a worldwide spectrum of barley genetic variance with diversity of row-types, end-uses, growth habits and geographical and environmental distribution. Out of the 530 genotypes (292 two-row and 238 six-row types), 288 are from the ICARDA Global Barley Breeding Program, 61 from the United States of America (USA), 48 from Europe, 40 from India, 23 from Australia, 19 from Canada, 12 from Africa, 6 from Latin America and 16 from other countries across the globe. The Panel also includes 17 landraces from different countries Figure 1CMplot package (The genotyping work was done in two events. The first 266 entries were genotyped as described in  package  for R st package .R2) and significant corresponding p-values ≤ 0.01. The R Statistical Software .From the set of 40,342 SNP markers, a subset of 40,256 polymorphic markers with known physical positions was selected to perform the linkage disequilibrium (LD) analysis for each chromosome using TASSEL 5.0 software  and a slSoftware  was usedpoppr  was conducted with the filtered SNP marker set using TASSEL version 5.0 , and thepoppr  to inves  gene, BK_14 (A/G) associated with HvPPD-H1 gene, BK_17 (C/G) associated to HvVRN-H1 gene, and BOPA2_12_30265 (A/G) associated with HvCEN gene (poppr (R2) calculated by TASSEL software  associated to CEN gene . AMOVA te  with any ancestry in the model  algorithm implemented in the R package LEA . This mefunction  to test R package GeneticSubsetter  which measures the kinship of genotypes in a subset and identifies the most dissimilar set of genotypes, a favorable trait for GWAS studies.To select a subset that represents the diversity of the population and at the same time provides an optimized set of entries for association mapping studies we used the ubsetter . For it,2 values for the whole genome decreased with increasing pairwise distance. In general, LD showed a fast rate of decline, and the decay distance was approximately 0.3 Mb  were considered for analysis. The cultivated landraces were considered as a separate group to avoid distorting the genetic integrity of the geographic groups, as the rest of the lines are either released varieties or advanced breeding lines. The AMOVA of this grouping explained up to 12.32% of the total genetic variation Table 2.Population subgrouping using sNMF, cross-validation and the cross-entropy criterion approaches gave further information regarding the genotypic structure of the GBP. The cross-entropy criterion did not exhibit a minimum value or a clear plateau and steadily decreased at higher k values Figure 4At K=7 (HvVRN-H3 (FT1), HvPPD-H1 HvVRN-H1 and HvCEN) and generating sixteen allelic combinations (AC) was studied. The AMOVA of the genetic differentiation between and within each flowering locus and their allelic combinations was conducted . The distribution of different allelic combinations within germplasm origin groups is shown in All sixteen allelic combinations were present in the 275 genotypes from ICARDA origin. Thirteen allelic combinations were detected in USA group, eight in European, Australian and “Other” barleys, and seven in Indian genotypes. The most frequent allelic combinations in the germplasm were the early flowering AC15 (21.17%), AC12 (12.62%) and AC16 (12.43%). AC11 and AC13 were less frequent and unique to the ICARDA and Landrace populations.  and the landraces. The reason for this was to fulfill the three objectives of the present study, that is, that the panel developed is of public domain and free to use; that is relevant to the developing world and that it represents a wide genetic diversity Figure 6The subset continues to preserve a good balance between the row type with a slightly larger proportion of 6-row types (55% of the 250 entries) over the 2-rowed types as compared with the Global population (46% 6-row and 54% 2-row) Figure 6The characterization and dissection of genetic diversity and structure present in current germplasm collections help the breeders to meet breeding goals through the identification of beneficial alleles for traits of interest associated to molecular markers . With thOut of the 43,461 scorable SNPs markers of the 50k iSelect SNP array , 40,342 This result is similar and often higher than other reports of 39,733 SNPs ; 33,818 Principal components analysis (PCA) and the NJ clustering partitioned the 530 entries into two clearly defined groups based on row-type (2-row vs 6-row) and highlighted the presence of subgroups characterized by common or closely related origins. Furthermore, AMOVA analysis indicated that germplasm origin could also explain a significant part of genetic diversity. The variation explained by geographic origin was higher than the value reported by Row type in barley has been shown in the past to be one of the main determinants of the genetic structure, both due to the inherent nature of the trait which is associated to major regional preferences and its association to the different barley end-uses . Most EuThe group of ICARDA germplasm showed high genetic diversity as revealed by the number of polymorphic loci, number of unique alleles and Nei’s unbiased gene diversity. Moreover, 99.72% of the 40,342 polymorphic SNPs in the panel were so in the ICARDA population too. Interestingly, the lower differentiation between ICARDA germplasm and most of the other origins evidenced the long-lasting collaborations between the Global Program and national and regional breeding programs. In fact, more than 250 spring and winter 2-row, 6-row and naked barley varieties of ICARDA origin have been released in 46 countries since 1979, including USA (5 varieties), Canada (15 varieties), Australia (4), India (8 varieties) and some African (70) and Latin American (27) countries among others. ICARDA germplasm has in addition being extensively used in crosses in the National programs. Interestingly, the Indian germplasm is closely related to the groups of Landrace, ICARDA and Africa, while distinct from the other groups. Landrace group exhibited the lowest Npl, MAF and PIC values which may be explained by the under-representation of Landrace genotypes during the development of the 50K SNP array .Latin American germplasm exhibited the highest He, MAF, PIC although having the lowest number of individuals (5) as compared to other origins. This could be due to the diverse source of genotypes originating from different countries . Despite American malting varieties being obtained through hybridization with European accessions, the national industrial standards for malting and brewing have led to the development of germplasm with specific characteristics . The EurHvCEN, HvVrn-H3, HvPpd and HvVrn-H1) and their additive effect on the phenology and adaptation of the panel studied. These highly polymorphic (PIC > 0.4) loci were not in LD . This subpopulation assembled almost exclusively the 6-row ICARDA lines issued from the ICARDA/CIMMYT Latin America program, notably the lines derived from the cultivars PETUNIA-1 and, especially, ‘DOÑA JOSEFA’ (aka V-MORALES) a widely adapted 6-row malt barley line. The last subpopulation consisted of genotypes mostly issued from crosses between entries from the Syrian and Mexican programs. Despite this differentiation, the PCA showed some level of overlap in Clusters 5, 6 and 8 suggesting that these subpopulations may have some genetic overlapping that goes beyond the origin.Cluster 5, 6 and 8 assembled most of the 6-row barley lines of the panel. Although in this case, the phylogenetic clustering did not completely overlap with the subpopulations at K=4, at larger K these three clusters were evident. Cluster 5 grouped two subpopulations at K=8. The first subpopulation consisted of USA and Canada 6-row feed barley entries. The second grouped mostly 6-row Indian varieties. Cluster 6 instead consisted of a distinct subpopulation from ICARDA origin (SubPop7.7 and SubPop8.5). Genotypes of this group were mostly derived from crosses with the cultivar Admixed genotypes at K=8 belonged to nine geographical origins and 57.6% of them were ICARDA breeding lines (47% two-row and 53% six-row). The higher number of admixed genotypes among the ICARDA lines can be explained by their largest population size (53.6% of genotypes present in the collection) and its extensive use of two-by-six row crosses for germplasm improvement . LikewisThe main objective of the present study was to identify and assemble an Association Mapping panel of barley genotypes that represented the diversity of the Global Barley Panel to serve as a CGIAR barley breeding toolbox (CBBT) especially for the Developing World. For it, the main criteria to select among the lines in the Global panel was: i) to be representative of the germplasm grown in the Developing World; ii) to cover a wide range of genetic variability, morphophysiological relevant traits and phenology groups and iii) be of public domain or international public goods to facilitate germplasm exchange.In order to meet these criteria and due to their large diversity, the CGIAR entries, including landraces hosted in the ICARDA genebank were pre-selected for a total of 241 lines. The Developing World representativity requirement was met due to the global target of the CGIAR Global Barley Breeding program especially in terms of adaptation and end-uses. In fact, most of the CGIAR lines included in the panel have been shared with and selected by National Partners as part of the Barley International Nurseries. These sets of diverse and elite barley genotypes distributed upon request to more than 70 collaborators in 20 countries in America, Europe, Africa and Asia  annuallyHowever, to facilitate future phenotyping studies and reduce redundancies a core subset of 250 entries was selected using Mean of Transformed Kinships method. The use of this method differs from others like the PIC based one used in other studies such as Germinate Database (https://germinateplatform.github.io/get-germinate/). All the data generated on this population will be freely available in Germinate for the global barley community to use.The genotypic data of the population is available in The main objective of the present study was to assemble a collection of diverse barley germplasm representative of the germplasm grown worldwide and with particular emphasis on Developing World. The results showed that the Global panel used in this study is highly diverse and covers a wide range of both genetic variability of cultivated barley and phenology groups. The CBBT assembled represents with fidelity the genetic diversity and key morphophysiological traits of the Global panel. This collection will be made available, together with the genotypic data, to breeders and researchers worldwide to serve as a collaborative tool to underpin the genetic mechanisms of traits of interest for barley cultivation. In addition, the collaborative approach to gene discovery will make this collection a toolbox for breeders that will be able to use the germplasm and the markers identified by researchers worldwide in their own breeding programs.https://germinateplatform.github.io/get-germinate/). All the data generated on this population will be freely available in Germinate for the global barley community to use.The genotypic data of the population is available in S-GM, VA, and BO formulated the research problem and designed the approaches. S-GM, VRPS, GS, and CF selected and obtained the germplasm and arranged the genotyping. BO, S-GM and VA performed statistical analysis of data, BO wrote the initial draft of the paper, VA and S-GM revised the manuscript. All authors contributed to the final draft of the paper and approved the final version of the manuscript. All authors reviewed the article and approved the submitted version.Modernization of crop breeding programs at ICARDA - building on past AFESD support to prepare for the future project funded by the Arab Fund for Economic and Social Development (AFESD).The present work was supported by the Accelerated Breeding Initiative (ABI) and the Sustainable Animal Productivity for Livelihoods, Nutrition and Gender inclusion (SAPLING) to the outcome of this research.The authors would like to thank the USDA small grains genotyping lab in Fargo  and Dr. Shiaoman Chao for the genotyping of 266 genotypes used in the present study. The authors acknowledge the support and commitment of the CGIAR Author SG was employed by Sakata Seed America Inc.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cytochrome P450 is an enzyme involved in the metabolism of phase 1 xenobiotics, toxins, endogenous hormones, and drugs, including those used in COVID-19 treatment. Cytochrome p450 genes are linked to the pathogenesis of some multifactorial traits and diseases, such as cancer, particularly prostate cancer, colorectal cancer, breast cancer, and cervical cancer. Genotyping was performed on 540 supposedly healthy individuals of 5 Finno-Permic populations from the territories of the European part of the Russian Federation. There was a statistically significant difference between Veps and most of the studied populations in the rs4986774 locus of the CYP2D6 gene; data on the rs3892097 locus of the CYP2D6 gene shows that Izhemsky Komis are different from the Mordovian and Udmurt populations. CYP1A1 gene [The cross-disciplinary integration of the latest research results is particularly important in modern science in order to ensure its effective practical application and reliability. Thus, population genetics studies may contribute to developing new pharmacogenetic approaches, such as tailored treatments targeting representatives of specific ethnic groups with drugs that are more effective for the population in question. The study of polymorphic allelic variants of the cytochrome P450 (CYP450s) genes is of a particular interest to us as its products are responsible for the Phase I biotransformation of drugs of some of the most important categories. CYP450s are heme-containing enzymes that are critical to many cellular processes including eicosanoid metabolism, cholesterol, and bile acid biosynthesis, synthesis, and metabolism of steroids and vitamin D3, biogenic amines formation, and the breakdown and hydroxylation of retinoic acid. There are many other functions of CYP450s including some still not fully understood. Evidence shows that polymorphic CYP450s genes variants are associated with predisposition to such serious diseases as malignant neoplasms (MNs), for example rs1048943 in the A study of 100 patients with prostate cancer and 150 healthy people reported an association of the AA rs1048943 genotype with the risk of developing prostate cancer in Iraqi residents . SimilarCYP1A1 gene were associated with the risk of developing this malignant neoplasm in the Asian population. At the same time, these associated risks were not true for the Caucasian population [Another meta-analysis caried out in 2016 included 748 patients with laryngeal cancer and a control group of 1558 individuals; it concluded that the G allele and G/G rs1048943 homozygotes in the CYP2D6 gene with worse disease-free survival and relapse in women receiving adjuvant treatment with tamoxifen dosage of 20 mg/day [In 2017, a meta-analysis of 15 studies of breast cancer in Asia  revealed an association of the rs1065852 *10/*10 (TT) polymorphism in the In addition, the role of CYP450s isoforms in the metabolism of neurotransmitters, neurosteroids, and cholesterol is currently being studied, as well as their possible effect on behavior including stress, depression, schizophrenia, cognitive processes, learning, and memory. Haduch and Daniel 2019) emphasize the significance of the CYP-mediated alternative pathways for the synthesis of dopamine and serotonin, as they are critical in the local production of these neurotransmitters specifically in the areas of the brain severely affected by depression and schizophrenia, where these neurotransmitter systems are impaired . Most an emphasizThe role of cytochrome P450 genes in the pathogenesis of infectious diseases, COVID-19 in particular, is currently being studied, as well as its effect on drug therapy. It was shown that the expression of CYP2D6 decreases in mice infected with hepatitis C virus (HCV) , while tThe Finno-Ugric ethno-linguistic community is currently one of the largest language groups in Europe with total of more than 25 million people. The Finno-Ugric branch of languages is divided into two large sub-branches: Finno-Permic and Ugric. Most modern Finno-Ugric languages belong to the Finno-Permic sub-branch while accounting for less than half of the population ,17.It is assumed that the ancestral pre-Finno-Ugric population belonged to a single anthropological group originated in ancient Ural. However, modern Finno-Ugric peoples are extremely diverse. Thus, modern Karelians and Vepsians can be described as Caucasians of White Sea-Baltic type, while most of the Mordovians-Erzi are of the Atlanto-Baltic Sura type, and the Mordovians-Mokshas are of the Subural type. The Udmurts belong to the Vyatka-Kama sublaponoid anthropological type, which is characterized by the predominance of Caucasian features over the also present Mongoloid ones.Population genetics studies of the Finno-Ugric peoples have shown that the modern speakers of these languages and their geographical neighbors are alike in terms of genetic composition of these biological populations. However, when studying connections between geographically distant populations, it is revealed that most of the speakers of these languages and some of their neighbors share a common genetic component, possibly of Siberian origin. In addition, it has been shown that the number of identical IBD segments is much higher among most Uralic-speaking peoples compared to their closest geographic neighbors belonging to other language families .The objective of this research is to study the main pharmacogenetic markers among the Finno-Permic peoples populating the European part of Russian Federation.The sample used in this study included 540 presumably healthy individuals of 5 Finno-Permic populations from the territories in the European part of the Russian Federation . The sam® tubes were used to collect, transport, and store the blood samples using 0.5 M EDTA solution as a preservative. After drawing the sample, each tube was shaken and stored at 4 °C.The DNA was extracted from peripheral blood samples using phenol-chloroform . Vacutai2 test (at p > 0.05). The significance of differences in allele frequencies in the sample was calculated by the χ2 test using the Yates correction for continuity. Surfer 24.1.181 was used to produce allele distribution maps.TaqMan real-time PCR technology was used for the genotyping of polymorphic loci. The incidence of allele variants in given populations were calculated based on observed genotype frequencies. The correspondence of the genotype frequencies to the Hardy–Weinberg equilibrium was assessed using Pearson’s χp < 0.05, as well as the distribution of genotypes of the rs1065852 polymorphic variant of the CYP2D6 gene in the Udmurt population. Based on this data alone, it is impossible to determine the cause of such a deviation, however, the effect of natural selection on these loci seems to be the most reasonable explanation for this phenomenon.In this paper we studied 4 polymorphic loci located in two genes of the cytochrome P450 system . The distribution of genotype frequencies corresponded to the Hardy–Weinberg equilibrium in most Finno-Permic populations studied by us. Among the few exceptions were the polymorphisms rs1048943, rs1065852, rs3892097 in Mordovian population with Paired comparison tests were run for allele frequencies and all selected markers in the studied ethnic groups. In addition, the analysis included data on some other world populations previously published in the academic literature, as well as the data obtained inthe 1000 genomes project .The ethnogenesis of modern Finno-Ugric peoples is an extremely complex topic. The collapse of the ancient Ural community, according to researchers ,22, occup-value), it can be concluded that there are no statistically significant differences between allele frequencies in all studied populations. At the same time, the statistically significant differences between the Besermyan and Erzya and the populations of Tatars and Bashkirs, as well as Komi and Bashkirs, are of interest. Even though both Tatars and Bashkirs live in the Volga-Ural region, may be explained by the greater effect of East Eurasian component on the gene pool of the indicated Turkic-speaking populations.In our study, it was found that the frequency of the genotype AA rs1048943 of the CYP1A1 gene is evenly distributed among all the studied populations and the minimum value is observed in the Udmurt population (88.54%) while the maximum value is in the Erzya subpopulation (96.15%). The GG genotype was found in the Mordovian and Komi populations with frequencies of 1.47% and 1.06%, respectively . Table 3p-value) revealed complex interrelations within the studied populations  in the Komi population from the Izhma region, and up to 18.23% (95% CI 13.04–24.43) in the Udmurt population . The populations . Thus, tp-value), a statistically significant difference was revealed between the Komi population from the Izhemsky district of the Komi Republic and three other populations: the Udmurt populations, the total sample of Mordovians, and with the Mordovian-Moksha subpopulation , as well as in the populations of East Asia over 30%) and Kazakhstan 28.4%) ,28,29,30.4% ,28,2% and KazCYP1A1 (2455G) allele occurs with frequencies typical for Western Asian and European populations. These new data on the xenobiotic biotransformation genes allele frequency distribution should be considered in further pharmacogenetic studies.In this paper, the polymorphism of the Phase I gene of the CYP1A1 xenobiotic biotransformation system  was studied for the first time in the Finno-Permic populations inhabiting the vast territories of the European part of the Russian Federation. The data obtained show no significant differences between the Finno-Permic populations included in the study, with the exception of Turkic-speaking populations of the Bashkirs and Tatars. In the studied populations, the CYP2D6 gene obtained for our sample of the Komi, Komi of the Izhma region, Veps, and Karelians are statistically different from the typical pan-European frequency values. The populations with remarkably similar results are of a particular interest, especially the Karelians and the Finn population [Cytochrome P450 2D6 is involved in the metabolism of many drugs including those used in treatment of cancer and cardiac diseases . Our stupulation , which aA worldwide study of rs1048943 in the CYP1A1 gene revealed an association of the G allele with prostate cancer  and coloIt is also important that a large number of antipsychotics and antidepressants, as well as drugs used for COVID-19 treatment, are metabolized by polymorphic CYP2D6 enzymes. Thus, understanding the distribution of CYP2D6 alleles in the Finno-Permic populations will allow us to develop new approaches to treatment targeting particular ethnic groups.This study of the main pharmacogenetic markers shows statistically significant difference between Veps and most of the studied populations in the rs4986774 locus of the CYP2D6 gene; as for the rs3892097 locus of the CYP2D6 gene, here we can see that Izhemsky Komis are different from the Mordovian and Udmurt populations.


Steel plate shear walls (SPSWs) are among the most desirable load-bearing systems, which have been used wildly in various structures. Recently, designers have tended to SPSWs with only beam connections showing several problems. In the present research, several SPSWs with various types of connection conditions between infill plate and boundary elements, and various stiffness of boundary elements have been studied. The result illustrates that by having the full connection between infill plate and boundary elements, at least a 33% interconnected infill plate to columns could eliminate the significant loss of fundamental factors in SPSWs connected to beam only. Furthermore, increasing the stiffness of columns has more effect on the performance of SPSWs in comparison with beams. SPSWs are used in many various lateral-load-resisting systems for having low weight, fast and appropriate workability, significant ultimate strength, sufficient ductility, and stiffness. Previous studies indicated the advantages of the use of these systems in significantly space-constrained areas and high seismic conditions ,2,3. RecThe cantilever wall system of SPSWs is developed, consisting of a vertical steel plate connected to surrounding boundary element members ,29,30,31Under lateral cyclic loading conditions, the SPSW undergoes in-plane and out-of-plane deformations. Due to the slenderness of the infill plate, buckling occurs at the initial loading. The infill plate folds in an out-of-plane direction, initiating the diagonal tension field action parallel to the principal tensile stresses, which leads to the postbuckling resistance capacity. Several studies indicated that the postbuckling strength of these walls is highly dependent on the development of tension field action, which is completely affected by the infill plate’s interconnectivity with boundary elements ,39. SeveFrom the laboratory investigations, it was shown that those SPSWs that infill plates were only attached to the one of the boundary elements; several desirable performances were obtained ,44,45,46Although only some research has been conducted regarding the performance of SPSWs with connection to beams, there are some hidden points about the minimum desirable interconnection between the infill plate and boundary elements and the simultaneous effects of stiffness of boundary elements on the performance of SPSWs. In this study, a number of computational SPSW models with various types of connection conditions of the infill plate to boundary elements and boundary element stiffness were designed based on the verified experimental specimen of Choi et al. . All mod. Columns were chosen to be H-150 × 150 × 8 × 20; beams of the first and second floors’ boundary elements were H-150 × 100 × 12 × 20; and the beam of the third floor was H-250 × 150 × 12 × 20. Loading was applied to the top beam of the specimen under ATC-24 protocol.In the present research, a parametric study, according to previous research methods ,49, baseFigure 1The verification specimen was modeled according to the experimental specimen’s geometry and material by ABAQUS 6.14-2. S4R elements were utilized for the FE model and the mesh size was 100 mm. Boundary conditions were defined in a way in which supports were rigid and out-of-plane movements of the specimen in the location of the beam and column connection were prevented. Hysteresis graphs of the FE model and experimental model are shown in Comparison between the FE model and experimental specimens are shown in All FE models were designed by modifying the verified computational model (S1). The geometry and materials of all models were similar to the S1 model; however, they had some changes in other sections, such as stiffness of elements and the type of connection between infill plate and boundary elements. Stiffness of the one of the columns in some models was increased by 100%; these were called S2X models. S3X models had a 100% increase on the beams of the first and second floors. S4X models experienced a 100% increase on the beam of the third floor. Moreover, SXC and SXB models were designed in a way that infill plates had connections just with columns or beams. In the former model, the infill plate has connections only with the columns and the latter has connections with beams. Another type of connection is displayed in the SXN models. These models have full connection of infill plate with beams and 33% with columns. The changes in designed models are shown in . In all models, columns buckled on the first floor, which relates to the soft story formation on this floor due to higher stiffness of the boundary elements, and beams in particular. From In the present section, some of the FE models after loading were investigated and shown in Figure 6As expected from the results of the line graphs, the column-only-connected models experienced 54.28–57.67%, the beam-only-connected 11.18–12.64%, and those fully connected to beams and 33% to columns had a 3.23–4.60% decline in ultimate strength in comparison with the classic type of connection, which is shown in From the bar chart in Based on the extracted result, it can be observed that the classic type of connection between infill plate and boundary elements (full connection) had the desirable performance; however, the aforementioned type could increase the demands on the columns. Accordingly, designers prefer to detach the connection of the infill plate to columns to achieve an economical design of columns. It is noteworthy to mention that according to the result, SPSWs with only beam connection can achieve considerably lower values in comparison with the classic type of SPSWs. Only 33% of the connection of the infill plate to the columns to some extent can eliminate the negative result of this type of connection. In addition, this connection has been expanded from the center of the column, which can keep the stress far from the beam-to-column-connection region. On average, the reductions in ultimate strength for the column-connected, for the beam-only-connected, and partially connected columns were 56%, 12.16%, and 4%, respectively. The decreases in energy absorption were 61%, 17%, and 3%, respectively. Furthermore, the result shows that the performance of the columns-only connection is not reliable. Even though the beams-only connection also had a considerable loss in fundamental factors, this can be rectified to some extent by the 33% connection of the infill plate to columns. Regarding the increase in stiffness in the boundary elements, it can be mentioned that although increasing the stiffness of the top beam had a more positive response in comparison with the first and second floors’ beams, this amount was negligible and the effect of the increase in the stiffness of one column had a much more positive result in comparison with the changes.