Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle.

The muscle myosins and hexomeric proteins consisting of two heavy chains and two pairs of light chains, the latter called essential (ELC) and regulatory (RLC). The light chains stabilize the long alpha helical neck of the myosin head. Their function in striated muscle, however, is only partially understood. We report here the identification of distinct missense mutations in a skeletal/ventricular ELC and RLC, each of which are associated with a rare variant of cardiac hypertrophy as well as abnormal skeletal muscle. We show that myosin containing the mutant ELC has abnormal function, map the mutant residues on the three-dimensional structure of myosin and suggest that the mutations disrupt the stretch activation response of the cardiac papillary muscles.

Design of an optofluidic biosensor using the slow-light effect in photonic crystal structures.

The authors propose a biosensor architecture based on the selective infiltration of photonic crystal (PhC) structures. The proposed sensor consists of a ring cavity coupled to an optofluidic slow-light waveguide in a PhC platform. A high potential sensitivity of 293 nm/refractive index unit is numerically demonstrated, while maintaining an ultracompact footprint.

[Bromhexine is a potential drug for COVID-19; From hypothesis to clinical trials].

COVID-19 (novel coronavirus disease 2019), caused by the SARS-CoV-2 virus, has various clinical manifestations and several pathogenic pathways. Although several therapeutic options have been used to control COVID-19, none of these medications have been proven to be a definitive cure. Transmembrane serine protease 2 (TMPRSS2) is a protease that has a key role in the entry of SARS-CoV-2 into host cells. Following the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptors of the host cells, TMPRSS2 processes and activates the S protein on the epithelial cells. As a result, the membranes of the virus and host cell fuse. Bromhexine is a specific TMPRSS2 inhibitor that potentially inhibits the infectivity cycle of SARS-CoV-2. Moreover, several clinical trials are evaluating the efficacy of bromhexine in COVID-19 patients. The findings of these studies have shown that bromhexine is effective in improving the clinical outcomes of COVID-19 and has prophylactic effects by inhibiting TMPRSS2 and viral penetration into the host cells. Bromhexine alone cannot cure all of the symptoms of SARS-CoV-2 infection. However, it could be an effective addition to control and prevent the disease progression along with other drugs that are used to treat COVID-19. Further studies are required to investigate the efficacy of bromhexine in COVID-19.

Comparison of Cattle Serum Antibody Responses to Five Different Mycobacterial Antigens in an ELISA System.

The presence of common zoonosis diseases caused by Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM), such as Johne's and Crohn's diseases, poses a public health threat and economic losses to Iranian livestock. Therefore, the early detection of mycobacteria is of paramount importance. In this regard, enzyme-linked immunosorbent assay (ELISA) is a new, simple to use, rapid, and useful diagnostic tool. This study was performed to evaluate different crude antigens obtained from Mycobacterium species using an indirect ELISA test to identify the mycobacterial infection in infected livestock. Five different strains of Mycobacteria including M. tuberculosis, M. phlei, M. bovis, M. aviumsubspecies paratuberculosis, and M. bovis AN5 were cultured. The crude antigens in the samples were precipitated with trichloroacetic acid 4%. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude antigens isolated from different Mycobacterium species was reported. The total level of protein was determined by the Lowry protein assay. After the crude antigen preparation, the ELISA test was performed and the results were compared with the purified protein derivative skin test. Data analysis was performed using SPSS software version 25. All five strains were detected in more than 92% of healthy animals. The highest sensitivity of ELISA tests was in M. bovis AN5 antigen which was greater than 83%. The highest diagnostic specificity and efficiency of assays were in M. avium subspecies paratuberculosis which was 95.83% and over 83%, respectively. Regarding the results, M. avium subspecies paratuberculosis and M. bovis AN5 antigens were promising candidates for the design of diagnostic ELISA due to their sensitivity, specificity, and efficiency.

Analysis and assessment of ground-level ozone measured at two stations in Tehran.

In this study, variations of ambient ozone level are thoroughly analysed according to the monitored data in a mixed residential, commercial and industrial city, Tehran, based on considering the meteorological factors. Ozone as a pollutant shows typical annual, weekly and diurnal cycles. This analysis has shown that the ozone level concentrations were below the WHO guidelines in Tehran during 2000-2003. The relation between ozone level at two different stations (Aghdasieh and Fatemi) is found (r = 0.51). The ozone level response to meteorological parameters is investigated. The results suggest that the ozone level is affected (positively or negatively) by meteorological conditions, e.g. relative humidity, solar radiation, air temperature, wind speed and wind direction.

Statistical models and time series forecasting of sulfur dioxide: a case study Tehran.

This study performed a time-series analysis, frequency distribution and prediction of SO(2) levels for five stations (Pardisan, Vila, Azadi, Gholhak and Bahman) in Tehran for the period of 2000-2005. Most sites show a quite similar characteristic with highest pollution in autumn-winter time and least pollution in spring-summer. The frequency distributions show higher peaks at two residential sites. The potential for SO(2) problems is high because of high emissions and the close geographical proximity of the major industrial and urban centers. The ACF and PACF are nonzero for several lags, indicating a mixed (ARMA) model, then at Bahman station an ARMA model was used for forecasting SO(2). The partial autocorrelations become close to 0 after about 5 lags while the autocorrelations remain strong through all the lags shown. The results proved that ARMA (2,2) model can provides reliable, satisfactory predictions for time series.

Impact of education in promoting the knowledge of and attitude to HIV/AIDS prevention: a trial on 17,000 Iranian students.

The aim of this study was to assess the impact of an educational course on knowledge and attitude of students regarding HIV/AIDS prevention in Tabriz, Iran. The study was conducted by self-assessment technique among university students before and after an educational training programme. The findings showed that the knowledge of students increased significantly (P<0.05). The attitude to the problem also improved positively in the subjects (P<0.05). It is concluded that short-term training courses and continuous educational programmes (i.e. peer education, etc.) should be provided to young students through the course materials in the universities and schools promoting the awareness and attitude to this ever-increasing health problem.

Cochlear implantation in children with Waardenburg syndrome.

Waardenburg syndrome is an autosomal-dominant trait resulting from mutations occurring in different genes. It is often characterized by varying degrees of: congenital hearing loss; dystopia canthorum; synophrys; broad nasal root; depigmentation of hair (white forelock), skin or both; and heterochromic or hypochromic irides. A retrospective case study was done to assess speech perception, speech production, general intelligence and educational setting in six profoundly hearing-impaired children with Waardenburg syndrome (four with type I, one with type II and one with type III) ranging in age from two years to 14 years, seven months (mean = six years, six months). None of the patients had malformation of the cochlea and were implanted using Nucleus 22/24 and Med-el combi40+. Five out of the six cases were of average intelligence and one had a borderline intelligence quotient. The follow-up period ranged from one year, 10 months to six years, six months (mean = three years, six months) after implantation. The evaluation of auditory perception in patients was accomplished using the Persian Auditory Perception Test for the Hearing-Impaired, a Persian Spondee words test and the Categories of Auditory Performance Index. The Speech Intelligibility Rating test was used to evaluate speech production ability. All the patients' speech perception and speech intelligibility capabilities improved considerably after receiving the implants, and they were able to be placed in regular educational settings. Patients used their cochlear-implant devices whenever awake, implying that they benefitted from the devices. We suggest that any further expansion of cochlear-implantation criteria in children include those with Waardenburg syndrome.

Outcomes of cochlear implantation in deaf children of deaf parents: comparative study.

OBJECTIVE: This retrospective study compared the cochlear implantation outcomes of first- and second-generation deaf children. METHODS: The study group consisted of seven deaf, cochlear-implanted children with deaf parents. An equal number of deaf children with normal-hearing parents were selected by matched sampling as a reference group. Participants were matched based on onset and severity of deafness, duration of deafness, age at cochlear implantation, duration of cochlear implantation, gender, and cochlear implant model. We used the Persian Auditory Perception Test for the Hearing Impaired, the Speech Intelligibility Rating scale, and the Sentence Imitation Test, in order to measure participants' speech perception, speech production and language development, respectively. RESULTS: Both groups of children showed auditory and speech development. However, the second-generation deaf children (i.e. deaf children of deaf parents) exceeded the cochlear implantation performance of the deaf children with hearing parents. CONCLUSION: This study confirms that second-generation deaf children exceed deaf children of hearing parents in terms of cochlear implantation performance. Encouraging deaf children to communicate in sign language from a very early age, before cochlear implantation, appears to improve their ability to learn spoken language after cochlear implantation.

High vero cell density and rabies virus proliferation on fibracel disks versus cytodex-1 in spinner flask.

To achieve higher titer of rabies virus higher density of host cells will need. In this study, capability of FibraCel disks packed in 500 mL spinner basket versus Cytodex-1 in 500 mL spinner flask was investigated for propagation of Vero cells and PV rabies virus proliferation. Minimal Essential Medium (MEM) + 10% Foetal Calf Serum (FCS) and Virus Production- Serum Free Medium (VP-SFM) +4 mM L-glutamine were used in growth phase and MEM+ 0.2% Bovine Serum Albumin (BSA) and VP-SFM were used in virus production phase. Adapted Vero cells grown in VP-SFM were used in all SFM experiments while batch and stepwise perfusion modes were applied and compared in growth stage. The highest Vero cell density were achieved in the trials with 10 g FibraCel disk in stepwise perfusion mode equal to 6.12 x 10(6) and 5.87 x 10(6) cells mL(-1) in MEM and VP-SFM, respectively while with 2.73 g Cytodex-1 lower density equal to 4.2 x 10(6) and 4.0 x 10(6) cells mL(-1) were achieved. The highest titer of rabies virus and overall virus production rate were resulted in VP-SFM and on 10 g disks equal to 2.9 x 10(7) Fluorescent Focus Unit (FFU) mL(-1) and 0.14 FFU/Cell/h, respectively versus 1.7 x 10(7) FFU mL(-1) and 0.08 FFU/cell/h on cytodex-1 in similar conditions. The second harvest of virus was also satisfactory in experiment with 10 g disks (1.7 x 10(7) FFU mL(-1)) in compare to Cytodex-1 (0.51 x 10(7) FFU mL(-1)). An equal surface area at 6600 and 12000 cm(-2) were provided in all comparable trials with seeding density of 12.5 x 10(3) cells cm(-2). Adapted Vero cells grown in VP-SFM were used in all SFM experiments while batch and stepwise perfusion modes were applied and compared in growth stage.

Prevalence of GJB2-associated deafness and outcomes of cochlear implantation in Iran.

OBJECTIVES: To investigate the prevalence of mutations in the coding exon of the GJB2 gene in Iranian children with cochlear implants, and to compare the outcomes of auditory perception and speech production in cochlear-implanted children with and without GJB2 mutation. MATERIALS AND METHODS: One hundred and sixty-six prelingually deaf children who had undergone cochlear implantation at the Iranian Cochlear Implant Center, Tehran, were selected from a pool of 428 implanted children. The prevalence of GJB2 gene mutations was assessed using nested polymerase chain reaction and direct sequencing. To enable comparisons, we also identified 36 implanted children with non-GJB2 deafness. Patients' speech perception and speech production were assessed using the Categorization of Auditory Performance and Speech Intelligibility Rating scales. RESULTS: Thirty-three of 166 probands (19.9 per cent) were found to have GJB2 deafness-causing allele variants and were diagnosed with DFNB1 deafness. Results also indicated a significant improvement in speech perception and production scores in both GJB2 and non-GJB2 patients over time. CONCLUSION: Children with GJB2-related deafness benefit from cochlear implantation to the same extent as those with non-GJB2-related deafness.

Cochlear implantation in children with Jervell, Lange-Nielsen syndrome.

Jervell, Lange-Nielsen syndrome is a condition that causes profound hearing loss and disruption of the normal cardiac rhythm. This disorder is a form of long QT syndrome, a cardiac disorder that causes the cardiac muscle to take longer than usual to recharge between beats. A retrospective case study was performed to document cochlear implantation in three profoundly deaf children (two of them siblings) with Jervell, Lange-Nielsen syndrome. We discuss diagnosis and management of this syndrome and also the long-term performance of cochlear implantation in these Iranian patients, referring especially to the role of the ENT specialist in diagnosis and treatment. The collected data show that cochlear implantation can be relatively safely performed in patients with Jervell, Lange-Nielsen syndrome and that these children received significant benefit from cochlear implantation.

Cochlear implantation in prelingually deaf persons with additional disability.

OBJECTIVES: We aimed to identify the frequency with which the following conditions were present as a second disability in cochlear-implanted, prelingually deaf persons: mild and moderate mental retardation; learning disability; attention deficit/hyperactivity disorder; cerebral palsy; congenital blindness; and autism. We also aimed to document the development of auditory perception in patients having one of these additional disabilities. STUDY DESIGN: A retrospective study was designed to pursue the above aims. METHODS: We examined the records of 398 cochlear-implanted, prelingually deaf patients who had received a cochlear implant at least one year previously. Patients were selected who showed a delay in motor, cognitive or emotional development. The selected cases were referred for psychological evaluation in order to identify patients with additional disabilities. We then compared these patients' auditory perception prior to and one year following cochlear implantation. RESULTS: A total of 60 (15 per cent) cochlear-implanted, prelingually deaf patients were diagnosed with additional disabilities. These were classified as: mild mental retardation in eight cases (13.33 per cent); moderate mental retardation in five (8.33 per cent); learning disability in 20 (33.33 per cent); attention deficit/hyperactivity disorder in 15 (25 per cent); cerebral palsy in five (8.33); congenital blindness in three (5 per cent); and autism in four (6.66 per cent). All patients showed significant development in speech perception, except for autistic and congenitally deaf-blind patients. CONCLUSION: Although cochlear implantation is not contraindicated in prelingually deaf persons with additional disabilities, congenitally deaf-blind and autistic patients showed limited development in auditory perception as a main outcome of cochlear implantation. These patients require unique rehabilitation in order to achieve more auditory development.

The stretch-activation response may be critical to the proper functioning of the mammalian heart.

The "stretch-activation" response is essential to the generation of the oscillatory power required for the beating of insect wings. It has been conjectured but not previously shown that a stretch-activation response contributes to the performance of a beating heart. Here, we generated transgenic mice that express a human mutant myosin essential light chain derived from a family with an inherited cardiac hypertrophy. These mice faithfully replicate the cardiac disease of the patients with this mutant allele. They provide the opportunity to study the stretch-activation response before the hearts are distorted by the hypertrophic process. Studies disclose a mismatch between the physiologic heart rate and resonant frequency of the cardiac papillary muscles expressing the mutant essential light chain. This discordance reduces oscillatory power at frequencies that correspond to physiologic heart-rates and is followed by subsequent hypertrophy. It appears, therefore, that the stretch-activation response, first described in insect flight muscle, may play a role in the mammalian heart, and its further study may suggest a new way to modulate human cardiac function.

The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation.

Evolution of the human heart has incorporated a variety of successful strategies for motion used throughout the animal kingdom. One such strategy is to add the efficiency of torsion to compression so that blood is wrung, as well as pumped, out of the heart. Models of cardiac torsion have assumed uniform contractile properties of muscle fibers throughout the heart. Here, we show how a spatial gradient of myosin light chain phosphorylation across the heart facilitates torsion by inversely altering tension production and the stretch activation response. To demonstrate the importance of cardiac light chain phosphorylation, we cloned a myosin light chain kinase from a human heart and have identified a gain-in-function mutation in two individuals with cardiac hypertrophy.