Journal of the Acoustical Society of America, Apr 1, 2016
The acoustic waveform of speech is characterized by slowly varying amplitude fluctuations (i.e., ... more The acoustic waveform of speech is characterized by slowly varying amplitude fluctuations (i.e., envelope) and an accurate representation of the envelope is essential for speech understanding. The post-cochlear representation of the contrast between peaks and valleys of the envelope (peak-to-valley contrast) may be reduced by cochlear compression. This study tested (1) whether amplitude modulation (AM) detection thresholds are consistent with cochlear compression and (2) whether the introduction of a precursor before the carrier results in improved AM thresholds, consistent with a decompressed cochlear response via the medial olivocochlear reflex (MOCR). In the no precursor condition, AM thresholds worsen at mid-levels, consistent with reduced peak-to-valley contrast from cochlear compression. In the precursor condition, AM thresholds improved at low modulation frequencies and mid-to-high levels, consistent with a reduction in cochlear amplifier gain and decompression of the cochlear input/output function via the MOCR. These findings suggest the MOCR may play a role in the perception of other amplitude-modulated stimuli, such as speech.
International Journal of Pediatric Otorhinolaryngology, Nov 1, 2020
OBJECTIVES:Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children s... more OBJECTIVES:Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children show evidence of synaptopathy.STUDY DESIGN:Murine model of CMV infection and case seriesSUBJECTS AND METHODS:C57 BL/6 mice were inoculated with murine-CMV (mCMV). Auditory function was assessed using Auditory Brainstem Response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Temporal bones from mCMV-infected mice were used for both ribbon synapse and hair cell quantification. Four groups of children (non-CMV normal hearing, non-CMV hearing impaired, CMV normal hearing and CMV hearing impaired) underwent ABRs between 2014-2018. The outcomes included raw amplitude, wave I:V amplitude ratio, absolute latency, and interpeak latency.RESULTS:Mice at 8 weeks post mCMV infection had higher ABR and DPOAE (P < 0.05) thresholds and increased outer hair cell loss compared to uninfected mice and mCMV-infected mice at 4- and 6-weeks post infection, indicating progressive hearing loss. A reduction in the wave I amplitude and synaptic counts were noted earlier at 4 weeks in CMV-infected mice (P < 0.05). The human data indicated that the wave I:V amplitude ratio was lower on average in CMV-infected groups when compared to the uninfected cohorts. The wave I:V amplitude ratio for the click and 4k stimuli were not significantly different between the congenital CMV-infected and uninfected children with normal or with hearing loss.CONCLUSION:This study suggests mCMV infection results in a synaptopathy before hair cell damage. Additional studies need to be performed to determine whether this effect is also observed in CMV-infected children.Level of evidence:animal studies and basic science- NA; human studies: level 4.
Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineur... more Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear... more The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear sensory epithelium and plays an essential role in auditory transduction. The TM forms facing the luminal endolymph-filled space and exhibits complex ultrastructure. Contrary to the current extracellular assembly model, which posits that secreted collagen fibrils and ECM components self-arrange in the extracellular space, we show that surface tethering of -tectorin (TECTA) via a glycosylphosphatidylinositol anchor is essential to prevent diffusion of secreted TM components. In the absence of surface-tethered TECTA, collagen fibrils aggregate randomly and fail to recruit TM glycoproteins. Conversely, conversion of TECTA into a transmembrane form results in a layer of collagens on the epithelial surface that fails to form a multilayered structure. We propose a three-dimensional printing model for TM morphogenesis: A new layer of ECM is printed on the cell surface concomitant with the release of a preestablished layer to generate the multilayered TM.
Adenylyl cyclase 6 (AC6) synthesizes second messenger cAMP in G protein-coupled receptor (GPCR) s... more Adenylyl cyclase 6 (AC6) synthesizes second messenger cAMP in G protein-coupled receptor (GPCR) signaling. In cochlear hair cells, AC6 distribution relies on an adhesion GPCR, ADGRV1, which is associated with Usher syndrome (USH), a condition of combined hearing and vision loss. ADGRV1 is a component of the USH type 2 (USH2) protein complex in hair cells and photoreceptors. However, the role of AC6 in the inner ear and retina has not been explored. Here, we found that AC6 distribution in hair cells depends on the USH2 protein complex integrity. Several known AC6 regulators and effectors, which were previously reported to participate in ADGRV1 signaling in vitro, are localized to the stereociliary compartments that overlap with AC6 distribution in hair cells. In young AC6 knockout (Adcy6 −/−) mice, the activity of cAMP-dependent protein kinase, but not Akt kinase, is altered in cochleas, while both kinases are normal in vestibular organs. Adult Adcy6 −/− mice however exhibit normal hearing function. AC6 is expressed in mouse retinas but rarely in photoreceptors. Adcy6 −/− mice have slightly enhanced photopic but normal scotopic vision. Therefore, AC6 may participate in the ADGRV1 signaling in hair cells but AC6 is not essential for cochlear and retinal development and maintenance. Usher syndrome (USH) is the leading cause of inherited deaf-blindness with a prevalence as high as 1 in 6000 in the United States 1-4. USH type 2 (USH2) is the most common of the three USH clinical types. USH2 manifests as congenital moderate to severe sensorineural hearing loss and retinitis pigmentosa, a condition caused by photoreceptor cell death. ADGRV1, USH2A, and whirlin proteins are encoded by the three known USH2 genes 5-7. They interact with one another to form the ankle link complex at the tapering point of the stereociliary basal shaft in hair cells and the periciliary membrane complex between the inner and outer segments in photoreceptors 8-10. The mechanism by which this USH2 complex functions in hair cells and photoreceptors has not been elucidated. ADGRV1 has a seven transmembrane (7-TM) domain and is an adhesion G protein-coupled receptor (GPCR) 11,12. In mammalian HEK293, PC12, and U251 cells, a short ADGRV1 fragment containing the 7-TM domain and the cytoplasmic C-terminal region constitutively couples with Gαi proteins and activates Gαi signaling 13. In primary oligodendrocytes and mouse embryo fibroblasts, a mini ADGRV1 fragment containing 4 instead of 35 extracellular calcium-binding Calxβ domains couples with Gαs and Gαq proteins and activates cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) δ/θ in response to extracellular calcium 14. Furthermore, in an Adgrv1 mutant mouse line (Adgrv1 tm1Msat), adenylyl cyclase 6 (AC6) distribution and expression level are altered in cochlear stereocilia 9. All these findings prompted us to propose that ADGRV1 activates Gαi, Gαs, and Gαq signaling under different physiological conditions and that AC6 may play a role downstream in the ADGRV1 signaling in hair cells and photoreceptors. Adenylyl cyclases (ACs) are a group of enzymes that catalyze second messenger cAMP synthesis from ATP in GPCR signaling 15. While all nine transmembrane ACs are stimulated by Gαs, only calmodulin-activated AC1 and Gαs-activated AC5 and AC6 are regulated by Gαi proteins, which are known to couple with and be activated by
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV... more Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a communicable disease transmitted through the respiratory route and bodily contact. The severity of infection and mortality rate of COVID-19 cases was significantly high in the initial stages of the pandemic. This study aims to investigate the hematological profile of COVID-19 survivors and non-survivors. Methods: This is a single-center retrospective study. A total of 108 hospitalized patients with laboratory-confirmed COVID-19 at East Jeddah Hospital between April and August 2020 were categorized into two groups based on outcome as survivors (n = 54) and non-survivors (n = 54). Hematological parameters and clinical profiles were analyzed and compared between the two groups. Results: The mean age and standard deviation of the survived (30-71 years) and non-survived (33-83) groups was 53 ± 10.8 and 57.9 ± 12.2 years, respectively, with no statistically significant difference in age between groups (p = 0.0513). Non-survivors had a significantly longer median length of stay in the intensive care unit (ICU) (7 days, IQR: 4.24 to 12) compared to survivors COVID-19 patients (5 days, IQR: 0 to 11.75) (p = 0.0151). For the survivors group, the participant's age positively correlated with the length of hospital stay (r(52) = 0.21, p = 0.0005) and ICU length of stay r(52) = 0.18, p = 0.001). The median red blood cells (RBC) counts were significantly higher in the survived group (4.56x10 9 /L, IQR: 4.02 to 5.11) in comparison with the non-survived (4.23x10 9 / L, IQR: 3.75 to 4.23) group (p = 0.0011). All COVID-19 patients exhibited lymphocytopenia and a significant negative correlation was observed between the lymphocyte values and length of hospital stay among the survived group (p < 0.001) as well as length of ICU stay among the survived group (p < 0.0480). Disease-related mortality was significantly associated with reduced white blood cells (WBCs) (8.5×10 9 /L, IQR: 6.1 to 11.7) and reduced basophils (0.09%, IQR: 0.02 to 0.19). Additionally, statistically significant differences were found between the survived and non-survived groups with respect to prothrombin time (PT) (12.5 sec. vs 14 sec., p < 0.0001) and partial thromboplastin time (PTT) (31.8 sec. vs 40 sec., p = 0.0008). Conclusion: Hematological parameters can serve as valuable indicators to identify patients with severe COVID-19 and expected poor-prognosis/outcomes upon hospital admission. Cell counts of lymphocytes, WBCs, basophils and parameters such as PT and PTT can serve as clinical indicators to assess disease severity and predict progression to critical illness.
Journal of the Acoustical Society of America, 2017
Amplitude modulation (AM) detection was measured with a short (50 ms), high-frequency carrier as ... more Amplitude modulation (AM) detection was measured with a short (50 ms), high-frequency carrier as a function of carrier level (Experiment I) and modulation frequency (Experiment II) for conditions with or without a notched-noise precursor. A longer carrier (500 ms) was also included in Experiment I. When the carrier was preceded by silence (no precursor condition) AM detection thresholds worsened for moderate-level carriers compared to lower-or higher-level carriers, resulting in a "mid-level hump." AM detection thresholds with a precursor were better than those without a precursor, primarily for moderate-to-high level carriers, thus eliminating the mid-level hump in AM detection. When the carrier was 500 ms, AM thresholds improved by a constant (across all levels) relative to AM thresholds with a precursor, consistent with the longer carrier providing more "looks" to detect the AM signal. Experiment II revealed that improved AM detection with compared to without a precursor is limited to low-modulation frequencies (<60 Hz). These results are consistent with (1) a reduction in cochlear gain over the course of the precursor perhaps via the medial olivocochlear reflex or (2) a form of perceptual enhancement which may be mediated by adaptation of inhibition. V
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background Cytomegalovirus (CMV) is the most common intrauterine congenital infection in humans. ... more Background Cytomegalovirus (CMV) is the most common intrauterine congenital infection in humans. Worldwide seropositive rates of CMV are considerably high among women of childbearing age. There is currently no optimal drug treatment nor a vaccine for congenital CMV infection and therefore the best available program to date of prevention is practicing standard hygienic measures. The success of this program relies on women’s knowledge of CMV modes of transmissions, and risk and preventative behaviors. Objective The current study aims to assess the awareness and knowledge of CMV infection among women in Saudi Arabia. Method In this cross-sectional study, an online self-administered questionnaire was distributed to women 18 years of age or older residing in all regions of Saudi Arabia. The questionnaire included questions to assess awareness of CMV, knowledge of symptoms, transmission, and preventative measures of CMV infection. Results Out of the 1004 women who completed the questionna...
This excel file contains all the demographics, clinical characteristics, and audiovestibular symp... more This excel file contains all the demographics, clinical characteristics, and audiovestibular symptoms among COVID 19 patients.
This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 ... more This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 patients.
Honey has a history of medical use and is known as bio-alternative therapy. This research assesse... more Honey has a history of medical use and is known as bio-alternative therapy. This research assessed the phytochemical and biological activity of the medical grade manuka honey (MH). Gas chromatography–mass spectrometry (GC–MS) was chosen to investigate bioactive compounds of the MH. The DPPH and ABTS free radical scavenging and beta-carotene antioxidant activities as well as the antibacterial and antibiofilm effects against S. aureus, B. subtilis, E. coli and P. aeruginosa were all determined. Furthermore, to gauge anticancer properties of MH, a MTT assay was opted towards three cell lines, including HCT-116 (colon), A549 (lung) and MCF-7 (breast) cancer cells. The GC–MS analysis of the tested MH revealed the identification of various chemical constituents belonging to the fatty acids, phenols, and esters. The MH was found to have higher reducing power activity (DPPH IC50: 7.36; ABTS IC50: 4.49 mg/mL) than the beta-carotene bleaching power (IC50: 37.51 mg/mL). Similarly, the MH was n...
During the initial phases of the COVID-19 pandemic, stress and anxiety were pervasive among the m... more During the initial phases of the COVID-19 pandemic, stress and anxiety were pervasive among the masses due to high morbidity and mortality. Besides the fear of coronavirus was also particularly driven by social media. Many people started to look for faith and spiritual connections to gain comfort. The role of spiritual ties and religious beliefs in relation to coping with pandemic stress has acquired the attention of researchers in some parts of the world. This cross-sectional survey aimed at assessing the intensity of stress and anxiety symptoms experienced by people and how much they were alleviated by employing spiritual connections. The study sample comprises 795 respondents with 52% males and 48% females living in Saudi Arabia. The brief online study questionnaire collected data about background variables, anxiety and stress scale from DASS-21, and items from the WHOQOL (SRBP) instrument assessed the use of spiritual beliefs to cope. Multiple regression models were tested to de...
Background: Audiovestibular symptoms during the acute stage have been reported in patients with s... more Background: Audiovestibular symptoms during the acute stage have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while very few studies investigated the long-term audiovestibular manifestations of SARS-CoV-2. Objective: The objective of this study was to examine the occurrence of short- and long-term audiovestibular symptoms associated with SARS-CoV-2 infection. Method: In this cross-sectional study, a questionnaire was distributed to severe hospitalized cases and nonhospitalized patients with mild disease, all with confirmed SARS-CoV-2 test results. Participants were inquired to report audiovestibular symptoms during the acute phase and at 6-month follow-up after contracting SARS-CoV-2. Results: A total of 301 participants completed the questionnaire. Auditory symptoms were reported by 21.9% and 1.99% of patients during the acute phase and 6 months post SARS-CoV-2 infection, respectively. During the acute phase of SARS-CoV-2 infection, a...
This excel file contains all the demographics, clinical characteristics, and audiovestibular symp... more This excel file contains all the demographics, clinical characteristics, and audiovestibular symptoms among COVID 19 patients.
This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 ... more This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 patients.
Journal of the Acoustical Society of America, Apr 1, 2016
The acoustic waveform of speech is characterized by slowly varying amplitude fluctuations (i.e., ... more The acoustic waveform of speech is characterized by slowly varying amplitude fluctuations (i.e., envelope) and an accurate representation of the envelope is essential for speech understanding. The post-cochlear representation of the contrast between peaks and valleys of the envelope (peak-to-valley contrast) may be reduced by cochlear compression. This study tested (1) whether amplitude modulation (AM) detection thresholds are consistent with cochlear compression and (2) whether the introduction of a precursor before the carrier results in improved AM thresholds, consistent with a decompressed cochlear response via the medial olivocochlear reflex (MOCR). In the no precursor condition, AM thresholds worsen at mid-levels, consistent with reduced peak-to-valley contrast from cochlear compression. In the precursor condition, AM thresholds improved at low modulation frequencies and mid-to-high levels, consistent with a reduction in cochlear amplifier gain and decompression of the cochlear input/output function via the MOCR. These findings suggest the MOCR may play a role in the perception of other amplitude-modulated stimuli, such as speech.
International Journal of Pediatric Otorhinolaryngology, Nov 1, 2020
OBJECTIVES:Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children s... more OBJECTIVES:Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children show evidence of synaptopathy.STUDY DESIGN:Murine model of CMV infection and case seriesSUBJECTS AND METHODS:C57 BL/6 mice were inoculated with murine-CMV (mCMV). Auditory function was assessed using Auditory Brainstem Response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Temporal bones from mCMV-infected mice were used for both ribbon synapse and hair cell quantification. Four groups of children (non-CMV normal hearing, non-CMV hearing impaired, CMV normal hearing and CMV hearing impaired) underwent ABRs between 2014-2018. The outcomes included raw amplitude, wave I:V amplitude ratio, absolute latency, and interpeak latency.RESULTS:Mice at 8 weeks post mCMV infection had higher ABR and DPOAE (P < 0.05) thresholds and increased outer hair cell loss compared to uninfected mice and mCMV-infected mice at 4- and 6-weeks post infection, indicating progressive hearing loss. A reduction in the wave I amplitude and synaptic counts were noted earlier at 4 weeks in CMV-infected mice (P < 0.05). The human data indicated that the wave I:V amplitude ratio was lower on average in CMV-infected groups when compared to the uninfected cohorts. The wave I:V amplitude ratio for the click and 4k stimuli were not significantly different between the congenital CMV-infected and uninfected children with normal or with hearing loss.CONCLUSION:This study suggests mCMV infection results in a synaptopathy before hair cell damage. Additional studies need to be performed to determine whether this effect is also observed in CMV-infected children.Level of evidence:animal studies and basic science- NA; human studies: level 4.
Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineur... more Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear... more The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear sensory epithelium and plays an essential role in auditory transduction. The TM forms facing the luminal endolymph-filled space and exhibits complex ultrastructure. Contrary to the current extracellular assembly model, which posits that secreted collagen fibrils and ECM components self-arrange in the extracellular space, we show that surface tethering of -tectorin (TECTA) via a glycosylphosphatidylinositol anchor is essential to prevent diffusion of secreted TM components. In the absence of surface-tethered TECTA, collagen fibrils aggregate randomly and fail to recruit TM glycoproteins. Conversely, conversion of TECTA into a transmembrane form results in a layer of collagens on the epithelial surface that fails to form a multilayered structure. We propose a three-dimensional printing model for TM morphogenesis: A new layer of ECM is printed on the cell surface concomitant with the release of a preestablished layer to generate the multilayered TM.
Adenylyl cyclase 6 (AC6) synthesizes second messenger cAMP in G protein-coupled receptor (GPCR) s... more Adenylyl cyclase 6 (AC6) synthesizes second messenger cAMP in G protein-coupled receptor (GPCR) signaling. In cochlear hair cells, AC6 distribution relies on an adhesion GPCR, ADGRV1, which is associated with Usher syndrome (USH), a condition of combined hearing and vision loss. ADGRV1 is a component of the USH type 2 (USH2) protein complex in hair cells and photoreceptors. However, the role of AC6 in the inner ear and retina has not been explored. Here, we found that AC6 distribution in hair cells depends on the USH2 protein complex integrity. Several known AC6 regulators and effectors, which were previously reported to participate in ADGRV1 signaling in vitro, are localized to the stereociliary compartments that overlap with AC6 distribution in hair cells. In young AC6 knockout (Adcy6 −/−) mice, the activity of cAMP-dependent protein kinase, but not Akt kinase, is altered in cochleas, while both kinases are normal in vestibular organs. Adult Adcy6 −/− mice however exhibit normal hearing function. AC6 is expressed in mouse retinas but rarely in photoreceptors. Adcy6 −/− mice have slightly enhanced photopic but normal scotopic vision. Therefore, AC6 may participate in the ADGRV1 signaling in hair cells but AC6 is not essential for cochlear and retinal development and maintenance. Usher syndrome (USH) is the leading cause of inherited deaf-blindness with a prevalence as high as 1 in 6000 in the United States 1-4. USH type 2 (USH2) is the most common of the three USH clinical types. USH2 manifests as congenital moderate to severe sensorineural hearing loss and retinitis pigmentosa, a condition caused by photoreceptor cell death. ADGRV1, USH2A, and whirlin proteins are encoded by the three known USH2 genes 5-7. They interact with one another to form the ankle link complex at the tapering point of the stereociliary basal shaft in hair cells and the periciliary membrane complex between the inner and outer segments in photoreceptors 8-10. The mechanism by which this USH2 complex functions in hair cells and photoreceptors has not been elucidated. ADGRV1 has a seven transmembrane (7-TM) domain and is an adhesion G protein-coupled receptor (GPCR) 11,12. In mammalian HEK293, PC12, and U251 cells, a short ADGRV1 fragment containing the 7-TM domain and the cytoplasmic C-terminal region constitutively couples with Gαi proteins and activates Gαi signaling 13. In primary oligodendrocytes and mouse embryo fibroblasts, a mini ADGRV1 fragment containing 4 instead of 35 extracellular calcium-binding Calxβ domains couples with Gαs and Gαq proteins and activates cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) δ/θ in response to extracellular calcium 14. Furthermore, in an Adgrv1 mutant mouse line (Adgrv1 tm1Msat), adenylyl cyclase 6 (AC6) distribution and expression level are altered in cochlear stereocilia 9. All these findings prompted us to propose that ADGRV1 activates Gαi, Gαs, and Gαq signaling under different physiological conditions and that AC6 may play a role downstream in the ADGRV1 signaling in hair cells and photoreceptors. Adenylyl cyclases (ACs) are a group of enzymes that catalyze second messenger cAMP synthesis from ATP in GPCR signaling 15. While all nine transmembrane ACs are stimulated by Gαs, only calmodulin-activated AC1 and Gαs-activated AC5 and AC6 are regulated by Gαi proteins, which are known to couple with and be activated by
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV... more Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a communicable disease transmitted through the respiratory route and bodily contact. The severity of infection and mortality rate of COVID-19 cases was significantly high in the initial stages of the pandemic. This study aims to investigate the hematological profile of COVID-19 survivors and non-survivors. Methods: This is a single-center retrospective study. A total of 108 hospitalized patients with laboratory-confirmed COVID-19 at East Jeddah Hospital between April and August 2020 were categorized into two groups based on outcome as survivors (n = 54) and non-survivors (n = 54). Hematological parameters and clinical profiles were analyzed and compared between the two groups. Results: The mean age and standard deviation of the survived (30-71 years) and non-survived (33-83) groups was 53 ± 10.8 and 57.9 ± 12.2 years, respectively, with no statistically significant difference in age between groups (p = 0.0513). Non-survivors had a significantly longer median length of stay in the intensive care unit (ICU) (7 days, IQR: 4.24 to 12) compared to survivors COVID-19 patients (5 days, IQR: 0 to 11.75) (p = 0.0151). For the survivors group, the participant's age positively correlated with the length of hospital stay (r(52) = 0.21, p = 0.0005) and ICU length of stay r(52) = 0.18, p = 0.001). The median red blood cells (RBC) counts were significantly higher in the survived group (4.56x10 9 /L, IQR: 4.02 to 5.11) in comparison with the non-survived (4.23x10 9 / L, IQR: 3.75 to 4.23) group (p = 0.0011). All COVID-19 patients exhibited lymphocytopenia and a significant negative correlation was observed between the lymphocyte values and length of hospital stay among the survived group (p < 0.001) as well as length of ICU stay among the survived group (p < 0.0480). Disease-related mortality was significantly associated with reduced white blood cells (WBCs) (8.5×10 9 /L, IQR: 6.1 to 11.7) and reduced basophils (0.09%, IQR: 0.02 to 0.19). Additionally, statistically significant differences were found between the survived and non-survived groups with respect to prothrombin time (PT) (12.5 sec. vs 14 sec., p < 0.0001) and partial thromboplastin time (PTT) (31.8 sec. vs 40 sec., p = 0.0008). Conclusion: Hematological parameters can serve as valuable indicators to identify patients with severe COVID-19 and expected poor-prognosis/outcomes upon hospital admission. Cell counts of lymphocytes, WBCs, basophils and parameters such as PT and PTT can serve as clinical indicators to assess disease severity and predict progression to critical illness.
Journal of the Acoustical Society of America, 2017
Amplitude modulation (AM) detection was measured with a short (50 ms), high-frequency carrier as ... more Amplitude modulation (AM) detection was measured with a short (50 ms), high-frequency carrier as a function of carrier level (Experiment I) and modulation frequency (Experiment II) for conditions with or without a notched-noise precursor. A longer carrier (500 ms) was also included in Experiment I. When the carrier was preceded by silence (no precursor condition) AM detection thresholds worsened for moderate-level carriers compared to lower-or higher-level carriers, resulting in a "mid-level hump." AM detection thresholds with a precursor were better than those without a precursor, primarily for moderate-to-high level carriers, thus eliminating the mid-level hump in AM detection. When the carrier was 500 ms, AM thresholds improved by a constant (across all levels) relative to AM thresholds with a precursor, consistent with the longer carrier providing more "looks" to detect the AM signal. Experiment II revealed that improved AM detection with compared to without a precursor is limited to low-modulation frequencies (<60 Hz). These results are consistent with (1) a reduction in cochlear gain over the course of the precursor perhaps via the medial olivocochlear reflex or (2) a form of perceptual enhancement which may be mediated by adaptation of inhibition. V
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background Cytomegalovirus (CMV) is the most common intrauterine congenital infection in humans. ... more Background Cytomegalovirus (CMV) is the most common intrauterine congenital infection in humans. Worldwide seropositive rates of CMV are considerably high among women of childbearing age. There is currently no optimal drug treatment nor a vaccine for congenital CMV infection and therefore the best available program to date of prevention is practicing standard hygienic measures. The success of this program relies on women’s knowledge of CMV modes of transmissions, and risk and preventative behaviors. Objective The current study aims to assess the awareness and knowledge of CMV infection among women in Saudi Arabia. Method In this cross-sectional study, an online self-administered questionnaire was distributed to women 18 years of age or older residing in all regions of Saudi Arabia. The questionnaire included questions to assess awareness of CMV, knowledge of symptoms, transmission, and preventative measures of CMV infection. Results Out of the 1004 women who completed the questionna...
This excel file contains all the demographics, clinical characteristics, and audiovestibular symp... more This excel file contains all the demographics, clinical characteristics, and audiovestibular symptoms among COVID 19 patients.
This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 ... more This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 patients.
Honey has a history of medical use and is known as bio-alternative therapy. This research assesse... more Honey has a history of medical use and is known as bio-alternative therapy. This research assessed the phytochemical and biological activity of the medical grade manuka honey (MH). Gas chromatography–mass spectrometry (GC–MS) was chosen to investigate bioactive compounds of the MH. The DPPH and ABTS free radical scavenging and beta-carotene antioxidant activities as well as the antibacterial and antibiofilm effects against S. aureus, B. subtilis, E. coli and P. aeruginosa were all determined. Furthermore, to gauge anticancer properties of MH, a MTT assay was opted towards three cell lines, including HCT-116 (colon), A549 (lung) and MCF-7 (breast) cancer cells. The GC–MS analysis of the tested MH revealed the identification of various chemical constituents belonging to the fatty acids, phenols, and esters. The MH was found to have higher reducing power activity (DPPH IC50: 7.36; ABTS IC50: 4.49 mg/mL) than the beta-carotene bleaching power (IC50: 37.51 mg/mL). Similarly, the MH was n...
During the initial phases of the COVID-19 pandemic, stress and anxiety were pervasive among the m... more During the initial phases of the COVID-19 pandemic, stress and anxiety were pervasive among the masses due to high morbidity and mortality. Besides the fear of coronavirus was also particularly driven by social media. Many people started to look for faith and spiritual connections to gain comfort. The role of spiritual ties and religious beliefs in relation to coping with pandemic stress has acquired the attention of researchers in some parts of the world. This cross-sectional survey aimed at assessing the intensity of stress and anxiety symptoms experienced by people and how much they were alleviated by employing spiritual connections. The study sample comprises 795 respondents with 52% males and 48% females living in Saudi Arabia. The brief online study questionnaire collected data about background variables, anxiety and stress scale from DASS-21, and items from the WHOQOL (SRBP) instrument assessed the use of spiritual beliefs to cope. Multiple regression models were tested to de...
Background: Audiovestibular symptoms during the acute stage have been reported in patients with s... more Background: Audiovestibular symptoms during the acute stage have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while very few studies investigated the long-term audiovestibular manifestations of SARS-CoV-2. Objective: The objective of this study was to examine the occurrence of short- and long-term audiovestibular symptoms associated with SARS-CoV-2 infection. Method: In this cross-sectional study, a questionnaire was distributed to severe hospitalized cases and nonhospitalized patients with mild disease, all with confirmed SARS-CoV-2 test results. Participants were inquired to report audiovestibular symptoms during the acute phase and at 6-month follow-up after contracting SARS-CoV-2. Results: A total of 301 participants completed the questionnaire. Auditory symptoms were reported by 21.9% and 1.99% of patients during the acute phase and 6 months post SARS-CoV-2 infection, respectively. During the acute phase of SARS-CoV-2 infection, a...
This excel file contains all the demographics, clinical characteristics, and audiovestibular symp... more This excel file contains all the demographics, clinical characteristics, and audiovestibular symptoms among COVID 19 patients.
This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 ... more This file contains the questionnaire used to investigate audiovestibular symptoms among COVID 19 patients.
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